Research Projects

Fluorine or fluorinated moieties can be incorporated into organic molecules to control their properties, such as lipophilicity, permeability, and metabolic stability. The geminal difluoro (CF?) functional group has gained attention as a bioisostere and modulator of oxidative stability and lipophilicity. The CF?H group is essential in drug design due to its lipophilic hydrogen-bond donor capability. Despite its importance, difluoromethylation is underdeveloped compared to trifluoromethylation transformations due to lack of efficient synthetic methods, availability of difluoromethyl sources, and insufficient mechanistic studies. Electroorganic synthesis has emerged as an attractive strategy for building organic molecules efficiently and resource-economically. Electrocatalysis can accomplish redox reactions without expensive and toxic chemical reagents. However, related difluoromethylation reactions are scarce, making research in this area still in the seminal stage. To develop a novel sustainable approach for incorporating difluoromethyl groups on organic molecules, electrocatalysis is proposed as an efficient method for synthesizing difluoromethylated organic compounds involving electro-generated difluoromethyl radical intermediate. The proposed research activities will be investigated in four work packages with 10 milestones. Tasks include electrochemical difluoromethylation of alkenes, electrochemical difluoromethylation of (hetero)arenes, electrochemical difluoromethylation using difluoromethyl (hetero)aryl sulfones, and late-stage functionalization of drug molecules and mechanistic studies.