Advancements in the diastereoselective synthesis of acyl pyrrolidines via the tandem aza-Cope—Mannich cyclization pathway

<p>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 <em>trans</em> to <em>cis</em> at elevated temperatures (60 °C) over the course of 150 minutes. We have demonstrated an improvement in our method yielding exclusively the <em>trans</em> 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.</p>

Name thesis:degree_name

Master of Science (MS)

Level thesis:degree_level

Open Access Thesis

Discipline thesis:degree_discipline

Chemistry

Year dc:date.available

2014

Author dc:creator

• St. Germaine, Danielle

Contributors dc:contributor

• Harriet Lindsay, PhD, Chair
• Cory Emal, PhD
• Timothy Friebe, PhD

• Ge
• Chemistry

Repository record dc:identifier

https://commons.emich.edu/theses/911

OAI identifier oai:identifier

oai:commons.emich.edu:theses-2287