ACS Publications. Most Trusted. Most Cited. Most Read
My Activity

Figure 1Loading Img

Experimental Investigation on the Mechanism of Chelation-Assisted, Copper(II) Acetate-Accelerated Azide–Alkyne Cycloaddition

View Author Information
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32306-4390, United States
Cite this: J. Am. Chem. Soc. 2011, 133, 35, 13984–14001
Publication Date (Web):August 1, 2011
Copyright © 2011 American Chemical Society

    Article Views





    Read OnlinePDF (6 MB)
    Supporting Info (7)»


    Abstract Image

    A mechanistic model is formulated to account for the high reactivity of chelating azides (organic azides capable of chelation-assisted metal coordination at the alkylated azido nitrogen position) and copper(II) acetate (Cu(OAc)2) in copper(II)-mediated azide–alkyne cycloaddition (AAC) reactions. Fluorescence and 1H NMR assays are developed for monitoring the reaction progress in two different solvents, methanol and acetonitrile. Solvent kinetic isotopic effect and premixing experiments give credence to the proposed different induction reactions for converting copper(II) to catalytic copper(I) species in methanol (methanol oxidation) and acetonitrile (alkyne oxidative homocoupling), respectively. The kinetic orders of individual components in a chelation-assisted, copper(II)-accelerated AAC reaction are determined in both methanol and acetonitrile. Key conclusions resulting from the kinetic studies include (1) the interaction between copper ion (either in +1 or +2 oxidation state) and a chelating azide occurs in a fast, pre-equilibrium step prior to the formation of the in-cycle copper(I)-acetylide, (2) alkyne deprotonation is involved in several kinetically significant steps, and (3) consistent with prior experimental and computational results by other groups, two copper centers are involved in the catalysis. The X-ray crystal structures of chelating azides with Cu(OAc)2 suggest a mechanistic synergy between alkyne oxidative homocoupling and copper(II)-accelerated AAC reactions, in which both a bimetallic catalytic pathway and a base are involved. The different roles of the two copper centers (a Lewis acid to enhance the electrophilicity of the azido group and a two-electron reducing agent in oxidative metallacycle formation, respectively) in the proposed catalytic cycle suggest that a mixed valency (+2 and +1) dinuclear copper species be a highly efficient catalyst. This proposition is supported by the higher activity of the partially reduced Cu(OAc)2 in mediating a 2-picolylazide-involved AAC reaction than the fully reduced Cu(OAc)2. Finally, the discontinuous kinetic behavior that has been observed by us and others in copper(I/II)-mediated AAC reactions is explained by the likely catalyst disintegration during the course of a relatively slow reaction. Complementing the prior mechanistic conclusions drawn by other investigators, which primarily focus on the copper(I)/alkyne interactions, we emphasize the kinetic significance of copper(I/II)/azide interaction. This work not only provides a mechanism accounting for the fast Cu(OAc)2-mediated AAC reactions involving chelating azides, which has apparent practical implications, but suggests the significance of mixed-valency dinuclear copper species in catalytic reactions where two copper centers carry different functions.

    Supporting Information

    Jump To

    Experimental procedures, characterization of new compounds, and additional figures. This material is available free of charge via the Internet at

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system:

    Cited By

    This article is cited by 152 publications.

