Synthesis 2018; 50(14): 2727-2740
DOI: 10.1055/s-0037-1610131
paper
© Georg Thieme Verlag Stuttgart · New York

Metal-Free Synthesis of Pyrrolo[1,2-a]quinoxalines Mediated by TEMPO Oxoammonium Salts

Heng-rui Huo
School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, P. R. of China   Email: gongyf@mail.hust.edu.cn   Email: xytang@hust.edu.cn
,
Xiang-Ying Tang*
School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, P. R. of China   Email: gongyf@mail.hust.edu.cn   Email: xytang@hust.edu.cn
,
School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, P. R. of China   Email: gongyf@mail.hust.edu.cn   Email: xytang@hust.edu.cn
› Author Affiliations
This project received financial support from the National Natural Science Foundation of China (21472053, 21172082).
Further Information

Publication History

Received: 29 October 2017

Accepted after revision: 08 April 2018

Publication Date:
13 June 2018 (online)


Abstract

We herein describe a novel TEMPO oxoammonium salt initiated Pictet–Spengler reaction of imines, generated in situ from carbonyl compounds and pyrrole- or indole-containing substrates, to afford 4,5-dihydropyrrolo[1,2-a]quinoxalines or 5,6-dihydroindolo[1,2-a]quin­oxalines in good to excellent yields. Moreover, a one-pot synthesis of a biologically important quinoxaline is achieved via a cyclization–dehydrogenation process using one equivalent of the oxoammonium salt.

