Six-Step Total Synthesis of Isohirsut-4-ene through [5+2+1] Cycloaddition and Transannular Epoxide-Alkene Cyclization

A six-step total synthesis of isohirsut-4-ene with a 5/5/5 tricyclic core has been achieved. The synthesis features a Rh(I)-catalyzed [5+2+1] cycloaddition, a Corey-Chaykovsky reaction, and a transannular epoxide-alkene cyclization that afford the skeleton of the target molecule. This three-step strategy was further utilized to synthesize more 5/5/5 tricyclic analogues with one or two bridgehead quaternary centers.

Automated summary

A six-step total synthesis of isohirsut-4-ene with a 5/5/5 tricyclic core has been achieved using a three-step strategy that involves a Rh(I)-catalyzed [5+2+1] cycloaddition, a Corey-Chaykovsky reaction, and a transannular epoxide-alkene cyclization. This strategy was further applied to synthesize more tricyclic analogues with one or two bridgehead quaternary centers.