    1. Wystan K. O. Teixeira, Danilo Yano de Albuquerque, Julio Zukerman-Schpector, Diego Seckler, Daniel S. Rampon, Ricardo S. Schwab. Copper-Mediated Intramolecular Interrupted CuAAC Selanylation. The Journal of Organic Chemistry 2023, 88 (15) , 10434-10447.
    2. Sergio Alcalde, Raúl Porcar, María Luz De La Puente, Graham R. Cumming, Carlos Mateos, Pablo García-Losada, Cristina Anta, Juan A. Rincón, Eduardo García-Verdugo. Continuous-Flow Supercritical CO2 Platform for In-Situ Synthesis and Purification of Small Molecules for Drug Discovery. Organic Process Research & Development 2023, 27 (2) , 276-285.
    3. Miguel González-Lainez, Miguel Gallegos, Julen Munarriz, Ramón Azpiroz, Vincenzo Passarelli, M. Victoria Jiménez, Jesús J. Pérez-Torrente. Copper-Catalyzed Azide–Alkyne Cycloaddition (CuAAC) by Functionalized NHC-Based Polynuclear Catalysts: Scope and Mechanistic Insights. Organometallics 2022, 41 (15) , 2154-2169.
    4. Julie Héron, David Balcells. Concerted Cycloaddition Mechanism in the CuAAC Reaction Catalyzed by 1,8-Naphthyridine Dicopper Complexes. ACS Catalysis 2022, 12 (8) , 4744-4753.
    5. Ravuri Srinath, Arindam Manna, Subhankar Shee, Vijay Babu Pathi, Saswati Ghosh, Krishnendu Khamaru, Nakul Chandra Maiti, Biswadip Banerji. Synthesis of N-Fused Triazole–Piperazine–Quinazolinones via One-Pot Tandem Click Reaction and Cross-Dehydrogenative Coupling. Organic Letters 2021, 23 (24) , 9365-9370.
    6. Lucy L. Fillbrook, Jan-Philipp Günther, Günter Majer, Daniel J. O’Leary, William S. Price, Hal Van Ryswyk, Peer Fischer, Jonathon E. Beves. Following Molecular Mobility during Chemical Reactions: No Evidence for Active Propulsion. Journal of the American Chemical Society 2021, 143 (49) , 20884-20890.
    7. Jasleen Kaur, Mokshika Saxena, Narayan Rishi. An Overview of Recent Advances in Biomedical Applications of Click Chemistry. Bioconjugate Chemistry 2021, 32 (8) , 1455-1471.
    8. Svitlana O. Sotnik, Andrii I. Subota, Anton Y. Kliuchynskyi, Dmytro V. Yehorov, Anton S. Lytvynenko, Alexander B. Rozhenko, Sergey V. Kolotilov, Sergey V. Ryabukhin, Dmitriy M. Volochnyuk. Cu-Catalyzed Pyridine Synthesis via Oxidative Annulation of Cyclic Ketones with Propargylamine. The Journal of Organic Chemistry 2021, 86 (11) , 7315-7325.
    9. Yolanda Navarro, Jesús García López, María José Iglesias, Fernando López Ortiz. Chelation-Assisted Interrupted Copper(I)-Catalyzed Azide–Alkyne–Azide Domino Reactions: Synthesis of Fully Substituted 5-Triazenyl-1,2,3-triazoles. Organic Letters 2021, 23 (2) , 334-339.
    10. Dasharath Kondhare, Aigui Zhang, Peter Leonard, Frank Seela. Alkynylated and Dendronized 5-Aza-7-deazaguanine Nucleosides: Cross-Coupling with Tripropargylamine and Linear Alkynes, Click Functionalization, and Fluorescence of Pyrene Adducts. The Journal of Organic Chemistry 2020, 85 (16) , 10525-10538.
    11. Chandrakanta Dash, Guocang Wang, Alvaro Muñoz-Castro, Tharun T. Ponduru, Adway O. Zacharias, Muhammed Yousufuddin, H. V. Rasika Dias. Organic Azide and Auxiliary-Ligand-Free Complexes of Coinage Metals Supported by N-Heterocyclic Carbenes. Inorganic Chemistry 2020, 59 (4) , 2188-2199.
    12. Yun-Peng Xie, Jun-Bo Wen, Chang-Wang Pan, Guang-Xiong Duan, Lan-Yun Li, Xing Lu. Assembly of Cu(I) Alkynyl Complexes: From Cluster to Infinite Cluster-Based Framework. Crystal Growth & Design 2019, 19 (10) , 5791-5797.
    13. Nozomu Inoue, Akira Onoda, Takashi Hayashi. Site-Specific Modification of Proteins through N-Terminal Azide Labeling and a Chelation-Assisted CuAAC Reaction. Bioconjugate Chemistry 2019, 30 (9) , 2427-2434.
    14. Marius M. Haugland, Stefan Borsley, Dominic F. Cairns-Gibson, Alex Elmi, Scott L. Cockroft. Synthetically Diversified Protein Nanopores: Resolving Click Reaction Mechanisms. ACS Nano 2019, 13 (4) , 4101-4110.
