Synthesis 2019; 51(09): 1969-1979
DOI: 10.1055/s-0037-1612089
paper
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Synthesis of Vicinally Bis(trifluoromethyl)-Substituted 3,3′-Pyrrolidinyl Spirooxindoles via Organocatalytic 1,3-Dipolar Cycloaddition Reactions

Wen-Run Zhu §
a  College of Pharmacy, Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, P. R. of China   Email: linning@gxtcmu.edu.cn   Email: chenqing@gxtcmu.edu.cn
,
Zhen-Wei Zhang §
a  College of Pharmacy, Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, P. R. of China   Email: linning@gxtcmu.edu.cn   Email: chenqing@gxtcmu.edu.cn
,
Wei-Hua Huang
b  Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, P. R. of China   Email: lugui@mail.sysu.edu.cn
,
a  College of Pharmacy, Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, P. R. of China   Email: linning@gxtcmu.edu.cn   Email: chenqing@gxtcmu.edu.cn
,
Qing Chen*
a  College of Pharmacy, Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, P. R. of China   Email: linning@gxtcmu.edu.cn   Email: chenqing@gxtcmu.edu.cn
,
Kai-Bin Chen
a  College of Pharmacy, Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, P. R. of China   Email: linning@gxtcmu.edu.cn   Email: chenqing@gxtcmu.edu.cn
,
Bi-Chuan Wang
a  College of Pharmacy, Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, P. R. of China   Email: linning@gxtcmu.edu.cn   Email: chenqing@gxtcmu.edu.cn
,
Jiang Weng
b  Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, P. R. of China   Email: lugui@mail.sysu.edu.cn
,
Gui Lu*
b  Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, P. R. of China   Email: lugui@mail.sysu.edu.cn
› Author Affiliations
We are grateful for grants from the National Natural Science Foundation of China (Nos. 21262008, 21502240 and 21861009), the Natural Science Foundation of Guangxi Province (Nos. 2018GXNSFAA281317, 2016GXNSFAA380178 and 2018GXNSFBA138032) and the Guangxi University of Chinese Medicine Research Foundation for introduced PhD (No. XB017027).
Further Information

Publication History

Received: 21 October 2018

Accepted after revision: 28 December 2018

Publication Date:
19 February 2019 (eFirst)

§ These two authors contributed equally to this work.

Abstract

Under bifunctional squaramide and thiourea organocatalysis, a series of vicinally bis(trifluoromethyl)-substituted 3,3′-pyrrolidinyl spirooxindoles were successfully synthesized via 1,3-dipolar cycloaddition reactions of 3-(trifluoroethylidene)oxindoles with diethyl 2-((2,2,2-trifluoroethyl)imino)malonate and N-(2,2,2-trifluoroethyl)isatin ketimines. The highlight of this protocol is the efficient construction of the vicinally bis(trifluoromethyl)-substituted pyrrolidine unit of spirooxindoles, including multiple contiguous stereogenic centres, in excellent yields and stereoselectivities.

Supporting Information

 
  • References


    • For books and reviews, see:
    • 1a Hiyama H. Organofluorine Compounds: Chemistry and Applications. Springer; Berlin: 2000
    • 1b O’Hagan D. Chem. Soc. Rev. 2008; 37: 308
    • 1c Berger R, Resnati G, Metrangolo P, Weber E, Hulliger J. Chem. Soc. Rev. 2011; 40: 3496
    • 1d Gillis EP, Eastman KJ, Hill MD, Donnelly DJ, Meanwell NA. J. Med. Chem. 2015; 58: 8315

      For reviews, see:
    • 2a Smits R, Cadicamo CD, Burger K, Koksch B. Chem. Soc. Rev. 2008; 37: 1727
    • 2b Manteau B, Pazenok S, Vors JP, Leroux FR. J. Fluorine Chem. 2010; 131: 140
    • 2c Wang J, Sánchez-Roselló M, Aceña JL, del Pozo C, Sorochinsky AE, Fustero S, Soloshonok VA, Liu H. Chem. Rev. 2014; 114: 2432

      For selected reviews, see:
    • 3a Tomashenko OA, Grushin VV. Chem. Rev. 2011; 111: 4475
    • 3b Merino E, Nevado C. Chem. Soc. Rev. 2014; 43: 6598
    • 3c Liu X, Xu C, Wang M, Liu Q. Chem. Rev. 2015; 115: 683
    • 3d Alonso C, de Marigorta EM, Rubiales G, Palacios F. Chem. Rev. 2015; 115: 1847
    • 4a Itoh Y, Yamanaka M, Mikami K. Org. Lett. 2003; 5: 4807
    • 4b Gao B, Zhao Y, Ni C, Hu J. Org. Lett. 2014; 16: 102
    • 4c Molander GA, Ryu D. Angew. Chem. Int. Ed. 2014; 53: 14181 ; Angew. Chem. 2014, 126, 14405
    • 4d Yang B, Xu X.-H, Qing F.-L. Org. Lett. 2015; 17: 1906
    • 4e You Y, Lu W.-Y, Wang Z.-H, Chen Y.-Z, Xu X.-Y, Zhang X.-M, Yuan W.-C. Org. Lett. 2018; 20: 4453
    • 5a Yanagimoto T, Toyota T, Matsuki N, Makino Y, Uchiyama S, Ohwada T. J. Am. Chem. Soc. 2007; 129: 736
    • 5b Schmidt BM, Seki S, Topolinski B, Ohkubo K, Fukuzumi S, Sakurai H, Lentz D. Angew. Chem. Int. Ed. 2012; 51: 11385 ; Angew. Chem. 2012, 124, 11548
    • 5c Schmidt BM, Topolinski B, Yamada M, Higashibayashi S, Shionoya M, Sakurai H, Lentz D. Chem. Eur. J. 2013; 19: 13872
    • 5d Kuvychko IV, Castro KP, Deng SH. M, Wang XB, Strauss SH, Boltalina OV. Angew. Chem. Int. Ed. 2013; 52: 4871 ; Angew. Chem. 2013, 125, 4971

