Dissertations, Theses, and Capstone Projects

Date of Degree

5-2019

Document Type

Dissertation

Degree Name

Ph.D.

Program

Chemistry

Advisor

Mark Biscoe

Committee Members

Shengping Zheng

Stephen O'Brien

Subject Categories

Inorganic Chemistry | Organic Chemistry

Keywords

transmetallation, suzuki, cross-coupling

Abstract

Through the past 40 years, carbon-carbon cross-coupling reactions have greatly enhanced the ability of chemists to synthesize C(sp2)-C(sp2) bonds and more recently C(sp2)-C(sp3) bonds. In particular, the Suzuki reaction has proven to be invaluable with its high yields, good functional group tolerance, and low toxicity of reagents. One of the component steps of the catalytic cycle of this reaction is transmetallation, in which the nucleophilic species transfers its organic component to the metal center (generally palladium). The mechanism of transfer from primary alkylboron nucleophiles was studied in the 1990's via use of deuterium-labeled probes and analysis by NMR, giving evidence to this being a stereoretentive SE2 mechanism. Subsequent work on secondary systems has highlighted the plausibility of both retentive and invertive mechanisms of transmetallation in Suzuki reactions. More recent research highlighted that the enantiospecificity of such C(sp2)-C(sp3) reactions is not reliant solely upon the nucelophilic species. The selectivity is influenced by multiple factors including the ligand electronics, ligand sterics, electrophile electronics, as well as the inclusion of exogenous additives. Herein, we described the development of a stereodivergent Suzuki reaction using optically active secondary alkylboron nucleophiles, in which the stereoselective pathway of transmetallation is controlled purely by ligand selection. A wide substrate scope of aryl halides and secondary alkylboron nucleophiles is displayed for this work. Secondly, we will describe our investigation into the mechanism of transmetallation for primary alkylboron systems. One drive for this research was the apparent incompatability of results between our stereoinvertive inactivated secondary alkylboron work and the mechanistic work in the 1990’s (that displayed complete stereoretention of primary alkylboron nucleophiles). In particular, the potential flaws may have been present in previous studies, and how well our stereodivergent ligand-controled Susuki system (for secondary alkylborons) translates to primary alkylboron systems.

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