    15. Rooholah Roohzadeh, Bahare Nasiri, Antony Chipman, Brian F. Yates, Alireza Ariafard. Disclosure of Some Obscure Mechanistic Aspects of the Copper-Catalyzed Click Reactions Involving N2 Elimination Promoted by the Use of Electron-Deficient Azides from a DFT Perspective. Organometallics 2019, 38 (2) , 256-267.
    16. Sivaraj Ramasamy, Chittibabu Petha, Shankar Tendulkar, Prantik Maity, Martin D. Eastgate, Rajappa Vaidyanathan. Synergistic Effect of Copper and Ruthenium on Regioselectivity in the Alkyne–Azide Click Reaction of Internal Alkynes. Organic Process Research & Development 2018, 22 (7) , 880-887.
    17. Victor R. Mann, Alexander S. Powers, Drew C. Tilley, Jon T. Sack, Bruce E. Cohen. Azide–Alkyne Click Conjugation on Quantum Dots by Selective Copper Coordination. ACS Nano 2018, 12 (5) , 4469-4477.
    18. Marine Z. C. Hatit, Ciaran P. Seath, Allan J. B. Watson, and Glenn A. Burley . Strategy for Conditional Orthogonal Sequential CuAAC Reactions Using a Protected Aromatic Ynamine. The Journal of Organic Chemistry 2017, 82 (10) , 5461-5468.
    19. Micah S. Ziegler, K. V. Lakshmi, and T. Don Tilley . Dicopper Cu(I)Cu(I) and Cu(I)Cu(II) Complexes in Copper-Catalyzed Azide–Alkyne Cycloaddition. Journal of the American Chemical Society 2017, 139 (15) , 5378-5386.
    20. Christopher J. Brassard, Xiaoguang Zhang, Christopher R. Brewer, Peiye Liu, Ronald J. Clark, and Lei Zhu . Cu(II)-Catalyzed Oxidative Formation of 5,5′-Bistriazoles. The Journal of Organic Chemistry 2016, 81 (24) , 12091-12105.
    21. Marine Z. C. Hatit, Joanna C. Sadler, Liam A. McLean, Benjamin C. Whitehurst, Ciaran P. Seath, Luke D. Humphreys, Robert J. Young, Allan J. B. Watson, and Glenn A. Burley . Chemoselective Sequential Click Ligations Directed by Enhanced Reactivity of an Aromatic Ynamine. Organic Letters 2016, 18 (7) , 1694-1697.
    22. Li-Min Zhang and Thomas C. W. Mak . Comproportionation Synthesis of Copper(I) Alkynyl Complexes Encapsulating Polyoxomolybdate Templates: Bowl-Shaped Cu33 and Peanut-Shaped Cu62 Nanoclusters. Journal of the American Chemical Society 2016, 138 (9) , 2909-2912.
    23. Sayantani Saha, Mandeep Kaur, and Jitendra K. Bera . Fluorinated Anions Promoted “on Water” Activity of Di- and Tetranuclear Copper(I) Catalysts for Functional Triazole Synthesis. Organometallics 2015, 34 (12) , 3047-3054.
    24. Takayuki Nakane, Yuta Tanioka, and Naofumi Tsukada . Synthesis of Multinuclear Copper Complexes Bridged by Diquinolylamidinates and Their Application to Copper-Catalyzed Coupling of Terminal Alkynes and Aryl, Allyl, and Benzyl Halides. Organometallics 2015, 34 (7) , 1191-1196.
    25. Stefano Santoro, Rong-Zhen Liao, Tommaso Marcelli, Peter Hammar, and Fahmi Himo . Theoretical Study of Mechanism and Stereoselectivity of Catalytic Kinugasa Reaction. The Journal of Organic Chemistry 2015, 80 (5) , 2649-2660.
    26. Saturnino Calvo-Losada, María Soledad Pino-González, and José Joaquín Quirante . Rationalizing the Catalytic Activity of Copper in the Cycloaddition of Azide and Alkynes (CuAAC) with the Topology of ∇2ρ(r) and ∇∇2ρ(r). The Journal of Physical Chemistry B 2015, 119 (4) , 1243-1258.
    27. Asif Noor, Gregory S. Huff, Sreedhar V. Kumar, James E. M. Lewis, Brett M. Paterson, Christine Schieber, Paul S. Donnelly, Heather J. L. Brooks, Keith C. Gordon, Stephen C. Moratti, and James D. Crowley . [Re(CO)3]+ Complexes of exo-Functionalized Tridentate “Click” Macrocycles: Synthesis, Stability, Photophysical Properties, Bioconjugation, and Antibacterial Activity. Organometallics 2014, 33 (24) , 7031-7043.
