Synergistic Effect of Copper and Ruthenium on Regioselectivity in the Alkyne–Azide Click Reaction of Internal Alkynes

Cu­(I) salts have been shown to improve the regioselectivity and rate of the Ru-catalyzed alkyne–azide click reaction of internal alkynes with azides. While Cu and Ru individually provide complementary regioselectivity in the case of terminal alkynes, the synergistic effect of these two species in situ significantly improves regiochemical outcomes in the case of internal alkynes. The substrate scope of these new reaction conditions is also reported.