Copper Nanoparticles in Click Chemistry

Abstract

2The challenges of the 21 st century demand scientific and technological achievements which must be developed under sustainable and environmentally benign practices. In this vein, Click Chemistry and Green Chemistry walk hand in hand on a pathway of rigorous principles which help to safeguard the health of our planet against negligent and uncontrolled production. The copper-catalyzed azide-alkyne cycloaddition (CuAAC), the paradigm of a click reaction, is one of the most reliable and widespread synthetic transformations in organic chemistry, with multidisciplinary applications. Nanocatalysis is a Green Chemistry tool which can increase the inherent effectiveness of the CuAAC because of the enhanced catalytic activity of nanostructured metals and their plausible reutilization capability as heterogeneous catalysts.In this account, our contribution to Click Chemistry is described using unsupported and supported copper nanoparticles (CuNPs) as catalysts prepared by chemical reduction. Cu(0)NPs (3.0 ± 1.5 nm) in tetrahydrofuran were found to catalyze the reaction of terminal alkynes and organic azides, in the presence of triethylamine, at rates comparable to those achieved under microwave heating (10-30 min in most cases). Unfortunately, the CuNPs underwent dissolution under the reaction conditions and, consequently, could not be recovered. Compelling experimental evidence on the in-situ generation of highly reactive copper(I) chloride and the participation of copper(I) acetylides was provided.The supported CuNPs were found to be more robust and efficient catalyst than the unsupported counterpart in the following terms: (a) the multicomponent variant of the CuAAC could be applied, (b) with substantial decrease in the metal loading, (c) reactions could be conducted in neat water, and (d) with easy recovery and reutilization of the catalyst. In particular, the catalyst composed of oxidized CuNPs/C (Cu 2 O/CuO, 6.0 ± 2.0 nm) was shown to be highly versatile and 3 very effective in the multicomponent and regioselective synthesis of 1,4-disubstituted-1,2,3-triazoles in water from organic halides as azido precursors; magnetically recoverable CuNPs (3.0 ± 0.8 nm)/MagSilica could be alternatively used for the same purpose under similar conditions. Incorporation of an aromatic substituent at the position 1 of the triazole could be accomplished using the same CuNPs/C catalytic system, but starting from aryl diazonium salts or anilines as azido precursors. CuNPs/C in water also catalyzed the regioselective double-click synthesis ofhydroxy-1,2,3-triazoles from epoxides. Furthermore, alkenes could be also used as azido precursors through a one-pot CuNPs/C-catalyzed azidosulfenylation-CuAAC sequential protocol, providing -methylsulfanyl-1,2,3-triazoles in a stereo-and regioselective manner. In all the types of reaction studied, CuNPs/C exhibited better behavior than some commercial copper catalysts as regards the metal loading, reaction time, yield and recyclability. Therefore, the results of this study also highlight the utility ...

Metal-catalyzed azide-alkyne “click” reactions: Mechanistic overview and recent trends

“…The other interesting ways to generate catalytic active species Cu(I) by using Cu (0) NPs is through comproportionation of Cu(0) and Cu(II) in the native oxide layer on the Cu surface [78]. In Alonso's proposed mechanism for the CuNP-catalyzed AAC, Cu(I) acetylides appeared as the true intermediate species [79]. The in-situ generation of CuCl was postulated after acetylene deprotonation, with the concomitant formation of triethylammonium chloride (in the presence of LiCl derived from CuNPs preparation), and the action of the latter on the CuNPs.…”

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