Categories: Synthesis of N-Heterocycles >
Synthesis of 1,2,3-triazoles
The synthesis of 1-monosubstituted aryl 1,2,3-triazoles was achieved in good yields using calcium carbide as a source of acetylene. The copper-catalyzed 1,3-dipolar cycloaddition reactions were carried out without nitrogen protection and in a MeCN-H2O mixture.
Y. Jiang, C. Kuang, Q. Yang, Synlett, 2009, 3163-3166.
A molecular iodine-mediated coupling cyclization reaction N-tosylhydrazones with sodium azide provides valuable 4-aryl-NH-1,2,3-triazoles via sequential C-N and N-N bond formation. Mechanistic studies suggest that the nitrogen atoms of the 1,2,3-triazoles are not entirely from sodium azide.
W.-M. Shu, X.-F. Zhang, X.-X. Zhang, M. Li, A.-J. Wang, A.-X. Wu, J. Org. Chem., 2019, 84, 14919-14925.
p-TsOH is a vital additive in the 1,3-dipolar cycloaddition of nitroolefins and sodium azide. This p-TsOH-mediated cycloaddition enables a rapid synthesis of valuable 4-aryl-NH-1,2,3-triazoles in high yields.
X.-J. Quan, Z.-H. Ren, Y.-Y. Wang, Z.-H. Guan, Org. Lett., 2014, 16, 5728-5731.
A highly efficient and effective synthesis of N-unsubstituted 4-aryl-1,2,3-triazoles is promoted by Amberlyst-15. The ion exchange resin can be recycled and reused up to eight times without loss of catalytic activity.
H. Zhang, D.-Z. Dong, Z.-L. Wang, Synthesis, 2016, 48, 131-135.
A Pd-catalyzed synthesis of 1H-triazoles from alkenyl halides and sodium azide represents a completely new reactivity pattern in the context of Pd chemistry.
J. Barluenga, C. Valdés, G. Beltrán, M. Escribano, F. Aznar, Angew. Chem. Int. Ed., 2006, 45, 6893-6896.
A regioselective one-pot synthesis of 1,5-disubstituted 1,2,3-triazoles through N/C-heterocyclization of allenylindium bromide across aryl azides is carried out under mild conditions in aqueous medium and proceeds in good yields.
A. H. Banday, V. J. Hruby, Synlett, 2014, 25, 1859-1862.
A tandem catalysis protocol based on decarboxylative coupling of alkynoic acids and 1,3-dipolar cycloaddition of azides avoids usage of gaseous or highly volatile terminal alkynes, reduces handling of potentially unstable and explosive azides to a minimum, and furnishes various functionalized 1,2,3-triazoles in excellent yields and a very good purity without the need for additional purification.
A. Kolarovič, M. Schnürch, M. D. Mihovilovic, J. Org. Chem., 2011, 76, 2613-2618.
Self-assembly of copper sulfate and a poly(imidazole-acrylamide) amphiphile provides a highly active, reusable, globular, solid-phase catalyst for click chemistry. The insoluble amphiphilic polymeric imidazole Cu catalyst drove the cycloaddition of various of alkynes and organic azides at very low catalyst loadings and can be readily reused without loss of activity to give the corresponding triazoles quantitatively.
Y. M. A. Yamada, S. M. Sarkar, Y. Uozumi, J. Am. Chem. Soc., 2012, 134, 9285-9286.
4-Aryl-1H-1,2,3-triazoles were synthesized from anti-3-aryl-2,3-dibromopropanoic acids and sodium azide by using inexpensive copper(I) iodide as the catalyst in the presence of cesium carbonate as base and DMSO as solvent.
Y. Jiang, C. Kuang, Q. Yang, Synthesis, 2010, 4256-4260.
4-Aryl-1H-1,2,3-triazoles were synthesized from anti-3-aryl-2,3-dibromopropanoic acids and sodium azide by a one-pot method using N,N-dimethylformamide as solvent in the presence of Pd2(dba)3 and Xantphos.
W. Zhang, C. Kuang, Q. Yang, Synthesis, 2010, 283-287.
1-Substituted-1,2,3-triazoles were conveniently synthesized from the corresponding aromatic and aliphatic azides in the presence of acetylene gas using mild, copper(I)-catalyzed ‘click chemistry'.
