N-Mannich Bases of Aromatic Heterocyclic Amides: Synthesis via Copper-Catalyzed Aerobic Cross-Dehydrogenative Coupling under Ambient Conditions

Org Lett. 2017 Mar 17;19(6):1322-1325. doi: 10.1021/acs.orglett.7b00125. Epub 2017 Mar 1.

Abstract

An efficient and facile method to synthesize N-Mannich bases has been developed using an inexpensive copper(I) bromide/air catalyst system at ambient temperature. A cross-dehydrogenative coupling of N,N-dimethylarylamines occurs efficiently with aromatic heterocyclic amides (oxindoles, isatins), cyclic amides (lactams), simple amides (benzamide), as well as imides (succinimide, phthalimide) to furnish the corresponding amidated/imidated derivatives in good to excellent yields. Preliminary mechanistic and isotope-labeling studies suggest the reaction follows a radical pathway and involves an iminium ion intermediate.

Publication types

  • Research Support, Non-U.S. Gov't