Organocatalyst-Controlled Highly α′-Selective Deuteration and α,α′-Deuteration of Enones

Herein, we report organocatalyst-controlled deuteration of enones at the α′-position or at both the α- and α′-positions under mild reaction conditions using D2O as the deuterium source. The key to the success of this protocol is the appropriate selection of the catalytic system. A quinine-derived primary amine-benzoic acid catalytic composite deuterated the α′-position of enones with high selectivity. On the other hand, the (1S,2S)-1,2-diphenylethane-1,2-diamine-benzoic acid catalytic system promotes deuteration at both the α- and α′-positions of enones. In addition, this flexible protocol also features a broad substrate scope (>48 examples), including drug molecules and natural products, mild reaction conditions, and facile scalability. A working mechanistic pathway is also proposed.