Cyclizations of substituted benzylidene-3-alkenylamines:: Synthesis of the tricyclic core of the martinellines

The martinellines (1 and 2) are natural products that possess both interesting biological activity and chemical structure. During the investigation of a hetero Diels-Alder route to these molecules, alternate Lewis acid-dependent cyclizations of (2'-amino-N'-tert-butoxycarbonyl-5'-chlorobenzylidene)-3-butenylamine (10) were observed. The reaction of a variety of imines with TMSOTf or TiCl4 led to the formation of different heterocycles including iminodibenzo[b,f][1,5]diazocines, hexahydropyrido[1,2-c]quinazolin-6-ones, tetrahydropyrrolo[1,2-c]quinazolin-5-ones, 2-arylpiperidines, and 2-arylpyrrolidines. Tetrahydropyrrolo[1,2-c]quinazolin-5-one 54, obtained via this new methodology, was used as an intermediate in the synthesis of the tricyclic ring system (65) of the martinellines.