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Synthesis 2003(11): 1722-1726
DOI: 10.1055/s-2003-40879
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Pyrrolidine-5,5-trans-lactams 3. Alternative Regiochemical Outcome of the Acyl-Iminium Coupling Reaction.

David M. Andrews*, Alan D. Borthwick, Helene Chaignot, Paul S. Jones, J. Ed Robinson, Pritom Shah, Martin J. Slater, Richard J. Upton
GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, UK
Fax: +44(1438)763620; e-Mail: david.m.andrews@astrazeneca.com;
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Publication History

Received 9 May 2003
Publication Date:
25 July 2003 (online)

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Abstract

Enantio- and regioselective syntheses of the pyrrolidine 5,5-trans-lactams benzyl (3aS,6aR)-6,6-dimethyl-5-oxohexahydropyrrolo[3,2-b]pyrrole-1(2H)-carboxylate and benzyl (3aS,6aR)-6S-ethyl-5-oxohexahydropyrrolo[3,2-b]pyrrole-1(2H)-carboxylate from a common intermediate 2-ethoxy-3S-(2,2,2-trifluoro-acetylamino)-pyrrolidine-1-carboxylic acid benzyl ester are reported. The key step in both syntheses is the acyl iminium ion mediated condensation of the pyrrolidine with a ketene acetal.

Key words

antiviral agents - lactams - neighboring-group effects - regioselectivity - steric hindrance

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