Studies on the total synthesis of disorazole C-1. An advanced macrocycle intermediate

Synthesis of protected tetradehydro-(6,6 ' -S)-(14,14 ' -S)-(16,16 ' -R)-di sorazole (3), a potential precursor to the natural product disorazole C-1 ( 1), is described. Key features of this work include (a) an unprecedented se quential 1.5 O --> O silyl rearrangement/Horner-Wadsworth-Emmons reaction u sed to construct 18, (b) a highly convergent Sonogashira reaction between t he dienyl iodide 7 and the alkyne 8 to assemble the dienyne monomeric fragm ent 5, and (c) the selective cyclization of 5 to give either the cyclic mon omer 23 or the dimer 3.