Reductive hydroxyalkylation/alkylation of amines with lactones/esters?

Organic & Biomolecular Chemistry Pub Date: 2012-06-14 DOI: 10.1039/C2OB25901J

Abstract

We have developed a one-pot method for the direct intermolecular reductive hydroxyalkylation or alkylation of amines using lactones or esters as the hydroxyalkylating/alkylating reagents. The method is based on the in situ amidation of lactones/esters with DIBAL-H–amine complex (for primary amines) or DIBAL-H–amine hydrochloride salt complex (for secondary amines), followed by reduction of the amides with an excess of DIBAL-H. Different from the reduction of Weinreb amides with DIBAL-H where aldehydes are formed, the reduction of the in situ formed Weinreb amides yielded amines. Moreover, this method is not limited to Weinreb amides, instead, it also works for other amides in general. A plausible mechanism is suggested to account for the outcome of the reactions.

Graphical abstract: Reductive hydroxyalkylation/alkylation of amines with lactones/esters
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