Azepine and [1,3]Oxazepine Fused Ring Construction through a Cationic Cyclization: An N-Acyliminium Ion Trapping of an Oxygen Atom or Olefin

Carbophilic addition on (and/or sodium borohydride reduction of) an imide ester functionality (3) proceeds with extremely high regioselectivety to produce bifunctionalized hydroxy-ω-carbinol lactam products (4) and (8).These species could act as N-acyliminium ion precursors and, via an O-cationic or πcationic cyclization, and they led regioselectively in high yields to fused triheterocyclic azepine (11) or [1,3]oxazepine (18).The α-amidoalkylation cyclization of N-acyliminium ions constitutes a versatile methodology for the carbon-carbon bond forming in organic synthesis. 1During these process, N-acyliminium ion intermediates which generated in an acidic medium are, in turn, capable of trapping a wide variety of nucleophiles producing polyheterocyclic systems. 1,2As an extension of our work on the synthetic utility of amidoalkylation reactions, allied with our interest in the development of synthetic approaches to diversely substituted polyheterocyclic systems, we have recently reported the preparation of polysubstituted benzoazepinoisoindolones and furoazepinoisoindolones by a tandem Grignard reaction-N-acyliminium ion cyclization in one pot reaction. 3We now wish to describe our findings from our investigations of this tandem sequence with thienylmethylpyrrolidine system.