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

摘要

We have developed an efficient and stereoselectivenroute to trans-fused octahydrocyclohepta[b]pyrrol-n4(1H)-ones. The key features of our synthesis include thenregioselective epoxide ring-opening of alkynyl oxiranes and anstereoselective aza-Cope−Mannich reaction. The target compoundsnwere prepared in 3−6 steps from commercially available starting materials (61−75% overall yield) with minimalnchromatographic purification. We have devised an stereoselective route to target compounds using Shi epoxidation or (R)-1-nphenylethylamine as a source of chirality.