Asymmetric Synthesis of α-Chloroamides via Photoenzymatic Hydroalkylation of Olefins

Yi Liu, Sophie G. Bender, Damien Sorigue, Daniel J. Diaz, Andrew D. Ellington, Greg Mann, Simon Allmendinger, Todd K. Hyster

Research output: Contribution to journalArticlepeer-review

Abstract

Photoenzymatic intermolecular hydroalkylations of olefins are highly enantioselective for chiral centers formed during radical termination but poorly selective for centers set in the C-C bond-forming event. Here, we report the evolution of a flavin-dependent “ene”-reductase to catalyze the coupling of α,α-dichloroamides with alkenes to afford α-chloroamides in good yield with excellent chemo- and stereoselectivity. These products can serve as linchpins in the synthesis of pharmaceutically valuable motifs. Mechanistic studies indicate that radical formation occurs by exciting a charge-transfer complex templated by the protein. Precise control over the orientation of molecules within the charge-transfer complex potentially accounts for the observed stereoselectivity. The work expands the types of motifs that can be prepared using photoenzymatic catalysis.

Original languageEnglish (US)
Pages (from-to)7191-7197
Number of pages7
JournalJournal of the American Chemical Society
Volume146
Issue number11
DOIs
StatePublished - Mar 20 2024

All Science Journal Classification (ASJC) codes

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

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