Categories: C-C Bond Formation > Nitrogen-containing molecules >
Synthesis of Nitro compounds
In a Pd-catalyzed formation of arylnitromethanes from readily available aryl halides or triflates, 2-10 equiv of nitromethane in dioxane as solvent can be employed in comparison to prior work that used nitromethane as solvent (185 equiv). The present transformation reduces the hazards associated with MeNO2, provides high yields at relatively low temperatures, and tolerates an array of functionality.
R. R. Walvoord, M. C. Kozlowski, J. Org. Chem., 2013, 78, 8859-8864.
An efficient cross-coupling reaction of aryl halides and nitromethane gives arylnitromethane products, that are precursors for numerous useful synthetic products. An efficient method for their direct conversion to the corresponding oximes and aldehydes in a one-pot operation has been discovered. The process exploits inexpensive nitromethane as a carbonyl equivalent, providing a mild and convenient formylation method.
R. R. Walvoord, S. Berritt, M. C. Kozlowski, Org. Lett., 2012, 14, 4086-4089.
An efficient, mild, and metal-free arylation of nitroalkanes with diaryliodonium salts gives convenient access to tertiary nitro compounds in high yields without the need for excess reagents. The C-arylation can be extended to α-arylation of nitroesters and tolerates other easily arylated functional groups, such as phenols and aliphatic alcohols.
C. Dey, E. Lindstedt, B. Olofsson, Org. Lett., 2015, 17, 4554-4557.
Pd-catalyzed asymmetric allylic alkylation of nitroalkanes and monosubstituted allylic substrates affords products with two adjacent chiral centers in excellent regio-, diastereo-, and enantioselectivities. Products can be transformed to optically active homoallylamines, 2,3-disubstituted tetrahydropyridines, and α,β-disubstituted amino acid derivatives.
X.-F. Yang, W.-H. Yu, C.-H. Ding, Q.-P. Ding, S.-L. Wan, X.-L. Hou, L.-X. Dai, P.-J. Wang, J. Org. Chem., 2013, 78, 6503-6509.
Allyl nitroacetates undergo decarboxylative allylation to provide tertiary nitroalkanes in high yield within several minutes under ambient conditions. The preparation of substrate allyl nitroacetates by tandem Knoevenagel/Diels-Alder sequences allows the facile synthesis of relatively complex substrates that undergo diastereoselective decarboxylative allylation.
A. J. Grenning, J.A. Tunge, Org. Lett., 2010, 12, 740-742.
A simple Cu(I) catalyst, generated in situ, is highly effective for C-benzylation of nitroalkanes using abundant benzyl bromides and related heteroaromatic compounds. This process proceeds via a thermal redox mechanism and allows access to a variety of complex nitroalkanes under mild reaction conditions.
P. G. Gildner, A. A. S. Gietter, D. Cui, D. A. Watson, J. Am. Chem. Soc., 2012, 134, 9942-9945.
A palladium-catalyzed double coupling of nitromethane with vinyl triflates and bromide generates homo allyl nitro products via a tandem cross-coupling/π-allylation sequence. The resultant process exploits the anion stabilizing and leaving group properties of nitromethane and provides a mild and convenient entry to nitroethylated products, which are versatile precursors to β,γ-unsaturated carbonyls, homoallylic amines, and nitrile oxides.
R. Padilla-Salinas. R. R. Walvoord, S. Tcyrulnikov, M. C. Kozlowski, Org. Lett., 2013, 15, 3966-3969.
A calcium vanadate apatite (VAp) acts as a high-performance heterogeneous base catalyst for various carbon-carbon bond-forming reactions such as Michael and aldol reactions in aqueous media. No vanadium leaching was detected and the catalyst was readily recycled with no loss of activity.
