Selective [alpha]-Oxyamination and Hydroxylation of Aliphatic Amides

Compared to the [alpha]-functionalization of aldehydes, ketones, even esters, the direct [alpha]-modification of amides is still a challenge because of the low acidity of [alpha]-CH groups. The [alpha]-functionalization of N-H (primary and secondary) amides, containing both an unactived [alpha]-C-H bond and a competitively active N-H bond, remains elusive. Shown herein is the general and efficient oxidative [alpha]-oxyamination and hydroxylation of aliphatic amides including secondary N-H amides. This transition-metal-free chemistry with high chemoselectivity provides an efficient approach to [alpha]-hydroxy amides. This oxidative protocol significantly enables the selective functionalization of inert [alpha]-C-H bonds with the complete preservation of active N-H bond.