Asymmetric redox-neutral radical cyclization catalysed by flavin-dependent 'ene'-reductases.

Autor: Black MJ; Department of Chemistry, Princeton University, Princeton, NJ, USA., Biegasiewicz KF; Department of Chemistry, Princeton University, Princeton, NJ, USA., Meichan AJ; Department of Chemistry, Princeton University, Princeton, NJ, USA., Oblinsky DG; Department of Chemistry, Princeton University, Princeton, NJ, USA., Kudisch B; Department of Chemistry, Princeton University, Princeton, NJ, USA., Scholes GD; Department of Chemistry, Princeton University, Princeton, NJ, USA., Hyster TK; Department of Chemistry, Princeton University, Princeton, NJ, USA. thyster@princeton.edu.
Jazyk: angličtina
Zdroj: Nature chemistry [Nat Chem] 2020 Jan; Vol. 12 (1), pp. 71-75. Date of Electronic Publication: 2019 Dec 02.
DOI: 10.1038/s41557-019-0370-2
Abstrakt: Flavin-dependent 'ene'-reductases (EREDs) are exquisite catalysts for effecting stereoselective reductions. Although these reactions typically proceed through a hydride transfer mechanism, we recently found that EREDs can also catalyse reductive dehalogenations and cyclizations via single electron transfer mechanisms. Here, we demonstrate that these enzymes can catalyse redox-neutral radical cyclizations to produce enantioenriched oxindoles from α-haloamides. This transformation is a C-C bond-forming reaction currently unknown in nature and one for which there are no catalytic asymmetric examples. Mechanistic studies indicate the reaction proceeds via the flavin semiquinone/quinone redox couple, where ground-state flavin semiquinone provides the electron for substrate reduction and flavin quinone oxidizes the vinylogous α-amido radical formed after cyclization. This mechanistic manifold was previously unknown for this enzyme family, highlighting the versatility of EREDs in asymmetric synthesis.
Databáze: MEDLINE
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