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Synlett 2008(7): 1053-1057  
DOI: 10.1055/s-2008-1072583
LETTER
© Georg Thieme Verlag Stuttgart · New York

Intramolecular Palladium-Catalyzed Oxidative Coupling on Thiophene and Furan Rings: Determinant Role of the Electronic Availability of the Heterocycle

Egle M. Beccallia, Elena Borsinib, Gianluigi Broggini*b, Micol Rigamontib, Silvia Sottocornolab
a Istituto di Chimica Organica ‘A. Marchesini’, Facoltà di Farmacia, Università di Milano, via Venezian 21, 20133 Milano, Italy
b Dipartimento di Scienze Chimiche e Ambientali, Università dell’Insubria, via Valleggio 11, 22100 Como, Italy
Fax: +39(031)2386449; e-Mail: gianluigi.broggini@uninsubria.it;
Further Information

Publication History

Received 20 December 2007
Publication Date:
31 March 2008 (online)

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Abstract

The cyclization of N-allyl-N-carbetoxy-substituted aminothiophenes and furans was performed by intramolecular Pd(II)-catalyzed oxidative coupling. The process involves a nucleophilic attack of a heteroaromatic carbon to the internal carbon of the π-olefin complex through a 5-exo-trig ring-formation. Better conditions required PdCl2(MeCN)2 as catalyst, CuCl2 as co-catalyst and an environmentally friendly reoxidant such as O2 to promote the catalytic cycle.

