Phosphine-Catalyzed α-Umpolung-Aldol Reaction for the Synthesis of Benzo[ b]azapin-3-ones

Org Lett. 2019 Jul 5;21(13):5143-5146. doi: 10.1021/acs.orglett.9b01749. Epub 2019 Jun 20.

Abstract

A novel phosphine-catalyzed intermolecular cyclization between 2-sulfonamidobenzaldehyes and ynones is reported. This methodology serves as a conduit for the construction of benzo[ b]azepin-3-ones in good to excellent yields under mild conditions. The resulting 2-benzylidene moieties are formed exclusively in the E-configuration. Mechanistically, this unusual annulation occurs through a phosphine-catalyzed α-umpolung addition, followed by an aldol reaction. One of the benzo[ b]azepin-3-one products was converted to the core structure of 3-amino-[ a]benzazepin-2-one-1-alkanoic acids, many of which function as angiotensin-converting enzyme inhibitors.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aza Compounds / chemical synthesis*
  • Aza Compounds / chemistry*
  • Catalysis
  • Chemistry Techniques, Synthetic
  • Phosphines / chemistry*
  • Stereoisomerism

Substances

  • Aza Compounds
  • Phosphines
  • phosphine