It has been estimated that the number of theoretically possible bioactive small molecules is between 1062 and 1063. To date, approximately 203 million organic and inorganic substances are disclosed in the CAS REGISTRY®, meaning only a minuscule fraction of chemical space has been accessed. This highlights that the vast majority of molecules with useful properties remain undiscovered. Given the extreme number of possibilities and finite resources, the indiscriminate synthesis of difficult compounds is no longer a viable strategy for functional discovery.
To enable the development of new chemistries, we present Diversity Oriented Clicking (DOC): a unified approach for the modular synthesis of lead-like structures. DOC leverages the wider family of click transformations to provide novel functionalities while conserving resources, improving efficiency, and minimising hazardous waste. This approach integrates classical click chemistry techniques, such as Huisgen cycloadditions, with next-generation Sulfur-Fluoride Exchange (SuFEx) chemistry to achieve “diversity with ease.”
This presentation will specifically focus on the discovery of three unprecedented alkyne and diazo DOC connectors.1-3 We demonstrate how these highly reactive S—F building blocks undergo thermodynamically driven transformations to rapidly assemble diverse molecular frameworks that are difficult or impossible to prepare using existing technologies.