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Low‐Temperature Nickel‐Catalyzed C−N Cross‐Coupling via Kinetic Resolution Enabled by a Bulky and Flexible Chiral N ‐Heterocyclic Carbene Ligand
Author(s) -
Wang ZiChao,
Xie PeiPei,
Xu Youjun,
Hong Xin,
Shi ShiLiang
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202103803
Subject(s) - kinetic resolution , carbene , enantioselective synthesis , amination , ligand (biochemistry) , chemistry , steric effects , combinatorial chemistry , aryl , reductive elimination , catalysis , oxidative addition , reactivity (psychology) , reductive amination , coupling reaction , stereochemistry , organic chemistry , medicine , biochemistry , alkyl , receptor , alternative medicine , pathology
Abstract The transition‐metal‐catalyzed C−N cross‐coupling has revolutionized the construction of amines. Despite the innovations of multiple generations of ligands to modulate the reactivity of the metal center, ligands for the low‐temperature enantioselective amination of aryl halides remain a coveted target of catalyst engineering. Designs that promote one elementary reaction often create bottlenecks at other steps. We here report an unprecedented low‐temperature (as low as −50 °C), enantioselective Ni‐catalyzed C−N cross‐coupling of aryl chlorides with sterically hindered secondary amines via a kinetic resolution process (s factor up to >300). A bulky yet flexible chiral N‐heterocyclic carbene (NHC) ligand is leveraged to drive both oxidative addition and reductive elimination with low barriers and control the enantioselectivity. Computational studies indicate that the rotations of multiple σ‐bonds on the C 2 ‐symmetric chiral ligand adapt to the changing needs of catalytic processes. We expect this design would be widely applicable to diverse transition states to achieve other challenging metal‐catalyzed asymmetric cross‐coupling reactions.