Date of Thesis

Spring 2020

Description

Copper-catalyzed conjugate additions represent an important and widely utilized transition metal reaction to form new carbon-carbon bonds. Their development with different transmetalating agents and tuned reactivity based on given conditions has promoted their broad usage to reach complex new molecules. α,β-unsaturated carbonyls have seen primary use as substrates in conjugate addition reactions with key reactivity patterns which allow further reaction at the beta or alpha positions. It is therefore desirable to optimize a strategy to make such sequential reactions viable to reach complex molecules more efficiently.

We have previously developed a copper-catalyzed conjugate addition of monoorganozinc reagents to cyclohexenone substrates which has been optimized starting with either a halide or carbon fragment, a β-disubstituted enone, at the beta position. The reactivity differences of adding to the vinylogous halide versus the β-disubstituted enone has opened the possibility of a controlled set of sequential additions of carbon nucleophiles to the beta position. We have made strides in the optimization of a one pot sequential addition of different monoorganozinc reagents starting from a vinylogous halide. This provides a means to access quaternary chiral centers which have been noted for their difficulty in synthesis and proven importance as markers for viable pharmaceutical candidates. Further, one pot reactions can greatly improve efficiency by minimizing time, cost, and materials.

By boosting the reactivity of the organozinc reagent using LiCl, the sequential addition starting from a vinylogous bromide to reach a saturated beta position with a new quaternary chiral center could be realized with minimized catalyst loading in 67% yield. Future investigation of halide effects and further additives and temperature could be necessary to then lead to a final set of conditions and substrate scope of complex molecules.

Keywords

organic chemistry, catalysis, organometallics

Access Type

Honors Thesis (Bucknell Access Only)

Degree Type

Bachelor of Science

Major

Chemistry

Minor, Emphasis, or Concentration

Mathematics

First Advisor

Michael R. Krout

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