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

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.