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Ketene Cycloadditions

  1. John A. Hyatt,
  2. Peter W. Raynolds

Published Online: 15 OCT 2004

DOI: 10.1002/0471264180.or045.02

Organic Reactions

Organic Reactions

How to Cite

Hyatt, J. A. and Raynolds, P. W. 2004. Ketene Cycloadditions. Organic Reactions. 45:2:159–646.

Author Information

  1. Eastman Chemical Co., Research Laboratories, Kingsport, Tennessee

Publication History

  1. Published Online: 15 OCT 2004

Abstract

The reaction of ketene with itself was described almost simultaneously in 1908 by Chick and Wilsmore in England, and by Staudinger and Klever in Germany; priority for the discovery was attributed to Wilsmore by the German group.

Ketene cycloaddition was an early example of a peculiar process, one that formed carbon–carbon bonds with ease, often without the need for solvent, catalyst, or high heat. Subsequent work by others was done in the shadow of Staudinger's exhaustive and rigorous study of all phases of ketene reactivity. Three factors led to a resurgence of interest in this reaction beginning in the 1960s. Haloketenes, which had previously eluded study, were found to have high reactivity, and the halogens could easily be removed after the reaction. The increasing sophistication of powerful analytical methods, particularly nuclear magnetic resonance spectroscopy, led to discovery of the interesting stereochemical aspects of this reaction. Finally, the new theory of orbital symmetry conservation provided a conceptual framework to rationalize these puzzling “no mechanism” reactions.

This chapter is a review of cycloaddition reactions of ketenes. Here, a cycloaddition is defined as a reaction of a ketene with an unsaturated organic compound to give a cyclic product by a mechanism that, in principle, involves the almost simultaneous formation of two bonds between two reactants. While there is no concern here as to whether bond formation is concerted or stepwise, no other chemical process can take place between the formation of the first and second bond. Definition here involves both structural and mechanistic factors, and it is difficult to avoid a certain amount of arbitrariness. Products, such as dehydroacetic acid, which seem to us to arise by concatenation of ketene molecules followed by cyclization are excluded. These reactions, are more properly considered to arise from a series of ionic reactions, and the prediction of the eventual product does not take advantage of the special mechanistic features commonly associated with true cycloadditions. Additions to imines to give β-lactams are numerous and will be covered in a separate review. The literature has been searched to the end of 1988.

Many reviews devoted partially or exclusively to ketene cycloadditions have been published. Specific topics that have been reviewed include haloketenes, fluoroketenes, cyanoketenes, intramolecular cycloadditions, conjugated ketenes, and β-lactam antibiotics. Ancillary topics pertinent to ketene cycloadditions that have been reviewed include cycloreversion reactions, ketene equivalents, which provide ketene functionality with olefin-like reactivity especially in [4 + 2] reactions, application of frontier molecular orbital theory to cycloadditions, and a critical discussion of cycloadditions with polar intermediates. Applications of cyclobutanones in synthesis have also been reviewed.

Keywords:

  • ketene cycloadditions;
  • cycloadditions;
  • acylketenes;
  • vinyl ketenes;
  • alpha, beta-unsaturated ketones;
  • alpha, beta-unsaturated thiones;
  • acyl isocyanates;
  • acyl azo compounds;
  • thioacyl imines;
  • thiacyl imines;
  • mesionic compounds;
  • experimental procedures;
  • scope;
  • limitations;
  • dienes;
  • azadienes;
  • amidines;
  • o-quinones;
  • heterocumulenes;
  • azo compounds