Selective α‐Oxyamination and Hydroxylation of Aliphatic Amides

Abstract

Compared to the a-functionalization of aldehydes, ketones,even esters,the direct a-modification of amides is still achallenge because of the low acidity of a-CH groups.The afunctionalization of N À H( primary and secondary) amides, containing both an unactived a-C À Hbond and acompetitively active N À Hbond, remains elusive.Shownherein is the general and efficient oxidative a-oxyamination and hydroxylation of aliphatic amides including secondary NÀHa mides.T his transition-metal-free chemistry with high chemoselectivity provides an efficient approach to a-hydroxy amides.T his oxidative protocol significantly enables the selective functionalization of inert a-C À Hbonds with the complete preservation of active N À Hb ond.Aldehydes,ketones,esters,acids,and amides are very Scheme 1. The significance and challenges for the a-modification of aliphatic amides. Tf = trifluoromethanesulfonyl, Ts = 4-toluenesulfonyl.

Recent Advances in Carbon‐Nitrogen/Carbon‐Oxygen Bond Formation Under Transition‐Metal‐Free Conditions

“…Apart from the organic catalysts discussed previously, organic promoters were also reported in such reactions. In 2017, the Jiao group described a general and efficient direct oxidative α‐hydroxylation of aliphatic secondary amides ( 223 ) under mild conditions (Scheme 46a) [129] . TEMPO was utilized as both an oxidant and the oxygen source, and TIPSOTf was demonstrated as an efficient activation reagent.…”