Introducing Molecular Complexity Using Organolithium Cross-Coupling Chemistry

Carbon-carbon bonds are found everywhere; diamonds and plastics are composed of large, interconnected C-C bond networks, while medicines are composed of smaller molecules in which carbon-carbon connections are essential. Studies on the coupling of two carbon-based fragments, analogous to welding two pieces of metal together, have been ongoing since the 20th century. These reactions however generally require elevated reaction temperatures and long reaction times, while also typically employing precious transition metal-catalysts. An alternative to the established methods is the use of so-called organolithium reagents, which are readily available and enable fast C-C bond formations at mild temperatures. Several limitations are however typically encountered using these reagents; i) they are incompatible with an array of sensitive compounds, ii) they cannot be used in air, and iii) the reactions generally require the use of scarce palladium catalysts.

The first part of this thesis focusses on our efforts to enable the synthesis of sensitive structures by either incorporating handles for the formation of the reactive functionalities, or by their direct introduction. We next developed a methodology for the formation of carbon-carbon bonds without requiring the use of a transition metal-catalyst by choosing an appropriate, readily available substrate. Addressing another limitation, we also found that these highly reactive organolithium reagents can be used to form C-C bonds in air by incorporating them in a gel structure. Finally, we explored the use of organolithium species in reactions that might shine light on a mechanism for the origin of homochirality in Nature.