New sulfur-based reactive intermediates for synthesis and catalysis

Sulfonyl units, that is the -SO2- arrangement of atoms, are functional groups that feature in a significant number of pharmaceuticals, argochemcials and materials. Variations in which one or more oxygen atoms of these groups are replaced with nitrogen atoms are also emerging as useful molecules for exploring biological processes. This proposal is focused on this latter class of compounds. The types of molecules this encompasses - primarily sulfoximines and sulfonimidamides - are less explored than then non-aza-equivalent, and this is largely due to the lack of convenient methods for their preparation. Conventional syntheses of these types of molecules usually involve three or four synthetic operations, and often feature low-yielding steps. The chemistry involved also limits the substrates that can be converted to aza-sulfonyl-containing molecules. This proposal seeks to develop new reagents and new reactions to this class of molecules; the proposed chemistry will be achieved in a single operation, employ readily available reagents and substrates, and be conducted under mild conditions. The key aspect of the proposal is the design of new nitrogen-containing reagents that will allow ready access to a little used class of reactive intermediates; sulfinylnitrenes. By delivering these reactive intermediates in a simple way, using readily available reagents, a host of new reactivity, and thus transformations, will be available. These reactions will be used to provide general routes to sulfoximines and sulfonimidamides, as well as primary sulfonamides. We will deliver user-friendly reactions. These transformations will significantly simplify the preparation of these molecules, and allow them to be routinely considered when new collections of molecules for biological evaluation are being designed. We will seek to make the reagents we develop commercially available, thus allowing the rapid take-up of the methods we develop.

The proposed methodology will provide new reagents and synthetic methods for the synthesis of a wide range of high-value molecules based on the use of readily available reagents. The types of molecules we will deliver using our new reactions are established as important constituents in a wide variety of biologically important molecules. The proposed methods are 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. Our new reactions will provide far more attractive routes to existing classes of molecules, but will also allow access to compounds that have been previously inaccessible.

In a ten-year timeframe, the successful realisation of the proposed research should see the 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 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 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 methods making the transition from 'discovery' chemistry tools, to being employed by process groups in the manufacture of these important molecules.