Synthesis of epibatidine analogues having a 2-substituted 2-azabicyclo[2.2.2]octane skeleton

Abstract

The synthesis of 1-cyano-2-aza-[2.2.2]bicyclooctanes has been studied using the dynamic cyanide addition to cyclohexanone derivatives. These compounds were further elaborated into a new class of epibatidine derivatives from which a number of examples were fully deprotected to give the potentially active compounds. The highly hydrophilic character of the compounds resulted in a difficult isolation and purification of the epibatidine analogues. 1-Cyano-2-aza-[2,2,2]bicyclooctanes have been prepared using the dynamic cyanide addition reaction from the corresponding cyclohexanone derivatives. These compounds have been further elaborated into a new class of epibatidine derivatives, and their biological activity has been studied. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.