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Synthesis of 2H-indazoles

Recent Literature

Either trifluoromethanesulfonic acid or copper(II) triflate promote general and selective procedures for the N2-alkylation of 1H-indazoles and 1H-azaindazoles with various primary, secondary, and tertiary alkyl 2,2,2-trichloroacetimidates to afford the corresponding 2-alkyl-2H-indazoles/azaindazoles.
J. Clemens, E. L. Bell, A. T. Londregan, Synthesis, 2022, 54, 3215-3226.

Pd catalyzes a direct and operationally simple regioselective synthesis of 2-aryl-substituted 2H-indazoles in good yields from easily available 2-bromobenzyl bromides and arylhydrazines via a regioselective intermolecular N-benzylation followed by intramolecular N-arylation and oxidation. The reaction employs Cs₂CO₃ as the base and t-Bu₃PHBF₄ as the ligand in DMSO at 120°C.
N. Alijaar, M. Al-Noaimi, H. Conrad, U. Beifuss, J. Org. Chem., 2021, 86, 1408-1418.

An efficient synthesis of 2H-indazole derivatives in a one-pot three-component reaction of 2-chloro- and 2-bromobenzaldehydes, primary amines and sodium azide is catalyzed by copper(I) oxide nanoparticles (Cu₂O-NP) under ligand-free conditions in polyethylene glycol (PEG 300) as a green solvent.
H. Sharghi, M. Aberi, Synlett, 2014, 25, 1111-1115.

2H-Indazoles are synthesized using a copper-catalyzed one-pot, three-component reaction of 2-bromobenzaldehydes, primary amines, and sodium azide. The catalyst plays the key role in the formation of C-N and N-N bonds. This method has a broad substrate scope with a high tolerance for various functional groups.
M. R. Kumar, A. Park, N. Park, S. Lee, Org. Lett., 2011, 13, 3542-3545.

In an operationally simple, mild and efficient one-pot synthesis of 2H-indazoles from commercially available reagents, ortho-imino-nitrobenzene substrates, generated via condensation, undergo reductive cyclization promoted by tri-n-butylphosophine to afford substituted 2H-indazoles. Various electronically diverse ortho-nitrobenzaldehydes and aromatic as well as aliphatic amines were examined.
N. E. Genung, L. Wei, G. E. Aspnes, Org. Lett., 2014, 16, 3114-3117.

1,2,2,3,4,4-hexamethylphosphetane catalyzes a deoxygenative N-N bond-forming Cadogan heterocyclization of o-nitrobenzaldimines and o-nitroazobenzenes with good functional group compatibility in the presence of phenylsilane as terminal reductant.
T. V. Nykaza, T. S. Harrison, A. Ghosh, R. A. Putnik, A. T. Radosevich, J. Am. Chem. Soc., 2017, 139, 6839-6842.

A palladium-catalyzed intramolecular amination enables the synthesis of various 2-aryl-2H-indazoles from N-aryl-N-(o-bromobenzyl)hydrazines. This reaction tolerates a wide range of electron-donating and electron-withdrawing substituents.
J. J. Song, N. K. Yee, Org. Lett., 2000, 2, 519-521.

A reductive cyclization of o-nitrobenzylidene amines under microwave conditions in the presence of MoO₂Cl₂(dmf)₂ as catalyst and Ph₃P as reducing agent delivers 2-aryl-2H-indazoles in good yields.
A. H. Moustafa, C. C. Malakar, N. Aljaar, E. Merisor, J. Conrad, U. Beifuss, Synlett, 2013, 24, 1573-1577.

An electrochemical oxidation-induced cyclization of ortho-alkyl-substituted azobenzenes provides 2H-indazole derivatives in good yields. This direct electrochemical benzylic C-H functionalization could proceed in the absence of any catalyst or external chemical oxidant.
A. Li, X. Li, F. Ma, H. Gao, H. Li, Org. Lett., 2023, 25, 5978-5983.

Azobenzenes were readily acylated at the 2-position with aldehydes in good yields through a Pd-catalyzed C-H functionalization in the presence of TBHP. The obtained acylated azobenzenes could be efficiently converted into the corresponding indazole derivatives in nearly quantitative yields.
H. Li, P. Li, L. Wang, Org. Lett., 2013, 15, 620-623.

1,2,3,5-Tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) catalyzes an efficient photosynthesis of various arylated 2-aryl-2H-indazoles in good yields. This mild protocol features wide substrate scope, good functional group tolerance, and operational simplicity. In addition, the strategy was successfully applied to the late-stage modification of drug molecules.
A. Shi, P. Xiang, Y. Wu, C. Ge, Y. Liu, K. Sun, B. Yu, Synlett, 2023, 34, 457-464.

A rapid and efficient synthesis of 2H-indazoles, which involves a [3 + 2] dipolar cycloaddition of arynes and sydnones, proceeds under mild reaction conditions in good to excellent yields.
C. Wu, Y. Fang, R. C. Larock, F. Shi, Org. Lett., 2010, 12, 2171-2173.

The use of N-fluorobenzenesulfonimide (NFSI) enables an efficient, simple, and metal-free fluorination of 2H-indazoles in water under ambient air. This transformation provides direct access to fluorinated indazole derivatives with broad functionalities in good yields. The experimental results suggest a radical mechanistic pathway.
P. Ghosh, A. Hajra, J. Org. Chem., 2021, 86, 10883-10888.

An organophotoredox-catalyzed oxidative coupling enables a general and practical C-H amination of 2H-indazoles with a series of amines including aliphatic primary amines, secondary amines, azoles, and sulfoximines at room temperature under ambient air conditions.
S. Neogi, A. K. Ghosh, K. Majhi, S. Samanta, G. Kibriya, A. Hajra, Org. Lett., 2020, 22, 5605-5609.

Under visible-light irradiation at room temperature, 2-((aryl/alkyl/H)ethynyl))aryltriazenes reacted with arylsulfinic acids to afford 3-functionalized 2H-indazoles without extra photocatalyst via an electron donor-acceptor complex. In the presence of arylsulfinic acid, 2-(ethynyl)aryltriazenes underwent an intramolecular oxidation/cyclization to provide 2H-indazole-3-carbaldehydes at 50 °C in air.
G. Zhang, Y. Zhang, P. Li, C. Zhou, M. Wang, L. Wang, J. Org. Chem., 2023, 88, 12341-12356.