Rhodium-Catalyzed Stereoselective Deuteration of Benzylic C-H Bonds via Reversible η 6 -Coordination.

We report a convenient method for benzylic H/D exchange of a wide variety of substrates bearing primary, secondary, or tertiary C-H bonds via a reversible η 6 -coordination strategy. A doubly cationic [Cp CF3 Rh III ] 2+ catalyst that serves as an arenophile facilitates deprotonation of inert benzylic hydrogen atoms (pK a >40 in DMSO) without affecting other hydrogen atoms, such as those on aromatic rings or in α-positions of carboxylate groups. Notably, the H/D exchange reactions feature high stereoretention. We demonstrated the potential utility of this method by using it for deuterium labeling of ten pharmaceuticals and their analogues.