Asymmetric Carbohydroxylation of Alkenes Using Photoenzymatic Catalysis

Yao Ouyang, Joshua Turek-Herman, Tianzhang Qiao, Todd K. Hyster

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Alkene difunctionalizations enable the synthesis of structurally elaborated products from simple and ubiquitous starting materials in a single chemical step. Carbohydroxylations of olefins represent a family of reactivity that furnish structurally complex alcohols. While examples of this type of three-component coupling have been reported, catalytic asymmetric examples remain elusive. Here, we report an enzyme-catalyzed asymmetric carbohydroxylation of alkenes catalyzed by flavin-dependent “ene”-reductases to produce enantioenriched tertiary alcohols. Seven rounds of protein engineering reshape the enzyme’s active site to increase activity and enantioselectivity. Mechanistic studies suggest that C-O bond formation occurs via a 5-endo-trig cyclization with the pendant ketone to afford an α-oxy radical which is oxidized and hydrolyzed to form the product. This work demonstrates photoenzymatic reactions involving “ene”-reductases can terminate radicals via mechanisms other than hydrogen atom transfer, expanding their utility in chemical synthesis.

Original languageEnglish (US)
Pages (from-to)17018-17022
Number of pages5
JournalJournal of the American Chemical Society
Volume145
Issue number31
DOIs
StatePublished - Aug 9 2023
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry

Fingerprint

Dive into the research topics of 'Asymmetric Carbohydroxylation of Alkenes Using Photoenzymatic Catalysis'. Together they form a unique fingerprint.

Cite this