CuI‐Catalyzed Alkyne–Azide “Click” Cycloadditions from a Mechanistic and Synthetic Perspective

CuI-catalyzed alkyne–azide cycloaddition provides 1,4-disubstituted 1,2,3-triazoles with such efficiency and scope that the transformation has been described as “click” chemistry. An overview of the mechanism of this remarkable reaction is presented as a means to explain the myriad of experimental results, particularly the various methods of catalyst generation, solvent and substrate effects, and choice of base or ligand. Both solution-phase and solid-phase results are comprehensively examined. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

[1]  Richard W. Mares,et al.  Preparation and pyrolysis of 1-(pyrazol-5-yl)-1,2,3-triazoles andrelated compounds1 , 1997 .

[2]  Doris Dallinger,et al.  Combining Biginelli multicomponent and click chemistry: generation of 6-(1,2,3-triazol-1-yl)-dihydropyrimidone libraries. , 2004, Journal of combinatorial chemistry.

[3]  Jan C M van Hest,et al.  Preparation of biohybrid amphiphiles via the copper catalysed Huisgen [3 + 2] dipolar cycloaddition reaction. , 2005, Chemical communications.

[4]  D. Darensbourg,et al.  Diamond‐Shaped Heterometallic Complexes of Iron(II) and Copper(I) Bridged by Cyanide Groups Containing Monodentate or Bidentate Phosphanes Bound to Copper(I), Including an Alternative Structure Based on the Nature of the Bidentate Phosphane Ligand , 2001 .

[5]  A. Katritzky,et al.  Synthesis of C-carbamoyl-1,2,3-triazoles by microwave-induced 1,3-dipolar cycloaddition of organic azides to acetylenic amides. , 2002, The Journal of organic chemistry.

[6]  D. Buckle,et al.  Studies on v-triazoles. 7. Antiallergic 9-oxo-1H,9H-benzopyrano[2,3-d]-v-triazoles. , 1983, Journal of medicinal chemistry.

[7]  Anna E Speers,et al.  Activity-based protein profiling in vivo using a copper(i)-catalyzed azide-alkyne [3 + 2] cycloaddition. , 2003, Journal of the American Chemical Society.

[8]  M. Finn,et al.  Kinetic resolution by copper-catalyzed azide–alkyne cycloaddition , 2005 .

[9]  G. Pampaloni,et al.  Olefin trifluoroacetato derivatives of copper(I) and their olefin/CO exchange reactions , 2005 .

[10]  Chi‐Huey Wong,et al.  Synthesis of sugar arrays in microtiter plate. , 2002, Journal of the American Chemical Society.

[11]  B. Skelton,et al.  Lewis-Base Adducts of Group 11 Metal(I) Compounds. LXXV Structural Systematics of the Binuclear Copper(I) Halide: 1,5-Cyclooctadiene (‘cod’) 2:2 Adducts, [(cod)Cu(μ-X)2Cu(cod)], X = Cl, Br, I , 2004 .

[12]  Yan Zhao,et al.  Efficient synthesis of water-soluble calixarenes using click chemistry. , 2005, Organic letters.

[13]  C. Fahrni,et al.  A Fluorogenic Probe for the Copper(I)-Catalyzed Azide−Alkyne Ligation Reaction: Modulation of the Fluorescence Emission via 3(n,π*)−1(π,π*) Inversion , 2004 .

[14]  R. Findlay,et al.  Electronic charge distribution and moments of five- and six-membered heterocycles , 1974 .

[15]  P. Gmeiner,et al.  Parallel synthesis and biological screening of dopamine receptor ligands taking advantage of a click chemistry based BAL linker. , 2005, Journal of combinatorial chemistry.

[16]  D. Buckle,et al.  Studies on v-triazoles. Part 4. The 4-methoxybenzyl group, a versatile N-protecting group for the synthesis of N-unsubstituted v-triazoles , 1982 .

[17]  G. H. Coombs,et al.  Combinatorial library of peptidotriazoles: identification of [1,2,3]-triazole inhibitors against a recombinant Leishmania mexicana cysteine protease. , 2004, Journal of combinatorial chemistry.

