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Synlett 2012; 23(20): 2913-2918
DOI: 10.1055/s-0032-1317588
letter
© Georg Thieme Verlag Stuttgart · New York

Diels–Alder Reactions of 2-Vinylindoles with Cyclic Dienophiles: Synthesis of [c]-Annulated Tetrahydrocarbazoles

Valentina Pirovano
Dipartimento di Scienze Farmaceutiche, Sezione di Chimica Generale e Organica ‘Alessandro Marchesini’, Università degli Studi di Milano, Via Venezian 21, 20133 Milano, Italy   Fax: +39(02)50314476   Email: elisabetta.rossi@unimi.it
,
Giorgio Abbiati
Dipartimento di Scienze Farmaceutiche, Sezione di Chimica Generale e Organica ‘Alessandro Marchesini’, Università degli Studi di Milano, Via Venezian 21, 20133 Milano, Italy   Fax: +39(02)50314476   Email: elisabetta.rossi@unimi.it
,
Monica Dell’Acqua
Dipartimento di Scienze Farmaceutiche, Sezione di Chimica Generale e Organica ‘Alessandro Marchesini’, Università degli Studi di Milano, Via Venezian 21, 20133 Milano, Italy   Fax: +39(02)50314476   Email: elisabetta.rossi@unimi.it
,
Diego Facoetti
Dipartimento di Scienze Farmaceutiche, Sezione di Chimica Generale e Organica ‘Alessandro Marchesini’, Università degli Studi di Milano, Via Venezian 21, 20133 Milano, Italy   Fax: +39(02)50314476   Email: elisabetta.rossi@unimi.it
,
Mara Giordano
Dipartimento di Scienze Farmaceutiche, Sezione di Chimica Generale e Organica ‘Alessandro Marchesini’, Università degli Studi di Milano, Via Venezian 21, 20133 Milano, Italy   Fax: +39(02)50314476   Email: elisabetta.rossi@unimi.it
,
Elisabetta Rossi*
Dipartimento di Scienze Farmaceutiche, Sezione di Chimica Generale e Organica ‘Alessandro Marchesini’, Università degli Studi di Milano, Via Venezian 21, 20133 Milano, Italy   Fax: +39(02)50314476   Email: elisabetta.rossi@unimi.it
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Further Information

Publication History

Received: 01 October 2012

Accepted after revision: 19 October 2012

Publication Date:
19 November 2012 (online)

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Abstract

Diels–Alder reactions of 2-vinylindoles with cyclic carbo- and heterodienophiles, in the presence of suitable Lewis acids, led to uncommon [c]-carbo- and furoannulated tetrahydrocarbazoles. The obtained compounds encompass a carbonyl group in an angular position, suitable for further transformations, and represent useful intermediates for the synthesis of more complex structures.