T. Hara, S. Kanai, K. Mori, T. Mizugaki, K. Ebitani, K. Jitsukawa, K. Kaneda, J. Org. Chem., 2006, 71, 7455-7462.
A catalytic enantioselective direct conjugate addition of nitroalkanes to α,β-unsaturated aldehydes using diphenylprolinol silyl ether as an organocatalyst enables short syntheses of therapeutically useful compounds.
H. Gotoh, H. Ishikawa, Y. Hayashi, Org. Lett., 2007, 9, 5307-5309.
Helical peptide foldamers catalyze Michael addition reactions of nitroalkanes or dialkyl malonates to α,β-unsaturated ketones to give Michael adducts with high enantioselectivities. The amide protons at the N terminus in the α-helical peptide catalyst are crucial for activating Michael donors, while the N-terminal primary amine activates Michael acceptors through the formation of iminium ion intermediates.
A. Ueda, T. Umeno, M. Doi, K. Akagawa, K. Kudo, M. Tanaka, J. Org. Chem., 2016, 81, 6343-6356.
The use of a sulfonamide-thiourea organocatalyst enabels an asymmetric conjugate addition of nitroalkanes to α,β-unsaturated ketones to provide the corresponding γ-nitro carbonyl products in high yields with excellent enantioselectivities.
M. Kawada, K. Nakashima, S.-i. Hirashima, A. Yoshida, Y. Koseki, T. Miura, J. Org. Chem., 2017, 82, 6986-6991.
C6'-OH cinchona alkaloid-catalyzed asymmetric nitroaldol reactions with α-ketoesters are highly efficient, operationally simple, and afford high enantioselectivity as well as good to excellent yield for a broad range of α-ketoesters.
H. Li, B. Wang. L. Deng, J. Am. Chem. Soc., 2006, 128, 732-733.
Racemic 1-nitroalkan-2-ols are obtained by reaction of bromonitromethane with a variety of aldehydes promoted by SmI2. Chiral N,N-dibenzyl amino aldehydes afford the corresponding enantiopure 3-amino-1-nitroalkan-2-ols with good diastereoselectivity.
J. M. Concellón, H. Rodríguez-Solla, C. Concellón, J. Org. Chem., 2006, 71, 7919-7922.
The Henry reaction can be performed under very mild reaction conditions in 0.025 M NaOH in the presence of cetyltrimethylammonium chloride as cationic surfactant. Short reaction times are required and both primary and secondary nitroalkanes give good results.
R. Ballini, G. Bosica, J. Org. Chem., 1997, 62, 425-427.
Quaternary ammonium derivatives of cinchona alkaloids are highly efficient catalysts for asymmetric nitro-Mannich reactions of amidosulfones. A very broad substrate generality was observed, and both enantiomers of the products can be synthesized in high enantio- and diastereoselectivity.
B. Wang, Y. Liu, C. Sun, Z. Wei, J. Cao, D. Liang, Y. Lin, H. Duan, Org. Lett., 2014, 16, 6432-6435.
A dinuclear zinc-AzePhenol complex catalyzes an asymmetric aza-Henry reaction of N-Boc imines and nitroalkanes to provide various nitroamines in good yields with excellent enantioselectivities and high diasteroselectivity. The method offers operational simplicity and mild reaction conditions.
S. Liu, W.-C. Gao, Y.-H. Miao, M.-C. Wang, J. Org. Chem., 2019, 84, 2654-2659.
Electrochemically Induced Aza-Henry Reaction: A New, Mild, and Clean Synthesis of α-Nitroamines
L. Rossi, G. Bianchi, M. Feroci, A. Inesi, Synlett, 2007, 2505-2508.
Heating a solution of an aldehyde, an aromatic amine, and a nitroalkane in 20% water-methanol at 60°C for five hours enables an environmentally benign three-component, one-pot synthesis of 2-nitroamines in the absence of a catalyst.
