Heterocyclic chemistry : unique role of heteroatoms in structure and reactivity
by Changjoo Lee
A thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in
Chemistry
Montana State University
© Copyright by Changjoo Lee (1991)
Abstract:
To examine the influences of heteroatom and ring size of structures and reactivity in propellane series,
propellanes are prepared using dianion ring annulation and Diels-Alder reaction.
A formal synthesis of maleimycin, an antibiotic natural product, was completed using, dianion
chemistry and flash vacuum thermolysis (F.V.T.) conditions.
Under F.V.T. condition, 1,2-dicarbomethoxycyclopentene was prepared in nearly 100% yield. This is
the key intermediate of cyclopentanoids such as antibiotic sarkomycin.
In a hydroboration study, the reactivities of propellanes are shown to depend on the HOMO energy and
the atomic coefficient of olefin. Also, we see an interesting correlation between the reactivity and
interatomic distance of heteroatom and the olefinic carbon atom, which is the steric control. And the
stereoisomer ratio of electrophilic additions to olefins depend on the steric hinderance.
In a solvolysis study, the rate enhancement (1.6 times) was observed for the anti-tosylate of [10]
relative to the syn-tosylate. Again, the big rate enhancement (70 times) was observed for the
anti-tosylate of [30] relative to the syn-tosylate. This was interpreted to mean that the heteroatom does
influence reactivity in these compounds. In examining the solvolysis of the different ring size and
dioxa-propellane series, steric and transannular dipole effects were observed.
The major ions in the (EI) mass spectrum of [2] and propellanes have been determined and
investigated. Mechanisms, illustrating the oxygen atom's role in the fragmentation process, have been
proposed.
Stereospecific hydrogenation was observed in the catalytic hydrogenation of [112] and modest
stereoselectivity, was observed in catalytic hydrogenation of [113] and [114]. 
HETEROCYCLIC CHEMISTRY- 
UNIQUE ROLE OF HETEROATOMS 
IN STRUCTURE AND REACTIVITY
By
Changjoo Lee
A thesis submitted in partial fulfillment 
of the requirements for the degree
of
Doctor of Philosophy 
in
Chemistry
MONTANA STATE UNIVERSITY 
Bozeman, Montana
August 1991
APPROVAL
of a thesis submitted by
Changjoo Lee
This thesis has been read by each member of the thesis 
committee and has been found to be satisfactory regarding 
content, English usage, format, citations, bibliographic 
style, and consistency, and is ready for submission to the 
College of Graduate Studies.
Approved for the Major Department
Approved for the college of Graduate Studies
Iiii
STATEMENT OF PERMISSION TO USE
In presenting this thesis in partial fulfillment of the 
requirements for a doctoral degree at Montana State 
University, I agree that the Library shall make it available 
to borrowers under rules of the Library. I further agree 
that copying of this thesis is allowable only for scholarly 
purposes, consistent with "fair use" as prescribed in the 
U .S. Copyright Law. Requests for extensive copying or 
reproduction of this thesis should be referred to University 
Microfilms International, 300 North Zeeb Road, Ann Arbor, 
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and from microfilm and the right to reproduce and distribute 
by abstract in any format".
Signature
i
iv
VACKNOWLEDGEMENTS
This endeavor would not have been possible without the 
help of a number of people. Special thanks are extended 
to.......
Dr. Mundy, for his everlasting encouragements,
understanding, and most of all, his support of 
students.
Dr. Hong, for teaching me to love organic chemistry.
Dr. Howald, for his help on kinetic experiments.
Dr. Callis, for his helpful discussions of our 
calculation data.
Dr. Sears, for his 1,000,000 th mass spectrum!! and 
discussions following.
Dr. Craig, for his enthusiastic discussions on physical 
organic chemistry.
Dr. Jennings, for his discussions on platinum catalyst.
Dr. Livinghouse, for his discussions on synthesis.
Dr. Houk, for providing advanced copies of his 
manuscript on hydroboration study.
Mr. Larson, for his help on X-ray crystallography.
Mr. Rees, for his friendship and his help on 'life USA'
Mr. Muiho, for showing me how to 'calculate'
Mr. Dunham, for his unselfish assistance.
My wife, for her understanding....
vi
TABLE OF CONTENTS
Page
LIST OF T A B L E S ....................................... vii
LIST OF FIGURES...................  xi
A B S T R A C T ...................... xx
1. INTRODUCTION.................................. .. . I
Neighboring Heteroatom Participation . . . . . . .  I
2. SYNTHETIC STUDIES ..............................  15
Propellane Synthesis ............................  15
Maleimycin Synthesis ............................  23
I,2-Dicarbomethoxyclyclopentene Synthesis . . . .  29
3. STERIC EFFECTS OF RING SIZE AND
HETEROATOM EFFECTS................ ............. 32
Competitive Hydroboration Studies . . . . . . . .  32
Hydroboration Studies and Stereochemistry . . . . 46
Solvolysis Studies ...........   57
Mass Spectrum Fragmentation of 
Propellanes and cis-8-Oxabicyclo-
[4,3,0]non-3-ene . ..................  78
Steric and Oxygen Effect on the 
Stereoselective Hydrogenation .................. 90
4. CONCLUSIONS..................................... 102
Synthesis Study ................................  102
Hydroboration Study ............................  102
Competitive Hydroboration .................. 102
Hydroboration ..............................  103
Solvolysis Study.................. ............. 103
Mass Spectrum Fragmentation S t u d y ............... 104
Stereoselective Hydrogenation .................. 104
5. EXPERIMENTAL..................................... 106
General Procedure for Solvolysis ..........  . . .  106
General Comments ................................ 107
REFERENCES........' ................ . . ...........202
APPENDICES...........     206
Appendix A-Kinetic Graphs ...................... 207
Appendix B-1HNMR Spectra of Tosylates . .......... 232
vii
LIST OF TABLES
Table Page
1. Relative Rate of Solvolysis of
p-Bromobenzenesulfonate in
Acetic Acid at SO0C .....................   3
2. Oxygen's Inductive Effect on Carbon-
Carbon Bond Participation ...................  6
3. Kinetic Results of the Solvolysis
of [13] and [14].............................. 12
4. Kinetic Results of the Solvolysis
of [15] and [16].............................. 12
5. Solvent Systems for Propellane Purification . . 21
6. Solvent Systems for para-Nitrobenzoate
Separation.......................... 23
7. Hydroboration Competition Results of
[10] , [25] , [26] and [27]   33
8. HOMO Energies of [10], [25], [26] and [27] . . 35
9. HOMO Pz Atomic Orbital Coefficients of
Olefinic Propellanes ........................ 36
10. HOMO Coefficient of O x y g e n .................... 38
11. HOMO Energies of [10], [28] and [34]  39
12. Hydroboration Competition Results ............ 40
13. HOMO Pz Atomic Orbital Coefficients of
Olefinic Propellanes ........................ 41
14. HOMO Heteroatom Coefficients ...............  42
15. HOMO Energies and Contribution (%) to
Molecular Orbital .......................... 43
16. Hydroboration Competition Results ............ 44
viii
17. Hydroboration Study of Propellanes .......... 46
18. Intensity of M+ and M+-H2O of
Hydroxypropellanes .......................... 49
19. Ground State Conformational Energies for
[69] , [70] , [11] and [12] ..................53
20. HOMO Conformational Energies of [69], [70]
[11] and [12] r ................................ 54
21. Rate Constants for the Tosylates............58
22. Activation Parameters . . . .   58
23. The Reactivity vs. the Distance
Relationship ................................ 63
24. Kinetic Results of the Solvolysis
of syn- and anti-Tosylates of
[10] and [30]    64
25. Activation Parameters of the Solvolysis
of syn- and anti-Tosylates
of [10] and [30]......................  65
26. Kinetic Results of the Solvolysis
of syn- and anti- Tosylates of
[10] , [25] , [26] and [27]  66
27. Activation Parameters of the Solvolysis
of syn- and anti- Tosylate of
[10] , [25] , [26] and [27] . . . .............68
28. Kinetic Results of the Solvolysis
of [16], [87], [88] and [89] . ................. 69
29. Activation Parameters of the Solvolysis
of [88] and [89].............................. 70
30. Calculated Carbocation Stabilities(Kcal/mol) . 74
31. Calculated Olefinic Energies (Kcal/mol) . . . .  75
32. Dehydration of Alcohols
LIST OF TABLES-Continued
Table Page
76
33. Product Studies of the Solvolysis of
[16], [84], [85], [87] and [89] ............77
34. Water Loss Summary ................  . . . . .  82
35. Loss of HOtiH2 in Propellanes ................87
36. Loss of CH3-0-tiH2 in Propellanes .............. 88
37. Loss of ti4H7 in Propellanes............... . 89
38. Relative Rates of Catalytic Hydrogenation . . .  92
39. Relative Catalyst Affinities ................ 93
40. Bond Lengths (A) of [95-OBP] . . . . . . . . .  118
41. Bond Angles ( ‘) of [95-OBP]  118
42. Bond Lengths (A) of [41-anti]..................128
43. Bond Angles ( °) of [41-anti]..................129
44. Bond Lengths (A) of [36-anti]..................141
45. Bond Angles ( ’) of [36-anti]..................141
46. Bond Lengths (A) of [37-syn] .................. 151
47. Bond Angles ( °) of [37-syn]  152
48. Bond Lengths (A) of [37-anti]..................153
49. Bond Angles ( °) of [37-anti] . . .............. 154
50. Bond Lengths (A) of [38-syn]  164
51. Bond Angles ( 0) of [38-syn]  165
52. Bond Lengths (A) of [38-anti].................. 166
53. Bond Angles ( °) of [38-anti].................. 167
54. Bond Lengths (A) of [39-anti]............. . 176
55. Bond Angles ( °) of [39-anti]
ix
LIST OF TJlBLES-Continued
Table Page
177
XLIST OF TABLES-Continued
Table Page
56. Bond Lengths (A) of [42-syn]  185
57. Bond Angles ( ’) of [42-syn]  186
58. Bond Lengths (A) of [42-anti].................. 187
59. Bond Angles ( °) of [42-anti]............. . 188
LIST OF FIGURES
Figure Page
1. A Remote Heteroatom Participation .............. 2
2. Oxygen Intermediate Stabilization ............... 4
3. Solvolysis of Oxygen Heterocyclic Compounds . . .  4
4. Transannular Dipole Effect ....................  5
5. Oxymercuration of cis-8-Oxabicyclo[4,3, 0]-
oct-3-ene.......... 7
6. Heteroatom Participation in Aza-
norbornyl Systems ................    8
7. Charge Stabilization by Oxygen Atom in
cis-Tetrahydrophthalan . . .    8
8. Steric Bias in cis-Tetrahydrophthalan .........  9
9. Conformational Equilibrium in cis-
Tetrahydrophthalan ............................. 9
10. 8-Oxatricyclo[4,3,3,0]dodec-3-ene .   10
11. Conformational Equilibrium of Oxapropellanes . 11
12. Absence of Oxygen Participation in 8-
Oxatricyclo[4,3,3f 0]dodec-3-ene.............. 11
13. Synthetic Routes to cis-1,6-Dicarbo-
methoxybicyclo[4,3,0]non-3-ene ........... . 16
14. Dianion of 3,4-Dicarbomethoxycyclohexene . . .  16
15. Dianion Mediated Syntheses of Different
Ring Size Diester Compounds . ................. 17
16. Syntheses of Propellanes...................... 18
17. Synthesis of 8-Thiatricyclo [4,. 3,3, 0] -
dodec-3-ene.................................. 19
xi
xii
18. Synthesis of Tetraethylethylene- .
tetracarboxylate........................ .. . 20
19. Synthesis of 8,Il-Dioxatricyclo[4,3,3,0]-
dodec-3-ene...............................20
20. Syntheses of syn- and anfci-Tricyclic-
tosylates Derived from the
Corresponding Propellane .................... 22
21. Structure of Maleimycin.....................24
22. Weinreb's Synthesis of Maleimycin ............ 25
23. Synthesis of N-benzylsuccinimide .   26
24. Attempted Synthesis of Cyclopentanones . . . .  26
25. Synthesis of cis-3-(N-benzyl)-2,4-
dioxo-3-azabicyclo[3,3,0]octane ............ 27
26. Attempted Synthesis of 3-(N-benzyl)-2,4-
dioxo-3-azabicyclo [3,3, 0] octA1,5- e n e .......... 27
27. Synthesis of 2,4-Dioxo-3-azabicyclo[3,3,0]-
octA1'5- e n e .................................... 28
28. Simple Cyclopentanoid Natural Products . . . .  29
29. Synthesis of I,2-Dicarbomethoxy-
cyclopentane ................................  30
30. Synthesis of If 2-Dicarbomethoxy-
cyclopentene.......... 30
31. Mechanism of the Dienolate Mediated
Oxidation of I,2-Dicarbomethoxy-
cycIopentane . ................................. 31
32. Synthesis of I,2-Dicarbomethoxy-
cyclopentene . ................................. 31
33. Relationship between the Relative Rate
and Atomic Coefficient of Double Bond . . . .  37
34. Relationship between the Relative Rate and
the Interatomic Distance of the Heteroatom and 
the Olefinic Carbon A t o m ...................... 45
LIST OF FIGURES-Continued
Figure Page
xiii
35. X-ray Structures of para-Nitrobenzoates . . . .  47
36. syn- and anti- Alcohol of Propellane........50
37. Partial NMR Spectrum of [64]-syn.
and - a n t i .................................... 51
38. ORTEP Drawings of X-ray Structure
of Two Conformational Isomers of
[36] -syn and [41] - a n t i............   56
39. syn- and anfci-Tosylate of [10]  59
40. Interatomic Distance of Wilder's Molecules . . 61
41. Interatomic Distance of para-
Nitrobenzoates of Propellane.................. 62
42. Interatomic Distance of Hydroxy Propellanes . . 62
43. Plot of Reaction Rate Constant vs.
Ring Size (syn-Tosylate) . . . . .  ............ 67
44. Plot of Reaction Rate Constant vs.
Ring Size (anfci-Tosylate) .................... 67
45. Product Studies of the Solvolysis
of [82]  71
46. Product Studies of the Solvolysis
of [83]  71
47. Product Studies of the Solvolysis
of [15]    71
48. Product Studies of the Solvolysis
of [86] .   72
49. Product Studies of the Solvolysis
of [88]  72
50. Deuterium Labeled Analogue of cis-8-
Oxabicyclo[4,3,0]non-ene, [2]   78
51. Synthesis of [98], [99] and [100] . . . . . . .  79
LIST OF FIGUKES-Continued
Figure Page
52. 7OeV EI Mass Spectrum of cls-1,1,9,9-
Tetradeutero-8-oxabicyclo[4,3,0]-
non-3-ene, [98]  80
53. 7OeV EI Mass Spectrum of cis-2,2,5,5-
Tetradeutero-8-oxabicyclo[4,3,0]-
non-3-ene, [99]  80
54. 7OeV EI Mass Spectrum of cis-2,2,5,5,1,7,
9,9-Octadeutero-8-oxabicyclo[4,3,0]-
non-3-ene, [100]   81
55. Loss of Water from cis-1,7,9,9-
Tetradeutero-8-oxabicyclo[4,3,0]-
non-3-ene, [98]    83
56. Loss of Water from cis-2,2,5,5,7,7,9,9-
Octadeutero-8-oxabicyclo[4,3,0]-
non-3-ene, [100]...............  84
57. Loss of Water from Propellanes................. 85
58. Loss of Water from [10]......................... 85
59. Loss of HOdH2 from [ 1 0 ] ..........  86
60. Loss of GH3-O-CH2 from [ 1 0 ] ..................... 87
61. Loss of C4H7 form [10]    88
62. Loss of C4H6 from [32], Retro-Diels-
Alder Process . ............................... 90
63. Complexation of cis-8-Oxabicyclo[4,3, 0]-
non-3-ene.........   94
64. Effect of Tetrahydrofuran on the Reduction
of Cyclohexene................................ 95
65. Stereospecific Hydrogenation of 2-
MethyI-cis-I,5-dicarbomethoxy
[3,3,0]oct-2-ene ............................  95
66. Synthesis of the Intermediate of epi-
Modhephene.................................... 96
67. Synthesis of [112], [113], and [114]  97
xiv
LIST OF FIGURES-Continued
Figure Page
XV
68. Stereospecific and Stereoselective
Hydrogenation with Different
Functional Group ............................  ,98
69. %Enhancement of NOE Experiment of the
3-Methyl-8-oxatricyclo[4,3,3,0]-
do de cane, [117]-Major Isomer............. 99
70. 7OeV EI Mass Spectrum of Major
Isomer of [117]   100
71. 7OeV EI Mass Spectrum of Minor
Isomer of [117]  100
72. Loss of Water from [117] -Minor Isomer........... 101
73. ORTEP Drawing of [95-OBP] ...................... 117
74. ORTEP Drawing of [41-anti]   128
75. ORTEP Drawing of [36-syn]......................140
76. ORTEP Drawing of [36-anti]   140
77. ORTEP Drawing of [37-syn]   151
78. ORTEP Drawing of [37-anti]  153
79. ORTEP Drawing of [38-syn]..............   164
80. ORTEP Drawing of [38-anti]  166
81. ORTEP Drawing of [39-anti]  176
82. ORTEP Drawing of [42-syn]...................... 185
83. ORTEP Drawing of [42-anti]    187
84. Plot of In (Ceo-Cx) vs. time (Seconds) for
the Solvolysis of [15] at 39.7 * C ............208
85. Plot of In (C00-Cx) vs. time (seconds) for
the Solvolysis of [15] at 50.10C ...............208
86. Plot of In (C00-Cx) vs. time (seconds) for
the Solvolysis of [15] at 59.9 0C ............209
87. Plot of In (k) vs. 1/T (K"1) for [15] . . . . .  209
LIST OF FIGUKES-Continued
Figure Page
xvi
88. Plot of In (Cco-Cx) vs. time (seconds) for
the Solvolysis of [16] at 40..1*C . . . . . . .  210
89. Plot of In (C00-Cx) vs. time (seconds) for
the Solvolysis of [16] at 49.8°C............210
90. Plot of In (C00-Cx) vs. time (seconds) for
the Solvolysis of [16] at 59.9°C............. 211
91. Plot of In (k) vs. 1/T (K-1) for [ 1 6 ] ...........211
92. Plot of In (C00-Cx) vs. time (seconds) for
the Solvolysis of [80] at 40.3°C............212
93. Plot of In (C00-Cx) vs. time (seconds) for
the Solvolysis of [80] at 50.16C1............212
94. Plot of In (C00-Cx) vs. time (seconds) for
the Solvolysis of [80] at 60.0°C............. 213
95. Plot of In (Jc) vs. 1/T (K-1) for [ 8 0 ] ...........213
96. Plot of In (C00-Cx) vs. time (seconds) for
the Solvolysis of [81] at 29.0' C ............214
97. Plot of In (C00-Cx) vs. time (seconds) for
the Solvolysis of [81] at 40.9 °C . .„........214
98. Plot of In (C00-Cx) vs. time (seconds) for
the Solvolysis of [81] at 49.2°C.............215
99. Plot of In (k) vs. 1/T (K-1) for [81] . . . . .  215
100. Plot of In (C00-Cx) vs. time (seconds) for
the Solvolysis of [82] at 40.5 6C ............216
101. Plot of In (C00-Cx) vs. time (seconds) for
the Solvolysis of [82] at 50.1 ° C ............216
102. Plot of In (C00-Cx) vs. time (seconds) for
the Solvolysis of [82] at 59.8' C .............217
103. Plot of In (k) vs. 1/T (IC1) for [ 8 2 ] .......... 217
104. Plot of In (C00-Cx) vs. time (seconds) for
the Solvolysis of [83] at 40.1 ° C ............218
LIST OF FIGORES-Continued
Figure Page
xvii
105. Plot of In (Cro-Cx) vs. time (seconds) for
the Solvolysis of [83] at 49.9°C............218
106. Plot of In (Cro-Cx) vs. time (seconds) for
the Solvolysis of [83] at 59.7' C ............219
107. Plot of In (k) vs. 1/T (K-1) for [ 8 3 ] ........219
108. Plot of In (Cro-Cx). vs. time (seconds) for
the Solvolysis of [84] at 40.1 ° C ............220
109. Plot of in (Cro-Cx) vs. time (seconds) for
the Solvolysis of [84] at 50.00C ..............220
HO. Plot of In (Cro-Cx) vs. time (seconds) for
the Solvolysis of [84] at 59.7 ° C .............. 221
111. Plot of In (k) vs. 1/T (K-1) for [ 8 4 ] ......... 221
112. Plot of In (Cro-Cx) vs. time (seconds) for
the Solvolysis of [85] at 40.S0C ............222
113. Plot of In (Cro-Cx) vs. time (seconds) for
the Solvolysis of [85] at 50.0°C..............222
114. Plot of In (Cro-Cx) vs. time (seconds) for
the Solvolysis of [85] at 59.9°C.............. 223
115. Plot of In (k) vs'. 1/T (K"1) for [ 8 5 ] ..........223
116. Plot of In (Cro-Cx) vs. time (seconds) for
the Solvolysis of [86] at 39.2 ° C ............224
117. Plot of In (Cro-Cx) vs. time (seconds) for
the Solvolysis of [86] at 49.10C ............224
118. Plot of In (Cro-Cx) vs. time (seconds) for
the Solvolysis of [86] at 57.8 ° C .............. 225
119. Plot of In (k) vs. 1/T (K-1) for [ 8 6 ] ..........225
120. Plot of In (Cro-Cx) vs. time (seconds) for
the Solvolysis of [87] at 29.7 ° C ............226
121. Plot of In (Cro-Cx) vs. time (seconds) for
the Solvolysis of [87] at 40.0 ° C ............226
LIST OF FIGURBS-Continued
Figure Page
Jl
xviii
LIST OF FIQURES-Continued
Figure Page
122. Plot of In (Cro-Cx) vs. time (seconds) for
the Solvolysis of [87] at 4 9.4 0C .............. 227
123. Plot of In (k) vs. 1/T (K-1) for [ 8 7 ] .......... 227
124. Plot of In (Cro-Cx) vs. time (seconds) for
the Solvolysis of [88] at 39.3°C............228
125. Plot of In (Cro-Cx) vs. time (seconds), for
the Solvolysis of [88] at 49.9°C............228
126. Plot of In (Cro-Cx) vs. time (seconds) for
the Solvolysis of [88] at 60.0 " C ............   229
127. Plot of In (k) vs. 1/T (K-1) for [ 8 8 ] .......... 229
128. Plot of In (Cro-Cx) vs. time (seconds) for
the Solvolysis of [89] at 4 0 . 9 C ............. 230
129. Plot of In (Cro-Cx) vs. time (seconds) for
the Solvolysis of [89] at 49.7 ° C ............230
130. Plot of In (Cro-Cx) vs. time (seconds) for
the Solvolysis of [89] at 60.2 ° C .............. 231
131. Plot of In (k) vs. 1/T .(IC1) for [ 8 9 ] .......... 231
132. 300.133 MHz 1HNMR: (syn)-3-Tosyl-8-
oxatricyclo[4,3,2,0]undecane, [82] .......... 233
133. 300.133 MHz 1HNMR: (anti)-3-Tosyl-8-
oxatricyclo[4,3,2,0]undecane, [83]   234
134. 300.133 MHz 1HNMR: (syn)-3-Tosyl-8-
oxatricyclo[4,3,3,0]dodecane, [15] . . . . . . 235
135. 300.133 MHz 1HNMR: (anti)-3-Tosyl-8-
oxatricyclo[4,3,3,0]dodecane, [16] .......... 236
136. 300.133 MHz 1HNMR: (syn)-3-Tosyl-8-
oxatricyclo[4,4,3,0]tridecane, [84]   237
137. 300.133 MHz 1HNMR: (anti)-3-Tosyl-8-
oxatricyclo[4,4,3,0]tridecane, [85] ........ 238
138. 300.133 MHz 1HNMR: (syn)-3-Tosyl-8-
oxatricyclo[5,4,3,0]tetradecane, [86] . . . .  239
xix
Figure Page
139. 300.133 MHz 1HNMR: (anti)-3-Tosyl-8-
oxatricyclo[5,4,3,0]tetradecane, [87] . . . .  240
140. 300.133 MHz 1HNMR: (syn)-3-Tosyl-8-
thiatricyclo[4,3,3,0]dodecane, [80] ........ 241
141. 300.133 MHz 1HNMR: (anti)-3-Tosyl-8-
thiatricyclo[4,3,3,0]dodecane, [81]   242
142. 300.133 MHz 1HNMR: 3-Tosyl-8,11-
dioxatricyclo[4,3,3,0]dodecane, [88]   243
143. 300.133 MHz 1HNMR: (anti)-Tosyl-8,12-
dioxatricyclo[5,4,3,0]tetradecane, [89] . . . 244
LIST OF FIGURES-Continued
ABSTRACT
To examine the influences of heteroatom and ring size 
of structures and reactivity in propellane series, 
propellanes are prepared using dianion ring annulation and 
Diels-Alder reaction.
A formal synthesis of maleimycin, an antibiotic natural 
product, was completed using, dianion chemistry and flash 
vacuum thermolysis (F.V.T.) conditions.
Under F.V.T. condition, I,2-dicarbomethoxycyclopentene 
was prepared in nearly 100% yield. This is the key 
intermediate of cyclopentanoids such as antibiotic 
sarkomycin.
In a hydroboration study, the reactivities of 
propellanes are shown to depend on the HOMO energy and the 
atomic coefficient of olefin. Also, we see an interesting 
correlation between the reactivity and interatomic distance 
of heteroatom and the olefinic carbon atom, which is the 
steric control. And the stereoisomer ratio of electrophilic 
additions to olefins depend on the steric hinderance.
In a solvolysis study, the rate enhancement (1.6 times) 
was observed for the anti-tosylate of [10] relative to the 
syn-tosylate. Again, the big rate enhancement (70 times) 
was observed for the anti-tosylate of [30] relative to the 
syn-tosylate. This was interpreted to mean that the 
heteroatom does influence reactivity in these compounds. In 
examining the solvolysis of the different ring size and 
dioxa-propellane series, steric arid transannular dipole 
effects were observed.
• The major ions in the (BI) mass spectrum of [2] and 
propellanes have been determined and investigated. 
Mechanisms, illustrating the oxygen atom's role in the 
fragmentation process, have been proposed.
Stereospecific hydrogenation was observed in the 
catalytic hydrogenation of [112] and modest
stereoselectivity, was observed in catalytic hydrogenation of 
[113] and [114].
ICHAPTER I 
INTRODUCTION
Neighboring Heteroatom Participation
Our lab has been interested in the unique role of 
heteroatoms in determining the structure and reactivity of 
heterocyclic compounds1'2'3.
In heteroatom containing molecules, the influence of 
the heteroatom on reactivity has been related to the degree 
in which it can stabilize positive charges, as interpreted 
through solvolysis reactions4. In some cases an oxygen 
atom has been shown to enhance reaction rates; while in 
other compounds, an oxygen has been shown to retard 
reactivity. Interpreting oxygen's effect in imparting 
reactivity on the molecule has been difficult because oxygen 
does not easily share its lone pair electrons in the 
stabilization of positive charges, a consequence of its high 
electronegativity. Yet, oxygen is very effective at 
stabilizing positive charge on an adjacent bonded carbon 
atom. As a result of these many differences, the various 
effects oxygen imparts on structure and reactivity are not 
completely understood.
Oxygen's influence is generally to be more subtle than 
that of nitrogen or sulfur, which have lower
2Often this subtle influence is reflected in small rate 
differences. Schleyer5 suggests, however, "the detection 
of any rate enhancement due to anchimeric assistance, no 
matter how small, is indicative of strong (not weak!) 
participation by the neighboring group". We, and others, 
have tried to analyze the participation effects.
Gratz and Wilder6 have proposed the possibility of an 
intermediate of the type, [1], to account for the large (750 
fold) rate increase of the endg-tricyclic sulfide relative 
to the carbon analog. This can be compared to the much 
smaller 2.52 rate increase of endg-tricyclic ether relative 
to the carbon analog. (Figure I)
electronegativities and more diffuse lone pair orbital.
Rel. Rate: 0.8 0.7
Figure I. A Remote Heteroatom Participation.
Closson7 also has found anchimeric assistance by the
tetrahydrofuranyl group. This rate enhancement was shown to
3be greater than that for the methoxy group, which in turn 
was far greater than the corresponding straight chain alkane 
(Table I).
Table I. Relative Rates of Solvolysis of p-Bromobenzene- 
sulfonates in Acetic Acid at 50 * C.
Compound Relative  Rate .
C 1
CH30/ ^ X / ^ X / ^ s‘0Bb 657
/  y — (C H z )H -O B s  
x Oz
n -1 13.1
n -2 2 6 .3
n -3 151 0
n=4 1 2 4 0 0
n -5 1 380
These systems are unlike the conformationally rigid 
norbornyl systems of Wilder, and greater conformational 
flexibility exists. As a result, oxygen is better able to 
stabilize positive charge through Neighboring Group 
Participation (NGP) (Figure 2).
4Figure 2. Oxygen Intermediate Stabilization.
Tarbell and Hazen9 investigated the effects of oxygen 
on the rates of solvolysis of carbo- and heterocyclic 
brosylates. They observed the rates of solvolysis to be an 
order of magnitude slower than would be expected from a 
simple through-bond dipole effect of the oxygen (Figure 3). 
This information, coupled with the fact that the 
corresponding heterocyclic ketones had higher carbonyl 
stretching frequencies than their carbocyclic counterparts, 
led Tarbell and Hazen to conclude that they were dealing 
with a transannular dipole effect as illustrated in Figure 
4.
OBs OBs
1.4 2.47 0.55 13.6
Rate x IO5 sec"1
Figure 3. Solvolysis of Oxygen Heterocyclic Compounds.
5X
Figure 4. Transannular Dipole Effect.
The dipole associated with the ether oxygen was 
destabilizing the incipient carbonium ion in the solvolysis 
and increasing the double bond character of the carbonyl 
group in the corresponding ketones.
Gassman9 used the method of "increasing electron 
demand" to determine the relative ability of the carbon- 
carbon bond of an epoxide, a cyclopropyl group, and a pi- 
bond to stabilize the carbonium ion formed during solvolyses 
of the compounds shown in Table 2.
6Table 2. Oxygen's Inductive Effect on Carbon-Carbon Bond 
Participation.
Compound Relative Ratio(Me/H)
IO11
IO 14-
TsO\/R
By examining the a-methyI/hydrogen ratio, the changing 
electronic effects could be isolated from the changing 
steric effects of the molecule. This method is based on the 
assumption that if the electron demand of the incipient 
carbonium ion in the transition states is satisfied by the 
electron density donated by a substituent on the carbon 
atom, then a remote functional group will not participate in 
the reaction. The relative ability of a functional group to 
be involved in NGP was determined by comparing the rate when 
the electron demand was satisfied by substituents (tertiary
7carbocations) to the ratio when electron demand was 
satisfied by remote functional groups. Note, however, the 
significantly reduced rate enhancement of the epoxide 
relative to its cyclopropyl group analog. This is 
attributed to oxygen's inductive effect on carbon-carbon 
bond participation.
In a study done by Otzenberger1 in 1971, oxymercuration 
of the tetrahydrophthalan, [2] was found to give 
predominantly syn-alcohol, [3] (Figure 5).
Figure 5. Oxymercuration of cis-8-0xabicyclo[4,3,0]oct-3- 
ene.
It had been previously demonstrated for norbornyl 
systems10 that heteroatom participation in the transition 
state leading to the products was responsible for the 
observed stereoselectivity of chemistry occurring at the 
double bond (Figure 6). Isolation of the nitrogen alkylated 
product, [6] was interpreted as firm evidence for remote 
heteroatom participation in these systems.
8HBr
Br*
H H
5 6
Figure 6. Heteroatom Participation in Aza-norbornyl System.
The question which faced Otzenberger was, could the 
same type of heteroatom effect be operating in the 
tetrahydrophthalan case? In his experimental results, 
Otzenberger suggested that the heteroatom effect was 
probably the main causative factor in determining the 
outcome of the oxymercuration of [2].
Figure 7. Charge Stabilization by Oxygen Atom in cis- 
Tetrahydrophthalan.
Figure 7 shows the transformation of the tetrahydrophthalan, 
[2], to the syn-alcohol, [3] via intermediate, [7], for 
which Otzenberger proposed that the developing charge of the 
mercurinium ion was stabilized by the neighboring oxygen 
atom. One unexplored possibility was the potential for 
simple steric effects to dominate the course of the
2 7 3
major
9reaction. As illustrated below, the pi-system of the 
cyclohexene ring is facially dissimilar (Figure 8);
Figure 8. Steric Bias in cis-Tetrahydrophthalan.
One face of the double bond is syn to the oxapropano group 
while the opposite face of the double bond experiences only 
two hydrogen atoms.
Thus, the question to be asked was: could observed 
product ratios be attributed to merely steric factors? 
Nuclear magnetic resonance experiments had suggested11 that 
the conformation of the tetrahydrophthalan molecule was 
predominantly the more stable unfolded isomer depicted in 
Figure 9.
8
un fo lded
9
fo lded
Figure 9. Conformational Equilibrium in cis- 
Tetrahydrophthalan .
In spite of these facts, the question of steric control 
remained insoluble for the system at hand. Clearly, in 
order to unambiguously address this question, a more
10
propitious molecule should eliminate the steric 
discrepancies inherent in the tetrahydrophthalan system, 
while concomitantly retaining the relationship of the oxygen 
atom to the alkene function. The best such molecule 
presented itself as the propellane, [10] illustrated below 
(Figure 10).
Figure 10. 8-Oxatricyclo[4,3,3,0]dodec-3-ene.
As can be seen from the drawing, the propellane 
presents nearly identical steric bulk to each face of the 
double bond; thereby permitting facial distinction only on 
the basis of heteroatom character. A possible objection to 
this statement could be proposed on the basis of a 
conformational preference for the double bond to fold toward 
or away from the heteroatom (Figure 11); however, [11] and 
[12] would seem to have equivalent reactivity by 
calculational methods. The ground state energies, energies 
of HOMO'S and Pz-orbital coefficients are essentially
identical.
11
O O
11 12
Figure 11. Conformational Equilibrium of Oxa-propellane.
When Wilkening12 subjected [11] to an epoxidation 
study using mCPBA and to an oxymercuration study catalyzed 
by trace amounts of nitric acid in methanol, he found no 
indication of oxygen participation influencing product 
stereochemistry. The product ratios in both studies were 
1:1 (Figure 12). As a result, he concluded that simple 
steric effect, not oxygen participation, controlled the 
reaction.
Figure 12. Absence of Oxygen Participation in 8- 
Oxatricyclo[4,3,3,0]dodec-3-ene.
Johnson3 carried out the solvolyses of the syn- and
anti- tosylate derived from [2] and [10] (Tables 3 and 4) .
A slight rate enhancement (1.53 times) was observed for the 
anti- tosylate, [16] relative to the syn- isomer. But,
12
identical reactivities were observed in the solvolysis of 
the syn- and anti- tosylates, [13] and [14].
Table 3. Kinetic Results of the Solvolysis of [13] and 
[14] .
Compound Temp. (eC) k x 104 (a"1) Ee (Kcol/mol)
35.84 0.607
50.00 3.47 28.2
13 hH 62.87 14.3
35.78 0.607
50.20 3.32 25.8
83.00 13.9
Table 4. Kinetic Results of the Solvolysis of [15] and
[16] .
Compound Temp. (eC) k x 104 (a"1) Ee (Kcol/mol)
35.82 1.91
" O r p 50.10 9.35 22.7V 83.00 37.9
15
35.70 2.90
- O r p 50.15 14.7 21.9V
16
62.90 52.7
13
Since there remain many unanswered questions concerning 
the influences of the heteroatoms on structure and 
reactivity, an effort has been made to obtain further 
insight into heteroatom effects. To examine the 
heteroatom's role on structure and reactivity, the following 
investigations were proposed.
