Copper(II)-Catalyzed Regioselective H/D Exchange Based on Reversible C-H Activation

Abstract

Despite the increasing use of copper in C-H functionalizations, the Cu-catalyzed direct deuteration of C-H bonds remains a significant challenge due to its inherent low reactivity in inverse C-H bond reconstruction. In this paper, a novel strategy had been developed to reverse the copper-catalyzed concerted metalation-deprotonation process by inhibiting the unexpected disproportionation of Cu(II) to Cu(III). Picolinic acid was identified as a powerful ligand for facilitating this H/D exchange with D2O as deuterium source, and its inhibition activity was supported by preliminary control experiments and DFT studies.

Keywords: Concerted Metalation-Deprotonation; Copper-catalysis; Deuteration; Heavy Water; reversible C-H activation.