Date of Thesis

2016

Description

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).

Keywords

conjugate addition, quaternary stereocenter, organozinc reagents, eudesmanes

Access Type

Masters Thesis (Bucknell Access Only)

Degree Type

Master of Science

Major

Chemistry

First Advisor

Michael R. Krout

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