Alkyne-azide click reaction catalyzed by metallic copper under ultrasound

This protocol is for the ultrasound (USUS)-assisted 1,3-dipolar cycloaddition reaction of azides and alkynes using metallic copper (Cu) as the catalyst. The azido group is a willing participant in this kind of organic reaction and its coupling with alkynes is substantially improved in the presence of Cu(I). This protocol does not require additional ligands and proceeds with excellent yields. The Cu-catalyzed azide–alkyne cycloaddition (CuAACAACAAC) is generally recognized as the most striking example of ‘click chemistry’. Reactions involving metals represent the favorite domain of sonochemistry because USUS favors mechanical depassivation and enhances both mass transfer and electron transfer from the metal to the organic acceptor. The reaction rate increases still further when simultaneous USUS and microwave irradiation are applied. The USUS-assisted click synthesis has been applied for the preparation of a wide range of 1,4-disubstituted 1,2,3-triazole derivatives starting both from small molecules and oligomers such as cyclodextrins (CDs). Using this efficient and greener protocol, all the adducts can be synthesized in 2–4 h (including work-up and excluding characterization). Click chemistry has been shown to be able to directly link chemistry to biology, thus becoming a true interdisciplinary reaction with extremely wide applicability.