CCHF Research | Novel Disconnection Strategies

Led by Jin-Quan Yu

Developing new strategies and new reactions to improve our ability to make organic molecules continues to play a central role in the sciences and innovation that spans medicines, agrochemicals and high performance materials. While the tremendous efforts over the past fifty years have elevated synthetic chemistry to a remarkable level of capability in making complex structures, synthetic chemists are facing ever more challenging problems. For instance, the advance of biology, especially the availability of genetic information points to the need for rapid access of as diverse as possible new molecular scaffolds in order to explore new chemical space for drug discovery. New understanding in molecular recognition and physical properties of organic materials presents exciting opportunities for developing high performance materials which would need highly effective synthesis of a particular organic molecule. On the other hand, the environmental concerns call for the development of synthetic technologies that will allow the preparation of organic molecules with optimum step-economy and atom-economy.

The remarkable progress in organic synthesis in the past fifty years can be largely attributed to the development of new disconnections based on wide range of reactions. However, vast majority of these reactions relies on the breaking of relatively reactive π-bond or carbon-oxygen and carbon-halogen bonds. On the other hand, in any given organic molecules being simple starting materials, intermediates or late-stage precursors, C-H bonds often outnumber other types of bonds. It is therefore crystal clear that if synthetic chemist can convert these C-H bonds selectively to the desired functional groups needed for the next step, synthetic routes can be drastically shortened. In addition, the use of bulky chemicals as starting materials for synthesis will be possible if C-H bonds in these chemicals can be selectively functionalized, thus making organic synthesis in the future more sustainable.

The past ten years have seen rapid growth of development of C-H activation reactions and their applications in synthesis have also been demonstrated with a few examples. The center aims to develop strategic disconnections based on C-H activation, and showcase broad application of these reactions in synthesis of a wide range of natural product family. These studies will not only identify the important reactions that need to be developed as a priority, but also provide a road map for implimenting C-H activation reactions in synthesis. In particular, the center will focus on the following three key strategies.

- We develop C-H activation reactions that will provide unprecedented convergency for making a representative class of molecules.

- We collectively identify synthetic targets that are difficult to make using conventional methods and design a C-H activation disconnection to simplify the synthesis via late-stage C-H functionalizations.

- We develop a C-H activation reaction to access the core structure that can be readily elaborated to make the natural product.

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