Unexpected reversible nitrogen atom transfer in the synthesis of polysubstituted imides and 7-aza-hexahydroindolones via enaminonitrile γ-lactams

An effective route to novel polysubstituted imides is described, which involves the reaction of enaminonitrile γ-lactams derived from N-alkylated α-bromoacetamides and malononitrile with acryloyl chloride derivatives. This preceded via a sequence 1,4-addition-intramolecular peptidic coupling and a γ-lactam hydrolysis in a one 'pot-procedure'. These imides were regioselectively reduced into corresponding N-acyliminium precursors, which subsequently submitted to an intramolecular aza-cyclization in acidic medium to provide novel 7-hexahydro-aza-indoles.

Graphical abstractThe scope of reactions of enaminonitrile γ-lactams, obtained easily from N-alkylated α-bromoacetamides and malononitrile, with acryloyl chloride derivatives has been extended successfully in forming novel polysubstituted imides. From these results, the tandem ring closure/ring opening seems to be effective and general. The latter systems obtained were then used to provide substituted 7-hexahydro-aza-indoles by using a regioselective reduction process followed ultimately by aza-cationic cyclization in acidic medium.Download full-size image