Catalytic and Computational Studies of N-Heterocyclic Carbene or Phosphine-Containing Copper(I) Complexes for the Synthesis of 5-Iodo-1,2,3-Triazoles

Lal, Steven; Rzepa, Henry; Díez‐González, Silvia

doi:10.1021/cs500326e

Cited by 64 publications

(60 citation statements)

References 85 publications

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“…Among the examples in Scheme , the formation of 5‐iodo‐1,2,3‐triazole has been studied most thoroughly on both synthetic method and mechanistic fronts 10,32,61. A variety of methods for its synthesis are available, many of which start from a terminal alkyne instead of an iodoalkyne, and an electrophilic iodination agent (ICl or N ‐bromosuccinimide (NBS)/CuI) 62.…”

Section: Cuaac Reactions Involving Internal Alkynesmentioning

confidence: 99%

On the Mechanism of Copper(I)-Catalyzed Azide-Alkyne Cycloaddition

Zhu

Brassard

Zhang

et al. 2016

The Chemical Record

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The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction regiospecifically produces 1,4-disubstituted-1,2,3-triazole molecules. This heterocycle formation chemistry has high tolerance to reaction conditions and substrate structures. Therefore, it has been practiced not only within, but also far beyond the area of heterocyclic chemistry. Herein, the mechanistic understanding of CuAAC is summarized, with a particular emphasis on the significance of copper/azide interactions. Our analysis concludes that the formation of the azide/copper(I) acetylide complex in the early stage of the reaction dictates the reaction rate. The subsequent triazole ring-formation step is fast and consequently possibly kinetically invisible. Therefore, structures of substrates and copper catalysts, as well as other reaction variables that are conducive to the formation of the copper/alkyne/azide ternary complex predisposed for cycloaddition would result in highly efficient CuAAC reactions. Specifically, terminal alkynes with relatively low pKa values and an inclination to engage in π-backbonding with copper(I), azides with ancillary copper-binding ligands (aka chelating azides), and copper catalysts that resist aggregation, balance redox activity with Lewis acidity, and allow for dinuclear cooperative catalysis are favored in CuAAC reactions. Brief discussions on the mechanistic aspects of internal alkyne-involved CuAAC reactions are also included, based on the relatively limited data that are available at this point.

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Section: Cuaac Reactions Involving Internal Alkynesmentioning

confidence: 99%

On the Mechanism of Copper(I)-Catalyzed Azide-Alkyne Cycloaddition

Zhu

Brassard

Zhang

et al. 2016

The Chemical Record

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“…Several reports in the literature feature the importance of nitrogen additives in this reaction, including our own work with the related [CuI(PPh 3 ) 3 ] complex …”

Section: Resultsmentioning

confidence: 99%

“…Fokin first suggested that cleavage of the carbon–iodine bond is not required for the cycloaddition to take place . Our DFT studies supported this and showed that either formation of a copper(III) metallacycle or direct activation of the iodoalkyne by π‐coordination of the copper catalyst accounted for the copper‐acceleration effect and regioselectivity of this cycloaddition reaction …”

Section: Introductionmentioning

confidence: 99%

Copper(I)–Phosphinite Complexes in Click Cycloadditions: Three‐Component Reactions and Preparation of 5‐Iodotriazoles

et al. 2016

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The remarkable activity displayed by copper(I)–phosphinite complexes of general formula [CuBr(L)] in two challenging cycloadditions is reported: a) the one‐pot azidonation/cycloaddition of boronic acids, NaN3, and terminal alkynes; b) the cycloaddition of azides and iodoalkynes. These air‐stable catalysts led to very good results in both cases and the expected triazoles could be isolated in pure form under ‘Click‐suitable’ conditions.

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“…Among the 5‐halo‐1,2,3‐triazoles, the synthesis of 5‐chloro‐1,2,3‐triazoles ( 44 ) was the most difficult task and there are few chemoselective procedures for this purpose in literature. As shown in Scheme , this mild and convenient tandem reaction method is a valuable addition.…”

Section: Premade 1‐copper(i) Alkynes In Cycloadditionsmentioning

confidence: 99%

“…In our earlier works (see Scheme ), 1‐iodoalkyne was produced quantitatively within 10 minutes by the reaction of the premade 1‐copper(I) alkyne and NIS . Since the synthesis and storage of 1‐iodoalkyne are not convenient using the existing methods in literature, we tried to use the combination of the premade 1‐copper(I) alkyne/molecule iodine as a synthetic equivalent of 1‐iodoalkyne. As shown in Scheme , when the mixture of the premade 1‐copper(I) alkyne 1 and azide 5 was treated by molecule iodine, the corresponding 5‐iodo‐1,4,5‐trisubstiuted 1,2,3‐triazoles 54 were obtained in high yields within 15 minutes.…”

Section: Premade 1‐copper(i) Alkynes In Cycloadditionsmentioning

confidence: 99%

In‐situ Generated and Premade 1‐Copper(I) Alkynes in Cycloadditions

Wang

et al. 2017

The Chemical Record

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The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) was discovered in 2002, which has become the most remarkable example for "click chemistry" to date. In CuAAC reaction, 1-copper(I) alkyne has been recognized to be a key intermediate. However, many contradictory experimental results for this intermediate were reported in literature. For example, only the in-situ generated 1-copper(I) alkyne was used, while the premade 1-copper(I) alkyne proved to be inefficient under the standard conditions. The kinetic studies indicated that CuAAC reaction had a strict second-order dependence on Cu(I) and the DFT studies demonstrated that 1-copper(I) alkyne intermediate should be a dinuclear copper(I) complex. But these results were inconsistent with the structure of the premade 1-copper(I) alkyne. Although hundreds of structurally different ligands were reported to significantly enhance the efficiency of CuAAC reaction, their functions were assigned to prevent the oxidation and the disproportionation of Cu(I) ion. Based on the investigation of the references and our works, we proposed that the in-situ generated 1-copper(I) alkyne in CuAAC reaction is not identical with the premade 1-copper(I) alkyne. The ligands may play dual roles to activate the 1-copper(I) alkyne by blocking the polymerization of the in-situ formed 1-copper(I) alkynes and dissociating the polymeric structures of the premade 1-copper(I) alkynes. As a result, we first disclosed that carboxylic acids can function as such activators and a novel carboxylic acid-catalyzed CuAAC strategy was developed, which has been proven to be the most convenient and highly efficient CuAAC method to date. Furthermore, highly efficient and regioselective methods for the syntheses of 1,4,5-trisubstituted 1,2,3-triazoles were developed by using the premade 1-copper(I) alkynes as substrates, in which the novel function of the premade 1-copper(I) alkynes as excellent dipolarophiles was first disclosed and applied. In this article, a series of works reported by our group for the in-situ generated and the premade 1-copper(I) alkynes in cycloadditions are reviewed.

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Catalytic and Computational Studies of N-Heterocyclic Carbene or Phosphine-Containing Copper(I) Complexes for the Synthesis of 5-Iodo-1,2,3-Triazoles

Cited by 64 publications

References 85 publications

On the Mechanism of Copper(I)-Catalyzed Azide-Alkyne Cycloaddition

On the Mechanism of Copper(I)-Catalyzed Azide-Alkyne Cycloaddition

Copper(I)–Phosphinite Complexes in Click Cycloadditions: Three‐Component Reactions and Preparation of 5‐Iodotriazoles

In‐situ Generated and Premade 1‐Copper(I) Alkynes in Cycloadditions

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