Weinreb ketone synthesis

The Weinreb amide ketone synthesis is a chemical reaction, which serves to convert carboxylic acids to ketones or aldehydes. Weinreb amides are N, O- Dimethylhydroxylamide a carboxylic acid. The names of reaction is named after Steven M. Weinreb.

Preparation of Weinreb amides

Weinreb amides are normally prepared by amidation of carboxylic acids, for example through its carbonyl halides.

Aminolysis of the carbonic acid esters with metalated N, O- dimethylhydroxylamine ( N, O- Dimethylhydroxylamid ) are a possibility to produce the Weinreb amides.

Mechanism

The reaction of carboxylic acid derivatives such as esters and acid chlorides with organometallic nucleophiles such as Grignard compounds not normally leads to the ketones, because here the leaving group is good and the ketone already formed during the reaction and this then another with a nucleophile can react further to give the corresponding alcohols. In Weinreb amides, the leaving group is relatively poor and the ketone is released only at workup with dilute aqueous acid. During the reaction, Weinreb amide remains at the level of stable chelate are tetrahedral, which prevents the addition of more than one equivalent of the organometallic compound. In the chelate complex is a hemiaminal.

Importance

Of Weinreb amides can be prepared in ketones, and formation of a carbon -carbon bond in two steps, and usually in good yield carboxylic acids. With the reducing agent is diisobutylaluminum hydride ( DIBAL -H) Weinreb amides are reduced to hemiaminals that provide aldehydes upon hydrolysis.