Chiral [6,5,3]Fused Bipyridine Ligand Enables Nickel-Catalyzed Asymmetric Coupling Reaction

Transition-metal-catalyzed cross-coupling is the most efficient strategy for constructing carbon–carbon and carbon–heteroatom bonds. While palladium catalysis has long dominated this field, nickel catalysis has emerged as an economical and sustainable alternative, offering unique reactivity via accessible multiple oxidation states. Its advancement in asymmetric reactions, however, is hindered by the scarcity of efficient, modular chiral ligands.

To address this, we developed a novel class of electron-rich, multidentate ligands. Inspired by enzyme architecture, a "dual coordination-layer steric control" strategy was proposed, enabling the modular synthesis of rigid, fused chiral bipyridine ligands (SBpy) with tunable remote and proximal steric profiles.These ligands proved highly effective in the nickel-catalyzed enantioconvergent carboxylation of benzylic (pseudo)halides. Under mild conditions without pre-formed organometallics or high pressure, valuable chiral carboxylic acids were obtained in up to 95% yield and 97% ee. Mechanistic studies support a radical pathway with Lewis acid-assisted CO₂ activation.Building on this tunable platform, a diverse library of chiral pyridine-based ligands was constructed. Their preliminary application in nickel-catalyzed enantioconvergent amidation gave promising results (88% yield, 92% ee), validating the design and opening new avenues for synthesizing chiral amides.

In summary, this work establishes a novel ligand design paradigm, advancing practical and sustainable nickel-catalyzed asymmetric synthesis of valuable chiral building blocks.