Different Behaviors of a Cu Catalyst in Amine Solvents: Controlling N and O Reactivities of Amide

Abstract

Controlling the reactivity of the nitrogen or oxygen nucleophile of an amide group to form C–N or C–O bonds by tuning reaction conditions is one of the most challenging issues in the use of amides in organic synthesis. Both nucleophiles in the amide group can individually participate in reactions, and most reactions employ a substrate-controlled methodology to achieve selectivity. However, in the reaction of α-bromoamides and acrylates, we successfully controlled the reactivity of the nitrogen or oxygen nucleophile of the amide group to afford a lactam via carboamidation or an iminolactone via carbooxygenation, using a copper catalyst system with an appropriate base.