Categories: Synthesis of N-Heterocycles >
Synthesis of quinolines and related compounds
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.
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 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.
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 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.
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 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.
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.
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 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 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.
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.
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.