Cobalt-catalyzed asymmetric hydrogenation of enamides enabled by single-electron reduction

Max R. Friedfeld, Hongyu Zhong, Rebecca T. Ruck, Michael Shevlin, Paul J. Chirik

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Identifying catalyst activation modes that exploit one-electron chemistry and overcome associated deactivation pathways will be transformative for developing first-row transition metal catalysts with performance equal or, ideally, superior to precious metals. Here we describe a zinc-activation method compatible with high-throughput reaction discovery that identified scores of cobalt-phosphine combinations for the asymmetric hydrogenation of functionalized alkenes. An optimized catalyst prepared from (R,R)-Ph-BPE (Ph-BPE, 1,2-bis[(2R,5R)-2,5-diphenylphospholano]ethane) and cobalt chloride [CoCl2·6H2O] exhibited high activity and enantioselectivity in protic media and enabled the asymmetric synthesis of the epilepsy medication levetiracetam at 200-gram scale with 0.08 mole % catalyst loading. Stoichiometric studies established that the cobalt (II) catalyst precursor (R,R)-Ph-BPECoCl2 underwent ligand displacement by methanol, and zinc promoted facile one-electron reduction to cobalt (I), which more stably bound the phosphine.

Original languageEnglish (US)
Pages (from-to)888-893
Number of pages6
JournalScience
Volume360
Issue number6391
DOIs
StatePublished - May 25 2018

All Science Journal Classification (ASJC) codes

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