Assembly of 1,2,3,4-Tetrahydropyrrolo[1,2- a]pyrazines via the Domino Reaction of 2-Imidazolines and Terminal Electron-Deficient Alkynes

J Org Chem. 2022 Mar 4;87(5):3242-3253. doi: 10.1021/acs.joc.1c02930. Epub 2022 Jan 20.

Abstract

The transformation of 2-imidazolines into 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazines has been realized. A pseudo-three-component reaction of 2-imidazolines with terminal electron-deficient alkynes (2 equiv) first generates imidazolidines, containing an N-vinylpropargylamine fragment. The latter can then undergo a base-catalyzed domino aza-Claisen rearrangement/cyclization reaction sequence, simultaneously constructing pyrrole and pyrazine rings. The process works in a broad substrate scope, delivering pyrrolo[1,2-a]pyrazines in good to excellent yields (45-90%). This two-step approach can be carried out in a one-pot fashion without a noticeable decrease in yield. Remarkably, a three-component protocol for the introduction of two different alkynes has been also developed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes*
  • Catalysis
  • Electrons
  • Imidazolines*
  • Molecular Structure
  • Pyrazines

Substances

  • Alkynes
  • Imidazolines
  • Pyrazines