Hexafluoroisopropanol: New Reactions and Mechanistic Insight by a Combined Experimental and Theoretical Approach – ElectroHIP

Hexafluoroisopropanol (HFIP) has emerged as a solvent uniquely capable of enabling various challenging yet desirable reactions in organic synthesis. HFIP possesses remarkable intrinsic properties: it can stabilize cationic and radical species and strongly donate hydrogen bonds through the formation of a supramolecular hydrogen bonding network. Yet, it possesses low nucleophilicity, mild acidity and high redox stability. Despite considerable progress, major opportunities for new chemical reactivity enabled by HFIP remain unexplored, in part because reactions are not typically designed with this solvent in mind, and in part because of a lack of mechanistic understanding. The current project will fill this gap by developing new HFIP-enabled multi-catalytic transformations. Overall, with the aid of catalysts operating in a single vessel, the envisioned protocols will directly convert simple starting materials into a range of value-added products, notably primary aliphatic amines, demonstrating both the efficacy and the advantages of the one-pot synthesis featuring linked catalytic cycles in a single complex system. In synergy with this goal, we will build a deeper understanding of its mechanism of action via the use of advanced computational and electrochemical analytical tools, notably to probe and quantify the non-covalent interactions at play.