Theses and Dissertations at Montana State University (MSU)
Permanent URI for this collectionhttps://scholarworks.montana.edu/handle/1/733
Browse
8 results
Search Results
Item Stereoselective allylic cyclizations and rearrangements(Montana State University - Bozeman, College of Letters & Science, 2022) Stankevich, Ksenia Sergeyevna; Chairperson, Graduate Committee: Sharon NeufeldtHerein, we aim to explore the unique reactivity of allyl groups in two different areas: synthesis of densely functionalized five-membered ring systems and mechanistic studies of Pd- catalyzed formation of complex quaternary nitriles. The first part addresses the paucity of methods available for the formation of highly substituted five-membered rings, which are a common motif in natural compounds and pharmaceuticals. We developed a method that provides access to cyclopentenols and methylene cyclopentenols via the union of the Claisen rearrangement and Sakurai allylation. In this instance, the Claisen rearrangement allows for the stereospecific generation of the carbon framework, whereas the intramolecular Sakurai allylation provides a stereoselective cyclization reaction. For 1,2,5-trisubstituted cyclopenten-1-ols this approach has proven to be highly general and stereoselective, furnishing a library of cyclized products in good and very good yields and >20:1 diastereomeric ratio. For 1,2,5-trisubstituted 3- methylene cyclopentan-1-ols, we have developed a stereodivergent method whereby the one-pot stepwise Claisen-Sakurai reaction provided anti-, anti- product and the cascade Claisen-Sakurai reaction furnished syn-, anti- product as a major diastereomer with good yield. In both cases reaction mechanism was investigated to uncover the origin of diastereoselectivity using density functional theory. The second part of this research covers investigating the mechanism of a Pd- catalyzed double rearrangement to form quaternary nitriles, which are molecules of synthetic interest. We studied the mechanism of recently developed highly complex auto-tandem catalytic double allylic rearrangement of N-alloc-N-allyl ynamides to complex quaternary nitriles using density functional theory. This reaction proceeds through two separate and distinct catalytic cycles with both decarboxylative Pd-pi-allyl and Pd(0)-promoted aza-Claisen rearrangements occurring. We discovered previously unreported concomitant decarboxylation/C-C bond formation, reversible C-N ionization and a Pd(0) catalyzed [3,3]-rearrangement along with its stepwise variant. These catalytic cycles are characterized by the highly dynamic nature of the catalyst systems with large degrees of conformational flexibility and a flat potential energy surface. Our studies have rationalized the reactivity observed and can be further developed into predictive models for ligand and catalyst screening.Item Mechanistic studies and new methodologies relevant to palladium-catalyzed chemodivergent cross-coupling reactions(Montana State University - Bozeman, College of Letters & Science, 2021) Reeves, Emily Kathryn; Chairperson, Graduate Committee: Sharon NeufeldtPalladium-catalyzed cross-couplings are powerful methods for constructing new carbon-carbon bonds in organic molecules. While the mechanism of these reactions are generally well studied, complexities are introduced when the starting materials involved in the reaction contain several possible sites at which the new C-C bond can be made. It is often desirable for the palladium catalyst to facilitate (chemo)selective cross-coupling at just one of the reaction sites while leaving the other(s) intact. This can be challenging and often requires extensive tuning of the palladium catalyst and the reaction conditions. In this work, we describe efforts to better understand the properties causing palladium catalysts to react chemoselectively at aryl chloride (C-Cl) or triflate (C-OTf) reaction sites. Using a combined approach of computational and experimental chemistry, we demonstrate that solvent plays a critical role in the reaction selectivity by coordinating to the palladium catalyst and promoting reaction at C-OTf sites via formation of bisligated palladium. Anionic additives like inorganic bases play a complementary role in promoting reaction at C-OTf sites. We additionally describe efforts to develop new chemodivergent cross-coupling methodologies using palladium-N-heterocyclic carbene precatalysts. These catalysts demonstrate robust reactivity under mild conditions, allowing for a greatly expanded scope of chemoselective cross-coupling products, especially