Formal [5+3] Cycloaddition between Isatin-Based α-(Trifluoromethyl)imine Ylides and Vinyloxiranes: Diastereoselective Access to Medium-Heterocycle-Fused Spirooxindoles

Abstract

In the presence of Pd₂(dba)₃·CHCl₃ (2.5 mol%), PPh₃ (10 mol%), and 60% NaH (1.5 equiv), the formal [5+3] cycloaddition between isatin-based α-(trifluoromethyl)imines and vinyloxiranes proceeded readily in 1,2-DCE at 40 ℃ and afforded cis-configured medium-heterocycle-fused spirooxindoles in the reasonable chemical yields with >20:1 dr. The relative stereochemical configuration of the title products was identified by X-ray diffraction analysis.

Key words

[5+3] cycloaddition - isatin-based α-(trifluoromethyl)imine - vinyloxirane - spirooxindole - diastereoselectivity

Publication History

Received: 05 August 2020

Accepted after revision: 21 September 2020

Article published online:
22 October 2020

• References and Notes


For selected reviews, see:
• 1a Pandey G, Banerjee P, Gadre SR. Chem. Rev. 2006; 106: 4484
• 1b Coldham L, Hufton R. Chem. Rev. 2005; 105: 2765
• 1c Tang S.-J, Zhang X, Sun J.-Y, Niu D.-W, Chruma JJ. Chem. Rev. 2018; 118: 10393
• 1d Hashimoto T, Maruoka K. Chem. Rev. 2015; 115: 5366
• 1e Gothelf KV, Jørgensen KA. Chem. Rev. 1998; 98: 863

For selected examples, see:
• 2a Mei G.-J, Shi F. Chem. Commun. 2018; 54: 6607
• 2b Cheng D.-Y, Ishihara Y, Tan B, Barbas CF. III. ACS Catal. 2014; 4: 743

For selected examples, see:
• 3a Ryu H, Seo J, Ko HM. J. Org. Chem. 2018; 83: 14102
• 3b Wu X.-Y, Gao Y.-N, Shi M. Eur. J. Org. Chem. 2019; 1620
• 3c Gao X.-Y, Yan R.-J, Xiao B.-X, Du W, Albrecht L, Chen Y.-C. Org. Lett. 2019; 21: 9628
• 3d Li B.-Y, Gao F.-Y, Feng X, Sun M.-M, Guo Y.-F, Wen D.-W, Deng YB, Huang J.-Q, Wang K.-R, Yan W.-J. Org. Chem. Front. 2019; 6: 1567
• 3e Zhao B.-L, Du D.-M. Adv. Synth. Catal. 2019; 361: 3412
• 3f Lin Y, Song YX, Du DM. Adv. Synth. Catal. 2019; 361: 1064
• 3g Wang C, Wen DW, Chen H, Deng Y.-B, Liu X.-T, Liu X, Wang L, Gao F.-Y, Guo Y.-F, Sun M.-M, Wang K.-R, Yan WJ. Org. Biomol. Chem. 2019; 17: 5514
• 3h Ponce A, Alonso I, Adrio J, Carretero JC. Chem. Eur. J. 2016; 22: 4952
• 3i Zhao X.-Y, Xiong J.-L, An JK, Yu J.-C, Zhu L.-P, Feng X, Jiang X.-X. Org. Chem. Front. 2019; 6: 1989
• 3j Ma M, Zhu Y, Sun Q, Li X, Su J, Zhao L, Zhao Y, Qiu S, Yan W, Wang K, Wang R. Chem. Commun. 2015; 51: 8789
• 3k Gui H.-Z, Gao Y.-N, Wei Y, Shi M. Chem. Eur. J. 2018; 24: 10038
• 3l Sun QT, Li XY, Su J.-H, Zhao L, Ma M.-X, Zhu Y.-Y, Zhao Y.-Y, Zhu R.-R, Yan W.-J, Wang K.-R, Wang R. Adv. Synth. Catal. 2015; 357: 3187
• 3m Wang Z.-H, Wu Z.-J, Yue D.-F, Hu W.-F, Zhang X.-M, Xu X.-Y, Yuan W.-C. Chem. Commun. 2016; 52: 11708
• 3n Huang W.-J, Chen Q, Lin N, Long X.-W, Pan WG, Xiong Y.-S, Weng J, Lu G. Org. Chem. Front. 2017; 4: 472
• 3o Song Y.-X, Du D.-M. J. Org. Chem. 2018; 83: 9278
• 3p You Y, Lu W.-Y, Wang Z.-H, Chen Y.-Z, Xu X.-Y, Zhang X.-M. Org. Lett. 2018; 20: 4453
• 4 Zhao H.-W, Guo J.-M, Wang L.-R, Ding W.-Q, Tang Z, Song X.-Q, Wu H.-H, Fan X.-Z, Bi X.-F. Org. Chem. Front. 2019; 6: 3891
• 5a Niu B, Wu X.-Y, Wei Y, Shi M. Org. Lett. 2019; 21: 4859
• 5b Zhao H.-W, Wang L.-R, Guo J.-M, Ding W.-Q, Song X.-Q, Wu H.-H, Tang Z, Fan X.-Z, Bi X.-F. Adv. Synth. Catal. 2019; 361: 4761

