Cobalt-catalyzed asymmetric hydrogenation of enamides enabled by single-electron reduction.
basic_science · Level V
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- Record sourced from PubMed, PMID 29798879.
- Also identified by DOI 10.1126/science.aar6117.
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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 (<i>R</i>,<i>R</i>)-Ph-BPE {Ph-BPE, 1,2-bis[(2<i>R</i>,5<i>R</i>)-2,5-diphenylphospholano]ethane} and cobalt chloride [CoCl<sub>2</sub>·6H<sub>2</sub>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 (<i>R</i>,<i>R</i>)-Ph-BPECoCl<sub>2</sub> underwent ligand displacement by methanol, and zinc promoted facile one-electron reduction to cobalt (I), which more stably bound the phosphine.