Metal charge-directed enantiodivergent asymmetric transfer hydrogenation of ketones

Because most pharmacologically active receptors are inherently asymmetric, the introduction of asymmetry into molecules that can bind to such receptors is a central topic in modern organic and bioorganic chemistry. We developed a metal charge-directed stereoinduction process in the asymmetric transfer hydrogenation of ketones catalyzed by first-row transition-metal (iron, cobalt, and nickel) amido-ene(amido)diphosphine complexes by elucidating an unprecedented role of catalyst metal charge in dictating the process of asymmetry creation. With a fixed enantiomer of the chiral ligand, the metal charge in the amino(hydrido) catalytic intermediates was the controlling factor that ultimately determined the configuration and the enantioselectivity percentage of the product in a predicted manner. By taking advantage of the rich redox properties of first-row transition metals, this method led to a novel version of enantiodivergent catalysis in which both enantiomers of the product could be generated with catalysts derived from a single chiral source and the same metal.