Visible-light mediated catalytic asymmetric radical deuteration at non-benzylic positions

Nat Commun. 2022 Aug 1;13(1):4453. doi: 10.1038/s41467-022-32238-8.

Abstract

Site- and enantioselective incorporation of deuterium into organic compounds is of broad interest in organic synthesis, especially within the pharmaceutical industry. While catalytic approaches relying on two-electron reaction manifolds have allowed for stereoselective delivery of a formal deuteride (D-) or deuteron (D+) at benzylic positions, complementary strategies that make use of one-electron deuterium atom transfer and target non-benzylic positions remain elusive. Here we report a photochemical approach for asymmetric radical deuteration by utilizing readily available peptide- or sugar-derived thiols as the catalyst and inexpensive deuterium oxide as the deuterium source. This metal-free platform enables four types of deuterofunctionalization reactions of exocyclic olefins and allows deuteration at non-benzylic positions with high levels of enantioselectivity and deuterium incorporation. Computational studies reveal that attractive non-covalent interactions are responsible for stereocontrol. We anticipate that our findings will open up new avenues for asymmetric deuteration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkenes* / chemistry
  • Catalysis
  • Deuterium / chemistry
  • Light*

Substances

  • Alkenes
  • Deuterium