Synthesis 2014; 46(07): 829-841
DOI: 10.1055/s-0033-1338596
review
© Georg Thieme Verlag Stuttgart · New York

The Nef Reaction of Isocyanides

Fabio La Spisa
a  Dipartimento di Scienze del Farmaco, Università degli Studi del Piemonte Orientale ‘A. Avogadro’, Largo Donegani 2, 28100 Novara, Italy   Email: tron@pharm.unipmn.it
,
Gian Cesare Tron*
a  Dipartimento di Scienze del Farmaco, Università degli Studi del Piemonte Orientale ‘A. Avogadro’, Largo Donegani 2, 28100 Novara, Italy   Email: tron@pharm.unipmn.it
,
Laurent El Kaïm*
b  UMR 7652 (Ecole Polytechnique/ENSTA/CNRS), Laboratoire Chimie et Procédés, ENSTA-Paristech, 828 Bd des maréchaux, 91120 Palaiseau, France   Email: laurent.elkaim@ensta-paristech.fr
› Author Affiliations
Further Information

Publication History

Received: 15 October 2013

Accepted after revision: 11 November 2013

Publication Date:
05 March 2014 (eFirst)

Abstract

The interaction of isocyanides with acyl chlorides was first reported by Nef in 1892. The resulting α-keto imidoyl chlorides may be hydrolyzed to form α-keto amides. Relatively few data are available on this reaction and the chemistry of α-keto imidoyl chlorides has been largely underestimated until some recent uses in intra­- and intermolecular couplings with a variety of nucleophiles. The present review brings a comprehensive presentation of the Nef reaction of isocyanides focusing on mechanism and regioselectivity issues.

1 Isocyanide Chemistry

2 Isocyanide Interaction with Acyl Chlorides and Analogues

2.1 General Considerations

2.2 Methods of Preparation of α-Keto Imidoyl Chlorides

2.3 Nef Reaction Mechanism

3 Reactivity of α-Keto Imidoyl Chlorides

3.1 General Behavior of α-Keto Imidoyl Chlorides

3.2 Intramolecular Trappings

3.3 Intermolecular Trappings and Three-Component Reactions

4 Extensions of the Nef Reaction

5 Conclusion

 
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