COAST · Chiral Organometallics for Asymmetric Synthesis

Chemical processes (synthesis) that create new C-C bonds from simpler molecules are also hugely important as this is how chemical complexity is built up. In a synthesis starting molecules are used to build new molecules by means of various chemical reactions. Organic synthesis generally involves the reaction between two molecules a nucleophile and an electrophile. These are attracted to each other rather like opposite poles of a magnet and a chemical bond is created between them. One class of useful nucleophiles are organometallic reagents as they readily react with electrophiles to make new bonds. However, chiral organometallic reagents are very rare, but clearly if they could be easily prepared they would be extremely useful as they would provide a direct synthesis of a broad range of chiral molecules. We propose a unique method for generating configurationally stable chiral organometallics and then we will explore what classes of electrophiles they react with. Our method involves initially generating a nucleophile (bearing a group that also leaves during the course of the reaction) (an organometallic reagent) and reacting it with another nucleophile (an organometallic reagent) to create a new chiral organometallic. We believe that reactions of this class of nucleophiles with conventional and non- conventional electrophiles will open up a whole new area of synthesis and provide a step change in asymmetric synthesis that could have far reaching consequences. With this information we will then apply the new chemistry in the synthesis of biologically important molecules that are otherwise difficult to make. This will particularly highlight the power of the new methodology.