Optical resolution of H/D isotopic chirality via asymmetric C-H amination.

Isotopic chirality arising from hydrogen/deuterium substitution has long resisted optical resolution because isotopic substitution introduces only minimal stereochemical differences, rendering such molecules structurally pseudo-achiral. Recognizing that the small yet distinct difference in C-H/C-D bond dissociation energies (BDEs) creates an energetic asymmetry, we envisioned that an enantioselective C-H functionalization exploiting this disparity could achieve the kinetic resolution of isotopically chiral molecules. Here, we report a catalytic method for the optical resolution of benzylic and allylic H/D isotopic chirality. This method achieved a remarkably high separation factor (S = 83.1), enabling the isolation of highly enantioenriched isotopically chiral substrates from racemic mixtures and revealing retention of stereochemical memory during radical recombination in asymmetric C-H functionalization.