Rhodium-Catalyzed Stereoselective Deuteration of Benzylic C-H Bonds via Reversible η6 -Coordination

Abstract

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 η⁶ -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.

Keywords: Acidity; C−H Activation; Hydrogen Isotope Exchange; Rhodium Catalysis; Stereoretention.