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

Ming‐Shang Liu, Wei Shu

2020ACS Catalysis103 citationsDOI

Abstract

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.

Topics & Concepts

UmpolungChemistryCatalysisAmideCombinatorial chemistryAtom economyCarbeneRadicalOrganocatalysisRedoxOrganic synthesisOrganic chemistryPhotochemistryEnantioselective synthesisNucleophileCatalytic Cross-Coupling ReactionsOrganoboron and organosilicon chemistryCatalytic C–H Functionalization Methods