β-Carbon functionalization of amines via α-amino Cu-carbenes.

Abstract

Limited by the weaker d-p π-backdonation capacity exhibited by copper catalysis in metal carbene chemistry and the available carbene precursors, the construction of α-amino copper carbenes had remained unrealized. Here, we report a leaving group-driven carbene precursor design based on an intermolecular approach, enabling the generation and divergent transformations of pyrrole-type α-amino copper carbenes. This strategy successfully reversed the established protonation pathway of electron-rich enamine-copper complexes, effectively inverting the conventional polarity at the β position of the amine in the form of a pyrrole-type α-amino copper carbene. Furthermore, by leveraging the extensive library of ligands in copper catalysis, we have achieved fine-tuned, switchable stereo- and regioselective divergent synthesis. Through multiple classical carbene insertion reactions, as well as carbene oxidation and metathesis reactions, this approach enables the functionalization of the β position of amines with diverse nucleophilic groups.