Date of Thesis

8-17-2016

Thesis Type

Masters Thesis (Bucknell Access Only)

Degree Type

Master of Science

Department

Chemistry

First Advisor

Michael R. Krout

Abstract

The total synthesis of biologically active natural products often presents interesting structural challenges to the organic synthetic chemist. The eudesmane family of natural products are a structurally diverse group of sesquiterpenoids characterized by their decalin skeleton, C(10) all carbon quaternary stereocenter, and contiguous stereogenic centers. Inspired by our initial attempts at implementing a double addition strategy toward the eudesmane family of natural products, we have developed the copper mediated 1,4-conjugate addition of functionalized mono-organozinc halides to a beta,beta-disubstituted alpha,beta-unsaturated carbonyls. They key component of our conditions for the conjugate addition of organozinc reagents is the synergistic use of N,N-dimethylacetamide (DMA) and chlorotrimethylsilane. Notably, the improved conditions are compatible with catalytic quantities (10¿20 mol %) of common copper(I) and copper(II) salts and organozinc halides prepared in situ or in solution which are filtered of excess zinc salts. Our conditions tolerate a diverse array of functionalized organozinc reagents and ,-disubstituted cyclohexenone systems (18 examples, 56¿96% isolated yields). Additionally, to the best of our knowledge, we are the first to disclose the conjugate addition of monoorganozinc halides to ,-disubstituted cyclopentenone and cycloheptenone systems in good yield (7 examples, 38¿69% isolated yields).

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