Mechanism and Origin of MAD-Induced Ni/NHC Catalyzed Regio- and Enantioselective C-H Cyclization of Pyridines with Alkenes
Abstract
This work presents a DFT-based computational study on the regio- and enantioselective C - H functionalization of pyridines with alkenes at the relatively unreactive C4-position, which was successfully achieved by Shi et al. [ J. Am. Chem. Soc. 2019 , 141 , 5628-5634] using Ni(0)/N-heterocyclic carbene (NHC) catalysis under the assistance of an aluminum-based Lewis acid additive (2,6-t-Bu 2 -4-Me-C 6 H 2 O) 2 AlMe (MAD). The calculations indicate that the selective functionalization involves a three-step mechanism where a unique H-migration assisted oxidation metalation (HMAOM) step is identified as the rate- and enantioselectivity-determining step. The newly proposed mechanism can well rationalize the experimental observation that the preferred product is the endo -type (vs exo -type), R -configuration (vs S -configuraton) product at the C4 (vs C2) position, and also unveil the reasons that the NHC ligand and the MAD additive can facilitate the reaction.
References
Enantioselective Ni-Al Bimetallic Catalyzed exo-Selective C-H Cyclization of Imidazoles with Alkenes
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