| Despite recent advances, the utility of metallacycle-mediated C-C bond formation in synthesis has been largely limited to either intramolecular processes or the bimolecular union of a small subset of unsaturated coupling partners. Basic issues associated with reactivity and control, including homo- versus hetero-coupling, and regio- and stereoselectivity, have remained as barriers to reaction discovery and development in this broad area of chemical reactivity. Alkoxide-directed titanium-mediated cross-coupling has potential for accomplishing new bond constructions.;The ability to generate carbon-carbon bonds in the presence of unprotected hydroxyl group has led to the development of a range of unique fragment coupling processes. In the following chapters, a novel titanium-mediated cross-coupling process is described which unites alkynes with polysubstituted alkenes. Subsequently, an alkyne-alkyne cross-coupling to access (E,E)-1,3-dienes is applied to the total synthesis of callystatin A. Finally, a convergent strategy to synthesize the general leptomycin backbone is developed and the preparation of a collection of synthetic analogues is discussed. |
