Copper-Catalyzed Cross-Coupling of Benzylic C–H Bonds and Azoles with Controlled N‑Site Selectivity

Azoles are important motifs in medicinal chemistry, and elaboration of their structures via direct N–H/C–H coupling could have broad utility in drug discovery. The ambident reactivity of many azoles, however, presents significant selectivity challenges. Here, we report a copper-catalyzed method that achieves site-selective cross-coupling of pyrazoles and other N–H heterocycles with substrates bearing (hetero)­benzylic C–H bonds. Excellent N-site selectivity is achieved, with the preferred site controlled by the identity of co-catalytic additives. This cross-coupling strategy features broad scope for both the N–H heterocycle and benzylic C–H coupling partners, enabling application of this method to complex molecule synthesis and medicinal chemistry.