Stereocontrolled Synthesis of a C1–C10 Building Block (“Southwestern Moiety”) for the Unnatural Enantiomers of the Polyene Polyol Antibiotics Filipin III and Pentamycin: A Sultone‐Forming Ring‐Closing Metathesis for Protection of Homoallylic Alcohols

Abstract

AbstractIn C2‐symmetric diol 10 one OH group was substituted by crotonic acid and the other was incorporated in an ethenesulfonate. A twofold ring‐closing metathesis under forcing conditions provided unsaturated lactone/unsaturated sultone 24. Conjugate addition of Li2(PhMe2Si)2Cu(CN) to both C=C bonds was followed by opening of the sultone moiety with Bu4N+F–. Resultant homoallylic alcohol 28 was carried on to acetonide‐containing lactone 31. Its CpTiCl2 enolate underwent a completely diastereoselective aldol addition to hexanal. Functional group interconversions rendered “southwestern” C1–C10 building block 37. The steps (1) ethenesulfonylation of a homoallylic alcohol, (2) sultone formation, (3) Li2(PhMe2Si)2Cu(CN) addition, and (4) alcohol release by fluoride‐induced fragmentation, from our main sequence represent a new protection/deprotection stragegy for a secondary homoallylic alcohol, as demonstrated with a model compound, too.