Synthesis 2019; 51(04): 899-906
DOI: 10.1055/s-0037-1609637
paper
© Georg Thieme Verlag Stuttgart · New York

Diastereoselective Synthesis of Spirobarbiturate-Cyclopropanes through Organobase-Mediated Spirocyclopropanation of Barbiturate-Based Olefins with Benzyl Chlorides

Yuanyuan Zhu
a  College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, P. R. of China   Email: xixisong@zzu.edu.cn   Email: changjunbiao@zzu.edu.cn
,
Shuang Zhao
a  College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, P. R. of China   Email: xixisong@zzu.edu.cn   Email: changjunbiao@zzu.edu.cn
,
Minli Zhang
a  College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, P. R. of China   Email: xixisong@zzu.edu.cn   Email: changjunbiao@zzu.edu.cn
,
Xixi Song*
a  College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, P. R. of China   Email: xixisong@zzu.edu.cn   Email: changjunbiao@zzu.edu.cn
,
Junbiao Chang*
a  College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, P. R. of China   Email: xixisong@zzu.edu.cn   Email: changjunbiao@zzu.edu.cn
b  Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou 450001, P. R. of China
› Author Affiliations
We are grateful to the NSFC (#21302173) and Henan Department of Education (#19A150049) for financial support.
Further Information

Publication History

Received: 13 September 2018

Accepted after revision: 10 October 2018

Publication Date:
06 November 2018 (eFirst)

Abstract

The organobase-mediated diastereoselective spirocyclopropanation of barbiturate-based olefins with 2,4-disubstituted benzyl chlorides has been developed. The reactions were carried out efficiently to afford the desired spirobarbiturate-cyclopropanes in up to 95% yield with more than 20:1 dr in favor of anti-isomers. In order to extend synthetic utility of the spiro-products, a Lewis acid induced cyclopropane-ring-expansion isomerization was also demonstrated.

