Date Approved

2014

Degree Type

Open Access Thesis

Degree Name

Master of Science (MS)

Department or School

Chemistry

Committee Member

Harriet Lindsay, PhD, Chair

Committee Member

Cory Emal, PhD

Committee Member

Timothy Friebe, PhD

Abstract

We have developed a Lewis-acid catalyzed, diastereoselective aza-Cope rearrangement— Mannich cyclization to form acyl pyrrolidines from conformationally mobile substrates. In earlier studies from our lab, Brønsted acid-catalyzed reactions to form the same acyl pyrrolidines resulted in diastereoselectivities of 8:1 trans to cis at elevated temperatures (60 °C) over the course of 150 minutes. We have demonstrated an improvement in our method yielding exclusively the trans isomers at ambient temperature with substoichiometric amounts of BF3•OEt2 within 3 minutes. Catalyst loadings as low as 0.05 equivalents of BF3•OEt2 initiate this transformation. Our synthetic method employs the oxazolidine starting material as a mixture of diastereomers to produce one pyrrolidine diastereomer. Both ethyland substituted phenyl-oxazolidines were successfully rearranged. This work is the first example of a truly catalytic aza-Cope—Mannich reaction and provides the first examples of diastereoselective syntheses of 2-phenyl-4-acylpyrrolidines via this reaction.

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