Synthesis of quinolines
Heteroaromatic tosylates and phosphates are suitable electrophiles in iron-catalyzed cross-coupling reactions with alkyl Grignard reagents. These reactions are performed at low temperature allowing good functional group tolerance with full conversion within minutes.
T. M. Gøgsig, A. T. Lindhardt, T. Skrydstrup, Org. Lett., 2009, 11, 4886-4888.
The success of a one-step transformation of heterocyclic N-oxides to 2-alkyl-, aryl-, and alkenyl-substituted N-heterocycles hinges on the combination of copper catalysis and activation by lithium fluoride or magnesium chloride. The utility for the scaffold decoration of a broad range of complex N-heterocycles is exemplified by syntheses of new structural analogues of several antimalarial, antimicrobial, and fungicidal agents.
O. V. Larionov, D. Stephens, A. Mfuh, G. Chavez, Org. Lett., 2014, 16, 864-867.
A heterogeneous cobalt oxide is an effective catalyst for aerobic dehydrogenation of various 1,2,3,4-tetrahydroquinolines to the corresponding quinolines in good yields under mild conditions. Other N-heterocycles are also successfully oxidized to their aromatic counterparts.
A. V. Iosub, S. S. Stahl, Org. Lett., 2015, 17, 4404-4407.
Visible light-mediated metallaphotoredox catalysis enables a highly chemoselective deoxygenation of N-heterocyclic N-oxides using Hantzsch esters as the stoichiometric reductants and only a tiny amount of the catalyst within a few minutes at room temperature. The reaction tolerates a wide range of functional groups, such as carbamates, esters, ketones, nitrile groups, nitro groups, and halogens.
J. H. An, K. D. Kim, J. H. Lee, J. Org. Chem., 2021, 86, 2876-2894.
Visible-light mediates a scalable and operationally simple method for the chemoselective deoxygenation of a wide range of N-heterocyclic N-oxides at room temperature using only commercially available reagents. This protocol offers an unprecedented chemoselective removal of the oxygen atom in a quinoline N-oxide in the presence of a pyridine N-oxide through the judicious selection of the photocatalyst.
K. D. Kim, J. H. Lee, Org. Lett., 2018, 20, 7712-7716.
ZnMe2 promotes a direct C2- or C4-selective primary and secondary alkylation of a broad range of pyridines and quinolines using 1,1-diborylalkanes as alkylation sources. While substituted pyridines and quinolines exclusively afford C2-alkylated products in good yields, simple pyridine delivers C4-alkylated pyridine with excellent regioselectivity.
W. Jo, S.-y. Baek, C. Hwang, J. Heo, M.-H. Baik, S. H. Cho, J. Am. Chem. Soc., 2020, 142, 13235-13245.
Pd(OAc)2/2,4,6-Collidine/Brønsted acid catalyze an aerobic oxidative aromatization of simple aliphatic alcohols and anilines to provide diverse substituted quinoline derivatives in high yields with wide functional group tolerance. Practically, the protocol can be easily scaled up to gram-scale.
J. Li, J. Zhang, H. Yang, G. Jiang, J. Org. Chem., 2017, 82, 3245-3251.
A Pd-catalyzed decarbonylative Suzuki cross-coupling of widely available heterocyclic carboxylic acids with arylboronic acids enabled the straightforward preparation of >45 heterobiaryl products using pyridines, pyrimidines, pyrazines, and quinolines in very good yields.
A. Cervantes-Reyes, A. C. Smith, G. M. Chinigo, D. C. Blakemore, M. Szostak, Org. Lett., 2022, 24, 1662-1667.
A [3+1+1+1] annulation of arylamines, arylaldehydes and dimethyl sulfoxide (DMSO) provides 3-arylquinolines in very good yields. In this annulation, arylamines provide two carbon atoms and one nitrogen atom, arylaldehydes furnish one carbon atom, and DMSO provides two nonadjacent methines (=CH-).
T. Yang, H. Li, Z. Nie, M.-d. Su, W.-p. Luo, Q. Liu, C.-C. Guo, J. Org. Chem., 2022, 87, 2797-2808.
A simple metal-ligand cooperative approach enables dehydrogenative functionalization of benzylic alcohols to various substituted quinolines and quinazolin-4(3H)-ones in good yields under relatively mild reaction conditions using simple and easy-to-prepare air-stable Cu(II) complexes featuring redox-active azo-aromatic scaffolds.
S. Das, S. Sinha, D. Samanta, R. Mondal, G. Chakraborty, P. Brandaõ, N. D. Paul, J. Org. Chem., 2019, 84, 10160-10171.
A convenient and eco-friendly nickel-catalyzed synthesis of quinoline and quinoxaline via double dehydrogenative coupling starting from 2-aminobenzyl alcohol/1-phenylethanol and diamine/diol, respectively, operates at mild reaction temperatures. The inexpensive molecularly defined catalyst can easly be regenerated under aerobic/O2 oxidation.
A. K. Bains, V. Singh, D. Adhikari, J. Org. Chem., 2020, 85, 14971-14979.
An annulation between 2-aminobenzyl alcohols, benzaldehydes, and DMSO provides quinolines. Interestingly, introducing substituent groups to the α-position of sulfoxides resulted in the interchange of the positions between benzaldehydes and sulfoxides in the product quinolines.
T. Yang, Z.-w. Nie, M.-d. Su, H. Li, W.-p. Luo, Q. Liu, C.-C. Guo, J. Org. Chem., 2021, 86, 15232-15241.
A visible-light-mediated oxidative cyclization of 2-aminobenzyl alcohols with secondary alcohols provides quinolines in good yields at room temperature. This photocatalytic method employes anthraquinone as an organic small-molecule catalyst and DMSO as an oxidant.
