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Synthesis of indazoles

Recent Literature

1,3-Dipolar cycloaddition reactions between α-substituted α-diazomethylphosphonates and arynes provide 3-alkyl/aryl-1H-indazoles and 3-alkyl/aryl-3H-indazole-3-phosphonates efficiently under simple reaction conditions. The phosphoryl group acted both as a tuning group and a traceless group.
G. Chen, M. Hu, Y. Peng, J. Org. Chem., 2018, 83, 1591-1597.

A one-pot metal-free reaction of easily available 2-aminophenones with hydroxylamine derivatives provides indazoles in very good yields. The reaction is operationally simple, mild, insensitive to air and moisture, and displayed a broad functional group tolerance.
J. Wang, D. Shi, Z. Wang, F. Ren, X. Li, Y. You, X. Liu, Y. Lou, J. Org. Chem., 2023, 88, 13049-13056.

A N-N bond-forming oxidative cyclization enables the synthesis of all three tautomeric forms of indazoles from readily available 2-aminomethyl-phenylamines. The method selectively gives access to various 2-substituted 2H-indazoles which are frequently used in drug design, and to less studied 3H-indazoles
A. S. Toledano, J. Bitai, D. Covini, J. Karolyi-Oezguer, C. Dank, H. Berger, A. Gollner, Org. Lett., 2024, 26, 1229-1232.

A radical-mediated decarboxylative C(sp³)-N cross-coupling of diacyl peroxides with nitrogen nucleophiles, including indazoles, triazoles, indoles, and anilines provides a broad range of alkylated products. The primary and secondary alkyl radicals derived from corresponding diacyl peroxides were generated by copper catalysis or by merging copper catalysis and photoredox catalysis, respectively.
Z. -L. Tang, X.-H. Ouyang, R.-J. Song, J.-H. Li, Org. Lett., 2021, 23, 1000-1004.

Readily available, stable, and inexpensive N-tosylhydrazones react with arynes under mild reaction conditions to afford 3-substituted indazoles in good yields. The reaction involves a 1,3-dipolar cycloaddition of in situ generated diazo compounds and arynes.
P. Li, J. Zhao, C. Wu, R. C. Larock, F. Shi, Org. Lett., 2011, 13, 3340-3343.

A one-pot metal-free reaction of easily available 2-aminophenones with hydroxylamine derivatives provides indazoles in very good yields. The reaction is operationally simple, mild, insensitive to air and moisture, and displayed a broad functional group tolerance.
J. Wang, D. Shi, Z. Wang, F. Ren, X. Li, Y. You, X. Liu, Y. Lou, J. Org. Chem., 2023, 88, 13049-13056.

Various N-aryl-1H-indazoles and benzimidazoles were synthesized from common arylamino oximes in good to excellent yields depending upon the base used in the reaction. Triethylamine promoted the formation of benzimidazoles, whereas 2-aminopyridine promoted the formation of N-arylindazoles.
B. C. Wray, J. P. Stambuli, Org. Lett., 2010, 12, 4576-4579.

CuI-catalyzed coupling of N-acyl-N′-substituted hydrazines with aryl iodides affords N-acyl-N′,N′-disubstituted hydrazines regioselectively. N-Acyl-N′-substituted hydrazines can also react with 2-bromoarylcarbonylic compounds in the presence of 4-hydroxy-L-proline as ligand to provide 1-aryl-1H-indazoles.
X. Xiong, Y. Jiang, D. Ma, Org. Lett., 2012, 14, 2552-2555.

1-Aryl-2-(2-nitrobenzylidene)hydrazines readily undergo intramolecular amination to afford 1-aryl-1H-indazole derivatives in good yields in the presence of potassium tert-butoxide in N,N-dimethylformamide at 100 °C. Displacement of the nitro group was achieved in the absence of significant electron-withdrawing substituents.
F. Esmaeili-Marandi, M. Saeedi, M. Mahdavi, I. Yavari, A. Foroumadi, A. Shafiee, Synlett, 2014, 25, 2605-2608.

The 1H-indazole skeleton can be constructed by a [3 + 2] annulation approach from arynes and hydrazones. Under different reaction conditions, both N-tosylhydrazones and N-aryl/alkylhydrazones can be used to afford various indazoles.
P. Li, C. Wu, J. Zhao, D. C. Rogness, F. Shi, J. Org. Chem., 2012, 77, 3127-3133.

The [3+2] cycloaddition of a variety of diazo compounds with o-(trimethylsilyl)aryl triflates in the presence of CsF or TBAF at room temperature provides a very direct, efficient approach to a wide range of potentially biologically and pharmaceutically interesting substituted indazoles in good to excellent yields under mild reaction conditions.
Z. Liu, F. Shi, P. D. G. Martinze, C. Raminelli, R. C. Larock, J. Org. Chem., 2008, 73, 219-226.

A Cu-catalyzed coupling reaction of 2-halobenzonitriles with hydrazine carboxylic esters and N′-arylbenzohydrazides proceed smoothly to provide substituted 3-aminoindazoles through a cascade coupling-(deacylation-)condensation process. A wide range of substituted 3-aminoindazoles can be prepared from the corresponding coupling partners.
L. Xu, Y. Peng, Q. Pan, Y. Jiang, D. Ma, J. Org. Chem., 2013, 78, 3400-3401.

A Cu-catalyzed coupling reaction of 2-halobenzonitriles with hydrazine carboxylic esters and N′-arylbenzohydrazides proceed smoothly to provide substituted 3-aminoindazoles through a cascade coupling-(deacylation-)condensation process. A wide range of substituted 3-aminoindazoles can be prepared from the corresponding coupling partners.
L. Xu, Y. Peng, Q. Pan, Y. Jiang, D. Ma, J. Org. Chem., 2013, 78, 3400-3401.

A general two-step synthesis of substituted 3-aminoindazoles from 2-bromobenzonitriles involves a palladium-catalyzed arylation of benzophenone hydrazone followed by an acidic deprotection/cyclization sequence. This procedure offers a general and efficient alternative to the typical SNAr reaction of hydrazine with o-fluorobenzonitriles.
V. Lefebvre, T. Cailly, F. Fabis, S. Rault, J. Org. Chem., 2010, 75, 2730-2732.

In an electrochemical method for the selective N1-acylation of indazoles, indazoles are reduced to indazole anions and H₂. A subsequent reaction with acid anhydrides results in selective acylation of the N1-position. This procedure can also be applied to the acylation of benzimidazoles and indoles.
D. M. M. M. Dissanayake, A. J. Vannucci, Org. Lett., 2019, 21, 457-460.