Studies on the total synthesis of disorazole C1.: An advanced macrocycle intermediate

Synthesis of protected tetradehydro-(6,6 ' -S)-(14,14 ' -S)-(16,16 ' -R)-disorazole (3), a potential precursor to the natural product disorazole C-1 (1), is described. Key features of this work include (a) an unprecedented sequential 1.5 O --> O silyl rearrangement/Horner-Wadsworth-Emmons reaction used to construct 18, (b) a highly convergent Sonogashira reaction between the dienyl iodide 7 and the alkyne 8 to assemble the dienyne monomeric fragment 5, and (c) the selective cyclization of 5 to give either the cyclic monomer 23 or the dimer 3.