J.-x. Xu, N.-l. Pan, J.-x. Chen, J.-w. Zhao, J. Org. Chem., 2021, 86, 10747-10754.
Treatment of 2-arylethylmagnesium bromides, prepared from 2-arylethyl bromides and magnesium, with aromatic nitriles, followed by reaction with water and then with N-iodosuccinimide under irradiation with a tungsten lamp, provides 2-arylquinolines in good yields under transition-metal-free conditions. 2-Alkylquinolines could be also obtained in moderate yields.
H. Naruto, H. Togo, Synthesis, 2020, 52, 1122-1130.
Visible-light-excited 9,10-phenanthrenequinone (PQ*) catalyzes a mild and efficient electrocyclization of 2-vinylarylimines for the synthesis of 2,4-disubstituted quinolines in very good yields.
J. Talvitie, I. Alanko, E. Bulatov, J. Koivula, T. Pöllänen, J. Helaja, Org. Lett., 2022, 24, 274-278.
The use of hydrazine under basic conditions enables an efficient and general construction of quinoline N-oxides from ortho-nitro chalcones via umpolung of carbonyl groups. This transition-metal free method offers good functional group tolerance, environmental friendliness, and mild reaction conditions with nitrogen gas as byproduct.
G. Zhang, K. Yang, S. Wang, Q. Feng, Q. Song, Org. Lett., 2021, 23, 595-600.
The use of hypervalent iodine(III) carboxylates as alkylating agents enables a highly site-selective alkylation of heteroarene N-oxides the presence of a cheap copper catalyst under visible light conditions. This mild method proceeds at room temperature in an air atmosphere.
D.-Y. Liu, X. Liu, Y. Gao, C.-Q. Wang, J.-S. Tian, T.-P. Loh, Org. Lett., 2020, 22, 8978-8983.
Eosin Y catalyzes a visible-light-promoted C2 selective arylation of quinoline and pyridine N-oxides with diaryliodonium tetrafluoroborate as an arylation reagent under mild conditions. This methodology offers high regioselectivity, simple operation and good functional group tolerance.
D. Li, C. Liang, Z. Jiang, J. Zhang, W.-T. Zhuo, F.-Y. Zou, W.-P. Wang, G.-L. Gao, J. Song, J. Org. Chem., 2020, 85, 2733-2742.
A nickel-catalyzed sequential dehydrogenation and condensation process enables a sustainable synthesis of a wide range of polysubstituted quinolines from α-2-aminoaryl alcohols. This strategy allows the use of both primary as well as secondary α-2-aminoaryl alcohols in combination with either ketones or secondary alcohols for desired product formation.
S. Das, D. Maiti, S. D. Sarkar, J. Org. Chem., 2018, 83, 2309-2316.
An Ir-catalyzed synthesis of functionalized quinolines from 2-aminobenzyl alcohols and α,β-unsaturated ketones tolerates a broad range of functional groups, offers high efficiency, is environmentally benign, and can be performed on a gram scale. Alkali is essential for the high selectivities of this catalytic system.
N. Luo, H. Shui, Y. Zhong, J. Huang, R. Luo, Synthesis, 2021, 53, 4516-4524.
By employing α-chlorodiazirines as thermal precursors to the corresponding chlorocarbenes, the traditional haloform-based protocol central to the parent Ciamician-Dennstedt rearrangement can be modified to directly afford 3-(hetero)arylpyridines and quinolines. Chlorodiazirines are conveniently prepared in a single step by oxidation of commercially available amidinium salts.
. D. Dherange, P. Q. Kelly, J. P. Liles, M. S. Sigman, M. D. Levin, J. Am. Chem. Soc., 2021, 143, 11337-11344.
COOH as a weakly coordinating and traceless directing group is essential for a synthesis of diverse polysubstituted quinolines from readily available acrylic acids and anthranils. Diverse polysubstituted quinolines were obtained under mild reaction conditions with simple H2O and CO2 as byproducts.
Y. Gao, J. Nie, Y. Li, X. Li, Q. Chen, Y. Huo, X.-Q. Hu, Org. Lett., 2020, 22, 2600-2605.
Autoxidation of organoboronic acids using 1 atm of O2 enables a simple, clean, and green carbon-carbon bond formation to provide structurally diverse heteroaromatics with medicinally privileged scaffolds.
L. Zhang, Z.-Q. Liu, Org. Lett., 2017, 19, 6594-9567.
The use of K2S2O8 and DMSO enables an efficient and transition-metal-free synthesis of 4-arylquinolines from readily available aryl alkynes and anilines with a diverse range of substitution patterns. DMSO acts as one carbon source, thus providing a highly atom-economical and environmentally benign approach for the synthesis of 4-arylquinolines.
M. Phanindrudu, S. B. Wakade, D. K. Tiwari, P. R. Likhar, D. K. Tiwari, J. Org. Chem., 2018, 83, 9137-9143.
A simple and efficient method enables a direct synthesis of substituted quinolines from anilines and aldehydes through C-H functionalization, C-C/C-N bond formation, and C-C bond cleavage in the presence of air as an oxidant.
R. Yan, X. Liu, C. Pan, X. Zhou, X. Li, X. Kang, G. Huang, Org. Lett., 2013, 15, 4876-4879.
An oxidative annulation involving anilines, aryl ketones, and DMSO as a methine (=CH−) equivalent promoted by K2S2O8 provides 4-arylquinolines, whereas activation of acetophenone-formamide conjugates enables the synthesis of 4-arylpyrimidines.
S. D. Jadhav, A. Singh, Org. Lett., 2017, 19, 5673-5676.
A highly efficient and regioselective Co(III)-catalyzed C-H activation/cyclization of simple, cheap, and easily available anilines with alkynes enables a direct synthesis of a broad range of privileged quinolines. In this reaction, DMSO serves both as the solvent and a C1 building block.
