Part 1: study toward the total synthesis of acutumine ; : Part 2: asymmetric intramolecular hydroamination catalyzed by group 3 metal complexes

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Montana State University - Bozeman, College of Letters & Science


Acutumine 1 is a tetracylic alkaloid isolated from Menispermum daurcum, which exhibits selective T-Cell cytotoxicity. It is potentially useful for specific therapy T-Cell related Leukemia and lymphoma. Acutumine is a highly functionalized tetracyclic natural product, containing a [4.3.3]-propellane core and a 5,5-spirocycle. The synthesis of the 5,5-spirocycle is prepared via enantioselective Pd II/IV catalyzed chloro-induced semi pinacol rearrangment. However, studies showed Pd catalyst functioned as Lewis acid to oxidant, PhI(OAc) 2 rather than forming a Pi-complex with the substrate as proposed. Fortunately, the preparation of the spirocycle can be accomplished from an asymmetric Pd II /Brønsted acid cocatalyzed semi pinacol rearrangement via direct allylic C-H activation. [4.3.3] propellane core was concisely synthesized in eight step sequences featuring a phosphoric Brønsted acid catalyzed aldol condensation and radical N-cyclization as the key transformations. Hydroamination, the addition of an amine N-H bond across an unsaturated carbon-carbon linkage, allows a highly atom economical access to industrial and pharmaceutical important alkaloids. The hydroamination of alkene by early transition metal has seen significant process. Herein, we reported the substrate structural effect in Yttrium(III)-catalyzed intramolecular hydroaminations. Aminoalkenes possessing a terminal 2- (5-trimethylsilyl)thienyl group exhibited substantially enhanced reactivity. Cyclization efficiency for a representative aminoalkene possessing a Z-configured 2-(phenyl)ethenyl group is considerably higher than that observed for the corresponding E-isomer. Enantioselective hydroamination/cyclization of representative aminoalkenes catalyzed by chelating diamide complexes of La(III) and Y(III) are described. The La(III) complex derived from the sterically demanding (R)-N,N'-dibenzosuberyl-1,1'-binaphthyl-2,2'-diamine proligand provides enantioselectivities that are in many cases significantly higher than those obtained with the corresponding Y(III) analog.




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