L.-Y. Wu, Y.-X. Xie, Z.-S. Chen, Y.-N. Niu, Y.-M. Liang, Synlett, 2009, 1453-1456.
A true Click catalytic system is based on commercially available [CuBr(PPh3)3]. This system is active at room temperature, with catalyst loadings of 0.5 mol % or less, in the absence of any additive, and it does not require any purification step to isolate pure triazoles.
S. Lal, S. Díez-González, J. Org. Chem., 2011, 76, 2367-2373.
A well-defined copper(I) isonitrile complex is an efficient, heterogeneous catalyst for azide-alkyne cycloadditions and three-component reactions of halides, sodium azide and alkynes to form 1,4-disubstituted 1,2,3-triazoles in high yields under mild conditions in water. The complex can be recycled for at least five runs without significant loss of activity by simple precipitation and filtration.
M. Liu, O. Reiser, Org. Lett., 2011, 13, 1102-1105.
Cycloadditions of copper(I) acetylides to azides and nitrile oxides provide ready access to 1,4-disubstituted 1,2,3-triazoles and 3,4-disubstituted isoxazoles, respectively. The process is highly reliable and exhibits an unusually wide scope with respect to both components. Computational studies revealed a nonconcerted mechanism involving unprecedented metallacycle intermediates.
F. Himo, T. Lovell, R. Hilgraf, V. V. Rostovtsev, L. Noodleman, K. B. Sharpless, V. V. Fokin, J. Am. Chem. Soc., 2005, 127, 210-216.
An efficient I2/TBPB mediated oxidative formal [4 + 1] cycloaddition of N-tosylhydrazones with anilines represents a simple, general, and efficient approach for the construction of 1,2,3-triazoles under metal-free and azide-free conditions.
Z.-J. Cai, X.-M. Lu, Y. Zi, C. Yang, L.-J. Shen, J. Li, S.-Y. Wang, S.-J. Ji, Org. Lett., 2014, 16, 5108-5111.
A mild, zinc-mediated method for regioselective formation of 1,5-substituted 1,2,3-triazoles from a wide range of azides and alkynes works at room temperature. Additionally, the triazole 4-position can be further functionalized by reaction of the intermediate aryl-zinc with various electrophiles to accommodate a diverse three-component coupling strategy.
C. D. Smith, M. F. Greaney, Org. Lett., 2013, 15, 4826-4829.
N3-Alkylation of 1-(pivaloyloxymethyl)-1,2,3-triazoles with alkyl triflates, followed by a nucleophile-promoted N1-dealkylation of the resulting strongly electrophilic intermediate triazolium salts, provides 1,5-disubstituted 1,2,3-triazoles.
Z. Monasterio, A. Irastorza, J. I. Miranda, J. M. Aizpurua, Org. Lett., 2016, 18, 2515-2518.
The Cp2Ni/Xantphos catalytic system enables the synthesis of 1,5-disubstituted 1,2,3-triazoles under aqueous and ambient conditions. This protocol is simple and scalable with a broad substrate scope including both aliphatic and aromatic substrates.
W. G. Kim, M. E. Kang, J. B. Lee, M. H. Jeon, S. Lee, J. Lee, B. Choi, P. M. S. D. Cal, S. Kang, J.-M. Kee, G. J. L. Bernardes , J.-U. Rohde, W. Choe, S. Y. Hong, J. Am. Chem. Soc., 2017, 139, 12121-12124.
A Ce(OTf)3-catalyzed [3 + 2] cycloaddition of organic azides with nitroolefins and subsequent elimination reaction selectively produces 1,5-disubstituted 1,2,3-triazoles in very good yields. Both benzyl and phenyl azides react with a broad range of aryl nitroolefins containing a wide range of functionalities.
Y.-C. Wang, Y.-Y. Xie, H.-E. Qu, H.-S. Wang, Y.-M. Pan, F.-P. Huang, J. Org. Chem., 2014, 79, 4463-4464.
1,5-Diarylsubstituted 1,2,3-triazoles are formed in high yield from aryl azides and terminal alkynes in DMSO in the presence of a catalytic amount of tetraalkylammonium hydroxide or t-BuOK for base-labile substrates. The reaction is experimentally simple, does not require a transition-metal catalyst, and is not sensitive to atmospheric oxygen and moisture.