(1) Prepare the sulfur analogues of [10] and determine the 
role of the sulfur atom in influencing the 
stereochemistry of electrophilic addition to the alkene 
bond. Examine the solvolysis of tosylates derived from 
this compound. The lone pair electron orbitals of the 
sulfur are more polarizable than oxygen, and one would 
expect greater influences in imparting both 
stereochemistry and reactivity on the molecule.
(2) Synthesize 8,11-dioxatricyclo[4,3,3,0]dodec-3-ene and 
examine the influence of the solvolysis of the 
tosylates derived from this compound. One would expect 
either an oxygen participation or a transannular dipole 
effect. What then is the experimental effect?
(3) Examine the role the oxygen atom plays in influencing 
structure and reactivity in a more conformationally 
flexible system. A system to address this question is 
found with 8,12-dioxatricyclo[5,4,3,0]tetradec-3-ene 
and the tosylates derived from this alkene.
Build different ring size analogues of [10] by using 
dianion ring annulation. It would be interesting to
(4)
14
examine the effect ring size plays in influencing 
structure and reactivity in the different ring size 
propellane systems.
(5) Synthesize a natural product such as maleimycin by 
using dianion chemistry and F.V.T.
(6) Synthesize and subject to catalytic hydrogenation 3- 
methyl-cis-1,6-dicarbomethoxybicyclo[4,3,0]non-3-ene,
3-methyl-cis-I,6-dihydroxymethyl bicyclo[4,3,0]non-3- 
ene, and 3-methyl-8-oxatricylo[4,3,3/0]dodec-3-ene. If 
oxygen is complexing with catalyst, one would expect a 
particular stereoselective reduction. If hydrogenation 
is controlled by steric factor, one would expect 
opposite stereochemistry.
(7) As a new experimental probe to observe oxygen's role in 
imparting reactivity on the molecule, elucidate the 
electron impact mass spectroscopy fragmentation 
mechanisms of a number of heterocyclic compounds, and 
determine oxygen's role in this process.
(8) Examine the MSU-deveioped interface for its use in 
measuring absolute kinetic experiments.
(9) Use calculations! approaches, particularly MM2 and 
MNDO, to investigate the propellane systems and their 
derivatives.
(10) Confirm the relative stereochemistry for the tricyclic 
para-nitrobenzoates, by X-ray data.
15
CHAPTER 2 
SYNTHETIC STUDIES
Propellane Synthesis
Previous work suggested that the tetrahydrofuran ring 
of the propellane was constructed by dehydration of a 1,4- 
diol. Since the I,4-dihydroxy functionality is easily 
obtained from succinate derivatives, the key intermediate 
for a synthesis of the desired propellanes was the diester, 
[17]; which presented two practical options for synthesis 
(Figure 13). The first of these required an addition of 
butadiene to a I,2-dicarboxycyclopentene such as the 
dimethyl ester, [18]. Literature preparations of [18] gave 
unsatisfactory yield13. There was ample reason for concern 
regarding the Diels-Alder reaction of [18] with butadiene as 
well; as tetra-substituted alkene are often sterically 
and/or electronically inhibited as dienophiles14.
16
OCCOgCCO2CH3 CO2CH3
I 8
CO2CH3 
I 7 aCO2CH3CO2CH3 +
19
Figure 13. Synthetic Routes to cis-1,6-
Dicarbomethoxybicyclo[4,3,0]non-3-ene.
The alternative approach proceeded from the readily 
available 3,4-dicarbomethoxycyclohexene, [19], by attaching 
different rings through dianion ring annulation methodology. 
One goal of this project was to demonstrate this type of 
ring annulation for constructing 4, 5, 6, and 7 membered 
rings.
It was postulated that a vicinal ester dianion 
generated from [19] might be a legitimate intermediate if a 
disubstituted alkane could be found to act as an 
electrophile in the dianion ring annulation reaction (Figure 
14) .
0" LI+
OCH3
-OCH3 
0" Li +
Figure 14. Dianion of 3,4-Dicarbomethoxycyclohexene.
17
Additional credence to this approach was gleaned from 
the anticipated stability of the dianion generated from the 
vicinal diester, as conjugation of the enolates would serve 
to stabilize the developing charge. Also, this reaction 
offered the expected formation of only a cis-vicinal 
diester. The dienolate, being presumably planar to permit 
conjugation, implied that once the first alkylation has 
occurred the second displacement would proceed from the same 
face, since formation of the trans ring juncture would 
require the alkyl group to twist between the two ester 
residues. This hypothesis was examined by performing the 
experiments outlined in Figure 15.
/^yCOOMe
^s/^COOMe
LDA/THF
COOMe
B ,C C Br Op20 COOMe
LDA/THF
COOMe
Br/’VXgi-
LDA/THF 
B r / W *  
LDA/THF
BrAA/\gr
LDA/THF
ar/V°Vv
17 COOMe 
'OOMe
21 COOMe 
COOMe
CD
22 COOMe 
COOMe
CD
23 COOMe
(50%)
(68%)
(80%)
(29%)
(82%)
Figure 15. Dianion Mediated Syntheses of Different Ring 
Size Diester Compounds.
18
When 1.5 equivalents of dibromoalkane were added to the 
cooled, bright red THF solution of the dienolate of 3,4- 
dicarbomethoxy cyclohexene, the bicyclic ester was obtained 
(Diester, [22], showed low yield, 29%, due to elimination 
bi-product). The synthesis of the heterocyclic propellane 
was accomplished in a straight-forward manner as described 
in Figure 16.
COOMe
COOMe
COOMe
COOMe
COOMe
COOMe
COOMe
LAH/THF
MeCl/Pyr.
LAH/THF
MeCl/Pyr.
LAH/THF
MeCl/Pyr.
LAH/THF
MeCl/Pyr.
COOMe
COOMe
CD
COOMe
LAH/THF
MeCl/Pyr.
%
28
Figure 16. Syntheses of Propellanes.
To make the sulfur-containing propellane, [30], the 
diester, [17] was first reduced with lithium aluminum 
hydride. Treatment of the resulting diol with 
methanesulfonyl chloride in pyridine gave the dimesylate.
19
[29] in 78% yield. Heating the dimesylate in dry 
hexamethylphosphoramide (HMPA) with anhydrous sodium sulfide 
led to sulfide, [30] in 86% yield. Paquette15 reported 
that the use of dry HMPA is essential to the success of this 
two-fold Sm2 displacement-cyclization. The high cation- 
solvating capacity of HMPA, which greatly reduces the 
effective size of the nucleophile relative to its bulk in 
other (especially protic) media, causes a marked 
acceleration of desired chemical change. The synthesis of 
propellane, [30] is illustrated in Figure 17.
Figure 17. Synthesis of 8-Thiatricyclo[4,3,3,0]dodec-3-ene.
The reaction of tetraethylethyIene tetracarboxylate, 
[32] with butadiene provided cyclohex-4-ene-(I,I,2,2)- 
tetraethylester, [33]. The synthesis of [32] was 
accomplished in a procedure used by Krapchols (Figure 18).
17 31
20
H
I
B r -  C— R + 
I
C C I f  ------------ HCCIj + B r - C —
I
- R
R 35
Bi— C— R +
I
R
H
I
I
R
I
R
R R
I I
——  Br —  C C— H ♦
I I
R R
B r
R R
I I
B r--- A ----  P U * CCIj"
EtOOCx ,COOEt HCCI3
I I EtOOCz ^ xCOOEt
+
B r
R R 
R -  COOEt
32
Figure 18. Synthesis of Tetraethylethylene- 
tetracarboxylate.
The tetra ester, [33] was reduced with lithium aluminum 
hydride and the resulting tetraol was extracted by 
continuous extraction. Treatment of the tetraol with KHSO4 
at 190-200 *C gave the desired 8,11- 
dioxatricyclo[4,3,3,0]dodec-3-ene, [34]. This 
dioxapropellane synthesis is described by Figure 19.
E tO O C ^yC O O E t 180°C,8hrs 
EtOOC^ XOOEt
I .LiAIH4 
2 .KHSO4 If
/-x^COOEt 
(| COOEt[ I  LfCOOEt 
COOEt
Figure 19. Synthesis of 8,Il-Dioxatricyclo[4,3,3,0]dodec-3- 
ene.
21
In the purification of propellanes, for example [10], 
[25], [26], [28], and [34], a florisil separation was
employed to cleanly separate unreacted starting material 
from the propellane system. Although structurally very 
similar, different solvent systems were needed for effective 
separations. The solvent systems are reported in Table 5.
Table 5. Solvent Systems for Propellane Purification.
Compound E thy |qce ta t< ;Haxon«
1 19
2
2
3
1
98
9
8
7
In general, the syn- and anti-tosylates, were
synthesized from its parent propellane alkene system. After 
hydroboration, the corresponding alcohol mixture was
22
converted to the para-nitrobenzoate derivatives. Flash 
chromatography was then employed to cleanly separate this 
mixture into isomerically pure syn-and anfci-tricyclic-para- 
nitrobenzoates. Saponification of the isomerically pure 
syn- and anti-tricyclic-para-nitrobenzoates afforded the 
respective syn- and anti-alcohols, which maintained their 
isomeric purity. The hydrolyzed alcohols were compared to 
known samples. No isomerization took place during 
hydrolysis. The alcohols were then easily converted to syn- 
and anti-tricyclic-tosylates (Figure 20).
BH3/THF HO PNBCI PNBO
Flash
TsCI/Pyr. HO KOH PNBO
EtOH
TsCI/Pyr.
PNBO
X-0.S
n-0,1(C,0),2,3(C,0)
Figure 20. Syntheses of syn- and anti-Tricyclic-tosylates 
Derived from the Corresponding Propellane.
Solvent systems used for para-nitrobenzoate separations
are reported in Table 6.
23
Table 6. Solvent Systems for para-Nitrobenzoate Separation.
As part of our continuing interest in the chemistry of 
propellanes, we have already applied the methodology to the 
synthesis of valerane17 and modhephene18. A consequence of 
our immediate concern was the realization that we could 
synthesize maleimycin. Our approach is outlined below.
Maleimvcin Synthesis
Maleimycin is a bicyclic maleimide antibiotic 
elaborated by Streptomyces Showdoensis, and assigned 
structure [43] by Suhadolnik19 (Figure 21). Maleimycin
24
shows activity against bacteria and is also active against 
leukemia L-1210 cells.
Figure 21. Structure of Maleimycin.
Kasugai20 reported that N-substituted imides of 
general structure, [44] are also known to have fungicidal 
and herbicidal activity.
Meleimycin was prepared by Weinreb21 according to the 
steps outlined in Figure 22.
25
X -B r , OCOCF3
a . ( I )S O C I2 , ( 2 ) Br2 , (3 )M eO H , (4 )N aH ,DM F
b. AcO2 lNH4OH c . TFAc)2
d. NBS1 then  Ag* TFAc-  e . P H -4
Figure 22. Weinreb's Synthesis of Maleimycin.
Our interest in making the five-five fused ring system 
of this molecule using dianion annulation suggested a 
simpler approach. Jun17 chose succinimide as a starting 
material for his earlier attempt. This was N-substituted 
with the benzyl group because the imide proton hinders 
formation of the needed dianion. Succinimide, [50], benzyl 
chloride and potassium carbonates were refluxed and to give 
N-benzyl succinimide, [51], (Figure 23).
26
O O
50 51
R=benzyl
Figure 23. Synthesis of N-benzyl succinimide.
When 2.5 equivalents of lithium diisopropyl amide were 
mixed with [51], a reddish black color of the dienolate was 
formed; but, this dianion did not react with 3-bromoethyI- 
propionate. Yamamoto22 reported difficulty in employing 3- 
bromoethy!propionate in condensations with the dianion and 
he suspected that the proton exchange process was fast 
(Figure 24).
Figure 24. Attempted Synthesis of Cyclopentanones.
We used I,3-dibromopropane for this dianion reaction 
and made cis-3-(N-benzyl)-2,4-dioxo-3-
azabicyclo[3,3,0]heptane, [52], in 60% yield (Figure 25).
27
In order to introduce the I,2-double bond in [52],
Wilkening's23 method was used. The dienolate of [52] was 
reacted with 1.1 equivalents of iodine in the established 
method, but this reaction did not result in formation of the 
double bond (Figure 2 6)17.
Figure 25. Synthesis of cis-3-(N-benzyl)-2,4-dioxo-3- 
azabicyclo[3,3,0]octane.
I  .LDA
Figure 26. Attempted Synthesis of 3-(N-benzyl)-2,4-dioxo-3- 
azabicyclo [3,3,0] oct-A1,5-ene.
The synthesis required modification. Readily available 
cis-1,2,3,6-tetrahydrophthalimide, [53], treated with 
potassium carbonate, and benzylchloromethyI ether, was 
refluxed to give N-benzyloxymethyl-cis-1,2,3,6- 
tetrahydrophthalimide [54] (91% yield). When 2.5
equivalents of lithium diisopropyl amide were mixed with 
[54], a red-colored dienolate was formed, and this dianion.
28
when reacted with I,3-dibromopropane, gave N- 
benzyloxymethyl-7,9-dioxo-8-azatricyclo[4,3,3,0]dodec-3-ene, 
[55] (61% yield) . Deprotection with BBr3 provided 7,9-
dioxo-8-azatricyclo[4,3,3,0]dodec-3-ene, [56] (83% yield).
Finally, this molecule readily underwent retro-Diels Alder 
reaction under F.V.T. condition (~600 *C) to provide 60%
[48], and 35% starting material (Figure 27). The four-step 
synthesis of [48], including the protection and deprotection 
steps, constitutes a formal synthesis of maleimycin and 
shows a simple, general entry to these molecules.
a. LDA /1 ,3 -d lb rom opropane
b. Heat
Figure 27. Synthesis of 2,4-Dioxo-3-azabicyclo[3,3,0]oct- 
A1,5-ene.
29
I,2-Dicarbomethoxvclvclopentene Synthesis 
Another versatile aspect of the vicinal ester dianion 
was revealed during the course of experimentation aimed at 
the synthesis of I,2-dicarbomethoxycyclopentene. Due to 
some interest in simple cyclopentanoids such as the 
antibiotic sarkomycin (Figure 2 6) 24, and the related 
compounds shown below25'26'27, (Figure 28) , we felt that 
the dianion methodology could be fruitfully employed in this 
area.
\
57 COOH
Sarkomyc in24
CH2OH 
""OH
58 COOH 
Pentenomyc in25
59 COOH 60 COOH
Xanthoc id in26 Methy lenomycin27
Figure 28. Simple Cyclopentanoid Natural Products.
When the dianion of dimethylsuccinate was treated with 
I,3-dibromopropane, I,2-dicarbomethoxycyclopentane, [61] was 
obtained in 51% yield following distillation (Figure 29).
30
Br
CH3OOC CCCOgCH3aCH3OOC COgCH3
B r 61
a .  2 . 5 e q u i .L D A /T H F , - 7 8 * C
Figure 29. Synthesis of I,2-Dicarbomethoxycyclopentane
In order to introduce the I,2-double bond in [61], a 
number of suitable oxidizing agents were tried - all to no 
available. However, when the dienolate of [61] was prepared 
and reacted with 1.1 equivalent of iodine, the desired 
cyclopentene, [18] was formed in 85% yield (Figure 30)18.
Figure 30. Synthesis of I,2-Dicarbomethoxycyclopentene.
The proposed mechanism of this transformation is shown 
in Figure 31. In subsequent experiments, it was discovered 
that cuprous iodide also affected this transformation in 
high yield.
61 1 8
31
O
OR
Figure 31. Mechanism of the Dienolate Mediated Oxidation of 
I,2-Dicarbomethoxycyclopentane.
Using F.V.T. condition, we converted cis-1,6- 
dicarbomethoxybicyclo[4,3,0]non-3-ene, [17] to the desired 
product, [18] in 99% yield (Figure 32). Also, we can 
prepare different ring size analogues of [18]. For future 
work, it will be interesting to examine the effect of ring 
size in the retro-Diels Alder reaction.
CO2CH3
CO2CH3
17 18 (99%yield)
Figure 32. Synthesis of I,2-Dicarbomethoxycyclopentene.
32
CHAPTER 3
STERIC EFFECTS OF RING SIZE AND HETEROATOM EFFECTS
Competitive Hvdroboration Studies
The hydroboration competition studies on compounds,
[10], [25], [26], [27] reported in Table 7, demonstrate
steric effects of ring size and electronic effects of . 
heteroatom.
After our initial studies, we found that the GC peak 
area indicated that there was a non-linear dependency on 
molecular size which would have to be determined for each 
set of compounds in some manner. The problem could be 
avoided if the GC analyses were carried out in such a manner 
that peak areas could be determined for both reactants with 
an internal standard, such as anthracene. The competitions 
were carried out with I equivalent of each propellane 
systems, internal standard and.0.1 equivalent of BH3:THF.
The large reactant peaks and very small product peaks had to 
be recorded in the GC trace of reaction mixture. The 
relative rate was determined from the equation below.
I FPll / [P21 \
in I r is i  I r is i  I
Relative Rate = I [SP1]I [SP2] \
In I [IS] I [IS] I
33
[PI]
[P2]
[SP1]
[SP2]
[IS]
Table 7.
G.C. peak area of propellane in a product
G.C. peak area of propellane in a reactant
G.C. peak area of standard propellane, [10] in a 
product
G.C. peak area of standard propellane, [10] in a 
reactant
G.C. peak area of internal standard, anthracene
Hydroboration Competition Results of [10], [25],
[26] and [27].
Compound Relative Rate *  5%
0.42*
0.17*
1.00*
1.10
*: Average of three runs
On the basis of hard and soft acid base theories28, 
electrophilic attack on olefins is governed by the Coulombic 
interactions between reactant and substrate at the reactive
34
site (charge control) and the interactions between the 
highest occupied molecular orbital of the olefin and the 
lowest unoccupied molecular orbital of the electrophile 
(orbital control). According to HSAB Theory, a soft acid 
(electrophile) is most likely to interact at the positions 
with the largest coefficients, ie. orbital control. We 
considered its LUMO to be constant. Therefore, the entire 
HOMOs of the olefins were examined to see if there were 
large coefficients, especially on the oxygen atom, that 
could favorably interact with the electrophile.
Within the framework of the FMO model, the reactivity 
of a olefin toward an electrophile should increase with 
decreasing energy separation between the olefin HOMO and 
LUMO on the electrophile. Since the LUMO of the 
electrophile remains constant for each study, this relative 
reactivity should parallel the relative HOMO energies, which 
are reported in Table 8. MNDO calculation suggested that 
these propellanes have similar HOMO energy (±15 cal) except 
for [25]. Therefore, based solely on orbital influences, 
three propellanes should have equal reactivities. But, 
experimentally, there were some differences on reactivities 
towards electrophile.
35
Table 8. HOMO Energies of [10], [25], [26], and [27].
C om pound  E n e rg y (e V ) (H 0 M 0 )
-9.92926
-9.93314
-9.93404
-9.93293
Based on FMO theory, the reactivity of electrophilic 
additions to olefins assumes that electrophilic attack will 
occur where the Tt-bond is most heavily concentrated. The 
HOMO Pz atomic orbital coefficients are reported in Table 9.
36
9. HOMO Pz Atomic Orbital 
Propellanes.
Coefficients of Olefinic
Con tribu tion (X ) to
Compound M 0(Av.o fPzi2,P z j2) CPzI CPzJ
< q
25
42 .461% -0 .6 4 9 6 7 -0 .6 5 3 5 7
<> ^  4 2 .5 06% -0 .6 5 1 0 2 -0 .6 5 2 9 1
42 .383% 0 .6 5 0 5 6 0 .6 5 1 4 7
42 .4 6 4% -0 .6 5 1 6 3 -0 .6 5 1 6 5
According to above data, we can see that there is a 
corresponding relationship between the relative reactivity 
and atomic coefficient of the double bond (Pz 
orbital)(Figure 33). It is still questionable about the 
relationship between the relative reactivity and atomic 
coefficient of the double bond (Pz orbital) since the 
differences of the coefficient (Pz orbital) shown between 
the four propellane are within 0.14% of contribution to HOMO 
(Figure 34).
37
42.38 42.42 42.44 42.46 42.48
CI.C2-Pz Coefficient(%) of HOMO
Figure 33. Relationship between the Relative Rate and 
Atomic Coefficient of Double Bond.
One would expect that the larger coefficient of the 
heteroatom would retard reactivity of hydroboration, due to 
this complexing effect. In examining the HOMO'S coefficient 
on oxygen, it is obvious that a small coefficient exists on 
oxygen (less then 1% contribution to HOMO) (Table 10).
38
Table 10. HOMO Coefficient of Oxygen.
Com pound
C o n tr ib u t io n (X )  to  MO 
(S f+ P x f+ P yZ + P z * )  C o e ff ic ie n t
10
2 6
S - 0 .0 0 3 6 5
Px - 0 .0 0 0 0 0
0 .0 7 9%
Py - 0 .0 0 5 6 5
Pz 0 .0 2 7 3 4
S 0 .0 0 5 9 3
Px 0 .0 0 1 3 9
0 .1 2% Py 0 .0 2 2 0 8
Pz 0 .0 2 5 9 4
S 0 .0 1 0 5 3
Px 0 .0 0 0 1 2
0 .3 3%
Py 0 .0 1 2 0 2
Pz 0 .0 5 5 2 6
S 0 .0 0 5 4 8
Px 0 .0 0 0 6 1
0 .1 3%
Py 0 .0 2 9 7 7
Pz 0 .0 2 0 5 6
It also appears that molecules in these series, [10], 
[25], [26], and [27] have very little contribution by oxygen
(which could possibly complex with borane) in their HOMO. 
Wood and Rickborn29 studied intramolecular dehydroboration- 
hydroboration of alkylborane, which indicated that THE plays 
no role in the transition state.
39
We have considered the effect of varying ring size on 
the carbocyclic portion of the molecule. What will be the 
consequence of additional heteroatom influences?
In examining two unique dioxapropellane molecules, the 
HOMO energies of both propellanes are lower than the HOMO 
energy of [10]. The HOMO energies are reported in Table 11.
Table 11. HOMO Energies of [10], [28], and [34].
Com pound  E ne rgy (eV )(H OM O )
- 9 .9 3 3 1 4
- 1 0 .1 1 2 9 3
- 1 0 .0 0 0 4 1
So, these low HOMO energy seem to correspond with 
retardation of the reactivities of dioxapropellanes in 
competitive hydroboration. The hydroboration competition 
results are reported in Table 12.
40
Table 12. Hydroboration Competition Results.
Compound Relative Rate + 5%
1.00*
W  
,— < 0 °
0.49*
0.36*
*: Average of three runs
Again, the electrophilic attack will occur where the Tt- 
bond density is most heavily concentrated. The HOMO Pz 
atomic orbital coefficient are reported in Table 13.
41
Table 13. HOMO Pz Atomic Orbital Coefficients of Olefinic 
Propellanes.
Compound
ContrTbution(X) to  
M0(Av.o f Pzi2tPzj2) CPzT CPzJ
O r p 42 .506% -0 .6 5 1 0 2 -0 .6 5 2 9 1ioV
of 42 .503% -0 .6 5 1 0 1 -0 .6 5 2 8 8
3* Vof 41 .703% 0 .6 4 4 1 0 0 .6 4 7 4 6
28
The difference of the coefficients (Pz orbital) between 
[10] and [34] were 0.001%, about the same contribution. 
However, 4.14 Kcal difference of HOMO energies in [10] and 
[34] has decreased by half the reactivity between [10] and 
[34]. The propellane, [28] also has lower HOMO energy (1.55 
Kcal) , and a smaller Pz coefficient (0.8%). These 
differences again are reflected in a retarding of the 
reactivity of [28] in competitive hydroboration.
It also appears that these dioxapropellane [28], [34]
have no contribution by oxygen (which could possibly complex 
with borane) in their HOMO. In examining the HOMO'S
42
coefficient existing on oxygen, we see less than 1% 
contribution to HOMO (Table 14).
Table 14. HOMO Heteroatom Coefficients.
Compound
34 0
28
C on trib u tio n (X ) to  MO
+ ______  C oe ffic ien t
01 0 2 01 0 2
S -0 .0 0 9 9 4 -0 .0 0 5 3 9
0 .3 0 X 0 .089% Px 0 .0 0 0 9 9 -0 .0 0 0 5 0
Py 0 .0 0 8 2 0 -0 .0 1 7 4 6
Pz 0 .0531  I 0 .0 2 3 5 6
S 0 .0 1 0 0 0 0 .0 0 2 7 5
0 .48% 0 .23% Px -0 .0 0 0 3 7 0 .0 0 6 4 7
Py 0 .0 2 3 7 6 0 .0 2 27 1
Pz 0 .0 6 4 1 9 0 .0 4 1  14
The thiapropellane has a different HOMO energy level 
and contribution of Pz on olefin and heteroatom (Table 15).
43
Table 15. HOMO Energies and Contribution (%) to Molecular
Orbital.
Compound Energy(eV) Contribution(X ) to MO
Av.OfPzl21PzI2 
(O lefin)
S2+Px2+Py2+Pz2 
( Hetero Atom)
10 V (HOMO)
-9 .9 3 3 1 4 42.51  X 0 .12X
30  V (HOMO)
-9 .4 2 6 6 7 0 .1 1X 86X
'
A
O Z 0 1
-9 .9 2 5 2 4 4 1 .87X 0.25%
MNDO calculation suggested that the thiapropellane's 
HOMO energy and HOMO-I energy were higher than the 
oxapropellane's by 11.67 Kcal, and 0.18 Kcal. In the HOMO 
of the thiapropellane, the coefficient of olefin is 0.11% of 
contribution from Pzi and Pzj, and 41.87% contribution in 
HOMO-I. Although the thiapropellane, [30] has 0.18 Kcal of 
the HOMO energy higher than oxapropellane, [10] but 0.632% 
difference of the Pzi, Pzj contribution to MO has decreased 
the reactivity between [10] and [30]. The hydroboration 
competition results are reported in Table 16.
44
Table 16. Hydroboration Competition Results.
Compound Relative Rate + 5%
O
I.CD"
5
0.48"
0.65(withBH3:DMS)
* Average of three runs 
DMS: Dimethyl sulfide
When the competition was carried out with both propellane, 
[10] and [30] with BH3:DMS reacted with olefin easier than 
BH3: THF . The BH3: THE can complex with the sulfur of [30] . 
This results in a decrease in reactivity. However, when we 
use BH3:DMS in hydroboration, the chances of complexing with 
same sulfur atom of thiapropellane are less.
We have considered the HOMO energies and coefficients 
of propellanes. From these combined data, the reactivity of 
competitive hydroboration of propellanes would seem to be 
dependent on these two factors. However these studies have 
not provided a definitive answer to why the reactivities are 
observed in these propellanes series. Examination of the 
conformations might be helpful to understand these 
reactivity differences.
45
Brown and coworkers30 have shown that the rates of 
hydroborations are influenced by the nature of alkene 
substrates and solvents, while the order of the rates are 
similar in various solvents. Ab initio calculations for the 
gas phase reactions indicate that reaction rates are 
similarly influenced by the structural variation of 
alkenes31.
From the MNDO calculations of propellanes, interatomic 
distance between the heteroatom and the olefinic carbon atom 
was available. We see an interesting correlation between 
the reactivity (competitive hydroboration) and distance 
(steric control) (Figure 34) .
Figure 34. Relationship between the Relative Rate and the 
Interatomic Distance of the Heteroatom and the 
Olefinic Carbon Atom.
46
Hvdroboration Studies and Stereochemistry 
In order to distinguish simple steric effects from any 
electronic effects imparted by the hetroatom in influencing 
the stereochemistry of electrophilic additions to the 
olefins, a hydroboration study was conducted on a series of 
propellanes (Table 17).
Table 17. Hydroboration Study of Propellanes.
Compound G.C
SynVAnti 
10 : 90
not separated
53 : 47
57 : 43
59 : 41
one isomer
not separated
43 : 57
13C INV. GATE 
SynVAntt
N.A
57 i 43 
51 : 49 
57 i 43 
N.A
26 : 74 
45 : 55
*:Syn to the 5-membered ring heteroatom bridge 
The reported stereochemistries are 
those of the alcohol products.
47
The product ratios were obtained from peak integrations 
of the GLC traces obtained on the VG-707OE-HF mass 
spectrometer and the peak integration of 13C-Inverse Gate 
experiment. The relative stereochemistries of the alcohols 
derived from propellanes were determined from the X-ray 
crystal structure obtained for the syn-tricyclic-para- 
nitrobenzoates and anfci-tricyclic-para-nitrobenzoate (Figure 
35)(See chapter 5 for larger X-ray structure).
[38]-syn [38]-anti
48
[95]-OBP
Figure 35. X-ray Structures of para-Nitrobenzoates.
In general, when a syn-tricyclic-para-nitrobenzoate was 
subjected to saponification (KOH in absolute ethanol) only 
one alcohol resulted, the corresponding syn-alcohol. The 
other alcohol, having a similar pattern, and 1H NMR spectra 
was obviously the corresponding anti-alcohol.
In the mass spectra of syn- and anti-alcohols of 
propellanes, different peak intensity of parent molecular 
ion and a loss of water was observed (Table 18). In the
49
generally observed trend, the syn-OH of propellanes have a 
strong intensity of M+-H2O and weak intensity of M+ because 
syn-OH is near the oxapropano ring.
Table 18. Intensity of M+ and M+-H2O of Hydroxypropellanes.
Syn*:Syn to the 5-membered ring heteroatom bridge
Analysis of the NMR spectrum for syn- and anti-alcohols 
of the propellane systems showed a unique d,d of Ha and Hb, 
and multiplet of He (Figure 36).
50
HbHa HbHa
Figure 36. syn- and anti- Alcohol of Propellane.
In Figure 37 is illustrated examples of Ha coupled with Hb 
and He. The mutiplets seen in different chemical shift 
versus syn- and anti- alcohols of [64] are reported.
51
[64]-syn
[64]-anti
Figure 37. Partial NMR Spectrum of [64]-syn and [64]-anti.
52
Johnson3 used the MM2 and MNDO methods to determine the 
relative equilibrium abundances of olefin [10]. One
i
strength of the MM2 method is its ability to determine 
conformational minima of a compound by calculating steric 
energies for all possible conformations of the molecule32.
MM2 considers a molecule as a collection of atoms held 
together by harmonic forces which can be described by 
potential energy functions of structural features such as 
bond lengths, bond angles, nonbonded interactions and so on. 
The combination of these potential energy functions 
constitutes the force field. The steric energy (ES) of the 
molecule in the force field arises from deviations from 
"identical" structural features and can be approximated by a 
sum of energy contributions.
ES=Eb+Est+Enb+....
Where Eb is the energy arising from bending bond angles from 
their "ideal" values, E8t is the energy arising from 
stretching bond lengths from their "ideal" lengths, and Enb 
is the energy of nonbonded interactions. The steric energy 
of the molecule is, therefore, the difference in energy 
between the actual molecule and a hypothetical molecule 
where all bond lengths and bond angles have exactly their 
"ideal" values33. The MNDO method is a semi -empirical 
molecular orbital calculation developed by Dewar and has, as 
one of its strengths, the ability to accurately calculate 
heats of formation (Hf) while requiring only modest
53
computational time. The initial geometries for the MNDO 
calculation were the optimized geometries obtained by the 
SIMS and PC MODEL molecular modeling programs. These 
geometries were then optimized at the SCF level by 
minimizing the energy with the Davidon-Fletcher-Powell (DFP) 
algorithm34. From these calculation methods, Johnson 
reported the energies of the two anticipated boat formations 
(Table 19).
Table 19. Ground State Conformational Energies for [69],
[70] , [11] and [12] .
Conform ation Ene rg y (K ca l/m o l)  
MM2(S teric ) MNDO(Hr)
fr 18 .7 6 -4 2 .9 0
1 0 .7 3 - 4 2 .8 4
2 7 .3 9 -4 8 .7 7
2 7 .2 4 -4 8 .8 1
These results suggest that the minima for the two 
anticipated boat conformation are energetically equivalent 
within the errors reported for each calculation35. As a
54
result, the relative conformational equilibrium abundances, 
as calculated as exp (-AE/RT) where AE is the conformational 
energy differences, R is the gas constant and T=298‘K, are 
approximately equal for the two anticipated boat 
conformations. Also, he calculated the olefin HOMO. 
According to the FMO theory, the reactivity of a olefin 
towards an electrophile should increase with decreasing 
energy separation between the olefin HOMO and the LUMO on 
the electrophile. Since LUMO of the electrophile remains 
constant for hydroboration study, this relative reactivity 
should parallel the relative HOMO energies, which are 
reported in Table 20.
Table 20. HOMO Conformational Energies of [69], [70], [11]
and [12].
Conformation Energy(eV )(H 0M 0)
-9 .9 6
-9 .9 4
-9 .6 9
-9 .6 9
12
55
The above calculation suggests that conformation of [69] and 
[70] have nearly identical reactivities and conformation
[11] and [12] have identical reactivities.
The results of Table 17 suggest that the 
stereochemistry ratio of electrophilic additions to olefins 
depends on steric hinderance. With the different size of 
ring systems, one face of the double bond is syn to the 
oxapropano group while the opposite face experiences a 
different ring size. Also, in the different sulfur 
heteroatom system, one face of the double bond is syn to a 
thiapropano group ring while the opposite face experiences 
the propano group. Since the %-faces of propellanes have 
different steric environments, electrophilic addition went 
to the sterically less hindered side. Again, there are 
obvious steric differences between the %-faces of [2]. In 
[2], the face anti to oxygen is much less hindered and the 
initial electrophilic attack anti to oxygen would be 
favored. In X-ray structures of para-nitrobenzoates of [25] 
and [28], we found two different conformational isomers 
(Figure 38). For [25], the ratio of stereoisomers favors 
syn to oxygen because one of the isomers provides more 
space. Also, compound [28] has two different conformational 
isomers. One conformational isomer provides more space, 
therefore, ratio of stereoisomer is favorable to syn to 
oxygen of 7-membered ring.
56
[36]-syn
C3 C4
[41]-anti
Figure 38. ORTEP Drawings of X-ray Structure of Two
Conformational Isomers of [36]-syn and [41] - 
anti.
57
Solvolvsis Studies
It was about thirty years ago that Brown and coworkers 
published their paper on Chemical Effects of Steric 
Strain36. In this work, Brown determined the rate 
constants and activation parameters associated with the 
solvolysis of cycloalkyltosylates with different ring sizes. 
We have tested an MSU-developed interface on these 
particular reactions. One of the unique features of this 
method is that research quality data are routinely gathered 
on milligram quantities. Efforts were thus focused on the 
preparation and solvolytic behavior of tosylate, 71-73.
71 72 73
Table 21 shows the observed individual first order rate 
constants for the three starting compounds. The last column 
shows Brown's rate constants for the tosylates at three 
temperatures of which there is a direct comparison.
58
Table 21. Rate Constants for the Tosylates.
Ring size Temp (0C) K exp (xlO 5) K Ref36 (xl0"s)
5
50 3.80 3.82
60 11.35 -
70 31.80 33.20
80 106.45 -
90 261.80 -
6
70 2.39 2.37
80 7.25 -
90 22.70 22.20
7
50 6.49 6.45
60 19.73 -
70 60.55 60.00
80 165.68 -
90 399.00 395.00
For these experiments, we have plotted In(k/T) vs 
1000/T. The excellent data allow us to assign the values of 
AS* of activation shown in the Table 22. Literature values 
are also included in this table. Our data support Brown's 
values and his conclusions.
Table 22. Activation Parameters.
5-ring 6-ring 7-ring
Ah* AS* Ah* AS* Ah* AS*
Ref36 24.1 -4.2 27.3 -0.5 23.3 -5.7
This Work 24.4 -3.4 27.6 -0.4 23.7 -4.6
With the knowledge that we could carry out precise
solvolysis studies using the equipment, we next investigated
59
whether we could measure long-range heteroatom influences. 
The series of propellane's tosylates were designed to 
attempt to elucidate the heteroatom's role in influencing 
reactivity in solvolysis. If NGP is occurring, an increase 
in rate would be predicted for the anti-tosylate relative to 
the corresponding syn-tosylate.