Key words

coupling - cyclizations - furans - fused ring systems - palladium

    References and Notes

  • 1 Handbook of C-H Transformations - Applications in Organic Synthesis   Dyker G. Wiley-VCH; Weinheim: 2005. 
    Google Scholar
  • 2a Beccalli EM. Broggini G. Martinelli M. Sottocornola S. Chem. Rev.  2007,  107:  5318 
    CrossrefPubMedGoogle Scholar
  • 2b Popp BV. Wendlandt JE. Landis CR. Stahl SS. Angew. Chem. Int. Ed.  2007,  46:  601 
    CrossrefPubMedGoogle Scholar
  • 2c Yang S. Li B. Wan X. Shi Z. J. Am. Chem. Soc.  2007,  129:  6066 
    CrossrefPubMedGoogle Scholar
  • 2d Liu G. Stahl SS. J. Am. Chem. Soc.  2007,  129:  6328 
    CrossrefPubMedGoogle Scholar
  • 2e Thiery E. Chevrin C. Le Bras J. Harakat D. Muzart J. J. Org. Chem.  2007,  72:  1859 
    CrossrefPubMedGoogle Scholar
  • 2f Penn L. Shpruhman A. Gelman D. J. Org. Chem.  2007,  72:  3875 
    CrossrefPubMedGoogle Scholar
  • 2g Beniazza R. Dunet J. Robert F. Schenk K. Landais Y. Org. Lett.  2007,  9:  3913 
    CrossrefPubMedGoogle Scholar
  • 2h Piera J. Persson A. Caldentey X. Bäckvall J.-E. J. Am. Chem. Soc.  2007,  129:  14120 
    CrossrefPubMedGoogle Scholar
  • 3a Itahara T. Ikeda M. Sakakibara T. J. Chem. Soc., Perkin Trans. 1  1983,  1361 
    CrossrefPubMedGoogle Scholar
  • 3b Itahara T. Kawasaki K. Ouseto F. Synthesis  1984,  236 
    CrossrefPubMedGoogle Scholar
  • 3c Melnyk P. Legrand B. Gashe J. Ducrot P. Thal C. Tetrahedron  1995,  51:  1941 
    CrossrefPubMedGoogle Scholar
  • 3d Yokoyama Y. Matsumoto T. Murakami Y. J. Org. Chem.  1995,  60:  1486 
    CrossrefPubMedGoogle Scholar
  • 3e Pindur U. Reinhard A. Helv. Chim. Acta  1990,  73:  827 
    CrossrefPubMedGoogle Scholar
  • 3f Grimster NP. Gauntlett C. Godfrey CRA. Gaunt MJ. Angew. Chem. Int. Ed.  2005,  44:  3125 
    CrossrefPubMedGoogle Scholar
  • 3g Capito E. Brown JM. Ricci A. Chem. Commun.  2005,  1854 
    CrossrefPubMedGoogle Scholar
  • 3h Itahara T. Kawasaki K. Ouseto F. Bull. Chem. Soc. Jpn.  1984,  57:  3488 
    CrossrefPubMedGoogle Scholar
  • 3i Beck EM. Hatley GR. Gaunt MJ. J. Am. Chem. Soc.  2006,  128:  2528 
    CrossrefPubMedGoogle Scholar
  • 4a Beccalli EM. Broggini G. Martinelli M. Paladino G. Tetrahedron  2005,  61:  1077 
    CrossrefGoogle Scholar
  • 4b Trost BM. Godleski SA. Genêt JP. J. Am. Chem. Soc.  1978,  100:  3930 
    CrossrefGoogle Scholar
  • 4c Ferreira EM. Stoltz BM. J. Am. Chem. Soc.  2003,  125:  9578 
    CrossrefGoogle Scholar
  • 4d Kong A. Han X. Lu X. Org. Lett.  2006,  8:  1339 
    CrossrefGoogle Scholar
  • 4e Beccalli EM. Broggini G. Tetrahedron Lett.  2003,  44:  1919 
    CrossrefGoogle Scholar
  • 4f Abbiati G. Beccalli EM. Broggini G. Zoni C. J. Org. Chem.  2003,  68:  7625 
    CrossrefGoogle Scholar
  • 4g Joucla L. Montaigne C. Fournet G. Joseph B. Lett. Org. Chem.  2005,  2:  707 
    CrossrefGoogle Scholar
  • 5a Maruyama O. Yoshidomi M. Fujiwara Y. Taniguchi H. Chem. Lett.  1979,  1229 
    CrossrefGoogle Scholar
  • 5b Fujiwara Y. Maruyama O. Yoshidomi M. Taniguchi H. J. Org. Chem.  1981,  46:  851 
    CrossrefGoogle Scholar
  • 5c Jia C. Lu W. Kitamura T. Fujiwara Y. Org. Lett.  1999,  1:  2097 
    CrossrefGoogle Scholar
  • 6 Broggini G. Chiesa K. De Marchi I. Martinelli M. Pilati T. Zecchi G. Tetrahedron  2005,  61:  3525 
    CrossrefGoogle Scholar
  • 8 Ohta T, Komoriya S, Yoshino T, Uoto K, Nakamoto Y, Naito H, Mochizuki A, Nagata T, Kanno H, Haginoya N, Yoshikawa K, Nagamochi M, Kobayashi S, and Ono M. inventors; US  481,269.  ; Chem. Abstr. 2005, 142, 176829
  • 9a Nakamura T, Takagi M, Kiguchi T, Ikenogami T, and Ueda N. inventors; WO  2004113345.  ; Chem. Abstr. 2005, 142, 93672
  • 9b Bussolotti DL, and Gammill RB. inventors; US  2004220229.  ; Chem. Abstr. 2004, 141, 379914
  • 9c Bussolotti DL, and Gammill RB. inventors; WO  2004092158.  ; Chem. Abstr. 2004, 141, 379911
  • 9d Bussolotti DL, Gammill RB, and Polivkova J. inventors; WO  2004041780.  ; Chem. Abstr. 2004, 140, 406799
  • 9e Onda K, Suzuki T, Shiraki R, Yonetoku Y, Ogiyama T, Maruyama T, and Momose K. inventors; WO  2003091213.  ; Chem. Abstr. 2003, 139, 364824
  • 9f Gammill RB. inventors; WO  2003072570.  ; Chem. Abstr. 2003, 139, 230757
  • 10a Desai PJ, Dunford PJ, Hofstra CL, Karlsson L, Leung W.-P, Ling P, and Thurmond RL. inventors; WO  2004021999.  ; Chem. Abstr. 2004, 140, 247611
  • 10b Cai H, Carruthers NI, Dvorak CA, Edwards JP, and Kwok AK. inventors; US  2004048878.  ; Chem. Abstr. 2004, 140, 235696
  • 11 Barker AJ, Kettle JG, and Faull AW. inventors; WO  9940914.  ; Chem. Abstr. 1999, 131, 170342
  • 12a Gill AL, and Harris W. inventors; WO  2002002567.  ; Chem. Abstr. 2002, 136, 85755
  • 12b Osswald M, Dorsch D, Mederski W, Amendt C, and Grell M. inventors; WO  2003039539.  ; Chem. Abstr. 2003, 138, 379204
  • 12c Rault S, Enguehard C, Lancelot J.-C, Robba M, Atassi G, Pierre A, Caignard D.-H, and Renard P. inventors; JP 2000 044  572.  ; Chem. Abstr. 2000, 132, 151677
  • 12d Bair KW. inventors; US  4910218.  ; Chem. Abstr. 1991, 114, 6292
  • 14 Beccalli EM. Broggini G. Martinelli M. Sottocornola S. Synthesis  2008,  136 
    Article in Thieme ConnectGoogle Scholar
7

