Highly Diastereo-, α-Regioselective Catalyst-Free Construction of Adjacent Dispirobisoxindoles with Three Contiguous Quaternary Carbon Centers

^§ These two authors contributed equally to this work

Abstract

A new methodology was developed for the highly diastereoselective construction of dispirobisoxindole scaffolds via a domino α-regioselective Michael/cyclization reaction sequence of 3-isothiocyanato oxindoles and isatylidene malononitriles under catalyst-free conditions. Complex polycyclic oxindoles featuring two side-by-side oxindole skeletons and three contiguous quaternary carbon centers were synthesized in up to 95% yield and >20:1 dr. This protocol could provide libraries of stereochemically rich small molecules that will help in the search for new bioactive molecules.

Key words

3-isothiocyanato oxindoles - quaternary carbon center - diastereoselective - α-regioselective - catalyst-free

• References

• 1a Kumar K. Waldmann H. Angew. Chem. Int. Ed. 2009; 48: 3224
• 1b Bon RS. Waldmann H. Acc. Chem. Res. 2010; 43: 1103
• 1c Wetzel S. Bon RS. Kumar K. Waldmann H. Angew. Chem. Int. Ed. 2011; 50: 10800
• 1d Sharma I. Tan DS. Nat. Chem. 2013; 5: 157
• 1e Koch MA. Schuffenhauer A. Scheck M. Wetzel S. Casaulta M. Odermatt A. Ertl P. Waldmann H. Proc. Natl. Acad. Sci. U.S.A. 2005; 102: 17272
• 1f Xu P.-W. Liu J.-K. Shen L. Cao Z.-Y. Zhao X.-L. Yan J. Zhou J. Nat. Commun. 2017;  8: 1619

For examples of biologically important dispirobisoxindoles, see:
• 2a Arun Y. Bhaskar G. Balachandran C. Ignacimuthu S. Perumal PT. Bioorg. Med. Chem. Lett. 2013; 23: 1839
• 2b Kia Y. Osman H. Kumar RS. Bioorg. Med. Chem. 2013; 21: 1696
• 2c Qu J. Fang L. Ren X.-D. J. Nat. Prod. 2013; 76: 2203
• 2d Chen Y. Cui B.-D. Wang Y. Han W.-Y. Wan N.-W. Bai M. Yuan W.-C. Chen Y.-Z. J. Org. Chem. 2018; 83 DOI: in press; DOI: 10.1021/acs.joc.8b01506.
• 3a Suman K. Srinu L. Thennarasu S. Org. Lett. 2014; 16: 3732
• 3b Han Y.-Y. Chen W.-B. Han W.-Y. Wu Z.-J. Zhang X.-M. Yuan W.-C. Org. Lett. 2012; 14: 490
• 3c Xiao J.-A. Zhang H.-G. Liang S. Ren J.-W. Yang H. Chen X.-Q. J. Org. Chem. 2013; 78: 11577
• 3d Lanka S. Thennarasu S. Perumal PT. Tetrahedron Lett. 2014; 55: 2585
• 3e Dandia A. Jain AK. Laxkar AK. Bhati DS. Tetrahedron 2013; 69: 2062
• 3f Liu J. Sun H. Liu X. Ouyang L. Kang T. Xie Y. Wang X. Tetrahedron Lett. 2012; 53: 2336
• 3g Jain R. Sharma K. Kumar D. Tetrahedron Lett. 2012; 53: 1993
• 4a He Q. Du W. Chen Y.-C. Adv. Synth. Catal. 2017; 359: 3782
• 4b 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
• 4c Zhao K. Zhi Y. Li X. Puttreddy R. Rissanen K. Enders D. Chem. Commun. 2016; 52: 2249
• 4d Dai W. Jiang X.-L. Wu Q. Shi F. Tu S.-J. J. Org. Chem. 2015; 80: 5737
• 4e Liu Y.-L. Wang X. Zhao Y.-L. Zhu F. Zeng X.-P. Chen L. Wang C.-H. Zhao X.-L. Zhou J. Angew. Chem. Int. Ed. 2013; 52: 13735
• 5a Mugishima T. Tsuda M. Kasai Y. Ishiyama H. Fukushi E. Kawabata J. Watanabe M. Akao K. Kobayashi J. J. Org. Chem. 2005; 70: 9430
• 5b Bond RF. Boeyens JC. A. Holzapfel CW. Steyn PS. J. Chem. Soc., Perkin Trans. 1 1979; 1751

