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

Electron-rich, electron-deficient, and non-activated alkenes can be rapidly functionalized by in situ -generated difluoromethyl nitrile oxide. The (3+2) cycloaddition proceeds at room temperature, has broad functional group tolerance, and can be used for the late-stage modification of bioactive molecules (finasteride and carbamazepine). The obtained CF 2 H-isoxazolines can be easily transformed into CF 2 H-containing building blocks for medicinal chemistry: amines, amino acids, amino alcohols, and spirocyclic scaffolds.