[4+2]-Cycloaddition Reactions of Aza-o-quinone Methides with Fulvenes: Construction of Tetrahydroquinoline Derivatives

Abstract

An efficient [4+2] cycloaddition reaction of fulvenes with aza-o-quinone methides, generated in situ from N-(o-chloromethyl)aryl sulfonamides with the assistance of a base, has been developed to afford a series of tetrahydroquinoline derivatives. The reaction tolerates a wide range of aza-o-quinone methides and fulvenes bearing four- to seven-membered rings to afford the corresponding tetrahydroquinolines in moderate to good yields. Based on a literature analysis, a plausible mechanism for this [4+2] cycloaddition is proposed.

Key words

cycloaddition - azaquinone methides - fulvenes - tetrahydroquinolines

Publication History

Received: 12 February 2022

Accepted after revision: 13 March 2022

Accepted Manuscript online:
13 March 2022

Article published online:
13 April 2022

• References and Notes

• 1a Crawley SL, Funk RL. Org. Lett. 2003; 5: 3169
• 1b Darras FH, Kling B, Heilmann J, Decker M. ACS Med. Chem. Lett. 2012; 3: 914
• 2 Sridharan V, Suryavanshi PA, Menéndez JC. Chem. Rev. 2011; 111: 7157
• 3 Gogoi S, Shekarrao K, Duarah A, Bora TC, Gogoi S, Boruah RC. Steroids 2012; 77: 1438
• 4 Ramesh E, Manian RD, Raghunathan R, Sainath S, Raghunathan M. Bioorg. Med. Chem. 2009; 17: 660
• 5 Pagliero RJ, Lusvarghi S, Pierini AB, Brun R, Mazzieri MR. Bioorg. Med. Chem. 2010; 18: 142
• 6 Steinhagen H, Corey EJ. Angew. Chem. Int. Ed. 1999; 38: 1928
• 7 Yang Q.-Q, Xiao C, Lu L.-Q, An J, Tan F, Li B.-J, Xiao W.-J. Angew. Chem. Int. Ed. 2012; 51: 9137
• 8 Yang Q.-Q, Wang Q, An J, Chen J.-R, Lu L.-Q, Xiao W.-J. Chem. Eur. J. 2013; 19: 8401
• 9 Huang H, Yang Y, Zhang X, Zeng W, Liang Y. Tetrahedron Lett. 2013; 54: 6049
• 10 Jong A.-W, Bao X, Wang Q, Zhu J.-P. Helv. Chim. Acta 2019; 102: e1900002
• 11 Zhang X, Pan Y, Liang P, Ma X, Jiao W, Shao H. Adv. Synth. Catal. 2019; 361: 5552
• 12 Gui H.-Z, Wu X.-Y, Wei Y, Shi M. Adv. Synth. Catal. 2019; 361: 5466
• 13 Han S.-J, Vogt F, May JA, Krishnan S, Gatti M, Virgil SC, Stoltz BM. J. Org. Chem. 2015; 80: 528
• 14 Zheng Y, Tu L, Li N, Huang R, Feng T, Sun H, Li Z, Liu J. Adv. Synth. Catal. 2018; 361: 44
• 15 Lei L, Yao Y.-Y, Jiang L.-J, Lu X.-Q, Liang C, Mo D.-L. J. Org. Chem. 2020; 85: 3059
• 16 Jiang S.-P, Lu W.-Q, Liu Z, Wang G.-W. J. Org. Chem. 2018; 83: 1959
• 17 Wang H.-Q, Ma W, Sun A, Sun X.-Y, Jiang C, Zhang Y.-C, Shi F. Org. Biomol. Chem. 2021; 19: 1334
• 18a Chen L, Yang GM, Wang J, Jia QF, Wei J, Du ZY. RSC Adv. 2015; 5: 76696
• 18b Meng Z, Yang W, Zheng J. Tetrahedron Lett. 2019; 60: 1758
• 19 Wang L, Li S, Blümel M, Philipps AR, Wang A, Puttreddy R, Rissanen K, Enders D. Angew. Chem. Int. Ed. 2016; 55: 11110
• 20a Long W, Chen S, Zhang X, Fang L, Wang Z. Tetrahedron 2018; 74: 6155
• 20b Zhang X, Pan Y, Liang P, Pang L, Ma X, Jiao W, Shao H. Adv. Synth. Catal. 2018; 360: 3015
• 20c Zheng Y.-S, Tu L, Gao L.-M, Huang R, Feng T, Sun H, Wang W.-X, Li Z.-H, Liu J.-K. Org. Biomol. Chem. 2018; 16: 2639
• 21 Guo Z, Jia H, Liu H, Wang Q, Huang J, Guo H. Org. Lett. 2018; 20: 2939
• 22 Paquette LA, Colapret JA, Andrews DR. J. Org. Chem. 1985; 50: 201
• 23a Hong B.-C, Wu J.-L, Gupta AK, Hallur MS, Liao J.-H. Org. Lett. 2004; 6: 3453
• 23b Nair V, Anilkumar G, Radhakrishnan KV, Sheel KC, Rath NP. Tetrahedron 1997; 53: 17361
• 23c Hong B.-C, Chen F.-L, Chen S.-H, Liao J.-H, Lee G.-H. Org. Lett. 2005; 7: 557
