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.
Authors
- Yuuya Kawasaki (ORCID: https://orcid.org/0000-0003-3354-1690)
- Tatsuya Uchida (ORCID: https://orcid.org/0000-0002-6511-5752)
- Yuta Nakagawa (ORCID: https://orcid.org/0000-0002-3306-9077)
- Naoki Watari
Institutions
- Kyushu University (JP)
- Japan Tobacco (Japan) (JP)
Publication Details
- Journal
- Science Advances
- Published
- 2026-10-07
- DOI
- https://doi.org/10.1126/sciadv.aed4187
- Primary Topic
- Asymmetric Synthesis and Catalysis
- Type
- article
- Field-Weighted Citation Impact
- 0.00