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Weinreb Ketone Synthesis

(Weinreb Acylation, Weinreb Amide reduction)

Published Online: 15 SEP 2010

DOI: 10.1002/9780470638859.conrr661

Comprehensive Organic Name Reactions and Reagents

Comprehensive Organic Name Reactions and Reagents

How to Cite

2010. Weinreb Ketone Synthesis. Comprehensive Organic Name Reactions and Reagents. 661:2963–2967.

Publication History

  1. Published Online: 15 SEP 2010

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Abstract

The synthesis of ketones by the treatment of the Weinreb amides (i.e., amides of N-methyl-N-methoxy hydroxylamine) with a variety of carbanions (e.g., Grignard reagent, alkyl lithium, lithium enolate, phosphonium ylides, etc.) followed by hydrolysis is known as the Weinreb ketone synthesis or Weinreb acylation and the reduction of the Weinreb amide by hydride (e.g., LiAlH4, DIBAL-H, etc.) to give aldehyde is referred to as the Weinreb amide reduction. It has been reported that the high chemoselectivity used to form either ketones or aldehydes from the Weinreb amides is because of the exceptional stability of intermediate alkoxide due to the chelation of metal cation with alkoxide oxygen and an oxygen atom of N-methoxy group. The yields of ketones from the Weinreb amides are generally higher, probably because of the higher nucleophilicity of the Weinreb amides. It is worth noting that the Weinreb amide group is very stable and can survive under different reaction conditions. This reaction is useful for the preparation of aldehydes and ketones.

Keywords:

  • benzyl ester;
  • Diisobutylaluminum hydride;
  • N,O-dimethylhydroxylamine;
  • N-methyl-N-methoxy hydroxylamine