Synfacts 2018; 14(08): 0819
DOI: 10.1055/s-0037-1610460
Metal-Catalyzed Asymmetric Synthesis and Stereoselective Reactions
© Georg Thieme Verlag Stuttgart · New York

Cobalt-Catalyzed Enantioselective Hydrogenation of Enamides

Hisashi Yamamoto
Takahiro Sawano
Friedfeld MR. Zhong H. Ruck RT. Shevlin M. * Chirik PJ. * Princeton University and Merck Research Laboratories, Rahway, USA
Cobalt-Catalyzed Asymmetric Hydrogenation of Enamides Enabled by Single-Electron Reduction.

Science 2018;
360: 888-893
Further Information

Publication History

Publication Date:
18 July 2018 (online)



On the basis of a discovery from high-throughput reaction studies, the authors have developed a low-catalyst-loading enantioselective hydrogenation of functionalized alkenes through activation by zinc instead of the more-usual alkyl reagents. The optimized catalytic system CoCl2·6H2O/(R,R)-Ph-BPE or CoCl2·6H2O/(R,R)-i-Pr-DuPhos realized a high reactivity and enantioselective hydrogenation in MeOH.



A series of mechanistic studies revealed that Co(II) metal dissociates from the Co(II)/phosphine complex in MeOH, and that Zn reduces Co(II) to Co(I) through one-electron reduction to form a more stable Co–phosphine bond, which is key to the efficient enantioselective reduction of alkenes. The hydrogenation can be applied to a large-scale reaction requiring only 0.08 mol% of the cobalt catalyst.