X. Xu, Y. Yang, X. Zhang, W. Yi, Org. Lett., 2018, 20, 566-569.
[4 + 2] Cycloaddition of azadienes (in situ generated from 2-aminobenzyl alcohol) and terminal alkynes enables a highly efficient metal and protection-free approach for the regioselective synthesis of C-3-functionalized quinolines, which are difficult to access.
R. K. Saunthwal, M. Patel, A. K. Verma, J. Org. Chem., 2016, 81, 6563-6572.
Singlet diradical Ni(II) featuring two antiferromagnetically coupled singlet diradical diamine type ligands catalyzes simple, straightforward, and atom economic syntheses of quinolines, 2-aminoquinolines, and quinazolines in good yields via biomimetic dehydrogenative condensation/coupling reactions.
G. Chakraborty, R. Sikari, S. Das, R. Mondal, S. Sinha, S. Banerjee, N. D. Paul, J. Org. Chem., 2019, 84, 2626-2641.
An annulation between 2-aminobenzyl alcohols, benzaldehydes, and DMSO provides quinolines. Interestingly, introducing substituent groups to the α-position of sulfoxides resulted in the interchange of the positions between benzaldehydes and sulfoxides in the product quinolines.
T. Yang, Z.-w. Nie, M.-d. Su, H. Li, W.-p. Luo, Q. Liu, C.-C. Guo, J. Org. Chem., 2021, 86, 15232-15241.
Selective addition of radicals to isonitriles enables a general route for the preparation of N-heteroaromatics. This method utilizes alkenes as synthetic equivalents of alkynes by coupling homoallylic ring expansion to yield the formal 6-endo products with aromatization via stereoelectronically assisted C-C bond scission.
C. J. Evoniuk, G. dos Passos Gomes, M. Ly, F. D. White, I. V. Alabugin, J. Org. Chem., 2017, 82, 4265-4278.
Benzylamine as the nucleophilic catalyst enables an on-water synthesis of 2-substituted quinolines in excellent yields from 2-aminochalcone derivatives. This protocol offers simple operation, broad substrate scope, good functional group tolerance, easy product isolation by simple filtration, recycling of the catalyst, and gram-scale synthesis.
S. Y. Lee, C.-H. Cheon, J. Org. Chem., 2018, 83, 13036-13044.
Quinolines can be synthesized from Δ2-isoxazolines under reductive conditions. The reductive cyclization to quinolines is achieved in the presence of iron or sodium dithionite under metal-free conditions.
P. Kamath, R. C. Viner, S. C. Smith, M. Lal, Synlett, 2017, 28, 1341-1345.
In a new benzylation protocol, various 1,2,3,4-tetrahydroquinolines were efficiently converted in combination with aryl aldehydes into β-benzylated quinolines by employing readily available [RuCl2(p-cymene)]2 as a catalyst and O2 as a sole green oxidant. This step- and atom-economic reaction offers excellent functional group tolerance and chemoselectivity.
Z. Tan, H. Jiang, M. Zhang, Org. Lett., 2016, 18, 3154-3157.
A highly chemoselective domino condensation/aza-Prins cyclization/retro-aldol between 2-alkenylanilines and β-dicarbonyl compounds provides a large variety of valuable 2-substituted quinolines in good yields. This metal-free reaction tolerates a broad range of functional groups and can even be simpliefied into a three component domino reaction.
J. Nan, P. Chen, Y. Zhang, Y. Yin, B. Wang, Y. Ma, J. Org. Chem., 2020, 85, 14042-14054.
In the presence of [Cp*Ir(6,6'-(OH)2bpy)(H2O)][OTf]2, an acceptorless dehydrogenative cyclization of o-aminobenzyl alcohols with ketones provided quinolines in high yields.
R. Wang, H. Fan, W. Zhao, F. Li, Org. Lett., 2016, 18, 3558-3561.
A practicable quinoline synthesis from aniline and two amino acids provides a wide range of quinolines with high efficiency and diversity including pharmaceutical derivatives, photochemical active compounds, and challenging scaffolds. Mechanistic studies revealed that I2 promotes decarboxylation, oxidative deamination, and selective formation of new C-N and C-C bonds.
J.-C. Xiang, Z.-X. Wang, Y. Cheng, S.-Q. Xia, M. Wang, B.-C. Tang, Y.-D. Wu, A.-X. Wu, J. Org. Chem., 2017, 82, 9210-9216.
A three-component cascade annulation of readily available aryl diazonium salts, nitriles, and alkynes enables an efficient, additive-free, and rapid synthesis of multiply substituted quinolines in good yields. Various aryl diazonium salts, nitriles, and alkynes can participate in this transformation.
H. Wang, Q. Xu, S. Shen, S. Yu, J. Org. Chem., 2017, 82, 770-775.
An oxidative annulation of o-allylanilines provides 2,4-diarylquinolines in good yields in the presence of chloranil as recyclable oxidant. Furthermore, a one-pot access to 2,4-diarylquinolines from easily available anilines and 1,3-diarylpropenes is described.
D. Cheng, X. Yan, J. Shen, Y. Pu, X. Xu, J. Yan, Synthesis, 2020, 52, 1833-1840.
A hydride Mn(I) PNP pincer complex catalyzes environmentally benign, sustainable, and practical syntheses of substituted quinolines and pyrimidines using combinations of 2-aminobenzyl alcohols and alcohols as well as benzamidine and two different alcohols, respectively. The reactions proceed with high atom efficiency via a sequence of dehydrogenation and condensation steps in very good isolated yields.
M. Mastalir, M. Glatz, E. Pittenauer, G. Allmaier, K. Kirchner, J. Am. Chem. Soc., 2016, 138, 15303-15306.
An efficient palladium(II)-catalyzed C-C coupling/cyclization reaction by directed C-H activation of benzamidine and terminal alkynes enables a practical and high-yielding synthesis of quinolines, in which the C-N bond acts as an internal oxidant. When using benzamidine with an ortho-methyl substituent, a [1,5]-hydrogen migration followed by a Diels-Alder reaction with terminal alkynes take place.
