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

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.

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 

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 

1d Yang CC. Jick SS. Jick H. Arch. Intern. Med.  2003,  163:  1926 

1e Mack A. Salazar JO. Formulary  2003,  38:  582 

2a Blake KW. Porter AEA. Sammes PG. J. Chem. Soc., Perkin Trans. 1  1972,  2494 

2b Birkofer L. Chem. Ber.  1947,  80:  83 

3a Bradbury RH. Griffiths D. Rivett JE. Heterocycles  1990,  31:  1647 

3b Rothkopf HW. Wöhrle D. Müller R. Kossmehl G. Chem. Ber.  1975,  108:  875 

3c Flament I. Stoll M. Helv. Chim. Acta  1967,  50:  1754 

3d Muehlmann FL. Day AR. J. Am. Chem. Soc.  1956,  78:  242 

3e Weijlard J. Tishler M. Erikson AE. J. Am. Chem. Soc.  1945,  67:  802 

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 

4b Guerra PV. Yaylayan VA. J. Agric. Food Chem.  2010,  58:  12523 

4c Krishnakumar B. Swaminathan M. J. Organomet. Chem.  2010,  695:  2572 

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 

5 Chiba S. Zhang L. Lee J.-Y. J. Am. Chem. Soc.  2010,  132:  7266 

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

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.

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 

9b Palla G. Tetrahedron  1981,  37:  2917 

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.

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 

12b Edwards OE. Purushothaman KK. Can. J. Chem.  1964,  42:  712 

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 

For recent reports on the azido-alkene 1,3-dipolar cycloaddition reaction, see:

14a Hui BW.-Q. Chiba S. Org. Lett.  2009,  11:  729 

14b Nair V. Suja TD. Tetrahedron  2007,  63:  12247 

14c Feldman KS. Iyer MR. López CS. Faza ON. J. Org. Chem.  2008,  73:  5090 

14d Zhou Y. Murphy PV. Org. Lett.  2008,  10:  3777 

14e Kim S. Lee YM. Lee J. Lee T. Fu Y. Song Y. Cho J. Kim D. J. Org. Chem.  2007,  72:  4886 

14f Huang X. Shen R. Zhang T. J. Org. Chem.  2007,  72:  1534 

14g Feldman KS. Iyer MR. Hester DK. Org. Lett.  2006,  8:  3116 

14h Feldman KS. Iyer MR. J. Am. Chem. Soc.  2005,  127:  4590 ; and references cited therein

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 

15b Wladkowski BD. Smith RH. Michejda CJ. J. Am. Chem. Soc.  1991,  113:  7893 ; and references cited therein

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 

16b Feldman KS. Iyer MR. Hester DK. Org. Lett.  2006,  8:  3116 

16c Feldman KS. Iyer MR. J. Am. Chem. Soc.  2005,  127:  4590