Download PDF
Synlett 2012(4): 585-588  
DOI: 10.1055/s-0031-1290333
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Highly Stereocontrolled Intramolecular Cycloaddition Reaction of Azomethine Ylide Activated by a Pyrimidine Ring: Access to Novel Tricyclic Hexahydro-1H-pyrrolo[2′,3′:4,5]pyrido[2,3-d]pyrimidines

Hongxiang Xie, Jinbao Xiang, Qun Dang*, Xu Bai*
The Center for Combinatorial Chemistry and Drug Discovery, The College of Chemistry and The School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, P. R. of China
Fax: +86(431)85188900; e-Mail: xbai@jlu.edu.cn; e-Mail: qdang@jlu.edu.cn;
Further Information

Publication History

Received 26 October 2011
Publication Date:
06 February 2012 (online)

    Permissions and Reprints All articles of this category

Abstract

A pyrimidine ring was discovered to aid formation of an azomethine ylide undergoing intramolecular cycloaddition reactions. This method enabled efficient synthesis of a novel tricyclic pyrimidine-piperidine-pyrrolidine scaffold from various pyri­midinemethyl amines and aldehydes in complete stereocontrol and could be rationalized by an S-shaped azomethine ylide intermediate.

Key words

azomethine ylide - intramolecular cycloaddition - 1,3-dipolar cycloaddition - pyrimidine - pyrrolidine

