Chiral Intramolecular Ether–Borane FLPs for Asymmetric Ketone Hydrogenation
- 1D-CHAB
- 2Laboratorium für Organische Chemie, ETH Zürich
Abstract
Asymmetric hydrogenation of ketones remains challenging in frustrated Lewis pair (FLP) catalysis, largely because the low basicity of ketones places stringent demands on both H 2 activation and stereocontrol. Here we introduce binaphthyl ether–boranes (BINEBs), a new class of chiral intramolecular FLPs featuring a bis-ether Lewis base tethered to a strongly Lewis acidic borane on an axially chiral binaphthyl scaffold. BINEBs catalyze the asymmetric hydrogenation of a broad range of aromatic ketones, delivering chiral secondary alcohols with high enantioselectivities. This platform also enables the first metal-free kinetic resolution of cyclic α-haloketones using H 2 as the reductant, providing enantioenriched cis-halohydrins with selectivity factors (s) exceeding 200. Mechanistic studies and DFT calculations support a multifunctional role for the key intramolecular bis-ether motif: it mediates heterolytic H 2 cleavage and, following proton transfer to the ketone, remains engaged through hydrogen bonding, orienting the substrate for stereoselective hydride transfer. This study illustrates how covalent Lewis acid–base preorganization can enhance substrate recognition and stereocontrol, providing catalyst design principles that may open opportunities in asymmetric FLP hydrogenation and Lewis acid catalysis.
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BibTeX
@misc{shcherbakov2026chiral,
title = {{Chiral Intramolecular Ether–Borane FLPs for Asymmetric Ketone Hydrogenation}},
author = {Nikolay V. Shcherbakov and Julius K. Kräutle and Josep Mas-Roselló},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15009927/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009927/v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Chiral Intramolecular Ether–Borane FLPs for Asymmetric Ketone Hydrogenation
AU - Nikolay V. Shcherbakov
AU - Julius K. Kräutle
AU - Josep Mas-Roselló
PY - 2026
DA - 2026/10/05
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009927/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009927/v1
AB - Asymmetric hydrogenation of ketones remains challenging in frustrated Lewis pair (FLP) catalysis, largely because the low basicity of ketones places stringent demands on both H 2 activation and stereocontrol. Here we introduce binaphthyl ether–boranes (BINEBs), a new class of chiral intramolecular FLPs featuring a bis-ether Lewis base tethered to a strongly Lewis acidic borane on an axially chiral binaphthyl scaffold. BINEBs catalyze the asymmetric hydrogenation of a broad range of aromatic ketones, delivering chiral secondary alcohols with high enantioselectivities. This platform also enables the first metal-free kinetic resolution of cyclic α-haloketones using H 2 as the reductant, providing enantioenriched cis-halohydrins with selectivity factors (s) exceeding 200. Mechanistic studies and DFT calculations support a multifunctional role for the key intramolecular bis-ether motif: it mediates heterolytic H 2 cleavage and, following proton transfer to the ketone, remains engaged through hydrogen bonding, orienting the substrate for stereoselective hydride transfer. This study illustrates how covalent Lewis acid–base preorganization can enhance substrate recognition and stereocontrol, providing catalyst design principles that may open opportunities in asymmetric FLP hydrogenation and Lewis acid catalysis.
ER -