biaryl triflates.Item Catalysis with early and late transition metals: C-H activation at tantalocene hydrides and oxidative addition at palladium solvato complexes(Montana State University - Bozeman, College of Letters & Science, 2021) Rehbein, Steven Mark; Chairperson, Graduate Committee: Sharon Neufeldt; Matthew J. Kania and Sharon R. Neufeldt were co-authors of the article, 'Experimental and computational evaluation of tantalocene hydrides for C-H activation of arenes' in the journal 'Organometallics' which is contained within this dissertation.; Steven M. Rehbein and Sharon R. Neufeldt were co-authors of the article, 'Solvent coordination to palladium can invert the selectivity of oxidative addition' in the journal 'Organometallics' which is contained within this dissertation.Herein we present our work on transition metal catalysis using metals from two sides of the periodic table: C-H activation catalyzed by early transition metals and cross-couplings catalyzed by late transition metals. In the first part, a synergistic experimental and computational approach was employed to investigate the possibility of extending the reactivity of bent tantalocene hydrides beyond aromatic C-H activation to enable activation of aliphatic substrates. In situ monitoring of the characteristic 1 H NMR metal hydride signals in the reaction of Cp 2TaH 3 and related complexes with deuterated aromatic substrates allowed for the evaluation of reaction kinetics of catalyst decomposition, H/D exchange, and off-cycle reactions. The insight gained from in situ reaction monitoring with aromatic substrates, combined with computational analyses, allowed for the extension of this chemistry to intra- and intermolecular aliphatic C-H activation. This work represents the first example of aliphatic C-H activation by homogeneous tantalum hydrides. In the second part, we provide compelling evidence that solvent coordination to palladium during oxidative addition of chloroaryl triflates can result in an inversion of chemoselectivity of this step. Previous investigations attributed a solvent-dependent switch in chemoselectivity to the propensity of polar solvents to stabilize anionic transition states of the type [Pd(P t Bu 3)(X)]- (X = anionic ligand). However, our detailed investigations show that solvent polarity alone is not a sufficient predictor of selectivity. Instead, solvent coordinating ability is selectivity-determining, with polar coordinating and polar noncoordinating solvents giving differing selectivity, even in the absence of anionic ligands 'X'. A solvent-coordinated bisligated transition state of the type Pd(P t Bu 3)(solvent) is implicated by density functional theory calculations. This work provides a new mechanistic framework for selectivity control during oxidative addition.Item The examination of chiral X-type ligands in Pd(II)-catalyzed enantioselective oxdiatative transformations(Montana State University - Bozeman, College of Letters & Science, 2015) Aebly, Andrew Henry; Chairperson, Graduate Committee: Trevor J. RaineyPalladium catalysis has been utilized extensively in organic chemistry for the synthesis of complex molecules. Despite its abundant use and many successful applications, there remain challenging transformations, specifically with developing new chiral centers. The aim of this research was to explore the underdeveloped, weakly coordinating X-type ligands and their applicability in enantioselective reactions. The electrophilic catalyst, generated by the coordination of sulfonic or phosphoric acid ligands, was utilized to explore underfunctionalized starting materials, such as unactivated alkenes and aryl C-H bonds. Herein we report two Pd II-catalyzed enantioselective transformations: oxidative amination and 1,2-carboamination. The Wacker-type oxidative amination was accomplished with good yields and modest enantioselectivity in the synthesis of chiral indolines and a cyclic carbamate. Substantial loss in enantioselectivity was seen with ortho-substituted anilines. The 1,2-carboamination coupled a mild, directing group facilitated C-H activation on a series of aryl ureas with a subsequent chiral C-N bond formation. Electron-rich, para-substituted aryl ureas provided the highest consistent yields and enantioselectivities. Electron deficient substrates provided little reactivity and substitutions at the ortho- and meta-positions gave inconsistent results. To our knowledge these transformations mark the first enantioselective examples of Pd II-catalyzed oxidative transformations utilizing chiral sulfonic acid ligands.Item