The Pseudotransannular Ring Opening of 1‐Aminocyclohept‐4‐ene‐derived Epoxides in the Synthesis of Tropane Alkaloids: Total Synthesis of (±)‐Ferrugine.

We have optimized a synthetic approach to (±)‐Ferrugine in 8 steps starting from 5‐aminocyclohept‐1‐ene and using the Brønsted 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. [ABSTRACT FROM AUTHOR]