Dissertations, Theses, and Capstone Projects

Date of Degree

9-2023

Document Type

Dissertation

Degree Name

Ph.D.

Program

Chemistry

Advisor

Mark R. Biscoe

Committee Members

Ryan P. Murelli

Urs Jans

Subject Categories

Organic Chemistry

Keywords

Palladium Catalysis, Cross-Coupling Reactions, Enantioenriched Electrophiles, Stille Cross-Coupling, Buchwald Ligands, Carbastannatrane

Abstract

We have developed a novel palladium-catalyzed stereospecific C(sp3)–C(sp3) Stille cross-coupling reaction between carbastannatrane nucleophiles and α-(trifluoromethyl) benzylic tosylates. This constitutes the first example of a stereospecific C(sp3)–C(sp3) cross-coupling reaction using an enantioenriched electrophile and an alkyltin nucleophile. This system has the potential to be extended to cross-coupling reactions using configurationally stable enantioenriched nucleophiles, thus enabling stereochemical control of two newly formed contiguous stereocenters. Generating enantioenriched α-(trifluoromethyl) benzylic compounds also has importance in pharmaceutical and agrochemical industries.

Through the development of this reaction, our findings show that the addition of copper, which is often added as a co-catalyst in Stille reactions, hampers the reaction. Mechanistic investigations suggest that oxidative addition with palladium proceeds through an SN2’ mechanism, which is not well known for palladium. Because of this, our electrophiles are limited to those bearing extended π-systems. We have observed that our nucleophiles are limited by the competing rates of β-hydride elimination products.

We have also synthesized and investigated the effects of novel Buchwald ligands in Suzuki and Stille reactions. Our observations indicate that the electronic properties of the electron-withdrawing groups on phosphine have a greater impact than the size of the alkyl substituents on the bottom ring of Buchwald ligands.

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