Efficient Synthesis of Pyrido[2,3-b]indole Derivatives via Vanadium(III)-Catalyzed
Cascade Cyclization of 2-(2-aminophenyl)acetonitrile and Enones

Donghan      Liu; Mingshuai      Zhang; Longkun      Chen; Zhuoyuan      Liu; Yemei      Zhu; Fuchao      Yu

doi:10.2174/1385272827666221216104419

Abstract

An efficient strategy for the synthesis of pyrido[2,3-b]indoles through VCl₃-catalyzed cascade cyclization reactions of N,N-dimethyl enaminones or chalcones with 2-(2-aminophenyl)- acetonitrile under mild reaction conditions was developed. This method features many advantages, such as readily available starting materials, good substrate, good functional group tolerance, and good yields. A plausible reaction mechanism was provided. Moreover, the high yields of N-unprotected substrates made this reaction system extremely advantageous with currently known methods.

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[1]
Kim, J.; Movassaghi, M. Biogenetically inspired syntheses of alkaloid natural products. Chem. Soc. Rev.,  2009, 38(11), 3035-3050.
 [http://dx.doi.org/10.1039/b819925f] [PMID: 19847339]

[2]
Moquin-Pattey, C.; Guyot, M. Grossularine-1 and grossularine-2, cytotoxic α-carbolines from the tunicate: Dendrodoa grossularia. Tetrahedron,  1989, 45(11), 3445-3450.
 [http://dx.doi.org/10.1016/S0040-4020(01)81023-1]

[3]
Cimanga, K.; De Bruyne, T.; Pieters, L.; Vlietinck, A.J.; Turger, C.A. In vitro and in vivo antiplasmodial activity of cryptolepine and related alkaloids from Cryptolepis sanguinolenta. J. Nat. Prod.,  1997, 60(7), 688-691.
 [http://dx.doi.org/10.1021/np9605246] [PMID: 9249972]

[4]
Kim, J.S.; Shin-ya, K.; Furihata, K.; Hayakawa, Y.; Seto, H. Structure of mescengricin, a novel neuronal cell protecting substance produced by Streptomyces griseoflavus. Tetrahedron Lett.,  1997, 38(19), 3431-3434.
 [http://dx.doi.org/10.1016/S0040-4039(97)00638-2]

[5]
Verbitski, S.M.; Mayne, C.L.; Davis, R.A.; Concepcion, G.P.; Ireland, C.M. Isolation, structure determination, and biological activity of a novel alkaloid, perophoramidine, from the Philippine ascidian Perophora namei. J. Org. Chem.,  2002, 67(20), 7124-7126.
 [http://dx.doi.org/10.1021/jo026012f] [PMID: 12354007]

[6]
Hu, Y.; Shi, H.; Zhou, M.; Ren, Q.; Zhu, W.; Zhang, W.; Zhang, Z.; Zhou, C.; Liu, Y.; Ding, X.; Shen, H.C.; Yan, S.F.; Dey, F.; Wu, W.; Zhai, G.; Zhou, Z.; Xu, Z.; Ji, Y.; Lv, H.; Jiang, T.; Wang, W.; Xu, Y.; Vercruysse, M.; Yao, X.; Mao, Y.; Yu, X.; Bradley, K.; Tan, X. Discovery of pyrido [2,3-b]indole derivatives with gram-negative activity targeting both DNA gyrase and topoisomerase IV. J. Med. Chem.,  2020, 63(17), 9623-9649.
 [http://dx.doi.org/10.1021/acs.jmedchem.0c00768] [PMID: 32787097]

[7]
Saundane, A.R.; Kalpana, R. Synthesis and biological evaluation of novel indolo [2,3-c]isoquinoline derivatives. Med. Chem. Res.,  2015, 24(4), 1681-1695.
 [http://dx.doi.org/10.1007/s00044-014-1243-2]

[8]
Rajanarendar, E.; Govardhan Reddy, K.; Ramakrishna, S.; Nagi Reddy, M.; Shireesha, B.; Durgaiah, G.; Reddy, Y.N. Synthesis and in vitro and in vivo anticancer activity of novel 3-methyl-5H-isoxazolo [5′,4′:5,6]pyrido [2,3-b]indoles. Bioorg. Med. Chem. Lett.,  2012, 22(21), 6677-6680.
 [http://dx.doi.org/10.1016/j.bmcl.2012.08.098] [PMID: 23031598]