Supporting Information

 
  • References

    • 1a Yan Q, Cao R, Yi W, Yu L, Chen Z, Ma L, Song H. Bioorg. Med. Chem. Lett. 2009; 19: 4055
    • 1b Vijaya Laxmi S, Thirupathi Reddy Y, Suresh Kuarm B, Narsimha Reddy P, Crooks PA, Rajitha B. Bioorg. Med. Chem. Lett. 2011; 21: 4329
    • 1c Wang J, Radomski MW, Medina C, Gilmer JF. Bioorg. Med. Chem. Lett. 2013; 23: 444
    • 1d Bihani M, Bora PP, Verma AK, Baruah R, Boruah HP. D, Bez G. Bioorg. Med. Chem. Lett. 2015; 25: 5732
    • 1e Zhang J, Yin G, Du Y, Yang Z, Li Y, Chen L. J. Org. Chem. 2017; 82: 13594
    • 1f Figueiredo J, Serrano JL, Cavalheiro E, Keurulainen L, Yli-Kauhaluoma J, Moreira VM, Ferreira S, Domingues FC, Silvestre S, Almeida P. Eur. J. Med. Chem. 2018; 143: 829
    • 2a Tietze LF, Ott C, Geißler H, Haunert F. Eur. J. Org. Chem. 2001; 1625
    • 2b Devi I, Bhuyan PJ. Tetrahedron Lett. 2004; 45: 7727
    • 2c Khoshkholgh MJ, Balalaie S, Gleiter R, Rominger F. Tetrahedron 2008; 64: 10924
    • 2d Pałasz A. Synthesis 2010; 4021
    • 2e Best D, Burns DJ, Lam HW. Angew. Chem. Int. Ed. 2015; 54: 7410
    • 2f Rajesh N, Prajapati D. Org. Biomol. Chem. 2015; 13: 4668
    • 3a Lakkakula S, Mitkin OD, Valiulin RA, Kutateladze AG. Org. Lett. 2007; 9: 1077
    • 3b Mahmudov KT, Kopylovich MN, Maharramov AM, Kurbanova MM, Gurbanov AV, Pombeiro AJ. L. Coord. Chem. Rev. 2014; 265: 1
    • 3c McGrath JM, Pluth MD. J. Org. Chem. 2014; 79: 711
    • 3d Tron A, Thornton PJ, Rocher M, Jacquot de Rouville H.-P, Desvergne J.-P, Kauffmann B, Buffeteau T, Cavagnat D, Tucker JH. R, McClenaghan ND. Org. Lett. 2014; 16: 1358
    • 3e Tron A, Rocher M, Thornton PJ, Tucker JH. R, McClenaghan ND. Asian J. Org. Chem. 2015; 4: 192
    • 3f Tron A, Thornton PJ, Lincheneau C, Desvergne J.-P, Spencer N, Tucker JH. R, McClenaghan ND. J. Org. Chem. 2015; 80: 988
    • 4a Seifert S, Seifert A, Brunklaus G, Hofmann K, Rüffer T, Lang H, Spange S. New J. Chem. 2012; 36: 674
    • 4b Zatsikha YV, Yakubovskyi VP, Shandura MP, Kovtun YP. RSC Adv. 2013; 3: 24193
    • 4c del Pozo S, Vera S, Oiarbide M, Palomo C. J. Am. Chem. Soc. 2017; 139: 15308
    • 4d Schade A, Tchernook I, Bauer M, Oehlke A, Breugst M, Friedrich J, Spange S. J. Org. Chem. 2017; 82: 8476
    • 5a Dox AW, Yoder L. J. Am. Chem. Soc. 1921; 43: 1366
    • 5b Bose AK, Garratt S, Pelosi JJ. J. Org. Chem. 1963; 28: 730
    • 5c Kato S, Poling M, Van der Helm D, Dryhurst G. J. Am. Chem. Soc. 1974; 96: 5255
    • 5d Lomlim L, Einsiedel J, Heinemann FW, Meyer K, Gmeiner P. J. Org. Chem. 2008; 73: 3608
    • 5e Bhuyan D, Sarma R, Prajapati D. Tetrahedron Lett. 2012; 53: 6460
    • 5f Dieskau AP, Holzwarth MS, Plietker B. J. Am. Chem. Soc. 2012; 134: 5048
    • 5g Vereshchagin AN, Elinson MN, Dorofeeva EO, Zaimovskaya TA, Stepanov NO, Gorbunov SV, Belyakov PA, Nikishin GI. Tetrahedron 2012; 68: 1198
    • 5h Hu Y, Shi D.-Q. J. Heterocycl. Chem. 2013; 50: E121
    • 5i Sarmah MM, Borthakur S, Bhuyan D, Prajapati D. RSC Adv. 2015; 5: 68839
    • 5j Gao X, Li Z, Yang W, Liu Y, Chen W, Zhang C, Zheng L, Guo H. Org. Biomol. Chem. 2017; 15: 5298
    • 5k Nagaraju S, Sathish K, Paplal B, Kashinath D. Tetrahedron Lett. 2017; 58: 2865
  • 6 Han B, Huang W, Ren W, He G, Wang J.-h, Peng C. Adv. Synth. Catal. 2015; 357: 561
    • 7a Liu H, Liu Y, Yuan C, Wang GP, Zhu SF, Wu Y, Wang B, Sun Z, Xiao Y, Zhou QL, Guo H. Org. Lett. 2016; 18: 1302
    • 7b Liu Y, Yang W, Wu Y, Mao B, Gao X, Liu H, Sun Z, Xiao Y, Guo H. Adv. Synth. Catal. 2016; 358: 2867
    • 8a Zhao H.-W, Tian T, Li B, Yang Z, Pang H.-L, Meng W, Song X.-Q, Chen X.-Q. J. Org. Chem. 2015; 80: 10380
    • 8b Zhao H.-W, Tian T, Pang H.-L, Li B, Chen X.-Q, Yang Z, Meng W, Song X.-Q, Zhao Y.-D, Liu Y.-Y. Adv. Synth. Catal. 2016; 358: 2619
    • 8c Zhao H.-W, Feng N.-N, Guo J.-M, Du J, Ding W.-Q, Wang L.-R, Song X.-Q. J. Org. Chem. 2018; 83: 9291
    • 9a Wong HN. C, Hon MY, Tse CW, Yip YC, Tanko J, Hudlicky T. Chem. Rev. 1989; 89: 165
    • 9b Kulinkovich OG. Chem. Rev. 2003; 103: 2597
    • 9c Reissig H.-U, Zimmer R. Chem. Rev. 2003; 103: 1151
    • 9d Wessjohann LA, Brandt W, Thiemann T. Chem. Rev. 2003; 103: 1625
    • 9e Brackmann F, de Meijere A. Chem. Rev. 2007; 107: 4493
    • 9f Chen DY. K, Pouwer RH, Richard J.-A. Chem. Soc. Rev. 2012; 41: 4631
    • 9g Cavitt MA, Phun LH, France S. Chem. Soc. Rev. 2014; 43: 804
    • 9h Schneider TF, Kaschel J, Werz DB. Angew. Chem. Int. Ed. 2014; 53: 5504
    • 10a McClenaghan ND, Absalon C, Bassani DM. J. Am. Chem. Soc. 2003; 125: 13004
    • 10b Elinson MN, Vereshchagin AN, Stepanov NO, Zaimovskaya TA, Merkulova VM, Nikishin GI. Tetrahedron Lett. 2010; 51: 428
    • 10c Dorofeeva EO, Elinson MN, Vereshchagin AN, Stepanov NO, Bushmarinov IS, Belyakov PA, Sokolova OO, Nikishin GI. RSC Adv. 2012; 2: 4444
    • 10d Mukherjee P, Das AR. J. Org. Chem. 2017; 82: 2794
    • 11a Chen X, Yu Y, Liao Z, Li H, Wang W. Tetrahedron Lett. 2016; 57: 5742
    • 11b Meazza M, Ashe M, Shin HY, Yang HS, Mazzanti A, Yang JW, Rios R. J. Org. Chem. 2016; 81: 3488

      Note:
    • 12a We could not obtain the single-step Michael addition product, which was the protonated form of the intermediate A or B in Scheme 3. The spirobarbiturate-cyclopropanes were the only separable products under various basic conditions in this study.
    • 12b Based on the experimental results, we could not rule out the mechanism of the reaction involving a concerted carbene-based cyclopropanation.