A new approach to (+)-brefeldin A via a nickel-catalyzed coupling reaction of cyclopentenyl acetate and lithium 2-furylborate

A Short Synthesis of (+)‐Brefeldin C through Enantioselective Radical Hydroalkynylation

“…The unique biological profile of brefeldin A, C, and analogues has attracted a lot of interest in the synthetic organic chemistry community. The first synthesis of the racemic brefeldin A was reported by Corey and Wollenberg in 1976 followed by around 40 total and formal syntheses . Brefeldin C was prepared for the first time by total synthesis in 1988 by Schreiber and Meyers followed by Takano, Guingant (along with aspects of the biological properties of BFA) and Tsunoda .…”

“…On the other hand, the preparation of the polysubstituted 5‐membered ring has been achieved using very diverse strategies. Among them, the one reported by Kobayashi which used a furan moiety to introduce the C(1)–C(4) carbon atoms retained all our attention due to its conciseness …”

A Short Synthesis of (+)-Brefeldin C via Enantioselective Radical Hydroalkynylation

“…(+)-Brefeldin Cw ill be prepared from the corresponding seco acid I by Yamaguchi macrolactonization and stereoselectiver eductiono ft he resulting a,b-unsaturated ketone according to the seminal work of Corey and Wollenberg. [11] In analogyt ot he work of Kobayashi in his syntheses of brefeldin A [35] and of macrosphelides Aa nd B, [74,75] the 3-carboxyacryloyl chain (carbon C1-C4)w ill be prepared by oxidative openingo f the furan ring of II.T he pentan-4-ol-1-yl side chain (carbon atoms C12-C16)w ill be inserted by aS uzuki-Miyaura crosscoupling process startingf rom iodide III in analogyt ot he work of Guingant. [48,53] The (E)-iodide III will be obtained from the alkyne IV by ah ydrozirconation-iodination process.…”

“…Amongt hem, the one reported by Kobayashi whichu sed af uran moiety to introducet he C(1)-C(4) carbon atoms retained all our attention due to its conciseness. [35] Recently,o ur group reported am ethodf or enantioselective hydroazidationo ft risubstitutedn onactivated alkenes. [56] This reactionw as extended to other enantioselective hydrofunctionalization processes such as hydrobromination, [56] hydrofluorination, [57] hydrosulfurization, [56] and hydroallylation.…”

“…Gratifyingly,t reatment of 7 in methanol with 4 m aqueous HCl affordedt he clean deprotected alcohol 8 in 89 %y ield. After another extensive screening of furan oxidation conditions, we used at wo-step one-pot procedure inspired by the work of Jørgensen, [86] Kobayashi, [35,75] and Blair. [87] Furan 8 was first treated with NBS in H 2 O/acetone in the presence of NaHCO 3 followed by treatment with pyridine to give the ring-opened 4-oxo-2-alken1-al intermediate 9 that was rapidly filtered through ap ad of silica gel.…”