C. G. Piscopo, G. Sartori, J. A. Mayoral, D. Lanari, L. Vaccaro, R. Maggi, Synlett, 2013, 24, 2596-2600.
A chiral bifunctional multiple hydrogen-bonding-donor amine-thiourea catalyzes a highly anti-selective and enantioselective nitro-Mannich reaction for a broad spectrum of substrates. Multiple hydrogen-bonding donors play a significant role in accelerating reactions and improving yields, diastereoselectivities, and enantioselectivities.
C.-J. Wang, X.-Q. Dong, Z.-H. Zhang, Z.-Y. Xue, H.-L. Teng, J. Am. Chem. Soc., 2008, 130, 8606-8607.
In the presence of only 5 mol% Na2CO3, N-tosyl ketoimines can react with nitromethane to give β-nitroamines via aza-Henry reaction in very good yields in THF at room temperature.
L. Wang, C. Tan, X. Liu, X. Feng, Synlett, 2008, 2075-2077.
An enantioselective synthesis of γ-nitroesters by a one-pot asymmetric Michael addition/oxidative esterification of α,β-unsaturated aldehydes is based on an enantioselective organocatalytic nitroalkane addition followed by an N-bromosuccinimide-based oxidation. The γ-nitroesters are obtained in good yields and enantioselectivities, and the method provides an attractive entry to optically active γ-aminoesters, 2-piperidones, and 2-pyrrolidones.
K. L. Jensen, P. H. Poulsen, B. S. Donslund, F. Morana, K. A. Jřrgensen, Org. Lett., 2012, 14, 1516-1519.
In a Michael addition of nitromethane to α,β-unsaturated aldehydes via iminium activation, a MeOPEG-supported, recyclable Jřrgensen-Hayashi catalyst provides unchanged reactivity and selectivity as compared to the homogeneous catalyst. The immobilization enables a simple, column-free isolation of pure, sensitive aldehyde products and therefore may be useful for application in more complicated syntheses.
I. Mager, K. Zeitler, Org. Lett., 2010, 12, 1480-1483.
A chiral primary amine-thiourea catalyst based on dehydroabietic amine enables a highly enantioselective Michael addition of nitroalkanes to α,β-unsaturated ketones to yield γ-nitro ketones with excellent enantioselectivities (up to 99% ee) and in up to 96% yield. This protocol was successfully applied in asymmetric syntheses of (R)-baclofen and (R)-phenibut.
X.-T. Guo, J. Shen, F. Sha, X.-Y. Wu, Synthesis, 2015, 47, 2063-2072.
An N-spiro C2-symmetric chiral quaternary ammonium bromide efficiently catalyzed the conjugate addition of various prochiral nitroalkanes to cyclic α,β-unsaturated ketones under solid-liquid phase-transfer conditions to afford the corresponding γ-nitro ketones in excellent yields with high levels of diastereo- and enantiocontrol.
T. Ooi, S. Takada, S. Fujioka, K. Maruoka, Org. Lett., 2005, 7, 5143-5146.
The conjugate addition of symmetrical 2-nitroalkanes to 2-cycloalkenones catalyzed by trans-4,5-methano-L-proline proceeds with excellent enantioselectivity and chemical yields. 1-Nitroalkanes afford diastereomeric syn/anti products that can be separated with good individual enantioselectivities.
S. Hanessian, Z. Shao, J. S. Warrier, Org. Lett., 2006, 8, 4787-4790.
The conversion of primary nitroalkanes into the corresponding α-nitro ketones readily proceeds using N-acylbenzotriazoles as acylation agents.
A. R. Katritzky, A. A. A. Abdel-Fattah, A. V. Gromova, R. Witek, P. J. Steel, J. Org. Chem., 2005, 70, 9211-9214.
The use of a commercially available Umemoto’s reagent enables a metal-free trifluoromethylation of nitroalkanes. This method provides quaternary α-(trifluoromethyl)nitroalkanes, that can be elaborated to various complex nitrogen-containing molecules, including α-(trifluoromethyl)amines.
A. S. Gietter-Burch, V. Devannah, D. A. Watson, Org. Lett., 2017, 19, 2957-2960.