Unlocking the Friedel–Crafts Arylation of Primary Aliphatic Alcohols and Epoxides Driven by Hexafluoroisopropanol
J. Moran and D. Lebœuf describe Friedel–Crafts reactions of primary aliphatic alcohols and epoxides with various arenes.
The Friedel–Crafts alkylation is an important way to form Csp2–Csp3 bonds. Since the 1940s, the scope of the Friedel–Crafts reaction with alcohols was successfully extended to various substitution patterns, such as benzylic, allylic, and propargylic alcohols, otherwise known as π-activated alcohols. However, highly electronically deactivated π-activated alcohols and primary aliphatic alcohols have always remained challenging due to the difficulty (or impossibility) of forming a carbocation intermediate from such substrates. In 2017, the group of Professor Joseph Moran at the University of Strasbourg (France) found that the combination of catalytic quantities of the strong Brønsted acid TfOH and the solvent hexafluoroisopropanol (HFIP) was an excellent promoter system for direct Friedel–Crafts reactions of electronically deactivated benzylic and propargylic alcohols. At the same time, Dr. David Lebœuf, who was then working at the University Paris-Saclay (France), had been exploring how Lewis and Brønsted acid catalysts in HFIP could push the boundaries of classic synthetic transformations such as the hydroarylation of highly deactivated styrenes and halofunctionalization of unactivated alkenes, making similar observations as Professor Moran regarding the role of HFIP. Both projects were merged upon Dr. Lebœuf move to Strasbourg in 2019.