The tosylates, [15] and [16], are unique in that the 
steric environments for the two compounds (Figure 39) seem 
to be identical. In [15], the tosylate group is syn to the 
oxapropano group while in [16] the tosylate group is anti to 
the oxapropano group. Therefore, the backside attack by 
solvent, on the carbon bearing the tosylate, should 
experience the same steric environment. So, any observed 
rate enhancement of [16] over [15] might then be attributed 
solely to oxygen participation.
Figure 39. syn- and anti-Tosylate of [10].
We initially chose para-nitrobenzoate as our leaving 
group. As previously described, the propellane systems were 
subject to hydroboration yielding the corresponding alcohol 
mixtures which were subsequently converted to the para- 
nitrobenzoate mixture. Flash chromatography was then
15 16
60
employed to isolate the product. Unfortunately, these para- 
nitrobenzoates proved to be surprisingly stable. In order 
to increase the reactivity of this series, we completed two 
new syntheses derivatizing the alcohols with tosylate, a 
better organic leaving group. We therefore used the schemes 
shown in Figure 20 to obtain the isomerically pure 
tosylates. Examples of 1HNMR spectra of tosylates are 
illustrated in Appendix B . para-Nitrobenzoates were white 
solids, which after a number of crystallizations yielded 
crystals in hexane (or ethanol) and dichloromethane (10:1, 
respectively) from which X-ray structures were obtained. 
These X-ray structures confirmed the relative
stereochemistries reported for the para-nitrobenzoate in the 
syntheses. Their ORTEP drawings are illustrated in Figure 
35.
All the solvolysis experiments used 50% aqueous 
methanol. The kinetic studies were completed 
conductrimetrically. A conductance cell and thermistor were 
interfaced to a computer allowing for the simultaneous 
acquisition of conductance, temperature, and time 
measurements. A standard solution of 50% aqueous methanol 
was used. The standard solution (20 mL) was added to the 
pretreated conductance cell which was then placed in the 
constant temperature bath. The reaction system was allowed 
to equilibrate for 2 hours, then approximately I mg of the 
tosylate was added to the cell and upon temperature
61
equilibration, data acquisition began. Data were collected 
approximately every second over 3 to 5 half-lives of the 
reaction and an infinity point was obtained after 
approximately 15 half-lives. Least squares method treatment 
on In (Cm-Cx) v s  time (seconds) yielded first order rate 
constant (k) for each tosylate. From examination of the 
rate constants obtained from tosylate of [10] and [30], 
there appears to be rate enhancement of the anti-tosylate 
over syn-tosylate.
By MNDO calculation of Wilder's molecules, [74] and 
[75], interatomic distances between the heteroatom and the 
carbon bearing the hydroxyl group are 3.67lA (oxygen), and 
3.888A (sulfur) (Figure 40).
74 75
Figure 40. Interatomic Distance of Wilder's Molecules.
In X-ray structures of anfci-tricyclic-para- 
nitrobenzoate, [76] and [77] the interatomic distances 
between the heteroatom and the carbon which has OPNB group 
are 4.067A (oxygen), 4.465A (sulfur) (Figure 41).
62
r-4.465A
PNB
Figure 41. Interatomic Distance of para-Nitrobenzoates of 
propellane.
MNDO calculation of hydroxy propellane, [78] and [79] 
also have similar interatomic distance, 3.814A (oxygen), 
4.261A (sulfur) (Figure 42).
r=3.841A r-4.261 A
Figure 42. Interatomic Distance of Hydroxy Propellanes.
This investigation suggested that the distance between 
the heteroatom and the carbon atom which was connected to 
the leaving group was related to reactivity of solvolysis. 
These reactivity versus the distance relationships are 
illustrated in Table 23.
63
Table 23. The Reactivity vs. the Distance Relationship.
Relative Rate
Compound (vb.Carbon)
D Ietance(A )
(by MNDO1X -OH )
PNBO
P N B O ^ ^ X
Tl0XZiSrp
2 .5 3
1.6
3 .6 7 1  A
3 .841A
3 .888A
4 .2 61  X
The rate enhancement (1.6 times) was observed for the 
anti-tosylate of [10] relative to the syn-isomer. Also, the 
big rate enhancement (70 times) was observed for the anti- 
tosylate of [30] relative to the syn-isomer. This was 
interpreted to mean that the heteroatom does influence 
reactivity in these compounds.
The lone pair electron orbital of the sulfur are more 
polarizable than oxygen. The big rate enhancement was 
observed for anti-tosylate of [30] versus anfci-tosylate of 
[10]. The results of these kinetic studies are reported in
Table 24.
64
Table 24. Kinetic Results of the Solvolysis of syn- and 
anti-Tosylates of [10] and [30].
Compound Temp(0C)t O-OS k x I 0"4(s"'
39.7 3.00
50.1 9.65
15 V 59.9 27.5
y 40.1 5.09^
Tso^ C_ir 49.8 15.0
16 V 59.9 43.6
TsOvn^ ----- -S 40.3 0.67
50.1 1.75
80 V 60.1 3.79
19.3 4.67
/ — rC 29.0 13.5
T s O ^ — pr 40.9 54.2
81 V 49.2 122
For these solvolysis studies, a plot of the logarithm 
of the rate constant against the reciprocal of the absolute 
temperature is approximately linear with negative gradient 
(i.e. the reaction is faster at higher temperature.). The 
Arrhenius equation was used to obtain energies of 
activation, Ea. Ea represents a critical energy which the 
molecule must possess in order for reaction to occur; for a 
given value of A, the rate constant decreases as Ea becomes 
larger. And the transition-state theory was employed to 
obtain the enthalpy, AH* and entropy, AS* of activation.
The term AH*, the enthalpy of activation, corresponds
65
closely to the activation energy term, Ea, in the Arrhenius 
equation (for liquids and solids, AE=AHN-RT) AS* is known as 
the entropy of activation. One important merit of 
transition-state theory is that it rationalizes the 
probability factor, P. A reaction in which the transition 
state is highly organized will have a large, negative AS*, 
corresponding to a small value for P . The results of these 
studies are reported in Table 25.
Table 25. Activation Parameters of the Solvolysis of syn- 
and anti-Tosylates of [10] and [30].
Compound
TsCk  / —<r y
15
T
Eo (K co l/m o l) AHt (Kco lZmoI) ASt (Ou) 
2 2 .7  2 2 .0  -4 .6 1
2 2 .5  2 1 .B -4 .2 9
TsO
80
Tscr V _
18.2 17.5 -21.9
20.6 20.0 -5.58
81
66
In examining the solvolysis of the different ring size 
analogues propellane, it appeared that the reaction rate 
constant depended on steric hinderance except for [86] and 
[87]. The results of these studies are reported in Table 26 
and Figures 43~44.
Table 26. Kinetic Results of the Solvolysis of syn- and 
anti-Tosylates of [10], [25], [26], and [27].
Compound
ri0X Z f r p
82 ^
Tt O ^ Z f p
83 N
'"IHf
-IHf
Tomp(lC) *0.05
40.5
50.1
59.8
40.1
49.9
59.7
39.7
50.1
59.9
40.1
49.8
59.9
40.1
50.0
59.7
40.3
50.1
59.9
39.2 
49.1
57.8 
29.7 
40.0
49.4
k x IQ-4Cb-1)
9.55
27.9
71.1
10.3
29.5
73.5 
3.00 
9.66
27.5 
5.09
15.0
43.6 
0.39 
1.21 
3.53 
0.49 
1.58 
4.99 
2.96
12.2
24.3 
26.5
61.9 
173
/
Tai
67
0.0015
Ring Size (Syn-OTs)
Figure 43. Plot of Reaction Rate Constant vs. Ring size 
(syn-Tosylate).
0.002
■= 0.001
0.0005
Ring Size (Anii-OTs)
Figure 44. Plot of Reaction Rate Constant vs. Ring size 
(anfci-Tosylate).
68
Again, the Arrhenius equation was used to obtain 
energies of activation, Ea and the transition-state theory 
was employed to obtain the enthalpy, AH*, and entropy, As* 
of activation. The results of these analyses are reported 
in Table 27.
Table 27. Activation Parameters of the Solvolysis of syn-
and anfci-Tosylates of [10], [25], [26], and [27].
Compound Eo(Kcal/mol) AHt (KcalZmoI) AST(eu)
r i 0 ^ r f
62 ^
T‘oiFfP
21.6 20.9 -5 .91
20.8 20.1 -8 .2 3
22.7 22.0 -4.61
22.5 21.8 -4 .29
23.3 22.6 -6 .8 6
24.5 23.9 -2 .3 3
23.4 22.8 -1 .4 5
18.4 17.8 -1 1 .8 0
Rate enhancements were again observed for anfci-tosylate 
relative to syn-tosylate for each of the different ring size
69
series. We found a significant Ea difference (5 Kcal/mol) 
between the anti- and syn-tosylate of 7 membered ring 
propellanes, [86] and [87]. The relative rate of [87]/[86] 
is 14 times at 50 * C .
From an examination of the rate constants obtained from 
the tosylates of [16], [88], [87] and [89] we observed a
rate retarding effect by the second oxygen (Table 28).
Table 28. Kinetic Results of the Solvolysis of [16], [87],
[88] and [89]
Compound Temp("C)*0.05 k x 10 -4Xs"1)
40.1
49.8
59.9
39.3
49.9 
60.0
29.7 
40.0
49.4
40.9
49.7
60.2
I 73
5.09
15.0
43.6
0.79
2.87
8.58
26.5
61.9
6.94
20.6
61.789
70
These results lead us to believe that we are dealing 
with a transannular dipole effect. The dipole associated 
with the second ether oxygen was destabilizing the incipient 
carbonium ion in the solvolysis, thus retarding the rate.
The results of activation parameters are reported in Table 
29.
Table 29. Activation Parameters of the Solvolysis of [88] 
and [89].
Compound Eo(Kcol/mol) AHT(Kco l/m o l) ASt (Ou)
23 .8  23 .2  -3 .2 7
23.5  22.9  -0 .2 3
Product studies were carried out by combining the three 
runs for each tosylate, distilling most of the methanol, and 
then extracting the resulting residue repeatedly with 
dichloromethane. Product studies were completed by 
comparing 1H spectra and GC-MS spectra of the observed 
products to those of the authentic samples that were 
synthesized and characterized previously. Product ratios 
were obtained from peak integration completed on GLC
71
capillary column equipped with a flame ionization detector. 
The results of those studies are summarized in Figures 
45~4 9.
TsO
unidentified olcohol(3X)
Figure 45. Product Studies of the Solvolysis of [82].
50%aq.Me0H HO-
(98%) ' (2%)
Figure 46. Product Studies of the Solvolysis of [83].
Figure 47. Product Studies of the Solvolysis of [15].
72
Figure 48. Product Studies of the Solvolysis of [86].
The product analysis for these tosylates, [82], [83],
[15], and [86] have been found to result, primarily, in 
products formed by substitution (with complete inversion of 
configuration, the SN2 mechanism) in different ratio of the 
methoxy and alcohol compounds. No retention of 
configuration is observed. This suggests no free 
carbocations (SN1 mechanism) are generated in these 
compounds.
TsO
50%aq.Me0H alcohol compound(47%) 
methoxy compound(38%)
(2%) (13%)
Figure 49. Product Studies of the Solvolysis of [88].
The product study for [88] shows a mixture of alkenes, 
[34] and [90], in the relative ratio of 2% : 13% and the
73
methoxy and alcohol compounds in the relative ratio of 47% : 
38%. These processes have been found to result in products 
formed by substitution (SN2 mechanism), and elimination 
(this elimination is the only example in these series). 
However, mass spectral fragmentation patterns of the 
substitution products are different to those of the 
authentic samples that were synthesized and characterized 
previously. The 1H spectra of the substitution products are 
very similar to authentic samples. From this data, we 
suggest a 1,2 hydride shift. A 1,2 hydride shift, followed 
by substitution, accounts for the hydroxy and methoxy 
compound at C2. Because the driving force to migration in 
solvolysis is the formation of a more stable carbocation37, 
carbocation stabilities were determined by the MNDO method 
(Table 30). These calculations illustrate a thermodynamic 
driving force promoting this rearrangement. The carbocation 
at C2 is favored by approximately 3-6 Kcal/mol over 
carbocation at C3.
74
Table 30. Calculated Carbocation Stabilities (Kcal/mol).
Compound
if
I
S
Hf
1 6 9 .8 5
1 6 1 .2 6
1 6 5 .3 4
1 7 0 .1 4
1 3 2 .4 6
1 4 3 .0 0
1 9 8 .5 2
a
1 65,81
1 5 5 .5 8  
1 5 9 .2 5
186 .29
1 2 9 .6 2  
1 4 1 .7 2
1 9 7 .0 5
Elimination of para-toluenesulfonic acid results in a 
mixture of olefins. An examination of the stabilities of 
olefins by MNDO calculation indicates that [90] is 
thermodynamically more stable than alkene, [34] by 3 
Kcal/mol (Table 31)
75
Table 31. Calculated Olefinic Energies (Kcal/mol).
Compound Q a.
-2 7 .5 0 4 -2 8 .7 1 8
-37 .551 -41 .0 75
-3 4 .6 8 8 -37 .389
r -2 8 .6 5 2 -31 .821
r -6 8 .1 9 3 -71 .2 92
f -5 7 .4 4 5 -55 .089VO I \
0 .439 -3 .2 4 3
Also, dehydration of hydroxy propellanes with catalytic 
amount of sulfuric acid provide two alkenes. Again, major 
alkenes are more stable by ~3 Kcal/mol thermodynamically by 
MNDO calculation (Table 32) .
76
Table 32. Dehydration of Alcohols.
C^I HVH2O a ■ a
1 : 3 .29
1 : 8.39
1 : 6 .44
N.A N.A
I : 8.10
2.10
I : 1.51
Other tosylates, mostly anfci-tosylates, have the same 
trends as [88] except for the elimination process. The 
product studies for [16], [84], [85], [87], and [89] show
the alcohol and methoxy compound (Table 33). Again, mass 
spectral fragmentation patterns of these substitution 
products are different from those of the authentic samples 
that were synthesized and characterized previously. But 1H 
spectra of the substitution products are similar to one of
77
the authentic spectrum. And the stabilities of carbocation 
at C2 and C3 position were determined by MNDO calculation 
(Table 30). These calculations suggest the I,2-hydride 
shift possibility for these processes.
Table 33. Product Studies of the Solvolysis of [16], [84],
[85], [87] and [89].
Compound Alcohol Compound Methoxy Compound
93%
79%
58%
26%
(two kinds)
87%
66%
9%
(two kinds)
21%
16%
13%
25%
In order to absolutely establish the identities of the 
products from these studies, future work will require the 
synthesis of authentic samples of hydroxy and methoxy 
compounds at C2 position.
78
Mass Spectrum Fragmentation of Propellanes 
and cis-8-Oxabicvclo[4,3,01non-3-ene 
Our interest was the preparation and characterization 
of a number of unique tricyclic (propellanes) and bicyclic 
non-aromatic heterocycles. In the spectrum of each 
compound, a loss of water is observed. It is obvious where 
the oxygen comes from in the loss. The fundamental question 
to account for the loss is the identification of the source 
of hydrogens. Assuming a similar mechanism accounts for the 
loss of water in each compound, we prepared propellanes and 
three specially deuterium-labeled substrates for study. To 
address the question as to where the protons originate in 
the loss of water, Johnson3 prepared a series of deuterium 
labelled analogues of [2]. In this series, the C2-C5 
positions were labelled to form [99], the C7-C9 positions 
were labelled to form [98], and both of these positions were 
labelled to form [100] (Figure 50).
9 8  9 9  1 0 0
Figure 50. Deuterium Labeled Analogue of cis-Q- 
Oxabicyclo[4,3,0]non-3-ene, [2].
For the synthesis of [98], the known anhydride, [101], 
was reduced with lithium aluminum deuteride. The resulting
79
I,4-diol was immediately cyclized to [98] with TsCl/Pyr.
The syntheses of [99] and [100] developed from a common 
intermediate, [102] . Non-Iabelled butadiene sulfone, [103], 
was dissolved in D2O to which was added a catalytic amount 
of sodium metal. After stirring at room temperature for 48 
hours, exchange had taken place to >95%. The labeled 
sulfone, [104], was refluxed with maleic anhydride in xylene 
to yield the Diels-Alder product, [102]. Reduction and 
cyclization of [102] led to [99] [100] (Figure 51 outlines
these synthesis).
0
1.LAD/THF 
b  2.TsCI/Pyr.
101
No
D2O
103 104 °2 
1.LAH/THF
0
99
102
I .  LAD/TH F
Figure 51. Synthesis of [98], [99], and [100] .
80
The EI mass spectra of these compounds are recorded in 
Figures 52-54.
Figure 52. 7OeV EI mass spectrum of cis-1,7,9,9-
Tetradeutero-8-oxabicyclo[4,3,0]non-3-ene,
Figure 53. 70 eV EI mass spectrum of cis-2,2,5,5-
Tetradeutero-8-oxabicyclo[4,3,0]non-3-ene.
[98] .
[99] .
81
L_J
Figure 54. 70 eV EI Mass Spectrum of cis-2,2,5,5,7,7,9,9,-
Octadeutero-8-oxabicyclo[4,3,0]non-3-ene, [100] .
From an examination of these spectra, there is a loss 
of 20 mmu from [100] . For [98] there is loss of 18 mmu and 
19 mmu; which for [99] there is loss of 19 mmu and 20 mmu. 
These data require that the protons associated with the 
water loss come from different sources. In loss of 18 from 
[98], the two protons must originate from the C2-C5 
position. In the loss of 19 mmu from [98], a proton comes 
from the C2-C5 position, and a deuterium atom is required 
from the C7-C9 position. Similarly, for the loss of 20 mmu 
from [99] two deuterium atoms originate from the C2-C5 
position; while for the loss of 19 mmu a deuterium atom 
originates from the C2-C5 position and a proton is derived
82
from the C7-C9 position. The loss of water from [98], [99],
and [100] is summarized in Table 34.
Table 34. Water Loss Summary.
C om pound  
9 8  ^
Loss o f  H2O Loss o f HDO Loss o f  D2O 
1 1 0 (1 2 % )  1 0 9 (1 0% )
Sf 10 9 (  5% ) I 0 8 (  5% )
11 3 (  5% ) 1 1 2 (1 3 % )
These data suggest that the loss of water results from at 
least two different processes. The following mechanism 
appears to account for the two different processes of the 
loss of water (Figure 55).
83
Figure 55. Loss of Water from cis-1,7,9,9-Tetradeutero-8- 
oxabicyclo[4,3,0]non-3-ene, [98].
Interestingly, there is a loss of 19 (HDO) with weak 
intensity (5%) and a loss of 20 (D2O) with strong intensity 
(13%) in [100] . These data also support our mechanism 
(Figure 56).
84
CD,
-TX
■D,
D1O
DO
HDO
DaO
Figure 56. Loss of Water from cis-2,2,5,5,7,7,9,9-
Octadeutero-8-oxabicyclo[4,3,0]non-3-ene, [100].
In the electron impact (EI) mass spectra of 
propellanes, [10], [25], [26], [27], and [34], the loss of
water is observed with different intensity. The intensities 
of the peaks are illustrated in Figure 57. It appears that 
there is the loss of water in [34] with 32% intensity. It 
is obvious that this propellane has two ethereal oxygen 
atoms, which is a main factor for the loss of water. By
85
changing ring size on the propellanes, the difference of the 
peak intensities for loss of water changes from 1% to 21%.
Figure 57. Loss of Water of Propellanes.
The following mechanism appears to account for the process 
of the loss of water in propellane systems (Figure 58).
CH2
Figure 58. Loss of Water from [10].
86
The rigidity of the 4-membered ring propellane, [25] 
appears to account for a small intensity of the loss of 
water (1%). In the EI mass spectrum of [25], the first 
major peak was (M+-28) , which suggest the loss of (C2H4) from 
the 4-membered ring.
In [10] second loss results in a ion m/z=133, in [26] 
m/z=147, in [27] m/z=161, in [34] m/z=135. This is a loss 
of 31 for [10], [26], [27], and [34]. These data suggest
the loss of (HOCH2) . The following mechanism illustrates 
the observed HOCH2 loss (Figure 59).
♦
m/z-133
Figure 59. Loss of HOCH2 from [10] .
Loss of HOCH2 is observed with similar intensity for the 
four molecules of interest as illustrated in Table 35.
87
Table 35. Loss of HOdH2 in Propellanes.
Compound In tensity
10
31%
26
34%
23%
32%
The major ion, m/z=119 in [10] seems to correspond to 
the major ion, m/z=133 in [26], m/z=147 in [27], m/z=121 in 
[34]. This is a loss of 45 for [10], [26], [27], and [34].
These data suggest the loss of (CH3-O-CH2) . The following 
mechanism illustrates the observed losses (Figure 60).
( Q D m/z=119
+
CH3OCH2 ( - 4 5 )
Figure 60. Loss of CH3-O-CH2 from [10] .
The intensities of these peaks are summarized in Table 36.
88
Table 36. Loss of CH3-O-CH2 in Propellanes.
Compound In tensity
10
32X
26
15%
23%
24%
The major ion, m/z=109 in [10] seems to correspond to 
the major ion, m/z=123 in [26] m/z=137 in [27], m/z=lll in 
[34]. This is a loss of 55 for [10], [26], [27], and [34].
These data suggest the loss of C4H7. The following 
mechanism illustrates the observed losses (Figure 61). The 
intensities of these peaks are summarized in Table 37.
c^ p —  CO0 (m/z-,o,)
V = / C H Z
/CH2
( (-55)
Figure 61. Loss of C4H7 from [10].
89
Table 37. Loss of C4H7 in propellanes.
Compound In tensity
7%
71%
64%
25%
From this examination, we found somewhat different 
intensity of each propellane. Obviously, bicyclic major ion 
of [10] and [34] show weak intensity (10%-20%) while the 
bicyclic major ion of [26] and [27] exhibit strong intensity 
(60%-70%). Probably, the stability of major ion depends on 
the strain of bicyclic system, and stable major ion shows 
strong intensity. Also we found strong ion (40%), m/z=112 
in [34]. The following mechanism illustrates the observed 
loss (Figure 62).
90
Figure 62. Loss of C4Hs from [32], Retro-Diels-Alder 
Process.
From this study, the oxygen atom's role in a number of 
fragmentation processes has been studied. The major ions in 
the (EI) mass spectrum of [2] and propellanes have been 
determined and investigated mechanisms, illustrating the 
oxygen atom's role in the fragmentation processes, have been 
proposed.
Steric and Oxygen Effect on the 
Stereoselective Hydrogenation 
The catalytic hydrogenation of olefins has been studied 
by a number of investigators using a variety of reaction 
techniques. Theodore2 investigated a series of catalytic 
hydrogenation studies. In the competitive study, the 
experiment was carried out by mixing the bicyclic alkene
91
with cyclohexene in the same reaction vessel. Each 
competition was carried out for a specified length of time 
and quenched by the removal of hydrogen. The catalyst used 
was 10% pd/c and the reactant-product distribution was 
monitored by gas chromatography. Bicyclic alkene, [2] in 
Table 38 seem to indicate a heteroatom rate enhancing effect 
(1.3 fold) over the carbon analogue, [106]. Also, the fact 
that [105] is slower (3.5 fold) than [2] is probably due, as 
a result of the trans configuration at the ring juncture of 
[105], to the steric difficulty encountered by the double 
bond in resulting on the catalytic surface. From these 
results, we are now dealing with the two effects (steric and 
heteroatom) in the catalytic hydrogenation.
92
Table 38. Relative Rates of Catalytic Hydrogenation.
Com pound  C om p e tit iv e  N o n -c o m p e t it iv e
0
Q>
CO
1 0 5
1.0
6 .5 9
1 .3 3
4 .9 2
2 3 .6 3
1.0
0 .7 8
0 .5 5
0 .1 3
0 .0 0 3 9
The fact that [106] appears to reduce faster than 
cyclohexene under competitive conditions can be attributed 
to a "bulk effect". Since an equivalent amount of [106] 
will occupy more space than cyclohexene in a fixed volume, 
and given a substrate to catalyst ratio of 1000:1, it seems 
reasonable that the probability of a catalyst particle 
coming in contact with [106] is high.
In the non-competitive study, carried out in separate 
reaction vessels for the same time period, the rates of 
reduction of all the bicyclic compounds were slower than
93
that of cyclohexene. The 7.7 fold rate difference between 
[106] and cyclohexene can be rationalized on the basis of 
steric arguments. In the case of [107], the nitrogen atom 
is complexing with the catalyst, tying up the catalyst 
sites, and prohibiting cyclohexene from being reduced under 
competitive conditions.
Theodore also completed a number of competitive and 
non-competitive hetroatom/catalyst affinity studies (Table 
39). These results represent the ratios of complexed to 
free substrate relative to the ratio of complexed to free 
cyclohexene.
Table 39. Relative Catalyst Affinities.
Com pound  C om p e tit iv e  N o n -c o m p e t it iv e
1.00 1.00
0.88 0 .1 3
1 0 6
3 .3 6 0 .7 5
2
107
4 0 .2 0 4 .2 2
94
In the affinity studies, a substrate to catalyst ratio of 
2:I was used to allow monitoring of the change in 
concentration of free substrate and minimize the "bulk 
effect".
The results of the competitive study suggest a greater 
affinity of heteroatom bicyclic compound, [2] to bind to the 
catalyst over carbon analogue, [106] or cyclohexene. And 
the results of the non-competitive study were also used to 
argue for a positive oxygen/catalyst affinity. We therefore 
envisioned one molecule of [2] having the ability to complex 
to more than one catalyst site as shown in Figure 63.
Figure 63. Complexation of cis-8-0xabicyclo[4,3,0]non-3- 
ene.
Glancy38 also observed an oxygen/catalyst interaction. 
He studied the effect of oxygen heterocycles on the 
catalytic hydrogenation of cyclohexene (Figure 64).
95
- 2.32 - 1.16 OlO
Figure 64. Effect of Tetrahydrofuran on the Reduction of 
Cyclohexene.
He rationalized these results by reasoning that the ethereal 
oxygen in tetrahydrofuran absorbed on to catalyst sites 
normally used for hydrogen absorption. This prevented 
cyclohexene from reaching the catalyst surface thus 
decreasing its rate of reduction.
Wilkening39'40 used the heteroatom interaction with 
catalyst in the reduction of 2-methyl-cis-l,5- 
dicarbomethoxy[3,3,0]oct-2-ene (Figure 65). This was used 
as a key step in his stereospecific synthesis of (dl) 
modhephene.
Figure 65. Stereospecific Hydrogenation of 2-Methyl-cis- 
1,5-dicarbomethoxy[3,3,0]oct-2-ene.
CO2CH3
108
CO2CH3
109
96
Unexpectedly, catalytic hydrogenation of [108] produced 
one isomer by reduction from the less hindered face without 
any interaction between the heteroatom and catalyst (Figure 
66) .
CH3 CO2CH3
less
hindered
face
CO2CH3
108
H2
Pd/C
110
Figure 66. Synthesis of the Intermediate of epi-Modhephene.
Recently, Kraus41 reported the synthesis of epi- 
modhephene. In this article, he suggests an alternative 
catalyst which is [Ir (COD) (PCy3) py] PF6 for the 
stereospecific hydrogenation toward modhephene.
However, Theodore and Glancy both observed the 
oxygen/catalyst interaction and some steric effect. In the 
catalytic hydrogenation, we should consider both the 
heteroatom coordination with the catalyst and steric effect 
of the substrate itself. In order to detect this proposed 
question, new systems, [112], [113], and [114] were
synthesized and subjected to catalytic hydrogenation. In 
the synthesis of [112], [113], and [114], 1.2 equivalents of
I,3-dibromopropane were added to the lithium dienolate of 
cis-1,6-dicarbomethoxy-3-methylcyclohex-3-ene, [111]. The 
diester, [112], was obtained in 72% yield. Reduction of the
97
diester with LAH afforded the diol, [113] (82% yield) which
was subsequently ring-closed to the desired propellane,
[114] (86% yield) (Figure 67).
H3C
COOMe
COOMe
111
1.LDA/THF
B r ^ ^ B r
COOMe
COOMe 
I 12
Figure 67. Synthesis of [112], [113], and [114].
In the catalytic hydrogenation of olefinic diester, 
[112], the experiment was carried out by mixing substrate 
and Pt/c in ethanol at 20 psi for overnight. A 
stereospecific addition was observed. In an identical 
procedure olefinic diol, [113] was reduced. A 
stereoselective addition was observed, and products were 
formed in the relative ratio of 65:35. Again, in the 
propellane, [114], the reduced products were formed in the 
relative ratio of 75:25 (Figure 68).
98
COOMe
P t /C ,H 2
COOMe
90
P tyC1H2
COOMe
COOMe
93
one s te reo isomer  
"s te reospec i f i c ”
Two s te reo isomer 
(65:35)
(75:25)
Figure 68. Stereospecific and Stereoselective Hydrogenation 
with Different Functional Group.
The reduced diester, [115] was formed as one 
stereoisomer (stereospecific hydrogenation). Reduction of 
this diester, [115] with LAH afforded the one stereoisomer 
diol, which is the same stereoisomer as the major isomer 
from [116]. Again, this major isomer subsequently ring- 
closed to the propellane, which is the same stereoisomer as 
major isomer from [117].
A difference Nuclear Overhouser Effect (NOE)42 1HNMR 
experiment was employed on the major isomer of [117] to
99
determine the stereochemistry of the methyl group. In the 
1HNMR spectrum, one of the doublets (3.52 ppm) was 
irradiated and a positive 4.7% NOE enhancement was observed 
at the methyl proton at 0.87 ppm. This is a first piece of 
evidence to support the structure as shown in Figure 69.
4.7%
Figure 69. % Enhancement of NOE Experiment of the 3-Methyl-
8-oxatricyclo[4,3,3,0]dodecane, [117]-Major 
Isomer.
In the electron impact mass spectroscopy fragmentations 
of the major and minor isomers of [117], different peak 
intensity due to the loss of water was observed, 1% and 18% 
respectively. (Figures 70-71)
100
Figure 70. 7OeV EI Mass Spectrum of Major Isomer of [117] .
Figure 71. 7OeV EI Mass Spectrum of Minor Isomer of [117] .
The following mechanism appears to account for the 
processes of the loss of water for [117]-minor isomer 
(Figure 72). This is consistent with our other detailed MS 
conclusions and is a second piece of evidence pointing to 
the structure of the reduction products.
101
Figure 72. Loss of Water from [117]-Minor Isomer.
These two investigations suggested that catalytic 
hydrogenation of [112] produced one isomer by reduction from 
less hindered face without any interaction between diester 
group and catalyst.
102
CHAPTER 4 
CONCLUSIONS
Synthesis Study
We prepared four kinds of different ring size 
propellanes using dianion ring annulation method.
We also prepared dioxapropeIlanes using Diels-Alder 
reaction and dianion chemistry.
A formal synthesis of maleimycin, an antibiotic natural 
product, was completed by dianion annulation and F.V.T. 
Using F.V.T. condition, we made 1,2-
dicarbomethoxycyclopentene in nearly 100% yield. This 
compound is the key intermediate of eyeIopentanoids 
such as the antibiotic sarkomycin.
After hydroboration, alcohol mixtures were converted to 
para-nitrobenzoates. We used different solvent systems 
for flash separation and prepared the isomerically pure 
syn- and anti-tricyclic para-nitrobenzoates. X-ray 
structures of para-nitrobenzoates confirmed the 
relative stereochemistry.
Hydroboration Study 
Competitive Hydroboration
The reactivities of different ring size would seem to 
be dependent on the atomic coefficient of olefin (Pz
Iorbital) based on FMO theory. There was no 
contribution by oxygen (which could possibly complex 
with borane) in their HOMO. The calculations! studies 
have not provided a definitive answer as to why the 
reactivities are observed in the different ring size. 
Examination of the conformations might be helpful to 
understand these reactivity differences. From MNDO 
calculation, we see an interesting correlation between 
the reactivity and the interatomic distance of 
heteroatom and the olefinic carbon atom, which is 
steric effect. In dioxapropellanes, [28] and [34] the
reactivities of these series depended on its HOMO 
energies and the atomic coefficient of olefin (Pz 
orbital). Again, there was no contribution by oxygen. 
In thiapropellane, the 0.623% difference of the Pzi,
Pzj contribution to MO and complex between sulfur and 
borane caused to retard the reactivity.
2. Hvdroboration
The results (Table 17) of hydroboration study suggested 
that the stereoisomer ratio of electrophilic additions 
to olefins depended on steric hinderance.
Solvolvsis Study
I. To test new MSU-developed interfaces, we have
reinvestigated H.C. Brown's solvolysis experiment.
The rate enhancement (1.6 times) was observed for the 
ahfci-tosylate of [10] relative to the syn-tosylate.
103
2.
104
Also, the large rate enhancement (70 times) was 
observed for the anti-tosylate of [30] relative to the 
syn- isomer. The rate enhancement of anti-tosylate 
over syn-tosylate is due to oxygen and sulfur 
participation. Also, the distance between the 
heteroatom and the carbon atom which was connected to 
leaving group was corresponded to reactivity of 
solvolysis.
3. In examining the solvolysis of the different ring size 
analogue of [10], it appears that the reaction rate 
constant depends on steric hinderance.
4. From an examination of the tosylates of 
dioxapropellane, [28] and [34], we observed a rate 
retarding effect by transannular dipole affect of the 
second oxygen.
Mass Spectrum Fragmentation Study 
The oxygen atom/s role in a number of fragmentation 
processes has been studied. The major ions in the (EI) mass 
spectrum of [2] and propellanes have been determined and 
mechanisms investigated, to illustrate the oxygen atom's 
role in the fragmentation process.
Stereoselective Hydrogenation 
Stereospecific hydrogenation was observed in the 
catalytic hydrogenation of [112], and modest 
stereoselectivity was observed in the catalytic 
hydrogenation of [113] and [114]. The NOE experiment and
105
(EI) mass spectroscopy fragmentation of major isomer of 
[117] suggested that catalytic hydrogenation of [112] 
produced only one isomer by reduction from less hindered 
face without any interaction between oxygen and catalyst.
106
CHAPTER 5 
EXPERIMENTAL
General Procedure for Solvolvsis 
20 mL of the standard 50% aqueous methanol solution 
were added to the oven-dried cell, which was placed in a 
constant temperature bath and allowed to equilibrate. 
Approximately I mg of the substrate (tosylate) was added to 
the cell. The substrate was allowed to dissolve and the 
temperature to equilibrate (3 minutes). Upon temperature 
equilibration, the solvolysis reactions were followed for 3 
5 half-lives, and after 15 half-lives an infinity 
conductance value (C00) was measured. The conductance and 
temperature measurements were recorded with a Laboratory 
Interface43. This digital to analog converter interfaced 
the conductivity cell and thermistor to a PC, allowing for 
simultaneous acquisition of conductance, temperature, and 
time measurements. Rate constants were calculated by a 
least-squares method of In (C00-Cx) vs. time (seconds) . 
Activation parameters were calculated by least squares 
method of In (k) vs. 1/T (6K)"1. All kinetic experiments 
were completed using the same conductance cell. Rate 
measurements were made at three different temperatures for 
each tosylate, usually over a range of 406 C. The
107
temperature was controlled ± 0.05°. Product analysis and 
peak integrations were obtained by GC-MS and ^HNMR.
Examples of plot of In (C66-Cx) vs. time (seconds) for 
the 50% aqueous methanolysis for each tosylate at three 
different temperatures are illustrated in Appendix A.
General Comments
Melting points were determined on a Fisher-Johns 
melting point apparatus and are uncorrected. 1H spectra 
(300.133 MHz) and 13C spectra (75.4 MHz) were obtained on a 
Bruker AC-300 300 MHZ spectrometer using a 5-mm 1HZ13C
switchable probe. Samples were dissolved in CDCl3. All 
spectra were obtained at 293K. Chemical shifts are reported 
in parts per million (ppm) relative to tetramethylsilane. 
Splitting patterns are designated as follows: s, singlet; d, 
doublet; t, triplet; p, pentet; m, multiplet. Infrared 
spectra were recorded on a Nicolet DX FT-IR spectrometer. 
