1,4-Diazepinone and pyrrolodiazepinone syntheses via homoallylic ketones from cascade addition of vinyl Grignard reagent to alpha-aminoacyl-beta-amino esters

Org Lett. 2006 Aug 3;8(16):3425-8. doi: 10.1021/ol061036k.

Abstract

[reaction: see text] 1,4-Diazepinones 5 and pyrrolodiazepinones 8 and 9 were synthesized from common homoallylic ketone precursors 4 prepared by copper-catalyzed cascade addition of a vinyl Grignard reagent to alpha-aminoacyl beta-amino esters 3. Nitrogen deprotection and intramolecular reductive amination yielded 1,4-diazepinones 5. Olefin oxidation, Boc removal, and intramolecular Paal-Knorr condensation gave pyrrolodiazepinones 8 and 9. X-ray structures of diazepinones 5c and 5d depicted dihedral angles about the alpha-amino acid moiety similar to those of the central residue in an ideal reverse gamma-turn.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry
  • Azepines / chemical synthesis*
  • Azepines / chemistry
  • Catalysis
  • Esters
  • Ketones / chemistry*
  • Molecular Structure
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Stereoisomerism

Substances

  • Amino Acids
  • Azepines
  • Esters
  • Ketones
  • Pyrroles