Reactions of alkyl and alkenyl zirconocene complexes(Montana State University - Bozeman, College of Letters & Science, 1992) Hanson, Klark ThorItem Development of palladium L-edge x-ray absorption spectroscopy and its application on chloro palladium complexes(Montana State University - Bozeman, College of Letters & Science, 2005) Boysen, Ryan Bradley; Chairperson, Graduate Committee: Robert K. SzilagyiX-ray Absorption Spectroscopy (XAS) is a synchrotron-based experimental technique that can provide information about geometric and electronic structures of transition metal complexes with unoccupied d orbitals. Combination of metal L-edge and ligand K-edge XAS has the potential to define the experimental ground state electronic structure. We developed a quantitative treatment for Pd L-edge spectroscopy based on the already established Cl K-edge XAS for a series of chloro palladium complexes, which are precatalysts in numerous organic transformations. We found that Pd-Cl bonds are highly covalent (23% per Cl in [PdCl₄]²⁻, 34% per Cl in [PdCl₆]²⁻, and 46% in PdCl₂). Dipole integrals for Pd(2p..4d) transitions of 42 eV for Pd(II) and 48 eV for Pd(IV) LIII-edges and 39 eV and 35 eV, respectively, at these Pd oxidation states for the LII-edges were determined. Application of the metal-ligand covalencies and transition dipole integrals by describing the ground state bonding in PdCl₂ with bridging Cl ligands was demonstrated. In future studies, a similar approach will be utilized for palladium phosphine, allyl, olefin complexes in order to define their experimental electronic structure and correlate this with their observed reactivity.Item Catalytic, enantioselective oxyallylation of activated carbonyl compounds(Montana State University - Bozeman, College of Letters & Science, 2012) Reaman, Bradley Earl; Chairperson, Graduate Committee: Trevor J. RaineyStereoselective alkylations are a very useful tool in synthetic chemistry and, specifically, natural product synthesis. One such reaction, named the Tsuji-Trost allylation, is a palladium-catalyzed substitution with the overall transformation being the replacement of an allylic leaving group with a nucleophile. First observed in 1965 with the allylation of diethyl malonate [1], and in 1973 made asymmetric with the use of chiral phosphine ligands by B. M. Trost [2], the reaction has been studied and utilized extensively over the years. While there have been many examples of this reaction in the literature, few explore functionalizing the allylic electrophile. Functionalizing the "2" position of an allylic acetate or carbonate could prove to be a useful synthetic tool. Allylic acetates, chlorides and carbonates bearing a methoxymethyl group at this middle position were synthesized. beta-carbonyl ketones which work well under the Tsuji-Trost conditions were also synthesized. Phosphine ligands that provided enantiomeric excess with a variety of nucleophiles in allylic alkylations were used. Upon reaction with a palladium (0) source, the pro-nucleophiles were successfully alkylated in a stereospecific manner. The work described herein investigates modification of the Tsuji-Trost allylation in which oxy-allylation is carried out with a high yield and high degree of enantioselectivity.Item Palladium (II)-catalyzed stereoselective formation of [alpha]-O-glycosides(Montana State University - Bozeman, College of Letters & Science, 2007) Schuff, Brandon Patrick; Chairperson, Graduate Committee: Hien NguyenThe development of new methods for stereoselective formation of a- or *-Oglycosides has been extensively investigated due to the critical roles carbohydrates play in a variety of biological systems. To date, many efforts have focused on developing new methods and reagents for the generation of isolated glycosyl donors which subsequently undergo glycosidic bond formation with nucleophilic glycosyl acceptors. Despite their potential applications to complex carbohydrate synthesis, each of these methods relies on the nature of the substrates to stereoselectively control the formation of glycosidic bonds. Recently, the use of glycal derivatives as glycosyl donors has been utilized in p- allylpalladium strategies for the stereoselective synthesis of O-glycosides. However, due to the poor reactivity of the glycal donors as well as the alcohol nucleophiles, these groups utilized the more activated pyranone donors. Lee, who recognized the challenge in this approach, utilized Zn(II) ion to activate both the alcohol acceptors for the nucleophilic addition and the glycal donors for the ionization.