Construction of Nitrogen-Oxygen-Heterocycles via Copper-Free Click Reactions of Nitrile Oxides

Click chemistry has been developed rapidly, which was initially proposed by Sharpless and co-workers since 2001. As the representative of click chemistry, the Cu(I)-catalyzed azide-alkyne cycloaddition (Cue-AAC) reaction has been applied widely for the preparation of new materials, drugs and catalyst carriers. The copper metal contamination in the final products is a major concern because of the use of copper salts catalytic system. These drawbacks counteract their applications in the fields of biomedicine and pharmaceuticals. Click reactions based on nitrile oxides with the feature of copper-free catalysis, not only can produce isoxazoles and isoxazolines by reacting with nitrile oxides and alkynes/alkenes, but also can synthesize oxadiazoles from nitrile oxides and nitriles. Copper-free nitrile oxides click reactions have good region- and stereo-selective properties and have been applied to the synthesis of drugs and bioactive compounds with particular structures. The new progress of click reactions based on nitrile oxide is reviewed.