For selected examples, see:
• 6a Onyeagusi CI, Shao XX, Malcolmson SJ. Org. Lett. 2020; 22: 1681
• 6b Gao Y.-N, Shi M. Eur. J. Org. Chem. 2017; 1552
• 6c Li X.-Y, Su J.-H, Liu Z, Zhu Y.-Y, Dong Z.-H, Qiu S, Wang J, Lin L, Shen Z, Yan W, Wang K, Wang R. Org. Lett. 2016; 18: 956
• 6d Shi L.-M, Sun X.-S, Shen C, Wang Z.-F, Tao H.-Y, Wang C.-J. Org. Lett. 2019; 21: 4842

For selected examples, see:
• 7a Zhou M.-B, Song R.-J, Wang C.-Y, Li J.-H. Angew. Chem. Int. Ed. 2013; 52: 10805
• 7b Majumdar KC. RSC Adv. 2011; 1: 1152
• 7c Zhao H.-W, Pang H.-L, Tian T, Li B, Chen X.-Q, Song X.-Q, Meng W, Yang Z, Liu Y.-Y, Zhao Y.-D. Adv. Synth. Catal. 2016; 358: 1826
• 7d Gao X, Xia M, Yuan C, Zhou L, Sun W, Li C, Wu B, Zhu D, Zhang C, Zheng B, Wang D.-Q, Guo H.-C. ACS Catal. 2019; 9: 1645

For selected examples, see:
• 8a He J, Ling J, Chiu P. Chem. Rev. 2014; 114: 8037
• 8b Suo J.-J, Du J, Liu Q.-R, Chen D, Ding CH, Peng Q, Hou X.-L. Org. Lett. 2017; 19: 6658
• 8c Cheng Q, Zhang H.-J, Yue W.-J, You SL. Chem 2017; 3: 428
• 8d Wu Y, Yuan C, Wang C, Mao B, Jia H, Gao X, Liao J, Jiang F, Zhou L, Wang Q, Guo H.-C. Org. Lett. 2017; 19: 6268
• 8e Yuan C, Wu Y, Wang D, Zhang Z, Wang C, Zhou L, Zhang C, Song B, Guo H.-C. Adv. Synth. Catal. 2018; 360: 652
• 8f Wang Y.-N, Yang L.-C, Rong Z.-Q, Liu T.-L, Liu R, Zhao Y. Angew. Chem. Int. Ed. 2018; 57: 1596
• 8g Guo B.-Y, Vitaku E, Njardarson JT. Tetrahedron Lett. 2014; 55: 3232
• 8h Matsui JK, Bonet AG, Rotella M, Alam R, Gutierrez O, Molander GA. Angew. Chem. Int. Ed. 2018; 57: 15847
• 8i Trost BM, Brown BS, McEachern EJ, Kuhn O. Chem. Eur. J. 2003; 9: 4442

