Weinreb amide ketone synthesis

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The Weinreb amide ketone synthesis is a chemical reaction which is used to convert carboxylic acids into ketones or aldehydes . Weinreb amides are N , O -dimethylhydroxylamides of a carboxylic acid . The name reaction was named after Steven M. Weinreb .

Representation of Weinreb amides

Weinreb amides are normally produced by amidating carboxylic acids, for example via their carboxylic acid halides .

Amidation of a carboxylic acid chloride

The aminolysis of carboxylic acid esters with metalated N , O -dimethylhydroxylamine is also a possibility to produce Weinreb amides.

Weinreb amidsynthesis GR V1-Seite001.svg

mechanism

The implementation of carboxylic acid derivatives such as esters and acid chlorides with organometallic nucleophiles such. B. Grignard compounds generally do not lead to the ketones because the leaving group is good here and the ketone is already formed during the reaction and this can then react with another nucleophile to form the corresponding alcohols . In the case of Weinreb amides, the leaving group is relatively poor and the ketone is only released after working up with dilute, aqueous acid. During the reaction, the Weinreb amide remains at the level of the stable tetrahedral chelate, which prevents the addition of more than one equivalent of the organometallic compound. The chelate complex is a hemi-aminal .

Weinreb ketone synthesis MECH V1-Seite001.svg

meaning

From Weinreb amides, ketones can be produced from carboxylic acids in two steps and usually in good yields, with the formation of a carbon-carbon bond. With the reducing agents diisobutylaluminum hydride (DIBAL-H) ​​or lithium aluminum hydride (LiAlH 4 ), Weinreb amides are reduced to hemiaminals which, after hydrolysis, yield aldehydes.

Individual evidence

  1. ↑ S. Nahm, SM Weinreb: in Tetrahedron Letters 'N-methoxy-n-methylamides as effective acylating agents' 1981 , 22 , 3815-3818.
  2. ↑ Entry on Weinreb amide. In: Römpp Online . Georg Thieme Verlag, accessed on August 5, 2019.
  3. ^ OP Goel, U. Krolls, M. Stier, S. Kesten: in Organic Synthesis Collectiv Volume 8 , 69 1989 .

literature

  • Kürti, László and Czakó, Barbara: Strategic Applications of Named Reactions in Organic Synthesis; Elsevier Academic Press, Burlington-San Diego-London 2005, 1st edition; ISBN 0-12-369483-3 .