S. W. Kwok, J. R. Fotsing, R. J. Fraser, V. O. Rodinov, V. V. Fokin, Org. Lett., 2010, 12, 4217-4219.
The use of t-BuOK in wet DMF as desilylating reagent in a cycloaddition reaction of aromatic azides and trimethylsilyl alkynes generated 1,5-disubstituted 1,2,3-triazoles regioselectively in good yields at ambient temperature.
L. Wu, X. Chen, M. Tang, X. Song, G. Chen, X. Song, Q. Lin, Synlett, 2012, 23, 1529-1533.
A Cu/Pd transmetalation relay catalysis enables a three-component click reaction of azide, alkyne, and aryl halide to yield 1,4,5-trisubstituted 1,2,3-triazoles in one step in high yields with complete regioselectivity. This reaction offers an alternative to the well-established CuAAC click reactions only working on terminal alkynes.
F. Wei, H. Li, C. Song, Y. Ma, L. Zhou, C.-H. Tung, Z. Xu, Org. Lett., 2015, 17, 2860-2863.
In the presence Cp*RuCl(PPh3)2 or Cp*RuCl(COD) as catalyst, primary and secondary azides react with a broad range of terminal alkynes containing a range of functionalities selectively producing 1,5-disubstituted 1,2,3-triazoles. Both complexes also promote the cycloaddition reactions of organic azides with internal alkynes, providing access to fully-substituted 1,2,3-triazoles.
B. C. Boren, S. Narayan, L. K. Rasmussen, L. Zhang, H. Zhao, Z. Lin, G. Jia, V. V. Fokin, J. Am. Chem. Soc., 2008, 130, 8923-8930.
In the presence of inexpensive copper (I) iodide as the catalyst, a series of 1,4-disubstituted 1,2,3-triazoles were synthesized in a one-pot process from anti-3-aryl-2,3-dibromopropanoic acids and organic azides in dimethyl sulfoxide.
X. Chen, Y. Yang, C. Kuang, Q. Yang, Synthesis, 2011, 2907-2912.
A copper(I)-catalyzed three-component reaction of amines, propargyl halides and azides forms 1-substituted-1H-1,2,3-triazol-4-ylmethyl)-dialkylamines in water. Synthetic advantages are high atom economy, low environmental impact, atmospheric oxygen, wide substrate scope, mild reaction condition and good yields.
Z.-Y. Yan, Y.-B. Zhao, M.-J. Fan, W.-M. Liu, Y.-M. Liang, Tetrahedron, 2005, 61, 9331-9337.
A method for the regiospecific synthesis of 1,4,5-trisubstituted-1,2,3-triazole catalyzed by copper(I) iodide was developed. This is the first example of a regiospecific synthesis of 5-iodo-1,4-disubstituted-1,2,3-triazole, which can be further elaborated to a range of 1,4,5-trisubstituted-1,2,3-triazole derivatives.
Y.-M. Wu, J. Deng, Y. L. Li, Q.-Y. Chen, Synthesis, 2005, 1314-1318.
Inexpensive copper catalysts enabled modular one-pot multicomponent syntheses of fully decorated triazoles through a sustainable “click” reaction/direct arylation sequence.
L. Ackermann, H. K. Potukuchi, D. Landsberg, R. Vicente, Org. Lett., 2008, 10, 3081-3084.
Microwave irradiation significantly enhances the rate of formation of 1,4-disubstituted 1,2,3-triazoles from alkynes and in situ generated azides. Azides are derived from an efficient one-pot azidation of anilines with the reagent combination t-BuONO and TMSN3.
A. D. Moorhouse, J. E. Moses, Synlett, 2008, 2089-2092.
A reliable and operationally simple one-pot reaction for a one-carbon homologation of various aldehydes followed by Cu-catalyzed azide-alkyne click chemistry gives 1,4-disubstituted 1,2,3-triazoles in good yields without the need for isolation of the alkyne intermediates.