Supporting Information

 
  • References

  • 1 Ajani OO. Eur. J. Med. Chem. 2014; 85: 688
  • 2 Szabó G. Kiss R. Páyer-Lengyel D. Vukics K. Szikra J. Baki A. Molnár L. Fischer J. Keserü GM. Bioorg. Med. Chem. Lett. 2009; 19: 3471
  • 3 Morelli E. Gemma S. Budriesi R. Campiani G. Novellino E. Fattorusso C. Catalanotti B. Coccone SS. Ros S. Borrelli G. Kumar V. Persico M. Fiorini I. Nacci V. Ioan P. Chiarini A. Hamon M. Cagnotto A. Mennini T. Fracasso C. Colovic M. Caccia S. Butini S. J. Med. Chem. 2009; 52: 3548
  • 4 Fan L.-L. Huang N. Yang R.-G. He S.-Z. Yang L.-M. Xu H. Zheng Y.-T. Lett. Drug Des. Discov. 2012; 9: 44
  • 5 Desplat V. Moreau S. Belisle-Fabre S. Thiolat D. Uranga J. Lucas R. de Moor L. Massip S. Jarry C. Mossalayi DM. Sonnet P. Déléris G. Guillon J. J. Enzym. Inhib. Med. Chem. 2011; 26: 657
  • 6 Pictet A. Spengler T. Ber. Dtsch. Chem. Ges. 1911; 44: 2030
    • 7a Cheeseman GW. H. Rafig M. J. Chem. Soc. C 1971; 2732
    • 7b Zhang C. Wang Z.-X. Appl. Organomet. Chem. 2009; 23: 9
    • 7c Tradtrantip L. Sonawane ND. Namkung W. Verkman AS. J. Med. Chem. 2009; 52: 6447
    • 7d Wang C. Li Y. Zhao J.-F. Cheng B. Wang H.-F. Zhai H.-B. Tetrahedron Lett. 2016; 57: 3908
    • 7e Li J.-X. Zhang J.-L. Yang H.-M. Gao Z. Jiang G.-X. J. Org. Chem. 2017; 82: 765
    • 8a Rustagi V. Aggarwal T. Verma AK. Green Chem. 2011; 13: 1640
    • 8b Xu H. Fan L.-L. Eur. J. Med. Chem. 2011; 46: 1919
    • 8c Li Y. Su Y.-H. Dong D.-J. Wu Z. Tian S.-K. RSC Adv. 2013; 3: 18275
    • 8d Lv W. Budke B. Pawlowski M. Connell PP. Kozikowski A. J. Med. Chem. 2016; 59: 4511
    • 8e Dai C.-S. Deng S.-Q. Zhu Q.-H. Tang X.-D. RSC Adv. 2017; 7: 44132
    • 9a Raines S. Chai SY. Palopoli FP. J. Heterocycl. Chem. 1976; 13: 711
    • 9b Abonia R. Insusaty B. Quiroga J. Kolshorn H. Meier H. J. Heterocycl. Chem. 2001; 38: 671
    • 9c Agarwal PK. Sawant D. Sharma S. Kundu B. Eur. J. Org. Chem. 2009; 292
    • 9d Verma AK. Jha RR. Sankar VK. Aggarwal T. Singh RP. Chandra R. Eur. J. Org. Chem. 2011; 6998
    • 9e Barve IJ. Chen C.-Y. Salunke DB. Chung W.-S. Sun C.-M. Chem. Asian J. 2012; 7: 1684
    • 9f Sharma A. Singh M. Rai NN. Sawant D. Beilstein J. Org. Chem. 2013; 9: 1235
    • 9g Patil NT. Konala A. Sravanti S. Singh A. Ummanni R. Sridhar B. Chem. Commun. 2013; 49: 10109
    • 9h Singh DK. Nath M. Beilstein J. Org. Chem. 2014; 10: 808
    • 9i Medda F. Hulme C. Tetrahedron Lett. 2014; 55: 3328
    • 9j Fan Y.-S. Jiang Y.-J. An D. Sha D. Antilla JC. Zhang S.-Q. Org. Lett. 2014; 16: 6112
    • 9k Kamal A. Babu KS. Ali Hussaini SM. Srikanth PS. Balakrishna M. Alarifi A. Tetrahedron Lett. 2015; 56: 4619
    • 9l Preetam A. Nath M. RSC Adv. 2015; 5: 21843
    • 9m Wang Y.-H. Cui L.-Y. Wang Y.-M. Zhou Z.-H. Tetrahedron: Asymmetry 2016; 27: 85
    • 9n Devi RV. Garande AM. Bhate PM. Synlett 2016; 27: 2807
    • 9o Raines S. Chal SY. Palopoli FP. ChemMedChem 2017; 12: 1279
    • 9p Rashidi R. Nasr-Esfahani M. Mohammadpoor-Baltork I. Tangestaninejad S. Moghadam M. Mirkhani V. Monatsh. Chem. 2018; 149: 557
    • 10a Wang C. Li Y. Guo R. Tian J.-J. Tao C. Chen B. Wang H.-Y. Zhang J. Zhai H.-B. Asian J. Org. Chem. 2015; 4: 866
    • 10b Ramamohan M. Sridhar R. Raghavendrarao K. Paradesi N. Chandrasekhar KB. Jayaprakash S. Synlett 2015; 26: 1096
  • 11 Lin PT. Salunke DB. Chen LH. Sun C.-M. Org. Biomol. Chem. 2011; 9: 2925
  • 12 Shibuya M. Tomizawa M. Iwabuchi Y. J. Org. Chem. 2008; 73: 4750
  • 13 Zhang Z.-Y. Xie C.-X. Tan X.-C. Song G.-L. Wen L.-L. Gao H. Ma C. Org. Chem. Front. 2015; 2: 942
  • 14 Badigenchala S. Rajeshkumar V. Sekar G. Org. Biomol. Chem. 2016; 14: 2297
  • 15 Thikekar TU. Selvaraju M. Sun C.-M. Org. Lett. 2016; 18: 316
  • 16 You W.-J. Rotili D. Li T.-M. Kambach C. Meleshin M. Schutkowski M. Chua KF. Mai A. Steegborn C. Angew. Chem. Int. Ed. 2017; 56: 1007
  • 17 He Z. Bae M. Wu J. Jamison TF. Angew. Chem. Int. Ed. 2014; 53: 14451