      For selected examples, see:
    • 6a Caron S, Do NM, Sieser JE, Arpin P, Vazquez E. Org. Process Res. Dev. 2007; 11: 1015
    • 6b Sophie P, Peter M, Steve RS, Véronique G. Chem. Soc. Rev. 2008; 37: 320
    • 6c Nance KD, Days EL, Weaver CD, Coldren A, Farmer TD, Cho HP, Niswender CM, Blobaum AL, Niswender KD, Lindsley CW. J. Med. Chem. 2017; 60: 1611

      For reviews, see:
    • 7a Marti C, Carreira EM. Eur. J. Org. Chem. 2003; 2209
    • 7b Galliford CV, Scheidt KA. Angew. Chem. Int. Ed. 2007; 46: 8748 ; Angew. Chem. 2007, 119, 8902
    • 8a Velikorodov AV, Ionova VA, Degtyarev OV, Sukhenko LT. Pharm. Chem. J. 2013; 46: 715
    • 8b Shangary S, Qin D, McEachern D, Liu M, Miller RS, Qiu S, Nikolovska-Coleska Z, Ding K, Wang G, Chen J, Bernard D, Zhang J, Lu Y, Gu Q, Shah RB, Pienta KJ, Ling X, Kang S, Guo M, Sun Y, Yang D, Wang S. Proc. Natl. Acad. Sci. U. S. A. 2008; 105: 3933
    • 8c Arun Y, Bhaskar G, Balachandran C, Ignacimuthu S, Perumal PT. Bioorg. Med. Chem. Lett. 2013; 23: 1839

      For the synthesis of racemic 3,3′-pyrrolidinyl spirooxindole products, selected examples, see:
    • 9a Xu Q, Wang D, Wei Y, Shi M. ChemistryOpen 2014; 3: 93
    • 9b Suman K, Srinu L, Thennarasu S. Org. Lett. 2014; 16: 3732
    • 9c Lanka S, Thennarasu S, Perumal PT. Tetrahedron Lett. 2014; 55: 2585
    • 9d Zhi Y, Zhao K, Liu Q, Wang A, Enders D. Chem. Commun. 2016; 52: 14011
    • 9e Lin B, Zhang W.-H, Wang D.-D, Gong Y, Wei Q.-D, Liu X.-L, Feng T.-T, Zhou Y, Yuan W.-C. Tetrahedron 2017; 73: 5176
    • 9f Huang W.-J, Chen Q, Zhu W.-R, Lin N, Long X.-W, Pan W.-G, Weng J, Lu G. Heterocycles 2017; 94: 879
    • 9g Basu S, Mukhopadhyay C. Eur. J. Org. Chem. 2018; 1496

      For the asymmetric synthesis of 3,3′-pyrrolidinyl spirooxindole products, see:
    • 10a Chen X.-H, Wei Q, Luo S.-W, Xiao H, Gong L.-Z. J. Am. Chem. Soc. 2009; 131: 13819
    • 10b Antonchick AP, Gerding-Reimers C, Catarinella M, Schürmann M, Preut H, Ziegler S, Rauh D, Waldmann H. Nat. Chem. 2010; 2: 735
    • 10c Liu T.-L, Xue Z.-Y, Tao H.-Y, Wang C.-J. Org. Biomol. Chem. 2011; 9: 1980
    • 10d Awata A, Arai T. Chem. Eur. J. 2012; 18: 8278
    • 10e Guo C, Song J, Gong L.-Z. Org. Lett. 2013; 15: 2676
    • 10f Wng L, Shi X.-M, Dong W.-P, Zhu L.-P, Wang R. Chem. Commun. 2013; 49: 3458
    • 10g Yang W.-L, Liu Y.-Z, Luo S, Yu X, Fossey JS, Deng W.-P. Chem. Commun. 2015; 51: 9212
    • 10h Arai T, Ogawa H, Awata A, Sato M, Watabe M, Yamanaka M. Angew. Chem. Int. Ed. 2015; 54: 1595 ; Angew. Chem. 2015, 127, 1615
    • 10i Dai W, Jiang X.-L, Wu Q, Shi F, Tu S.-J. J. Org. Chem. 2015; 80: 5737
    • 10j Zhao K, Zhi Y, Li X.-Y, Puttreddy R, Rissanen K, Enders D. Chem. Commun. 2016; 52: 2249
    • 10k Tan Y, Feng E.-L, Sun Q.-S, Lin H, Sun X, Lina G.-Q, Sun X.-W. Org. Biomol. Chem. 2017; 15: 778

