1,4-Diazepinone and pyrrolodiazepinone syntheses via homoallylic ketones from cascade addition of vinyl Grignard reagent to alpha-aminoacyl-beta-amino esters.
[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.
Iden
Hassan S
HS
Département de chimie, Université de Montréal, C.P. 6128, Succursale Centre Ville, Montréal, Québec, Canada H3C 3J7.
Lubell
William D
WD
D000596:Amino Acids / Q000737:chemistry; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D004952:Esters; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000596:Amino Acids; D001381:Azepines; D004952:Esters; D007659:Ketones; D011758:Pyrroles