    28. Timothy U. Connell, Christine Schieber, Ilaria Proietti Silvestri, Jonathan M. White, Spencer J. Williams, and Paul S. Donnelly . Copper and Silver Complexes of Tris(triazole)amine and Tris(benzimidazole)amine Ligands: Evidence that Catalysis of an Azide–Alkyne Cycloaddition (“Click”) Reaction by a Silver Tris(triazole)amine Complex Arises from Copper Impurities. Inorganic Chemistry 2014, 53 (13) , 6503-6511.
    29. Hao Jiang, Tianqing Zheng, Aime Lopez-Aguilar, Lei Feng, Felix Kopp, Florence L. Marlow, and Peng Wu . Monitoring Dynamic Glycosylation in Vivo Using Supersensitive Click Chemistry. Bioconjugate Chemistry 2014, 25 (4) , 698-706.
    30. David M. Patterson, Lidia A. Nazarova, and Jennifer A. Prescher . Finding the Right (Bioorthogonal) Chemistry. ACS Chemical Biology 2014, 9 (3) , 592-605.
    31. Sae Hume Park, Jaesung Kwak, Kwangmin Shin, Jaeyune Ryu, Yoonsu Park, and Sukbok Chang . Mechanistic Studies of the Rhodium-Catalyzed Direct C–H Amination Reaction Using Azides as the Nitrogen Source. Journal of the American Chemical Society 2014, 136 (6) , 2492-2502.
    32. Suresh S. Pujari and Frank Seela . Parallel Stranded DNA Stabilized with Internal Sugar Cross-Links: Synthesis and Click Ligation of Oligonucleotides Containing 2′-Propargylated Isoguanosine. The Journal of Organic Chemistry 2013, 78 (17) , 8545-8561.
    33. Feng Zhou, Chen Tan, Jing Tang, Yan-Yan Zhang, Wei-Ming Gao, Hai-Hong Wu, Yi-Hua Yu, and Jian Zhou . Asymmetric Copper(I)-Catalyzed Azide–Alkyne Cycloaddition to Quaternary Oxindoles. Journal of the American Chemical Society 2013, 135 (30) , 10994-10997.
    34. Matthew A. Pellow, T. Daniel P. Stack, and Christopher E. D. Chidsey . Squish and CuAAC: Additive-Free Covalent Monolayers of Discrete Molecules in Seconds. Langmuir 2013, 29 (18) , 5383-5387.
    35. Balazs Pinter, Damijana Urankar, Andrej Pevec, Frank De Proft, and Janez Košmrlj . Platinum-Mediated Dinitrogen Liberation from 2-Picolyl Azide through a Putative Pt═N Double Bond Containing Intermediate. Inorganic Chemistry 2013, 52 (8) , 4528-4533.
    36. Sachin A. Ingale and Frank Seela . Stepwise Click Functionalization of DNA through a Bifunctional Azide with a Chelating and a Nonchelating Azido Group. The Journal of Organic Chemistry 2013, 78 (7) , 3394-3399.
    37. Christopher B. Anderson, Anastasia B. S. Elliott, C. John McAdam, Keith C. Gordon, and James D. Crowley . fac-Re(CO)3Cl Complexes of [2-(4-R-1H-1,2,3-Triazol-1-yl)methyl]pyridine Inverse “Click” Ligands: A Systematic Synthetic, Spectroscopic, and Computational Study. Organometallics 2013, 32 (3) , 788-797.
    38. Amanda E. King, Bradford L. Ryland, Thomas C. Brunold, and Shannon S. Stahl . Kinetic and Spectroscopic Studies of Aerobic Copper(II)-Catalyzed Methoxylation of Arylboronic Esters and Insights into Aryl Transmetalation to Copper(II). Organometallics 2012, 31 (22) , 7948-7957.
    39. Wendy S. Brotherton, Ronald J. Clark, and Lei Zhu . Synthesis of 5-Iodo-1,4-disubstituted-1,2,3-triazoles Mediated by in Situ Generated Copper(I) Catalyst and Electrophilic Triiodide Ion. The Journal of Organic Chemistry 2012, 77 (15) , 6443-6455.
    40. Zhao Yuan, Gui-Chao Kuang, Ronald J. Clark, and Lei Zhu . Chemoselective Sequential “Click” Ligation Using Unsymmetrical Bisazides. Organic Letters 2012, 14 (10) , 2590-2593.
    41. Pampa M. Guha, Hoa Phan, Jared S. Kinyon, Wendy S. Brotherton, Kesavapillai Sreenath, J. Tyler Simmons, Zhenxing Wang, Ronald J. Clark, Naresh S. Dalal, Michael Shatruk, and Lei Zhu . Structurally Diverse Copper(II) Complexes of Polyaza Ligands Containing 1,2,3-Triazoles: Site Selectivity and Magnetic Properties. Inorganic Chemistry 2012, 51 (6) , 3465-3477.