[18]  M. Ghadiri,et al.  Heterocyclic Peptide Backbone Modifications in an α-Helical Coiled Coil , 2004 .

[19]  M Reza Ghadiri,et al.  A heterocyclic peptide nanotube. , 2003, Journal of the American Chemical Society.

[20]  F. Bohlmann,et al.  Polyacetylenverbindungen, LII. Über den Mechanismus der oxydativen Dimerisierung von Acetylenverbindungen , 1964 .

[21]  D. Buckle,et al.  Studies on 1,2,3-triazoles. 13. (Piperazinylalkoxy) [1]benzopyrano[2,3-d]-1,2,3-triazol-9(1H)-ones with combined H1-antihistamine and mast cell stabilizing properties. , 1986, Journal of medicinal chemistry.

[22]  Hua-Li Qin,et al.  Regioselective synthesis of 1,2,3-triazole derivatives via 1,3-dipolar cycloaddition reactions in water. , 2003, Chemical communications.

[23]  G. Whitesides,et al.  SELECTIVE REDUCTION OF DISULFIDES BY TRIS(2-CARBOXYETHYL) PHOSPHINE , 1991 .

[24]  A. Akar,et al.  Synthesis and investigation of tuberculosis inhibition activities of some 1,2,3-triazole derivatives. , 2003, European journal of medicinal chemistry.

[25]  F. Himo,et al.  Copper(I)-catalyzed synthesis of azoles. DFT study predicts unprecedented reactivity and intermediates. , 2004, Journal of the American Chemical Society.

[26]  Y. Tohda,et al.  A convenient synthesis of acetylenes: catalytic substitutions of acetylenic hydrogen with bromoalkenes, iodoarenes and bromopyridines , 1975 .

[27]  F. Rutjes,et al.  Expedient synthesis of triazole-linked glycosyl amino acids and peptides. , 2004, Organic letters.

[28]  T. Kirley Reduction and fluorescent labeling of cyst(e)ine-containing proteins for subsequent structural analyses. , 1989, Analytical biochemistry.

[29]  Philipp Holzer,et al.  Click chemistry in materials synthesis. 1. Adhesive polymers from copper‐catalyzed azide‐alkyne cycloaddition , 2004 .

[30]  H. Kolb,et al.  The growing impact of click chemistry on drug discovery. , 2003, Drug discovery today.

[31]  D. Tirrell,et al.  Cell surface labeling of Escherichia coli via copper(I)-catalyzed [3+2] cycloaddition. , 2003, Journal of the American Chemical Society.

[32]  G. Majetich,et al.  Application of commercial microwave ovens to organic synthesis. , 1987 .

[33]  M. B. Davies Reactions of L-ascorbic acid with transition metal complexes , 1992 .

[34]  K. Gothelf,et al.  Asymmetric 1,3-Dipolar Cycloaddition Reactions. , 1998, Chemical reviews.

[35]  R. Gedye,et al.  The use of microwave ovens for rapid organic synthesis , 1986 .

[36]  P. Gmeiner,et al.  Click linker: efficient and high-yielding synthesis of a new family of SPOS resins by 1,3-dipolar cycloaddition. , 2003, Organic letters.

[37]  G. Rothenberg,et al.  Click Chemistry: Copper Clusters Catalyse the Cycloaddition of Azides with Terminal Alkynes , 2005 .

[38]  K. Sharpless,et al.  Polytriazoles as copper(I)-stabilizing ligands in catalysis. , 2004, Organic letters.

[39]  M. Finn,et al.  Mechanism of the ligand-free CuI-catalyzed azide-alkyne cycloaddition reaction. , 2005, Angewandte Chemie.

[40]  P. Schultz,et al.  Adding amino acids with novel reactivity to the genetic code of Saccharomyces cerevisiae. , 2003, Journal of the American Chemical Society.

[41]  A. Loupy Microwaves in organic synthesis , 2002 .