Experimental Procedure
A mixture of PdCl2(MeCN)2 (39 mg, 0.15 mmol) and CuCl2 (20 mg, 0.15 mmol) in DMF (13 mL) was stirred at r.t. for 30 min under oxygen atmosphere. After addition of a solution of 5a (225 mg, 1 mmol) in DMF (13 mL), the mixture was heated at 100 °C for 2 h under an O2 atmosphere. The mixture was washed with brine and extracted with Et2O (2 × 20 mL). The organic layer was dried over Na2SO4 and the solvent removed under reduced pressure. The residue was chromatographed on a silica gel column with light PE-EtOAc (10:1) as eluent to give 6a.
Data for 6-Carbethoxy-2,4-dimethyl-6 H -thieno[2,3- b ]pyrrole (6a) Oil. IR (nujol): 1635 cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.45 (3 H, t, J = 7.2 Hz), 2.20 (3 H, s), 2.53 (3 H, s), 4.45 (2 H, q, J = 7.2 Hz), 6.65 (1 H, s), 7.11 (1 H, s). 13C NMR (100 MHz, CDCl3): δ = 11.4 (q), 14.7 (q), 16.3 (q), 63.8 (t), 114.7 (d), 117.7 (s), 120.3 (d), 133 (s), 136.6 (s), 150.1 (s), 162.9 (s). MS: m/z 223 [M+]. Anal. Calcd for C11H13NO2S: C, 59.17; H, 5.87; N, 6.27. Found C, 59.01; H, 6.06; N, 6.41.

13

6-Carbethoxy-4-methyl-2-phenyl-6 H -furo[2,3- b ]pyrrole (8e)
Oil. IR (nujol): 1635 cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.50 (3 H, t, J = 7.1 Hz), 2.19 (3 H, s), 4.50 (2 H, q, J = 7.1 Hz), 6.77 (1 H, s), 6.79 (1 H, br s), 7.24-7.26 (1 H, m), 7.40 (2 H, dd, J = 7.8, 7.5 Hz), 7.70 (2 H, d, J = 7.5 Hz). 13C NMR (100 MHz, CDCl3): δ = 12.0 (q), 14.8 (q), 63.8 (t), 100.2 (d), 115.0 (s), 115.4 (s), 116.0 (d), 123.6 (d), 127.3 (d), 129.1 (d), 131.7 (s), 147.4 (s), 149.4 (s), 154.5 (s). MS: m/z = 269 [M+]. Anal. Calcd for C16H15NO3: C, 71.36; H, 5.61; N, 5.20. Found C, 71.32; H, 5.80; N, 5.05.