Synthesis of Ring-Fluorinated Thiophene Derivatives Based on Single C–F Bond Activation of CF<sub>3</sub>-Cyclopropanes: Sulfanylation and 5-<i>endo</i>-<i>trig</i> Cyclization
Kohei Fuchibe, Tatsuki Fushihara, Junji Ichikawa
Abstract
The treatment of CF3-bearing cyclopropanes with Et2AlCl generated stabilized difluorocarbocations, which underwent a nucleophilic addition of thiocarboxylic acids or thiols. The sulfur functionality was introduced at the position δ to the fluorine substituents in a regioselective manner (single activation of CF3-cyclopropanes). The formed 1,1-difluoro-1-alkenes underwent successive deesterification/5-endo-trig cyclization. Intramolecular vinylic substitution proceeded in an aprotic solvent, whereas intramolecular addition proceeded in a protic solvent to afford pharmaceutically and agrochemically promising 2-fluoro-4,5-dihydrothiophene and 2,2-difluorotetrahydrothiophene scaffolds, respectively.