| The development of strategies for convergent carbon-carbon (C--C) bond formation remains a central interest in modern organic chemistry. Metallacycle-mediated transformations represent a class of carbon-carbon bond forming processes that proceed through the arrangement of pi-systems around a metal center with concurrent C--C bond formation. Several challenges have defined a significant barrier to the development of synthetically powerful fragment coupling reactions based on this chemistry including: the variable reactivity of different pi-systems, control of regioselection, control of stereoselection, and the competition between reductive cross-coupling and homodimerization. In light of the synthetic limitations imposed by these challenges, we sought to define a general strategy for reductive cross-coupling by rendering the reaction of metal--pi complexes "directed" by a ubiquitous functional group present in biologically active natural products. The science described in this thesis is focused on the development of "directed" reductive cross-coupling chemistry based on the reactivity of titanium-alkoxides, and seeks to further define an emerging class of novel fragment coupling reactions for complex molecule synthesis. Further, the utility of "directed" titanium-mediated reductive cross-coupling has been illustrated through the development of a synthesis strategy for the construction of complex and diverse polyketide-inspired small molecules. |