For selected examples, see:
• 9a Aguilar A, Lu J.-F, Liu L, Du D, Bernard D, McEachern D, Przybranowski S, Li XQ, Luo RJ, Wen B, Sun D.-X, Wang H.-B, Wen J.-F, Wang G.-F, Zhai Y.-F, Guo M, Yang D.-J, Wang S.-M. J. Med. Chem. 2017; 60: 2819
• 9b Zhao Y.-J, Yu S.-H, Sun W, Liu L, Lu J.-F, McEachern D, Shargary S, Bernard D, Li X.-Q, Zhao T, Zou P, Sun D.-X, Wang SM. J. Med. Chem. 2013; 56: 5553
• 9c Gicquel M, Gomez C, Concepcion M, Alvarez G, Pamlard O, Guerineau V, Jacquet E, Bignon J, Voituriez A, Marinetti A. J. Med. Chem. 2018; 61: 9386
• 9d Kornet MJ, Thio AP. J. Med. Chem. 1976; 19: 892
• 9e Zhang W.-H, Chen S, Liu X.-L, Feng T.-T, Yang W.-D, Zhou Y. Bioorg. Med. Chem. 2019; 27: 115109
• 9f Kumar RS, Almansour AI, Arumugam N, Mohammad F, Kotresha D, Menendez JC. Bioorg. Med. Chem. 2019; 27: 2487
• 10 Typical Procedure and Characterization Data for 3ba A mixture of isatin-based α-(trifluoromethyl)imine 1 (1.0 equiv, 0.1 mmol), vinyloxirane 2 (1.5 equiv, 0.15 mmol), Pd₂(dba)₃·CHCl₃ (2.5 mol%), PPh₃ (10.0 mol%), and 60% NaH (1.5 equiv, 0.15 mmol) in 1,2-DCE (1.0 mL) was stirred at 40 ℃ for 3 h. After the reaction was completed as indicated by TLC plate, the solvent was removed by evaporation and the resulted crude product was purified by flash column chromatography on silica gel (petroleum ether/EtOAc, 6:1 to 10:1) to afford cis-configured 3ba. Analytical Data White solid; yield: 22.1 mg (52%); mp 204.1–205.0 ℃. ¹H NMR (400 MHz, CDCl₃): δ = 7.54–7.52 (m, 2 H), 7.46–7.42 (m, 2 H), 7.39–7.35 (m, 2 H), 7.21 (d, J = 2.0 Hz, 1 H), 6.87 (d, J = 8.3 Hz, 1 H), 6.31 (t, J = 8.3 Hz, 1 H), 4.97–4.91 (m, 1 H), 4.87 (d, J = 13.7 Hz, 1 H), 4.71 (d, J = 13.7 Hz, 1 H), 3.27 (s, 3 H), 3.00 (dd, J = 13.6, 8.2 Hz, 1 H), 2.86 (d, J = 12.0 Hz, 1 H), 2.50–2.45 (m, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 175.9, 141.5, 140.8, 140.3, 132.4, 129.1, 128.8, 128.2, 128.1, 125.9, 125.7, 124.7, 122.9 (q, J _C,_F = 280.0 Hz), 109.9, 80.3 (q, J _C,_F = 34.0 Hz), 64.7, 62.2, 36.0, 26.6. HRMS (ESI): m/z calcd for C₂₁H₁₉ClF₃N₂O₂ [M + H]⁺: 423.1082; found: 423.1097.
• 11 CCDC 2000593 (cis-3ba) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Center via www.ccdc.cam.ac.uk/getstructures.