Categories: Synthesis of N-Heterocycles >
Synthesis of pyrazoles and indazoles
An iron-catalyzed route for the regioselective synthesis of 1,3- and 1,3,5-substituted pyrazoles from the reaction of diarylhydrazones and vicinal diols allows the conversions of a broad range of substrates.
N. Panda, A. K. Jena, J. Org. Chem., 2012, 77, 9401-9406.
An efficient, general, one-pot, three-component procedure for the preparation of 3,5-disubstituted 1H-pyrazoles includes condensation of substituted aromatic aldehydes and tosylhydrazine followed by cycloaddition with terminal alkynes. The reaction tolerates various functional groups and sterically hindered substrates to afford the desired pyrazoles in good yields.
L.-L. Wu, Y.-C. Ge, T. He, L. Zhang, X.-L. Fu, H.-Y. Fu, H. Chen, R.-X. Li, Synthesis, 2012, 44, 1577-1583.
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.
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.
An unprecedented ruthenium(II)-catalyzed oxidative C-N coupling method enables a facile intramolecular synthesis of various synthetically challenging tri- and tetrasubstituted pyrazoles in the presence of oxygen as oxidant. The reaction demonstrates excellent reactivity, functional group tolerance, and high yields.
J. Hu, S. Chen, Y. Sun, J. Yang, Y. Rao, Org. Lett., 2012, 14, 5030-5033.
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.
Alumino-heteroles are obtained from simple precursors in a fully chemo- and regioselective manner by a metalative cyclization. The carbon-aluminum bond is still able to react further with several electrophiles, without the need of transmetalation providing a straightforward access to 3,4,5-trisubstituted isoxazoles and 1,3,4,5-tetrasubstituted pyrazoles.
O. Jackowski, T. Lecourt, L. Micouin, Org. Lett., 2011, 13, 5664-5667.
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 tandem catalytic cross-coupling/electrocyclization allows the conversion of differentially substituted acyclic and cyclic enol triflates and an elaborated set of diazoacetates to provide the corresponding 3,4,5-trisubstituted pyrazoles with a high degree of structural complexity.
D. J. Babinski, H. R. Aguilar, R. Still, D. E. Frantz, J. Org. Chem., 2011, 76, 5915-5923.
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.
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.
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.
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.
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.
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.
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.