Schmidt Reaction of Hydroxyalkyl Azides with Acyclic Ketones

J Org Chem. 2026 Feb 27;91(8):3256-3261. doi: 10.1021/acs.joc.5c02945. Epub 2026 Feb 11.

Abstract

The Schmidt reaction of hydroxyalkyl azides with acyclic ketones has been investigated. Specifically, we show that this reaction consistently generates an ester product via hydrolysis of an intermediate iminium ether. This is in contrast to most cyclic ketones, which provide lactams. Moreover, the addition of nucleophiles to the intermediate affords amide products through a mechanistically distinct pathway. Studies related to the reaction scope, regioselectivity, and mechanism are also reported.