Catalytic, Metal-Free Amide Synthesis from Aldehydes and Imines Enabled by a Dual-Catalyzed Umpolung Strategy under Redox-Neutral Conditions

The synthesis of amides is a long-term theme in chemistry and related areas. The use of readily available and cost-effective precursors for straightforward amide synthesis with atom economy under mild conditions is attractive yet challenging. Herein, we report the direct synthesis of amides from aldehydes and imines in a 100% atom-economical manner. The redox-neutral C-N bond-forming process was enabled by the dual catalysis of visible light and an N-heterocyclic carbene (NHC) at room temperature. This protocol features the unprecedented umpolung of imines to generate N-centered radicals. Mechanistic investigations reveal this reaction undergoes nontrivial radical-radical coupling between an N-centered radical and a C-centered radical to forge a C-N bond. This operationally simple protocol tolerates a wide range of functional groups, providing rapid access to amides from aromatic or aliphatic aldehydes with imines without producing any byproduct.