Selective α-Oxyamination and Hydroxylation of Aliphatic Amides.

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