[42]  Joel Morris,et al.  Substituent effects on the antibacterial activity of nitrogen-carbon-linked (azolylphenyl)oxazolidinones with expanded activity against the fastidious gram-negative organisms Haemophilus influenzae and Moraxella catarrhalis. , 2000, Journal of medicinal chemistry.

[43]  H. Lang,et al.  (η2-Alkyne)2CuMe as a Synthetic Tool in the Preparation of Numerous Inorganic and Organic Copper(I) Species , 2000 .

[44]  W. Guida,et al.  The art and practice of structure‐based drug design: A molecular modeling perspective , 1996, Medicinal research reviews.

[45]  H. Tian,et al.  Synthesis of hemicyanine dyes for ‘click’ bioconjugation , 2005 .

[46]  E. De Clercq,et al.  1,2,3-Triazole-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D- ribofuranosyl]-3'-spiro-5"-(4"-amino-1",2"-oxathiole 2",2"-dioxide) (TSAO) analogues: synthesis and anti-HIV-1 activity. , 1994, Journal of medicinal chemistry.

[47]  M. Finn,et al.  Discovery and characterization of catalysts for azide-alkyne cycloaddition by fluorescence quenching. , 2004, Journal of the American Chemical Society.

[48]  Morten Meldal,et al.  Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(i)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. , 2002, The Journal of organic chemistry.

[49]  P. Woodward,et al.  Formation of ?3-bonded lactone complexes and eight-membered ring metallacycles with ketene groups by the insertion of acetylenes into carbon?molybdenum and ?tungsten ? bonds; molecular and crystal structures of carbonyl(?-cyclopentadienyl)(3?5-?-2,3-dihydro-3,4,5-trimethyl-2-oxo-3-furyl)(t-butyl iso , 1978 .

[50]  Diederich,et al.  Acetylenic Coupling: A Powerful Tool in Molecular Construction. , 2000, Angewandte Chemie.

[51]  David R. Liu,et al.  Two enabling architectures for DNA-templated organic synthesis. , 2003, Angewandte Chemie.

[52]  I. Akritopoulou‐Zanze,et al.  A versatile synthesis of fused triazolo derivatives by sequential Ugi/alkyne-azide cycloaddition reactions , 2004 .

[53]  M. G. Finn,et al.  Click Chemistry: Diverse Chemical Function from a Few Good Reactions. , 2001, Angewandte Chemie.

[54]  P. Selvin,et al.  A comparison between the sulfhydryl reductants tris(2-carboxyethyl)phosphine and dithiothreitol for use in protein biochemistry. , 1999, Analytical biochemistry.

[55]  T. Seo,et al.  1,3-Dipolar cycloaddition of azides with electron-deficient alkynes under mild condition in water , 2004 .

[56]  J. Coetzee,et al.  Polarography in Acetonitrile. II. Metal Ions Which Have Significantly Different Polarographic Properties in Acetonitrile and in Water. Anodic Waves. Voltammetry at Rotated Platinum Electrode , 1957 .

[57]  A. Ponti,et al.  Arylazide cycloaddition to methyl propiolate: DFT-based quantitative prediction of regioselectivity. , 2003, Chemistry.

[58]  Luke G Green,et al.  A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective "ligation" of azides and terminal alkynes. , 2002, Angewandte Chemie.

[59]  Russolina B Zingali,et al.  Antiplatelet properties of novel N-substituted-phenyl-1,2,3-triazole-4-acylhydrazone derivatives. , 2003, Bioorganic & medicinal chemistry.

[60]  C. Barbas,et al.  Towards organo-click chemistry: development of organocatalytic multicomponent reactions through combinations of aldol, Wittig, Knoevenagel, Michael, Diels-Alder and Huisgen cycloaddition reactions. , 2004, Chemistry.

[61]  Alessandro Massi,et al.  Assembling heterocycle-tethered C-glycosyl and alpha-amino acid residues via 1,3-dipolar cycloaddition reactions. , 2004, Organic letters.

