More efficacious and better-tolerated drugs are crucial for the treatment of serious and common medical conditions. Scientists involved in discovering drug compounds require synthetic methods that allow them to design molecules with optimal properties. The development of new methods will also influence the design of such compounds by providing new structural motifs as design options, and by providing new ways to connect and functionalise molecules. Small rings (examples include oxetanes and azetidines) are highly attractive in drug discovery, but are vastly understudied, not least through lack of suitable preparative methods. This prevents their exploitation. The incorporation of these rings can lead to improved properties in a drug molecule. Furthermore, they can be envisaged as replacements for other more common structures that can fine-tune and improve the properties of a compound (the idea of being a 'bioisostere'). This research will harness these ring structures in novel, stable and easily handled reagents that can be prompted to react in a new type of coupling process that generates a reactive intermediate under mild conditions. The new reagents allow the generation of collections of valuable compound collections and the 'late-stage' functionalisation complex drug candidates and biological molecules to improve and tailor their molecular properties. The research consists of 3 parts. The first will prepare new reagents and establish their reactivity and synthetic characteristics. These will be used to prepare new molecules that will be valuable for testing in drug discovery, for example in fragment based drug discovery, a strength of UK industry. Analogues of current drug molecules will also be prepared replacing key features with the new small rings as bioisosteres. Part 2 will compare the properties of some of the new types of molecules prepared with those containing different more common groups to establish the change in properties. This will inform synthetic and medicinal chemists on when to exploit the new designs in drug design. Derivatives that will be prepared in this work present a exciting potential as bioisosteres for amides, perhaps the most common functional group in drug compounds. Finally, the new reagents will be examined in peptide functionalisation using water tolerant derivatives and to establish selectivity. These fundamental studies will lead to new types of probes to investigate biological systems. Each stage will develop new synthetic chemistry and reactivity features, and provide new insights for medicinal chemists.