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

Institutions

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
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

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

Yuuya Kawasaki, Tatsuya Uchida, Yuta Nakagawa, Naoki Watari
Science Advances
Asymmetric Synthesis and Catalysis
article

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

Yuuya Kawasaki, Tatsuya Uchida, Yuta Nakagawa, Naoki Watari
article en

Abstract

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.

Science AdvancesVol. 12(41)
Kyushu University (JP), Japan Tobacco (Japan) (JP)
Openalex Percentile: Top 24%
Asymmetric Synthesis and Catalysis
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.

Optical resolution of H/D isotopic chirality via asymmetric C–H amination — Yuuya Kawasaki, Tatsuya Uchida, et al. · Science Advances (2026) | TGRS Research Map | TGRS