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A New Method for the Preparation of Non‐Terminal Alkynes: Application to the Total Syntheses of Tulearin A and C
Author(s) -
Lehr Konrad,
Schulthoff Saskia,
Ueda Yoshihiro,
Mariz Ronaldo,
Leseurre Lucie,
Gabor Barbara,
Fürstner Alois
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201404873
Subject(s) - chemistry , alkyne , substituent , hydrosilylation , reagent , wittig reaction , silylation , olefin fiber , alkylation , ring (chemistry) , total synthesis , combinatorial chemistry , stereochemistry , organic chemistry , catalysis
Abstract 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.