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

In organic synthesis, development of new reactivities or activation modes is fascinating since it could open the door of new synthetic transformations. Herein we report organocatalyst-controlled deuteration of enones at the αʹ-or α, αʹ-positions position under mild reaction conditions using D2O as deuterium source. The key to success of this protocol is the appropriate selection of catalytic system. Quinine-derived primary amine-benzoic acid catalytic composite deuterated the αʹ-position of enones with high selectivity. On the other hand, (1S,2S)-1,2-diphenylethane-1,2-diamine-benzoic acid catalytic system promotes deuteration at both the α, αʹ-positions of enones. In addition, this flexiable protocol also features broad substrate scope (50 examples) including drug molecules and natural products, mild reaction conditions and facile scalability. Mechanistically, the elusive α-deuteration of enones is realized due to unique reactivity of a diamine based organocatalyst-a reversible internal aza-Michael addition of the free amine of the diamine organocatalyst in the iminium ion to the βsite of the enone facilitates α-deuteration. Thereby, open up new reactivity.