Av ery conciset otal 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 cyclopentanes tereocenters in as ingle step. The use of a furan substituent allows ah igh trans diastereoselectivity to be achieved duringt he radicalp rocess and it contains the four carbona toms C1-C4 of the natural product in an oxidation state closely relatedt ot he one of the target molecule. The eight-step synthesis requires six product purifications and it provides (+ +)-brefeldin Ci n1 8% overall yield.[**] Ap revious versiono ft his manuscript has been deposited on ap reprint server (https://doi.org/10.26434/chemrxiv.8397731.v1)Supporting information and the ORCID identification number(s) for the author(s) of this articlecan be found under: https://doi.

<div><div><div><div><p>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.</p></div></div></div></div>

Av ery conciset otal 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 cyclopentanes tereocenters in as ingle step. The use of a furan substituent allows ah igh trans diastereoselectivity to be achieved duringt he radicalp rocess and it contains the four carbona toms C1-C4 of the natural product in an oxidation state closely relatedt ot he one of the target molecule. The eight-step synthesis requires six product purifications and it provides (+ +)-brefeldin Ci n1 8% overall yield.[**] Ap revious versiono ft his manuscript has been deposited on ap reprint server (https://doi.org/10.26434/chemrxiv.8397731.v1)Supporting information and the ORCID identification number(s) for the author(s) of this articlecan be found under: https://doi.Scheme3.Conversion of alkyne 2b into (+ +)-brefeldin C. X-ray single-crystal structureof(+ +)-brefeldin C( 50 %p robability ellipsoids).