For representative examples, see:
• 6a Chen W.-B. Wu Z.-J. Hu J. Cun L.-F. Zhang X.-M. Yuan W.-C. Org. Lett. 2011; 13: 2472
• 6b Kato S. Yoshino T. Shibasaki M. Kanai M. Matsunaga S. Angew. Chem. Int. Ed. 2012; 51: 7007
• 6c Kato S. Kanai M. Matsunaga S. Chem. Asian J. 2013; 8: 1768
• 6d Liu X.-L. Han W.-Y. Zhang X.-M. Yuan W.-C. Org. Lett. 2013; 15: 1246
• 6e Han W.-Y. Li S.-W. Wu Z.-J. Zhang X.-M. Yuan W.-C. Chem. Eur. J. 2013; 19: 5551
• 6f Cao Y.-M. Shen F.-F. Zhang F.-T. Wang R. Chem. Eur. J. 2013; 19: 1184
• 6g Wu H. Zhang L.-L. Tian Z.-Q. Huang Y.-D. Wang Y.-M. Chem. Eur. J. 2013; 19: 1747
• 6h Du D. Jiang Y. Xu Q. Shi M. Adv. Synth. Catal. 2013; 355: 2249
• 6i Jiang Y. Pei C.-K. Du D. Li X.-G. He Y.-N. Xu Q. Shi M. Eur. J. Org. Chem. 2013; 7895
• 6j Chen Q. Liang J.-Y. Wang S.-L. Wang D. Wang R. Chem. Commun. 2013; 49: 1657
• 6k Tan F. Lu L.-Q. Yang Q.-Q. Guo W. Bian Q. Chen J.-R. Xiao W.-J. Chem. Eur. J. 2014; 20: 3415
• 6l Tan F. Cheng H.-G. Feng B. Zou Y.-Q. Duan S.-W. Chen J.-R. Xiao W.-J. Eur. J. Org. Chem. 2013; 2071

For representative examples, see:
• 7a Higashiyama K. Otomasu H. Chem. Pharm. Bull. 1980; 28: 1540
• 7b Chen W.-B. Wu Z.-J. Pei Q.-L. Cun L.-F. Zhang X.-M. Yuan W.-C. Org. Lett. 2010; 12: 3132
• 7c Lan Y.-B. Zhao H. Liu Z.-M. Liu G.-G. Tao J.-C. Wang X.-W. Org. Lett. 2011; 13: 4866
• 7d Zhong F. Han X. Wang Y. Lu Y. Angew. Chem. Int. Ed. 2011; 50: 7837
• 7e Liu L. Wu D. Li X. Wang S. Li H. Li J. Wang W. Chem. Commun. 2012; 48: 1692
• 7f Liu L. Wu D. Zheng S. Li T. Li X. Wang S. Li J. Li H. Wang W. Org. Lett. 2012; 14: 134

For reviews, see:
• 8a Cheng D. Ishihara Y. Tan B. Barbas CF. III. ACS Catal. 2014; 4: 743
• 8b Singh GS. Desta ZY. Chem. Rev. 2012; 112: 6104
• 8c Hong L. Wang R. Adv. Synth. Catal. 2013; 355: 1023
• 8d Yu B. Zheng YC. Shi XJ. Qi PP. Liu HM. Anti-Cancer Agents Med. Chem. 2016; 16: 1315
• 8e Han WY. Zhao JQ. Zuo J. Xu XY. Zhang XM. Yuan WC. Adv. Synth. Catal. 2015; 357: 3007
• 8f Ball-Jones NR. Badillo JJ. Franz AK. Org. Biomol. Chem. 2012; 10: 5165
• 8g Zhou F. Liu YL. Zhou J. Adv. Synth. Catal. 2010; 352: 1381
• 8h Hong L. Wang R. Adv. Synth. Catal. 2013; 355: 1023
• 8i Vetica F. Figueiredo RM. Orsini M. Tofani D. Gasperi T. Synthesis 2015; 47: 2139
• 9a Hu F. Chen H. Zhang M. Yu S. Xu X. Yuan W. Zhang X.-M. J. Heterocycl. Chem. 2017; 54: 2922
• 9b Cao J. Dong S.-D. Jiang D.-L. Zhu P.-Y. Zhang H. Li R. Li Z.-Y. Wang X.-Y. Tang W.-F. Du D. J. Org. Chem. 2017; 82: 4186
• 9c Gui H.-Z. Wei Y. Shi M. Eur. J. Org. Chem. 2018; DOI: in press; 10.1002/ejoc.201801091.
• 10a CCDC 1855873, 1855874, 1855875, 1855876, 1855877, 1855878, 1855879, and 1855881 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.
• 10b For other crystallographic data, see the Supporting Information.