X. Zhang, X. Xu, Y. Wu, Z. Wang, L. Yu, Q. Zhao, F. Shi, Synlett, 2015, 26, 1885-1889.
An iron-catalyzed intermolecular [4 + 2] cyclization of arylnitrones with geminal-substituted vinyl acetates enables the synthesis of 2,4-disubstituted quinolines in good yields with good functional group compatibilities. Preliminary mechanistic studies suggest an iron-catalyzed C-H activation process.
M. Zhong, S. Sun, J. Cheng, Y. Shao, J. Org. Chem., 2016, 81, 10825-10831.
In an efficient cascade copper-catalyzed intermolecular Ullmann-type C-N coupling/enamine condensation reaction, ortho-acylanilines and alkenyl iodides are converted to multisubstituted quinolines in very good yields.
J. Zheng, L. Huang, C. Huang, W. Wu, H. Jiang, J. Org. Chem., 2015, 80, 1235-1242.
A regioselective 6-endo-trig intramolecular oxidative cyclization enabled an efficient synthesis of 2-aryl 4-substituted quinolines from stable and readily available o-cinnamylanilines with KOtBu as a mediator and DMSO as an oxidant at rt. The reaction showed a broad substrate scope with very good yields.
M. Rehan, G. Hazra, P. Ghorai, Org. Lett., 2015, 17, 1668-1671.
A silver-catalyzed sequential formation of two C-C bonds enabels the construction of a series of polysubstituted quinolines from anilines, aldehydes, and alcohols under mild conditions. The transformation is effective for a broad range of substrates, including aliphatic alcohols, arylalkanols, cycloalkanols, and ethylene glycol.
X. Zhang, W. Liu, R. Sun, X. Xu, Z. Wang, Y. Yan, Synlett, 2016, 27, 1563-1568.
A tandem reaction consisting of a [IrCp*Cl2]2/KOH catalyzed isomerization/cyclization of allylic alcohols with 2-aminobenzyl alcohol enables the synthesis of quinolines. Secondary and primary allylic alcohols afford differently substituted quinoline derivatives in good yields.
S.-j. Chen, G.-p. Lu, C. Cai, Synthesis, 2015, 47, 976-984.
A series of 2,4-disubstituted quinolines were easily prepared through a one-pot reaction of structurally diverse 2-aminoaryl ketones with various arylacetylenes in the presence of K5CoW12O40 • 3 H2O as a reusable and environmentally benign catalyst under microwave irradiation and solvent-free conditions.
I. Mohammadpoor-Baltork, S. Tangestaninejad, M. Moghadam, V. Mirkhani, S. Anvar, A. Mirjafari, Synlett, 2010, 3104-3112.
An eco-friendly method allows the synthesis of 2,4-disubstituted quinolines via Meyer-Schuster rearrangement of 2-aminoaryl ketones and phenylacetylenes in the presence of a catalytic amount of zinc trifluoromethanesulfonate in the ionic liquid [hmim]PF6. The ionic liquid can be recycled.
R. Sarma, D. Prajapati, Synlett, 2008, 3001-3005.
A facile and efficient iron-catalyzed intramolecular allylic amination of 2-aminophenyl-1-en-3-ols proceeded smoothly to afford 1,2-dihydroquinoline and quinoline derivatives under mild reaction conditions with good yields.
Z. Wang, S. Li, B. Wu, Y. Wang, X. Sun, J. Org. Chem., 2012, 77, 8615-8620.
A cross-coupling of unprotected ortho-bromoanilines with a wide range of cyclopropanols yields quinolines in a single operation via an intramolecular condensation and palladium-catalyzed oxidation sequence. Deuterium-labeling experiments provide direct evidence of a second equivalent of bromoaniline serving as the terminal oxidant.
A. Nikolaev, N. Nithiy, A. Orellana, Synlett, 2014, 25, 2301-2305.
An efficient one-pot procedure allows the preparation of substituted quinolines from activated acetylenes and o-tosylamidocarbonyl compounds under base-catalyzed, mild conditions. The generation of a β-phosphonium enoate α-vinyl anion in situ is followed by Michael addition of the deprotonated tosylamides and subsequent rapid aldol cyclization. Detosylation of the dihydroquinoline intermediates occurred readily in the presence of aqueous HCl.
S. Khong, O. Kwon, J. Org. Chem., 2012, 77, 8257-8267.
An unprecedented synthesis of aromatic ring annulated pyridines from suitably substituted primary allylamines via intramolecular electrophilic aromatic cyclization is mediated by molecular iodine under mild conditions.
H. Batchu, S. Bhattacharyya, S. Batra, Org. Lett., 2012, 14, 6330-6333.
The use of vinyl ethers as robust, inexpensive acetyl sources enables a mild, operationally simple Minisci C-H acetylation of N-heteroarenes. The reaction does not require a catalyst or high temperature and is therefore significantly more sustainable than previously reported methods in terms of cost, reagent toxicity, and waste generation.
J. Dong, J. Liu, H. Song, Y. Liu, Q. Wang, Org. Lett., 2021, 23, 4374-4378.
A highly efficient I2-promoted formal [4 + 2] cycloaddition enables the synthesis of 2-acylquinolines from methyl ketones and arylamines using 1,4-dithane-2,5-diol as an ethylene surrogate. This reaction occurred via an iodination/Kornblum oxidation/Povarov/aromatization sequence with an important role of the arylamine substrate in promoting the reaction.
