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

Autor: Friedfeld MR; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA., Zhong H; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA., Ruck RT; Department of Process Research and Development, Merck Research Laboratories, Rahway, NJ 07065, USA., Shevlin M; Department of Process Research and Development, Merck Research Laboratories, Rahway, NJ 07065, USA. michael_shevlin@merck.com pchirik@princeton.edu., Chirik PJ; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA. michael_shevlin@merck.com pchirik@princeton.edu.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2018 May 25; Vol. 360 (6391), pp. 888-893.
DOI: 10.1126/science.aar6117
Abstrakt: 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[(2 R ,5 R )-2,5-diphenylphospholano]ethane} and cobalt chloride [CoCl 2 ·6H 2 O] 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-BPECoCl 2 underwent ligand displacement by methanol, and zinc promoted facile one-electron reduction to cobalt (I), which more stably bound the phosphine.
(Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE
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