Low-resolution mass spectra were obtained on a VG-MMl6 
instrument. High-resolution and chemical ionization(Cl) 
mass spectra were completed on the VG-7070E-HF mass 
spectrometer. To obtain HREI on those samples which gave no 
observed M+, larger sample quantities and greater detection 
sensitivity were used. X-ray crystallographic data were 
obtained with a Nicolet R3ME diffractometer. Analytical 
thin-layer chromatography (TLC) was performed on aluminum 
backed silica gel plates (Whatman ALSIL G/UV), and flash 
chromatography was completed using 500 mL flash column
packed with 4OjlM diameter silica gel and equipped with a UV 
absorbance monitor. MgSO4 was used for drying organic 
solvents unless noted otherwise. THF and diethyl ether were 
freshly distilled from sodium / benzophenone. Diisopropyl 
amine and pyridine and dimethylsulfoxide (DMSO) were 
distilled from calcium hydride. All other reagents were 
used as received. All reactions involving moisture- 
sensitive reagents were carried out in oven or a flame- 
dried apparatus under argon.
Bromination of ethyl malonate44
A mixture of ethyl malonate (112 g, 0.700 mol), N- 
bromosuccinimide (150 g, 0.843 mol), and 200 mL of CCl4 was 
refluxed with benzoyl peroxide (2 g). After overnight 
reflux the solid succinimide was filtered off and the 
solvent was removed from the filtrate by rotary evaporation 
to yield a yellow-colored liquid. GC analysis showed ethyl 
monobromomalonate (80%) and ethyl dibromomalonate (18%), 
starting material (2%). The yellow liquid was distilled to 
yield ethyl monobromomalonate as a pale yellow oil (115 g, 
0.481 mol) (69% yield).
Diethyl monobromomalonate, (351
IR (neat, cm"1) : 2984, 1742, 1469, 1370, 1303, 1250, 1151, 
1031, 865, 646
1HNMR (300.133 MHz, CDCl3): 8 1.26 (6H, t, J=7. IHz) , 4.24 
(4H, q, J=7.IHz), 4.79 (1H,s)
108
109
13CNMR (75.4 MHz, CDCl3) : 5 13.78 (q) , 42.29 (d) , 63.09 (t) , 
164.50 (s)
LRMS(EI) m/e (%abundance) : 238 (M% 3), 193 (19) , 166 (35), 
138 (100), 122 (26), 87 (12), 69 (28), 45 (22), 39(12) 
HRMS (EI) m/e calculated for C7H11O4Br = 237.9841 ; found = 
237.9836
Preparation of tetraethvlethvlene tetracarboxylate16, [32]
A solution of diethylmonobromo malonate (17.8 g, 0.075 
mol) and sodium trichloroacetate (13.9 g, 0.075 mol) in 50 
mL of I,2-dimethoxyethane was refluxed under a nitrogen 
atmosphere for 5 hours. The precipitated salt was filtered 
from the hot solution and washed with ether. The solvent 
was removed by rotary evaporation and ethanol:hexane (1:1) 
mixture was added to the resultant red oil. After standing 
in the freezer overnight, pale yellow crystals separated. 
Recrystallization from ethanol/hexane yield pure product as 
white feathery solid (15.2 g, 0.048 mol) (64% yield) 
Tetraethvlethvlene tetracarboxylate, [32] 
mp = 51-52°C (Ref16 52-53°C)
IR (Nujol, cm"1) : 2935, 1735, 1457, 1371, 1254, 1025 
1HNMR (300.133 MHz, CDCl3): 5 1.29 (12H, t, J=7.2Hz) 4.29 
(8H, q, J=7.2Hz)
13CNMR (75.4 MHz, CDCl3) : 8 13.78 (q) , 62.47 (t), 135.43 (s) ,
162.32 (s)
LRMS (EI) m/e: 271, 243, 226, 215, 187, 169, 152, 143, 97,
44 (base)
H O
LRMS (Cl) (Methane) m/e (%abundance) : 317 (M+H+, 7) , 271 
(IOO)f 243 (13)
Preparation of cvclohex-4-ene-(I,If2,2)-tetraethylester,
1331
Tetraethylethylene tetracarboxylate (5.00 g, 0.016 mol) 
was mixed with butadiene (5 mL) in bomb at 180”C . After 
heating 8 hours, a brown colored liquid was obtained. The 
liquid was distilled in high vacuum to yield pure product 
(5.70 g, 0.015 mol) as a pale yellow oil (96% yield). 
Cvclbhex-4-ene- n, 1,2,2) -tetraethylester45, [33]
IR (neat, cm-1) : 3072, 2980, 2935, 1736, 1442, 1391, 1365, 
1264, 1198, 1040, 863
1HNMR (300.133 MHz, CDCl3): 5 1.23 (12H, t, J=7.2Hz), 2.79 
(4H, s), 4.18 (8H, q, J=7.2Hz), 5.67 (2H, t, J=1.4Hz) 
13CNMR (75.4 MHz,CDCl3) : 5 13.78 (q) , 31.28 (t) , 56.87 (s) ,
61.58 (t), 124.05 (d), 167.01 (s)
LRMS (EI) m/e: 370 (Mf) 325, 297, 251, 223, 177 (base) , 149, 
105, 79, 44
HRMS (EI) m/e calculated for C18H26O8 = 370.1628 ; found = 
370.1630
Preparation of (I,1 ,2 ,21-tetrahvdroxvmethvlcvclohex-4-ene 
A solution of LiAlH4 (1.20 g, 0.032 mol) in 27 mL of 
THE was placed in a 250 mL three necked flask equipped with 
reflux condenser, dropping funnel and stirrer and protected 
from moisture until completion of the reaction by CaCl2 tube 
attached to opening. Through the dropping funnel, the tetra
i
Ill
ester compound (4.10 g,, 0.011 mol) was introduced at a rate 
such as to produce gentle reflux. Reflux was maintained for 
20 hours with continuous stirring, after which time water 
was added dropwise and cautiously. The resulting solid was 
filtered off and the solvent was removed by rotary 
evaporation to yield white solid. Continuous extraction 
with ether yield pure product as a white powder (0.80 g, 
0.004 mol) (36% yield).
(1,1,2,21-Tetrahvdroxvmethvlcvclohex-4-ene 
mp = 220-225° C (Ref45 mp = 220 °C)
IR (Nujol, cm”1) : 3369, 3049, 2927, 2853, 1651, 1460, 1379, 
1114, 1066, 897
Preparation, of 8,ll-dioxatricvclo(4,3,3,0]dodec-3-ene,[34]
[I,I,2,2]-Tetrahydroxymethylcyclohex-4-ene (3.00 g, 
0.015 mol) was mixed with KHSO4 (3.00 g, 0.022 mol) and 
heated to 190 - 200 °C in an oil bath. After 15 minutes, 
foaming was nearly finished. The reaction mixture became 
solid at a room temperature. The resulting solid was 
extracted with ether. The combined extracts were dried over 
MgSO4 and the solvent removed at reduced pressure to yield 
product as a colorless oil (1.73 g, 0.010 mol) (70% yield). 
Florisil separation was employed to cleanly separate the 
pure compound. A solvent system of ethy!acetate-.hexane in 
the relative ratio 2:8 was used in this separation.
112
8,Il-Dioxatricvclo[4,3,3,01dodec-3-ene, [341 
IR (neat, cm-1) : 3038, 2925, 2853, 1646/ 1460, 1377, 1096, 
1054, 940, 719
1HNMR (300.133 MHz, CDCl3)': 8 2.08 (4H, d, J=3.1Hz), 3.65 
(4H, d, J=8.9Hz), 3.58 (4H, d, J=8.9Hz), 5.84 (2H, t, 
J=3.IHz)
13CNMR (75.4 MHz,CDCl3) : 8 29.76 (t) , 57.67 (s) , 79.42 (t) ,
128.22 (d)
LRMS (EI) m/e (%abundance) : 166 (M+, 14), 148 (31), 135 (30), 
121 (25), 112 (39), 105 (49), 99 (33), 91 (100), 79 
(69) , 67 (29) , 53 (25) , 39 (55)
HRMS (EI) m/e calculated for C10H14O2 = 166.0994 ; found = 
166.0990
Hvdroboration of (341
The alkene, [34] (0.830 g, 0.005 mol) was dissolved in
50 mL of dry THE to which was added NaBH4 (0.190 g) . An 
argon atmosphere was created and the reaction mixture was 
cooled to 0°C. Then BF3O(C2H5)2 (0.620 mL, 0.005 mol) was 
syringed into system. The reaction mixture was warmed to 
room temperature and stirred overnight. Excess NaBH4 was 
quenched with H2O and followed by 3mL of NaOH, 3 mL of H2O2 
and stirred overnight. The reaction mixture was then, 
neutralized with dilute HCl followed by extraction with 
dichloromethane. The extracts were dried over MgSO4 and the 
solvent removed at reduced pressure to yield product as a 
colorless oil (0.900 g, 0.005 mol) (98% yield).
113
8,Il-Dioxatricvclo[4,3,3,01dodec-3-6l, F 661 
IR (neat, cm"1) : 3426, 2968, 2927, 2866, 1653, 1458, 1060, 
912, 730 .
1HNMR (300.133. MHz, CDCl3): 5 1.33-1.93 (6H, m) , 2.25 (1H, 
br s), 3.65-3.86 (9H, m)
13CNMR (75.4 MHz, CDCl3) : 5 26.84 (t) , 30.41 (t) , 37.01 (t) , 
51.82 (s), 53.79 (s), 66.24 (d) , 75.59 (t), 75.75 (t),
79.02 (t), 79.57 (t)
LRMS (EI) m/e (%abundance): 166 (39), 153 (13), 139 (100),
131 (13), 121 (42), 105 (19), 91 (42), 79 (53), 67 
(52), 55 (81), 41 (97)
LRMS (Cl) (NH3) m/e (%abundance) : 185 (M+H+, 100)
HRMS (Cl) m/e calculated for C10H17O3 = 185.1178; found = 
185.1196
Preparation of tosvlate derivatives of [66]
Alcohol, [66] (1.19 g, 6.47 mmol) was dissolved in 3 mL
of dry pyridine under argon atmosphere in ice bath. Then 
TsCl (1.90 g, 9.97 mmol) in pyridine was added dropwise to 
the stirring solution. The reaction mixture was stirred at 
room temperature overnight. The reaction mixture was poured 
over cone. HCl on ice. The resulting acidic solution was 
extracted three times with dichloromethane. The extracts 
were combined and washed with sodium bicarbonate solution 
followed by an aqueous wash. After drying over MgSO4 
removal of solvent by rotary evaporation yielded product. 
Flash separation was employed to cleanly separate the
114
product [88] (1.50 g, 4.44 mmol) (68% yield). A solvent
system of ethylacetate:hexane in the relative ratio 1:1 was 
used in this separation.
S-Tosvl-8,11-dioxatricvclo[4,3,3,01dodecahe, [881 
mp = 68-70°C
IR (neat, cm-1) : 2935, 2869, 1735, 1598, 1448, 1359, 1246, 
11.74, 1096, 1066, 1049, 935, 917, 868, 816, 673 
1HNMR (300.133 MHz, CDCl3): 5 1.48-1.92 (6H, m) , 2.43 (3H,
s), 3.59-3.78 (8H, m) , 4.61-4.70 (1H, m), 7.31 (2H, d, 
J=8.3Hz), 7.75 (2H, d, J=8.3Hz)
13CNMR (75.4 MHz, CDCl3): 5 21.53 (q) , 25.94 (t) , 26.83 (t), 
33.80 (t), 51.78 (s), 53.51 (s), 76.58 (t), 76.66 
(t), 77.34 (d) , 78.16 (t), 78.30 (t), 127.56 (d),
129.81 (d) , 134.46 (s), 144.64 (S)
LRMS (EI) m/e (%abundance):166 (15), 148 (8), 135 (24), 121 
(37), 106 (58), 91 (100), 79 (48), 65 (14), 53 (13), 39 
(30)
HRMS (EI) m/e calculated for C17H22O5S1 = 338.1188; found = 
338.1197
Preparation of para-nitrobenzoate derivatives of [66]
Alcohol, [66] (0.199 g, 1.08 mmol) was dissolved in 3
mL of dry pyridine under argon atmosphere in an ice bath. 
Then PNBCl (0.306 g, 1.65 mmol) was added dropwise to the 
stirring solution. The reaction mixture was stirred at room 
temperature overnight. The reaction mixture was poured over 
cone. HCl on ice. The resulting acidic solution was
extracted three times with dichior©methane. The extracts 
were combined and washed with sodium bicarbonate solution 
followed by an aqueous wash. After drying over MgSO4 and 
the removal of solvent by rotary evaporation to yield 
product. Flash separation was employed to cleanly separate 
the product, [40] (0.32 g, 0.961 mmol) (87% yield). A
solvent system of ethylacetate:hexane in the relative ratio 
1:1 was used in this separation.
para-Nitrobenzoate-8,11-dioxatricvclo14,3,3,01dodecane, [40] 
mp = 78-80°C
1HNMR (300.133 MHz, CDCl3): 5 1.62-2.09(6H, m), 3.67-3.82 
(BH, m), 5.16-5.24 (1H, m), 8.11-8.23 (4H, m)
13CNMR (75.4 MHz, CDCl3) : 5 26.16 (t), 32.90 (t) , (two carbon 
overlap), 52.00 (s), 53.36 (s), 70.72 (d), 76.15 (t),
76.55 (t), 78.13 (t) , 78.59 (t), 123.41 (d) , 130.50 
(d), 135.68 (s), 150.54 (s), 163.92 (s)
LRMS (ET) m/e (%abundance) : 333 (M+, I) , 303 (12) , 183 (6) , 
166 (76), 150 (72), 136 (92), 120 (100), 104 (60), 91 
(60), 79 (48), 67 (26), 55 (18), 41 (38)
HRMS (EI) m/e calculated for C17H19O6N1 = 333.1212; found = 
333.1212
Preparation of 4-biphenvl carboxylate derivatives of [66]
Alcohol, [66] (0.115 g, 0.623 mmol) was dissolved in 5
mL of dry pyridine under argon atmosphere in ice bath. Then 
4-biphenyl carbonyl chloride (0.202 g 0.935 mmol) was added 
dropwise to the stirring solution. The reaction mixture was
115
I
116
stirred at room temperature overnight. The reaction mixture 
was poured over cone. HCl on ice. The resulting acidic 
solution was extracted three times with dichloromethane.
The extracts were combined and washed with sodium 
bicarbonate solution followed by an aqueous wash. After 
drying over MgSO4 solvent was removed by rotary evaporation 
to yield the product (0.203 gr 0.558 mmol) (90% yield).
Flash separation was employed to cleanly separate the pure 
product [95-OBP]. A solvent system of ethylacetate:hexane 
in the relative ratio 1:1 was used in this separation. 
Crystallization of the product was accomplished in 
hexane:dichloromethane in a relative ratio of 10:1, 
respectively^
4-Biphenyl carboxvlate-8,11-dioxatricvclo T4,3,3,Oldodecane,
T95-OBPI *1
mp = IOS-Ild0C
1HNMR (300.133 MHz, CDCl3) : 8 1.62-2.09 (6H, m) , 3.75-3.86 
(BH, m) , 5.19-5.27 (1H, m), 7.32-8.09 (9H, m)
13CNMR (75.4 MHz, CDCl3): 5 26.03 (t) , 26.21 (t) , 32.87 (t) , 
51.87 (s), 53.20 (s), 69.35 (d) , 76.42 (t), 76.71 (t), 
78.05 (t), 78.47 (t), 126.87 (d), 127.06 (d), 127.98 
(d), 128.75 (d), 129.04 (s), 129.88 (d), 139.77 (s),
145.51 (s), 165.58 (s)
LRMS (BI) m/e (%abundance): 364 (M+, 15), 198 (44), 181 
(100), 166 (69), 152 (41), 136 (72), 121 (21), 107 
(18), 91 (22), 79 (19), 41 (15)
117
364.1675
Crystallization of the product, [95-OBP] was 
accomplished in dichloromethane:hexane in a relative ratio 
of 10:1.
X-ray analysis:
HRMS (EI) m/e calculated for C23H24O4 = 364.1675; found =
Figure 73. ORTEP Drawing of [95-OBP].
118
Table 40. Bond Lengths (A) of [95-OBP].
C(I) -C (2) 1.532 (4) CO) -C (6) 1.536(4)
C(I) -C (8) 1.510 (5) C(I) -C (9) 1.530 (4)
C (2) -C(3) 1.515 (4) CO) -C (4) 1.502 (4)
C (3) -0(3) 1.465 (4) C (4) -C(5) 1.512(5)
C(5) -C (6) 1.527 (4) C (6)-C (7) 1.522 (5)
C (6) -C(IO) 1.512(5) C (7)-0(1) 1.396 (5)
0(1) -C (8) 1.412(5) C (9) -0(2) 1.406 (4)
0(2) -C(IO) 1.413 (4) 0(3) -C(Il) 1.343(4)
C(Il) -0(4) 1.206(4) C(Il) -C (12) 1.479(4)
C (12)-C(13) 1.382 (4) C (12)-C (17) 1.387(4)
C (13)-C (14) 1.389(4) C (14)-C(15) 1.386(4)
C (15)-C(16) 1.395(4) C (15)-C (18) 1.480 (4)
C (16) -C(17) 1.382(4) C (18)-C(19) 1.390 (4)
C (18) -C(23) 1.390(4) C (19)-C (20) 1.391 (5)
C (20) -C (21) 1.382(5) C (21)-C(22) 1.370 (5)
C (22)-C(23) 1.385(5)
Table 41. Bond Angles ( °) of [95-OBP].
C (2) -C(I) -C (6) 114.6(2) C (2) -C(I) -C(8) 114.1(3)
C (6) -C(I) -C(8) 102.9(3) C (2) -C(I) -C (9) 110.7(3)
C (6) -C(I) -C (9) 100.9(2) C (8) -C(I) -C (9) 112.8(3)
C(I) -C (2) -CO) 112.9(3) C(2) -CO) -C (4) 110.7(2)
C (2) -CO) -0(3) 109.6(2) C (4) -CO) -0(3) 106.7(2)
CO) -C (4) -C(5) 109.6(3) C (4) -C(5) -C (6) 114.6(3)
119
(Table 41. Continued)
C(I)-C(6)-C(5) 114.3(3) C(I)-C(6)-C(7) 101.0(3)
C (5) -C (6) -C (7) H O  . 6 (3) C(I) -C (6) -C(IO) 103.4(2)
C (5) -C (6) -C(IO) 114.3(3) C (7) -C (6) -C(IO) 112.2(3)
C (6) -C (7) -0(1) 108.5(3) C (7) -O(I) -C (8) 110.2(3)
C(I) -C (8) -0(1) 107.3(3) C(I) -C (9) -0(2) 108.6(3)
C (9) -0(2) -C(IO) 110.1(3) C(6) -C(IO) -0(2) 107.1(3)
C (3) -0(3) -C(Il) 116.7(2) 0(3)-C(Il)-0(4) 123.2(3)
0(3) -C(Il) -C (12) 112.9(3) 0(4) -C(Il) -C (12) 123.9(3)
C(Il)-C(12)-C(13) 123.7(3) C(H)-C (12)-C (17) 117.8(3)
C (13)-C(12)-C(17) 118.5(3) C (12) -C (13) -C (,14) 120.7(3)
C (13) -C (14) -C(IS) 121.1(3) C (14)-C(15)-C(16) 117.9(3)
C(14)-C(IS)-C(18) 122.2 (3) C (16) -C (15) -C (18) 119.9(3)
C (15)-C(16)-C(17) 120.9(3) C(12)-C(17) -C (16) 120.9(3)
C(IS) -C (18) -C (19) 121.1(3) C (15)-C(18)-C(23) 121.6(3)
C (19)-C(18)-C(23) 1 1 7.2 (3) ; C (18)-C(19)-C (20) 121.6(3)
C (19) -C (20) -C (21) 119.5 (3) C (20) -C (21) -C (22) 119.9(3)
C (21)-C(22)^C(23) 120.3(3) C (18)-C(23)-C(22) 121.5(3)
Preparation of I,5-dibromoethvl ether, [24]
I,5-Dihydroxyethyl ether (24.0 g, 0.226 mol) was placed 
in a 100 mL flask under argon. PBr3 (20.0 mL, 0.211 mol) 
was added dropwise. The reaction mixture was refluxed 
overnight, after the solution was poured over ice water.
The resulting solution was extracted three times with 
dichloromethane. The combined extracts were.dried over
120
MgSO4 and the solvent was removed by rotary evaporation to 
yield product as a colorless oil. (46.6 g, 0.201 mol) (89% 
yield)
IfS-Dibromoethvl ether, f241
IR (neat, cm"1) : 2964, 2880, 2852, 1419, 1357, 1279, 1.223, 
1190, 1117, 1038, 949, 663
1HNMR (300.133 MHz, CDCl3): 5 3.44 (4H, t, J=6.2Hz), 3.79 
(4H, t, J=6.2Hz)
13CNMR (75.4 MHz, CDCl3) : 5 29.97 (t) , 70.94 (t)
LRMS (EI) m/e: 232, 231, 230, 139, 137, 109, 107, 95, 93, 43 
Preparation of cis-1,6-dicarbomethoxv-9-oxa-bicvclo 
(5,4,01undec-3-ene, [231
A solution of 100 mL of dry THE, 70 mL of 2.5 M n-BuLi 
(0.175 mol) and 25 mL of diisopropylamine (0.180 mol) was 
stirred under argon at -IO0C for 30 minutes. The 
temperature was taken down to -78 0C and cis-3,4- 
dicarbomethoxycyclohexene (14.0 g, 0.071 mol) was added 
dropwise, creating a bright red solution. After addition 
was completed the solution was allowed to stir for 15 
minutes. I,5-dibromoethyl ether (9 mL, 0.085 mol) was added 
dropwise. The solution was allowed to warm to room 
temperature and stirred overnight. The reaction mixture was 
then neutralized with dilute HCl. The resulting phases were 
separated and the remaining solution was extracted with 
dichloromethane. The combined extracts were dried over 
MgSO4 and the solvent removed by rotary evaporation. The
1 1  .Ii
121
resulting liquid was distilled to yield a product as a 
yellow, viscous oil (11.8 g, 0.044 mol) (62% yield). 
cis-1,6-Dicarbomethoxv-9-oxa-bicvclo[5,4,01undec-3-ene, [231 
IR (neat, cm'1) : 3028, 2948, 1734, 1434, 1280, 1200, 1145, 
753, 673
1HNMR (300.133 MHz, CDCl3) : 5 2.02-2.28 (4H, m) , 2.39 (2H, 
d, J=17.4Hz), 2.66 (2H, d, J=17.4Hz), 3.65 (6H, s), 
3.72-3.77 (4H, in) , 5.56 (2H, s)
13CNMR (75.4 MHz, CDCl3) : 5 34.00 (t) , 36.72 (t) , 49.10 (s) ,
51.71 (q), 65.88 (t), 124.10 (d), 175.64 (s)
LRMS (BI) m/e: 268, 236, 224, 208, 178, 163 (base), 150,
131, 118, 91, 77, 59, 41
HRMS (BI) m/e calculated for C14H20O5 = 268.1311 ; found = 
268.1301
Preparation of cis-1,6-dihvdroxvmethv.l-9-oxabicvclo 
(5,4,01undec-3-ene
A solution of [23] 1 (3.30 g, 0.0123 mol) in 10 mL of dry 
THE was added dropwise at 0°C to a stirring solution of LAH 
(0.700 g, 0.0185 mol) in 100 mL of dry THE. The reaction 
mixture was stirred overnight at a room temperature and then 
hydrolyzed with wet ether. The white lithium salts were 
filtered off and the solvent removed by rotary evaporation 
to yield (1.50 g, 7.10 mmol) product as a white solid. (58% 
yield)
i
I122
cis-lr6-Dihvdroxvmethvl-9-oxabicvclo[5,4,Olundec-3-ene 
IR (Nujol, cm"1) : 3215, 3012, 2862, 1458, 1374, 1122, 1026, 
666
1HNMR (300.133 MHz, CDCl3) : 5 1.79 (4H, t, J= 6.5Hz) , 2.01
(2H, d), 2.10 (2H, d), 3.67 (4H, s), 3.65-3.80 (4H, m), 
5.56 (2H, t, J=I.3Hz)
13CNMR (75.4 MHz, CDCl3) : 8 33.18 (t) , 35,75 (t) , 42.00 (s) , 
64.44 (t), 67.39 (t), 124.27 (d)
LRMS (EI) m/e: 176, 148, 117, 91 (base), 77, 65, 44 
LRMS (Cl) (Methane) m/e (%abundance) : 213 (M+H+, 7) , 195 
(100), 177 (27), 165 (26),159 (18), 149 (21), 133 
(32), 121 (19), 107 (21)
HRMS (Cl) m/e calculated for C12H21O3 = 213.1491/ found = 
213.1462
Preparation of 8,12-dioxatricvcloF5,4,3,0]tetradec-3-ene, 
(281
cis-1,6-Dihydroxymethyl-9-oxabicyclo[5,4,0]undec-3-ene 
(1.22 g, 5.76 mmol) was dissolved in 5 mL of dry pyridine 
and then 0.45 mL of MsCl (0.660 g, 5.76 mmol) were added 
dropwise to the stirring solution under argon in an ice 
bath. The reaction mixture was stirred at room temperature 
overnight. The reaction mixture was then poured over 
concentrated HCl on ice to acidify. Extraction with 
dichloromethane yielded the desired product as a colorless 
oil (1.03 g, 5.30 mmol) (92% yield). Florisil separation 
was employed to cleanly separate the pure product. A
i
123
solvent system of ethylacetate:hexane in the relative ratio 
3:7 was used in this separation.
8,12-Dioxatricvclo[5,4,3,01tetradec-3-ene, [281 
IR (neat, CirT1) : 3036, 2922, 2860, 1460, 1273, 1126, 1047, 
950, 993, 814, 712, 661
1HNMR (300.133 MHz, CDCl3): 5 1.67-2.05 (8H, m), 3.55 (2H,
d, J=8.5Hz), 3.68 (2H, d, J=8.5Hz), 3.64-3.81 (4H, m), 
5.78-5.80 (2H, m)
13CNMR (75.4 MHz, CDCl3) : 5 32.73 (t) , 40.15 (t) , 47.58 (s) , 
65.83 (t), 80.20 (t), 127.09 (d)
LRMS (EI) m/e (%abundance) : 194 (M+, 2) , 176 (7) , 166 (61) , 
139(44), 131 (38), 119(49), 105(72), 91 (100), 79(68),
67 (35), 53(28), 41 (59)
HRMS (EI) m/e calculated for C12H180Z = 194.1307 ; found = 
194.1306
Hvdroboration of 8,12-dioxatricvclof5,4,3,01 tetradec-3-ene, 
(281
The propellane, [28] (0.260 g, 1.340 mmol) was
dissolved in 5 mL of dry THF and then 2 mL of BH3:THF 
(0.0312 g, 2.26 mmol) were added dropwise to the stirring 
solution under argon at OeC. The solution was warmed to 
room temperature and stirred overnight. The reaction 
mixture was quenched with a small amount of water followed 
by the slow addition of I mL of SN-NaOH and I mL 30% H2O2. 
After the addition was complete, the solution was stirred 
for overnight. The reaction mixture was then neutralized
i
L i
124
with dilute HCl followed by extraction with dichloromethane. 
The solvent was dried over MgSO4 and the solvent removed by 
rotary evaporation to yield alcohol mixture (0.284 g, 1.34 
mmol) (99% yield). Capillary GC analysis showed the syn- 
and anti- alcohol in the ratio of 26:74. 
svn-8,12-Dioxatricvclo(5,4,3,01tetradec-3-ol, F 67-svnl 
IR (neat, cm"1) :3421, 2930, 2868, 1714, 1456, 1358, 1260, 
1118, 1051, 946, 922
1HNMR (300.133 MHz, CDCl3) : 5 1.32-2.37 (10H, m) , 3.47 (1H, 
d, J=8.4Hz), 3.60 (1H, d, J=8.1Hz), 3.90 (1H, d, 
J=8.3Hz), 4.09 (IH, d, J=8.4Hz), 3.59-4.01 (4H, m)
13CNMR (75.4 MHz,CDCl3) : 5 25.78 (t) , 30.74 (t) , 35.95 (t) , 
36.40 (t), 43.05 (t), 45.18 (s), 46.00 (s), 62.65 (t), 
64.38 (t), 66.78 (d) , 78.22 (t), 78.41 (t)
LRMS (EI) m/e (%abundance) : 194 (7), 166 (24), 149 (10) , 139 
(100), 131 (14), 121 (56), 105 (34), 91 (70), 79 (74), 
67 (51), 55 (59), 41 (80) .
LRMS (Cl) (Methane) m/e (%abundance) :213 (M+H+, 13) , 211 
(34), 195 (100), 177 (17), 165 (19), 159 (14), 151
(22), 139 (19), 133 (25), 121 (26), 107 (20), 97 (13), 
93 (16)
HRMS (Cl) m/e calculated for C12H21O3 = 213.1491; found = 
213.1487
anti-8,12-Dioxatricvclo15,4,3,01tetradec-3-ol, [67-anti]
IR (neat, cm"1) : 3421, 293.0, 2868, 1714, 1456, 1358, 1260, 
1118, 1051, 946, 922
,
I
125
1HNMR (300.133 MHzr CDCl3) : 8 1.27-2.04 (IOHr m) r 3.46 (IHr 
dr J=8.4Hz)r 3.49 (IHr dr J=8.3Hz), 3.91 (IHr dr 
J=8.4Hz), 3.99 (IHr dr J=8.4Hz)r 3.58-3.95 (4Hr m)
13CNMR (75.4 MHzrCDCl3) :5 31.18 (t) r 33.41 (t) r 35.14 (t) r
36.04 (t)r 37.14 (t)r 44.00 (s)r 47.44 (s)r 62:53 (t)r 
64.51 (t)r 66.95 (t)r 77.33 (t)r 79.00 (t)
LRMS (EI) m/e (%abundance) : 212 (M+r 2) r 194 (7) r 166 (45) , 
149 (16)r 139 (97)r 131 (22)r 121 (55)r 105 (44)r 91 
(92)r 79 (IOO)r 67 (60)r 55 (60)r 41 (84)
LRMS (Cl) (Methane) m/e (%abundance) : 213 (M+H+r 13) , 211 
(20)r 195 (IOO)r 177 (23)r 165 (17)r 159 (13)r 151
(23)> 139 (19)r 133 (27)r 121 (25)r 107 (15)r 93 (13) 
HRMS (Cl) m/e calculated for C12H21O3 = 213.1491/ found = 
213.1488
Preparation of para-nitrobenzoate derivatives of 8,12- 
dioxatricvclo[5,4,3,01tetradec-3^ene, (281
The mixture of syn- and anti- alcohols derived from the 
hydroboration of [28] (0.284gr 1.11 mmol) was dissolved in
10 mL of dry pyridine and an argon atmosphere was created. 
Then PNBCl (0.310gr 1.67 mmol) was dissolved in dry pyridine 
and added dropwise to the stirring solution at 0°C. The 
reaction was stirred at room temperature overnight. The 
reaction mixture was poured over ice water and neutralized 
with HCl. A white solid, (pyridine hydrochloride) formed 
which was filtered off and the resulting solution was 
extracted three times with dichloromethane. The extracts
126
were combined and washed with sodium bicarbonate solution■ 
followed by an aqueous wash. After drying over MgSO4 and 
the solvent was removed by rotary evaporation to yield the 
product as a white solid. Flash chromatography was employed 
to cleanly isolate the isomers (0.313 gr 0.867 mmol) (78% 
yield). A solvent system of ethylacetate:hexane in the 
relative ratio 1:1 was used in this separation; 
svn-3-para-Nitrobenzoate-8,12-dioxatficvclo(5,4,3,01 
tetradecane, r41-sy.nl
1HNMR (300.133 MHz, CDCl3): 5 1.45-2.30 (10H, m), 3.61 (1H, 
d, J=8.4Hz), 3.71 (1H, d, J=8:4Hz)f 3.91 (1H, df
J=8.4Hz)r 4.07 (!Hf d, J-8;4Hz), 3.67-3.86 (4H, m), 
5.21-5.30 (IH, m) , 8.14-8.28 (4H, m)
13CNMR (75.4 MHzfCDCl3) : 5 26.18 (t) , 26.67 (t) 7 35:76 (t) ,
36.17 (t), 38:02 (t), 45.07 (s), 46:04 (s), 62,82 (t),
64.10 (t), 71.65 (d) , 78.16 (t) (2 carbon), 123.49 (d),
130.61 (d), 135.90 (S)7 150.52 (s)7 164.05 (s)
LRMS (EI) m/e (%abundance): 210 (9), 164 (13)7 151 (100)7 
136 (28)7 121 (29)7 109 (31)7 91 (Sl)7 79 (34)7 67
(24), 55 (21)
LRMS (HPEC) (NH3) m/e (%abundance) : 361 (M+7 100) 7 345 (4) 7 
329 (5), 148 (2), 127 (I)
HRMS (HPEC) (NH3) m/e calculated for C19H23O6N1 = 361.1525; 
found = 361.1529
127
anfci-3-para-Nitrobenzoate-8,12^dioxatricvclo[5,4,3,01
tetradecane, T41-antil
1HNMR (300.133 MHz, CDCl3): 5 l;36-2.42 (10H,m)f 3.55 (1H, 
d/ J=8.3Hz), 3.58 (IHz dz J=SHz)z 3.91 (IHz dz 
J=8.3Hz)z 4.09(IHz dz J=8.5Hz)z 3.68-3.86 (4HZ m)z 
5,25-5.35 (IHz m)z 8.16-8.28 (4HZ m)
13CNMR (75.4 MHzzCDCl3): 5 26.98 (t) z 32.40 (t) z 32; 53 (t) z
35;47 (t)z 36.89 (t)z 44.19 (s) z 47.24 (s)z 62.87 (t),
64.70 (t), 71.85 (d)z 77.50 (t)z 78.88 (t)z 123.48 (d)z
130.65 (d)z 135.95 (s)z 150.59 (s)z 164.14 (s)
LRMS (EI) m/e (%abundance) : 196 (10), 165 (47) , 151 (24) ,
137 (61), 123 (100), 107 (30), 93 (58), 79 (7), 67 
(54), 55 (37)
LRMS (HPEC) (NH3) m/e (%abundance) : 361 (M+, 100) , 148 (30) 
HRMS (HPEC) (NH3) m/e calculated for C19H23O6N1 = 361.1525; 
found = 361.1511
128
Crystallization of the product, [41-anti] was 
accomplished in dichloromethane:hexane in a relative ratio 
of 1:20 respectively.
X-ray analysis:
02
Figure 74. ORTEP Drawing of [41-anti].
Table 42. Bond Lengths (A) of [41-anti].
Cd) -C (2) 1.537 (9) C(I) -C (6) 1.563 (7)
C(I) -C (8) 1.534 (11) C(I) -C (9) 1.508 (8)
C (2)-C(3) 1.504 (7) CO) -C (4) 1.504 (7)
C O ) -0(3) 1.463 (8) C (4) -Cd) 1.527 (9)
C(5) -C (6) 1.543(8) C (6)-C(7) 1.543 (11)
C( (6) -C (12) 1.524 (11) C (7) -0(1) 1.411(9)
0(1) -C(8) 1.423 (9) C (9)-C(IO) 1.489(13)
C(IO) -H(IOa) 0.960 (I) C(IO) -H(IOb) 0.960 (I)
C(IO) -H(IOc) 0.960 (I) C (10) -H(IOd) 0.960 (I)
C(IO) -0(2) 1.430 (11) C(IO) -0(2' ) 1.430 (11)
1 1
129
(Table 42. Continued)
0(2) -C(Il) 1.430 (12) 0(2') -C (11') 1:430(18)
C(Il)-H(Ila) 0.960 (I) C(Il) -H(Ilb) 0:960 (I)
C(Il) -C (12) 1.540 (13) C(ll')-H(Ilc) 0.960(I)
C(ll') -H(Ild) 0.960 (I) C (ll')-C(12) I; 540 (12)
C (12)-H(12a) 0.960 (I) C (12)-H(12b) 0.960 (I)
C (12)-H(12c) . 0.960 (I) C (12)-H(12d) 0,960(I)
0(3) -C(13) 1.328 (7) C (13)-0(4) 1:189 (9)
C (13) -C(14) 1.514 (9) C (14) -C (15) 1.364(8)
C (14) -C(19) 1.385 (9) C (15)-C(16) 1:391 (10)
C (16)-C(17) 1.382 (10) C (17)-C(18) 1.373 (8)
C (17)-N 1.493 (10) C (18)-C(19) 1:380 (9)
N-O (5) 1.201(8) N-O(6) 1:200 (10)
Table 43. Bond Angles ( °) of [41-anti].
