Highly Enantioselective Hydrogenation of Non- ortho-Substituted 2-Pyridyl Aryl Ketones via Iridium- f-Diaphos Catalysis

Org Lett. 2019 Jul 19;21(14):5392-5396. doi: 10.1021/acs.orglett.9b01415. Epub 2019 Jun 26.

Abstract

This work disclosed a highly enantioselective hydrogenation of non-ortho-substituted 2-pyridyl aryl ketones via Ir/f-diaphos catalysis. This catalytic system allows for full control over the configuration of the stereocenter, affording two enantiomers of the desired products with extremely high enantioselectivity (up to >99% ee in most cases) and excellent reactivity (TON of up to 19600, TOF of 1633 h-1) under mild conditions. Density functional theory calculations and control experiments revealed that the relay hydrogen bonding among the solvent isopropanol, substrate, and ligand is crucial for high ee's.