Ultrastable Copper Cluster Enables Highly Site-Selective and Chemoselective Carbocation C(sp³)–H and C(sp²)–H Bonds Functionalization

The C-H functionalization represents a universal and important method for constructing new C-C bonds by carrying out reactions directly on inert C-H bonds. The major challenges are to control the site-selectivity and chemoselectivity because most complex organic compounds have many similar C-H bonds or different functional groups, such as a C═C bond or O-H bond. Here, we develop a versatile copper cluster (Cu₃NC^(NHC)) with high stability and dynamic catalytic sites. Unlike traditional copper catalysts (which activate diazoesters to form intermediate Cu-carbenes, catalyzing cyclopropanation and O-H insertion), the Cu₃NC^(NHC), as a versatile catalyst, has resolved the site-selective and chemoselective challenges of the C(sp³)-H bond and C(sp²)-H bond functionalization by forming Cu₃NC^(NHC) stabilized carbocations. Moreover, turnover number (TON) values of the C-H functionalization are elevated to a whole new level (up to 123,200). Mechanistic studies and density functional theory (DFT) demonstrate that site-selectivity and chemoselectivity derive from the energy differences among these key intermediates. The diverse applicability of Cu₃NC^(NHC) provides a generic platform for optimizing chemical reactions and fostering their innovative development, thereby promoting the rapid development of the intersection between cluster chemistry and organic chemistry.