C (2) -C (I) -C (6) 113.0(4) 0 1 0 H 1 O CO 111.2(6)
C (6) -C(I) -C (8) 100.4(5) C (2) -C(I) -C (9) 110:1(5)
C (6) -C(I) -C (9) 114.9(5) C (8) -C(I) -C (9) 106.7(5)
C(I) -C (2) -C (3) 115.0(5) C (2) -C (3) -C (4) 110.6(5)
CO01COUCMU 109.4 (5) C (4) -C (3) -0 (3) 107.4(4)
C (3) -C (4) -C (5) 108.2(5) C (4) -C (5) -C (6) 112.2(5)
C(I) -C (6) -C (5) 110.3(5) C (I) -C (6) -C (7) 99.5(4)
C (5) -C (6) -C (7) 107.7(6) C(I) -C (6) -C (12) 117.3(6)
C (5) -C (6) -C (12) 109.7(5) C (7)-C(6)-C(12) 111.7(5)
C (6)-C(7)-0(1) 107.3(5) C (7) -0(1) -C (8) 109.8(6)
I130
(Table 43. Continued)
C(I)-C(S)-O(I) 106.9(5) 0 H 1 0 <£> 1 O H O 120.0(6)
C(9) -C(IO) -H(IOa) 107 0(1) C (9) -C(IO) -H(IOb) 108.2(1)
H(IOa) -C(IO) -H(IOb) 109.7(1) C (9) -C(IO) -C(IOc) 106.6(1)
C(9) -C(IO) -H(IOd) 107.0(1) H(IOc) -C(IO) -H(IOd) 109.5(1)
C O ) -C(IO)-0(2) 114.7 (8) H(IOa) -C(IO) -0(2) 107.9(1)
H(IOb) -C(IO) -0(2) 108.2(1) C (9)-C(10)-0 (2f) 119;6(8)
H(IOc) -C(IO) -0(2') 106.6(1) H(IOd)-C(IO)-0(2f) 107.3(1)
C(IO) -0(2) -C(Il) 107.5(8) C(IO) -0 (2f ) -C (Ilf) 107.8(12)
0(2) -C(Il) -H(Ila) 108.2(1) 0(2) -C(Il) -H(Ilb) 108.6(I)
H(Ila) -C(Il) -H(Ilb) 109.4 (I) 0(2)-C(Il)-C(12) 113.8(10)
H(Ila) -C(Il) -C (12) 108.3(1) H(Ilb) -C(Il) -C (12) 108.4(1)
0(2')-C(Ilf) -H (Ilc) 110.0(1) 0 (2f) -C(llf) -H(Ild) 110.5(1)
H(Ilc) -C(Ilf)H- (Ild) 110.0(1) 0(2f)-C(Ilf)-C(12) 104:9(10)
H(IlC) -C(Ilf) -C (12) 110.3(1) H(Ild) -C(llf ) -C (12) 111.0(1)
C(G)-C(12)-C(Il) 124. (7) C (6)-C(12)-C(Ilf) 121.7(8)
C(G) -C (12) -H (12a) 105.6(1) C(Il) -C (12) -H (12a) 105.7(1)
C(G) -C (12) -H (12b) 105.6 (I) C(Il) -C (12) -H (12b) 105.7(1)
H (12a) -C (12) -H(IZb) 109.6 (I) C (6) -C(12)-H(12c) 106.3(1)
C(Ilf)-C(12)-H(12c) 106.2(1) C (6)-C(12)-H(12d) 106.2(1)
C(Ilf)-C(12)-H(12d) 106.6(1) H (12c) -C(12)-H(12d) 109.6 (I)
C (3) -0(3) -C (13) 116.1(5) 0(3) -C (13) -0(4) 125.2(6)
0 (3) -C (13) -C (14) 111.7(6) 0(4) -C(13) -C (14) 123.1(5)
C (13)-C(14)-C(15) 117.4(6) C (13)-C(14)-C(19) 122.1(5)
C (15)-C(14)-C(19) 120.5(6) C.(14) -C (15) -C (16) 121.6(6)
C (15) -C(IG) -C (17) 116.3(6) C (16)-C(17)-C(18) 123.5(6)
131
(Table .43. Continued)
C (16)-C(17)-N 117.3(6) C (18)-C(17)-N 119.2(6)
C (17)-C(18)-C(19) 118.6(6) C (14)-C(19)-C(18) 119.6(5)
C (17)-N-O(5) 118.5(7) C (17)-N-O(6) 117.7(6)
O (5) -N-Q (6) 123.8(7)
Preparation of .gyn—tosylate derivative of [28T
The syn-para-nitrobenzoate derivative of[28] (33.0 mg,
0.0914 mmol) was dissolved in 0.2 mL dichloromethane and 
then added to a 80% aqueous ethanol solution that was 0.5% 
by weight in KOH. The reaction was stirred overnight. Most 
of the solvent was removed by rotary evaporation, then 5 mL 
of water was added to the residue. The solution was 
extracted with dichloromethane. The combined extracts were 
dried over MgSO4 and the solvent was removed by rotary 
evaporation to give syn-alcohol(17.8 mg, 0.0841 mmol) (92% 
yield). The syn-alcohol (12.7 mg, 0.0599 mmol) was 
dissolved in 0.2 mL of dichloromethane to which was added I 
mL of pyridine. The solution was cooled to 0°C and TsCl 
(45.8mg, 0.240 mmol) was added dropwise. The reaction was 
warmed to room temperature and stirred overnight. The 
solution was poured over ice water to neutralize with HCl 
and the solution was extracted with dichloromethane. The 
extracts were combined and washed with sodium bicarbonate 
solution followed by an aqueous wash. After drying over 
MgSO4 the solvent was removed by rotary evaporation to yield
132
syn-tosylate as a white solid . Flash chromatography was 
employed to cleanly isolate the pure syn-tosylate (13.59 mg, 
0.0371 mmol)(62% yield) * A solvent system of 
ethylacetate:hexane in the relative ration 1:1 was used in 
this separation.
Preparation of anti-tosylate derivative of [281
In a similar fashion, saponification of the anti-para- 
nitrobenzoate derivative of [28]; (38.8 mg, 0.107 mmol)
afforded 17.7 mg (0.0834 mmol) of the anti-alcohol (78% 
yield). Using the identical workup as reported above, the 
anti-alcohol (17.7 mg, 0.0834 mmol) were dissolved in 0.2 mL 
of dichloromethane to which was added I mL of pyridine and 
TSCl (24.0 mg, 0.16 mmol). The anti-tosylate was cleanly 
separated as a white solid 14.04 mg (0.0384 mmol) (46% 
yield)
anti-Tosvl-8,12-dioxatricvclo[5.4.3.01tetradecane, [891 
1HNMR (300.133 MHz, CDCl3): 8 1.32-2.29 (10H,m) , 2.43 (3H,
s), 3.46 (1H, d, J=8.7Hz), 3.50 (1H, d, J=8.5 Hz), 3.80 
(1H, d, J=8.5Hz), 3.84 (1H, d, J=8.6Hz), 3.62-3.80 (4H, 
m), 4.71-4.81 (1H, m), 7.32 (2H, d, J=8.3Hz), 7.77 (2H, 
d, J=8.3Hz)
13CNMR (75.4 MHz, CDCl3) : 5 21.61 (g) , 27.61 (t) , 32.07 (t) , 
34.04 (t), 35.77 (t), 37.09 (t), 44.03 (s), 47.35 (s), 
63.02 (t), 64.67 (t), 77.66 (t), 78.56 (d) , 78.86 (t),
127.62 (d) , 129.80 (d), 134.68 (s), 144.55 (S)
133
LRMS (BI) m/e (%abundance): 212 (I), 194 (18), 166 (23), 139 
(19) r 119 (22) , 105 (29) , 91 (100) , 79 (54) , 65 (28) ,
55 (17) , 41 (20)
LRMS (Cl) (NH3) m/e (%abundance) : 384 (M+NH4+, 9) 7 212 (69) , 
195 (100)
HRMS (BI) m/e calculated for C23H26O1S3 = 366.1501; found = 
366.1502
Preparation of cis-1,6^dicarbomethoxvbicvclo(4,2,OToct-3- 
ene, T 2 01
A solution of 200 mL of dry THF, 140 mL of 2.5 M n-BuLi 
(0.350 mol) and 50 mL of diisopropylamine (0.360 mol) was 
stirred under argon at -10°C for 30 minutes. The 
temperature was taken down to -78°C and cls-3,4- 
dicarbomethoxy cyclohexene 28 g (0.141 mol) was added 
dropwise, creating a bright red solution. After addition 
was completed, the solution was allowed to stir for 15 
minutes and 14.56 mL of 1,2-dibromo ethane (0.169 mol) were 
added dropwise. The solution was allowed to warm to room 
temperature and stirred overnight. Identical workup (page 
120) and distillation yielded product as a Colorless oil 
(15.8 g, 0.071 mol)(50% yield).
cis-1,6-Dicarbomethoxvbicvclo[4,2,01oct-3-ene, [20]
IR (neat, cm"1) : 3037, 2997, 2950, 2844, 1735, 1436, 1277, 
1237, 1118, 1011
1HNMR (300.133 MHz, CDCl3); 5 1.59-2.42 (8H, m) , 3.62 (6H, 
s), 5.99 (2H, t, J=I.4Hz)
134
13CNMR (75.4 MHz, CDCl3): 5 26.02 (t) , 31.62 (t) , 50.14 (s) , 
51.67 (q), 127.15 (d), 176.05 (s)
LRMS (EI) m/e: 192, 164, 133, 105 (base), 91, 77, 59, 51,
41
LRMS (Cl) (Methane) m/e (%abundance) : 225 (M+H+, 39) , 193 
(100), 165 (18), 105 (14)
HRMS (Cl) m/e calculated for C12H17O4 = 225.1127; found = 
225.1149
Preparation of cis-1,6-dihvdroxvmethvlbicvclo[4,2,01 oct-3- 
ene
A solution of [20] (8.60 g, 0.0384 mol) in 20 mL of dry
THF was added dropwise at O0C to a stirring solution of LAH 
(2.20 g, 0.0576 mol) in 250 mL of dry THE. The reaction 
mixture was stirred overnight at a room temperature. An 
identical workup (page 121) yielded a product as a white 
solid (5.40 g, 0.032 mol) (84% yield). 
cis-1,6-Dihvdroxvmethylbicvclo[4,2,0]oct-3^ene 
mp = 112-114'C
IR (nujol, cnT1) : 3256, 3023, 2964, 2897, 2837, 1642, 1483, 
1430, 1317, 1184, 1038, 865, 686
1HNMR (300;133 MHz, CDCl3): 5 1.35-1.50 (4H, m) , 1.68-1.75 
(2H, m), 2,37 (2H, d, J=14.9Hz), 3.23 (2H, d, .
J=Il.4Hz), 4.01 (2H, d, J=Il.4Hz), 5.97 (2H, t,
J=3.2Hz)
13CNMR (75.4 MHz, CDCl3) : 5 24.88 (t) , 32.78 (t) , 44.07 (s) , 
68.01 (t), 128.01 (d)
135
LRMS (EI) m/e: 150, 132, 117, 91 (base), 79, 65, 51, 41 
LRMS (Cl) (Methane) m/e (%abundance) : 169 (M+H+, 19) , 151 
(20), 133 (100), 121 (21), 105 (17)
HRMS (Cl) m/e calculated for C10H17O2 = 169.1129; found = 
169.1237
Preparation of 8-oxatricvclo[4,3,2,01undec-3-ene, [251
cis-1,6-Dihydroxymethylbicyclo[4,2,0]oct-3-ene (2.92 g, 
0.0174 mol) was dissolved in 5 mL of dry pyridine and then 
1.35 mL of MsCl (1.99 g, 0.0174 mol) were added dropwise to 
the stirring solution under argon in ice bath. The reaction 
mixture was stirred at room temperature overnight.
Identical workup (page 122) and flofisil separation 
(hexane:ethylacetate, 19:1) yield a product as a pale yellow 
oil (1.88 g, 0.0125 mol)(72% yield).
8-Oxatricvclo[4,3,2,01undec-3-ene, (251
IR (neat, cm"1) : 3030, 2964, 2924, 2837, 1642, 1436, 1084, 
1038, 932, 905
ilHNMR (300.133 MHz, CDCl3): 5 1.62-2.13 (8H, m) , 3.29 (2H, 
d, J=8.8Hz), 3.88 (2H, d, J=8.8Hz), 5.93 (2H, m)
13CNMR (75.4 MHz, CDCl3) : .5 28.50 (t) , 30.78 (t) , 47.05 (s) , 
80.41 (t), 127.39 (d)
LRMS (BI) m/e (%abundance): 150 (M+, 27), 122 (18), 107 
(11), 93 (100), 79 (39), 65 (13), 53 (12), 39 (34)
HRMS (EI) m/e calculated for C10H14O1 = 150.1045; found =
150.1045
I I
136
Hvdroboration of 8-oxatricyclo[4,3,2,01undec-3-ene, 1251 
The propellane, [25], (0 * 104 g, 0.693 mmol) was
dissolved in 10 mL of dry THF to which was added NaBH4 (26.2 
mg, 0.693 mmol). An argon atmosphere was created and the 
reaction was cooled to 0°C. Then BF3O(C2H5)2 (0.085 mL,
0.693 mmol) were syringed into system. The solution was 
warmed to room temperature and stirred overnight. The 
reaction was quenched with a small amount of water followed 
by the slow addition of 0.5.mL of SN-NaOH and 0.5 mL of 30% 
H2O2. After the addition was complete, the solution was 
stirred overnight. The reaction mixture was then 
neutralized. Identical workup (page 123) yielded 57:43 
mixture of syn-OH and anti-OH as a colorless oil (0;093 g, 
0.554 mmol) (80% yield).
syn-8-Oxatricvclo[4,3,2,01undec-3-ol, F 62-svnl 
IR (neat, cm"1) : 3428, 2930, 2857, 1775, 1456, 1363, 1171, 
1038, 925, 732, 666
1HNMR (300.133 MHz, CDCl3): 5 1.21-1.95 (IOH, m) , 3.36 (1H, 
d, J=8.9Hz), 3.49 (1H, d, J=6.9Hz), 3.74 (1H, d,
J=8.9Hz), 3.90 (1H, d, J=8.9Hz), 3.93-4.02 (1H, m) 
13CNMR (75.4 MHz, CDCl3) : 5 26.89 (t) , 28.38 (t) , 28.56 (t) ,
30.37 (t), 40.42 (t), 45.20 (s), 46.57 (s), 67;59 (d), 
79.15 (t), 82.75 (t)
LRMS (EI) m/e (%abundance) ; 168 (M+, I) , 150 (26) , 140 (37) , 
122 (67), 106 (19), 93 (100) , 79 (96), 67 (31), 55 (26)
137
LRMS (Cl) (Methane) m/e (%abundance) : 169 (M+H+A 26) , 151 
(80) 133 (100) 121 (29) 107 (42)'95 (16)
HRMS (Cl) m/e calculated for C10H17O2 = 169*1129; found = 
169.1263
anti-8-Oxatricvclo (4,3,2,01 undec-3^ol, F62-anfcil.
IR (neat, cm"1) : 3428, 2930, 2857, 1775, 1456, 1363, 1171, 
1038, 925, 732, 666
1HNMR (300.133 MHz, CDCl3) : 5 1.32-2.03 (IOH, m) , 2.14 (1H, 
s), 3.32 (1H, d, J=8.9Hz), 3.42 (1H, d, J=9Hz), 3.60- 
3.69 (1H, m), 3.71 (1H, d, J=8.9Hz), 3,91 (lH, d,
J=9.OHz)
13CNMR (75.4 MHz, CDGl3) : 5 25.69 (t) , 29.81 (t) , 29; 86 (t) , 
30.89 (t), 39.80 (t), 44.75 (s), 47.30 (s), 67:14 (d) , 
79.11 (t), 82.07 (t)
LRMS (BI) m/e (%abundance) : 168 (M+, I) , 150 (14) , 140 (61) , 
122 (86), 107 (16), 93 (100), 79 (88), 67 (27), 55 (23) 
LRMS (Cl) (Methane) m/e (%abundance) : 169 (M+H+, 4) , 167 (M- 
H+., 14), 151 (60) , 133 (100) , 121 (19), 107 (46), 95 
(13)
HRMS (Cl) m/e calculated for C10H17O2 = 169.1229; found = 
169.1278
Preparation of para-nitrobenzoate derivatives of 8- 
oxatricvclo T 4,3,2,01undec-3-ene, [25]
The mixture of syn- and anti-alcohol derived from the 
hydroboration of [25] (0.370 g, 2.20 mmol) was dissolved in
5 mL of dry pyridine and an argon atmosphere was created.
I l 'I
Then PNBCl (0.612 g, 3.30 mmol) was dissolved in dry 
pyridine and added dropwise to the stirring solution at O0C. 
The reaction was allowed to stir at room temperature 
overnight. Identical workup (page 125) and flash 
chromatography (dichloromethane:ethylacetate:hexane, 10:1:1) 
isolated the isomers as a white powder (0.411 g, 1.30 mmol) 
(50% yield)i
svn-3-para-Nitrobenzoate-8-oxatricvclo[4,3,2,01undec^3-ene, 
r36-sy.nl *1
mp = 73-74°C
1HNMR (300.133 MHz,. CDCl3): 5 1.70-2.10 (10H, m) , 3.47 (IHf 
d, J=8.9Hz), 3.51 (IHf df J=8.9Hz), 3,89 (IHf df 
J=8.7Hz)t 3.92 (IHf df J=8.7Hz)f 5.34-5.42 (IHf m)f 
8.14-8.29 (4Hf m)
13CNMR (75.4 MHzf CDCl3) : 5 26.36 (t) f 27; 60 (t) (two carbon) f 
27.83 (t), 35.96 (t)f 45,17 (s)f 45.62 (s)f 71,92 (d)f 
80.12 (t)f 81.83 (t)f 123.56 (d)f 130.62 (d) f 136.04 
(s)f 151,00 (s)f 164.14 (s)
LRMS (Ei) m/e (%abundance): 150 (47)f 122 (69)f 104 (28)f 93 
(100)f 79 (25)f 41 (16)
HRMS (HPEC) (NH3) m/e calculated for C17H19O5N1 = 317.1263;
138
found = 317,1257
139
anti-3-para-Nitrobenzoate-8-oxatricvclo[4,3,2,PT undecane, 
r36-anfc.il 
mp = 113-115'C
1HNMR (300.133 MHzr CDCl3): S 1.54-2.05 (10H, m) , 3.43 (1H> 
d, J=8.4Hz)f 3.46 (1H, d, J-8.1Hz), 3.86 (1H, d,
J=9.OHz)/ 3.94 (1H, d, J=9.OHz), 5.13-5;21 (1H, m), 
8.18-8.30 (4Hr m) f
13CNMR (75.4 MHz r CDCl3) : 5 26.54 (t) , 26.91 (t) , 28.29 (t) , 
29.23 (t)f 35.67 (t)f 44.93 (s), 45.86 (s), 71.79 (d), 
80.17 (t), 80.94 (t), 123.56 (d) , 130.61 (d) f 136.11 
(s)r 151.00 (s), 164.14 (s)
LRMS (EI) m/e (%abundance): 150 (31), 122 (83), 104 (30), 93 
(100), 79 (23), 41 (15)
HRMS (HPEC) (NH3) m/e calculated for C17H19O5N1 = 317.12 63;
found 317.1255
140
Crystallization of the product, [36-syn] was 
accomplished in dichloromethane:methanol in a relative ratio 
of 1:10, respectively. The product, [36-anti] was
recrystallized from dichloromethane:hexane in a relative 
ratio of 1:5, respectively.
X ray analysis:
3
Figure 75. ORTEP Drawing of [36-syn].
a
Figure 76. ORTEP Drawing of [36-anti].
J !
Table 44. Bond Lengths (A)
141
of [36-anti].
G(I) -C (21 1.524 (7) C(I) -C (6) 1.561 (8)
C(I)-C(S) I;525 (7) C(I)-C(9) 1.541(9)
C (2)-C(3) 1.517 (6) C (3)-C (4) 1.502(9)
C (3) -0(2) 1.462 (6) C (4) -C(5) 1.512 (8)
C (5) -C(6) 1.494 (7) C (6)-C(7) 1;508 (7)
C (6) -C(IO) 1.556 (9) C (7)-0(1) 1.416(8)
O(I) -C(S) 1.405 (8) C (9) -C(IO) 1.499 (9)
0(2) -C(Il) 1.330 (6) C(Il) -0(3) 1.213 (7)
C(Il) -C (12) 1.454(7) C (12)-C(13) 1.686 (8)
C (12)-C(17) 1.400 (7) C (13)-C(14) 1.349 (7)
C (14)-C(15) 1.388 (7) C (15) -C (16) 1.381 (8)
C (15)-N 1.465 (6) C (16) -C (17) 1.367 (7)
N-O(4) 1.216(7) N-O(5) 1.218 (5)
Table 45. Bond Angles ( °) of [36-anti].
C (2) -C(I) -C (6) 117.7(4) C (2) -C(I) -C (8) 113.6 (4)
C (6) -C(I) -C (8) 101.4(4) O M 0
 
H 1 O VO 117.8(5)
C(6) -C(I) -C(9) 89.1(4) C (8) -C(I) -C (9) 113.9(4)
C(I) -C (2) —C (3) 113.9(4) C (2) -C (3) -C (4) 111.4(4)
C (2) -C (3) -0(2) 111.3(4) C (4) -C (3) -0(2) 105.9(4)
C (3) -C (4) -C (5) 112.2(5) C (4) -C (5) -C (6) 112.5(5)
C(I) -C (6) -C (5) 120.3(4) C(I) -C (6) -C (7) 102.8(4)
C (5) -C (6) -C (7) 114.6 (5) C(I) -C (6) -C(IO) 88.3(4)
C (5) -C (6) -C(IO) 115.3(4) C (7) -C (6) -C(IO) 112.4(4)
142
(Table 45. Continued)
C (6) -C (7) -0(1) 106.5(5)
C(I) -C (8) -0(1). 108.2(5)
C (6) -C(IO) -C (9) 90.8(5)
0(2) -C(Il) -0(3) 123.3(5)
0(3) -C(Il) -C (12) 123.5(5)
C(Il)-C(12)-C(17) 122.7(5)
C (12)-C(13)-C(14) 122.5(5)
C (14)-C(15)-C(16) 121.3(4)
C (16)-C(15)-N 119.2(4)
C (12)-C(17)-C(16)' 121.5(5)
C (15) -N-0(5) 118.8(4)
0 ~j 1 0 H 1 O CO 102.5(4)
C(I) -C (9) -C(IO) 91.2(5)
C (3) -0(2) -C(Il) 118.4(4)
0(2) -C(Il) -C (12) 113.2(4)
C(Il) -C (12) -C (13) 119.9(4)
C (13)-C(12)-C (17) 117.4(4)
C (13)-C(14)-C(15) 118.6(5)
C (14)-C(15)-N 119;4(5)
C (15)-C(16)-C (17) 118.6(5)
C (15)-N-O (4) 117.8 (4)
O (4) -N-O(S) 123.3(4)
Preparation of svn-tosvlate derivative of F251
The syn-para-nitrobenzbate derivative of [25] (70.0 mg,
0.220 mmol) was dissolved in 0.2 mL of dichloromethane and 
then added to a 80% aqueous ethanol solution that was 0.5% 
by weight in KOH. The reaction was stirred overnight. 
Workup yielded a syn-alobhol as a colorless oil (34;7 mg, 
0.210 mmol)(94% yield). The syn-alcohol (34.7 mg, 0.210 
mmol) was dissolved in 2 mL of dichloromethane to which was 
added 0.1 mL of pyridine. The solution was cooled to O0C 
and TsCl (57.2 mg, 0.300 mmol) was added in small portions. 
The reaction was warmed to room temperature and stirred 
overnight. Workup (page 131) and flash chromatography
143
(Hexane:ethylacetate, 1:1) yielded a syn-tosylate as 
colorless oil. (30.0 mg, 0.093 mol) (46% yield) 
syn-3-Tosvl-8-oxatrlcvclo(4,3,2,Olundecane, (821 
1HNMR (300.133 MHz, CDCl3): 5 1.53-1:88 (10H, m) , 2.43 (3H, 
s) , 3.34 (1H, d, J=9Hz), 3.39 (1H, d, J=9.0Hz), 3.80 
(2H, d, J=9.0Hz), 4.80-4.89 (1H, m), 7:32 (2H, d, 
J=8.3Hz)
13CNMR (75.4 MHz, CDCl3) : 8 21.58 (q) , 27.02 (t) , 27.10 (t) ,
27.55 (t), 27.62 (t), 36.67 (t), 44.72 (s) , 45:35 (s), 
78.80 (d), 79.83 (t), 81.34 (t), 127.56 (d) , 129.79 
(d), 134.71 (s), 144.52 (s)
IiRMS (EI) m/e (%abundance) : 277 (5) , 172 (8) , 167 (5) , 155
(12), 150 (89), 135 (14), 122 (100), 107 (30), 93 (99), 
79 (60), 65 (35), 55 (27), 41 (36)
LRMS (Cl) (NH3) m/e (%abundance) : 340 (M+NH/, 100) , 195
(24), 186 (14), 168 (79)z 151 (32), 122 (13), 108 (29) 
HRMS (EI) m/e calculated for C17H22O4S1 = 322.1239; found = 
322.1236
Preparation of anti-tosylate derivative of [25]
In a similar fashion, saponification of the anti-para- 
nitrobenzoate derivative of [25] (84.5 mg,.0.270 mmol)
afforded 40.0 mg (0.240 mmol) of the anti-alcohol (88% 
yield). Again, with identical workup (page 131), the anti­
alcohol (40 . 0 mg, 0.240 mmol) were dissolved in 2 mL of 
dichloromethane to which was added pyridine (0.1 mL, 1.24 
mmol) and TsCl (69.0 mg, 0.360 mmol). The anti-tosylate was
144
cleanly separated as a colorless oil 49.1 mg (0.150 
mmol)(64% yield).
anfci^3-Tosvl-8-oxatricvclo[4,3,2,01 undecane, 1831
1HNMR (300.133 MHzf CDCl3): 5 1.40-1.91 (IOHf m) f 2; 42 (3Hf
s), 3.25 (1H, d, J=9.OHz), 3.34 (1H, d, J=9.0Hz), 3.75
(1H, d, J=9.0 Hz) , 3.83 (1H, d, J=9.0Hz), 4.55-4.63
(1H, m), 7.31 (2H, d, J=8.3Hz)/ 7.77 (2H, d, J=8.3Hz)
13CNMR (75.4 MHzfCDCl3): 8 21.56 (q) f 26.73 (t) f 27.08 (t) f 
27.78 (t)f 28.73 (t)f 36.29 (t)f 44.61 (s) f 45.67 (s)f 
78.61 (d), 80.16 (t)f 80.60 (t)f 127.58 (d)f 129.78 
(d), 134.59 (s)f 144.52 (s)
LRMS (EI) m/e (%abundance) : 172 (7)f 150 (16), 122 (100) f 
107 (16) f 93 (48), 79 (25), 65 (13), 55 (11), 41 (19) 
LRMS (Cl) (NH3) m/e (%abundance) : 340 (MtNH41", 0.2), 184 
(100), 108 (15)
HRMS (EI) m/e calculated for C17H22O4S1 = 322.1239; found = 
322.1241
Preparation of cis-l,6-dicarbbmethoxvbicvclo[4,3,01non-3- 
ene, [171
A solution of 200 mL of dry THE, 140 mL of 2.5 M n-BuLi 
(0.350 mol) and 50 mL of diisopropylamine (0.360 mol) was 
stirred under argon at -IOcC for 30 minutes. The 
temperature was taken down to -780C and cis-3,4- 
dicarbomethoxy cyclohexene (28.0 g, 0.141 mol) was added 
dropwise, creating a bright red solution. After addition 
was completed, the solution was allowed to stir for 15
145
minutes, then I,3-dibromopropane (17.2 mL, 0.169 mol) was 
added dropwise . The solution was allowed to warm to room 
temperature and stirred overnight. Workup, (page 120) and 
distillation yielded a product as a pale yellow oil (23.0 g, 
0.097 mol) (68% yield)
cis-lr6-Dicarbomethoxybicvclo[4,3,01non-3-ene, [17]
IR (neat, cm"1) : 3030, 2953, 2846, 1733, 1626, 1597, 1436, 
1382, 1293, 1210, 1097, 1043, 1002, 942, 764, 656 
1HNMR (300.133 MHz, CDCl3): 8 I;61-1.80 (4H, m) , 2.11-2.49 
(6H, m), 3.63 (6H, s), 5.60 (2H, t, J=1.5Hz)
13CNMR (75.4 MHz, CDCl3) : 5 18.73 (t) , 31.74 (t) , 34.63 (t) ,
51.70 (q) , 52.22 (s), 123.32 (d) , 176.45 (s)
LRMS (EI) m/e: 206, 178, 119 (base), 91, 77, 59, 41 
LRMS (Cl) (Methane) m/e (%abundance) : 239 (M+H+, 2) , 207 
(100), 179 (28), 119 (35)
HRMS (Cl) m/e calculated for C13H19O4 = 239.1283; found = 
239.1280
Preparation of cis-1,6-dihvdroxvmethvlbicvclo[4,3,0]non-3- 
ene, T 311
A solution of [17] (14.0 g, 0.059 mol) in 20 mL of dry 
THE was added dropwise at 0°C to a stirring solution LAH 
(3.00 g,0.080 mol) in 350 mL of dry THE. The reaction 
mixture was stirred overnight at a room temperature; Workup 
(page 121) yielded a product as a white solid (9.00 g, 0.049 
mol) (84% yield).
146
cis-l, 6-Dih.ydroxvmethvlbicvcloT4f 3, Olnon-S-ene, , T311. 
mp = 152-153"C
IR (nujo.l, Cm"1) : 3321, 3.022, 2946, 2882, 1664, 1465, 1430, 
1201, 1049, 915, 879
1HNMR (300.133 MHz, CDCl3): 8 1.44-1.74 (6H, m) , 1.90 (2H, 
d, j=16.6Hz), 2.11 (2H, d, J=I6.8Hz) , 3.43 (2H, d,
J=Il.5Hz), 3.61 (2H, d, J=I1.5Hz), 5.58 (2H, s)
13CNMR (75.4 MHz, CDCl3) : 5 18.54 (t) , 31.46 (t) , 33.58 (t) ,
46.46 (s), 67.29 (t), 124.60 (d)
LRMS (EI) m/e: 164, 133, 117, 106, 91 (base), 77, 65, 41 
LRMS (Cl) (Methane) m/e (%abundance) : 183 (M+H+, I) , 181
(3), 165 (20), 147 (100), 135 (38), 119 (27), 105 (14) 
HRMS (Cl) m/e calculated for C11H19O2 = 183.1385; found = 
183.1385
Preparation of 8-oxatricvcloF4,3,3,01dodec-3-ene, (101
The diol [31] (1.00 g, 5.49 mmol) was dissolved in 5 mL
of dry pyridine and then 0*43 mL of MsCl (0.630 g, 5.50 
mmol) was added dropwise to the stirring solution under 
argon in ice bath. The reaction mixture was stirred at room 
temperature overnight. Workup (page 122) and flofisil 
separation (hexane:ethylacetate, 9:1) yielded a product as a 
colorless oil (0.730 g, 4.45 mmol) (81% yield)
8-Oxatricvclo[4,3,3,01dodec-3-ene, [101
IR (neat, cm"1) : 3037, 2930, 2835, 1651, 1544, 1449, 1385,
1175, 1066, 943, 842, 711
147
1HNMR (300.133 MHz, CDCl3): 5 1.46-1.67 (6H, m) , 2.00 (2H, 
d, J=3.OHz), 1.99 (2H, d, J=3.0Hz), 3.54 (4H, d,
J=I.3Hz), 5.82 (2H, t, J=3.0Hz)
13CNMR (75.4 MHz, CDCl3) : 5 23.96 (t) , 32.68 (t) , 40.19 (t) , 
55.30 (s), 81.38 (t), 128.63 (d)
LRMS (EI) m/e (%abundance) : 164 (M+, 18), 146 (11), 133
(31), 119 (32), 109 (26), 104 (14), 95 (31), 91 (100), 
79 (39), 67 (25), 53 (16), 41 (33)
HRMS (EI) m/e calculated for C11H16O1 = 164.1202/ found = 
164.1205 .
Hvdroboration of 8-oxatricvcloF4,3>3r01dodec-3-ene, FlOI
The propellane, [10] (0.450 g, 2.74 mmol) was dissolved
in 10 mL of dry THF and then 4 mL of BH3.THF (62.4 mg, 4.52 
mmol) were added dropwise to the stirring solution under 
argon at O0C. The solution was warmed to room temperature 
and stirred overnight. Workup (page 123) yielded a 51:49 
mixture of syn-OH and anti-OK as a colorless oil (0.443 g, 
2.43 mmol) (89% yield).
syn-8-Oxatricvclo[4,3,3,01dodec-3-ol, F 63-syn]
1HNMR (300.133 MHz, CDCl3): 6 1.34-1.89 (12H, m) , 3.58 (1H, 
d, J=8.5Hz), 3.66 (1H, d, J=8:4Hz), 3.68 (1H, d, 
J=8.4Hz), 3.73-3.82 (1H, m) , 3.84 (1H, d, 8.5Hz),
13CNMR (75.4 MHz,CDCl3) : 8 21.98 (t), 28.34 (t) , 31.11 (t) ,
33.37 (t), 38.20 (t), 40.27 (t), 51.06 (s), 53.24 (s), 
67.20 (d) , 77.22 (t), 80.98 (t)
148
LRMS (EI) m/e (%abundance) : 182 (M+, I), 164 (49), 146 (13), 
133 (35), 119 (55), 10.9 (100) , 91 (67), 79 (43), 67
(25) , 55 (15)
LRMS (Cl) (Methane) m/e (%abundance) : 183 (M+H+, 'll), 181 
(15), 165 (100), 147 (44), 135 (24), 121 (16)
HRMS (Cl) m/e calculated for C11H19O2 = 183.1385; found = 
183.1386
anfci-8-0xatricvclo[4,3,3,01dodec-3-ol, F 63-anfcil 
1HNMR (300.133 MHz, CDCl3) : 5 1.27-1.89 (12H, m) , 3.60 (1H, 
d, J=8.9Hz), 3.63 (1H, d, J=8.9Hz), 3.70 (1H, d, 
J=8.2Hz), 3.75 (IH, d, J=8.2Hz), 3.75-3.84 (1H, m) 
13CNMR (75.4 MHz, CDCl3) : 6 22.11 (t) , 29.83 (t) , 31.14 (t) , 
32.65 (t), 38.47 (t), 39.53 (t), 51.18 (s), 53.42 (s),
67.29 (d), 77.20 (t), 80.22 (t)
LRMS (EI) m/e (%abundance) : 182 (M+, 3) , 164 (23), 151 (18), 
133 (48), 119 (100), 105 (37), 91 (96), 86 (15), 79 
(47), 67 (27), 55 (17)
LRMS (Cl) (Methane) m/e (%abundance) : 183 (M+H+, 5) , 181
(26) , 165 (100), 147 (79), 135 (41), 121 (13)
HRMS (Cl) m/e calculated for C11H19O2 = 183.1385; found =
183.1385
Preparation of para-nitrobenzoate derivatives of 8- .
oxatricvclo(4,3,3,01dodec-3-ene, FlOI
The mixture of syn-and anti-alcohols derived from the 
hydroboration of [10] (0.560 g, 3.08 mmol) was dissolved in
5 mL of dry pyridine and an argon atmosphere was created.
