Fast Enantio- and Chemoselective Arylation of Ketones with Organoboronic Esters Enabled by Nickel/N-Heterocyclic Carbene Catalysis

A general, efficient, highly enantio- and chemoselective N-heterocyclic carbene (NHC)/Ni-catalyzed addition of readily available and stable arylboronic esters to ketones is reported. This protocol provides unexpectedly fast access (usually 10 min) to various chiral tertiary alcohols with exceptionally broad substrate scope and excellent functional group tolerance (76 examples, up to 98 % ee). This process is orthogonal to other known Ni-mediated Suzuki-Miyaura couplings, as it tolerates aryl chlorides, fluorides, ethers, esters, amides, nitriles, and alkyl chlorides. The reaction is applied to late-stage modifications of various densely functionalized medicinally relevant molecules. Preliminary mechanistic studies suggest that a rare enantioselective eta(2)-coordinating activation of ketone carbonyls is involved. This cross-coupling-like mechanism is expected to enable other challenging transformations of ketones.

Automated summary

This study reports a highly efficient NHC/Ni-catalyzed addition reaction of arylboronic esters to ketones, providing rapid access to chiral tertiary alcohols with broad substrate scope and excellent functional group tolerance. The reaction differs from other Ni-mediated reactions, exhibiting good specificity and tolerance to various functional groups.