Abstract
An efficient one-pot synthesis of 1,2-dihydro-2-oxo-3-pyridinecarboxylate derivatives starting from enones and ethyl cyanoacetate in moderate to good yields is described. This novel tandem [3+3] annulation method mediated by FeCl3 involves Michael addition and ketone-nitrile annulation followed by aromatization-dehydrogenation. A plausible mechanism is also proposed.
Key words
ethyl cyanoacetate - 1,2-dihydro-2-oxo-3-pyridinecarboxylate - ferric chloride - [3+3] annulation
References
1a Mckillop A.
Boulton AJ. In Comprehensive Heterocyclic Chemistry
Part 2A, Vol 2:
Katritzky AR.
Rees CW.
Pergamon;
New York:
1984.
1b Harrity JPA.
Provoost O.
Org. Biomol. Chem.
2005,
3:
1349
2a Hong H.
Comins DL.
J. Org. Chem.
1996,
61:
391
2b Villemin D.
Liao L.
Tetrahedron Lett.
1996,
37:
8733
3a Van Le K, Georges B, Hevesi L, Cauvin C, Boland S, Durant F, Demonte D, Van Lint C, Burny A, Bollen A, Jacquet A, and Dewalque S. inventors; EP 1516873.
; Chem. Abstr. 2005 , 142 , 336254
3b Meurer LC.
Finke PE.
Mill SG.
Walsh TF.
Toupence RB.
Goulet MT.
Wang J.
Tong X.
Fong TM.
Lao J.
Schaeffer M.-T.
Chen J.
Shen C.-P.
Sloan SD.
Shearman LP.
Strack AM.
Van der Ploeg LHT.
Bioorg. Med. Chem. Lett.
2005,
15:
645
3c Liverton NJ, Claremon DA, Butcher JW, and Theberge CR. inventors; WO 2001000208.
; Chem. Abstr. 2001 , 134 , 86270
4a Morimoto K, Furusawa H, Terachi T, Nawamaki T, Watanabe S, Nakahira K, and Noguchi J. inventors; WO 9857957.
; Chem. Abstr. 1998 , 130 , 66511
4b Miyazaki M, Matsuzawa M, Toyabe K, and Hirata M. inventors; JP 06041116.
; Chem. Abstr.
1994 , 121 , 57525
5a Chen Y.
Zhang H.
Nan F.
J. Comb. Chem.
2004,
6:
684
5b Thomas OP.
Dumas C.
Zaparucha A.
Husson H.-P.
Eur. J. Org. Chem.
2004,
1128
6a Carles L.
Narkunan K.
Penlou S.
Rousset L.
Bouchu D.
Ciufolini MA.
J. Org. Chem.
2002,
67:
4304
6b Jain R.
Roschangar F.
Ciufolini MA.
Tetrahedron Lett.
1995,
36:
3307
7a Soto JL.
Seoane C.
Zamorano P.
Rubio MJ.
Monforte A.
Quinteiro M.
J. Chem. Soc., Perkin Trans. 1
1985,
1681
7b Kuthan J.
Nesvadba P.
Popl M.
Fahnrich J.
Collect. Czech. Chem. Commun.
1979,
44:
2409
8a Katritzky AR.
Chassaing C.
Barrow SJ.
Zhang Z.
Vvedensky V.
Forood B.
J. Comb. Chem.
2002,
4:
249
8b Katritzky AR.
Belyakov SA.
Sorochinsky AE.
Henderson SA.
Chen J.
J. Org. Chem.
1997,
62:
6210
9a Wang S.
Sun J.
Yu G.
Hu X.
Liu JO.
Hu Y.
Org. Biomol. Chem.
2004,
2:
1573
9b Yu G.
Wang S.
Wang K.
Hu Y.
Hu H.
Synthesis
2004,
1021
9c Wang S.
Yu G.
Lu J.
Xiao K.
Hu Y.
Hu H.
Synthesis
2003,
487
10 Wang S.
Pan J.
Hu Y.
Hu H.
Synthesis
2005,
753
11a Christoffers J.
Chem. Commun.
1997,
943
11b Pelzer S.
Kauf T.
Van Wullen C.
Christoffers J.
J. Organomet. Chem.
2003,
684:
308
11c Christoffers J.
Synlett
2001,
723
12a Chibiryaev AM.
De Kimpe N.
Tkachev AV.
Tetrahedron Lett.
2001,
41:
8011
12b Lu J.
Ma H.
Synlett
2000,
63
13
General Procedure for Ethyl 1,2-Dihydro-2-oxo-3-pyridinecarboxylates 3a-l.
2a -l (2.5 mmol), ethyl cyanoacetate (2.5 mmol) and FeCl3 (7.5 mmol) were dissolved in propionic acid (5.0 mL), and the mixture was refluxed for about 0.5 h (monitored by TLC). After cooling, the mixture was poured into 1.0 N HCl (30.0 mL), then extracted by CH2 Cl2 (3 × 30.0 mL). The combined organic layer was washed successively with aq NaHCO3 (30.0 mL) and H2 O (30.0 mL). The organic layer was dried (Na2 SO4 ) and the solvent was removed by distillation. The crude products obtained were purified by flash column chromatography (EtOAc-PE, 1:3) to give ethyl 1,2-dihydro-2-oxo-3-pyridinecarboxylates 3a -l .