149
Then PNBCl (0.820 g, 4.42 mmol) was dissolved in dry 
pyridine and added dropwise to the stirring solution at O0C. 
The reaction was stirred at room temperature overnight. 
Workup (page 125) and flash chromatography
(dichloromethane:ethylacetate:hexane, 10:1:1) isolated the 
isomers as a pale yellow solid (0.810 g, 2.45 mmol) (80 % 
yield).
svn-3-para-Nitrobenzoate-8-oxatricvclo(4,3,3,01 dodecane, 
r37-sy.nl *1
mp = 115-1170C
1HNMR (300.133 MHz, CDCl3): 8 1.51-2.01 (12H, m), 3.63 (1H, 
d, J=8.5Hz), 3.72 (1H, d, J=8.5Hz), 3.73 (1H, d, 
J=8.5Hz), 3.85 (1H, d, J=8.5Hz), 5.13-5.22 (1H, m), 
8.15-8.29 (4H, m)
13CNMR (75.4 MHz, CDCl3) : 5 22.19 (t) , 26.90 (t) z 27.95 (t) , 
34.17 (t), 35.74 (t), 37.28 (t), 51.20 (s), 52.84 (s), 
71.91 (d), 78.18 (t), 80.67 (t), 123.51 (d) , 130.64 
(d), 136.11 (s), 150.65 (s), 164.23 (s)
LRMS (EI) m/e (%abundance): 181 (7), 164 (82), 150 (31), 135 
(33), 119 (54), 109 (100), 91 (52), 79 (29), 67 (21),
55 (15), 41 (28)
HRMS (EI) m/e calculated for C18H21O5N1 = 331.1420 ; found =
331.1426
J L I I I  HI I
150
anfci-3-para-Nitrobenzoate-8-oxatricvclo f4,3,3,01 dodecane,
F37-antiI 
mp = IlS-Iie0C
1HNMR (300,133 MHz, CDCl3) : 5 1.57-2.06 (12H, m), 3.65 (IH/ 
d, J=8.6Hz), 3.70 (IH, d, 8.6Hz), 3.71 (IH, d, 8.6Hz), 
3.83 (IH, d, 8.6 Hz), 5.15-5.24 (IH, m) , 8.15-8.29 , (4H, 
m)
13CNMR (75.4 MHz, CDCl3) : 5 22.46 (t) , 26.88 (t) , 29.09 (t) , 
34.38 (t), 34.77 (t), 38.84 (t), 51.27 (s), 52.85 (s),
72.03 (d), 77.97 (t), 79.92 (t), 123.51 (d) , 130.61 
(d) , 136.15 (s) , 150.'63 _ (s) , 164.14 (s)
LRMS (BI) m/e (%abundance) : 331 (M+, I) , 181 (39) , 164 (50) , 
151 (72), 137 (82), 119 (100), 104 (37), 91 (70), 79 
(33), 67 (21), 55 (15), 41 (27)
HRMS (BI) m/e calculated for C18H21O5N1 = 331.1420 ; found = 
331.1432
151
Crystallization of the product, [37-syn] was 
accomplished in dichloromethane:hexane in a relative ratio 
of 1:5 respectively and the product, [37-anti] was 
accomplished in dichloromethane:methanol in a relative ratio 
of 1:10, respectively.
X-ray analysis:
Figure 77. ORTEP Drawing of
Table 46. Bond Lengths (A)
C(I) -C (2) 1.556 (17)
C(I) -C (8) 1.568 (19)
C (2) -C(3) 1.472 (18)
C (3) -0(2) 1.457 (14)
C (5) -C(6) 1.526 (19)
C (6)-C(11) 1.567 (20)
0(1) -C (8) 1.354 (19)
[37-syn]. 
f [37-syn].
Cd) -C (6) 1.510(19)
C(I) -C (9) 1.495 (22)
C (3)-C (4) 1.484 (18)
C (4)-C(5) 1.557 (18)
C (6)-C(7) 1.517 (20)
C (7)-0(1) 1.388 (19)
C (9) -C(IO) 1.512 (28)
I I I IJ Li.
152
(Table 46. Continued)
C(IO) -C(Il) 1.449 (26) 0(2)-C(12) 1.325 (15).
C (12) -0(3) 1.209 (16) C (12)-C(13) 1.464 (17)
C (13)-C(14) 1.385(16) C (13)-C (18) 1.400 (16)
C (14)-C (15) 1.369 (16) C (15)-C(16) 1.380 (16)
C (16) -C (17) 1.373(16) C (16) -N 1.475 (16)
C(IV) -C (18) 1.380 (16) N-O (4) 1.195(15)
N-O (5) 1.214(14)
Table 47. Bond Angles ( °) of [37-syn] .'
C (2) -C(I) -C (6) 111.6(11) C (2)-C(I) -C (8) 109.3(11)
C(6)-C(I)-C(S) 100.2(10) C (2) -C (I) -C (9) 113.1(12)
C (6) -C(I) -C (9) 107.2(12)
CT>0i—iU1coU 114.7(12)
C(I) -C (2) -C (3) 113.3(11) C (2) -C (3) -C (4) 108.9(10)
C (2) -C (3) -0V(2) 106.6(10) C (4) -C (3) -0(2) 110.0(10)
C (3) -C (4) -C (5) 110.2(11) O 0 Ui 1 O m 111.4(11)
C(l).-C (6)-C (5) 115.6(11) C(I) -C (6) -C (7) 104.4(11)
C (5)-C (6)-C (7) 115.1(12) C(I) -C (6) -C(Il) 101.2(11)
C(S)-C(6)-C(Il) 108.2(11) C (7) -C (6) -C(Il) 111.5(11)
C(6)-C(V)-O(I) 106.2(12) C (7) -0(1) -C (8) 113.5(12)
C(I) -C (8) -0(1) 105.7 (12) C(I) -C (9) -C(IO) 105.0(14)
C (9) -C(IO) -C(Il) 109.2(17) C (6) -C(Il) -C(IO) 104.3(13)
C (3) -0(2) -C (12) 118.9(9) 0(2)-C (12)-0(3) 122.5(11)
0(2)-C(12) -C (13) 112.7(11) 0(3) -C (12) -C (13) 124.7(11)
C (12)-C(13)-C(14) 122.5(10) C (12)-C(13)-C(18) 118.7(11)
153
(Table 47. Continued)
C (14) -C(13)-C(18) 118.7(10) C (13)-C(14)-C(15) 120.0(10)
C (14)-C(15)-C(16) 120.5(11) C (15)-C(16)-C(17) 121.1 (11)
C (15)-C(16)-N 120.1(10) C (17)-C (16)-N 118.8(11)
C (16)-C(17)-C(18) 118.4(11) C (13)-C(18)-C(17) 121.3(11)
C (16)-N-O (4) 117.6(10) C (16) -N-O(S) 115.6(11)
0(4) -N-O (5) 126.8(11)
X-ray analysis:
Figure 78. ORTEP Drawing of [37-anti].
Table 48. Bond Lengths (A) of [37-anti].
Cd) -C (2) 
Cd) -C (8) 
C (2)-C (3)
1.565 (10) 
1.506 (12) 
1.460 (9)
Cd) -C (6) 
Cd) -C (9) 
C (3)-C (4)
1.546(10) 
1.526(10) 
1.521 (10)
C (3) -0(2) 1.472 (7) C (4) -C(5) 1.539(10)
! H  i;i
(Table 48. Continued)
154
C(S)-C(G) 1.4 V 9 (11) C(G) -C(V) 1.551(12)
C(G)-C(Il) 1,550(9) C(V)-O(I) 1.380 (13)
O(I)-C(S) 1.420(10) C (9)-C(IO) 1.524 (15)
C(IO) -C(Il) 1.529 (11) 0(2) -C (12) 1.324 (V)
C (12) -0(3) 1.192 (9) C (12)-C(13) 1.486(9)
C (13)-C(14) 1.399 (V) C (13)-C (18) 1.396(9)
C (14) -C (IS) 1.382 (8) C (15) -C(IG) 1.369 (9)
C(IG) -C(IV) 1.394(8) C (IG) -N 1.4V1 (8)
C(IV) -C (18) 1.3 V 5 (8) N-O (4) 1.209 (6)
N-O(S) 1.213(8)
Table 49. Bond Angels ( °) of [3V-anti].
C (2)-C(I)-C(G) 113.3(V) C (2)-C(I)-C(8) 110.3(6)
C(G)-C(I)-C(S) 103.8(5) . C (2) -C (I) -C (9) 110.4(5)
C(G) -C(I) -C (9) 103.V(G) C (8)-C (I)-C (9) 115.1(8)
C(I) -C.(2) -C (3) 113.2(5) C (2) -C(3) -C (4) 111.0(5)
C (2) -C (3)-0(2) 108.6(4) C (4)-C (3)-O (2) IOV .8(6)
C (3) -C (4) -C (5) 10V.V (V) C (4) -C(S) -C(G) 112.1(5)
C(I)-C(G)-C(5) 116.4(5) C(I)-C(G)-C(V) 98.5(V)
C(S)-C(G)-C(V) 109:9 (5) C(I)-C(G)-C(Il) 105.2(5)
C (5) -C(G) -C(Il) 113.1 (V) C(V) -C(G) -C(Il) 112.9(6)
C(G) -C(V) -0(1) 108.V (6) C(V)-O(I)-C(S) 110.1 (V)
C(I)-C(S)-O(I) 10V.1 (V) C(I) -C (9) -C(IO) 106.2(8)
C (9) -C(IO) -C(Il) 105.3(6) C(G) -C(Il) -C(IO) 10V.V (V)
155
(Table 49. Continued)
C (3) -0(2) -C (12) 116.7(5) O (2)-C (12) -0(3) 123.9(6)
0(2) -C (12) -C (13) 1117(6) 0(3) -C (12) -C (13) 124.3(5)
C (12)-C(13)-C (14) 117.5(6) C (12)-C(13) -C(18) 122.6(5)
C (14)-C(13)-C(18) 119.9(5) C (13)-C (14) -C(15) 120.6(6)
C (14)-C(15)-C(16) 118.3(5) C (15)-C(16) -C (17) 122.5(6)
C (15)-C(16)-N 119.2(5) C (17)-C(16) -N . 118.3(6)
C (16)-C(17)-C(18) 119.2(6) C (13)-C (18) -C(17) 119.5(5)
C (16)-N-O(4) 117.6(5) C (16) -N-O(S) 119.7(5)
0(4) -N-O(S) 122.7(5)
Preparation of gyn-tosylate derivative of FlOl
The syn-para-nitrobenzoate derivative of [10] (0.132 g,
0.400 mmol) was dissolved in 0.2 mL dichloromethane and then 
added to a 80% aqueous ethanol solution that was 0.5% by 
weight in KOH. The reaction was stirred overnight. Workup 
yielded a syn-alcohol as a colorless oil (68.8 mg, 0.378 
mmol) (95% yield). The syn-alcohol (68.8 mg, 0.378 mmol) 
was dissolved in 3 mL of dichloromethane to which was added 
0.2 mL of pyridine. The solution was cooled to 0 °C and TsCl 
(176 mg, 0.920 mmol) was added dropwise. The reaction was 
warmed to room temperature and stirred overnight. Workup 
(page 131) and flash chromatography (hexane:ethylacetate, 
1:1) yielded a syn-tosylate as a white powder (103 mg, 0.307 
mmol) (81% yield)
156
gy.n-3-Tosvl-8-oxa-tricvclo T4,3,3, Oldodecane, TlSl 
mp = 85-87’C
1HNMR (300.133 MHz, CDCl3) : 5 1.17-1.70 (12H, m) , 2.42 (3H,
s), 3.37 (1H, d, J=8.6Hz), 3.46 (1H, d, J=8.6Hz), 3.47
(1H, d, J=8.6Hz), 3.57 (1H, d, J=8.6Hz), 4.41-4.51 (1H, 
m), 7.15 (2H, d, J=8.3Hz), 7.60 (2H, d, J=8.3Hz)
13CNMR (75.4 MHz, CDCl3) : 8 21.60 (q) , 21.99 (t) , 27.63 (t) , 
27.68 (t), 33.73 (t), 36.68 (t), 37.14 (t), 50.81 (s), 
52.99 (s), 77,76 (t), 78.78 (d), 80.33 (t), 127.59 (d), 
129.77 (d), 134.86 (s), 144.47 (s)
LRMS (EI) m/e (%abundance) : 172 (12), 164 (50) , 146 (13) ,
133 (30), 119 (47), 109 (45), 91 (100), 79 (34), 65 
(30), 55 (16), 41 (22)
LRMS (Cl) (NH3) m/e (%abundance) : 354 (M+NH/, 76) , 182 
(100), 108 (18)
HRMS (EI) m/e calculated for C18H24O4S1 = 336.1395; found = 
336.1393
Preparation of anti-tosylate derivative of FlOl
In a similar fashion, saponification of the anti-para- 
nitrobenzoate derivative of [10] (0.113 g, 0.340 mmol)
afforded 60.0 mg (0.330 mmol) of the anti-alcohol (97% 
yield). Again, using the identical workup (page 131), the 
anti-alcohol (77.6 mg, 0.426 mmol) was dissolved in 2 mL of 
dichloromethane to which was added pyridine (0.1 mL, 1.24 
mmol) arid TsCl (97.5 mg, 0.511 mmol) . The anti-tosylate was
157
cleanly separated as a white powder H O  mg (0.327 mmol) (77% 
yield).
anti-3-Tosvl-8-oxatricvclo(4,3,3,01dodecane, (161 
mp = 5 7-5 8 0 C
1HNMR (300.133 MHz, CDCl3): 5 1.41-1.84 (12H,m) , 2.41 (3H,
s), 3.52-3.90 (4H, m) , 4.53-4.63 (1H, m), 7.30 (2H, d, 
J=8.2Hz)r 7.74 (2H, d, J=8.2Hz)
13CNMR (75.4 MHzfCDCl3): 8 21.53 (q) f 22.23 (t) , 27.34 (t)f 
28.74 (t), 34.16 (t)f 35.49 (t)f 38.30 (t)f 50.84 (s), 
52.82 (s)f 77.76 (t)f 78.75 (d) f 79.61 (t), 127.55 (d)f 
129.73 (d), 134.48 (s), 144.45 (s)
LRMS (EI) m/e (%abundance): 181 (51)f 164 (37)f 145 (11)f 
133 (29)f 119 (54)f 105 (21)f 91 (IOO)f 79 (30)f 65 
(30) f 55 (26) f 41 (22)
LRMS (Cl) (NH3) m/e (%abundance) : 354 (M+NH4+f 12) f 196 (35) f 
182 (IOO)f 108 (15)
HRMS (Cl) m/e calculated for C18H24O4S1 = 336.1395; found = 
336.1402
Preparation of cis-1,6-dicarbomethoxvbicvcloF4,4,01dec-3- 
ene, (211
A solution of 200 mL of dry THFf 140 mL of 2.5 M n-BuLi 
(0.350 mol) and 50 mL of diis©propylamine (0.360 mol) was 
stirred under argon at -10 ° C for 30 minutes. The 
temperature was taken down to -780C and cis-3,4- 
dicarbomethoxy cyclohexene (28.0 gf 0.141 mol) was added 
drOpwisef creating a bright red solution. After addition
was completed, the solution was allowed to stdr for 15 
minutes, then I,4-dibromobutane (20.2 mL, 0.169 mol) was 
added dropwise. The solution was allowed to warm to room 
temperature and stirred overnight. Workup (page 120) and 
distillation yielded a product as a colorless oil (28.5 g, 
0.113 mol) (80% yield)
cis-1,G-Dicarbomethoxvbicvclo(4,4,01dec-3-ene, (211 
IR (neat, cm"1) : 3026, 2946, 2860, 1731, 1460, 1429, 1294, 
1238, 1201, 1140, 1072, 1023, 757 
1HNMR (300.133 MHz, CDCl3): 5 1.38^-2.47 (12H, m) , 3.64 (6H, 
s), 5.57 (2H, s)
13CNMR (75.4 MHz,CDCl3) : 8 22.05 (t) , 31.62 (t) , 33.15 (t) , 
45.94 (s), 51.56 (q), 123.27 (d) , 176.58 (s)
LRMS (EI) m/e: 252, 220, 192, 133 (base), 91,.77, 59, 41 
LRMS (Cl) . (Methane) m/e (%abundance) : 253 (MtH-V  5) , 221 
(100), 193 (58), 133 (86)
HRMS (Cl) m/e calculated for C14H21O4 = 253.1440; found = 
253.1465
Preparation of cis-1,6-dihvdroxvmethvlbicvcloT4,4,01dec-3- 
ene
A solution of [21] (21.2 g, 0:084 mol) in 20 mL of dry 
THE was added dropwise at 0°C to a stirring solution of LAH 
(4.80 g, 0.130 mol) in 350 mL of dry THE. The reaction 
mixture was heated to a gentle reflux under argon overnight 
Workup (page 121) yielded a product as a white powder (12.0 
g, 0.061 mol) (73% yield).
158
1 1  Ii r  k  i
159
cis-1,6-Dihvdroxvmethvlbicvclo F4,4,PT dec-3-ene 
mp = 145-1470 C (Ref17 143-145’C)
IR (nujol, CirT1) : 3329, 3023, 2970, 2930, 1715, 1662, 1456, 
1084, 1051, 878
1HNMR (300.133 MHz, CDCl3) : 8 1.35-1.52 (8H, methylene
envelope), 2.03 (4H, methylene envelope), 2.90 (2H, s),
3.55 (2H, d, J=Il.5Hz), 3.67 (2H, d, J=Il.5Hz), 5.55 
(2H, d, J=I.3Hz)
13CNMR (75.4 MHz, CDCl3) : 5 20.90 (t) , 30.35 (t) , 31.50 (t) , 
38.66 (s), 67.68 (t), 123.87 (d)
LRMS (EI) m/e (%abundance): 178, 160, 147, 132, 117, 91 
(base), 79, 67, 41
LRMS (Cl) (Methane) m/e (%abundance) : 195 (M-H+, 4) , 179 
(34), 161 (100) , 149 (24), 133 (26), 95 (23)
Preparation of 8-oxatricvcloT4,4,3,01tridec-3-ene, 1261
cis-1,6-Dihydroxymethylbicyclo[4,4,0]dec-3-ene (4.41 g, 
0.0225 mol) was dissolved in 16 mL of dry pyridine and then 
1.74 mL of MsCl (2.58 g, 0.0225 mol) were added dropwise to 
the stirring solution under argon in ice bath. The reaction 
mixture was stirred at room temperature overnight. Workup 
(page 122) and florisil separation■(hexane:ethylacetate, 
98:2) yielded a product as a pale yellow oil (3.40 g, 0.0191 
mol) (85% yield). -
8-Oxatricvclo(4,4,3,01tridec-3-ene, (261
IR (neat, cm"1) : 3023, 2924, 2857, 1635, 1456., 1058, 1038,
912, 726, 659,
I J L
160^
1HNMR (300.133 MHz, CDCl3): 5 1.37-1.59 (8H, m) , 1.89-2.06 
(4H, m), 3.58 (2H, d, J=7.6Hz), 3.79 (2H, d, J=7.6Hz),
5.56 (2H, s)
13CNMR (75.4 MHz, CDCl3) : 5 22.15 (t) , 30.79 (t), 31.30 (t) ,
40.62 (s), 77.42 (t), 123.69 (d)
LRMS (EI) m/e (%abundance) : 178 (M% 13), 160 (21), 147
(35), 132 (21), 123 (70), 117 (14), 105 (34), 95 (41), 
91 (100), 79 (41), 67 (33), 55 (16), 51 (9), 41 (37) 
HRMS (EI) m/e calculated for C12H18O1 = 178.1359 ; found = 
178.1355 ' ’
Hvdroboration of 8-oxatricvloF4,4,3,01tridec-3-ene, (261
The propellane, [26] (0.480 g, 2.70 mmol) was dissolved
in 10 mL of dry THF and then 4 mL of BH3.THF (0.0624 g, 4.52 
mmol) were added dropwise to the stirring solution under 
argon at 0°C. The solution was warmed to room temperature 
and stirred overnight. Workup (page 123) yielded 57:43 
mixture of syn-OH and anti-OH as. colorless oils (0.460 g, 
2.35 mmol) (87% yield).
svn-8-Oxatricvlof4,4,3,01tridec-3-ol, F 64-synl 
IR (neat, cm"1) : 3395, 2984, 2930, 2864, 1489, 1450, 1058, 
918, ,719, 666
1HNMR (300.133 MHz, CDCl3) : 8 1.26-1.84 (14H, m) , 2.13 . (1H,
s), 3.39 (1H, d, J=8.0Hz), 3.45 (1H, d, J=8.0Hz), 3.69- 
3.79 (1H, m), 3.99 (1H, d, J=7.9Hz), 4.00 (1H, d, 
J=7.9Hz)
161
13CNMR (75.4 MHz, CDCl3) : 5 21.61 (t) , 22.14 (t) , 25.78 (t) ,
28.05 (t), 31.43 (t), 33.61 (t), 41.48 (s), 43.18 (t),
43.65 (s), 67.01 (d) , 77.14 (t) (two carbon)
LRMS (EI) m/e (%abundance) : 196 (M+, I) , 178 (28) , 147 (20) , 
133 (31), 123 (100), 105 (22), 91 (53), 79 (28), 67 
(26), 55 (13)
HRMS (EI) m/e calculated for C12H20O2 = 196.1463 ; found = 
196.1452
anfci.-8-bxatricvclo 14,4,3, 01 tridec-3-ol, f 64-antil
IR (neat, cm"1) : 3395, 2984, 2930, 2864, 1489, 1450, 1058, 
918, 719, 666
1HNMR (300.133 MHz, CDCl3): 5 1.20-1.80 (14H,m), 2.22 (1H, .
s), 3.38 (1H, d, J=7.9Hz), 3.39 (1H, d, J=7.9Hz), 3.77- 
3.89 (1H, m), 3.90 (1H, d, J=8.0Hz), 4.00 (1H, d,
J=8.OHz)
13CNMR (75.4 MHz,CDCl3) : 5 21.55 (t) , 22.15 (t) , 26.38 (t) , 
31.21 (t), 33.35 (t), 34.78 (t), 35.87 (t), 41.40 (s), 
43.97 (s), 67.39 (d), 76.41 (t), 77.78 (t)
LRMS (EI) m/e (%abundance) : 196 (M+, 13), 178 (30), 165
(21), 147 (50), 133 (100), 123 (28), 105 (39), 91 (82), 
79 (44), 67 (36), 55 (22)
HRMS (EI) m/e calculated for C12H20O2 = 196.1463 ; found =
196.1455
162
Preparation of para-nitrobenzoate derivatives of 8- 
oxatricvclo[4,4,3,01tridec-3-ene, f 2 61
The mixture of syn-and anti-alcohols derived from the 
hydroboration of [26] (0.618 g, 3.15 mmol) was dissolved in
15 mL of dry pyridine and an argon atmosphere was created. 
Then PNBCl (0.878 g, 4.73 mmol) was dissolved in dry 
pyridine and added dropwise to the stirring solution at O0C. 
The reaction was stirred at room temperature overnight. 
Workup (page 125) and flash chromatography 
(dichloromethane:ethylacetate:hexane, 10:1:1) isolated the 
isomers as white powders (0.569 g, 1.65 mmol) (52% yield). 
svn-3-para-Nitrobenzoate-8-oxatficvclo[4,4,3,01tridec-3-ene, 
FSS-svnl *1
mp = 172-1730C
1HNMR (300.133 MHz, CDCl3): 5 1.37-2.02 (14H, m), 3.57 (1H, 
d, J=8.IHz), 3.61 (1H, d, J=8.1Hz), 4.00 (1H, d, 
J=8.3Hz), 4.03 (1H, d, J=8.3Hz), 5.16-5.25 (1H, d,
J=4.9Hz), 8.17-8.28 (4H, m)
13CNMR (75.4 MHz,CDCl3) : 5 21.73 (t) , 22.15 (t) , 26.17 (t) , 
27.42 (t), 28.83 (t), 32.89 (t), 38.16 (t), 41.66 (s) ,
43.64 (s), 72.21 (d) , 77.23 (t), 77.32 (t), 123.52 (d),
130.65 (d), 136.12 (s), 150.80 (s), 164.18 (s)
LRMS (EI) m/e (%abundance): 178 (64), 147 (25), 133 (39),
123 (100), 105 (23), 91 (43), 79 (21), 67 (20), 55 
(15), 41. (21)
I \ Il I
163
LRMS (HPEC) (NH3) (Methane) m/e (%abundance) : 345 (100) , 314 
(33), 136 (10)
HRMS (HPEC) (NH3) m/e calculated for C19H23O5N1 = 345.1576 ; 
found = 345.1579
anti-3-para-Nitrobetzoate-8-oxatricvclo[4,4,3,01 tridecane, 
r38-anti1 1
mp = 144-145 °C
1HNMR (300.133 MHz, CDCl3) : 5 1.32-2.01 (14Hf m), 3.49 (IHf 
df J=8.1Hz), 3.53 (IHf df J=8.2Hz)f 4.04 (IHf d> 
J=8.2Hz)f 4.05 (IHf df J=8.1Hz)f 5.19-5.29 (IHf df 
J=5.IHz)r 8.17-8.28 (4Hf m)
13CNMR (75.4 MHzfCDCl3): 5 21.72 (t) f 22.22 (t) f 26.99 (t) f 
27.33 (t)f 32.40 (t)f 32.55 (t)f 34.47 (t)f 41.57 ( s ) f
44.05 (s)f 72.58 (d) f 76.45 (t)> 77.61 (t)f 123.51 (d)f
130.65 (d)f 136.12 (s)f 150.80 (s)f 164.14 (s)
LRMS (EI) m/e (%abundance): 315 (10)f 195 (14)f 178 (50),
147 (54), 133 (100), 120 (36), 107 (45), 91 (60), 79 
(32), 67 (28), 55 (22), 41 (28)
LRMS (HPEC) (NH3) m/e (%abundance) : 345 (100) , 314 (27)
HRMS (HPEC) (NH3) m/e calculated for C19H23O5N1 = 345.1576 ; 
found = 345.1565
164
Crystallization of the product, [38-syn] was 
accomplished in dichloromethane:hexane in a relative ratio 
of 1:10 respectively and the product, [38-anti] was 
accomplished in dichloromethane:hexane in a relative ratio 
of 1:10, respectively.
X-ray analysis:
Figure 79. ORTEP Drawing of [38-syn].
Table 50. Bond Lengths (A) of [38-syn].
C(I)-C(2) 1.546 (3) Cd) -C (6) 1.557(3)
C(I) -C (8) 1.535(3) C(I) -C (9) 1.533(3)
C (2) -C(3) 1.506(3) C (3)-C (4) 1.508 (4)
C (3) -0(2) 1.470 (3) 0 iU 1 O Ul 1.531 (3)
C(S)-C(6) 1.529 (3) C (6) -C (7) 1.528 (4)
C (6)-C(12) 1.546 (3) C (7)-0(1) 1.419(4)
0(1) -C (8) 1.415 (4) C (9)-C(IO) 1.532 (4)
165
(Table 50. Continued)
C(IO) -C(Il) 1.508(4)
0(2) -C (13) 1.337 (3)
C (13)-C(14) 1.489 (3)
C (14) -C(19) 1.389(3)
C (16) -C(17) 1.374 (3)
C (17)-N 1.474(3)
N-O (4) 1.219 (3)
C(Il) -C (12) 1.519(4)
C(13)-0(3) . 1.201(3)
C (14)-C(15) 1.397 (3)
C (15)-C(16) 1.378 (3)
C (17)-C (18) 1.379 (3)
C (18)-C(19) 1.382(3)
N-O(5) 1.220 (3)
Table 51. Bond Angles ( °) of [38-syn].
C (2) -C(I) -C (6) 111.0(2) C (2) -C(I) -C (8) 108.4(2)
C (6)-C(I)-C(8) 100.7(2) C (2) -C(I)-C (9) 109.1(2)
C (6)-C(I)-C(9) 114.9(2) C (8) -C(I) -C (9) 112.3(2)
C(I)-C(2)-C(3) 112.4(2) C (2) -C (3) -C (4) 110.9 (2)
C (2) -C (3) -0 (2) 106.3(2) C (4) -C (3) -0 (2) 110,4(2)
C (3) -C (4) -C (5) 108.7(2) C (4) -C (5) -C (6) 114.6(2)
C (I) -C (6)-C (5) 114.1(2) C(I)-C(6)-C(7) 100.8(2)
C (5) -C (6) -C (7) 113.5(2) C(I) -C (6) -C (12) 110.8(2)
C (5) -C (6) -C (12) 109.2(2) C (7) -C(6)-C(12) 108.1(2)
C (6)-C(7)-0(1) 107.5(2) C (7) -0(1) -C (8) 109.5(2)
C(I) -C (8) -0(1) 107.9(2) C(I)-C(9)-C(10) 113.9(2)
C (9) -C(IO) -C(Il) 110.2(2) C(IO) -C(Il) -C (12) 110.2 (2)
C (6) -C (12) -C(Il) 113.8(2) C (3) -0(2) -C (13) 116.5(2)
0(2) -C (13) -0(3) 124.5(2) 0(2) -C (13) -C (14) 111.9(2)
0(3) -C (13) -C (14) 123.5(2) C (13)-C(14)-C(15) 122.5(2)
166
(Table 51. Continued)
C (13)-C(14)-C(19) 117.7(2)
C (14)-C(15)-C(16) 119.6(2)
C (16)-C(17)-C(18) 122.5(2)
C (18)-C(17)-N 118.4(2)
C (14)-C(19)-C(18) 120.7(2)
C (17) -N-O(S) 117.7(2)
C (15)-C(14)-C(19) 119.8(2)
C (15)-C(16)-C(17) 119.3(2)
C (16)-C(17)-N 119.1(2)
C (17)-C(18)-C(19) 118.0(2)
C (17)-N-O(4) 118.0(2)
0(4) -N-0(5) 124.3(2)
X-ray analysis:
Figure 80. ORTEP Drawing of [38-anti].
Table 52. Bond Lengths (A) of [38-anti].
C(I) -C (2) 
Cd) -C (8) 
C (2)-C (3) 
C (3) -0(2) 
C (5) -C(6)
1.561 (7) 
1.522 (8) 
1.475 (7) 
1.464(5) 
1.502(8)
Cd) -C (6) 
Cd) -C (9) 
C (3)-C (4) 
C (4)-C (5)
1.523(7) 
1.514(9) 
1.518 (9) 
1.560 (8)
C (6)-C(7) 1.570 (7)
167
(Table 52. Continued)
C (6) -C(12) 1.517(7) . C (7) -O (I) 1.380(8)
0(1) -C (8) 1.466 (8) C (9) -C(IO) 1.473(16)
C(IO) -C(Il) 1.500 (17) C(Il) -C (12) 1.504(16)
0(2) -C (13) 1.330(5) C (13) -0(3) 1.198(7)
C (13) -C(14) 1.492 (6) C (14)-C(15) 1.393(6)
C (14) -C(19) 1.394 (7) C (15)-C(16) 1.373 (6)
C (16)-C (17) 1.388 (7) C (17)-C(18) 1.378(6)
C (17)-N 1.470 (6) C (18)-C(19) 1.365(6)
N-O(4) 1.209(6) N-O(S) 1.216(7)
Table 53. Bond Angles ( °) of [38-anti].
VDUii—IUCMU 113.4(5) C (2) -C(I) -C (8) 109.9(4)
C (6) -C (I) -C (8) 102.1(4) C (2)-C(I)-C(9) 110.0(4)
C (6) -C(I) -C (9) 110.8(5) C (8) -C(I) -C (9) 110.4(7)
C(I)-C(2)-C(3) 114.2(3) C (2) -C (3) -C (4) 111.1(4)
C (2) -C (3) -0 (2) 108.5(3) C (4) -C (3) -O (2) 106.0(5)
C (3) -C (4) -C (5) 107.8(6) C (4) -C (5) -C (6) 111.3(4)
C(I) -C (6) -C (5) 112.3(4) C(I) -C (6) -C(I) 100.3(5)
C (5) -C (6) -C (7) 106.0(4) Cd) -C (6) -C (12) 115.6(4)
C (5) -C(6)-C (12) 109.4(6) C (7) -C(6)-C (12) 112.6(4)
C (6)-C(7)-0(1) 106.4(4) C (7)-O (I)-C (8) 111.2(5)
C(I) -C (8) -0(1) 104.3(5) C(I) -C (9) -C(IO) 115.2(9)
C (9) -C(IO) -C(Il) 110.3(7) C(IO) -C(Il) -C (12) 112.2(8)
C (6) -C (12) -C (Il) 113.1(8) C(3)-0(2)-C(13) 117.5(4)
168
(Table 53. Continued)
0(2) -C (13) -0(3) 124.0(4) 0(2) -C (13) -C (14) 111.6(4)
0(3) -C (13) -C (14) 124.3(4) C (13)-C(14)-C(15) 117.5(4)
C (13) -C(14)-C(19) ' 122.6(4) C (15)-C(14)-C(19) 119.8(4)
C (14)-C(15)-C(16) 120.3(5) C (15)-C(16)-C(17) 118.2(4)
C (16)-C(17)-C(18) 122.4(4) C (16)-C (17)-N 118.4(4)
C (18) -C(17)-N 119.1(4) C (17)-C(18)-C(19) 118.8(5)
C (14) -C(19)-C(18) 120.3(4) C (17)-N-O(4) 118.8(5)
C (17) -N-O(S) 118.5(4) 0 (4) -N-0(5) 122.7(4)
Preparation of svn--tosvlate derivative of [261
The syn-para-nitrobenzoate derivative of [26] (0.107 g,
0.310 mmol) was dissolved in 0.2 mL dichioromethane and then 
added to a 80% aqueous ethanol solution that was 0.5% by 
weight in KOH. The reaction was stirred overnight. Workup 
yielded a syn-alcohol as a colorless oil (60.0 mg, 0.306 
mmol) (99% yield). The syn-alcohol (60.0 mg, 0.306 mmol) 
was dissolved in 2 mL of dichloromethane to which was added 
0.2 mL of pyridine. The solution was cooled to 0 ° C and TsCl 
(193 mg, 1.01 mmol) was added dropwise. The reaction was 
warmed to room temperature and stirred overnight. Workup 
(page. 131) and flash chromatography (hexane:ethylacetate, 
1:1) yielded a syn-tosylate as a white solid (104 mg, 0*297 
mmol) (97% yield).
169
■svn-3-Tosvl-8-oxatricvclo [4,4,3, Oltridecane, T841 
mp = 116-117*C
1HNMR (300.133 MHz, CDCl3) : 8 1.25-1.79 (14H, m) , 2.40 (3H,
s), 3.45 (1H, d, J=8.OHz), 3.48 (1H, d, J=8.OHz), 3.86 
(1H, d, J=8.IHz), 3i87 (1H, d, J=8.1Hz), 4.57-4.67 (1H, 
m), 7.29 (2H, d, J=8.3Hz), 7.74 (2H, d, J=8.3Hz)
13CNMR (75.4 MHz, CDCl3) : 8 21.44 (t) , 21.51 (q) , 21.86 (t) , 
25.80 (t), 28.16 (t), 28.42 (t), 32.52 (t), 38.66 (t), 
41.18 (s), 43.61 (s), 76.83 (t) (two carbon), 78.98 
(d), 127.46 (d) , 129.69 (d), 134.68 (s), 144.42 (s)
LRMS (EI) m/e (%abundance): 178 (73), 160 (13), 147 (23),
133 (27), 123 (91), 105 (23), 91 (100), 79 (44), 67 
(43), 55 (26), 41 (20)
LRMS (Cl) (NH3) m/e (%abundance) : 368 (M+NH4+, 7), 196 (100) 
HRMS (EI) m/e calculated for C19H26O4S1 = 350.1552; found = 
350.1553
Preparation of anti-tosylate derivative of (261
In a similar fashion, saponification of the anti-para- 
nitrobenzoate derivative of [26] (0.101 g, 0.293 mmol)
afforded 53.4 mg (0.272 mmol) of the anti-alcohol (93% 
yield). Again, identical workup (page 131) gave the anti- 
alcohol (53.4 mg, 0.272 mmol). The alcohol was dissolved in 
2 mL of dichioromethane to which was added pyridine (0.2 mL, 
2.48 mmol) and TSCl (156 mg, 0.818 mmol). The anti-tosylate 
was cleanly separated as a white solid (94.0 mg, 0.269 mmol) 
(99% yield).
