Atomically Precise Copper Cluster for Highly Chemoselective Carbenoid Insertion into the N–H Bond of Aliphatic Amine
Teng Jia, Miaomiao Zhang, Rui Liu, Cai-Fang Sun, Jie Ai, Zheng Wang, Yu Lan, Shuang‐Quan Zang
Abstract
Due to the strong coordination effect between aliphatic amines and transition metal catalysts, the activity of the catalyst is inhibited by aliphatic amines’ strong Lewis basicity, leading to poor chemoselectivity and a significant challenge to the N–H insertion reaction. Here, we report a highly stable copper cluster (Cu 3 NC (NHC) ) with dynamic catalytic sites for the first time that is used to efficiently and chemoselectively catalyze the N–H insertion reaction of aliphatic amines. Pyridine groups as dynamic ligands and aliphatic amines could compete for coordination to prevent catalyst deactivation due to passivation. The dissociated dynamic ligands could regulate the steric effect of the catalyst to achieve highly selective alkylation of primary amines. Moreover, the reaction afforded high chemoselectivity between the C═C bond and the N–H bond by forming a Cu 3 NC (NHC) -carbenoid intermediate. TON of the N–H insertion reaction has reached 79200. The reaction could be applied in pharmaceutical synthesis and late-stage functionalization. Mechanistic studies and density functional theory demonstrate that this process of generating Cu 3 NC (NHC) -carbenoid was both kinetically and thermodynamically favorable and that this process may not be the rate-limiting step. This investigation highlights the broad application prospects of metal nanoclusters in the field of organic catalysis, providing a new idea for the development of cluster chemistry.