D. Luvino, C. Amalric, M. Smietana, J.-J. Vasseur, Synlett, 2007, 3037-3041.
1,2,3-Triazoles were prepared in good to modest yields by cycloaddition of alkyl azides onto enol ethers under solventless conditions. The reaction can access ring-fused triazoles that are unavailable by azide-alkyne cycloadditions and is easily scalable. The 1,2,3-triazole products bear functionality that may be readily derivatized.
D. R. Rogue, J. L. Neill, J. W. Antoon, E. P. Stevens, Synthesis, 2005, 2497-2502.
Triazoles have been synthesized via a three-component coupling reaction of unactivated terminal alkynes, allyl carbonate, and trimethylsiyl azide under Pd(0)-Cu(I) bimetallic catalysis. The deallylation of the resulting allyltriazoles is described.
S. Kamijo, T. Jin, Z. Huo, Y. Yamamoto, J. Am. Chem. Soc., 2003, 125, 7786-7787.
Reaction of 4-bromo-NH-1,2,3-triazoles with alkyl halides in the presence of K2CO3 in DMF produced the corresponding 2-substituted 4-bromo-1,2,3-triazoles in a regioselective process. Subsequent Suzuki cross-coupling reaction provided an efficient synthesis of 2,4,5-trisubstituted triazoles, whereas hydrogenation furnished an efficient synthesis of 2,4-disubstituted triazoles.
X.-j. Wang, K. Sidhu, L. Zhang, S. Campbell, N. Haddad, D. C. Reeves, D. Krishnamurthy, C. H. Senanayake, Org. Lett., 2009, 11, 5460-5493.
A catalyst-free and regioselective N arylation enables the synthesis of N2-aryl-1,2,3-triazoles in very good yields. This scalable postmodification protocol is effective for a wide range of substrates.
S. Roshandel, M. J. Lunn, G. Rasul, D. S. M. Ravinson, S. C. Suri, G. K. S. Prakash, Org. Lett., 2019, 21, 6255-6258.
Phenyl esters of α-azido acids react with trialkylphosphines in THF/H2O to give 5-substituted 2H-1,2,3-triazol-4-ols in very good yields, whereas their reaction with PPh3 provides amino esters as the major product and no triazoles.
S. D. Taylor, C. R. Lohani, Org. Lett., 2016, 18, 4412-4415.
A copper-catalyzed three-component reaction of methyl ketones, organic azides, and DMF as one-carbon (C1) donor provides 4-acyl-1,2,3-triazoles in good yields. The transformation proceeds via an oxidative C-H/C-H cross-dehydrogenative coupling followed by an oxidative 1,3-dipolar cycloaddition.
Y. Liu, G. Nie, Z. Zhou, L. Jia, Y. Chen, J. Org. Chem., 2017, 82, 9198-9203.
The three-component reactions of enaminones, tosylhydrazine and primary amines enabled a regioselective construction of 1,5-disubstituted 1,2,3-triazoles via cascade dual C-N bond formation, N-N bond formation and an acyl migration-based C-C bond formation. This metal- and azide-free method proceeds in the presence of only molecular iodine.
J.-P. Wan, S. Cao, Y. Liu, J. Org. Chem., 2015, 80, 9028-9033.
Domino reactions between NH-based secondary enaminones and tosyl azide enable the synthesis of various N-substituted 1,2,3-triazoles via a key Regitz diazo-transfer process by employing t-BuONa as the base promoter. The reactions proceed efficiently at room temperature with good substrate tolerance.
J.-P. Wan, S. Cao, Y. Liu, Org. Lett., 2016, 18, 6034-6037.
A palladium-catalyzed and ultrasonic promoted Sonogashira coupling/1,3-dipolar cycloaddition of acid chlorides, terminal acetylenes, and sodium azide in one pot enables an efficient synthesis of 4,5-disubstituted-1,2,3-(NH)-triazoles in excellent yields.
J. Li, D. Wang, Y. Zhang, J. Li, B. Chen, Org. Lett., 2009, 11, 3024-3027.
A mild and metal-free multi-component reaction enables the synthesis of 4,5-disubstituted 1H-1,2,3-triazoles from phosphonium salts, aldehydes, and sodium azide. An organocatalyzed coupling of the formyl group with the phosphonium group provides an olefinic phosphonium salt as key intermediate, that undergoes [3+2] cycloaddition with the azide.
