An efficient Cu-catalyzed azide–alkyne cycloaddition (CuAAC) reaction in aqueous medium with a zwitterionic ligand, betaine

Abstract

Cu-catalyzed azide–alkyne cycloaddition reaction in aqueous medium was dramatically accelerated by a simple zwitterionic additive, betaine, at ambient temperature. In the presence of betaine, 1,4-disubstituted-1,2,3-triazoles were obtained from azides and terminal alkynes in excellent yields under 2.5–200 ppm levels of Cu^(I) in water. This method resulted in the remarkable reduction of the Cu^(I) concentration down to ppm levels. The advantages of this protocol include the use of a conventional Cu catalytic system with commercially available betaine, which is generally non-toxic for biological application. Therefore, this efficient catalytic system should have broad applications in life science research and materials science.