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

Abstract

AbstractWe 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 [CpCF3RhIII]2+ catalyst that serves as an arenophile facilitates deprotonation of inert benzylic hydrogen atoms (pKa>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.