Substitution of Two Fluorine Atoms in a Trifluoromethyl Group: Regioselective Synthesis of 3-Fluoropyrazoles

摘要

Fluorine atoms in vinylic and allylic positions are highly versatile substituents. Among the compounds bearing these fluorine atoms, 2-trifluoromethyl-1-alkenes and 1,1-difluoro-1-alkenes are attractive as building blocks for organic syntheses. Because these fluoroalkenes are electron-deficient, they inherently react with nucleophiles instead of electrophiles. 2-Trifluoromethyl-1-alkenes are subjected to nucleophilic attack at the carbon atom in the position y with respect to the fluorine substituents (Scheme 1 A). Succes- sive elimination of fluoride ions proceeds, which is caused by migration of the double bond, resulting in the formation of 1,1-difluoro-1-alkenes (S_N2'-type reaction).On the other hand, nucleophilic substitution occurs in the 1,1-difluoro-1- alkenes at the vinylic CF2 carbon atom (Scheme 1B). This substitution provides monofluorinated and non-fluorinated alkenes through an addition-elimination process (S_NV reaction). Both substitutions have been useful in organic syntheses.