Journal of Organic Chemistry 2012-12-07

A stereoselective cyclization strategy for the preparation of γ-lactams and their use in the synthesis of α-methyl-β-proline.

Souvik Banerjee, Justin Smith, Jillian Smith, Caleb Faulkner, Douglas S Masterson

Index: J. Org. Chem. 77(23) , 10925-30, (2012)

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Abstract

A straightforward stereoselective and enantiodivergent cyclization strategy for the construction of γ-lactams is described. The cyclization strategy makes use of chiral malonic esters prepared from enantiomerically enriched monoesters of disubstituted malonic acid. The cyclization occurs with the selective displacement of a substituted benzyl alcohol as the leaving group. A Hammett study illustrates that the cyclization is under electronic control. The resulting γ-lactam can be readily converted into a novel proline analogue.