X. Wu, X. Geng, P. Zhao, J. Zhang, X. Gong, Y.-d. Wu, A.-x. Wu, Org. Lett., 2017, 19, 1550-1553.
Iron(II) phthalocyanine catalyzes a photo-thermo-mechanochemical synthesis of quinolines. This solvent-free transformation features a cost-efficient catalytic system and operational simplicity, and shows good substrate tolerance, providing a green alternative to existing thermal approaches.
L. Liu, J. Lin, M. Pang, H. Jin, X. Yu, S. Wang, Org. Lett., 2022, 24, 1146-1151.
A synergistic I2/amine promoted formal [4 + 2] cycloaddition of methyl ketones, arylamines, and aryl(alkyl)acetaldehydes provides various 2-acyl-3-aryl(alkyl)quinolines via an iodination/Kornblum oxidation/Povarov/aromatization sequence. Notably, the arylamine reactants also acted as indispensable catalysts to promote enamine formation.
X. Geng, X. Wu, P. Zhao, J. Zhang, Y.-D. Wu, A.-X. Wu, Org. Lett., 2017, 19, 4179-4182.
A ruthenium-catalyzed [5 + 1] annulation of 2-alkenylanilines with sulfoxonium ylides provides highly functionalized quinolines with good yields and excellent functional group tolerance.
P. Chen, J. Nan, Y. Hu, Q. Ma, Y. Ma, Org. Lett., 2019, 21, 4812-4815.
Synergistic control of the temperature and amount of catalyst enables a divergent synthesis of N-arylenaminones and 3-aroylquinolines from 2-aminoaryl ketones and N,N-dimethylenaminones in the presence of 4-toluenesulfonic acid. The protocols offers mild conditions, good functional-group tolerance, operational simplicity, and excellent yields.
P. Zhou, B. Hu, K. Rao, L. Li, J. Yang, C. Gao, F. Wang, F. Yu, Synlett, 2018, 29, 519-524.
A one-pot reaction cascade reaction enables a transition-metal-free construction of functionalized quinolines from readily available acetophenones and anthranils. The reaction involves in situ generation of α,β-unsaturated ketones from the acetophenone via one-carbon homologation by DMSO followed by the aza-Michael addition of anthranils and subsequent annulation. DMSO acts not only as solvent but also as one carbon source.
S. B. Wakade, D. K. Tiwari, P. S. K. P. Ganesh, M. Phanindrudu, P. R. Likhar, D. K. Tiwari, Org. Lett., 2017, 19, 4948-4951.
A palladium-catalyzed Heck reaction enables an efficient synthesis of 2,3-disubstituted quinoline derivatives from easily accessible (het)aryl-substituted Morita-Baylis-Hillman adducts via α-benzyl β-keto ester derivatives that can cyclize into the corresponding quinolines in good yields.
K. Selvakumar, K. A. P. Lingam, R. V. L. Varma, V. Vijayabaskar, Synlett, 2015, 26, 646-650.
A Pd-catalyzed oxidative cyclization of o-vinylanilines and alkynes in the presence of molecular oxygen enables the construction of 2,3-disubstituted quinolines via intermolecular amination of alkyne, insertion of the olefin, and oxidative cleavage of a C-C bond.
J. Zheng, T. Li, L. Huang, W. Wu, J. Li, H. Jiang, Org. Lett., 2016, 18, 3514-3517.
A visible-light induced photocatalytic aerobic oxidative dehydrogenative coupling/aromatization tandem reaction of glycine esters with unactivated alkenes provides quinoline derivatives in good yield under mild and operationally simple reaction conditions.
X. Yang, L. Li, Y. Li, Y. Zhang, J. Org. Chem., 2016, 81, 12433-12442.
A highly efficient molecular iodine mediated formal [3 + 2 + 1] cycloaddition reaction enables the direct synthesis of substituted quinolines from methyl ketones, arylamines, and styrenes. A self-sequenced iodination/Kornblum oxidation/Povarov/aromatization mechanism has been proposed.
Q. Gao, S. Liu, X. Wu, A. Wu, Org. Lett., 2014, 16, 4582-4585.
A domino C-H functionalization of glycine derivatives for the production of a series of quinolines was achieved under catalytic radical cation salt induced conditions. A mechanism is proposed, that includes a peroxyl radical cation, which is generated by the coupling between O2 and TBPA+•.
X. Jia, F. Peng, C. Qing, C. Huo, X. Wang, Org. Lett., 2012, 14, 4030-4033.
An iron-promoted tandem reaction of anilines with styrene oxides via C-C cleavage and C-H activation utilizes inexpensive FeCl3 as promoter and is suitable for forming various 3-arylquinolines from simple and readily available starting materials.
Y. Zhang, M. Wang, P. Li, L. Wang, Org. Lett., 2012, 14, 2206-2209.
An efficient single-step approach toward the synthesis of 2-alkylquinolines is mediated by a Lewis acid through [3 + 3] annulation reaction between 3-ethoxycyclobutanones and aromatic amines. Various multisubstituted 2-alkylquinoline derivatives were prepared regioselectively at room temperature.
G. Shan, X. Sun, Q. Xia, Y. Rao, Org. Lett., 2011, 13, 5770-5773.
An environmentally friendly and highly efficient procedure gives 2,4-disubstituted quinoline derivatives by a simple alkynylation-cyclization reaction of 2-aminoaryl ketones with phenylacetylenes in the presence of indium(III) trifluoromethanesulfonate In(OTf)3 under microwave irradiation and solvent-free conditions. The catalyst can be reused.
K. C. Lekhok, D. Prajapati, R. C. Boruah, Synlett, 2008, 655-658.
A cooperative catalytic system, consisting of CuI and pyrrolidine enables an efficient synthesis of 2-substituted quinolines. A combination of both catalysts is necessary; the use of either catalyst alone does not give the product.
