Enantioselective Transition-Metal Catalysis via an Anion-Binding Approach – Nature

Asymmetric transition-metal catalysis represents a powerful strategy for accessing enantiomerically enriched molecules^1–3. The classical strategy for inducing enantioselectivity with transition-metal catalysts relies on direct complexation of chiral ligands to produce a sterically constrained reactive metal site that allows formation of the major product enantiomer while effectively inhibiting the pathway to the minor enantiomer through steric repulsion⁴. The chiral-ligand strategy has proven applicable to a wide variety of highly enantioselective transition-metal-catalyzed reactions, but important scenarios exist that impose limits to its successful adaptation. Here, we report a new approach for inducing enantioselectivity in transition-metal-catalyzed reactions that relies on neutral hydrogen-bond donors (HBDs)^5,6 that bind anions of cationic transition-metal complexes to achieve enantiocontrol and rate enhancement through ion pairing in concert with other noncovalent interactions^7–9. A cooperative anion-binding effect of a chiral bis-thiourea HBD is demonstrated to lead to high enantioselectivity (up to 99% enantiomeric excess) in intramolecular ruthenium-catalyzed propargylic substitution reactions¹⁰. Experimental and computational mechanistic studies reveal the attractive interactions between electron-deficient arene components of the HBD and the metal complex that underlie enantioinduction and the acceleration effect.