G.-L. Wu, Q.-P. Wu, Synthesis, 2018, 50, 2768-2774.
TBAF-catalyzed [3 + 2] cycloadditions of 2-aryl-1-cyano- or 2-aryl-1-carbethoxy-1-nitroethenes with TMSN3 under solvent free conditions allow the preparation of 4-aryl-5-cyano- or 4-aryl-5-carbethoxy-1H-1,2,3-triazoles under mild reaction conditions with good to excellent yields.
D. Amantini, F. Fringuelli, O. Piermatti, F. Pizzo, E. Zunino, L. Vaccaro, J. Org. Chem., 2005, 70, 6526-6529.
Triazole-based monophosphine ligands have been prepared via efficient cycloadditions. Palladium complexes derived from these ligands are highly active catalysts for Suzuki-Miyaura coupling and amination reactions of aryl chlorides.
D. Liu, W. Gao, Q. Dai, X. Zhang, Org. Lett., 2005, 7, 4907-4910.
A highly efficient method for the synthesis of multisubstituted 1,2,3-triazoles via a direct Pd-catalyzed C-5 arylation has been developed.
S. Chuprakov, N. Chernyak, A. S. Dudnik, V. Gevorgyan, Org. Lett., 2007, 9, 2333-2336.
The use of nontoxic polyethylene glycol (PEG) as solvent and MesCO2H as cocatalyst enabled user-friendly palladium(0)-catalyzed C-H bond functionalizations under air in the absence of phosphine ligands. Direct arylations of 1,2,3-triazoles gave substituted triazoles in good yields. Recycling of the catalytic system led to a slight decrease of activity.
L. Ackermann, R. Vicente, Org. Lett., 2009, 11, 4922-4925.
Conditions for the palladium-catalyzed direct arylation of a wide range of heterocycles with aryl bromides employ a stoichiometric ratio of both coupling partners, as well as a substoichiometric quantity of pivalic acid, which results in significantly faster reactions. An evaluation of the influence of the nature of the aryl halide has also been carried out.
B. Liégault, D. Lapointe, L. Caron, A. Vlassova, K. Fagnou, J. Org. Chem., 2009, 74, 1826-1834.
A general and regioselective metal-free cycloaddition of organic azides to a hitherto underexplored bromovinylsulfonyl fluoride building block provides 4-fluorosulfonyl 1,2,3-triazoles. This reaction was extended to the synthesis of various sulfonates, sulfonamides, and sulfonic acid derivatives of triazoles.
J. Thomas, V. V. Fokin, Org. Lett., 2018, 20, 3749-3752.
A copper-catalyzed [3 + 2] cycloaddition/oxidation reaction of nitro-olefins with organic azides affords a broad range of 1,4(-NO2),5-trisubstituted 1,2,3-triazoles with high regioselectivities and in very good yields without elimination of HNO2.
Y. Chen, G. Nie, Q. Zhang, S. Ma, H. Li, Q. Hu, Org. Lett., 2015, 17, 1118-1121.
A ruthenium-catalyzed cycloaddition of N-Boc ynamides with azides gives protected 5-amino-1,2,3-triazole-4-carboxylic acids, which are suitable for the preparation of peptidomimetics. When aryl or alkyl azides are reacted with N-Boc-aminopropiolates or arylynamides, the cycloaddition occurs with complete regiocontrol, while N-Boc-alkyl ynamides yield a mixture of regioisomers.
S. Ferrini, J. Z. Chandanshive, S. Lena, M. C. Franchini, G. Giannini, A. Tafi, M. Taddei, J. Org. Chem., 2015, 80, 2562-2572.
The reaction of 4,4-dichloro-1,2-diazabuta-1,3-dienes with sodium azide provides extremely rare 1,1-bisazides. These highly unstable compounds are prone to eliminate N2 to cyclize into 4-azido-1,2,3-triazoles bearing two aryl groups at positions 2 and 5. This reaction enables a highly efficient synthesis of various 4-azidotriazoles. These heterocycles are highly attractive building blocks.
A. V. Shastin, B. T. Tsyrenova, P. G. Sergeev, V. A. Roznyatovsky, I. V. Smolyar, V. N. Khrustalev, V. G. Nenajdenko, Org. Lett., 2018, 20, 7803-7806.