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 CF2H-isoxazolines can be easily transformed
into CF2H-containing building blocks for medicinal chemistry:
amines, amino acids, amino alcohols, and spirocyclic scaffolds.