‘Click’ cycloaddition catalysts: copper(i) and copper(ii) tris(triazolylmethyl)amine complexes

Abstract

The CuI complex of the 'click' ligand tris(benzyltriazolylmethyl)amine is an unusual dinuclear dication with one triazole unit bridging two metal centers, and is an effective catalyst for the 'click' cycloaddition reaction.

Efficient Syntheses of 1,2,3-Triazoloamide Derivatives Using Solid- and Solution-Phase Synthetic Approaches

“…The selective [3+2] Hüisgen cycloaddition [24][25][26][27][28][29] was performed with α-azidoamide resin 8 and terminal acetylene 9 (the third diversity element R 3 ; Figure 4) according to optimized reaction condition (3 equiv. CuI, 3 equiv.…”

“…Under the general cleavage conditions of AMEBA resin (30% TFA, CH2Cl2, room temperature), the resulting polymer-bound product 10aaa gave the desired α-1,2,3-triazoloamide 1aaa (44%) and by-product 13 (30%), while unreacted resin 10aaa remained as was confirmed by ATR-FTIR analysis (Scheme 3). The selective [3 + 2] Hüisgen cycloaddition [24][25][26][27][28][29] was performed with α-azidoamide resin 8 and terminal acetylene 9 (the third diversity element R 3 ; Figure 4) according to optimized reaction condition (3 equiv. CuI, 3 equiv.…”

“…The reaction was confirmed by ATR-FTIR analysis of resin 11 and the cleavage of the resin 11 under 30% TFA in CH2Cl2 at room temperature provided an N-phenylacrylamide (12) [22,23] as a major product. The selective [3+2] Hüisgen cycloaddition [24][25][26][27][28][29] was performed with α-azidoamide resin 8 and terminal acetylene 9 (the third diversity element R 3 ; Figure 4) according to optimized reaction condition (3 equiv. CuI, 3 equiv.…”

“…Under the general cleavage conditions of AMEBA resin (30% TFA, CH2Cl2, room temperature), the resulting polymer-bound product 10aaa gave the desired α-1,2,3-triazoloamide 1aaa (44%) and by-product 13 (30%), while unreacted resin 10aaa remained as was confirmed by ATR-FTIR analysis (Scheme 3). Finally, the α-1,2,3-triazoloamide resin 10aaa was cleaved from the solid support under 30% TFA in CH2Cl2 at 45 °C to provide the desired α-1,2,3-triazoloamide 1aaa [24,27,30] (93% over six steps, from Merrifield resin) without formation of by-product 13.…”

“…The completion of selective [3 + 2] Hüisgen cycloaddition of 7aa and 9a was confirmed by the disappearance of the azide stretching band. Finally, the α-1,2,3-triazoloamide resin 10aaa was cleaved from the solid support under 30% TFA in CH2Cl2 at 45 °C to provide the desired α-1,2,3-triazoloamide 1aaa [24,27,30] (93% over six steps, from Merrifield resin) without formation of by-product 13.…”