Oxidative Cross-Coupling of -Amino Ketones with Alcohols Enabled by I₂-Catalyzed C-H Hydroxylation

An I-2-catalyzed oxidative cross-coupling of alpha-amino ketones with a wide range of alcohols is described. Using a combination of air and dimethyl sulfoxide (DMSO) as oxidants, the protocol allows an efficient synthesis of alpha-carbonyl N,O-acetals with high functional group tolerance and enables the late-stage introduction of alpha-amino ketones into biorelevant alcohols. Moreover, the present method can be used in the coupling of alpha-amino ketones with other kinds of nucleophiles, which demonstrates great generality for the functionalization of alpha-amino ketones. A preliminary mechanistic investigation suggests that C-H hydroxylation of alpha-amino ketones has been recognized as the key step followed by subsequent dehydration coupling.