    References and Notes

  • For recent reviews about 1,3-dipolar cycloaddition reactions of azomethine ylides, see:
  • 1a Nájera C. Sansano JM. Curr. Org. Chem.  2003,  7:  1105 
    Search in Google Scholar
  • 1b Pandey G. Banerjee P. Gadre SR. Chem. Rev.  2006,  106:  4484 
    Search in Google Scholar
  • 1c Pellissier H. Tetrahedron  2007,  63:  3235 
    Search in Google Scholar
  • 1d Stanley LM. Sibi MP. Chem. Rev.  2008,  108:  2887 
    Search in Google Scholar
  • 1e Álvarez-Corral M. Muñoz-Dorado M. Rodríguez-García I. Chem. Rev.  2008,  108:  3174 
    Search in Google Scholar
  • 1f Burrell AJM. Coldham I. Curr. Org. Synth.  2010,  7:  312 
    Search in Google Scholar
  • 1g Adrio J. Carretero JC. Chem. Commun.  2011,  47:  6784 
    Search in Google Scholar
  • For one review and recent reports about intramolecular 1,3-dipolar cycloaddition reactions of azomethine ylides, see:
  • 2a Coldham I. Hufton R. Chem. Rev.  2005,  105:  2765 
    Search in Google Scholar
  • 2b Burrell AJM. Coldham I. Watson L. Oram N. Pilgram CD. Martin NG. J. Org. Chem.  2009,  74:  2290 
    Search in Google Scholar
  • 2c Kathiravan S. Ramesh E. Raghunathan R. Tetrahedron Lett.  2009,  50:  2389 
    Search in Google Scholar
  • 2d Bakthadoss M. Sivakumar N. Synlett  2009,  1014 
  • 2e Pankova AS. Voronin VV. Kuznetsov MA. Tetrahedron Lett.  2009,  50:  5990 
    Search in Google Scholar
  • 2f Pandey G. Gupta NR. Pimpalpalle TM. Org. Lett.  2009,  11:  2547 
    Search in Google Scholar
  • 2g Bélanger G. Darsigny V. Doré M. Lévesque F. Org. Lett.  2010,  12:  1396 
    Search in Google Scholar
  • 2h Kathiravan S. Vijayarajan D. Raghunathan R. Tetrahedron Lett.  2010,  51:  3065 
    Search in Google Scholar
  • 2i Sirisha N. Raghunathan R. Tetrahedron Lett.  2010,  51:  2515 
    Search in Google Scholar
  • 2j Purushothaman S. Prasanna R. Niranjana P. Raghunathan R. Nagaraj S. Rengasamy R. Bioorg. Med. Chem. Lett.  2010,  20:  7288 
    Search in Google Scholar
  • 2k Kathiravan S. Raghunathan R. Synlett  2010,  952 
  • 2l Burrell AJM. Watson L. Martin NG. Oram N. Coldham I. Org. Biomol. Chem.  2010,  8:  4530 
    Search in Google Scholar
  • 2m Coldham I. Burrell AJM. Guerrand HDS. Oram N. Org. Lett.  2011,  13:  1267 
    Search in Google Scholar
  • 3a Martin SF. Cheavens TH. Tetrahedron Lett.  1989,  30:  7017 
    Search in Google Scholar
  • 3b Grigg R. Sridharan V. Thornton-Pett M. Wang J. Xu J. Zhang J. Tetrahedron  2002,  58:  2627 
    Search in Google Scholar
  • 3c Pospíšil J. Potáček M. Tetrahedron  2007,  63:  337 
    Search in Google Scholar
  • 4a Ardill H. Fontaine XLR. Grigg R. Henderson D. Montgomery J. Sridharan V. Surendrakumar S. Tetrahedron  1990,  46:  6449 
    Search in Google Scholar
  • 4b Wang B. Mertes MP. Mertes KB. Takusagawa F. Tetrahedron Lett.  1990,  31:  5543 
    Search in Google Scholar
  • 4c Deb I. Das D. Seidel D. Org. Lett.  2011,  13:  812 
    Search in Google Scholar
  • For examples, see:
  • 5a Jang M. Lin Y. Jonghe SD. Gao L. Vanderhoydonck B. Froeyen M. Rozenski J. Herman J. Louat T. Belle KV. Waer M. Herdewijn P. J. Med. Chem.  2011,  54:  655 
    Search in Google Scholar
  • 5b Saravanan K. Barlow HC. Barton M. Calvert AH. Golding BT. Newell DR. Northen JS. Curtin NJ. Thomas HD. Griffin RJ. J. Med. Chem.  2011,  54:  1847 
    Search in Google Scholar
  • 5c Jorda R. Havlíček L. McNae IW. Walkinshaw MD. Voller J. Šturc A. Navrátilová J. Kuzma M. Mistrik M. Bártek J. Strnad M. Kryštof V. J. Med. Chem.  2011,  54:  2980 
    Search in Google Scholar
  • 5d Maruoka H. Jayasekara MPS. Barrett MO. Franklin DA. Castro SD. Kim N. Costanzi S. Harden TK. Jacobson KA. J. Med. Chem.  2011,  54:  4018 
    Search in Google Scholar
  • For examples, see:
  • 6a Merritt JR. Liu J. Quadros E. Morris ML. Liu R. Zhang R. Jacob B. Postelnek J. Hicks CM. Chen W. Kimble EF. Rogers WL. O’Brien L. White N. Desai H. Bansal S. King G. Ohlmeyer MJ. Appell KC. Webb ML. J. Med. Chem.  2009,  52:  1295 
    Search in Google Scholar
  • 6b Ueda J. Takagi M. Shin-ya K. J. Nat. Prod.  2009,  72:  2181 
    Search in Google Scholar
  • 6c Vartak AP. Nickell JR. Chagkutip J. Dwoskin LP. Crooks PA. J. Med. Chem.  2009,  52:  7878 
    Search in Google Scholar
  • 6d Xue F. Kraus JM. Labby KJ. Ji H. Mataka J. Xia G. Li H. Delker SL. Roman LJ. Martásek P. Poulos TL. Silverman RB. J. Med. Chem.  2011,  54:  6399 
    Search in Google Scholar
  • 7 During the preparation of this manuscript, we noticed a recent report on an intermolecular reaction of 4,6-dimethylpyrimidine-activated secondary amines with different aryl/heteroaryl and N-methylmaleimide or maleimide by: Elboray EE. Grigg R. Fishwick CWG. Kilner C. Sarker MAB. Aly MF. Abbas-Temirek HH. Tetrahedron  2011,  67:  5700 
    Search in Google Scholar
  • 8a Stohler R. Wahl F. Pfaltz A. Synthesis  2005,  1431 
  • 8b Grigg R. Sarker MAB. Tetrahedron  2006,  62:  10332 
    Search in Google Scholar
  • 8c Padilla S. Tejero R. Adrio J. Carretero JC. Org. Lett.  2010,  12:  5608 
    Search in Google Scholar
  • 9 Confalone PN. Huie EM. J. Am. Chem. Soc.  1984,  106:  7175 
    Search in Google Scholar
10

CCDC 848492 (11a), CCDC 848493 (11q) and CCDC 848494 (11v) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.