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Synthesis of pyrazoles and indazoles

Recent Literature

1,3-Diketones, which were synthesized in situ from ketones and acid chlorides, were converted into pyrazoles by the addition of hydrazine. This method allows a fast and general synthesis of previously inaccessible pyrazoles and synthetically demanding pyrazole-containing fused rings.
S. T. Heller, S. R. Natarajan, Org. Lett., 2006, 8, 2675-2678.

A highly regioselective synthesis of 1-aryl-3,4,5-substituted pyrazoles based on the condensation of 1,3-diketones with arylhydrazines proceeds at room temperature in N,N-dimethylacetamide and furnishes pyrazoles in good yields.
F. Gosselin, P. D. O'Shea, R. A. Webster, R. A. Reamer, R. D. Tillyer, E. J. J. Grabowski, Synlett, 2006, 3267-3270.

Pyrazole or isoxazole derivatives are prepared by a palladium-catalyzed four-component coupling of a terminal alkyne, hydrazine (hydroxylamine), carbon monoxide under ambient pressure, and an aryl iodide.
M. S. M. Ahmed, K. Kobayashi, A. Mori, Org. Lett., 2005, 7, 4487-4489.

A simple one-pot method allows the synthesis of diversely functionalized N-arylpyrazoles from aryl nucleophiles, di-tert-butylazodicarboxlate, and 1,3-dicarbonyl or equivalent compounds.
B. S. Gerstenberger, M. R. Rauckhorst, J. T. Starr, Org. Lett., 2009, 11, 2097-2100.

M. S. M. Ahmed, K. Kobayashi, A. Mori, Org. Lett., 2005, 7, 4487-4489.

A regioselective synthesis of tri- or tetrasubstituted pyrazoles by the reaction of hydrazones with nitroolefins mediated with strong bases such as t-BuOK exhibits a reversed, exclusive 1,3,4-regioselectivity. Subsequent quenching with strong acids such as TFA is essential to achieve good yields. A stepwise cycloaddition reaction mechanism is proposed.
X. Deng, N. S. Mani, Org. Lett., 2008, 10, 1307-1310.

Two general protocols for the reaction of electron-deficient N-arylhydrazones with nitroolefins allow a regioselective synthesis of 1,3,5-tri- and 1,3,4,5-tetrasubstituted pyrazoles. Studies on the stereochemistry of the key pyrazolidine intermediate suggest a stepwise cycloaddition mechanism.
X. Deng, N. S. Mani, J. Org. Chem., 2008, 73, 2412-2415.

A regioselective one-pot synthesis of substituted pyrazoles from N-monosubstituted hydrazones and nitroolefins gives products in good yields. A key nitropyrazolidine intermediate is characterized and a plausible mechanism is proposed.
X. Deng, N. S. Mani, Org. Lett., 2006, 8, 3505-3508.

A general, highly flexible Cu-catalyzed domino C-N coupling/hydroamination reaction constitutes a straightforward alternative to existing methodology for the preparation of pyrroles and pyrazoles.
R. Martin, M. R. Rivero, S. L. Buchwald, Angew. Chem. Int. Ed., 2006, 45, 7079-7082.

Various 1-acyl-5-hydroxy-4,5-dihydro-1H-pyrazoles have been prepared in good yields from the corresponding 2-alkyn-1-ones. The resulting dihydropyrazoles undergo dehydration and iodination in the presence of ICl and Li₂CO₃ at room temperature to provide 1-acyl-4-iodo-1H-pyrazoles.
J. P. Waldo, S. Mehta, R. C. Larock, J. Org. Chem., 2008, 73, 6666-6670.

A series of 4-substituted 1H-pyrazole-5-carboxylates was prepared from the cyclocondensation reaction of unsymmetrical enaminodiketones with tert-butylhydrazine hydrochloride or carboxymethylhydrazine. The compounds were obtained regiospecifically and in very good yields.
F. A. Rosa, P. Machado, P. S. Vargas, H. G. Bonacorso, N. Zanatta, M. A. P. Martins, Synlett, 2008, 1673-1678.

An easy and efficient copper-catalyzed reaction for the synthesis of polysubstituted pyrazoles from phenylhydrazones and dialkyl ethylenedicarboxylates tolerates a range of functionalities, and the corresponding adducts can be obtained in moderate to good yields.
C. Ma, Y. Li, P. Wen, R. Yan, Z. Ren, G. Huang, Synlett, 2011, 1321-1323.

The reaction of diazo(trimethylsilyl)methylmagnesium bromide with aldehydes or ketones gave 2-diazo-2-(trimethylsilyl)ethanols, which were applied to the synthesis of di- and trisubstituted pyrazoles via [3+2] cycloaddition reaction with ethyl propiolate or dimethyl acetylenedicarboxylate.
Y. Hari, S. Tsuchida, R. Sone, T. Aoyama, Synthesis, 2007, 3371-3375.

In the presence of activated carbon, Hantzsch 1,4-dihydropyridines and 1,3,5-trisubstituted pyrazolines were aromatized with molecular oxygen to the corresponding pyridines and pyrazoles in excellent yields.
N. Nakamichi, Y. Kawashita, M. Hayashi, Synthesis, 2004, 1015-1020.

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.

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.

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.

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.

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.