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Fast Enantio‐ and Chemoselective Arylation of Ketones with Organoboronic Esters Enabled by Nickel/N‐Heterocyclic Carbene Catalysis
Author(s) -
Cai Yuan,
Ruan LinXin,
Rahman Abdul,
Shi ShiLiang
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202015021
Subject(s) - carbene , chemistry , aryl , catalysis , ketone , enantioselective synthesis , combinatorial chemistry , substrate (aquarium) , alkyl , functional group , organic chemistry , polymer , oceanography , geology
Abstract 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 η 2 ‐coordinating activation of ketone carbonyls is involved. This cross‐coupling‐like mechanism is expected to enable other challenging transformations of ketones.