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Synlett 2011(15): 2167-2170  
DOI: 10.1055/s-0030-1261185
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Copper(II)-Catalyzed Synthesis of Pyrazinones from α-Azido-N-allylamides under an Oxygen Atmosphere

Line Zhanga, Jian-Yuan Leea, Naomi Yamazakib, Shunsuke Chiba*a
a Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore
Fax: +6567911961; e-Mail: shunsuke@ntu.edu.sg;
b Department of Chemistry, Tohoku University, Aoba-ku, Sendai, 980-8578, Japan
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Received 13 May 2011
Publikationsdatum:
12. August 2011 (online)

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Abstract

A copper(II)-catalyzed reaction of α-azido-N-allylamide synthetic under an oxygen atmosphere resulted in the formation of 2-formyl pyrazinones. The present transformation was characterized by the following steps: 1) 1,3-dipolar cycloaddition of the azido part onto the intramolecular alkene to give bicyclic aziridine intermediates; 2) further copper(II)-catalyzed oxygenation-oxidation of the aziridines to give 2-formyl pyrazinones.

Key words

pyrazinone - organic azides - 1,3-dipolar cycloaddition - copper - oxygen

    References and Notes

  • For recent reports on the bioactivity study of substituted pyrazines and their derivatives, see:
  • 1a Kerekes AD. Esposite SJ. Doll RJ. Tagat JR. Yu T. Xiao Y. Zhang Y. Prelusky DB. Tevar S. Gray K. Terracina GA. Lee S. Jones J. Liu M. Basso AD. Smith EB. J. Med. Chem.  2011,  54:  201 
    Suche in Google Scholar
  • 1b Andjelkovic M. inventors; WO  2008,040,651. 
  • 1c Parlow JJ. Case BL. Dice TA. Fenton RL. Hayes MJ. Jones DE. Neumann WL. Wood RS. Lachance RM. Girard TJ. Nicholson NS. Clare M. Stegeman RA. Stevens AM. Stallings WC. Kurumbail RG. South MS. J. Med. Chem.  2003,  46:  4050 
    Suche in Google Scholar
  • 1d Yang CC. Jick SS. Jick H. Arch. Intern. Med.  2003,  163:  1926 
    Suche in Google Scholar
  • 1e Mack A. Salazar JO. Formulary  2003,  38:  582 
    Suche in Google Scholar
  • 2a Blake KW. Porter AEA. Sammes PG. J. Chem. Soc., Perkin Trans. 1  1972,  2494 
  • 2b Birkofer L. Chem. Ber.  1947,  80:  83 
    Suche in Google Scholar
  • 3a Bradbury RH. Griffiths D. Rivett JE. Heterocycles  1990,  31:  1647 
    Suche in Google Scholar
  • 3b Rothkopf HW. Wöhrle D. Müller R. Kossmehl G. Chem. Ber.  1975,  108:  875 
    Suche in Google Scholar
  • 3c Flament I. Stoll M. Helv. Chim. Acta  1967,  50:  1754 
    Suche in Google Scholar
  • 3d Muehlmann FL. Day AR. J. Am. Chem. Soc.  1956,  78:  242 
    Suche in Google Scholar
  • 3e Weijlard J. Tishler M. Erikson AE. J. Am. Chem. Soc.  1945,  67:  802 
    Suche in Google Scholar
  • For recent reports on the synthesis of substituted pyrazines and their derivatives, see:
  • 4a Modha SG. Trivedi JC. Mehta VP. Ermolat’e DS. Van der Eycken EV.
    J. Org. Chem.  2011,  76:  846 
    Suche in Google Scholar
  • 4b Guerra PV. Yaylayan VA. J. Agric. Food Chem.  2010,  58:  12523 
    Suche in Google Scholar
  • 4c Krishnakumar B. Swaminathan M. J. Organomet. Chem.  2010,  695:  2572 
    Suche in Google Scholar
  • 4d Adama I. Orainb D. Meier P. Synlett  2004,  2031 
  • 4e Sato N. Matsumoto K. Takishima M. Mochizuki K. J. Chem. Soc., Perkin Trans. 1  1997,  3167 
  • 4f Buchi G. Galindo J. J. Org. Chem.  1991,  56:  2605 
    Suche in Google Scholar
  • 5 Chiba S. Zhang L. Lee J.-Y. J. Am. Chem. Soc.  2010,  132:  7266 
    CrossrefSuche in Google Scholar
  • 6 Wang H. Wang Y. Liang D. Liu L. Zhang J. Zhu Q. Angew. Chem. Int. Ed.  2011,  50:  in press; DOI: 10.1002/anie.201100362
    Suche in Google Scholar
  • Dihydropyrazinone 4 might be formed from the proposed primary alkyl radical D (in Scheme 7) by hydrogen abstraction from the solvent DMF. For the process of hydrogen abstraction from the solvent DMF:
  • 9a Minisci F. Citterio A. Vismara E. Giordano C. Tetrahedron  1985,  41:  4157 
    Suche in Google Scholar
  • 9b Palla G. Tetrahedron  1981,  37:  2917 
    Suche in Google Scholar
  • For generation of imine from α-azido ketones and esters under the strong basic conditions, see:
  • 12a Manis PA. Rathke MW. J. Org. Chem.  1980,  45:  4952 
    Suche in Google Scholar
  • 12b Edwards OE. Purushothaman KK. Can. J. Chem.  1964,  42:  712 
    Suche in Google Scholar
  • 13 One of the possibilities of the reaction course for the formation of deallylated amide 7 is outlined below. It might commence with radical 1,5-H shift from putative iminyl copper species to give allylic radical, further oxidation of which would afford allylic cation species. Addition of water to the carbocation followed by C-N bond cleavage from resulting hemiaminal could deliver deallylated amide 7 (Scheme 8). We recently reported similar 1,5-H shift from iminyl copper species, see: Zhane L. Ang GY. Chiba S. Org. Lett.  2011,  13:  1622 
    CrossrefSuche in Google Scholar
  • For recent reports on the azido-alkene 1,3-dipolar cycloaddition reaction, see:
  • 14a Hui BW.-Q. Chiba S. Org. Lett.  2009,  11:  729 
    Suche in Google Scholar
  • 14b Nair V. Suja TD. Tetrahedron  2007,  63:  12247 
    Suche in Google Scholar
  • 14c Feldman KS. Iyer MR. López CS. Faza ON. J. Org. Chem.  2008,  73:  5090 
    Suche in Google Scholar
  • 14d Zhou Y. Murphy PV. Org. Lett.  2008,  10:  3777 
    Suche in Google Scholar
  • 14e Kim S. Lee YM. Lee J. Lee T. Fu Y. Song Y. Cho J. Kim D. J. Org. Chem.  2007,  72:  4886 
    Suche in Google Scholar
  • 14f Huang X. Shen R. Zhang T. J. Org. Chem.  2007,  72:  1534 
    Suche in Google Scholar
  • 14g Feldman KS. Iyer MR. Hester DK. Org. Lett.  2006,  8:  3116 
    Suche in Google Scholar
  • 14h Feldman KS. Iyer MR. J. Am. Chem. Soc.  2005,  127:  4590 ; and references cited therein
    Suche in Google Scholar
  • For reports on the mechanism of the elimination of dinitrogen from triazoline intermediates with heterolytic cleavage of the N-N bond, see:
  • 15a Shea KJ. Kim J.-S.
    J. Am. Chem. Soc.  1992,  114:  4846 
    Suche in Google Scholar
  • 15b Wladkowski BD. Smith RH. Michejda CJ. J. Am. Chem. Soc.  1991,  113:  7893 ; and references cited therein
    Suche in Google Scholar
  • A radical pathway via homolytic cleavage of the N-N bond of triazoline intermediates is proposed, see:
  • 16a Broeckx W. Overbergh N. Samyn C. Smets G. L’abbé G. Tetrahedron  1971,  27:  3527 
    Suche in Google Scholar
  • 16b Feldman KS. Iyer MR. Hester DK. Org. Lett.  2006,  8:  3116 
    Suche in Google Scholar
  • 16c Feldman KS. Iyer MR. J. Am. Chem. Soc.  2005,  127:  4590 
    Suche in Google Scholar
7

