HAT-induced sequential catalytic enantioselective C-alkylations of native diols – BO-HAT

Free radicals as molecular scalpels to the synthesis of complex molecules.

This project aims to combine two types of molecular catalysis to convert readily available diols into complex and valuable molecules in a fast and controlled process. This approach would provide a more direct access to biologically relevant compounds while adressing some fundamental challenges as the selective functionalisation of poorly reactive C-H bonds.

Fast increase of molecular complexity by surgical functionalisation of diols.

More than ever, the discovery and development of original molecular scaffolds displaying therapeutic properties (antiviral, antibiotics, antitumor and others) are major concerns in our society. Nature remains an inexhaustible reservoir of biologically relevant molecules and the formation of such complex compounds is ensured by strickingly efficient enzymatic processes. Indeed, enzymatic pools are able to control both the shape of the carbon backbone, the correct positioning of chemical functions with the good oxidation degree and the three-dimensional layout of the different bonds. At the opposite, forging such molecules in laboratory or industry remains a major challenge in modern organic synthesis. This issue, combined to environmental concerns, had led organic pactitioners to design highly efficient synthetic pathways displaying limited costs, numbers of steps and amount of waste while increasing quickly the molecular complexity from simple and abundant substrates. As enzymes, the efficiency of such reactions requires a perfect control of the selectivity. As a matter of fact, setting up methodologies allowing the selective cleavage of a single C-H bonds (often numerous in organic molecules) to convert it in a new C-C bond without the need of intermediate and superfluous transformations, is an appealing goal of this research area. In this framework, the present project aims to convert simple diols in complex molecules through successive C-H bond cleavage/C-C bond formation sequences. The challenging selective cleavage of a defined C-H and the geometrical control of the new-formed C-C bond will be adressed by an original combination of catalysts mimicking enzymes.