A Mild and Catalyst-Free Synthesis of Cannabidiols and Regioisomers Mediated by Fluorinated Alcohols.

This study presents a novel and practical strategy for synthesizing cannabinoids using a fluorinated alcohol solvent for the first time. Hexafluoroisopropanol (HFIP) was found to efficiently promote intermolecular Friedel-Crafts alkylation between allylic alcohols and electron-rich aromatics. This approach enabled the successful synthesis of cannabidiol (CBD) derivatives bearing various alkyl substituents, as well as the corresponding unnatural regioisomer (abnCBD), achieving moderate to high yields under mild conditions without the need for additional catalysts or other reagents.