Highly Stereoselective and Scalable Synthesis of trans-Fused Octahydrocyclohepta[b]pyrrol-4(1H)-ones via the Aza-Cope–Mannich Rearrangement in Racemic and Enantiopure Forms

Abstract

We have developed an efficient and stereoselective route to trans-fused octahydrocyclohepta[b]pyrrol-4(1H)-ones. The key features of our synthesis include the regioselective epoxide ring-opening of alkynyl oxiranes and a stereoselective aza-Cope-Mannich reaction. The target compounds were prepared in 3-6 steps from commercially available starting materials (61-75% overall yield) with minimal chromatographic purification. We have devised an stereoselective route to target compounds using Shi epoxidation or (R)-1-phenylethylamine as a source of chirality.