N. T. Patil, V. S. Raut, J. Org. Chem., 2010, 75, 6961-6964.
A three-component reaction of nitroarenes, aldehydes, and phenylacetylene in the presence of indium in dilute hydrochloric acid produces quinoline derivatives under reflux. The conversion involves reduction of the nitroarenes to anilines followed by coupling of the anilines, aldehydes, and phenylacetylene, followed by cyclization of the resulting species and dehydrogenation of the cyclic intermediates.
B. Das, P. Jangili, J. Kashanna, R. A. Kumar, Synthesis, 2011, 3267-3270.
A straightforward and efficient Yb(OTf)3 catalyzed three-component reaction of aldehydes, alkynes, and amines under microwave irradiation in an ionic liquid provides 2,4-disubstituted quinolines in excellent yield under mild reaction condition. The catalyst can be recycled up to four times.
A. Kumar, V. K. Rao, Synlett, 2011, 2157-2162.
A Fe(acac)3/TBAOH-catalyzed three-component coupling-cycloisomerization reaction of aldehydes, terminal alkynes, and amines provides a diverse range of heterocyclic compounds such as aminoindolizines and quinoline derivatives in good yields.
S. S. Patil, S. V. Patil, V. D. Bobade, Synlett, 2011, 2379-2383.
A modified Larock method enables a one-pot synthesis of substituted quinolines via a Heck reaction of 2-bromoanilines and allylic alcohols followed by dehydrogenation with diisopropyl azodicarboxylate (DIAD).
M. T. Stone, Org. Lett., 2011, 13, 2326-2329.
An efficient and regioselective alkenylation of azaheterocycle N-oxides with alkenes is catalyzed by iodine under metal- and external oxidant-free reaction conditions to provide various (E)-2-styrylazaheterocycles in good yields. The N-oxide group plays a dual role as both the directing group and an internal oxidant.
Z. Zhang, C. Pi, H. Tong, X. Cui, Y. Wu, Org. Lett., 2017, 19, 440-443.
A novel copper-catalyzed [5 + 1] annulation of 2-ethynylanilines with an N,O-acetal gives quinoline derivatives with an ester substituent on the 2-position. A combination of CuBr2 and trifluoroacetic acid (TFA) promotes a [5 + 1] annulation of 2-ethynylaniline with ethyl glyoxylatein the presence of piperidine.
N. Sakai, K. Tamura, K. Shimamura, R. Ikeda, T. Konakahara, Org. Lett., 2012, 14, 836-839.
Treatment of N-tosyl-2-propynylamines with diphenyliodonium triflate in the presence of K3PO4 and a catalytic amount of CuCl at room temperature followed by N-iodosuccinimide and BF3·OEt2 at 0°C, and then NaOH in methanol solution provided 3-iodo-4-arylquinolines. Products underwent various cross-coupling reactions and were smoothly dehalogenated with zinc.
T. Sasaki, K. Moriyama, H. Togo, J. Org. Chem., 2017, 82, 11727-11734.
An electrophilic cyclization of alkynyl imines provides polysubstituted 3-haloquinolines using CuX-activated N-halosuccinimdes (NXS) as electrophiles. The NXS/CuX system is more active than single NXS and can be applied in the electrophilic cyclization of electron-deficient substrates.
L. Liu, D. Chen, J. Yao, Q. Zong, J. Wang, H. Zhou, J. Org. Chem., 2017, 82, 4625-4630.
Highly substituted 3-iodoquinolines bearing different alkyl and aryl moieties can be synthesized in good yields by a regioselective 6-endo-dig iodocyclization of 2-tosylaminophenylprop-1-yn-3-ols with molecular iodine under mild conditions. The resulting 3-iodoquinolines can be further functionalized by various coupling reactions.
S. Ali, H.-T. Zhu, X.-F. Xia, K.-G. Ji, Y.-F. Yang, X.-R. Song, Y.-M. Liang, Org. Lett., 2011, 13, 2598-2601.
Upon photoirradiation of o-alkynylaryl isocyanides in the presence of iodine, an intramolecular cyclization affords the corresponding 2,4-diiodoquinolines in good yields. 2,4-Diiodoquinolines can be employed in regioselective transition metal-catalyzed cross-coupling reactions.
T. Mitamura, A. Ogawa, X. Pan, J. Org. Chem., 2011, 76, 1163-1166.
A Pd-catalyzed Wacker-type oxidative cyclization under air allows the construction of 2-methylquinolines in good yields under mild conditions.
Z. Zhang, J. Tang, Z. Wang, Org. Lett., 2008, 10, 173-175.
A direct reaction between 2-aminobenzylic alcohol derivatives and either ketones or alcohols in the presence of a base and benzophenone as hydride scavenger allows the synthesis of polysubstituted quinolines without any transition-metal catalyst.
R. Martínez, D. J. Ramón, M. Yus, J. Org. Chem., 2008, 73, 9778-9780.
An efficient and convenient nickel-catalyzed cyclization of 2-iodoanilines with alkynyl aryl ketones gives 2,4-disubstituted quinolines. Naturally occurring quinoline derivatives have been prepared in good yields. The mechanism is discussed.
R. P. Korivi, C.-H. Cheng, J. Org. Chem., 2006, 71, 7079-7082.
A direct convergent two-component synthesis of quinolines from α,β-unsaturated ketones and o-aminophenylboronic acid derivatives is regiocomplementary to the traditional Skraup-Doebner-Von Miller synthesis and proceeds under basic rather than strongly acidic conditions.
J. Horn, S. P. Marsden, A. Nelson, D. House, G. G. Weingarten, Org. Lett., 2008, 10, 4117-4120.
An efficient reductive cyclization of o-nitrocinnamoyl compounds was achieved by employing Hantzsch 1,4-dihydropyridine diethyl ester as a biomimetic reducing agent in the presence of catalytic palladium on carbon. This approach was successfully applied to the synthesis of substituted quinolines.
