Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation of 1,4-Diazepan-5-ones

Org Lett. 2019 Nov 15;21(22):9158-9161. doi: 10.1021/acs.orglett.9b03530. Epub 2019 Oct 31.

Abstract

We report the palladium-catalyzed asymmetric allylic alkylation of 1,4-diazepan-5-ones. This reaction proceeds smoothly to give gem-disubstituted diazepanone heterocycles bearing various functional groups in up to >99% yield and up to 95% ee. An electron-rich p-anisoyl lactam protecting group and the use of a nonpolar solvent proved crucial to obtaining high enantioselectivity in most cases. Additionally, we demonstrate the use of our methodology in the synthesis of a gem-disubstituted analogue of the FDA-approved anti-insomnia drug suvorexant.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Azepines / chemical synthesis*
  • Azepines / chemistry
  • Catalysis
  • Palladium / chemistry*
  • Sleep Aids, Pharmaceutical / chemical synthesis*
  • Sleep Aids, Pharmaceutical / chemistry
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry

Substances

  • Azepines
  • Sleep Aids, Pharmaceutical
  • Triazoles
  • suvorexant
  • Palladium