Other bases, such as K3PO4 and NaOAc exhibited similar reactivity, while MgO was not a viable catalyst for this transformation.

8

The structures of 3b and 3i were secured by X-ray crystallographic analysis (see Supporting Information). The supplementary crystallographic data of these molecules are contained in CCDC 824717 and 824717, respectively. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/conts/retrieving.html.

10

General Procedure for the Cu(II)-Catalyzed Synthesis of Pyrazinones from α-Azido- N -allylamides
To a solution of N-allyl-2-azido-N-benzyl-2-phenyl-acetamide (1b, 156.1 mg, 0.510 mmol) in DMF (5.1 mL) were added Cu(OAc)2 (18.9 mg, 0.104 mmol) and K2CO3 (70.4 mg, 0.509 mmol), and the mixture was stirred at 80 ˚C for 2 h under an O2 atmosphere (1 atm). After cooling to r.t., the solid was filtered through a Celite pad. To the mixture,
1 M aq HCl was added, and the organic materials were extracted twice with Et2O. The combined extracts were then washed with H2O, brine, and dried over MgSO4. Filtration and removal of the solvent under reduced pressure afforded a crude mixture, which was subjected to flash column chromatography (hexane-EtOAc = 90:10) to afford 2-formyl pyrazinone 3b (91.8 mg, 0.316 mmol) in 62% yield.

11

For the synthesis of α-azido-N-allylamides 1 as well as characterization of all new compounds, see the Supporting Information.