Functionalization of Alkenes with Difluoromethyl Nitrile Oxide to Access the Difluoromethylated Derivatives

The study presents a scalable method for functionalizing alkenes using difluoromethyl nitrile oxide via a (3+2) cycloaddition reaction at room temperature, producing difluoromethyl-substituted isoxazolines. These can be converted into valuable medicinal chemistry building blocks such as amino alcohols, amines, and spirocycles. The method shows high functional group tolerance and can be applied to the late-stage modification of complex bioactive molecules, though it is ineffective for tri- and tetrasubstituted alkenes. The synthesis of these compounds is demonstrated on a multigram scale, highlighting their potential applications in medicinal and agricultural chemistry.