Efficient synthesis of β-substituted amines via combining deoxygenation of amides with photochemical organocatalysis

Abstract

Catalytic deoxygenative conversion of amides to substituted amines is an efficient pathway for amine synthesis. α-Substituted amines are generally obtained by classic nucleophilic addition of nucleophiles to active electrophilic intermediates formed from amides. Here, we develop a deoxygenative reaction of amides that combines iridium catalysis and photochemical organocatalysis, giving structurally diverse β-substituted tertiary alkylamines with moderate to excellent yields (up to 93%) with broad substrate scope (57 examples). Mechanistic studies suggest that the combination of iridium (Ir)-catalyzed partial reduction of amides and photochemical organocatalysis of α-bromoketones under visible light plays a crucial role in cross-coupling of these two readily accessible feedstocks. The active electrophilic radicals from photochemical organocatalysis act as functionalization partners with the in-situ -formed enamine intermediates from the Ir-catalyzed reduction of amides instead of traditional nucleophilic addition to iminium ions, leading to formation of β-substituted amines. • Combination of Ir-catalyzed reduction of amide and photochemical organocatalysis • Coupling of active electrophilic radicals with enamine intermediates • Tandem catalysis: Ir catalysis, photochemical organocatalysis, Ir catalysis • Deoxygenative functionalization of amides to β-substituted amines Deoxygenative functionalization of ubiquitous amides to synthetically important amines is of great significance. Jiang et al. develop deoxygenative cross-coupling of amides with electrophilic radicals by rational combination of Ir-catalyzed reduction of amides with photochemical organocatalysis, leading to a suite of functionally and structurally diverse β-substituted amines.