Chiral-Ligand-Modulated Nickel-Catalyzed Stereoselective Radical Migratory C2-Arylation of Carbohydrates

Catalytic, stereoselective carbon-carbon bond formation at nonanomeric positions of carbohydrates remains a long-standing challenge in organic synthesis. Here, we report a chiral-ligand-modulated, nickel-catalyzed stereoselective radical migratory cross-coupling that achieves highly diastereoselective C2-arylation of carbohydrates directly from readily available 1-halosugars. A previously underexplored class of chiral 2-(aminomethyl)pyridine (Ampy) ligands is shown to impart catalyst-modulated stereocontrol in nickel-catalyzed cross-coupling. The reaction accommodates a broad range of aryl boronic acids and carbohydrate substrates, tolerates diverse functional groups and complex molecular architectures, and is amenable to gram-scale synthesis. Experimental and computational studies support a mechanism involving radical migration followed by a stereoselectivity-determining nickel-mediated radical capture governed by stabilizing ligand-substrate hydrogen-bonding interactions and destabilizing steric repulsion. This newly uncovered reactivity of chiral Ampy ligands provides a new strategy for stereocontrolled radical cross-coupling in polyoxygenated frameworks and expands the scope of stereoselective nickel catalysis.