Enantioselective Synthesis of N-Benzylic Heterocycles by Ni/Photoredox Dual Catalysis

An asymmetric cross-coupling of α-N-heterocyclic trifluoroborates with aryl bromides using Ni/photoredox dual catalysis has been developed. This C(sp²)-C(sp³) cross-coupling provides access to pharmaceutically relevant chiral N-benzylic heterocycles in good to excellent enantioselectivity when bioxazolines (BiOX) are used as the chiral ligand. High-throughput experimentation significantly streamlined reaction development by identifying BiOX ligands for further investigation and by allowing for rapid optimization of conditions for new trifluoroborate salts.