Photocatalytic and highly regioselective H/D exchange at alpha-thio C(sp3)-H bonds

Deuterated compounds used in drug discovery and live-cell imaging have recently gained the attention of various scientific fields. Although hydrogen-deuterium (H/D) exchange reactions are straightforward deuteration methods, achieving perfect regioselectivity is challenging. We report the highly regioselective deuteration of alpha-thio C(sp3)-H bonds using a thioxanthone or anthraquinone organic photocatalyst bearing an aromatic ketone skeleton and D2O as an inexpensive deuterium source under 390-nm irradiation. Notably, deuterium incorporation at the alpha-positions of O/N atoms, benzylic positions, and aromatic rings was not observed. The present regioselectivity was accomplished via a single electron transfer mechanism between the photocatalyst and S-containing substrates, as proven by laser-induced time-resolved transient absorption spectroscopic measurements. Furthermore, the proposed deuteration method could be applied to various S-containing substrates including pharmaceuticals and biologically active compounds with high regioselectivities. The available deuterated compounds as novel deuterated alkylation reagents for future drug discovery and as materials for Raman imaging were also demonstrated.