170
anfci-3-Tosvl-8-oxatricvclo[4,4,3,Oltridecane, F851 
mp = 53-55 °C
1HNMR (300.133 MHz, CDCl3): 5 1.22-1.81 (14H, m), 2.40 (3H, 
s), 3.37 (in, d, J=8.IHz), 3.41 (1H, d, J=8.2Hz), 3.74 
(1H, d, J=8.2Hz), 3.92 (IH7 d7 J=8.1Hz)7 4.56-4.66 (IH7 
m), 7.29 (2H7 d7 J=8.3Hz)7 7.74 (2H7 d7 J=8.3Hz)
13CNMR (75.4 MHz7CDCl3): 5 21.47 (t) 7 21.57 (q) 7 21.91 (t) 7 
26.86 (t)7 27.91 (t)7 31.91 (t)7 33.18 (t)7 33.94 (t)7 
41.09 (S) 7 44.01 (S) 7 76.14 (t) 7 77.19 (t) 7 79.20 (d) 7 
127.49 (d)7 129.70 (d)7 134.48 (s)7 144.46 (s)
LRMS (BI) m/e (%abundance): 195 (37)7 178 (37)7 147 (40)7 
133 (92)7 123 (33)7 105 (36)7 91 (IOO)7 79 (32)7 67 
(24)7 55 (28)7 41 (66)
LRMS (Cl) (NH3) m/e (%abundance) : 368 (M+NH/7 28) 7 196 (IOO)7 
108 (12)
HRMS (BI) m/e calculated for C19H26O4S1 = 350.1552; found = 
350.1556
Preparation of cis-1,6-dicarbomethoxvbicvcloF5,4,01undec-3- 
ene, (221
A solution of 100 mL of dry THF7 70 mL of 2.5 M n-BuLi 
(0.175 mol) and 25 mL of diisopropylamine (0.180 mol) was 
stirred under argon at -IO0C for 30 minutes. The temperature 
was taken down to -78 °C and cis-3,4-
dicarbomethoxycyclohexene (14.0 g7 0.070 mol) was added 
dropwise, creating a bright red solution. After, addition 
was completed the solution was allowed to stir for 15
11 I I ;.|
171
minutes, then I,5-dibromopentane(11.6 mL, 0.085 mol) was 
added dropwise. The solution was allowed to warm to room 
temperature and stirred overnight. Workup (page 120) and 
distillation yielded a product as a yellow oil (5.21 g,
0.020 mol) (29% yield).
cis-1,6-Dicarbomethoxybicvclo[5,4,01undec-3-ene, (221 
LRMS (EI) m/e: 234, 206, 147, 131, 91 (base), 77, 59, 41 
HRMS (Cl) m/e calculated for C15H22O4 = 266.1518 ; found = 
266.1510
Preparation of cis-1,6^dihvdroxvmethvlbicvclo (5,4,01undec- 
3-ene
A solution of [22] (2.70 g, 10.2 mmol) in 5 mL of dry
THE was added dropwise at 0 °C to a stirring solution of LAH 
(0.58 g, 0.015 mol) in 5 mL of dry THE. The reaction 
mixture was stirred overnight at a room temperature. Workup 
(page 121) yielded a product as a white powder (1.70 g, 8.10 
mmol) (79% yield).
cis-1,6-Dihvdroxymethvlbicvclo[5,4,01undec-3-ene 
mp = 152-153'C
LRMS (EI) m/e: 192 (-H2O), 179, 174 (-H2O), 161, 137, 121, 
106, 91 (base), 79, 67, 41
LRMS (Cl) (Methane) m/e (%abuhdance) : 211 (M+H+, 3) , 209
(5), 193 (23), 175 (100), 163 (22), 147 (14), 133 (15), 
119 (11), 109 (27), 95 (49)
HRMS (Cl) m/e calculated for C13H23O2 = 211.1698; found =
211.1687
172
Preparation of 8-oxatricvclo[5,4,3,01tetradec-3-ene, [271 
cis-1,6-Dihydroxymethylbicyclo[5,4,0]undec-3-ene (1.7 
g, 8.10 mmol) was dissolved in 7 mL of dry pyridine and then 
0.63 mL of MsCl (0.928 g, 8.10 mmol) were added dropwise to 
the stirring solution under argon in ice bath. The reaction 
mixture was stirred at room temperature overnight. Workup 
(page 122) and flash chromatography (hexane:ethylacetate,
1:1) yield a product as a colorless oil (1.02 g, 5.31 mmol) 
(66% yield)
8-Oxatricvclo(5,4,3,01tetradec-3-ene, (271
1HNMR (300.133 MHz, CDCl3): S 1.39-1.97 (14H, m), 3.48 (2H, 
d, J=8.7Hz), 3.63 (2H, d, J=8.7Hz), 5.84-5.86 (2H, m) 
13CNMR (75.4 MHz, CDCl3) : 5 24.61 (t) , 30.97 (t) , 34.34 (t) , 
39.41 (t), 49.55 (s), 81.68 (t), 128.59 (d)
LRMS (EI) m/e: 192 (M+) , 161, 136, 123, 109, 91 (base) , 82, 
67, 41
HRMS (EI) m/e calculated for C13H20O1 = 192.1514; found = 
192.1516
Hvdroboratioh of 8-oxatricvcloF5,4,3,01tetradec-3-ene, (271 
The propellane, [27] (0.044 g, 0.228 mmol) was
dissolved in 2 mL of dry THE and then I mL of BH3.THE (15.6 
mg, 1.13 mmol) were added dropwise to the stirring solution 
under argon at 0 °C. The solution was warmed to room 
temperature and stirred overnight. Workup (page 123) 
yielded a 59:4I mixture of syn-OH and anti-OH as colorless 
oils (38.9 mg, 0.185 mmol) (81% yield).
173
SVii-8-Oxatricvclo [5,4,3,01 tetradec-3-ol, f 65-gynl 
1HNMR (300.133 MHzr CDCl3): 8 1.28-2.06 (16H, m) , 3.43 (IHf 
df J=8.7Hz)r 3.59 (IHf df J=8.5Hz)f 3.80 (IHf df 
J=8.5Hz)f 3.83-3.92 (IHf m)f 4.00 (IHf df J=8.7Hz) 
13CNMR (75.4 MHzfCDCl3): 5 22.49 (t)f 22.61 (t)f 28.32 (t)f
29.03 (t)f 30.76 (t)f 35.42 (t)f 37.01. (t)f 44.26 (t) ,
45.59 (s)f 46.98 (s)f 66.68 (d) f 79.89 (t)f 80.09 (t)
LRMS (BI) m/e (%abundance) : 192 (13)f 147 (17)f 137 (100) f
119 (12)f 105 (20)r 91 (50)f 79 (47)f 67 (44)f 55 (35)f
41 (46)
HRMS (Cl) m/e calculated for C13H23O3 = 211.1698/ found = 
211.1693
anti-8-Oxatricvclo (5,4,3,01 tetradec-3-ol, F65-anfc.il 
1HNMR (300.133 MHzf CDCl3): 5 1.30-1.97 (16Hf m)f 3.42 (IHf 
df J=8.3Hz)r 3.50 (IHf df J=8.3Hz)f 3.82 (IHf df 
J=8.3Hz)r 3.90 (IHf df .J=8.3Hz), 3.93-4.03 (IHf m) 
13CNMR (75.4 MHzfCDCl3): 5 22.25 (t) f 22.36 (t) f 28.42 (t) f 
30.91(t)f 34.04 (t)f 34.82 (t)f 37.22 (t)f 38.29 (t)f 
45.10 (s)f 47.55 (s)f 67.07 (d) f 78.98 (t)f 80.47 (t)
LRMS (BI) m/e (%abundance) : 210 (Mff 2) f 192 (Il)f 179 (13),
161 (IT)f 147 (53),f 137 (18), 119 (29), 105 (47), 91
(100), 79 (88), 67 (66), 55 (66), 41 (71)
HRMS (Cl) m/e calculated for C13H23O2 = 211.1698; found =
211.1698
IPreparation of para-nitrobenzoate derivatives of 8- 
oxatricvclo[5,4,3,01tetradec-3-ene, F271
The mixture of syn- and anti- alcohols derived from the 
hydroboration of [27] (38.9 mg, 0.185 mmol) was dissolved in
5 mL of dry pyridine and an argon atmosphere was created. 
Then PNBCl (51.5 mg, 0.278 mmol) was dissolved in dry 
pyridine and added dropwise to the stirring solution at OeC. 
The reaction was stirred at room temperature overnight. 
Workup (page 125) and flash chromatography
(dichloromethane:ethylacetate:hexane, 10:1:1) isolated the 
isomers as white solids (0.036 g, 0.010 mmol) (55% yield). 
gvn-3-para-Nitrobenzoate-8-oxatricvclo[5,4,3,01 tetradecane, 
[39-synl 1
1HNMR (300.133 MHz, CDCl3): 5 1.40-2.10 (16H, m) , 3.60 (1H, 
d, J=8.7Hz), 3.63 (1H, d, J=8.6Hzj, 3.90 (1H, d, 
J=8.3Hz), 3.97 (IH, d, J=8.6Hz), 5.18-5.27 (1H, m),
8.15-8.19 (2H, m), 8.24-8.28 (2H, m)
“CNMR (75.4 MHz, CDCl3) : 5 22.33 (t) , 22.48 (t) , 26.89 (t) z 
28.55 (t), 28.64 (t), 35.56 (t), 36.66 (t), 40.04 (t), 
45.70 (s), 47.14 (s), 72.02 (d) , 79.33 (t), 79.60 (t), 
123.50 (d), 130.63 (d), 136.17 (s), 150.65 (s), 164.23 
(s)
LRMS (EI) m/e (%abundance).: 192 (55), 161 (15), 147 (32),
137 (100), 120 (25), 104 (17), 91 (32), 81 (22), 67 
(20), 55 (13), 41 (27)
174
11 It
175
LRMS (HPEC) (NH3) m/e (%abundance) : 359 (100) , 328 "(27) , 136
(13)
HRMS (HPEC) (NH3) m/e calculated for C20H25O5N1 = 359.1733; 
found = 359.1725
anfci-3-para-Nitrobenzoate-8-oxatricvclo 
F5,4,3,01tetradecane, r39-anfci1
1HNMR (300.133 MHzt CDCl3) : 8 1.41-2.26 (16H, m) , 3.51 (1H, 
dz J=8.7Hz), 3.64 (IHf df J=8.6Hz)f 3.75 (IHf df 
J=8.6Hz)f 4.00 (IHf df J=8.7Hz), 5.31-5.41 (IHf m)f 
8.17-8.21 (2Hf m) , 8.25-8.29 (2Hf m)
13CNMR (75.4 MHzfCDCl3): 5 22.87 (t)f 22.91 (t) f 26.77 (t)f
29.26 (t) f 32.75 (t) f 35.46 (t) f 35.68 (t)f 37.33 (t)f
45.46 (S)f 34.36 (s)f 72.28 (d) , 79.69 (t)f 80.58 (t)f
123.46 (d) , 130.62 (d) f 136.26 (s)f 150.61 (s)f 164.22 
(s) f
LRMS (EI) m/e (%abundance) : 359 (Mtif, 2) f 209 (41) f 192 (34) f 
174 (Il)f 161 (39)f 147 (77)f 137 (IOO)f 120 (42)f 105 
. (58) f 91 (71) f 81 (50)f 67 (45) f 55 (27) f 41 (54)
LRMS (HPEC) (NH3) m/e (%abundance) : 359 (100) f 328 (21)
HRMS (HPEC) (NH3) m/e calculated for C20H25O5N1 = 359.1733; 
found = 359.1728
176
Crystallization of the product, [39-anti] was 
accomplished in dichloromethane:hexane in a relative ratio 
of 1:10, respectively.
X-ray analysis:
Figure 81. ORTEP Drawing of [39-anti].
Table 54. Bond Length (A) of [39-anti].
C(I) -C (2) 1.524 (30)
Cd) -C (8) 1.588 (26)
C (2) -C(3) 1.555 (28)
C (3) -0(2) 1.422 (25)
C (5) -C(6) 1.505(31)
C (6)-C(13) 1.560 (28)
O(I)-C(S) 1.427 (27)
C(IO) -C(Il) 1.461 (36)
C (12)-C(13) 1.497 (32)
Cd) -C (6) 1.558(30)
Cd) -C (9) 1.499 (29)
C (3)-C(4) 1.519(31)
C (4) -C (5) 1.493(30)
C (6)-C(7) 1.579(30)
C (7) -0(1) 1.405(27)
C (9)-C(IO) 1.507(26)
C(Il) -C (12) 1.459(32)
0(2) -C (14) 1.316(27)
177
(Table 54. Continued)
C (14) -0(3) 1.252(30) C (14)-C(15) 1.444 (32)
C (15)-C(16) 1.379(32) C (15)-C(20) 1.376 (33)
C (16)-C(17) 1.366 (32) C (17)-C (18) 1.351(33)
C (18) -C (19) 1.360(29) C (18)-N 1.472 (29)
C (19) -C (20) 1.390 (32) N-O (4) 1.184(30)
N-O (5) 1.215(33)
Table 55. Bond Angles ( °) of [39-anti].
C(2) -C(I) -C(6) 110.9(18) C (2) -C(I) -C (8) 109.3(16)
C (6)-C(I)-C(S) 99.7(14) C (2)-C (I)-C (9) 110.3(15)
C(6)-C(l)-C(9) 118.5(18) C (8)-C(I)-C(9) 107.4(18)
C(I)-C(2)-C(3) 117.2(14) C (2) -C (3) -C (4) 106.8(16)
C (2) -C (3) -0(2) 108.3(13) C (4) -C(3) -0(2) 107.1(18)
C (3) -C (4) -C (5) 109.8(19) C (4)-C(S)-C(6) 113.9(15)
C(I)-C(6)-C(5) 112.3(17) C (I) -C (6) -C (7) 99.4(18)
C(S)-C(6)-C(7) 109.3(14) C(I)-C(6)-C(13) 118.1(13)
C (5) -C(6)-C (13) 107.9(19) C (7) -C(6)-C(13) 109.5(16)
C (6)-C (7) -0 (1) 104.1(16) C (7)-O(I)-C(S) 114.0(15)
C(I)-C(S) -0(1) 102.9(16) . C (I) -C (9) -C (10) 117.8(21)
C (9)-C(IO)-C (Il) 120.3(18) C(IO)-C(Il)-C (12) 12Q.2 (19)
C(Il) -C (12) -C (13) 117.0(21) C (6)-C(13)-C(12) 120.1(21)
C O ) -0(2)-C (14) 117.7(17) 0(2) -C (14) -0(3) 122.1(20)
0(2)-C(14)-C(15) 117.1(21) 0(3) -C (14) -C (15) 120.8 (20)
C (14)-C(15)-C(16) 121.1(21) C (14)-C(15)-C(20) 121.0(21)
178
(Table 55. Continued)
C (16) -C (15) -C (20) 117.8(21) C (15)-C(16)-C(17) 121,9(22)
C (I6)-C(17)-C(18) 119.0(21) C (17)-C(18)-C(19) 121.3(20)
C (17)-C (18)-N 118.0(19) C (19)-C (18)-N 120.7(20)
C (18) -C (19) -C (20) 119.4(21) C (15)-C(20)-C(19) 120.3(21)
C (18)-N-O(4) 120.5 (22) C (18) -N-O(S) 117.0(19)
0(4) -N-O(S) 122.2(22)
Preparation of syn-tosvlate derivative of [271
The syn-para-nitrobenzoate derivative of [27] (10.0 mg,
0.025 mmol) was dissolved in 0.5 mL dichloromethane and then 
added to a 80% aqueous ethanol solution that was 0.5% by 
weight in KOH. The reaction was stirred overnight. Workup 
yielded a syn-alcohol as a colorless oil (5.00 mg, 0.024 
mmol) (94% yield). The syn-alcohol (5.00 mg, 0.024 mmol) 
was dissolved in 0.5 mL of dichloromethane to which was 
added I mL of pyridine. The solution was cooled to O0C and 
TsCl (5.40 mg, 0.029 mmol) was added dropwise. The reaction 
was warmed to room temperature and stirred overnight.
Workup (page 131) and flash chromatography
(hexane:ethylacetate, 7:3) yielded a syn-tosylate as a white 
solid (2.00 mg, 0.0055 mmol) (23% yield). 
svn-3-Tosvl-8-oxatricvclo[5,4,3,01tetradecane, [861 
1HNMR (300.133 MHz, CDCl3) : 5 1.0-1.92 (16H, m) , 2.43 (3H,
s) , 3.49 (1H, d, J=8.5Hz), 3.50 (1H, d, J=8.5Hz), 3.82
179
(1H, d, J=8.6Hz), 3.85 (1H, d, J=8.6Hz), 4.63-4.73 (1H, 
m), 7.32 (2H, d, J=8.3Hz), 7.77 (2H, df J=8.3Hz)
13CNMR (75.4 MHzfCDCl3) : 5 21.63, 22.01, 22.19, 27.75, 28.10, 
28.22, 35.08, 36.40, 40.84, 45.29, 47.29, 78.76, 78.92, 
79.20, 127.60, 129.77, 134.75, 144.49 
Preparation of anti-tosylate derivative of (271.
In a similar fashion, saponification of the anti-para- 
nitrobenzoate derivative of [27] (20.0 mg, 0.051 mmol)
afforded 10.0 mg (0.048 mmol) of the anti-alcohol (93% 
yield). Again, using the identical workup (page 131), the 
anti-alcohol (10.0 mg, 0.048 mmol) was dissolved in 0.5 mL 
of dichloromethane to which was added I mL of pyridine and 
TsCl (10.8 mg, 0.057 mmol). The anti-tosylate was cleanly 
separated to give 3 mg (010082 mmol) of tosylate (17% yield) 
and starting material.
anti-3-Tosvl-8-oxatricvclo[5,4,3,Oltetradecane, [871 
1HNMR (300.133 MHz, CDCl3): 5 1,0-1.92 (16H, m) , 2.43 (3.H,
s), 3.39 (1H, d, J=8.8Hz), 3.53 (1H, d, J=8.7Hz), 3.61 
(1H, d, J=8.7Hz), 3.70 (1H, d, J=8.8Hz), 4.74-4.84 (1H, 
m), 7.32 (2H, d, J=8.3Hz), 7.77 (2H, d, J=8.3Hz)
13CNMR (75.4 MHz,CDCl3) : 8 21.64, 22.84 (2 carbons), 27.17,
29.28, 32.21, 35.60, 36.55, 36.88, 45.08, 47.44,, 79.24, 
79.83, 80.64, 127.70, 129.80, 134.79, 144.54
. 180
Preparation of cig-9,10-methanesulfonvloxvmethvlbi-cvclo 
f4,3,01non-3-ene, [291
To an ice-cold stirred solution of methanesulfonyl 
chloride (10.0 mL, 0.130 mol) in 15 mL of pyridine was added 
dropwise to a solution of the diol [31] (6.75 mg, 0.037 mol)
at 0°C. After an additional 2 hours stirring in the cold 
ice bath, workup (page 125) yielded a product as a white 
powder (9.80 g, 0.029 mol) (78% yield).
cis-9,10-Methanesulfonyloxymethylbicvclo[4,3,01non-3-ene,
[291
mp = 73-74 0 C
IR (nujol, cm-1) : 3030, 2951, 2857, 1456, 1337, 1171, 991, 
951, 839, 759, 679
1HNMR (300.133 MHz, CDCl3): 5 1.66- 1.87 (6H, m) , 1.98-2.16 
(4H, m), 3.00 (6H, s), 4.08-4.17 (4H)
13CNMR (75.4 MHz, CDCl3) : 5 18.39 (t) , 30.35 (t) , 33.44 (t) ,
37.30 (q), 45.29 (s), 72.83 (t), 123.54 (d)
LRMS (EI) m/e: 146, 131 (base), 118, 104, 77, 63, 44. 
Preparation of 8-thiatricvcio[4,3,3,01dodec-3-ene, [301
The dimesylate, [29], (4.2 g, 0.012 mol) was mixed with
sodium sulfide (3.43 g, 0.044 mol) (sodium sulfide.9 hydrate 
was treated with benzene azeotrope to remove water), and 50 
mL of dry hexamethylphosporamide, and heated to 120°C for 24 
hours. The brownish colored contents were cooled to room 
temperature and treated .with 50 mL of water, and extracted 
with ether. The ether layer was washed with water,
181
saturated brine, dried over MgSO4 and reduced in volume to 
give the product as-white powder (1.92 g, 0.0107 mol) (86% 
yield)
S-Thiatricvclo T4,3;3,01dodec-3-ene, (301 
mp = 84-85 °C
IR (nujol, cnf1) : 3025, 2967, 2902, 2855, 1460, 1214, 733,
6 6 3
1HNMR (300.133 MHz, CDCl3): 6 1.54-1.82 (6H, m) , 1.97 (2H, 
d, J=I6.7Hz), 2.13 (2H, d, J=16.7Hz), 2.69 (2H, d,
J=10.IHz), 2.81 (2H, d, J=10.IHz), 5.56 (2H, t,
J=I.8Hz)
13CNMR (75.4 MHz, CDCl3) : 5 19.75 (t) , 31.90 (t) , 36.09 (t) , 
42.53 (t), 53.97 (s), 124.74 (d)
LRMS (EI) m/e (%abundance): 180 (M+, 61), 147 (8), 133 (37), 
125 (15), 119 (98), 105 (28), 98 (12), 91 (100), 79 
(25), 65 (12), 53 (12), 41 (21) .
HRMS (EI) m/e calculated for C11H16S1 = 180.0974; found = 
180.0979
Hvdroboration of 8-thiatricvcloT4,4,3,01dodec-3-ene, [301
The propellane, [30] (0.400 g, 2.22 mmol) was dissolved
in 5 mL of dry THE and then 2 mL of BH3. THE (0.031 mg, 2.26 
mmol) were added dropwise to the stirring solution under 
argon at O0C. The solution was warmed to room temperature 
and stirred overnight. Workup (page 123) yielded a 45:55 
mixture of syn-OH and anti-OH as white solids (0.365 g,I.84 
mmol) (83% yield).
182
syn-8-Thiatricvclb [4,4,3,01 dodec-3-ol, f68-syr»l 
IR (neat, cm-1) : 3375, 2930, 2864, 1465, 1303, 1071, 1051, 
998, 732, 666
1HNMR (300.133 MHz, CDCl3): 8 1.36-1.87 (12H, m) , 2.55 (1H, 
d, J=IO.8Hz), 2.69 (1H, d, J= 10.7Hz), 2.89 (1H, d, 
J=IO.8Hz), 3.02 (1H, d, J=IO.7Hz), 3.70-3.80 (1H, m) 
13CNMR (75.4 MHz, CDCl3) : 5 19.49 (t) , 29.61 (t) , 31.45 (t) , 
33.00 (t), 36.78 (t), 38.53 (t) , 38.93 (t), 44.50 (t), 
54.16 (s), 57.07 (s), 67.48 (d)
LRMS (EI) m/e (%abundance) : 198 (M+, 39), 180 (46), 133
(36), 125 (100), 119 (84), 105 (13), 97 (10), 91 (38), 
79 (21), 67 (13), 53 (11)
HRMS (EI) m/e calculated for C11H18O1S1 = 198.1078; found = 
198.1071
anti-8-Thiatricvclo[4,4,3,01dodec-3-ol, F 68-antiI 
IR (neat, cm"1) : 3375, 2930, 2864, 1465, 1303, 1071, 1051, 
998, 732, 666
1HNMR (300.133 MHz, CDCl3): 5 1.25-1.88 (12H, m) , 2.51 (1H, 
d, J=IO.8Hz), 2.72 (1H, d, J=IO.8Hz), 2.89 (1H, d, 
J=IO.8Hz), 2.91 (1H, d, J=IO.8Hz), 3.70-3.79 (1H, m)
13CNMR (75.4 MHz,CDCl3): 5 19.54 (t) , 28.50 (t) , 31.27 (t) , 
31.95 (t), 37.99 (t), 39.25 (t), 39.61 (t), 43.32 (t), 
54.70 (s), 56.52 (s), 67.24 (d)
LRMS (EI) m/e (%abundance) : 198 (M+, 94), 180 (8), 151 (37), 
133 (100), 119 (49), 109 (16), 93 (42), 79 (26), 67 
(18), 60 (12), 53 (14), 45 (12)
183
HRMS (EI) m/e calculated for C11H18O1S1 = 198.1078; found = 
198.1072
Preparation of para-nitrobenzoate derivatives of 8- 
thiatricvclo f4,3., 3, 0 T dodec-3-ene, (301
The mixture of syn- and anti-alcohol derived from the 
hydroboration of [30] (0.283 q, 1.43 mmol) was dissolved in
5 mL of dry pyridine and an argon atmosphere was created. 
Then PNBCl (0.398 g, 2.15 mmol) was dissolved in dry 
pyridine and added dropwise to the stirring solution at OeC. 
The reaction was stirred at room temperature overnight. 
Workup (page 125) and flash chromatography 
(dichloromethane:ethylacetate:hexane, 25:1:1) isolated the 
isomers as white powders (0.288 g, 0.830 mmol) (58% yield). 
svn-3-para-Nitrobenzoate-8-thiatricvclo[4,3,3,01 dodecane,
[ 42-synl *1
mp = 146-147 ° C
1HNMR (300.133 MHz, CDCl3): 5 1.52-1.98 (12H, m) , 2.60 (1H, 
d, J=Il.0Hz), 2.76 (1H, d, J=10.8Hz), 2.93 (1H, d,
J=Il.OHz), 3.05 (1H, d, J=IO.8Hz), 5.10-5.19 (1H, m), 
8.13-8.25 (4H, m)
13CNMR (75.4 MHz,CDCl3): 5 19.48 (t) , 27.31 (t), 28.98 (t) , 
33.13 (t), 34.71 (t), 36.46 (t) , 38.77 (t) , 44.1,3 (t) , 
54.18 (s), 56.77 (s), 72.13 (d), 123.40 (d) , 130.56 
(d), 135.95 (s), 150.48 (s), 164.06 (s)
184
LRMS (EI) m/e (%abundance): 347 (M+, 8), 317 (6), 180 (90), 
150 (I), 125 (100) , 104. (19), 91 (38), 79 (17), 65 
(11), 41 (15)
HRMS (EI) m/e calculated for C18H21O4N1S1 = 347.1191; found = 
.347.1191
anti-3-para-Nitrobenzoate-8-thiatricvclo(4,3,3,01 dodecane, 
r42-anfci1 1
mp = 123-124 0C
1HNMR (300.133 MHz, CDCl3): 5 1.58-1.99 (12H, m), 2.61 (1H, 
d, J=IO.9Hz), 2.82 (IH, d, J=IO.9Hz), 2.92 (1H, d, 
J=IO.9Hz), 3.00 (IH, d, J-10.9Hz), 5.11-5.20 (IH, m) , 
8.14-8.26 (4H, m)
13CNMR (75.4 MHz, CDCl3) : 5 19.63 (t) , 27.18 (t) , 28.04 (t) , 
32.53 (t), 35.47 (t), 37.63 (t), 39.53 (t), 42.75 (t),
54.65 (s), 56.31 (s), 72.12 (d), 123.45 (d), 130.58 
(d), 136.00 (s), 150.51 (s), 164.03 (s)
LRMS (EI) m/e (%abundance): 347 (M+, 18), 317 (8), 180
(100), 150 (27), 125 (70), 104 (25), 91 (53), 79 (20),
(
67 (16) , 60 (16) , .41 (20)
HRMS (EI) m/e calculated for C18H21O4N1S1 = 347.1191; found =
347.1185
185
Crystallization of the product, [42-syn] was 
accomplished in hexane:dichloromethane in a relative ratio 
of 10:1 respectively and the product, [42-anti] was 
accomplished in hexane:dichloromethane in a relative ratio 
of 10:1, respectively.
X-ray analysis:
Figure 82. ORTEP Drawing of [42-syn].
Table 56. Bond Lengths (A) of [42-syn].
C(I) -C (2) 1.570 (8)
Cd) -C (8) 1.516 (10)
C (2) -C(3) 1.478 (9)
C(S)-O(I) 1.466(6)
C (5) -C(6) 1.522 (11)
C (6) -C(11) 1.526(10)
S-C(S) 1.751 (10)
Cd) -C (6) 1.493(10)
Cd) -C (9) 1.534 (11)
C (3)-C (4) 1.505 (10)
C (4) -C (5) 1.554(10)
C (6)-C(I) 1.573(13)
C(I) -S 1.754 (11)
C (9)-C(IO) 1.572 (12)
I186
(Table 56. Continued) .
C(IO) -C(Il) 1.458(13) O(I) -C (12) 1.339(7)
C (12) -0(2) 1.188(7) C (12)-C(13) 1.497 (8)
C (13)-C(14) 1.399 (8) C (13)-C (18) l'396(7)
C (14) -C(15) 1.375 (8) C (15) -C (16) 1.382 (8)
C (16) -C(17) 1.381(8) C (16).-N 1.475(7)
C (17)-C (18) 1.380 (8) N-O(3) 1.217 (7)
N-O(4) 1.225(6)
Table 57. Bond Angles ( °) of . [42-syn] .
C (2) -C(I) -C (6) 112.4(6) C (2) -C(I) -C (8) 109.4(5)
C (6) -C(I) -C (8) 106.0(6) C(2)-C(I)-C(9) 113.1(5)
C (6) -C(I) -C (9) 104.7(6) 0(8)-C(I)-C(9) 111.0(6)
C (I) -C (2) -C (3) 112.4(5) 0(2) -C (3) -C (4) 111.1(5)
C (2)-C(S)-O(I) 106.2(5) 0(4) -C (3) -0(1) 109.8(5)
C (3) -C (4) -C (5) 108.2(6) C (4) -C (5) -C (6) 112.4(7)
C(I) -C (6) -C (5) 112.3(5) Cd) -C (6) -C (7) 107.3(6)
C (5) -C (6) -C (7) 114.1(7) C(I) -C (6) -C(Il) 102.1(6)
C (5) -C (6) -C(Il) 110.3(6) 0(7) -C (6) -C(Il) 110.1(5)
C (6)-C(7)-S 106.8(7) 0(7)-S-C(S) 95.2(5)
C(I) -C (8) -S 110.0(6) C(I) -C(9) -C(IO) 102.4(6)
C (9) -C(IO) -C(Il) 107.6(7) C (6) -C(Il) -C(IO) 105.1(6)
C (3) -0(1) -C (12) 117.0(1) 0(1) -C (12) -0(2) 125.2(5)
0(1) -C (12) -C (13) 110.8(5) 0(2) -C (12) -C (13) 124.0(5)
C (12) -C(13)-C(14) 123.0(5) C (12)-C(13)-C(18) 117.1(5)
187
(Table 57. Continued)
C (14)-C(13)-C (18) 119.9 (5) 0(13) -0(14) -0(15) 120.3(5)
C (14)-C(15)-C(16) 118.0(5) 0(15) -0(16) -C (17) 123.5(5)
C (15)-C(16)-N 118.5(5) C (17)-C(16) -N 118.0(5)
C (16)-C(17)-C(18) 117.9(5) 0(13) -0(18) -0(17) 120.3(5)
C (16)-N-O(3) 118.4(5) 0(16) -N-O (4) 118.0(5)
0(3) -N-O (4) 123.6 (5)
X-ray analysis:
S
Figure 83. ORTEP Drawing of [42-anti].
Table 58. Bond Lengths (A) of [42-anti].
C(I)-C(2) 1.553(6) C(I)-C(S) 1.555(6)
C(I)-C(S) 1.531(6) C(D-CO) 1.528 (7)
0(2)-C(3) 1.511 (6) 0(3) -0(4) 1.513(6)
188
(Table 58. Continued)
C(3)-0(l) 1.467 (5)
C (5) -C(G) 1.516 (6)
C(G) -C(Il) 1.526 (6)
S-C(S) 1.805(5)
C(IO) -C(Il) 1.536 (7)
C (12) -0(2) 1.203(5)
C (13)-C(14) 1.384(5)
C (14)-C(15) 1.372(6)
C(IG) -C (17) 1.376 (5)
C (17)-C(18) 1.370 (5)
N-O(4) 1.212(5)
C (4)-C(5) 1.527(6)
C(G)-C(7) :1.536(6)
C (7)-S 1.806 (5)
C (9) -C(IO) 1.527 (7)
0(1) -C (12) 1.337 (5)
C (12)-C(13) 1.489 (5)
C (13)-C (18) 1.400 (5)
C (15) -C(IG) 1.374(6)
C(IG)-N 1.486 (5)
N-O(3) 1.218(5)
Table 59. Bond Angles ( 6) of [42-anti].
C (2)-C(I)-C(G) 111.7(3)
C (6)-C(I)-C(S) 108.6(4)
<T>UIT—IUI<£>U 102.7(3)
C (I)-C (2)-C (3) 112.6(3)
C (2) -C (3) -0 (I) 109.9(3)
C (3) -C (4 j -C (5) 110.0(3)
C (I)-C(G)-C(S) 112,5(3)
C (5) -C (6) -C (7) 110.0(4)
C (5) -C (6) -C(Il) 114.6(4)
C (6)-C(7)-S 108.7(3)
C(I) -C (8) -S 107.6 (3)
C (2) -C(I)-C (8) 111.1(3)
VHOCNU 109.2(4)
C (8) -C(I) -C (9) 113.3(3)
C (2) -C (3) -C (4) 109.9(3)
C (4)-C(3)-0(l) . 105.6(3)
C (4) -C (5) -C (6) 113.0(4)
C(I) -C (6) -C (7) 104.6(3)
C (I)-C(6)-C(11) - 104.4(4)
C (7) -C (6) -C(Il) 110.2(4)
C (7)-S-C (8) 94.5(2)
C(I) -C (9) -C(IO) 105.6(4)
189
(Table 59. Continued)
C (9)-C(IO)-C(Il) 107.3(4) C (6) -C(Il) -C(IO) 105.6 (4)
C (3)-0(1)-C(12) 117.5(3) 0(1) -C (12) -0(2) 124.4(4)
0(1) -C (12) -C (13) 111.9(3) 0(2) -C (12) -C (13) 123.7(4)
C (12)-C(13)-C (14) 118.0(3) C (12)-C(13)-C(18) 122.6(3)
C (14) -C(13)-C(18) 119.4(4) C (13) -C (14) -C (15) . 120.3(4)
C (14)-C(15)-C(16) 118.7(4) C (15)-C(16)-C (17) 122.9(4)
C (15)-C(16)-N 118.5(4) C (17)-C(16)-N 118.6(3)
C (16)-C(17)-C(18) 117.9(4) C (13)-C(18)-C(17) 120.8(4)
C (16) -N-O (3) 118.2(3) C (16)-N-O(4) 118.1(3)
0(3) -N-O (4) 123.7(4)
Preparation of svn--tosvlate derivative of [301
The syn-para-nitrobenzoate derivative of [30] (47.7 mg,
0.137 mmol) was dissolved in 0.2 mL dichioromethane and then 
added to a 80% aqueous ethanol solution that was 0.5% by 
weight in KOH. The reaction was stirred overnight. Workup 
yielded a product as a white solid (24.8 mg, 0.125 mmol)
(91% yield). The syn-alcohol (24.8 mg, 0.125 mmol) was 
dissolved in 0.2 mL of dichloromethane to which was added 
0.1 mL of pyridine. The solution was cooled to O'C and TsCl 
(71.5 mg, 0.375 mmol) was added dropwise. The reaction was 
warmed to room temperature and stirred overnight. Workup 
(page 131) and flash chromatography (hexane:ethylacetate, 
1:1) yielded a product as a white solid (28.7 mg, 0.082 
mmol) (65% yield).