[9]
Das, S.K.; Roy, S.; Khatua, H.; Chattopadhyay, B. Ir-catalyzed intramolecular transannulation/C(sp2)-H amination of 1,2,3,4-tetrazoles by electrocyclization. J. Am. Chem. Soc.,  2018, 140(27), 8429-8433.
 [http://dx.doi.org/10.1021/jacs.8b05343] [PMID: 29953229]

[10]
Malapel-Andrieu, B.; Mérour, J.Y. Reactions of 3-([(trifluoromethyl)sulfonyl]oxy)-1H-indole derivatives with diamines and carbon nucleophiles. Synthesis of 6H-indolo [2,3-b]quinoxaline derivatives. Tetrahedron,  1998, 54(37), 11095-11110.
 [http://dx.doi.org/10.1016/S0040-4020(98)00650-4]

[11]
Wang, G.; You, X.; Gan, Y.; Liu, Y. Synthesis of δ-and α-carbolines via nickel-catalyzed [2+2+2] cycloaddition of functionalized alkyne-nitriles with alkynes. Org. Lett.,  2017, 19(1), 110-113.
 [http://dx.doi.org/10.1021/acs.orglett.6b03385] [PMID: 27966985]

[12]
Kolle, S.; Barak, D.S.; Ghosh, A.; Jaiswal, V.; Kant, R.; Batra, S. Dehydrative transformation of spirooxindoles to Pyrido [2,3- b]indoles via POCl 3. ACS Omega,  2019, 4(3), 5617-5629.
 [http://dx.doi.org/10.1021/acsomega.9b00396] [PMID: 31459716]

[13]
Sheng, G.; Ma, S.; Bai, S.; Qian, J.; Huang, K.; Lang, B.; Lu, P.; Wang, Y. Rhodium-catalyzed reactions of 3-diazoindolin-2-imines with enamines and their extensions towards 5 H -pyrazino [2,3-b]indoles. Tetrahedron,  2018, 74(17), 2151-2157.
 [http://dx.doi.org/10.1016/j.tet.2018.03.021]

[14]
Yu, S.; Li, Y.; Zhou, X.; Wang, H.; Kong, L.; Li, X. Access to structurally diverse quinoline-fused heterocycles via rhodium(III)-catalyzed C−C/C−N coupling of bifunctional substrates. Org. Lett.,  2016, 18(12), 2812-2815.
 [http://dx.doi.org/10.1021/acs.orglett.6b01032] [PMID: 27267178]

[15]
Jha, M.; Dhiman, S.; Cameron, T.S.; Kumar, D.; Kumar, A. Au-catalyzed synthesis of thiopyrano [2,3-b]indoles featuring tandem rearrangement and hydroarylation. Org. Lett.,  2017, 19(8), 2038-2041.
 [http://dx.doi.org/10.1021/acs.orglett.7b00617] [PMID: 28378595]

[16]
Wadsworth, A.D.; Naysmith, B.J.; Brimble, M.A. A review of the synthesis of α-carbolines. Eur. J. Med. Chem.,  2015, 97, 816-829.
 [http://dx.doi.org/10.1016/j.ejmech.2014.11.038] [PMID: 25499235]

[17]
Lassagne, F.; Langlais, T.; Caytan, E.; Limanton, E.; Paquin, L.; Boullard, M.; Courtel, C.; Curbet, I.; Gédéon, C.; Lebreton, J.; Picot, L.; Thiéry, V.; Souab, M.; Baratte, B.; Ruchaud, S.; Bach, S.; Roisnel, T.; Mongin, F. From quinoxaline, pyrido [2,3-b]pyrazine and pyrido [3,4-b]pyrazine to pyrazino-fused carbazoles and carbolines. Molecules,  2018, 23(11), 2961.
 [http://dx.doi.org/10.3390/molecules23112961] [PMID: 30428591]

[18]
Li, Y.; Jie, J.; Xiao, W.; Yang, H.; Fu, H. Palladium-catalyzed [3 + 3] annulations of 1-alkyl-indolin-2-imines and dialkyl (2-methylenepropane-1,3-diyl) dicarbonates. Org. Chem. Front.,  2022, 9(13), 3515-3520.
 [http://dx.doi.org/10.1039/D2QO00318J]

[19]
Fan, L.; Liu, M.; Ye, Y.; Yin, G. Synthesis of 6-substituted 6H-indolo [2,3-b]quinolines from isoindigos. Org. Lett.,  2017, 19(1), 186-189.
 [http://dx.doi.org/10.1021/acs.orglett.6b03484] [PMID: 27936788]