    42. Niko Fischer, Ethan D. Goddard-Borger, Robert Greiner, Thomas M. Klapötke, Brian W. Skelton, and Jörg Stierstorfer . Sensitivities of Some Imidazole-1-sulfonyl Azide Salts. The Journal of Organic Chemistry 2012, 77 (4) , 1760-1764.
    43. Daniel J. Stone, Miguel Macias-Contreras, Shaun M. Crist, Christelle F. T. Bucag, Gwimoon Seo, Lei Zhu. SNAP-tagging live cells via chelation-assisted copper-catalyzed azide–alkyne cycloaddition. Organic & Biomolecular Chemistry 2023, 21 (36) , 7419-7436.
    44. Perla Islas-Jácome, Cecilia García-Falcón, Sandra L. Castañón-Alonso, Ernesto Calderón-Jaimes, Daniel Canseco-González, Alejandro Islas-Jácome, Eduardo González-Zamora. 2-Benzyl-7-(4-chlorophenyl)-3-morpholino-6-((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one. Molbank 2023, 2023 (3) , M1693.
    45. Kavita Singh, Rajdeep Tyagi, Vinay Kumar Mishra, Ghanshyam Tiwari, Ram Sagar. Recent Advances in the Synthesis of Bioactive Glycohybrids via Click-Chemistry. SynOpen 2023, 07 (03) , 322-352.
    46. Shanmugam Revathi, Tapas Ghatak. N‐Heterocyclic Imine‐Supported Bimetallic Cu(II) Catalyst for Azide‐Alkyne Cycloaddition: Solvent‐free, Reductant‐free, ppm‐level Catalysis to Access 1,4‐Disubstituted Triazoles. Chemistry – An Asian Journal 2023, 18 (10)
    47. Lingyu Li, Jingrong Li, Liyan Ma, Hai Shang, Zhongmei Zou. SAR-guided development of indole-matrine hybrids as potential anticancer agents via mitochondrial stress/cytochrome c/caspase 3 signaling pathway. Bioorganic Chemistry 2023, 134 , 106341.
    48. Chunwei Dong, Saidkhodzha Nematulloev, Peng Yuan, Osman M. Bakr. Atomically Precise Copper Nanoclusters. 2023, 257-283.
    49. Subramaniyam Kalaivanan, Ganesan Prabusankar. Highly Active Cu(II) Diimine Catalyzed Click Reactions: A Mild Yet Fast Approach to Carbazole Substituted 1,2,3-Triazoles. Catalysis Letters 2023, 153 (1) , 167-177.
    50. Daniela I. Bezuidenhout, George Kleinhans, Aino J. Karhu. Nonclassical carbenes as noninnocent ligands. 2023, 234-314.
    51. Fabian Schlimpen, Tun Ast, Valérie Bénéteau, Patrick Pale, Stefan Chassaing. From A 3 /KA 2 to AYA/KYA multicomponent coupling reactions with terminal ynamides as alkyne surrogates – a direct, green route to γ-amino-ynamides. Green Chemistry 2022, 24 (17) , 6467-6475.
    52. Qi Peng, Dejian Hou, Yanwu Chen, Litian Lin, Seyed Mohsen Sadeghzadeh. Cu(II)-Based Ionic Liquid Supported on SBA-15 Nanoparticles Catalyst for the Oxidation of Various Alcohols into Carboxylic Acids in the Presence of CO2. Catalysis Letters 2022, 152 (5) , 1308-1320.
    53. Grysette Daher, Gustavo Seoane. Readily accessible azido-alkyne-functionalized monomers for the synthesis of cyclodextrin analogues using click chemistry. Organic & Biomolecular Chemistry 2022, 20 (8) , 1690-1698.
    54. Ali Oubella, Abdoullah Bimoussa, Abdellah N’ait Oussidi, Mourad Fawzi, Aziz Auhmani, Hamid Morjani, Abdelkhalek Riahi, M’hamed Esseffar, Carol Parish, Moulay Youssef Ait Itto. New 1,2,3-Triazoles from (R)-Carvone: Synthesis, DFT Mechanistic Study and In Vitro Cytotoxic Evaluation. Molecules 2022, 27 (3) , 769.
    55. Akinobu Matsuzawa, Jeremy N. Harvey, Fahmi Himo. On the Importance of Considering Multinuclear Metal Sites in Homogeneous Catalysis Modeling. Topics in Catalysis 2022, 65 (1-4) , 96-104.
    56. Yun-Dong Cao, Hui-Ping Hao, Hua-Shi Liu, Di Yin, Ming-Liang Wang, Guang-Gang Gao, Lin-Lin Fan, Hong Liu. A 20-core copper( i ) nanocluster as electron–hole recombination inhibitor on TiO 2 nanosheets for enhancing photocatalytic H 2 evolution. Nanoscale 2021, 13 (38) , 16182-16188.
    57. Lahoucine Bahsis, El‐Houssaine Ablouh, Mouhi Eddine Hachim, Hafid Anane, Moha Taourirte, Miguel Julve, Salah‐Eddine Stiriba. Copper(I)‐chitin biopolymer based: An efficient and recyclable catalyst for click azide–alkyne cycloaddition reactions in water. Applied Organometallic Chemistry 2021, 35 (8)