[62]  C. Hawker,et al.  Dendronized linear polymers via "click chemistry". , 2004, Journal of the American Chemical Society.

[63]  D. Macintyre,et al.  Human beta3-adrenergic receptor agonists containing 1,2,3-triazole-substituted benzenesulfonamides. , 2000, Bioorganic & medicinal chemistry letters.

[64]  Sukbok Chang,et al.  Highly efficient one-pot synthesis of N-sulfonylamidines by Cu-catalyzed three-component coupling of sulfonyl azide, alkyne, and amine. , 2005, Journal of the American Chemical Society.

[65]  C. Kappe,et al.  Controlled microwave heating in modern organic synthesis. , 2004, Angewandte Chemie.

[66]  M. Finn,et al.  Head-to-tail peptide cyclodimerization by copper-catalyzed azide-alkyne cycloaddition. , 2005, Angewandte Chemie.

[67]  O. Temkin,et al.  Polynuclear complexes of copper(I) halides: coordination chemistry and catalytic transformations of alkynes , 2001 .

[68]  Mark S. Taylor,et al.  Highly Enantioselective Conjugate Additions to α,β-Unsaturated Ketones Catalyzed by a (Salen)Al Complex , 2005 .

[69]  D. Gin,et al.  Synthesis of readily modifiable cyclodextrin analogues via cyclodimerization of an alkynyl-azido trisaccharide. , 2004, Journal of the American Chemical Society.

[70]  Q. Wang,et al.  A fluorogenic 1,3-dipolar cycloaddition reaction of 3-azidocoumarins and acetylenes. , 2004, Organic letters.

[71]  W. Fischer,et al.  In situ reduction suitable for matrix-assisted laser desorption/ionization and liquid secondary ionization using tris(2-carboxyethyl)phosphine. , 1993, Rapid communications in mass spectrometry : RCM.

[72]  C. Bertozzi,et al.  Cell surface engineering by a modified Staudinger reaction. , 2000, Science.

[73]  Qian Wang,et al.  Bioconjugation by copper(I)-catalyzed azide-alkyne [3 + 2] cycloaddition. , 2003, Journal of the American Chemical Society.

[74]  C. Eyermann,et al.  Identification of 4-substituted 1,2,3-triazoles as novel oxazolidinone antibacterial agents with reduced activity against monoamine oxidase A. , 2005, Journal of medicinal chemistry.

[75]  B. Loeb,et al.  Experimental evidence of the disproportionation equilibrium in copper mixed-valence complexes , 2000 .

[76]  J. Yli-Kauhaluoma,et al.  Solid-phase synthesis of 1,2,3-triazoles via 1,3-dipolar cycloaddition. , 2003, Journal of combinatorial chemistry.

[77]  C. Creutz Complexities of ascorbate as a reducing agent , 1981 .

[78]  Yong-ming Wu,et al.  Regioselective synthesis of fluoroalkylated [1,2,3]-triazoles by Huisgen cycloaddition , 2004 .

[79]  William P. Purcell,et al.  Electronic and molecular structure of selected unsubstituted and dimethyl amides from measurements of electric moments and nuclear magnetic resonance , 1967 .

[80]  G. Rothenberg,et al.  Palladium-free and ligand-free Sonogashira cross-coupling , 2004 .

[81]  William S. Striejewske,et al.  Copper Complexes with N-Alkylated NS2-Macrocyclic Ligands: Synthesis, Characterization, and Capabilities as Aziridination Precatalysts , 2004 .

[82]  Camelia Gabriel,et al.  Dielectric parameters relevant to microwave dielectric heating , 1998 .

[83]  H. Komber,et al.  Novel Hyperbranched Poly([1,2,3]‐triazole)s Derived from AB2 Monomers by a 1,3‐Dipolar Cycloaddition , 2004 .

[84]  G. D. Bennett,et al.  Notes - Use of Amines in the Glaser Coupling Reaction , 1957 .

[85]  Hyun-Ju Park,et al.  Synthesis and biological evaluation of novel 2-pyridinyl-[1,2,3]triazoles as inhibitors of transforming growth factor β1 type 1 receptor , 2004 .

