The catalytic translocation of a metal catalyst along a saturated hydrocarbon side chain constitutes a powerful strategy for enabling bond-forming reactions at remote, yet previously unfunctionalized, sp3 C-H sites. In recent years, Ni-catalyzed chain-walking reactions have offered counterintuitive strategies for forging sp3 architectures that would be difficult to accomplish otherwise. Although these strategies have evolved into mature tools for advanced organic synthesis, it was only recently that chemists showed the ability to control the motion at which the catalyst "walks" throughout the alkyl chain. Specialized ligand backbones, additives and a judicious choice of noninnocent functional groups on the side chain have allowed the design of "a la carte" protocols that enable regiodivergent bond-forming scenarios at different sp3 C-H sites with distinct topological surface areas. Given the inherent interest in increasing the fraction of sp3 hybridized carbons in medicinal chemistry, Ni-catalyzed regiodivergent chain-walking reactions might expedite the access to target leads in drug discovery campaigns.
© 2023 The Authors. Published by American Chemical Society.