Carbene-Protected Copper Nanocluster for Highly Efficient Difunctionalization of C(sp ^<i>2</i> )–H and O–H Bonds

The difunctionalization of C(sp2)–H and O–H bonds represents an important and efficient way to directly form C–C and C–O bonds simultaneously, but achieving high site-selectivity, chemoselectivity, and turnover number is a significant challenge. Here, we prepare a stable copper cluster (Cu3NC(NHC)) with two attributes, rigidity and flexibility. The Cu3NC(NHC) catalyst has been successfully used to catalyze the difunctionalization reaction with high site-selectivity and chemoselectivity, which represented a significant advancement in copper catalysts for catalyzing the C(sp2)–H and O–H bonds. As expected, the turnover number was elevated to 126,000, and the turnover frequency reached 445 h–1 in the difunctionalization reaction. Mechanistic studies and density functional theory illustrate that the property of the Cu3NC(NHC)-carbenoid may be closer to that of a Cu3NC(NHC)-stabilized carbocation, thus providing difunctionalization products that are completely different from those of traditional copper catalysts. A proton shift model was found that the N atom of pyridine assisted in catalyzing proton shift. This work highlights the importance of copper clusters in cascade reactions, affords an efficient method to generate “carbophilic carbocations”, and provides a reference for the development of cluster organic catalysis.