The Pseudotransannular Ring Opening of 1-Aminocyclohept-4-ene-derived Epoxides in the Synthesis of Tropane Alkaloids: Total Synthesis of (+/-)-Ferrugine

Abstract

We have optimized a synthetic approach to (+/-)-Ferrugine in 8 steps starting from 5-aminocyclohept-1-ene and using the Bronsted acid-catalyzed pseudotransannular ring-opening of the epoxide derived from this cycloheptene as the key step for the construction of the 8-azabicyclo[3.2.1]octane central core. While attempting the enantioselective synthesis of this natural product from enantiopure 2-hydroxy-8-azabicyclo[3.2.1]octane we have found that this compound shows a pronounced tendency to racemize via an achiral symmetric aziridinium intermediate. This racemization side process has been studied in detail using both experimental and computational methods.