R.-G. Xing, Y.-N. Li, Q. Liu, Y.-F. Han, X. Wei, J. Li, B. Zhou, Synthesis, 2011, 2066-2072.
Reduction of secondary and tertiary o-nitrophenyl propargyl alcohols followed by acid-catalyzed Meyer-Schuster rearrangement gave 2-substituted and 2,4-disubstituted quinolines, respectively in good yields.
M. J. Sandelier, P. DeShong, Org. Lett., 2007, 9, 3209-3212.
A one-pot dehydrogenative Povarov/oxidation tandem reaction of N-alkyl anilines with mono- and 1,2-disubstituted aryl and alkyl olefins enables the synthesis of a various substituted quinolines. The simple protocol uses cheap and benign iron(III)chloride as the Lewis acid catalyst and a TEMPO oxoammonium salt as a nontoxic, mild, efficient oxidant.
H. Richter, O. G. Mancheño, Org. Lett., 2011, 13, 6066-6069.
A domino reaction of benzimidoyl chlorides with 1,6-enynes gives quinoline derivatives via palladium-catalyzed Sonogashira coupling and subsequent cyclization. The reaction conditions and the scope of the process are examined, and a plausible mechanism is proposed. The procedure is simple, rapid, and general, and the substrates are readily available.
G.-L. Gao, Y.-N. Niu, Z.-Y. Yan, H.-L. Wang, G.-W. Wang, A. Shaukat, Y.-M. Liang, J. Org. Chem., 2010, 75, 1305-1308.
The intramolecular cyclization of 1-azido-2-(2-propynyl)benzene proceeds smoothly in the presence of electrophilic reagents in CH3NO2 at room temperature or in the presence of catalytic amounts of AuCl3/AgNTf2 in THF at 100°C to afford the corresponding quinolines 2 in good to high yields.
Z. Huo, I. D. Gridnev, Y. Yamamoto, J. Org. Chem., 2010, 75, 1266-1270.
4-Aryl and 4-vinyl quinolines were prepared via a sequential procedure involving regioselective rhodium-catalyzed hydroarylation/hydrovinylation of β-(2-aminophenyl)-α,β-ynones with arylboronic acids or potassium aryl and vinyl trifluoroborates, followed by nucleophilic attack of the amino group onto the carbonyl.
G. Abbiati, A. Arcadi, F. Marinelli, E. Rossi, M. Verdecchia, Synlett, 2006, 3218-3224.
A simple, efficient and convenient copper-catalyzed method allows the synthesis of quinoline-2-carboxylate derivatives through sequential intermolecular addition of alkynes onto imines and subsequent intramolecular ring closure by arylation at room temperature.
H. Huang, H. Jiang, K. Chen, H. Liu, J. Org. Chem., 2009, 74, 5476-5480.
A copper-catalyzed tandem annulation of alkynyl imines with diazo compounds enables an efficient synthesis of a broad range of C4-functionalized quinolines in good yields via in situ formation of allene and intramolecular electrocyclization. The reaction offers high efficiency, mild reaction conditions, easy operation, and broad functional-group tolerance.
R. Zhu, G. Cheng, C. Jia, L. Xue, X. Cui, J. Org. Chem., 2016, 81, 7539-7544.
An efficient [2 + 1 + 3] cyclization reaction of aryl methyl ketones, arylamines, and 1,3-dicarbonyl compounds provides 2-aryl-4-quinolinecarboxylates in good yields under mild conditions. This metal-free process achieved a C-C bond cleavage of 1,3-dicarbonyl compounds for use as a C1 synthon.
Y. Zhou, P. Zhao, L.-S. Wang, X.-X. Yu, C. Huang, Y. D. Wu, A.-X. Wu, Org. Lett., 2021, 23, 6461-6465.
A highly efficient I2-catalyzed Povarov-type reaction of methyl ketones, arylamines, and α-ketoesters provides substituted quinolones in very good yields. The convenient procedure offers good functional group compatibility.
Q. Gao, S. Liu, X. Wu, J. Zhang, A. Wu, J. Org. Chem., 2015, 80, 5984-5991.
Cu-catalyzed aerobic cyclization of N-(2-alkynylaryl)enamine carboxylates via intramolecular carbo-oxygenation of alkynes gives highly substituted quinolines. This strategy was further applied for N-alkynylamidines leading to imidazole and quinazoline derivatives.
K. K. Toh, S. Sanjaya, S. Sahnoun, S. Y. Chong, S. Chiba, Org. Lett., 2012, 14, 2290-2292.
A single-step conversion of various N-vinyl and N-aryl amides to the corresponding pyridine and quinoline derivatives involves amide activation with trifluoromethanesulfonic anhydride in the presence of 2-chloropyridine followed by π-nucleophile addition to the activated intermediate and annulation. Compatibility of this chemistry with various functional groups is noteworthy.
M. Movassaghi, M. D. Hill, O. K. Ahmad, J. Am. Chem. Soc., 2007, 129, 10096-10097.
The direct conversion of amides, including sensitive N-vinyl amides, to the corresponding trimethylsilyl alkynyl imines followed by a ruthenium-catalyzed protodesilylation and cycloisomerization gives various substituted pyridines and quinolines.
M. Movassaghi, M. D. Hill, J. Am. Chem. Soc., 2006, 128, 4592-4593.
o-Quinone-based catalysts enable an oxidative dehydrogenation of tetrahydroquinolines to afford quinolines. Use of a Co(salophen) cocatalyst allows the reaction to proceed efficiently with ambient air at room temperature. The utility of the catalytic method is demonstrated in the preparation of a number of medicinally relevant quinolines.
