A New and Efficient Synthesis of Derivatives of Octahydro-4H-pyrrolo[1,2-c]pyrido[1′,2′-a]imidazole

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.