Dissertations, Theses, and Capstone Projects
Date of Degree
2-2024
Document Type
Dissertation
Degree Name
Ph.D.
Program
Chemistry
Advisor
Mark Biscoe
Committee Members
Ryan Murelli
Shenping Zheng
Subject Categories
Other Life Sciences
Keywords
chemistry, cross-coupling, organic synthesis, Stille reactions, enantioenriched molecules
Abstract
Transition metal-catalyzed cross-coupling reactions have evolved into a remarkable instrument for the formation of new bonds, and have significantly impacted how we approach to access complex organic molecules. Palladium is currently one of the most popular elements for catalytic applications due to its ability to facilitate powerful carbon-carbon and carbon-heteroatom couplings. Traditional Pd-catalyzed cross-coupling reactions have primarily concentrated on C(sp2)-C(sp2) cross-couplings, yielding planar products. Considering the use of C(sp3) nucleophiles would offer a viable control of the three dimensional arrangement in molecules. Herein, the first chapter details the history and development of Pd-catalyzed Stille cross-coupling reactions. The use of configurationally stable, enantioenriched secondary alkyltin nucleophiles that enable couplings with high stereofidelity have been discussed.
Nitrogen is the most prevalent heteroatom in FDA-approved pharmaceuticals. Specifically,alfa-chiral pyrrolidines serve not only as valuable components in pharmaceuticals but also as chiral control agents in asymmetric synthesis. The second chapter introduces a general approach to the stereospecific cross-coupling of enantioenriched nitrogen-containing heterocycles. In these systems, a change from n-butyl spectator ligands to cyclohexyl spectator ligands is sufficient to enable the selective transmetallation and coupling of nitrogen-containing stereocenters in Pd-catalyzed cross-coupling reactions supported by JackiePhos ligand.
Aryl-substituted stereocenters are common structural components of biologically active molecules. The third chapter describes a general process for the preparation of enantioenriched benzylic stereocenters through stereospecific Pd-catalyzed cross-coupling reactions of enantioenriched benzylic tricyclohexyltin nucleophiles. The use of JackiePhos as a supporting phosphine ligand facilitates transmetallation of alkyl groups from organostannanes in Stille cross-coupling reactions when CuCl is included as a co-transmetallating agent. As noted in chapter 2, this study further demonstrates the potential benefits of incorporating cyclohexyl spectator ligands into organostannanes used in Stille reactions.
Recommended Citation
Binayeva, Meruyert, "Stereospecific Cross-Coupling Reactions of Enantioenriched Secondary Alkyltricyclohexyltin Nucleophiles" (2024). CUNY Academic Works.
https://academicworks.cuny.edu/gc_etds/5605