Diastereoselective aza-cope rearrangement-mannich cyclizations of conformationally mobile iminium cations

<p>We have developed a Lewis-acid catalyzed, diastereoselective aza-Cope rearrangement— Mannich cyclization (ACM) to form acyl pyrrolidines from conformationally mobile substrates. Earlier studies from our lab have shown that substituted acyl pyrrolidines can be synthesized with diastereoselectivity of 50:1 <em>trans</em> to <em>cis</em>, and that unsubstituted pyrrolidines can be synthesized with 13:1 enantioselectivity. This study attempted to observe the stereochemical outcomes of the ACM for disubstituted pyrrolidine systems using oxazolidine starting materials. A proof of concept dimethyl-substituted oxazolidine was subjected to ACM conditions, producing the pyrrolidine with good yields. However, when methyl-phenyl substituted oxazolidine was subjected to ACM conditions, undesired byproduct was formed. We believe that the requisite iminium cation for the ACM reaction is quite stable, causing an unusually high aza- Cope activation barrier and allowing for an undesired pathway to be favored. Destabilization of the iminium cation intermediate via an electron withdrawing group may allow for the reaction to proceed. Enantiomeric control of dimethyl substituted oxazolidine was also observed. Under ACM conditions, 8.5:1 beta to alpha selectivity was observed with good yields. This work emphasizes the ability of the ACM reaction to produce stereoselective pyrrolidine products.</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

2016

Author dc:creator

• Hunt, Joshua

Contributors dc:contributor

• Cory Emal, Ph.D.
• Maria Milletti, Ph.D.

• Aza-Cope
• chirality transfer
• Diastereoselectivity
• oxazolidine
• pyrrolidine
• stereochemistry
• Chemistry

Repository record dc:identifier

https://commons.emich.edu/theses/684

OAI identifier oai:identifier

oai:commons.emich.edu:theses-2067