Asymmetric synthesis of thiophene S-monoxides as cyclones of dienes and as a core step for new atroposelective syntheses of biaryl compounds

The chemistry of thiophenes and thiophene-S,S-dioxides has been the subject of intense research and has led to a diversity of applications in medicinal and polymer or materials chemistry. While these compounds have been used as substrates in cycloaddition reactions to build up more complex and useful organic structures, this often requires high temperatures, long reaction times, and is difficult to control in term of stereochemistry. Efficient methods that enable the synthesis of only one mirror image (enantiomer) of these cycloadducts are not widespread. Recently, more and more attention is devoted to the corresponding monoxides and the exploration of thiophene monoxides is still in its infancy. For example, an asymmetric mono-oxidation of the S-atom in thiophenes has only been described using enzymes (with low isolated yields). This project will focus on the development of selective chemical oxidation methods towards thiophene monoxides for use in direct cycloaddition reactions. A major application of this method that will be studied, is the atroposelective synthesis of hindered biaryl compounds. These are structures where two aromatic rings are linked via a C-C single bond but where rotation around this bond is restricted giving rise to axial chirality. This feature can be found in many bioactive natural products, but is difficult to obtain chemically in a stereoselective manner. The use of thiophene monoxides can form a solution to reach such compounds.