The Development of the First Catalyzed Reaction of Ketenes and Imines:  Catalytic, Asymmetric Synthesis of β-Lactams

Andrew E. Taggi, Ahmed M. Hafez, Harald Wack, Brandon Young, Dana Ferraris, and Thomas Lectka*
Contribution from the Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218
J. Am. Chem. Soc., 2002, 124 (23), pp 6626–6635
DOI: 10.1021/ja0258226
Publication Date (Web): May 16, 2002
Copyright © 2002 American Chemical Society
*

 Corresponding author. E-mail:  lectka@jhunix.hcf.jhu.edu.

Abstract

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We report practical methodology for the catalytic, asymmetric synthesis of β-lactams resulting from the development of a catalyzed reaction of ketenes (or their derived zwitterionic enolates) and imines. The products of these asymmetric reactions can serve as precursors to a number of enzyme inhibitors and drug candidates as well as valuable synthetic intermediates. We present a detailed study of the mechanism of the β-lactam forming reaction with proton sponge as the stoichiometric base, including kinetics and isotopic labeling studies. Stereochemical models based on molecular mechanics (MM) calculations are also presented to account for the observed stereoregular sense of induction in our reactions and to provide a guidepost for the design of other catalyst systems.

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History

  • Published In Issue June 12, 2002
  • Received February 5, 2002

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