Science of Synthesis

Tomé, A. C., Science of Synthesis Knowledge Updates, (2015) 2, 59.

In the absence of a catalyst, the Huisgen 1,3-dipolar cycloaddition of an organic azide and a terminal alkyne affords a mixture of 1,4- and 1,5-disubstituted 1,2,3-triazole regioisomers ‌1‌ and ‌2‌.[‌1‌] However, at the beginning of the 21st century it was found that in the presence of a suitable catalyst, this reaction may give exclusively 1,4- or 1,5-disubstituted 1,2,3-triazoles (‌Scheme 1‌). This major breakthrough was discovered independently by the groups of Meldal[‌2‌] and Fokin and Sharpless,[‌3‌] which reported that the copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reactions lead regioselectively to 1,4-disubstituted 1,2,3-triazoles. Later, Fokin and Sharpless reported that the ruthenium(II)-catalyzed azide–alkyne cycloaddition (RuAAC) reaction affords exclusively the 1,5-disubstituted 1,2,3-triazoles.[‌4‌] Recently, it was discovered that metal complexes of silver,[‌5‌,‌6‌] iridium,[‌7‌] lutetium,[‌8‌] scandium,[‌8‌] and samarium[‌9‌] are also selective catalysts for the azide–alkyne cycloaddition reaction.

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References