    58. Aicha Talha, Asmae Mourhly, Hamza Tachallait, Mohsine Driowya, Adnane El Hamidi, Suhana Arshad, Khalid Karrouchi, Said Arsalane, Khalid Bougrin. One-pot four-component tandem synthesis of novel sulfonamide-1, 2, 3-triazoles catalyzed by reusable copper (II)-adsorbed on mesoporous silica under ultrasound irradiation. Tetrahedron 2021, 90 , 132215.
    59. Miguel Macias‐Contreras, Lei Zhu. The Collective Power of Genetically Encoded Protein/Peptide Tags and Bioorthogonal Chemistry in Biological Fluorescence Imaging. ChemPhotoChem 2021, 5 (3) , 187-216.
    60. Chengyang Yin, Shuang Liu, Zhaoxian Qin, Yifei Zhang, Gao Li, Zhen Zhao. Butterfly‐Like Tetranuclear Copper(I) Clusters for Efficient Alkyne Homocoupling Reactions. European Journal of Inorganic Chemistry 2021, 2021 (4) , 392-397.
    61. Ana Karina Seguin, Kerry Wrighton-Araneda, Diego Cortés-Arriagada, Carlos Cruz, Diego Venegas-Yazigi, Verónica Paredes-García. A new CuII-dinuclear paddlewheel complex. Structural and electronic properties. Journal of Molecular Structure 2021, 1224 , 129172.
    62. Zhiying Fan, Zheng Wang, Mirza Cokoja, Roland A. Fischer. Defect engineering: an effective tool for enhancing the catalytic performance of copper-MOFs for the click reaction and the A 3 coupling. Catalysis Science & Technology 2021, 48
    63. Jiahao Ma, Shengtao Ding. Transition Metal‐Catalyzed Cycloaddition of Azides with Internal Alkynes. Asian Journal of Organic Chemistry 2020, 9 (12) , 1872-1888.
    64. Abdallah Mahmoud, Piotr Smoleński, M. Guedes da Silva, Armando Pombeiro. Water-Soluble O-, S- and Se-Functionalized Cyclic Acetyl-triaza-phosphines. Synthesis, Characterization and Application in Catalytic Azide-alkyne Cycloaddition. Molecules 2020, 25 (22) , 5479.
    65. Vladimir A. Larionov, Anna R. Stashneva, Aleksei A. Titov, Alexey A. Lisov, Michael G. Medvedev, Alexander F. Smol'yakov, Andrey M. Tsedilin, Elena S. Shubina, Victor I. Maleev. Mechanistic study in azide-alkyne cycloaddition (CuAAC) catalyzed by bifunctional trinuclear copper(I) pyrazolate complex: Shift in rate-determining step. Journal of Catalysis 2020, 390 , 37-45.
    66. Lahoucine Bahsis, El-Houssaine Ablouh, Hafid Anane, Moha Taourirte, Miguel Julve, Salah-Eddine Stiriba. Cu( ii )-alginate-based superporous hydrogel catalyst for click chemistry azide–alkyne cycloaddition type reactions in water. RSC Advances 2020, 10 (54) , 32821-32832.
    67. Ananya Anubhav Saikia, R. Nishanth Rao, Soumyadip Das, Sushovan Jena, Sourav Rej, Barnali Maiti, Kaushik Chanda. Sequencing [3+2]-cycloaddition and multicomponent reactions: A regioselective microwave-assisted synthesis of 1,4-disubstituted 1,2,3-triazoles using ionic liquid supported Cu(II) precatalysts in methanol. Tetrahedron Letters 2020, 61 (36) , 152273.
    68. Youshan Li, Hua Fu. Bioorthogonal Ligations and Cleavages in Chemical Biology. ChemistryOpen 2020, 9 (8) , 835-853.
    69. Kaliyan Prabakaran, Selvaraj Loganathan, Muthu Seenivasa Perumal, Savarimuthu Philip Anthony. Synthesizing Bis(β‐iminoenolate)copper(II) Complexes and Exploring Substitution Dependent Green Catalytic Application for Azide‐Alkyne Cycloaddition Reaction. ChemistrySelect 2020, 5 (28) , 8773-8778.
    70. Natalija Pantalon Juraj, Marko Krklec, Tiana Novosel, Berislav Perić, Robert Vianello, Silvana Raić-Malić, Srećko I. Kirin. Copper( ii ) and zinc( ii ) complexes of mono- and bis-1,2,3-triazole-substituted heterocyclic ligands. Dalton Transactions 2020, 49 (26) , 9002-9015.