      For the asymmetric organocatalytic synthesis of trifluoromethyl-containing 3,3′-pyrrolidinyl spirooxindole products, see:
    • 11a Su J, Ma Z, Li X, Lin L, Shen Z, Yang P, Li Y, Wang H, Yan W, Wang K, Wang R. Adv. Synth. Catal. 2016; 358: 3777
    • 11b Huang W.-J, Chen Q, Lin N, Long X.-W, Pan W.-G, Xiong Y.-S, Weng J, Lu G. Org. Chem. Front. 2017; 4: 472

      For the asymmetric organocatalytic synthesis of trifluoromethyl-containing pyrrolidinyl spirooxindole products, see:
    • 12a Du D, Jiang Y, Xu Q, Tang X.-Y, Shi M. ChemCatChem 2015; 7: 1366
    • 12b Ma M.-X, Zhu Y.-Y, Sun Q.-T, Li X.-Y, Su J.-H, Zhao L, Zhao Y.-Y, Qiu S, Yan W.-J, Wang K.-Y, Wang R. Chem. Commun. 2015; 51: 8789
    • 12c Sun Q, Li X, Su J, Zhao L, Ma M, Zhu Y, Zhao Y, Zhu R, Yan W, Wang K, Wang R. Adv. Synth. Catal. 2015; 357: 3187
    • 12d Yuan X, Zhang S.-J, Du W, Chen Y.-C. Chem. Eur. J. 2016; 22: 11048
    • 12e 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
    • 12f Zhi Y, Zhao K, Essen C, Rissanen K, Enders D. Synlett 2017; 28: 2876
    • 12g Zhu W.-R, Chen Q, Lin N, Chen K.-B, Zhang Z.-W, Fang G, Weng J, Lu G. Org. Chem. Front. 2018; 5: 1375
    • 12h Song Y.-X, Du D.-M. J. Org. Chem. 2018; 83: 9278

      For reviews, see:
    • 13a Jose CN, Sansano M. Angew. Chem. Int. Ed. 2005; 44: 6272 ; Angew. Chem. 2005, 117, 6428
    • 13b Coldham I, Hufton R. Chem. Rev. 2005; 105: 2765
    • 13c Pandey G, Banerjee P, Gadre SR. Chem. Rev. 2006; 106: 4484
    • 13d Stanley LM, Sibi MP. Chem. Rev. 2008; 108: 2887
    • 13e Narayan R, Potowski M, Jia ZJ, Antonchick AP, Waldmann H. Acc. Chem. Res. 2014; 47: 1296
  • 14 Zhao Y.-L, Lou Q.-X, Wang L.-S, Hu W.-H, Zhao J.-L. Angew. Chem. Int. Ed. 2017; 56: 338; Angew. Chem. 2017, 129, 344

    • For reviews on squaramide catalysts, see:
    • 15a Storer RI, Aciro C, Jones LH. Chem. Soc. Rev. 2011; 40: 2330
    • 15b Alemán J, Parra A, Jiang H, Jørgensen KA. Chem. Eur. J. 2011; 17: 6890
    • 15c Chauhan P, Mahajan S, Kaya U, Hack D, Enders D. Adv. Synth. Catal. 2015; 357: 253
  • 16 Lin N, Long X.-W, Chen Q, Zhu W.-R, Wang B.-C, Chen K.-B, Jiang C.-W, Weng J, Lu G. Tetrahedron 2018; 74: 3734

    • For selected examples, see:
    • 17a McCooey SH, Connon SJ. Angew. Chem. Int. Ed. 2005; 44: 6367 ; Angew. Chem. 2005, 117, 6525
    • 17b Vakulya B, Varga S, Csámpai A, Soós T. Org. Lett. 2005; 7: 1967
    • 17c Jiang H, Paixão MW, Monge D, Jørgensen KA. J. Am. Chem. Soc. 2010; 132: 2775
    • 17d Marcos V, Alemán J, Ruano JL. G, Marini F, Tiecco M. Org. Lett. 2011; 13: 3052
    • 17e Moccia M, Fini F, Scagnetti M, Adamo MF. A. Angew. Chem. Int. Ed. 2011; 50: 6893 ; Angew. Chem. 2011, 123, 7025
  • 18 See the Supporting Information for the optimization of reaction conditions.
    • 19a Matsugi A, Nunokawa S, Watanabe N, Nakata Y, Nakano K, Ichikawa Y, Kotsuki H. Heterocycles 2016; 92: 1953
    • 19b 6b was prepared from 3b (Scheme 4).
  • 20 CCDC 1851257 (3a), CCDC 1851258 (5e) and CCDC 1855690 (6b) contain the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.