A chiral route to the synthesis of (2S,3aR,7aS)-tert-butyl hexahydro-2,5-methanopyrrolo[3,2-c]pyridine-1(4H)-carboxylate, an intermediate for nicotinic acetylcholine receptors agonists

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A synthesis of (2S,3aR,7aS)-tert-butyl hexahydro-2,5-methanopyrrolo[3,2-c]pyridine-1(4H)-carboxylate (1A), a key intermediate for tricyclic compounds found as potent α7 nicotinic acetylcholine receptor ligands, following a novel chiral route is described here. The new chiral route circumvented two major challenges in the earlier route by avoiding high catalyst loading of pyrophoric Pd/C and reduced reaction time for the hydrogenation. The current methodology starts with a chirally defined intermediate which gives a strategic advantage over the previous scheme by being more convergent. Some of these improvements are discussed in detail in the current work.