1,4-Diazepinone and Pyrrolodiazepinone Syntheses via Homoallylic Ketones from Cascade Addition of Vinyl Grignard Reagent to α-Aminoacyl-β-amino Esters

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 α-aminoacyl β-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 α-amino acid moiety similar to those of the central
residue in an ideal reverse γ-turn.