• 23d Nair V, Mathew B, Menon RS, Mathew S, Vairamani M, Prabhakar S. Tetrahedron 2002; 58: 3235
• 23e Tanaka K, Yoshizawa H, Atobe M. Synlett 2019; 30: 1194
• 23f Zhang J, Lin L, He C, Xiong Q, Liu X, Feng X. Chem. Commun. 2017; 54: 74
• 23g Wei L, Zhu Q, Song Z.-M, Liu K, Wang C.-J. Chem. Commun. 2018; 54: 2506
• 23h Nair V, Mathew B. Tetrahedron Lett. 2000; 41: 6919
• 23i Nair V, Jayan CN, Radhakrishnan KV, Anilkumar G, Rath NP. Tetrahedron 2001; 57: 5807
• 24a Gugelchuk MM, Chan PC.-M, Sprules TJ. J. Org. Chem. 1994; 59: 7723
• 24b Manikandan S, Shanmugasundaram M, Raghunathan R. Tetrahedron 2002; 58: 597
• 24c Zhang J, Qiu Z, Xie Z. Organometallics 2017; 36: 3806
• 24d Zhang J, Qiu Z, Xu P, Xie Z. ChemPlusChem 2014; 79: 1044
• 24e Hong B.-C, Shr Y.-J, Liao J.-H. Org. Lett. 2002; 4: 663
• 24f Bhojgude SS, Kaicharla T, Bhunia A, Biju AT. Org. Lett. 2012; 14: 4098
• 25 Hong B.-C, Shr Y.-J, Wu J.-L, Gupta AK, Lin K.-J. Org. Lett. 2002; 4: 2249
• 26a Lee KJ, Choi J.-K, Yum EK, Cho SY. Tetrahedron Lett. 2009; 50: 6698
• 26b Barluenga J, Martínez S, Suárez-Sobrino LA, Tomás M. J. Am. Chem. Soc. 2001; 123: 11113
• 26c Hong B.-C, Sun S.-S, Tsai Y.-C. J. Org. Chem. 1997; 62: 7717
• 26d Hong B.-C, Gupta AK, Wu M.-F, Liao J.-H, Lee G.-H. Org. Lett. 2003; 5: 1689
• 26e Kuthanapillil JM, Thulasi S, Rajan R, Krishnan KS, Suresh E, Radhakrishnan KV. Tetrahedron 2011; 67: 1272
• 26f Potowski M, Bauer JO, Strohmann C, Antonchick AP, Waldmann H. Angew. Chem. Int. Ed. 2012; 51: 9512
• 26g Potowski M, Antonchick AP, Waldmann H. Chem. Commun. 2013; 49: 7800
• 27a Hong B.-C, Jiang Y.-F, Kumar ES. Bioorg. Med. Chem. Lett. 2001; 11: 1981
• 27b Wu T.-C, Mareda J, Gupta YN, Houk KN. J. Am. Chem. Soc. 1983; 105: 6996
• 27c Gupta YN, Doa MJ, Houk KN. J. Am. Chem. Soc. 1982; 104: 7336
• 27d McLeod D, Cherubini-Celli A, Sivasothirajah N, McCulley CH, Christensen ML, Jørgensen KA. Chem. Eur. J. 2020; 26: 11417
• 27e Lou Y, Chang J, Jorgensen J, Lemal DM. J. Am. Chem. Soc. 2002; 124: 15302
• 28 He Z.-L, Teng H.-L, Wang C.-J. Angew. Chem. Int. Ed. 2013; 52: 2934
• 29 He Z.-L, Wang C.-J. Chem. Commun. 2015; 51: 534
• 30 CCDC 2126748 contains the supplementary crystallographic data for compound 3v. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
• 31 1-(1-Methylethylidene)-4-tosyl-3a,4,9,9a-tetrahydro-1H-cyclopenta[b]quinoline; Typical Procedure Na₂CO₃ (63.6 mg, 0.6 mmol, 1.2 equiv) was added to a mixture of sulfonamide 1a (148 mg, 0.5 mmol, 1.0 equiv) and fulvene 2a (64 mg, 0.6 mmol, 1.2 equiv) in CHCl₃ (5 mL). When the starting material had been consumed (TLC), the solvent was removed and the residue was purified by column chromatography (silica gel, PE–EtOAc) to give a white solid; yield: 155 mg (85%); mp 143–145 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.54 (d, J = 8.2 Hz, 2 H), 7.47 (d, J = 7.5 Hz, 1 H), 7.23–7.18 (m, 3 H), 7.10–7.05 (m, 1 H), 6.88 (d, J = 7.4 Hz, 1 H), 6.24 (dd, J = 5.6, 1.8 Hz, 1 H), 5.66 (d, J = 8.3 Hz, 1 H), 5.53 (dd, J = 5.6, 2.0 Hz, 1 H), 3.45 (t, J = 7.9 Hz, 1 H), 2.41 (s, 3 H), 2.26 (d, J = 14.6 Hz, 1 H), 1.68 (s, 3 H), 1.65–1.57 (m, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 143.4, 140.9, 137.9, 135.9, 134.8, 134.7, 132.6, 129.7, 128.2, 128.1, 127.0, 126.8, 126.7, 123.8, 64.6, 43.1, 30.8, 21.6, 21.1, 20.9. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₂H₂₄NO₂S: 366.1522; found: 366.1523.