Photoenzymatic Hydrogenation of Heteroaromatic Olefins Using ‘Ene’-Reductases with Photoredox Catalysts

Yuji Nakano, Michael J. Black, Andrew J. Meichan, Braddock A. Sandoval, Megan M. Chung, Kyle F. Biegasiewicz, Tianyu Zhu, Todd K. Hyster

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Flavin-dependent ‘ene’-reductases (EREDs) are highly selective catalysts for the asymmetric reduction of activated alkenes. This function is, however, limited to enones, enoates, and nitroalkenes using the native hydride transfer mechanism. Here we demonstrate that EREDs can reduce vinyl pyridines when irradiated with visible light in the presence of a photoredox catalyst. Experimental evidence suggests the reaction proceeds via a radical mechanism where the vinyl pyridine is reduced to the corresponding neutral benzylic radical in solution. DFT calculations reveal this radical to be “dynamically stable”, suggesting it is sufficiently long-lived to diffuse into the enzyme active site for stereoselective hydrogen atom transfer. This reduction mechanism is distinct from the native one, highlighting the opportunity to expand the synthetic capabilities of existing enzyme platforms by exploiting new mechanistic models.

Original languageEnglish (US)
Pages (from-to)10484-10488
Number of pages5
JournalAngewandte Chemie - International Edition
Volume59
Issue number26
DOIs
StatePublished - Jun 22 2020

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)

Keywords

  • biocatalysis
  • enantioselectivity
  • heteroaromatic reduction
  • photoenzymatic reaction
  • ‘ene’-reductase

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