[20]
Sheikh, S.; Fazlinia, A. Preparation of pyrido [2,3-b]indole derivatives using silicates of group 1 and 2 metals. J. Heterocycl. Chem.,  2018, 55(10), 2291-2296.
 [http://dx.doi.org/10.1002/jhet.3284]

[21]
Yan, Z.; Wan, C.; Wan, J.; Wang, Z. An efficient iron-promoted synthesis of 6H-indolo [2,3-b]quinolines and neocryptolepine derivatives. Org. Biomol. Chem.,  2016, 14(19), 4405-4408.
 [http://dx.doi.org/10.1039/C6OB00469E] [PMID: 27117399]

[22]
Song, B.; Wang, M.; Xu, M.; Kong, L.; Xie, H.; Wang, C.; Li, Y. Controllable synthesis of pyrido [2,3- b]indol-4-ones or indolo [3,2-b]quinolines via formal intramolecular C(sp 2)-H functionalization. Org. Biomol. Chem.,  2019, 17(46), 9960-9965.
 [http://dx.doi.org/10.1039/C9OB02108F] [PMID: 31730146]

[23]
Lu, X.; Xiao, X.; Zhang, M.; Wan, C.; Hou, H.; Wan, J. Highly selective synthesis of 2-substituted pyrido [2,3-b]indole derivatives catalyzed by iron salts. Youji Huaxue,  2021, 41(11), 4444-4449.
 [http://dx.doi.org/10.6023/cjoc202107028]

[24]
Xu, Y.; Chen, X.; Gao, Y.; Yan, Z.; Wan, C.; Liu, J.B.; Wang, Z. Synthesis of trifluoromethyl- and ester group-substituted α-carbolines via iron-catalyzed tandem cyclization reaction. J. Org. Chem.,  2020, 85(6), 4354-4364.
 [http://dx.doi.org/10.1021/acs.joc.0c00048] [PMID: 32090568]

[25]
Chen, X.; Li, L.; Wan, C.; Liu, J.B. FeCl3-catalyzed sequential cyclization for the construction of 12-aryl 5,7-dihydropyrido [2,3-b:6,5-b′]diindoles. Tetrahedron Lett.,  2020, 61(37), 152334.
 [http://dx.doi.org/10.1016/j.tetlet.2020.152334]

[26]
Pal, S.; Choudhury, L.H.; Parvin, T. VCl3 catalyzed imine-based multicomponent reactions for the facile access of functionalized tetrahydropyridines and β-amino carbonyls. Mol. Divers.,  2012, 16(1), 129-143.
 [http://dx.doi.org/10.1007/s11030-011-9339-9] [PMID: 22042610]

[27]
Sabitha, G.; Reddy, G.S.K.K.; Reddy, K.B.; Reddy, N.M.; Yadav, J.S. Vanadium(III) chloride: A mild and efficient catalyst for the chemoselective deprotection of acetonides. J. Mol. Catal. Chem.,  2005, 238(1-2), 229-232.
 [http://dx.doi.org/10.1016/j.molcata.2005.05.028]

[28]
Sabitha, G.; Reddy, G.S.K.K.; Reddy, K.B.; Yadav, J.S. Vanadium(III) chloride catalyzed Biginelli condensation: solution phase library generation of dihydropyrimidin-(2H)-ones. Tetrahedron Lett.,  2003, 44(34), 6497-6499.
 [http://dx.doi.org/10.1016/S0040-4039(03)01564-8]

[29]
Fu, L.; Xu, W.; Pu, M.; Wu, Y.D.; Liu, Y.; Wan, J.P. Rh-catalyzed [4+2] annulation with a removable monodentate structure toward iminopyranes and pyranones by C-H annulation. Org. Lett.,  2022, 24(16), 3003-3008.
 [http://dx.doi.org/10.1021/acs.orglett.2c00912] [PMID: 35442046]

[30]
Ying, J.; Liu, T.; Liu, Y.; Wan, J.P. Base-promoted annulative difluoromethylenation of enaminones with BrCF2CO2Et toward 2,2-difluorinated 2,3-dihydrofurans. Org. Lett.,  2022, 24(12), 2404-2408.
 [http://dx.doi.org/10.1021/acs.orglett.2c00671] [PMID: 35302379]