    71. Suyan Qiu, Yihua Wei, Tianhua Tu, Jianjun Xiang, Dawen Zhang, Qinglong Chen, Linguang Luo, Zhenyu Lin. Triazole-stabilized fluorescence sensor for highly selective detection of copper in tea and animal feed. Food Chemistry 2020, 317 , 126434.
    72. Kun Liu, Prince Kumar Lat, Hua-Zhong Yu, Dipankar Sen. CLICK-17, a DNA enzyme that harnesses ultra-low concentrations of either Cu+ or Cu2+ to catalyze the azide-alkyne ‘click’ reaction in water. Nucleic Acids Research 2020, 114
    73. Anna Canela-Xandri, Mercè Balcells, Gemma Villorbina, Paul Christou, Ramon Canela-Garayoa. Preparation and Uses of Chlorinated Glycerol Derivatives. Molecules 2020, 25 (11) , 2511.
    74. Victor Flon, Magalie Bénard, Damien Schapman, Ludovic Galas, Pierre-Yves Renard, Cyrille Sabot. Fluorophore-Assisted Click Chemistry through Copper(I) Complexation. Biomolecules 2020, 10 (4) , 619.
    75. Baixue Li, Rong Hu, Anjun Qin, Ben Zhong Tang. Copper-based ionic liquid-catalyzed click polymerization of diazides and diynes toward functional polytriazoles for sensing applications. Polymer Chemistry 2020, 11 (12) , 2006-2014.
    76. Peiye Liu, Christopher J. Brassard, Justin P. Lee, Lei Zhu. Cu II ‐Catalyzed Oxidative Formation of 5‐Alkynyltriazoles. Chemistry – An Asian Journal 2020, 15 (3) , 380-390.
    77. Leon Li-Min Zhang, Guodong Zhou, Guoqing Zhou, Hung-Kay Lee, Ni Zhao, Oleg V. Prezhdo, Thomas C. W. Mak. Core-dependent properties of copper nanoclusters: valence-pure nanoclusters as NIR TADF emitters and mixed-valence ones as semiconductors. Chemical Science 2019, 10 (43) , 10122-10128.
    78. Roberto S. Gomes, Guilherme A.M. Jardim, Renato L. de Carvalho, Maria H. Araujo, Eufrânio N. da Silva Júnior. Beyond copper-catalyzed azide-alkyne 1,3-dipolar cycloaddition: Synthesis and mechanism insights. Tetrahedron 2019, 75 (27) , 3697-3712.
    79. Julia Beerhues, Kevin Fauché, Federico Cisnetti, Biprajit Sarkar, Arnaud Gautier. A dicopper( i )-dimesoionic carbene complex as a click catalyst: mechanistic implications. Dalton Transactions 2019, 48 (24) , 8931-8936.
    80. Abdallah G. Mahmoud, M. Fátima C. Guedes da Silva, Kamran T. Mahmudov, Armando J. L. Pombeiro. Arylhydrazone ligands as Cu-protectors and -catalysis promoters in the azide–alkyne cycloaddition reaction. Dalton Transactions 2019, 48 (5) , 1774-1785.
    81. Rohit Singh Chauhan, Dhvani Oza, Seema Yadav, Chandrakanta Dash, Alexandra M. Z. Slawin, Neelam Shivran. Copper complexes of arylselenolate-based ligands: synthesis and catalytic activity in azide–alkyne cycloaddition reactions. New Journal of Chemistry 2019, 43 (5) , 2381-2388.
    82. Mohamed M. El-bendary, Tamer S. Saleh, Abdullah S. Al-Bogami. Ultrasound Assisted High-Throughput Synthesis of 1,2,3-Triazoles Libraries: A New Strategy for “Click” Copper-Catalyzed Azide-Alkyne Cycloaddition Using Copper(I/II) as a Catalyst. Catalysis Letters 2018, 148 (12) , 3797-3810.
    83. Floyd C. D. Andrade, Lucas V. B. L. Pugnal, Hugo L. I. Betim, Jéssica F. Vani, Julio Zukerman‐Schpector, Ricardo S. Schwab. A Straightforward Sequential Approach for the Enantioselective Synthesis of Optically Active α‐Arylmethanol‐1,2,3‐Triazoles. European Journal of Organic Chemistry 2018, 2018 (40) , 5467-5476.
    84. Die Huang, AnJun Qin, Ben Zhong Tang. Transition Metal-catalyzed Click Polymerization. 2018, 36-85.
    85. Haoqing Chen, Chirine Soubra-Ghaoui, Zhiling Zhu, Siheng Li, Thomas A. Albright, Chengzhi Cai. Isolation of an acetylide-CuI3-tris(triazolylmethyl)amine complex active in the CuAAC reaction. Journal of Catalysis 2018, 361 , 407-413.
    86. Smriti Srivastava, Devla Bimal, Kapil Bohra, Balram Singh, Prija Ponnan, Ruchi Jain, Mandira Varma-Basil, Jyotirmoy Maity, M. Thirumal, Ashok K. Prasad. Synthesis and antimycobacterial activity of 1-(β-d-Ribofuranosyl)-4-coumarinyloxymethyl- / -coumarinyl-1,2,3-triazole. European Journal of Medicinal Chemistry 2018, 150 , 268-281.
