Cooperative heterometallic platforms enabling selective C–H bond activation and functionalization of pyridines

The development of methodologies for regioselective C–H functionalization of N-heterocycles has seen sustained growth over the last two decades. Cooperative reactivity stemming from the addition of Lewis-acidic metals to late-transition-metal complexes has enabled regioselective catalytic transformations. Progress in the design of ligands and Lewis-acidic metal precursors has led to development of in situ cooperative catalysts able to facilitate C–H functionalization of pyridine at C-2, C-3, and C-4 positions. Very recently, focused efforts toward well-defined heterometallic complexes facilitating C-H bond catalysis have been targeted. Transformations showcasing regioselective C-2 transformations have been achieved. This perspective examines select examples delineating the evolution of strategies to better facilitate cooperative reactivity between Lewis-acidic metals and late transition metals in regioselective C–H functionalization. Potential pathways to further evolve methods to access modular regiodivergence in pyridine C–H bond catalysis will be discussed.