[86]  B. Suh,et al.  Vitamin D side chain triazole analogs via cycloaddition `click' chemistry , 2004 .

[87]  G. Marriott,et al.  Synthesis and characterization of the 7-(4-aminomethyl-1H-1,2,3-triazol-1-yl) analogue of kabiramide C. , 2005, Journal of natural products.

[88]  S. García‐Granda,et al.  Synthesis and characterization of triangulo copper(I) complexes containing mono- and bicapping systems of asymmetric .mu.3-.eta.1-acetylide ligands: molecular structures of [Cu3(.mu.3-.eta.1-C.tplbond.CPh)(.mu.-dppm)3][BF4]2, [Cu3(.mu.3-.eta.1-C.tplbond.CPh)2(.mu.-dppm)3][BF4], and [Cu3(.mu.3-.eta.1 , 1993 .

[89]  Y. Fall,et al.  Vitamin D and click chemistry. Part 1: A stereoselective route to vitamin D analogues with triazole rings in their side chains , 2004 .

[90]  S. Chittaboina,et al.  One-pot synthesis of triazole-linked glycoconjugates , 2005 .

[91]  E. De Clercq,et al.  Regiospecific Synthesis and Anti-Human Immunodeficiency Virus Activity of Novel 5-Substituted N-Alkylcarbamoyl and N,N-Dialkyl Carbamoyl 1,2,3-Triazole-TSAO Analogues , 1998, Antiviral chemistry & chemotherapy.

[92]  H. Lang,et al.  Synthese und Reaktionsverhalten monomerer Bis(η2-Alkin)-Kupfer(I)-Fluorid- und-Kupfer(I)-Hydrid-Komplexe , 1998 .

[93]  S. Schindler Reactivity of Copper(I) Complexes Towards Dioxygen , 2000 .

[94]  N. Devaraj,et al.  "Clicking" functionality onto electrode surfaces. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[95]  Carolyn R Bertozzi,et al.  Incorporation of azides into recombinant proteins for chemoselective modification by the Staudinger ligation , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[96]  Craig J Hawker,et al.  Efficiency and fidelity in a click-chemistry route to triazole dendrimers by the copper(i)-catalyzed ligation of azides and alkynes. , 2004, Angewandte Chemie.

[97]  Y. Isome,et al.  Regioselective synthesis of [1,2,3]-triazoles catalyzed by Cu(I) generated in situ from Cu(0) nanosize activated powder and amine hydrochloride salts , 2005 .

[98]  W. Dehaen,et al.  A microwave-assisted click chemistry synthesis of 1,4-disubstituted 1,2,3-triazoles via a copper(I)-catalyzed three-component reaction. , 2004, Organic letters.

[99]  F. Santoyo-González,et al.  Multivalent neoglycoconjugates by regiospecific cycloaddition of alkynes and azides using organic-soluble copper catalysts. , 2003, Organic letters.

[100]  P. Gmeiner,et al.  Click chemistry on solid support: synthesis of a new REM resin and application for the preparation of tertiary amines , 2004 .

[101]  Chi‐Huey Wong,et al.  A Potent and Highly Selective Inhibitor of Human α-1,3-Fucosyltransferase via Click Chemistry , 2003 .

[102]  E. Weiss,et al.  Metallorganische verbindungen des kupfers: VII. Synthese und struktur von alkin-alkinyl-kupfer(I)-komplexen (alkin = 3,3,6,6-tetramethyl-1-thia-4-cycloheptin; alkinyl = CCC6H5, CCtC4H9)☆ , 1994 .

[103]  D. Michael P. Mingos,et al.  Applications of Microwave Dielectric Heating Effects to Synthetic Problems in Chemistry , 1991 .

[104]  R. Walter,et al.  The development of new triazole based inhibitors of tumor necrosis factor-α (TNF-α) production , 2003 .

[105]  Anna E Speers,et al.  Profiling enzyme activities in vivo using click chemistry methods. , 2004, Chemistry & biology.