ИСТИНА

Copper-catalyzed azide-alkyne cycloaddition (CuAAC) has become useful synthetic tool in modern organic chemistry and related disciplines due to its high efficiency, selectivity, and tolerance to numerous functional groups when performed in mild conditions. In calixarene chemistry CuAAC is intensively applied, in particular, for grafting several aminoacid or sugar units onto macrocyclic platform and also for the preparation of efficient ionophores, sensors etc. Interaction of cone tetrakis(propargyloxy)calix[4]arene with excess azides under CuAAC conditions processed efficiently at elevated temperature thus furnishing different tetrakis(triazolyl)calix[4]arenes in good yield. Surprisingly, when the calixarene was reacted with only 1 eq of an azide (while the exhaustive reaction required at least 4 eq of RN3) ~70 mol. % of starting tetrakis(propargyloxy)calixarene returned unchanged, and only trace amounts of expected partially modified calixarenes were obtained in the mixture, while the major product was calix[4]arene bearing four triazole units at narrow rim. In other words, nearly all the available azide was spent to exhaustive modification of calix[4]arene. Though established for some oligoazides, this selectivity of CuAAC is unique for oligoalkynes. Different azides, catalysts and reaction conditions were probed for this 1:1 reaction, and in all the cases corresponding tetrakis(triazolyl)calix[4]arenes were proved to be major products. Expecting the influence of number and mutual orientation of propargyl groups at narrow rim of calixarene onto the selectivity, other propargylated macrocycles were studied in CuAAC with ethyl-2-azidoacetate and/or benzylazide. The results showed that the selectivity of CuAAC was observed only for calixarenes with at least two proximal propargyl groups with syn-orientation (conformationally). The observed selectivity of CuAAC with propargylated calixarenes is discussed in terms of both thermodynamic (efficient stabilization of Cu+ inside the cavity of calix[4]arene by triazole units until all four propargyl groups being reacted) and kinetic reasons (lowering the activation barrier of the reaction when the just-formed triazole unit and the next-reacting propargyl group are properly arranged).