Synthesis 2017; 49(17): 4065-4081
DOI: 10.1055/s-0036-1588454
paper
© Georg Thieme Verlag Stuttgart · New York

Transition-Metal-Free Synthesis of Pyrrolo[1,2-a]pyrazines via Intramolecular Cyclization of N-Propargyl(pyrrolyl)enaminones

Lyubov N. Sobenina
Unsaturated Heteroatomic Compounds Laboratory, A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences, 1 Favorsky Str., 664033 Irkutsk, Russian Federation   eMail: [email protected]
,
Elena F. Sagitova
Unsaturated Heteroatomic Compounds Laboratory, A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences, 1 Favorsky Str., 664033 Irkutsk, Russian Federation   eMail: [email protected]
,
Igor A. Ushakov
Unsaturated Heteroatomic Compounds Laboratory, A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences, 1 Favorsky Str., 664033 Irkutsk, Russian Federation   eMail: [email protected]
,
Boris A. Trofimov*
Unsaturated Heteroatomic Compounds Laboratory, A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences, 1 Favorsky Str., 664033 Irkutsk, Russian Federation   eMail: [email protected]
› Institutsangaben
This work was supported by the President of the Russian Federation (programs for the support of leading scientific schools, grant NSh-7145.2016.3).
Weitere Informationen

Publikationsverlauf

Received: 07. April 2017

Accepted after revision: 12. Mai 2017

Publikationsdatum:
11. Juli 2017 (online)


Abstract

A concise transition-metal-free strategy for the synthesis of pyrrolo[1,2-a]pyrazines with enone substituents has been developed. It includes the following key steps: (a) cross-coupling of pyrroles with acyl(bromo)acetylenes in solid alumina at room temperature to give 2-(acylethynyl)pyrroles; (b) addition of propargylamine to the above acetylenes to form the corresponding N-propargylenaminones; and (c) chemo- and stereoselective base-catalyzed (Cs2CO3/DMSO) intramolecular cyclization of the synthesized propargylic derivatives to form (acylmeth­ylidene)pyrrolo[1,2-a]pyrazines of Z-configuration.

