Stereoselective synthesis of functionalized trisubstituted olefins via palladium(0)-catalyzed cross-coupling reaction

[GRAPHICS] A highly flexible and stereoselective protocol for the synthesis of branched (E)- and (Z)-trisubstituted alkenes has been developed. The key steps are hydrozirconation-iodination of (1-alkynyl)trimethylsilane followed by Negishi-type cross-coupling. The resultant (Z)-vinyl silane is iododesilylated and subjected to a second cross-coupling reaction to give the trisubstituted olefin. Model studies aimed at the construction of the C14-C15 (Z)-trisubstituted olefin of discodermolide and the C8-C9 (Z)-trisubstituted olefin of callystatin A and analogues are also described.