Standard Article

The Synthesis of β-Lactams

  1. John C. Sheehan1,
  2. Ellas J. Corey2

Published Online: 15 MAR 2011

DOI: 10.1002/0471264180.or009.06

Organic Reactions

Organic Reactions

How to Cite

Sheehan, J. C. and Corey, E. J. 2011. The Synthesis of β-Lactams. Organic Reactions. 388–408.

Author Information

  1. 1

    Massachusetts Institute of Technology

  2. 2

    University of Illinois

Publication History

  1. Published Online: 15 MAR 2011

Abstract

The four-membered ring appears to be the smallest cyclic system that is capable of accommodating the amide function as a constituent. Such four-membered cyclic amides are commonly referred to as beta-lactams. The reluctance with which beta-lactams are formed using conventional methods of lactam synthesis has necessitated unique approaches to the problem. After 1943, interest in beta-lactams was stimulated by the importance of natural penicillins. Although there are at present several useful approaches to the beta-lactam ring systems, the synthesis of beta-lactams by a single general method is not possible. In principle, the synthesis of the beta-lactam ring might be accomplished by the formation of one, two, three, or all four bonds of the ring during the cyclization step. Of these four possibilities, only the last has been realized.

Keywords:

  • β-lactams;
  • synthesis;
  • cyclization;
  • β-amino acid derivative;
  • α-bromoesters;
  • zinc;
  • ketenes;
  • imines;
  • nitroso compounds;
  • imine;
  • acid chlorides;
  • amines;
  • dehydrohalogenation;
  • haloacylaminomalonic esters;
  • direct combination