Supporting Information

 
  • References

    • 1a Elassar A.-ZA. El-Khair AA. Tetrahedron 2003; 59: 8463
    • 1b Cheng Y. Huang Z.-T. Wang M.-X. Curr. Org. Chem. 2004; 8: 325
    • 1c Stanovnik B. Svete J. Chem. Rev. 2004; 104: 2433
    • 1d Al-Zaydi KM. Nhari LM. Orient. J. Chem. 2006; 22: 38808
    • 1e Dar’in DV. Lobanov PS. Russ. Chem. Rev. 2015; 84: 601
  • 2 White JD. Ihle DC. Org. Lett. 2006; 8: 1081
    • 3a Yavari I. Anary-Abbasinejad M. Nasiri F. Djahaniani H. Alizadeh A. Bijanzadeh HR. Mol. Divers. 2005; 9: 209
    • 3b Bellur E. Langer P. Tetrahedron Lett. 2006; 47: 2151
    • 3c Cacchi S. Fabrizi G. Filisti E. Org. Lett. 2008; 10: 2629
    • 3d Estévez V. Villacampa M. Menéndez JC. Chem. Soc. Rev. 2010; 39: 4402
    • 3e Saito A. Konishi T. Hanzawa Y. Org. Lett. 2010; 12: 372
    • 3f Shen J. Cheng G. Cui X. Chem. Commun. 2013; 49: 10641
    • 3g Li E. Cheng X. Wang C. Sun X. Li Y. RSC Adv. 2013; 3: 22872
  • 4 Cruz MC. Jiménez F. Delgado F. Tamariz J. Synlett 2006; 749
  • 5 Uršič U. Bevk D. Pirc S. Pezdirc L. Stanovnik B. Svete J. Synthesis 2006; 2376
    • 6a Yang J. Wang C. Xie X. Li H. Li Y. Eur. J. Org. Chem. 2010; 4189
    • 6b Martins MA. P. Rossatto M. Frizzo CP. Scapin E. Buriol L. Zanatta N. Bonacorso HG. Tetrahedron Lett. 2013; 54: 847
    • 6c Shao Y. Zhu K. Qin Z. Li E. Li Y. J. Org. Chem. 2013; 78: 5731
  • 7 Karpov AS. Müller TJ. J. Synthesis 2003; 2815
  • 8 Sobenina LN. Tomilin DN. Gotsko MD. Ushakov IA. Mikhaleva AI. Trofimov BA. Tetrahedron 2014; 70: 5168
  • 9 Rochais C. Lisovsky V. Dallemagne P. Rault S. Bioorg. Med. Chem. 2006; 14: 8162
  • 10 Zhou Y. Wei Y. Yang J. Li H. Liu M. Huang N. Adv. Mater. Res. 2014; 830: 115
  • 11 Kumar S. Kumar N. Roy P. Sondhi SM. Mol. Divers. 2013; 17: 753
  • 12 Reker D. Seet M. Pillong M. Koch CP. Schneider P. Witschel MC. Rottmann M. Freymond C. Brun R. Schweizer B. Illarionov B. Bacher A. Fischer M. Diederich F. Schneider G. Angew. Chem. Int. Ed. 2014; 53: 7079
  • 13 Tiwari RK. Singh D. Singh J. Yadav V. Pathak AK. Dabur R. Chhillar AK. Singh R. Sharma GL. Chandra R. Verma AK. Bioorg. Med. Chem. Lett. 2006; 16: 413
  • 14 Fisher TE. Kim B. Staas DD. Lyle TA. Young SD. Vacca JP. Zrada MM. Hazuda DJ. Felock PJ. Schleif WA. Gabryelski LJ. Anari MR. Kochanskyd CJ. Wai JS. Bioorg. Med. Chem. Lett. 2007; 17: 6511
    • 15a Bamberg JT. Joe DuB. D. Elworthy TR. Hendricks RT. Hermann JC. Jahangir A. Kondru RK. Lemoine R. Lou Y. Owens TD. Park J. Smith DB. Soth M. Yang H. Patent WO2009106441 A1, 2009
    • 15b Soth M. Hermann JC. Yee C. Alam M. Barnett JW. Berry P. Browner MF. Frank K. Frauchiger S. Harris S. He Y. Hekmat-Nejad M. Hendricks T. Henningsen R. Hilgenkamp R. Ho H. Hoffman A. Hsu P.-Y. Hu D.-Q. Itano A. Jaime-Figueroa S. Jahangir A. Jin S. Kuglstatter A. Kutach AK. Liao C. Lynch S. Menke J. Niu L. Patel V. Railkar A. Roy D. Shao A. Shaw D. Steiner S. Sun Y. Tan S.-L. Wang S. Vu MD. J. Med. Chem. 2013; 56: 345
    • 15c Padilla F. Bhagirath N. Chen S. Chiao E. Goldstein DM. Hermann JC. Hsu J. Kennedy-Smith JJ. Kuglstatter A. Liao C. Liu W. Lowrie LE. Jr. Luk KC. Lynch SM. Menke J. Niu L. Owens TD. O-Yang C. Railkar A. Schoenfeld RC. Slade M. Steiner S. Tan Y.-C. Villaseñor AG. Wang C. Wanner J. Xie W. Xu D. Zhang X. Zhou M. Lucas MC. J. Med. Chem. 2013; 56: 1677
  • 16 Burdick DJ. Wang S. Heise C. Pan B. Drummond J. Yin J. Goeser L. Magnuson S. Blaney J. Moffat J. Wang W. Chen H. Bioorg. Med. Chem. Lett. 2015; 25: 4728
  • 17 Chang-Fong J. Addo J. Dukat M. Smith C. Mitchell NA. Herrick-Davis K. Teitler M. Glennon RA. Bioorg. Med. Chem. Lett. 2002; 12: 155
  • 18 Rault S. Lancelot J.-C. Prunier H. Robba M. Delagrange P. Renard P. Adam G. Patent US5599812 A, 1997
  • 19 Arban R. Bianchi F. Buson A. Cremonesi S. Di Fabio R. Gentile G. Micheli F. Pasquarello A. Pozzan A. Tarsi L. Terreni S. Tonelli F. Bioorg. Med. Chem. Lett. 2010; 20: 5044
  • 20 Micheli F. Bertani B. Bozzoli A. Crippa L. Cavanni P. Di Fabio R. Donati D. Marzorati P. Merlo G. Paio A. Perugini L. Zarantonello P. Bioorg. Med. Chem. Lett. 2008; 18: 1804
  • 21 Cheng L. Patent WO2005051953 A2, 2005
  • 22 Beccalli EM. Broggini G. Martinelli M. Paladino G. Tetrahedron 2005; 61: 1077
  • 23 Alfonsi M. Dell’Acqua M. Facoetti D. Arcadi A. Abbiati G. Rossi E. Eur. J. Org. Chem. 2009; 2852
  • 24 Chen W. Hu M. Wu J. Zou H. Yu Y. Org. Lett. 2010; 12: 3863
  • 25 Nayak M. Pandey G. Batra S. Tetrahedron 2011; 67: 7563
  • 26 Basceken S. Balci M. J. Org. Chem. 2015; 80: 3806
    • 27a Trofimov BA. Stepanova ZV. Sobenina LN. Mikhaleva AI. Ushakov IA. Tetrahedron Lett. 2004; 45: 6513
    • 27b Trofimov BA. Sobenina LN. In Targets in Heterocyclic Systems . Vol. 13. Attanasi OA. Spinelli D. RSC Publishing; Cambridge: 2009: 92
    • 27c Sobenina LN. Tomilin DN. Petrova OV. Gulia N. Osowska K. Szafert S. Mikhaleva AI. Trofimov BA. Russ. J. Org. Chem. 2010; 46: 1373
    • 27d Gotsko MD. Sobenina LN. Tomilin DN. Ushakov IA. Dogadina AV. Trofimov AB. Tetrahedron Lett. 2015; 56: 4657
    • 27e Tomilin DN. Pigulski B. Gulia N. Arendt A. Sobenina LN. Mikhaleva AI. Szafert S. Trofimov BA. RSC Adv. 2015; 5: 73241
    • 27f Tomilin DN. Gotsko MD. Sobenina LN. Ushakov IA. Afonin AV. Soshnikov DY. Trofimov AB. Koldobsky AB. Trofimov BA. J. Fluorine Chem. 2016; 186: 1
    • 27g Pigulski B. Arendt A. Tomilin DN. Sobenina LN. Trofimov BA. Szafert S. J. Org. Chem. 2016; 81: 9188
    • 28a Sobenina LN. Tomilin DN. Petrova OV. Ushakov IA. Mikhaleva AI. Trofimov BA. Synthesis 2010; 42: 2468
    • 28b Sobenina LN. Tomilin DN. Petrova OV. Ushakov IA. Mikhaleva AI. Trofimov BA. Synthesis 2012; 44: 2084
  • 29 Menges N. Sari O. Abdullayev Y. Erdem SS. Balci M. J. Org. Chem. 2013; 78: 5184
  • 30 Trofimov BA. Curr. Org. Chem. 2002; 6: 1121