Ru-Catalyzed [3 + 2] Cycloaddition of Nitrile Oxides and Electron-Rich Alkynes with Reversed Regioselectivity.

Polarity reversal ("umpolung") of a functional group can override its inherent reactivity and lead to distinct bond-forming modes. Herein we describe a rarely studied cycloaddition between nitrile oxides and electron-rich alkynes with reversed regioselectivity, leading to the useful 4-heterosubstituted isoxazoles. The use of a ruthenium catalyst completely overrides the inherent polarity of nitrile oxides. This reversed regioselectivity was also observed for their reactions with a range of electron-deficient alkynes.