A New Method for the Preparation of Non‐Terminal Alkynes: Application to the Total Syntheses of Tulearin A and C

Lactones are known to react with the reagent generated in situ from CCl 4 and PPh 3 in a Wittig‐type fashion to give gem ‐dichloro‐olefin derivatives. Such compounds are now shown to undergo reductive alkylation on treatment with organolithium reagents RLi to furnish acetylene derivatives bearing the substituent R at their termini (R=Me, n ‐, sec ‐, tert ‐alkyl, silyl); the reaction can be catalyzed with either Cu(acac) 2 or Fe(acac) 3 /1,2‐diaminobenzene. Two alkynol derivatives prepared in this way from readily accessible lactone precursors served as the key building blocks for the total syntheses of the cytotoxic marine macrolides tulearin A ( 1 ) and C ( 2 ). The assembly of these fragile targets hinged upon ring closing alkyne metathesis (RCAM) followed by a formal trans ‐reduction of the resulting cycloalkynes via trans ‐hydrosilylation/protodesilylation.