A new and efficient synthesis of derivatives of octahydro-4H-pyrrolo[1,2-c] pyrido[1′,2′-a]imidazole

Article abstract of DOI:10.1002/ejoc.201001704

When diethyl malonate was added to a solution of Δ¹- piperideine, generated in situ by oxidative desamination and decarboxylation of L-lysine by N-bromosuccinimide (NBS), formation of the unexpected tricyclic compound 6 (4-diethylmalonyl-octahydro-4H-pyrrolo[1,2-c]pyrido[1′, 2′-a]imidazole)was observed. The structure of 6 was deduced from analysis of its spectroscopic data and was confirmed both by chemical degradation and by total synthesis. We proved that 3-bromo-1-piperideine was implicated in its formation. Moreover, based on this feature, a new and efficient synthesis of 6 was developed. The elaborated pathway was adapted to access derivatives related to 6 that differed in their C-4 substituent. A new and efficient synthesis of derivatives of the tricyclic heterocycle A from lysine is described. A mechanism involving 3-halopiperideines as intermediates and based on a ring contraction followed by Michael reaction is proposed and tested. Copyright