Cationic Copper Iminophosphorane Complexes as CuAAC Catalysts: A Mechanistic Study

Abstract

We have combined Cu K-edge X-ray absorption spectroscopy with NMR spectroscopy ( 1 H and 31 P) to study the Cu-catalyzed azide−alkyne cycloaddition (CuAAC) reaction under operando conditions. A variety of novel, well-defined Cu I iminophosphorane complexes were prepared. These ligands, based on the in situ Staudinger reduction when [Cu(PPh 3 ) 3 Br] is employed, were found to be active catalysts in the CuAAC reaction. Here, we highlight recent advances in mechanistic understanding of the CuAAC reaction using spectroscopic and kinetic investigations under strict air-free and operando conditions. A mononuclear Cu triazolide intermediate is identified to be the resting state during catalysis; cyclization and protonation both have an effect on the rate of the reaction. A key finding of this study includes a novel group of highly modular Cu I complexes that are active in the base-free CuAAC reaction.

Azide–Alkyne “Click” Reaction in Water Using Parts-Per-Million Amine-Functionalized Azoaromatic Cu(I) Complex as Catalyst: Effect of the Amine Side Arm

“…The literature survey showed that the coordinated phenylacetylene moiety in mononuclear complexes could lead to the dimeric complex formation by coordinating acetylenic π bonds. − ,,, Thus, it is proposed that a significant amount of deprotonated phenyl-acetylene-coordinated mononuclear complex I was dimerized with the unreacted second Cu­(I) metal center to generate dimeric complex II in addition to the monomeric complex I (Figure C). Measurement of the ESI-MS spectrum of the acetonitrile solution of the complex 5 upon addition of 15 equiv of phenyl acetylene showed two intense peaks at m / z = 379.1 and 695.2 amu (Figure S116), which were assigned to the molecular ion peak of formulas [C 20 H 17 CuN 3 O] + and [C 32 H 29 Cl 2 Cu 2 N 6 ] + , respectively.…”

“…in industry as well as in academia. Thus, after the independent selective synthesis of 1,4-disubstituted triazoles by Sharpless–Fokin and Meldal using Cu­(I) compounds as catalysts, considerable attention has been given to the CuAAC reaction. − It has been observed that any Cu­(I) source may act as a catalyst for the CuAAC reaction. , Generally, an easily available Cu­(II) source like CuSO 4 by the chemical reduction of sodium l -ascorbate was used to generate the Cu­(I) catalyst . However, this type of Cu source is not desirable because the Cu­(I) oxidation state is very unstable; it may disproportionate to Cu(0) and Cu­(II) or may get oxidized to its Cu­(II) compound. ,, Thus, a larger quantity of Cu­(II) compound is required for the selective synthesis of triazoles .…”

“…Moreover, in electronics and biomedicine applications, removal of copper ions is a problem. , It has been shown that ancillary ligand coordinated Cu­(I) complexes can decrease the catalyst loading and increase the selectivity of the CuAAC reaction, as these Cu­(I) complexes are more stable. ,, Employing this strategy, Astruc et al have reported amphiphilic and dendrimer nanoreactors, Uozumi et al have reported amphiphilic self-assembled polymers, Zimmerman et al have reported a metal–organic nanoparticles for parts-per-million (ppm) Cu­(I) catalysis in water. However, though a library of Cu­(I) complex catalyzed CuAAC reaction is known, − such catalysis in water at a low ppm catalyst loading is still rare. − As Cu­(I) is the lower oxidation state of copper, it is important to use a strong π-acceptor-type chelating ligand for the development efficient catalyst for CuAAC reactions. Here, we report a series of amine-functionalized azo-aromatic copper­(II) complexes (Scheme A) that showed interesting ligand hemilability upon reduction, and the reduced Cu­(I) complexes are highly efficient (up to low ppm level catalysis) for selective CuAAC reaction via intramolecular acid–base cooperation solely in water under air (Scheme B).…”

“…Both of these two component and three component synthetic strategies were also employed to synthesize a number of useful functional triazoles having medicinal, catalytic, and targeting properties efficiently at ppm level catalyst loading. Though various ligand-containing copper complexes have been explored for CuAAC reactions, − azo-aromatic ligand-supported copper complexes remain unexplored to date.…”

Copper-Catalyzed Azide–Alkyne Cycloaddition (CuAAC) by Functionalized NHC-Based Polynuclear Catalysts: Scope and Mechanistic Insights

“…These findings have increased the interest in mechanistic studies of CuAAC processes . As a result, several groups have reported very significant experimental and theoretical studies, which mainly focus on identifying, isolating, and characterizing resting states with special interest in the nuclearity and the explicit role of the copper atoms involved in the process. , This has led to a relatively well-established Fokin-like catalytic cycle, although some authors have proposed some modifications, for example, the coordination of the azide to the Cu atom σ-bound to the alkynyl group instead of to the ligand-bound Cu center (Cu′ in Figure ).…”