A. E. Wendlandt, S. S. Stahl, J. Am. Chem. Soc., 2014, 136, 11910-11913.
A [5 + 1] cyclization of 2-vinylanilines with polyfluoroalkanoic acids as both C1 synthons and fluoroalkyl building blocks under catalyst- and additive-free conditions provides concise access to diverse 2-fluoroalkylated quinolines in good yields with excellent functional group tolerance in high yield on a gram scale.
J. Nan, Y. Hu, P. Chen, Y. Ma, Org. Lett., 2019, 21, 1984-1988.
Pyridine N-oxides were converted to 2-aminopyridines in a one-pot fashion using Ts2O-tBuNH2 followed by in situ deprotection with TFA. The amination proceeded in high yields, excellent 2-/4-selectivity, and with good functional group compatibility.
J. Yin, B. Xiang, M. H. Huffman, C. E. Raab, I. W. Davies, J. Org. Chem., 2007, 72, 4554-4557.
A sustainable synthesis of quinazoline and 2-aminoquinoline via acceptorless dehydrogenative annulation is catalyzed by earth-abundant well-defined manganese complexes bearing NNS ligands.
K. Das, A. Mondal, D. Pal, D. Srimani, Org. Lett., 2019, 21, 3223-3227.
A palladium-catalyzed annulation of N-acyl-o-alkynylanilines with isocyanides provides functionalized 2-aminoquinolines with high atom economy via an unconventional 6-endo-dig cyclization process. Further investigations of the mechanism revealed that an intramolecular acyl migration of the N-protecting groups is involved.
M. Li, J. Zheng, W. Hu, C. Li, J. Li, S. Fang, H. Jiang, W. Wu, Org. Lett., 2018, 20, 7245-7248.
A [3+2] dipolar cycloaddition of azine N-oxide withs carbodiimides provides 2-amino azines smoothly under simple heating conditions without any transition metal catalyst, activator, base, and solvent. This transformation demonstrates a broad substrate scope and produces CO2 as the only co-product.
B. K. Sarmah, M. Konwar, A. Das, J. Org. Chem., 2021, 86, 10762-10772.
Mn(III) acetate as a mild one-electron oxidant promotes a radical process to construct polysubstituted quinolin-3-amines from 2-(2-isocyanophenyl)acetonitriles and organoboron reagents. This method is practical, mild, efficient, and offers good functional group compatibility.
S. Wang, J. Xu, Q. Song, Org. Lett., 2021, 23, 6789-6794.
A robust and regioselective palladium-catalyzed intermolecular aerobic oxidative cyclization of 2-ethynylanilines with isocyanides enables the synthesis of 4-halo-2-aminoquinolines with good yields and broad substrates scope. Furthermore, this process can be easily extended to synthesis of various 6H-indolo[2,3-b]quinolines via an intramolecular Buchwald-Hartwig cross-coupling reaction in a two-step one-pot manner.
B. Liu, H. Gao, Y. Yu, W. Wu, H. Jiang, J. Org. Chem., 2013, 78, 10319-10328.
A nucleophile-induced intramolecular cyclization of o-alkynylisocyanobenzenes provides 2,3-disubstituted quinoline derivatives in high yields. In addition to oxygen and nitrogen nucleophiles such as methanol and diethylamine, the nucleophilic carbon of the enolate of malonate induced the cyclization effectively.
M. Suginome, T. Fukuda, Y. Ito, Org. Lett., 1999, 1, 1977-1979.
An efficient intermolecular amidation of quinoline N-oxides with sulfonamides in the presence of PhI(OAc)2 and PPh3 provides N-(quinolin-2-yl)sulfonamides in very good yields.
X. Yu, S. Yang, Y. Zhang, M. Guo, Y. Yamaoto, M. Bao, Org. Lett., 2017, 19, 6088-6091.
In a ligand-free chromium(II)-catalyzed amination reaction of various N-heterocyclic chlorides, CrCl2 regioselectively catalyzes the reaction of chloropyridines, chloroquinolines, chloroisoquinolines, and chloroquinoxalines with a broad range of magnesium amides in the presence of lithium chloride as additive. The reactionse provide the desired aminated products in good yield.
A. K. Steib, S. Fernandez, O. M. Kuzmina, M. Corpet, C. Gosmini, P. Knochel, Synlett, 2015, 26, 1049-1054.
A rapid synthesis of quinolines from 2-alkenylanilines involves an unexpected DMAP-catalyzed cyclization of 2-alkenylanilines with di-tert-butyl dicarbonate providing a series of tert-butyl quinolin-2-yl carbonates with various functional groups in good yields under mild conditions. Furthermore, the tert-butyl quinolin-2-yl carbonate can be easily converted into corresponding quinolinones and 2-(pseudo)haloquinolines.
Y.-N. Huang, Y.-L. Li, J. Li, J. Deng, J. Org. Chem., 2016, 81, 4645-4653.
4-Aminoquinolines can be prepared in a three-step synthesis: A condensation of substituted anthranilonitriles with 1,1,1-trichloro-4-ethoxybut-3-enone proceeded efficiently either neat or in refluxing EtOH. Cyclization in superacidic trifluoromethanesulfonic acid provided an unstable intermediate, which upon treatment with NaOEt in ethanol, afforded the expected ethyl 4-aminoquinoline-3-carboxylates.
H. Lavrard, P. Larini, F. Popowycz, Org. Lett., 2017, 19, 4203-4206.
A copper-catalyzed regiocontrolled three-component reaction of nitriles, diaryliodoniums, and ynamides provides diversified 4-aminoquinolines. The C7-substituted regioisomers were formed regioselectively when meta-substituted phenyliodonium salts were used. [1,3] N-to-C rearrangement of the products to quinolin-4-ylmethanesulfonamides and simultaneous deprotection of benzyl and sulfonamide group are also reported.
K. H. Oh, J. G. Kim, J. K. Park, Org. Lett., 2017, 19, 3994-3997.