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

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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