Graduation Year

2016

Document Type

Thesis

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

Chemistry

Major Professor

Jon Antilla, Ph.D.

Committee Member

Bill Baker, Ph.D.

Committee Member

Wayne Guida, Ph.D.

Committee Member

Robert Potter, Ph.D.

Committee Member

Edward Turos, Ph.D.

Keywords

Enantioselective synthesis, 1, 4-reduction, BINOL-derived boro-phosphate catalysts, α, β-unsaturated enones, ketones, reductive aldol, organocatalysis, boro-phosphate catalysis

Abstract

The biological activity of the pharmaceutical drugs often depends on how it fits with a receptor making stereochemistry a key component. Selective reactions can limit or avoid the mixture of enantiomers obtained. One such reaction is the selective reduction of a carbon-carbon double bond in the presence of a carbonyl. Although efficient, current asymmetric synthesis methods have limitations such as harsh reaction conditions, the high costs of chiral catalysts and the toxicity of the metal-based catalysts. Catalysts derived from small organic molecules have become an attractive alternative which have been explored more rigorously in recent years. Using a BINOL-derived boro-phosphate catalyst, we have developed a methodology that selectively reduces the carbon-carbon double bond of linear α, β-unsaturated ketones, exclusively giving the corresponding saturated ketone. To the best of our knowledge, this reaction is the first of its kind to accomplish this transformation and results give high yields of >93% and enantioselectivities >90% at room temperature. Furthermore, the products of this novel reaction can be subjected to a choice electrophile, in example benzaldehyde, to afford diastereoselective tertiary alcohol products with enantioselectivities of >88% and diastereoselectivities of up to 99:1.

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