[31]
Xing, Q.; Liang, H.; Bao, M.; Li, X.; Zhang, J.; Bi, T.; Zhang, Y.; Xu, J.; Du, Y.; Zhao, K. Metal‐free Synthesis of spiro‐2,2′‐benzo [b]furan‐3,3′‐ones via PhI(OAc)2‐mediated cascade spirocyclization. Adv. Synth. Catal.,  2019, 361(20), 4669-4673.
 [http://dx.doi.org/10.1002/adsc.201900652]

[32]
Xu, Z.; Fu, L.; Fang, X.; Huang, B.; Zhou, L.; Wan, J.P. Tunable trifunctionalization of tertiary enaminones for the regioselective and metal-free synthesis of discrete and proximal phosphoryl nitriles. Org. Lett.,  2021, 23(13), 5049-5053.
 [http://dx.doi.org/10.1021/acs.orglett.1c01581] [PMID: 34137270]

[33]
Fu, L.; Liu, Y.; Wan, J.P. Pd-catalyzed triple-fold C(sp2)-H activation with enaminones and alkenes for pyrrole synthesis via hydrogen evolution. Org. Lett.,  2021, 23(11), 4363-4367.
 [http://dx.doi.org/10.1021/acs.orglett.1c01301] [PMID: 34013729]

[34]
Yu, Q.; Zhang, Y.; Wan, J.P. Ambient and aerobic carbon-carbon bond cleavage toward α-ketoester synthesis by transition-metal-free photocatalysis. Green Chem.,  2019, 21(12), 3436-3441.
 [http://dx.doi.org/10.1039/C9GC01357A]

[35]
Sun, J.; Cheng, X.; Mansaray, J.K.; Fei, W.; Wan, J.; Yao, W. A copper-catalyzed three component reaction of aryl acetylene, sulfonyl azide and enaminone to form iminolactone via 6π electrocyclization. Chem. Commun. (Camb.),  2018, 54(99), 13953-13956.
 [http://dx.doi.org/10.1039/C8CC06868B] [PMID: 30474656]

[36]
Wan, J.P.; Cao, S.; Liu, Y. Base-promoted synthesis of N-substituted 1,2,3-triazoles via enaminone-azide cycloaddition involving regitz diazo transfer. Org. Lett.,  2016, 18(23), 6034-6037.
 [http://dx.doi.org/10.1021/acs.orglett.6b02975] [PMID: 27934360]

[37]
Duan, Y.G.; Hu, X.M.; Cao, X.L.; Lv, K.H.; Yan, S.J. Multicomponent cascade reaction of 3-formylchromones: highly selective synthesis of functionalized 9-azabicyclo [3.3.1]nonane derivatives. Org. Lett.,  2021, 23(17), 6866-6871.
 [http://dx.doi.org/10.1021/acs.orglett.1c02431] [PMID: 34410137]

[38]
Du, X.X.; Zi, Q.X.; Wu, Y.M.; Jin, Y.; Lin, J.; Yan, S.J. An environmentally benign multi-component reaction: regioselective synthesis of fluorinated 2-aminopyridines using diverse properties of the nitro group. Green Chem.,  2019, 21(6), 1505-1516.
 [http://dx.doi.org/10.1039/C8GC03698E]

[39]
Tao, S.; Xu, L.; Yang, K.; Zhang, J.; Du, Y. Construction of the 2-amino-1,3-selenazole skeleton via PhICl2/KSeCN-mediated selenocyanation/cyclization. Org. Lett.,  2022, 24(23), 4187-4191.
 [http://dx.doi.org/10.1021/acs.orglett.2c01468] [PMID: 35670516]

[40]
Xu, H.; Zhou, B.; Zhou, P.; Zhou, J.; Shen, Y.; Yu, F.C.; Lu, L.L. Insights into the unexpected chemoselectivity in Brønsted acid catalyzed cyclization of isatins with enaminones: convenient synthesis of pyrrolo [3,4-c]quinolin-1-ones and spirooxindoles. Chem. Commun. (Camb.),  2016, 52(51), 8002-8005.
 [http://dx.doi.org/10.1039/C6CC02659A] [PMID: 27264102]

[41]
Zhang, B.; Zhou, P.; Xu, H.; Huang, J.; Sun, Y.; Liu, D.; Yu, F. Copper(II)-mediated intermolecular radical [3+2]-annulation of N,N-dimethyl enaminones: direct access to 5-acyl-3-furancarboxaldehydes. Adv. Synth. Catal.,  2021, 363(18), 4354-4359.
 [http://dx.doi.org/10.1002/adsc.202100633]

