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Updated: Jan 13, 2026
A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
Published on: February 16, 2020
Intermolecular Enantioselective Nickel-Catalyzed Arylation of Un-Activated C(sp3)─H Bond
Erwan Brunard1, Fengjie Huang1, Àlex Díaz-Jiménez1
1Institute of Organic Chemistry, JMU Würzburg, Am Hubland, 97074, Würzburg, Germany.
Abstract:
We report the first example of an intermolecular, enantioselective Ni(II)-catalyzed C(sp3)─H arylation, providing direct access to challenging all-carbon quaternary stereogenic centers. Key to this success is the use of a specially designed BINOL-derived ligand, which enables efficient desymmetrization of gem-dimethyl groups through a rate- and enantio-determining C─H activation step. This catalytic system demonstrates remarkable functional group tolerance, affording a wide variety of arylated products in high yields (up to 85%) and with excellent enantioselectivities (up to 95:5 e.r.). Mechanistic studies, combining kinetic isotope effect measurements, deuterium labeling, and DFT calculations, reveal that the Ni-BINOL complex promotes a unique concerted metalation-deprotonation pathway assisted by ligand coordination and π-π interactions. This work establishes nickel as a powerful and sustainable alternative to precious metals for asymmetric C─H activation, opening new perspectives for the construction of enantioenriched quaternary carbon centers of high relevance in drug discovery and materials science.
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