Cobalt-Catalyzed Asymmetric\nHydrogenation of Ketones\nEnabled by the Synergism of an N–H Functionality and a Redox-Active\nLigand

The transition metal-catalyzed asymmetric hydrogenation\n(AH) of\nketones to produce enantioenriched alcohols is an important reaction\nin organic chemistry with applications in the pharmaceutical and agrochemical\nfields. Using earth-abundant, biorelevant cobalt as the central metal\nin the catalyst has a high potential to improve sustainability and\nachieve hydrogenation reactions that are scalable. However, due to\nthe high d-electron count, designing cobalt catalysts that exhibit\nturnover numbers (TONs, ≥1000) and enantioselectivities (≥90%)\nsufficient for synthetic utility and practical scalability (≥1\nkg scale) remains a challenge. In this work, an efficient catalyst\ndesign strategy utilizing an amino(imino)diphosphine Co(II) bromide\nprecatalyst is presented to achieve this goal. The quantitative production\nof a wide range of secondary chiral alcohols with TONs of up to 150,000\nand an enantiomeric excess (e.e.) of up to 99% at a scale of up to\n1.35 kg was achieved, indicating that the proposed cobalt catalyst\nis highly promising for AH and scale-up reactions. A mechanistic study\nrevealed that the synergism of an N–H functionality and a redox-active\nligand endows the cobalt catalyst with a high productivity and excellent\nenantioselectivity.