    87. Nan Sun, Zhongqi Yu, Hong Yi, Xiayue Zhu, Liqun Jin, Baoxiang Hu, Zhenlu Shen, Xinquan Hu. Synthesis of a heterogeneous Cu(OAc) 2 -anchored SBA-15 catalyst and its application in the CuAAC reaction. New Journal of Chemistry 2018, 42 (3) , 1612-1616.
    88. Leon Li‐Min Zhang, Thomas C. W. Mak. Temperature‐Mediated Template Release: Facile Growth of Copper(I) Mixed Ethynediide/Isopropylethynide Nanoclusters. Angewandte Chemie 2017, 129 (51) , 16446-16450.
    89. Leon Li‐Min Zhang, Thomas C. W. Mak. Temperature‐Mediated Template Release: Facile Growth of Copper(I) Mixed Ethynediide/Isopropylethynide Nanoclusters. Angewandte Chemie International Edition 2017, 56 (51) , 16228-16232.
    90. Haoqing Chen, Chengzhi Cai, Siheng Li, Yong Ma, Sijin Luozhong, Zhiling Zhu. Intermediates Stabilized by Tris(triazolylmethyl)amines in the CuAAC Reaction. Chemistry – A European Journal 2017, 23 (19) , 4730-4735.
    91. Ciaran P. Seath, Glenn A. Burley, Allan J. B. Watson. Determining the Origin of Rate-Independent Chemoselectivity in CuAAC Reactions: An Alkyne-Specific Shift in Rate-Determining Step. Angewandte Chemie 2017, 129 (12) , 3362-3366.
    92. Ciaran P. Seath, Glenn A. Burley, Allan J. B. Watson. Determining the Origin of Rate-Independent Chemoselectivity in CuAAC Reactions: An Alkyne-Specific Shift in Rate-Determining Step. Angewandte Chemie International Edition 2017, 56 (12) , 3314-3318.
    93. Gavin M. Mitchell, Amelia Hesketh, Christie Lombardi, Cally Ho, Thomas M. Fyles. A membrane-spanning macrocyclic bolaamphiphile lipid mimic of archaeal lipids. Canadian Journal of Chemistry 2017, 95 (3) , 253-262.
    94. Cihan Özen, Nurcan Şenyurt Tüzün. Mechanism of CuAAC reaction: In acetic acid and aprotic conditions. Journal of Molecular Catalysis A: Chemical 2017, 426 , 150-157.
    95. Nader Noshiranzadeh, Marzieh Emami, Rahman Bikas, Anna Kozakiewicz. Green click synthesis of β-hydroxy-1,2,3-triazoles in water in the presence of a Cu( ii )–azide catalyst: a new function for Cu( ii )–azide complexes. New Journal of Chemistry 2017, 41 (7) , 2658-2667.
    96. Andrijana Meščić, Anita Šalić, Tomislav Gregorić, Bruno Zelić, Silvana Raić-Malić. Continuous flow-ultrasonic synergy in click reactions for the synthesis of novel 1,2,3-triazolyl appended 4,5-unsaturated l -ascorbic acid derivatives. RSC Advances 2017, 7 (2) , 791-800.
    97. Hong Yan Zou, Ming Xuan Gao, Tong Yang, Qiao Ling Zeng, Xiao Xi Yang, Feng Liu, Mark T. Swihart, Na Li, Cheng Zhi Huang. Nonstoichiometric copper chalcogenides for photo-activated alkyne/azide cycloaddition. Physical Chemistry Chemical Physics 2017, 19 (10) , 6964-6968.
    98. Fen Xu, Wei-Fen Kang, Xiao-Ning Wang, Hao-Dong Kou, Zhen Jin, Chun-Sen Liu. Synergic effect of copper-based metal–organic frameworks for highly efficient C–H activation of amidines. RSC Advances 2017, 7 (81) , 51658-51662.
    99. Claudio Iacobucci, Alexandre Lebon, Francesco De Angelis, Antony Memboeuf. CuAAC Click Reactions in the Gas Phase: Unveiling the Reactivity of Bis-Copper Intermediates. Chemistry - A European Journal 2016, 22 (52) , 18690-18694.
    100. Xiaoguang Zhang, Peiye Liu, Lei Zhu. Structural Determinants of Alkyne Reactivity in Copper-Catalyzed Azide-Alkyne Cycloadditions. Molecules 2016, 21 (12) , 1697.
    Load all citations

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    You’ve supercharged your research process with ACS and Mendeley!

    STEP 1:
    Click to create an ACS ID

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Your Mendeley pairing has expired. Please reconnect