Synthesis of Mono- and Binuclear Cu(II) Complexes Bearing Unsymmetrical Bipyridine–Pyrazole–Amine Ligand and Their Applications in Azide–Alkyne Cycloaddition

Abstract

Mono- and binuclear Cu­(II) complexes bearing an unsymmetrical bipyridine–pyrazole–amine ligand were synthesized and characterized using X-ray diffraction. The mononuclear complex could be converted to the corresponding binuclear complexes under basic conditions due to the lability of the pyrazolyl N– H . Both complexes proved to be effective catalysts for azide–alkyne cycloaddition to form triazoles, with the binuclear complex exhibiting higher catalytic activity than the corresponding mononuclear one. The binuclear complex was effective at catalyst loadings as low as 0.0125 mol %, making it one of the most active catalysts for this reaction to date. Therefore, this catalyst was applied in the synthesis of potentially biologically active molecules. At 0.1–0.3 mol % catalyst loading, three precursors of Sorafenib analogs were synthesized in excellent yields. A one-pot variant of the reaction, generating the azide in situ, could also be performed using the binuclear complex as the catalyst. The transition metal complex bearing an unsymmetrical ligand may exhibit excellent catalytic activity, which represents a direction for developing new highly active catalysts.

Synthesis and Antitumor Activity of Triazole-Containing Sorafenib Analogs

“…Alkynes 5k and 5l were prepared using the Seyferth–Gilbert reaction from the corresponding aldehydes 4k and 4l , which were treated with 1.5 equivalents of the Bestmann–Ohira reagent in the presence of 2.0 equivalents of potassium carbonate in methanol (MeOH) at room temperature [ 22 ]. The azides 7a and 7b were synthesized using a previously reported method [ 20 ]. Next, a library of triazolic derivatives was synthesized by cycloaddition reactions between various alkynes and azides using the binuclear complex 2 as the catalyst with a 0.1–0.3 mol % catalyst loading and sodium l -ascorbate as the reductant in MeOH ( Scheme 2 ).…”

“…The chemical structures of the triazoles were confirmed using nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). The object products were 1,4-disubtituted triazoles, which were determined by comparing the NMR spectra of 8a – y with those of our previously reported triazoles [ 20 ].…”

“…Intermediates 5k and 5l were prepared according to a literature procedure. The characterization of compounds 8a , 8h , and 8q have been reported in [ 20 ]. All of the solvents were purified according to the routine methods before being used.…”

“…Numerous efficient catalytic systems have been developed for accelerating the catalytic process and decreasing the amount of metal catalyst needed over the past decade [ 17 , 18 , 19 ]. Very recently, we explored Cu complexes 1 – 3 bearing an unsymmetrical bipyridine-pyrazole-amine ligand and demonstrated their applications in the CuAAC reaction ( Scheme 1 ) [ 20 , 21 ]. To the best of our knowledge, the binuclear complex 2 is currently one of the most active catalyst systems used in the CuAAC reaction.…”

Phosphino-Triazole Ligands for Palladium-Catalysed Cross-Coupling

“…7 The utility of further synthetic transformations has been probed, particularly in the derivatisation at the 5-position (Figure 1, 3). 8 Copper-catalysed triazole formation has been exploited in a wide range of scenarios 9 and has been the subject of various mechanistic studies, 10 leading to the proposal of a binuclear transition state involving two copper atoms. 1,2,3-Triazole derivatives have been employed as nitrogen-coordinating ligands, 11 e.g.…”