SYNTHESIS OF ANATOXIN-A VIA INTRA-MOLECULAR CYCLIZATION OF IMINIUM SALTS

Anatoxin a (1) has been synthesized by exploiting intramolecular cyclization between an iminium salt and a nucleophilic carbon to construct the 9-azabicyclo[4.2.1] nonane ring system. Cyclization of malonate iminium salt 16 at alkaline pH afforded a low yield of bicyclic malonate 18 owing to an unfavorable equilibrium constant and lability of the iminium salt in base. In contrast, cyclization of ketoiminium salt 31 afforded a good yield of bicyclic ketone 34 in acidic methanol. Dihydropyrrolium salts 16 and 31 were generated quantitatively by decarbonylation of substituted N-methylproIines 15 and 30b, obtained by reduction of the corresponding pyrroles. © 1979, American Chemical Society. All rights reserved.