A Short Synthesis of (+)-Brefeldin C via Enantioselective Radical Hydroalkynylation
A very concise total synthesis of (+)-brefeldin C starting from 2-furanylcyclopentene is described. This approach is based on an unprecedented enantioselective radical hydroalkynylation process to introduce the two cyclopentane stereocenters in a single step. The use of a furan substituent allows to achieve a high trans diastereoselectivity during the radical process and it contains the four carbon atoms C1–C4 of the natural product in an oxidation state closely related to the one of the target molecule. The eight-step synthesis require six product purifications and it provides (+)-brefeldin C in 18% overall yield.