Hydrogen Isotope Exchange Catalyzed by Pyridine Dicarbene Cobalt Complexes Using Deuterium Gas

Abstract The catalytic performance of the pyridine dicarbene cobalt complex (iPrACNC)CoPh was evaluated for the hydrogen isotope exchange (HIE) of arenes, heteroarenes, and active pharmaceutical ingredients using D2 gas as the isotope source. The C–H functionalization reaction exhibited a broad substrate scope, tolerated an array of common organic functional groups and enabled the deuteration of a host of sterically accessible C(sp2)–H bonds. The cobalt catalyst was also effective for HIE at low pressures of D2 in polar aprotic solvents. Mechanistic studies support a pyridine dicarbene cobalt(I) aryl complex as the catalytic resting state and a catalytic cycle involving cobalt(I)–hydride-mediated C(sp2)–H activation. Taken together, this work establishes (iPrACNC)CoPh as an effective catalyst for HIE and expands the application of earth-abundant metal catalysis in late-stage isotopic labeling of organic molecules.