Harnessing Sulfur Dioxide for Catalysis

Sulfonyl units, that is the -SO2- arrangement of atoms, are functional groups that feature in a significant number of pharmaceuticals, argochemcials and materials. Conventional syntheses of these types of molecules usually involve two or three synthetic operations, and often feature low-yielding steps. The chemistry involved also limits the substrates that can be converted to sulfonyl-containing molecules. This proposal seeks to develop an alternative synthesis of this class of molecules; the proposed synthesis will be achieved in a single operation, employ readily available reagents and substrates, and be conducted under mild conditions. The key to the proposed synthesis is to employ a three-component synthesis involving the catalytic combination of an aryl halide, an nucleophile and sulfur dioxide. Achieving the synthesis in a single operation will have significant advantages in terms of waste production, energy required, as well as the time needed to prepare the desired compounds. These are important considerations for both small scale discovery synthesis, as well as the large scale synthesis of these materials. The developed methodology should also be applicable to the preparation of related molecules derived from alternative starting materials such as non-functionalised arenes or alkene and alkynes. The project will explore the application of the developed method to the synthesis or selected target structures that are difficult to access using conventional methods, and to the synthesis of heterocycles. Application of the developed catalytic methods to the synthesis of new materials, using polymerisation chemistry, will also be preliminarily investigated.

The proposed methodology represents a new catalytic approach to the synthesis of sulfonyl containing molecules based on the use of sulphur dioxide as a basic feedstock. Sulfonyl groups are established as important constituents in a wide variety of biologically important molecules and in important materials. The proposed method is direct, i.e., a single step operation, and uses easy to handle reagents. The beneficiaries will be chemists involved in research, either academic or industrial, who require access to these types of molecules. In particular this will include chemists involved in pharmaceutical and agrochemical research as well as biomedical scientists. Materials scientists exploring the use of sulfonyl-containing polymers would also benefit from new and more efficient means to access these types of materials.

In a ten-year timeframe, the successful realisation of the proposed research should see the catalytic methods we have developed being routinely used by researchers in the pharmaceutical and agrochemical industries to prepare molecules for evaluation. This is a very real possibility, as not only will these new catalytic methods allow the one-step preparation of valuable molecules, these transformations will be achieved using simple experimental procedures that will not require specialist equipment or training. On a longer-term, 50 year, timeframe, molecules originally prepared using these new catalytic methods could be in the market place and being used to treat diseases and/or protect crops. The longer-term could also see the developed catalytic methods making the transition from 'discovery' chemistry tools, to being employed by process groups in the manufacture of these important molecules.