190
gvn-3-Tosvl-8—thiatricvclo[4,3,3,01dodecane, [801 
mp = 77-79°C
1HNMR (300.133 MHzf CDCl3): 5 1.32-1.85 (12H, m) , 2.43 (3H, 
s) , 2.54 (IHf df J=Il.OHz)f 2.70 (IHf df J=IO.8Hz)f
2.85 (IHf df J=Il.OHz), 2.94 (IHf df J=IO.8Hz)f 4.57- 
4.67 (IHf m), 7.31 (2Hf df J=7.9Hz)f 7.77 (2Hf df 
J=8.3Hz)
13CNMR (75.4 MHzfCDCl3): 5 19.44 (t) , 21.58 (q) f 28.29 (t) f 
28.94 (t)f 33.12 (t)f 35.55 (t)f 36.30 (t)f 38.68 (t),
43.91 (t)f 53.92 (s)f 56.95 (s)f 79.02 (d) f 127.55 (d)f 
129.75 (d)f 134.89 (s)f 144.44 (s)
LRMS (EI) m/e ): 352 (M+) f 180, 152, 125 (base) , 105, 91,
79, 65, 55, 49, 41
LRMS (Cl) (NH3) m/e (%abundance) : 370 (M+NH4+, 99), 353 (6) ,
214 (22), 197 (26), 181 (100)
HRMS (EI) m/e calculated for C18H24O3S2 = 352.1167; found =
352.1163
Preparation of anfci-tosvlate derivative of (301
In a similar fashion, saponification of the antl-para- 
nitrobenzoate derivative of [30] (67.0 mg, 0.193 mmol)
afforded 38.2 mg (0.193 mmol) of the anti-alcohol (100% 
yield). Again, using the identical workup (page 131), the 
anti-alcohol (38.2 mg, 0.193 mmol) was dissolved in 0.5 mL 
of dichloromethane to which was added 0.I mL of pyridine 
and TsCl (0.115 g, 0.579 mmol). The antf-tosylate was 
cleanly separated as white solid (53.6 mg, 0.152 mmol) (79% yield)
191
anfci-3-Tosvl-8-thiatricvclo F4,3,3,01dodecane, FSll
1HNMR (300.133 MHz, CDCl3): S 1.52-1.82 (12H, m), 2.43 (3H,
s), 2.53 (1H, d, J=IO.9Hz), 2.73 (2H, s), 2.85 (1H, d,
J=IO.9Hz), 4.51-4.60 (IH, m), 7.32 (2H, d, J=S.IHz), 7.77 
(2H, d, J=8.3Hz)
13CNMR (75.4 MHz, CDCl3): 5 19.54 (t) , 21.60 (q) , 27.89 (t) , 
27.99 (t), 32.61 (t), 36.19 (t), 37.38 (t), 39.58 (t), 
42.50 (t), 54.37 (s) , 56.45 (s) , 78.98 '(d), 127.64 (d) 
129.81 (d), 134.95 (s), 144.50 (s)
LRMS (EI) m/e (%abundance) : 352 (M+, I) , 307 (2) , 197 (4) ,
180 (35), 149 (31), 119 (47), 105 (19), 97 (19), 91 
(78), 81 (48), 69 (100), 57 (44), 40 (58)
LRMS (Cl) (NH3) m/e (%abundance) : 370 (M+NH/, I) , 230 (7) ,
181 (100)
HRMS (EI) m/e calculated for C18H24O3S1 = 352.1167; found = 
352.1168
Preparation of N-benzvloxvmethyl-c.is-1,2,3,6- 
tetrahvdrophthalimide, (541
A solution, prepared from cis-1,2,3,6- 
tetrahydrophthalimide (2.0 g, 0.013 mol), benzyl 
chloromethyl ether (2.2 mL, 0.016 mol), and K2CO3 (2.7 g, 
0.02 mol), under argon atmosphere was refluxed overnight. 
After neutralization with HCl, the reaction mixture was 
extracted with dichloromethane. The combined extracts were 
washed with brine, dried over anhyd MgSO4, filtered and 
reduced in volume by rotary evaporation. Flash
192
chromatography (silica gel, hexane:ethylacetate, 1:1) gave 
2.6 g (91%) of the desired protected imide as a pale yellow 
oil.
N-benzyloxymethyl-cis-l,2,3.6-tetrahvdrophthalimide, F541 
1HNMR (300.133 MHz, CDCl3) : 5 2.16-2.23 (2H, m) , 2.53-2.60
(2H, m), 2.95-2.99 (2H, m), 4.53 (2H, s), 4.95 (2H, s), 
5.86-5.88 (2H, m), 7.29 (5H, m)
13CNMR (75.4 MHz,CDCl3) : 8 23.36 (t) , 39.08 (d) , 67.77 (t) , 
71.97 (t), 126.96 (d), 127.61 (d), 127.68 (d) , 128.35 
(d) , 128.54 (d) , 137.57 (s), 179.70 (s)
LRMS (EI) m/e (%abundance): 271 (M+, 3), 165 (100), 136 (4), 
111 (10), 91 (36), 79 (25), 65 (7), 41 (2)
HRMS (EI) m/e calculated for C16H17O3N = 271.1208; found = 
271.1209 •
Preparation of N-benzvloxvmethvl-7,9,-dioxo-8-azatricvclo 
T4,3,3,01dodec-3-ene, (551
A solution of 15 mL dry THF, 0.56 mL of 10M n-BuLi 
(0.0058 mol) and 0.83 mL of diisopropylamine (0.0059 mol) 
was stirred under argon at -78 0C of 15 minutes. To this 
solution was slowly added 0.50 g of [54] (0.0023 mol),
resulting in a red-colored solution of the dianion. After 
stirring of an additional 15 minutes, I,3-dibromopropane 
(0.28 mL, 0.0028 mol) was added, dropwise. After the 
addition was completed the reaction mixture was allowed to 
warm to room temperature. After several more hours of 
stirring, the reaction mixture was neutralized with cone.
193
HCl. The salts were removed by filtration and excess 
solvent was removed from the filtrated by rotary 
evaporation. The residue was extracted with 
dichioromethane, and after drying the combined extracts over 
anhyd MgSO4, the excess solvent was removed by rotary 
evaporation. The crude residue was subjected to flash 
chromatography (silica gel, hexane:ethylacetate, 1:1) to 
give 0.36 g (61%) of product as a yellow oil. 
N-benzyloxymethyl-?,9-dioxo-8-azatricvcloT4,3,3,01dodec-3- 
ene, (551
1HNMR (300.133 MHz, CDCl3) : S 1.21-2.70 (10H, m), 4.50 (2H, 
s), 4.92 (2H, s), 5.88-5.90 (2H, m), 7.29 (5H, m)
13CNMR (75.4 MHz,CDCl3) : 5 24.46 (t) > 31.12 (t) , 38.18 (t) ,
56.05 (s), 67.72 (t), 71.76 (t), 127.69 (d) , 127.78 
(d) , 127.94 (d) , 128.34 (d) , 128.50 (d), 131.86 (d),
137.46 (s), 182.32 (s)
LRMS (EI) m/e (%abundance) : 311 (M+) , 205 (100) , 176 (4),
148 (6), 119 (20), 91 (84), 65 (13), 41 (2)
HRMS (EI) m/e calculated for C19H21O3N = 311.1521; found =
311.1529
Preparation of 7,9-dioxo-8-azatricvcloF4,3,3,01dodec-3-ene, 
(561
A. solution of [55] (33 mg, 0.13 mmol) , BBr3 (0.3.5 mL,
0.15 mmol) and 5 mL benzene was stirred at room temperature 
for I hour. Methanol (0.2 mL) was added to the reaction 
mixture and after 30 minutes the low-boiling solvents were
removed by rotary evaporation. The residue, in.4 mL water, 
was heated to boiling for 30 minutes. . Water was removed by 
vacuum and the resulting solid was extracted with 
dichloromethane. The combined extracts were dried over 
anhyd MgSO4, and after removal of solvent the crude product 
was chromatographed (silica gel, hexane:ethylacetate, 1:1) 
to yield 20 mg (83%) of product as pale/yellow powder.
7,9-Dioxo-8-azatricvclo(4,3,3,01dodec-3-ene, (561 
mp = 162-163 ° C
1HNMR (300.133 MHz, CDCl3) : 8 1.33-2.68 (IOH, m), 5.90-5.92 
(2H, m), 8.85 (1H, br)
13CNMR (75.4 MHz,CDCl3) : 8 24.46 (t) , 30.96 (t) , 38.-05 (t) , 
57.19 (s), 128.44 (d) , 182.90 (s)
LRMS (EI) m/e (%abundance): 191 (M+, 100), 148 (42), 120 
(47) , 91 (61) , 65 (9) , 41 (5)
HRMS (EI) m/e calculated for C11H13O2N = 191.0946; found = 
191.0938
Preparation of 2,4-dioxo-3-azabicvclo T3,3,01 oct-A1,5-ene,
(481
The propellane [56] (20 mg, 0.11 mmol) was passed
through a FVT apparatus at about 600 0C and under high 
vacuum. The products were collected in a trap cooled by dry 
ice, and consisted of 35% starting material, 60% product and 
5% of an unidentified material. The product was purified by 
flash chromatography (silica gel,
dichloromethane:hexane:ethylacetate, 20:1:1) to give a
195
crystalline sample, mp 178-179 * (Ref21, 177-179" ) as a white 
solid.
2,4-Dioxo-3-azabicvclo F3,3,01 Oct-A1f5-Sne, (481 
1HNMR (300.133 MHz, CDCl3): 8 2.43 (2H, pentet,. J=7.3Hz) ,
2.65 (4H, t, J=7.3Hz), 7.05 (1H, br)
13CNMR (75.4 MHz, CDCl3): 5 26.40 (t), 27.55 (t) , 154.61 (s) , 
166.66 (s)
LRMS (EI) m/e (%abundance) : 137 (M+, 13), 94 (77), 66 (100), 
52 (8), 41 (3)
HRMS (EI) m/e calculated for C7H7O2N = 137.0477; found = 
137.0474
Preparation of dimethyl-1,2-cvclopentene dicarboxvlate, (181 
cis-I,6-Dicarbomethoxybicyclo[4,3,0]non-3-ene, [17]
(36.4 mg, 0.0153 mmol) was passed through a FVT apparatus at 
about 600 C^ and under high vacuum. The products were 
collected in a trap cooled by dry ice. Extraction with 
dichloromethane yielded only product, [18] as a pale yellow 
oil (28.0 mg, 0.152 mmol)(99% yield).
Dimethyl—I,2-cvciopentene dicarboxvlate, [181
1HNMR (300.133 MHz, CDCl3): 5 1.99 (2H, pentet, J=7.6Hz),
2.72 (4H, t, J=7.6Hz), 3.75 (6H, s)
13CNMR (75.4 MHz,CDCl3) : 5 22.27 (t) , 34.60 (t), 51.90 (q) , 
140.11 (s), 166.09 (s)
LRMS (EI) m/e: 184 (M+) , 152 (base), 124, 93, 79, 59, 41 
HRMS (EI) m/e calculated for C9H12O4 = 184.0736; found =
184.0740
196
Preparation of 3-methyl-cis-l,6-dicarbomethoxvbicvclo 
[4,3,01non-3-ene, [1121
A solution of 20 mL of dry THF7 3.38 mL of IOM n-BuLi 
(0.0338 mol) and 4.38 mL of diisopropylamine (0.0341 mol) 
was stirred under argon at -IO0C for 30 minutes. The 
temperature was taken down to -78°C and diester (2.89 g7 
0.0136 mol) was added dropwise7 creating a bright red 
solution. After addition was completed the solution was 
allowed to stir for 15 minutes, then I,3-dibromo propane 
(1.67 mL, 0.0163 mol) was added dropwise. The solution was 
allowed to warm to room temperature and stirred overnight. 
Identical workup (page 120) and distillation yielded a 
product as a yellow oil (2.47 g, 9.80 mmol) (72% yield).
3-Methyl-cis-I,6-dicarbomethoxvbicvclo T4,3,Olnon-S-ehe,
ril21
1HNMR (300.133 MHz, CDCl3): 8 1.65 (3H, d, J=1.5Hz), 1.61- 
2,88 (10H, m), 3.63 (3H, s), 3.64 (3H, s), 5.26-5.31 
(1H, m)
13CNMR (75.4. MHz, CDCl3) : 5 18.92 (t) , 23.15 (q) , 32.45 (t) ,
34.63 (t), 34.89 (t), 36.40 (t), 51.66 (q) (two carbon), 
51.96 (s), 53.23 (s), 117.25 (d), 130.42 (s), 176.55 
(s)
LRMS (EI) m/e (%abundance) : 252 (M+,0.4) , 220 (6) , 192 (29), 
133 (100), 105 (30), 91 (16)
LRMS (Cl) (NH3) m/e (%abundance) : 270 (M+NH/, 10), 253 
(M+H\ 100), 221 (24)
197
HRMS (Cl) m/e calculated for C14H21O4 = 253.1440/ found = 
253.1437
Preparation of 3-methyl-cis-I,6-dihvdroxvmethyl bicvclo 
(4,3,01 non-3-ene, [1131
A solution of [112] (1.21 g, 4.80 mmol) in 2 mL of dry
THE was added dropwise at .Oe C-to a stirring solution of LAH 
(0.40 g, 0.011 mol) in 10 mL of dry THE. The reaction 
mixture was stirred overnight at room temperature and then 
hydrolyzed. Workup (page 121) yielded a product as a pale 
yellow oil (0.771 g, 3.93 mmol) (82% yield).
3-Methvl-cis-l, 6-dihvdroxvmethvl bicvclo [4,3,01 non^-3-ene, 
[1131
1HNMR (300.133 MHz, CDCl3): 8 1.63 (3H, d, J=1.2Hz) , 0.83- 
2.10 (10H, m), 3.40 (1H, d, J=Il.4Hz)r 3.45 (1H, d, 
J=Il.4Hz), 3.58 (1H, d, J=Il.4Hz), 3.61 (1H, d,
J=Il.4Hz), 5.27 (IHf m)
13CNMR (75.4 MHzfCDCl3): 5 18.57 (t)f 23.44 (q) f 32.16 (t) f 
33.29 (t)f 33.71 (t)f 36.25 (t)f 46.01 (s)f 47.03 (s)f 
67.21 (t)f 67.27 (t)f 118.27 (d) f 131.54 (s)
LRMS (EI) m/e (%abundance): 178 (7)f 160 (Il)f 147 (26)f 133 
(19)f 119 (22)f 105 (IOO)f 91 (74)f 79 (37)f 67 (22)f 
53 (21)f 41 (32)
LRMS (Cl) (Methane) m/e (%abundance) : 197 (M+H+f 20) f 179 
(42)f 161 (IOO)f 149 (28)f 133 (21)f 119 (20)f 105 
(41), 96 (33)
HRMS (Cl) m/e calculated for C12H21O2 = 197.1542; found = 
197.1544
Preparation of 3-methvl-8-oxatricvcloF4,3,3,01dodec-3-ene.
ni41
The diol, [113], (0.112 gr 0.571 mmol) was combined
with 2 mL' of dry pyridine under argon. Then TsCl (0.108 g, 
0.571 mmol) dissolved in 2mL of dry pyridine was added 
dropwise to the stirring solution. The reaction was stirred 
overnight. Workup (page .122) and florisil separation 
(hexane:ethylacetate, 9:1) yielded a product as a pale 
yellow oil (87.4 mg, 0.491 mmol) (86% yield). 
3-Methvl-8-oxatricvclo[4,3,3,01dodec-3-ene, [1141 
1HNMR (300.133 MHz, CDCl3): 5 1.65-1.93 (10H, m), 2.21 (3H, 
s), 3.73-3.84 (4H, m), 5.74-5.78 (1H, m)
13CNMR (75.4 MHz, CDCl3) : 8 24.05 (q) , 24.15 (t), 33.07 (t) ,
38.05 (t), 39.91 (t), 40.06 (t), 55.13 (s), 55.84 (s),
81.06 (t), 81.30 (t), 121.16 (d), 136.54 (s)
LRMS (EI) m/e (%abundance) : 178 (M+, 29) , 160 (33), 147 (
46), 133 (34), 119 (26), 105 (92), 91 (100), 81 (50),
67 (18), 41 (37)
HRMS (EI) m/e calculated for C12H18O1 = 178.1358; found = 
178.1362
Hydrogenation of 3-methyl-cis-l,6-dicarbomethoxvbicvclo 
[4,3,01non-3-ene, [1121
Diester, [112] (367 mg, 1.46 mmol) was combined with 20
mg of pt/c catalyst and 20 mL of absolute ethanol. The
198
reaction vessel was shaken under 20 psi of H2 at room 
temperature for overnight. The catalyst was then filtered 
off and the ethanol was removed by rotary evaporation. 
Extraction with dichloromethane yielded only one 
stereoisomer as an oil (317 mg, 1.25 mmol) (86% yield).
3-Methyl-cis-I,6-dicarbomethoxybicvclo(4,3,Olnonane, (1151 
1HNMR (300.133 MHz, CDCl3): 5 0.90 (3H, d, J=6.4Hz) , 1.38-
1.86 (13H, m), 3.61 (3H,s), 3.62 (3H, s)
13CNMR (75.4 MHz,CDCl3): 5 19.51 (t) , 22.17 (q) , 27.45 (d) , 
30.50 (t), 33.27 (t), 34.37 (t), 36.14 (t), 36.66 (t), 
51.42 (q) , 51.64 (q) , 53.60 (s), 55.19 (s), 176.57 (s), 
177.77 (s)
LRMS (EI) m/e (%abundance) : 254 (Mf, I), 222 (8), 194 (40),
. I
181 (7), 153 (8), 135 (100), 93 (13), 77 (6), 59 (7), 
41' (8)
HRMS (EI) m/e calculated for C14H22O4 = 254.1518; found = 
254.1512
Hydrogenation of 3-methyl-cis-I,6-dihvdroxvmethyIbicvclo 
[4,3,01non-3-ene, [1131
Vl
In an identical procedure for [112], hydrogenation of 
the diol, [113] (159 mg, 0.820 mmol) afforded the reduced
products in a ratio of 65:35, respectively.
3-Methyl-cis-1,6-dihvdroxymethvIbicvclo[4,3,01 nonane, [1161-
199
maior isomer
200
1HNMR (300.133 MHz, CDCl3) : 5 0.86 (3H, d, J=6.4Hz), 1.11- 
. 2.07 (13H, m)r 3.10 (1H, d, J=Il.26Hz), 3.41 (1H, d,
J=Il.59Hz), 3.60 (1H, dr J=Il.32Hz)f 3.83 (1H, d,
J=Il.47Hz)
13CNMR (75.4 MHz, CDCl3) : 5 18.78 (t) , 22.62 (q) , 27.61 (d) , 
31.33 (t), 32.26 (t), 33.04 (t), 34.22 (t), 36.74 (t), 
46.48 (t), 48.48 (t), 66.02 (t), 69.08 (t)
LRMS (EI) m/e (%abundance): 180 (9), 162 (9), 149 (94), 135 
(100), 119 (10), 107 (38), 93 (63), 79 (58), 67 (33),
55 (27), 41 (17)
Hydrogenation of 3-methvl-8-oxatricvclo(4,3,3,01dodec-3-ene, 
(1141
In an identical procedure for [112], hydrogenation of 
the propellane, [114] (19.4 mg, 0.107 mmol) yielded the
reduced products in a ratio of 3:1, respectively. 
3-Methvl-8-oxatricvclo14,3,3,Oldodecane, [1171-manor isomer
1HNMR (300.133 MHz, CDCl3): 8 0.87 (3H, d, J=6.1Hz), 0.95- 
1.78 (13H, m), 3.52 (1H, d, J=8.12Hz), 3.61 (1H, d, 
J=8.12Hz), 3.66 (1H, d, J=8.19Hz), 3.78 (1H, d,
J=8.11Hz)
13CNMR (75.4 MHz, CDCl3) : 5 21.73 (t) , 22.60 (q) , 27.64 (d) ,
29.26 (t), 30.47 (t), 31.44 (t), 39.02 (t), 40.45 (t), 
50.93 (s), 52.55 (s), 76.35 (t), 81.36 (t)
LRMS (EI) m/e (%abundance) : 180 (M+, 6) , 162 (I) , 150 (21) , 
135 (100), 121 (9), 107.(18), 95 (37), 79 (31), 67 
(19) , 55 (14), 41 (23)
201
HRMS (EI) m/e calculated for C12H20O1 = 180.1514; found = 
180.1510
3-Methvl-8-oxatricvclo(4,3,3,01dodecane, (1171-minor isomer 
LRMS (EI) m/e (%abundance) : 180 (Mff 19) , 162 (18) , 149
(90)f 135 (IOO)f 121 (27)f 107 (41)f 95 (88)f 79 (69)f 
67 (41)f 55 (34)f 41 (53)
HRMS (EI) m/e calculated for C12H20O1 = 180.1514; found =
180.1524
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203
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(1985), 50, 5727, .
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Spec., (1983), 15, 353.
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Howald, and B.E. Ivey, Journal of Computers in 
Mathematical and Science Teaching, (1989), 95-105.
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18, 649.
Von Emil Buchta, Siegfried Billenstein, Liebigs Ann. 
Chem., (1967), 702, 51-54.
45.
APPENDICES
APPENDIX A
Plot of In (Cm-Cx) v s . time (seconds) for the 
Solvolysis of tosylates at three different 
temperatures.
Plot of In (k) vs. 1/T (K-1) for tosylates.
208
E 2 5HI$-$YH(3),7) y : -8.8862994333 x + 4.83(234 Cow.: -8.9999649
Figure 84. Plot of In (C„-C,) vs. time (seconds) for the 
Solvolysis of [15] at 39.7 *C.
E-15§-0T$-$W5l.lKC) y = 8 8889652884 x 1 4.815242 Cow.: -8,9999755
Figure 85. Plot of In (Cw-Cx) vs. time (seconds) for the
Solvolysis of [15] at 50.I"C.
209
M  Se-OTS-SVN(SMBEG) y = -0.882751254 x ♦ 4.273125 Cerr.: -8.MMTB
Figure 86. Plot of In (C.-Cx) vs. time (seconds) for the 
Solvolysis of [15] at 59.9'C.
SO-OTs-Syn1 Ea=-11.4146*R, R=0.999987
C  -7-
302 3.04 3.06 3.08 3.1 3.12 3.14 3.16 3.18 3.2
I000/T (l/K )
Figure 87. Plot of In (Jc) vs. 1/T (K-1) for [15] .
210
E-I Se-OTS-ANTMti.lDEG) g = -8,9865*4524 x + 4.885978 Copp,: -0,9999389
18 12 14 16 18 29 22 24 26 28 39 32 34 3E+2
Figure 88. Plot of In (C_-C,) vs. time (seconds) for the 
Solvolysis of [16] at 40.I*C.
E-I 56-0T$-4NII(49.8IEC) y = -9,881583236 x + 3,987625 Copp.: -8.999171
Figure 89. Plot of In (C_-CJ vs. time (seconds) for the
Solvolysis of [16] at 49.8'C.
211
OTS-ANTI y : -8.004362365 x + 3.941547 Copp.: -0.9999414 
<. ( ,s i .r o s * )
Figure 90. Plot of In (C„-Cx) vs. time (seconds) for the 
Solvolysis of [16] at 59.9’C.
50-OTs-Anti, Ea=-11.3086*R, R=0.999998
3 3.02 3.04 3.06 3.0S 3.1 3.12 3.14 3.16 3.18 3.2
I0 0 0 /T (l/K )
Figure 91. Plot of In (k) vs. 1/T (K"1) for [16] .
212
M  SS-OtS-SNy :  -6,735936e-685 x t  4.689716 Copp.: -0.9996767
( 4 0 3 )
Figure 92. Plot of In (Cw-Cx) vs. time (seconds) for the 
Solvolysis of [80] at 40.3*C.
H  5S-OIS-SWK50.1) y = -0,0061748891 x ♦ 3,889204 Copp,: -0.999892
Figure 93. Plot of In (Cw-Cx) vs. time (seconds) for the
Solvolysis of [80] at 50.1'C.
213
E-I 5S-0!S-S¥N(68,8) y = -8,8883788578 x ♦ 4.227612 Copp.: -8.9999421
Figure 94. Plot of In (C„-C,) vs. time (seconds) for the 
Solvolysis of [80] at 60.0 *C.
5S-OTs-Syn, Ea=-9.13881*R, R=0.997454
C  -8.8-
3.02 3.04 3.06 3.08 3.1 3.12 3.14 3.16 3.18 3.2
lOOOmi/K)
Figure 95. Plot
214
H  SS-OTS-AIfTI(2?, 0) y : -0,00134965 x + 0,7899663 Corr,: -0,9995987
Figure 96. Plot of In (C„-Cx) vs. time (seconds) for the 
Solvolysis of [81] at 29.0’C.
H  5S-0TS-ANTK48.9) y :-0.005420198 x M , 550008 C o r M -0.9998639
Figure 97. Plot of In (C„-Cx) vs. time (seconds) for the
Solvolysis of [81] at 40.9'C.
215
E-I 5S-0IS-tWTl(49,2) y : -9,81221948 x ♦ 2.13967 Corr,: -0.9994357
Figure 98. Plot of In (C„-Cx) vs. time (seconds) for the 
Solvolysis of [81] at 49.2*C.
SS-OTs-Anti, Ea=10.3803*R, R=0.999257
Figure
3.25 3.3
I(X)OzT(IZK)
216
E-I 48-0I$-$YN(4e,5DEG,) y : -0,0009545752 x ♦ 3,565602 Copp.: -0.9999354
SEC.
Figure 100. Plot of In (C„-C,) vs. time (seconds) for the 
Solvolysis of [82] at 40.5 *C.
E-I M -O I$-SM (50.16EC .) y = -0.002792547 x + 4.126893 Copp.: -0 .9999546
Figure 101. Plot of In (C_-CJ vs. time (seconds) for the
Solvolysis pf [82] at 50.1"C.
217
M  48-0TS-SYN(59.8DEG,) y : -8,887187312 x + 4,879« Corr,: -8,9999452
Figure 102. Plot of In (C„-Cx) vs. time (seconds) for the 
Solvolysis of [82] at 59.8'C.
40-0Ts-Syn, Ea=-10.8564*R, R=0.999374
3.02 3.04 3.06 3.08 3.1 3.12 3.14 3.16 3.18 3.2
lOOO/TO/K)
Figure 103. Plot of In (k) vs. 1/T (K"1) for [82] .
218
M  4W THN II(4A .1DEC . y :  -0.001034147 x + 3.799595 C orr,: -0,9999824
Figure 104. Plot of In (C„-Cx) vs. time (seconds) for the 
Solvolysis of [83] 40.I*C.
E-I 40-OTS-ANTK49.9DEG. y : -0.002953225 x + 3.682091 Corr,: -0.9999901
Figure 105. Plot of In (C„-Cx) vs. time (seconds) for the
Solvolysis of [83] at 49.9 *C.
219
E-I 48-0IS-MUM59.7DEG. y : -8,967350953 x t 4,874264 Copp.: -0,9999723
Figure 106. Plot of In (C„-Cx) vs. time (seconds) for the 
Solvolysis of [83] at 59.7 *C.
40-0Ts-Anti, Ea=-10.4484*R, R=0.999453
-4.5
-5.5-
-6.5-
3 3.02 3.04 3.06 3.08 3.1 3.12 3.14 3.16 3.18 3.2
I000/T(i/K)
Figure 107. Plot of In (k) vs. 1/T (K'1) for [83] .
220
£-1 6HTHYN(48.1DEG) y : -3.984*15,-0*5 x ♦ 4,275162 Corr.: -0.99989*2
Figure 108. Plot of In (C„-C,) vs. time (seconds) for the 
Solvolysis of [84] at 40.I"C.
E-I 6B-OTS-SVN(SB1S) y = -8.8881211996 x + 4.541824 C o r M  -8.999978*
Figure 109. Plot of In (C_-CJ vs. time (seconds) for the
Solvolysis of [84] at 50.0'C.
221
M 68-0IS-S¥N(59,7) y : -8,8W3529713 x + 4,434837 Corp,:-0.9999682
45 E+2
Figure HO. Plot of In (C„-C,) vs. time (seconds) for the 
Solvolysis of [84] at 59.7*C.
60-OTs-Syn, Ea=-11.7058*R. R=0.999947
-7.51------------------------------------------------------------------------------------------------
10.5-------------------- ---------- .----------------------------- - -------- - -------- - -------- - --------
3 3.02 3.04 3.06 3.08 3.1 3.12 3.14 3.16 3.18 3.2
I000/T( 1/K)
Figure 111. Plot of In (k) vs. 1/T (K'1) for [84].
222
M  68-OTS-MTi (48,3) y = -4.845546e-885 x ♦ 4,384615 Copp,: -8.9998479
Figure 112. Plot of In (C„-C,) vs. time (seconds) for the 
Solvolysis of [85] at 40.3*C.
E-I iHI$-AHII(5B,8) y = -8,8861577759 x t 4.396861 Copp.: -0,9999916
Figure 113. Plot of In (Cm-Cx) v s . time (seconds) for the
Solvolysis of [85] at 50.0 * C.
223
M  68-0TS-ANTK59.9) y : -0.9084999296 x t 4,715639 Corr,: -0,9999643
10 12 14 16 18 20 22 24 26E+2
Figure 114. Plot of In (C„-C,) vs. time (seconds) for the 
Solvolysis of [85] at 59.9’C.
60-0Ts-Anti, Ea=-12.3469*R, R=0.999848
3.02 3.04 3.06 3.08 3.1 3.12 3.14 3.16 3.18 3.2
1000/TU/K)
224
H  78-0TS-S¥N(39,2) y : -8.068295664 x + -8.3577438 Corr.: -0.9994799
Figure 116. Plot of In (C.-C,) va. time (seconds) for the 
Solvolysis of [86] at 39.2 *C.
M  78-0TS-8¥H(49,1) S :-0,061217543 x U.878077 Corr.l -0,9999347
18 12 14 16 18
Figure 117. Plot of In (Cm-Cx) v s . time (seconds) for the
Solvolysis of [86] at 49.I*C.
225
E-I 7fcOTS-S¥N(57,8) y :  -8,862434484 x t  g.5157844 Cow ,: -8 99)8654
18 15 28 25 38 35 48 45
Figure 118. Plot of In (C_-C,) vs. time (seconds) for the 
Solvolysis of [86] at 57.8"C.
70-OTs-Syn, Ea=-11.7809*R, R=O.979676
.02 3.04 3.06 3.08 3.1 3.12 3.14 3.16 3.18 3.2
1000/T(l/K)
Figure 119.
226
M  78-0IHHIK29,)) s : -0,W264HI x * 8.56M7S3 Corr,: -9,99W174
Figure 120. Plot of In (Cw-Cx) vs. time (seconds) for the 
Solvolysis of [87] at 29.7*C.
M  7e-0I$-AHTI(ie,8) a : *8.88419334 x + 2,355351 Corr.: -8,9998374
Figure 121. Plot of In (Cw-Cx) vs. time (seconds) for the
Solvolysis of [87] at 40.0*C.
227
M  7e-0I$-ANTI(49.4) y :  -0,81730389 x t  8,628559 Corr,: -6.9998621
Figure 122. Plot of In (C„-C,) vs. time (seconds) for the 
Solvolysis of [87] at 49.4*C.
70-0Ts-Anti, Ea=-9.25292*R, R=0.990107
3.2 3.25 3.3
IOOOa -(IZK)
3.35
Figure 123. Plot of In (Jc) vs. 1/T (K'1) for [87].
228
H  55W -O rS (39 ,3DEU  y :  -7 ,892746HJ05 x t 4,316253 Copp.: -9,9999524
Figure 124. Plot of In (C_-C.) vs. time (seconds) for the 
Solvolysis of [88] at 39.3’C.
E-I SStt-OTS (49,9EM) y = -9,8992867522 x + 4,814244 Copp.: -9.9999416
Figure 125. Plot of In (C_-C,) vs. time (seconds) for the
Solvolysis of [88] at 49.9*C.
229
M  55W-0TS (605EG.) y : -0.886857688 x t 4.491W3 Corr,: -9.999)73
Figure 126. Plot of In (Cw-Cx) vs. time (seconds) for the 
Solvolysis of [88] at 60.0‘C.
5050-OTs, Ea=-11.9886*R, R=0.999783
Figure 127. Plot of In (k) vs. 1/T (K-1) for [88].
230
E-I 57W-0THNTI(4@.9) y : -9,8866934843 x t 2,669518 Corr.: -0.9999188
Figure 1 2 8 . Plot of In (C _ -C .)  vs. time (seconds) for the 
Solvolysis of [ 8 9 ]  at 4 0 . 9 * C .
E-I 5788-0IS-8HTI(49.7) y = -8.882057711 x t 2.887883 Corr,: -0.9999687
15 28 38 35
Figure 129. Plot of In (C_-CJ vs. time (seconds) for the
Solvolysis of [89] at 49.7'C.
231
M  57B8-0I$-#NII(6fl,2) a : -8,866167283 x ♦ 2,83)699 Corr,: -8,W9686
Figure 130. Plot of In (C„-Cx) vs. time (seconds) for the 
Solvolysis of [89] at 60.2*C.
5070-OTs-Anti, Ea=-11.8285*R, R=0.99901
Figure 131. Plot of In (k) vs. 1/T (K-1) for [89].
2 3 2
APPENDIX B
o 1HNMR spectra of syn- and anti-tosylates of 
propellanes.
5  =
/ \ llll ' '
I
I
I
I
oxatricyclo[4,3,2,0]undecane, 
[82] .
Figure 132. 300.133 MHz 1HNMR: (syn)-3-Tosyl-8-
233
Figure 133. 300.133 MHz 1HNMR: (anti)-3-Tosyl-8-
oxatricyclo[4,3,2,0]undecane, 
[83] .
Figure 134. 300.133 MHz 1HNMR: (syn)-3-Tosyl-8-
oxatricyclo[4,3,3,0]dodecane, 
[15] .
235
Figure 135. 300.133 MHz 1HNMR: (anti)-3-Tosyl-8-
oxatricyclo[4,3,3,0]dodecane, 
[16] .
236
Figure 136. 300.133 MHz 1HNMR: (syn)-3-Tosyl-8-
oxatricyclo[4,4,3,0]tridecane, 
[84] .
Figure 137. 300.133 MHz 1HNMR: (anti)-3-Tosyl-8-
oxatricyclo[4,4,3,0]tridecane,
[85] .
238
I 3
& ;
1*1 rv
wl
/
Figure 138. 300.133 MHz 1HNMR: (syn)-3-Tosyl-8-
oxatricyclo[5,4,3f 0]tetradecane,
[86] .
239
assiisitifiSitiSiiSiiiiiiiSiii
/
I
Figure 139. 300.133 MHz 1HNMR: (anti)-3-Tosyl-8-
oxatricyclo[5,4,3,0]tetradecane,
[87] .
240
I_ I A I ji*
5 0
PPM
Figure 140. 300.133 MHz 1HNMR: (syn)-3-Tosyl-8-
thiatricyclo[4,3,3,0]dodecane,
[80] .
241
ft 1]C SI!
" -
Z
,I I i i S S i i i i
300.133 MHz 1HNMR: (anti)-3-Tosyl-8-
thiatricyclo[4,3,3,0]dodecan©,
[81] .
Figure 141.
242
Figure 142. 300.133 MHz 1HNMR: 3-Tosyl-8,11-
dioxatricyclo[4,3,3,0]dodecane,
[88] .
243
Figure 143. 300.133 MHz 1HNMR: (anti)-Tosyl-8,12-
dioxatricyclo[5,4, 
[89] .
,0]tetradecane,
244
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