[42]
Zhang, B.; Liu, D.; Sun, Y.; Zhang, Y.; Feng, J.; Yu, F. Preparation of thiazole-2-thiones through TBPB-promoted oxidative cascade cyclization of enaminones with elemental sulfur. Org. Lett.,  2021, 23(8), 3076-3082.
 [http://dx.doi.org/10.1021/acs.orglett.1c00751] [PMID: 33769063]

[43]
Chen, X.B.; Huang, S.T.; Li, J.; Yang, Q.; Yang, L.; Yu, F. Highly regioselective and chemoselective [3+3] annulation of enaminones with ortho-fluoronitrobenzenenes: divergent synthesis of aposafranones and their n-oxides. Org. Lett.,  2021, 23(8), 3032-3037.
 [http://dx.doi.org/10.1021/acs.orglett.1c00710] [PMID: 33792341]

[44]
Zhang, B.; Fu, Z.; Yang, H.; Liu, D.; Sun, Y.; Xu, Y.; Yu, F.; Yan, S.J. Transition-metal-free C(sp2)−H phosphorothiolation/cyclization of o-hydroxyarylenaminones: access to s-3-chromon phosphorothioates. Adv. Synth. Catal.,  2022, 364(9), 1602-1606.
 [http://dx.doi.org/10.1002/adsc.202200089]

[45]
Liu, D.; Lu, X.; Zhang, Q.; Zhao, Y.; Zhang, B.; Sun, Y.; Dai, W.; Xu, Y.; Yu, F. Facile approach to multifunctionalized 5-alkylidene-3-pyrrolin-2-ones via regioselective oxidative cyclization of 2,4-pentanediones with primary amines and sodium sulfinates. Org. Chem. Front.,  2022, 9(15), 4078-4084.
 [http://dx.doi.org/10.1039/D2QO00473A]

[46]
Thomas, E.J. Hetarenes and related ring systems (fused five-membered hetarenes with one heteroatom) || product class 13: indole and its derivatives. Sci. Synthes.,  2000, 10, 361-652.

[47]
Deepak, T.; Machhindra, L. Synthesis of 2,4 disubstituted 1,5 benzodiazepines promoted by efficient silica alumina catalyst. Chem. Rev. Lett.,  2021, 4, 30-36.

[48]
Farooq, S.; Ngaini, Z. Chalcone derived pyrazole synthesis via one-pot and two-pot strategies. Curr. Org. Chem.,  2020, 24(13), 1491-1506.
 [http://dx.doi.org/10.2174/1385272824999200714101420]

[49]
Ferreira, J.R.M.; Nunes da Silva, R.; Rocha, J.; Silva, A.M.S.; Guieu, S. 1,2,4-Triphenylpyrroles: synthesis, structure and luminescence properties. Synlett,  2020, 31(6), 632-634.
 [http://dx.doi.org/10.1055/s-0039-1690828]

[50]
Wakade, S.B.; Tiwari, D.K.; Phanindrudu, M.; Pushpendra; Tiwari, D.K. Synthesis of 3-keto-quinolines from enaminones, anilines and DMSO: Transition metal free one pot cascade. Tetrahedron,  2019, 75(30), 4024-4030.
 [http://dx.doi.org/10.1016/j.tet.2019.06.030]

[51]
Ma, F.; Liu, J.; Zhou, T.; Lei, M.; Chen, J.; Wang, X.; Zhang, Y.; Shen, X.; Hu, L. Discovery and structure-activity relationships study of thieno [2,3-b]pyridine analogues as hepatic gluconeogenesis inhibitors. Eur. J. Med. Chem.,  2018, 152, 307-317.
 [http://dx.doi.org/10.1016/j.ejmech.2018.04.028] [PMID: 29733999]

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DOI https://dx.doi.org/10.2174/1385272827666221216104419	Print ISSN 1385-2728
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Current Organic Chemistry

Efficient Synthesis of Pyrido[2,3-b]indole Derivatives via Vanadium(III)-Catalyzed Cascade Cyclization of 2-(2-aminophenyl)acetonitrile and Enones

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Catalytic C-H bond activation as a tool for functionalization of heterocycles

Current Organic Chemistry

Efficient Synthesis of Pyrido[2,3-b]indole Derivatives via Vanadium(III)-Catalyzed Cascade Cyclization of 2-(2-aminophenyl)acetonitrile and Enones

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Catalytic C-H bond activation as a tool for functionalization of heterocycles

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