Assessing the whole range of CuAAC mechanisms by DFT calculations—on the intermediacy of copper acetylides

Cantillo, David; Авалос, M.; Babiano, Reyes; Cintas, Pedro; Jiménez, José L.; Palacios, Juan C.

doi:10.1039/c0ob01001d

Cited by 60 publications

(62 citation statements)

References 40 publications

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“…This mechanistic picture was supported by recent calculations carried out by the group of Cantillo [199]. In their DFT study, the authors compare different mechanistic proposals from literature on the same level of theory (B3LYP/LANL2DZ, solvent model CPCM for water).…”

Section: Reviewmentioning

confidence: 59%

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

Berg

Straub

2013

Beilstein J. Org. Chem.

204

139

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SummaryThe copper-catalyzed azide–alkyne cycloaddition (CuAAC) is one of the most broadly applicable and easy-to-handle reactions in the arsenal of organic chemistry. However, the mechanistic understanding of this reaction has lagged behind the plethora of its applications for a long time. As reagent mixtures of copper salts and additives are commonly used in CuAAC reactions, the structure of the catalytically active species itself has remained subject to speculation, which can be attributed to the multifaceted aggregation chemistry of copper(I) alkyne and acetylide complexes. Following an introductory section on common catalyst systems in CuAAC reactions, this review will highlight experimental and computational studies from early proposals to very recent and more sophisticated investigations, which deliver more detailed insights into the CuAAC’s catalytic cycle and the species involved. As diverging mechanistic views are presented in articles, books and online resources, we intend to present the research efforts in this field during the past decade and finally give an up-to-date picture of the currently accepted dinuclear mechanism of CuAAC. Additionally, we hope to inspire research efforts on the development of molecularly defined copper(I) catalysts with defined structural characteristics, whose main advantage in contrast to the regularly used precatalyst reagent mixtures is twofold: on the one hand, the characteristics of molecularly defined, well soluble catalysts can be tuned according to the particular requirements of the experiment; on the other hand, the understanding of the CuAAC reaction mechanism can be further advanced by kinetic studies and the isolation and characterization of key intermediates.

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Section: Reviewmentioning

confidence: 59%

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

Berg

Straub

2013

Beilstein J. Org. Chem.

204

139

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“…Indeed, complexes with acetylide ligands that bind copper species may be resting states of the catalyst in such click reaction mixtures that are not acidic [58c]. Following these pioneering computational works, several theoretical mechanistic investigations on the CuAAC reactions have been carried out, considering various copper systems, most of them multinuclear, and leading basically to similar qualitative conclusions [34,[58][59][60][61][62]. A recent investigation pointed out the possibility for a concerted vs. stepwise nature of the mechanism, however, depending on the ligand nature [63].…”

Section: Introductionmentioning

confidence: 99%

“…Since the early reports, a variety of transition-metal catalysts have been used for the reactions between mono-or disubstituted alkynes and azides (vide infra). For the Cu(I) catalyzed reaction, a variety of mechanisms involving Cu(I)-aryl intermediates have been proposed in which the key-step species contains either mononuclear [35] or binuclear copper species [30][31][32][33][34][35][36][37][38]. Theoretical studies of the RuAAC reaction have also been reported [28,[39][40][41].…”

Section: Introductionmentioning

confidence: 99%

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

Changlong

Ikhlef

Kahlal

et al. 2016

Coordination Chemistry Reviews

287

162

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Highlights-The review is focused on the mechanistic aspects and recent trends (since 2012) of the metal-catalyzed azide-alkyne cycloaddition (MAAC) so-called "click" reactions with catalysts based on various metals (Cu, Ru, Ag, Au, Ir, Ni, Zn, Ln), although Cu (I) catalysts are still the most used ones.-These MAAC reactions are by far the most common click reactions relevant to the "green chemistry" concept.-Mechanistic investigations are essential to reaction improvements and subsequent applications, and indeed as shown in this review the proposed mechanisms have been multiple during the last decade based on theoretical computations and experimental search of intermediates.-New trends are also presented here often representing both exciting approaches for various applications and new challenges for further mechanistic investigations.

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“…[33] In their DFT study, the authors compare different mechanistic proposals from literature on the same level of theory (B3LYP/LANL2DZ, solvent model CPCM for water). In conclusion, they confirm dinuclear copper acetylides to be the essential catalytic intermediates, whereas the corresponding copper alkyne pcomplexes need to be deprotonated before the crucial C-N bond forming step can take place.…”

Section: Mechanistic Investigation Of the Cuaacmentioning

confidence: 99%

Highly Active Dinuclear Copper Catalysts for Homogeneous Azide–Alkyne Cycloadditions

et al. 2012

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It is better to light a candle than to curse the dark. AbstractThe copper-catalyzed azide-alkyne cycloaddition for the synthesis of 1,4-disubstituted 1,2,3-triazoles (CuAAC) is a variant of Huisgen's 1,3-dipolar cycloaddition which disburdens the thermal reaction from its major drawbacks such as poor regioselectivity, long reaction times and harsh conditions. In contrast to the widely used "black box" reagent mixtures, a molecularly defined, highly active catalyst system for homogeneous CuAAC reactions has been developed in this PhD project. In dependence on the postulated stepwise mechanism, its most important structural feature is the presence of two copper(I) ions irreversibly bound in the same catalyst molecule.A highly modular and profitable synthesis for bistriazolium hexafluorophosphate salts as precursors for the ancillary ligand system was devised. In analogy to the CuAAC catalyst systems of general formula [(NHC) 2 Cu]PF 6 described in literature, novel dinuclear copper(I) complexes with a bistriazolylidene ligand backbone and 1,3-bis(2,6-diisopropylphenyl)-imidazol-2-ylidene (IPr) as sacrificial ligand were prepared.However, these complexes did not show the expected high catalytic activity, most probably due to the strong coordination of the IPr ligands. In consequence, another family of dinuclear copper(I) complexes with m-coordinated acetate as labile ligand was synthesized by reaction of the bistriazolium hexafluorophosphate ligand precursors with copper(I) acetate in the presence of a base.The broad applicability and high catalytic activity of one of these bistriazolylidene dicopper acetate complexes was confirmed by a series of gaschromatographically mo-

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Assessing the whole range of CuAAC mechanisms by DFT calculations—on the intermediacy of copper acetylides

Cited by 60 publications

References 40 publications

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

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

Highly Active Dinuclear Copper Catalysts for Homogeneous Azide–Alkyne Cycloadditions

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