Publication Date

April 2019

Advisor(s)

Michael Calter

Major

Chemistry

Language

English (United States)

Abstract

This thesis describes the development of methodology on expanding the scope and investigating the mechanism to enantioselective induction of the catalytic, asymmetric Interrupted Feist-Bénary (IFB) reaction. We demonstrate the development of a new IFB reaction using 4-hydroxycoumarin as the nucleophile to synthesize a highly functionalized hydroxydihydrofuranoid with 60 to 90% yield. Based on previous work on the IFB reaction, pyriminidinyl bis-quinidine cinchona alkaloids catalysts were screened in hopes of producing the IFB product with synthetically useful enantioselectivities. At this point, we found that the addition of a 6-methoxypyridin-2-yl group on the front group of the catalyst increased the enantioselectivity to 29% ee. In order to further understand the IFB reaction, we have implemented computational studies into our work and reinvestigated the classic IFB reaction. We first gauged the effects on the 6-position of the pyrimidinyl ring and synthesized a new set of catalysts. It was discovered experimentally and computationally that a chlorine at the 6-position had the highest level of enantioselective induction followed by a methoxy then a quinidine. We then probed the effects of the front group through a series of competition reactions and computational studies, where we discovered each catalyst’s mechanism to inducing enantioselectivity. In this thesis, we will report that our cinchona alkaloid catalysts increase the energy of the Si face attack. However, certain front groups also lower the energy of the Re face attack to further increase enantioselectivity. Meanwhile, other, less effective, catalysts maintain the Re attack energy to be similar to the achiral pathway while destabilizing the Si attack.

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