Copper Catalysis for Selective Heterocoupling of Terminal Alkynes

Su, Lebin; Dong, Jianyu; Liu, Long; Sun, Mengli; Qiu, Renhua; Zhou, Yongbo; Yin, Shuang‐Feng

doi:10.1021/jacs.6b07984

Cited by 136 publications

(100 citation statements)

References 43 publications

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“…37 In that study, we discovered that oxidative coupling of terminal alkynes could be achieved using a gold catalyst under suitable conditions (Phen as ligand and bisacetoxyiodobenzene(PIDA) as oxidant). When comparing with the copper-promoted Glaser-Hay conditions, 38–41 gold catalysts gave excellent cross-coupling selectivity between aromatic alkynes and aliphatic alkynes. Besides the excellent selectivity, we also observed a much faster reaction rate with gold-catalyzed condition over the copper.…”

Section: Resultsmentioning

confidence: 99%

Gold-Catalyzed Oxidative Coupling of Alkynes toward the Synthesis of Cyclic Conjugated Diynes

Peng

Wei

et al. 2018

Chem

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A gold-catalyzed oxidative coupling of alkynes was developed as an efficient approach for the synthesis of challenging cyclic conjugated diynes (CCD). Compared to the classical copper-promoted oxidative coupling reaction of alkynes, this gold-catalyzed process exhibits a faster reaction rate due to the rapid reductive elimination from the Au(III) intermediate. This unique reactivity thus allowed a challenging diyne macrocyclization to take place in high efficiency. Condition screening revealed a [(n-Bu)4N]+[Cl-Au-Cl]− salt as the optimal pre-catalyst. Macrocycles with ring size between 13 to 28 atoms were prepared in moderate to good yields, which highlighted the broad substrate scope of this new strategy. Furthermore, the synthetic utilities of the cyclic conjugated diynes for copper-free click chemistry have been demonstrated, which showcased the potential application of this strategy in biological systems.

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Section: Resultsmentioning

confidence: 99%

Gold-Catalyzed Oxidative Coupling of Alkynes toward the Synthesis of Cyclic Conjugated Diynes

Peng

Wei

et al. 2018

Chem

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“…6‐(4‐(tert‐butyl)phenyl)‐2‐methylhexa‐3,5‐diyn‐2‐ol (5 b) : Yield: 72% (colorless solid; 56 mg, 0.213 mmol). 1 H NMR (400 MHz, CDCl 3 ) δ 7.40 (d, J =8.3 Hz, 2H), 7.32 (d, J =8.3 Hz, 2H), 1.93 (s, 1H), 1.56 (s, 6H), 1.29 (s, 9H).…”

Section: Methodsmentioning

confidence: 99%

“…2‐methyl‐6‐(4‐pentylphenyl)hexa‐3,5‐diyn‐2‐ol (5 c) : Yield: 68% (colorless solid; 52 mg, 0.204 mmol). 1 H NMR (400 MHz, CDCl 3 ) δ 7.37 (dd, J =7.9, 3.7 Hz, 2H), 7.10 (dd, J =7.6, 3.4 Hz, 2H), 2.62–2.53 (m, 2H), 1.92 (s, 1H), 1.55 (s, 8H), 1.29 (d, J =3.1 Hz, 4H), 0.91–0.81 (m, 3H).…”

Section: Methodsmentioning

confidence: 99%

Carbazole‐Based N‐Heterocyclic Carbenes for the Promotion of Copper‐Catalyzed Palladium‐Free Homo‐/Hetero‐Coupling of Alkynes and Sonogashira Reactions

et al. 2020

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Alkynes are useful synthetic building blocks that occur in many naturally occurring molecules and have the potential to be easily modified for further natural products and drug synthesis applications. Given the‐versatility of the alkyne functionality,‐various synthetic methods (mostly palladium‐based) are known in the literature, allowing the installation to take place under different reaction conditions. A single catalytic system (without Pd) however, if developed could provide a single point solution for the installation of the alkyne moiety and keeping this in mind, we report herein a highly active palladium‐free Cu/carbazole‐based NHC catalyst system allowing homocoupling and heterocoupling of alkynes at ambient temperature. Using a combination of Cu/NHC‐catalyzed homocoupling/deprotection/heterocoupling sequence tetraynes have also been synthesized in good yields. The Cu/NHC catalyst system was also able to catalyze a palladium‐free Sonogashira reaction of synthetically useful nucleosides.

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“…Along the productive route, dimer II engages two different alkynes and undergoes O 2 -mediated oxidation to yield III , the existence of which has been verified in analogous systems. [47–51] Indeed, preventing the formation of a high-oxidation intermediate such as III by adding an excess of sodium ascorbate shuts down the reaction completely, Figure 3B; entry 2. Bimetallic reduction of III produces the desired 1,3-diyne and regenerates CuCl/bpy-diol I , thereby completing the catalytic cycle.…”

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confidence: 99%

Adapting the Glaser Reaction for Bioconjugation: Robust Access to Structurally Simple, Rigid Linkers

2017

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The copper-mediated coupling between alkynes to generate a structurally rigid, linear 1,3-diyne linkage has been known for over a century. However, the mechanistic requirement to simultaneously maintain Cu(I) and an oxidant has limited its practical utility, especially for complex functional molecules in aqueous solution. We find that addition of a specific bpy-diol ligand protects unprotected peptides from Cu(II) mediated oxidative damage through formation of an insoluble Cu(II) gel which solves the critical challenge of applying the Glaser coupling to substrates that are degraded by Cu(II). The generality of this method is illustrated through conjugation of a series of polar and nonpolar labels onto a fully unprotected GLP-1R agonist through a linear 7 Å diynyl linker.

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Copper Catalysis for Selective Heterocoupling of Terminal Alkynes

Cited by 136 publications

References 43 publications

Gold-Catalyzed Oxidative Coupling of Alkynes toward the Synthesis of Cyclic Conjugated Diynes

Gold-Catalyzed Oxidative Coupling of Alkynes toward the Synthesis of Cyclic Conjugated Diynes

Carbazole‐Based N‐Heterocyclic Carbenes for the Promotion of Copper‐Catalyzed Palladium‐Free Homo‐/Hetero‐Coupling of Alkynes and Sonogashira Reactions

Adapting the Glaser Reaction for Bioconjugation: Robust Access to Structurally Simple, Rigid Linkers

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