An efficient approach to isoindolo[2,1- b][2]benzazepines via intramolecular [4+2] cycloaddition of maleic anhydride to 4-α-furyl-4- N-benzylaminobut-1-enes

Abstract

Acylation of 4-α-furyl-4- N-benzylaminobut-1-enes with maleic anhydride gave 4-oxo-3-aza-10-oxatricyclo[5.2.1.0 1,5]dec-8-ene-6-carboxylic acid via amide formation followed by intramolecular Diels–Alder reaction of furan (IMDAF). The cycloaddition proceeded under mild reaction conditions (25 °C) and provided only the exo-adduct in quantitative yield. Treatment of this compound with PPA gave isoindolo[2,1- b][2]benzazepine derivatives via ring opening, aromatization and intramolecular electrophilic alkylation. In order to extend the scope of the reaction sequence, 7-oxo-5,11b,12,13-tetrahydro-7 H-isoindolo[2,1- b][2]benzazepine-8-carboxylic acids were further transformed into useful synthetic intermediates.