Key words

Diels–Alder reaction - heterocycles - polycycles - Lewis acids - indoles

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information
 

  • References

    • 1a Loh CC. J, Enders D. Angew. Chem. Int. Ed. 2012; 51: 46
      Crossref
    • 1b Roy J, Jana AK, Mal D. Tetrahedron 2012; 68: 6099
      Crossref
    • 1c Bauer I, Knoelker H.-J. Top. Curr. Chem. 2012; 309: 203
      PubMed
    • 1d Schmidt AW, Reddy KR, Knoelker H.-J. Chem. Rev. 2012; 112: 3193
      CrossrefPubMed
    • 1e Choshi T, Hibino S. Heterocycles 2011; 83: 1205
      Crossref
    • 1f Juwarker H, Suk J.-M, Jeong K.-S. Top. Heterocycl. Chem. 2010; 24: 177
    • 1g Zhang D, Song H, Qin Y. Acc. Chem. Res. 2011; 44: 447
      Crossref
    • 1h Forke R, Gruner KK, Knott KE, Auschill S, Agarwal S, Martin R, Boehl M, Richter S, Tsiavaliaris G, Fedorov R, Manstein DJ, Gutzeit HO, Knoelker H.-J. Pure Appl. Chem. 2010; 82: 1975
      Crossref
    • 1i Yaqub G, Hussain EA, Rehman MA, Mateen B. Asian J. Chem. 2009; 21: 2485
    • 1j Knoelker H.-J. Chem. Lett. 2009; 38: 8
      Crossref
    • 1k Knoelker H.-J, Reddy KR. Chem. Rev. 2002; 102: 4303
      Crossref
    • 2a Kester RF, Berthel SJ, Firooznia F. Top. Heterocycl. Chem. 2010; 26: 327
    • 2b Gioia C, Bernardi L, Ricci A. Synthesis 2010; 161
      Article in Thieme Connect
    • 2c Wang X.-F, Chen J.-R, Cao Y.-J, Cheng H.-G, Xiao W.-J. Org. Lett. 2010; 12: 1140
      Crossref
    • 2d Zheng C, Lu Y, Zheng J, Chen X, Chai Z, Na W, Zhao G. Chem.–Eur. J. 2010; 16: 5853
    • 2e Cao YJ, Cheng H.-G, Lu L.-Q, Zhang J.-J, Cheng Y, Chen JR, Xiao WJ. Adv. Synth. Catal. 2011; 353: 617
      Crossref
    • 2f Tan F, Li F, Zhang X.-X, Wang X.-F, Cheng H.-G, Chen J.-R, Xiao W.-J. Tetrahedron 2011; 67: 446
      Crossref
    • 2g Mohamed YA. M, Inagaki F, Takahashi R, Mukai K. Tetrahedron 2011; 67: 5133
      Crossref
  • 3 Abbiati G, Canevari V, Facoetti D, Rossi E. Eur. J. Org. Chem. 2007; 517
  • 4 Rossi E, Abbiati G, Canevari V, Celentano G. Synthesis 2006; 299
    Article in Thieme Connect
    • 5a Ishihara K, Kurihara H, Matsumoto M, Yamamoto H. J. Am. Chem. Soc. 1998; 120: 6920
      Crossref
    • 5b Huang Y, Iwama T, Rawal VH. J. Am. Chem. Soc. 2000; 122: 7843
    • 5c Canales E, Corey EJ. Org. Lett. 2008; 10: 3271
    • 6a Akgün E, Tunali M, Erdönmez G. J. Heterocycl. Chem. 1989; 26: 1869
    • 6b Narasimhan NS, Kusurkar RS, Dhavale DD. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 1983; 22: 1004
    • 6c Eitel M, Pindur U. J. Org. Chem. 1990; 55: 5368
      Crossref
    • 6d Eitel M, Pindur U. Heterocycles 1988; 27: 2353
      Crossref
    • 6e Çavdar H, Saraçoĝlu N. J. Org. Chem. 2006; 71: 7793
      Crossref
  • 7 TePaske MR, Gloer JB, Wicklow DT, Dowd PF. J. Org. Chem. 1990; 55: 5299
    Crossref
  • 8 See ref. 1d, pages 3268 and 3273, respectively.
    • 9a Ito C, Katsuno S, Ruangrungsi N, Furukawa H. Chem. Pharm. Bull. 1998; 46: 344
      Crossref
    • 9b Wu T.-S, Huang S.-C, Wu P.-L. Chem. Pharm. Bull. 1998; 46: 1459
      Crossref
    • 9c Ito C, Itoigawa M, Aizawa K, Yoshida K, Ruangrungsi N, Furukawa H. J. Nat. Prod. 2009; 72: 1202
      Crossref
    • 9d Lebold TP, Kerr MA. Org. Lett. 2008; 10: 997
      Crossref
    • 9e Ito C, Katsuno S, Itoigawa M, Ruangrungsi N, Mukainaka T, Okuda M, Kitagawa Y, Tokuda H, Nishino H, Furukawa H. J. Nat. Prod. 2000; 63: 125
      Crossref
    • 9f Jana AK, Mal D. Chem. Commun. 2010; 46: 4411
      Crossref
    • 10a Forke R, Krahl MP, Krause T, Schlechtingen G, Knoelker H.-J. Synlett 2007; 268
    • 10b Lebold TP, Kerr MA. Org. Lett. 2007; 9: 1883
      CrossrefPubMed
    • 11a Diedrich CL, Frey W, Christoffers J. Eur. J. Org. Chem. 2007; 4731
    • 11b Christoffers J. Synlett 2006; 318
      Article in Thieme Connect
    • 11c Bender M, Christoffers J. Z. Naturforsch., B 2011; 66: 1209
      Crossref
  • 12 General Procedure, Method A: To a nitrogen-flushed solution of Sc(OTf)3 (13 mol%) in CH2Cl2 (1 mL) a solution of 1a (1.00 mmol) and 2a,b,d,f,g (1.00 mmol) in CH2Cl2 (3 mL) was added and the mixture was refluxed for 24 h. The solvent was then removed in vacuo and the residue was purified by flash silica gel chromatography. 4a: yield: 60.7%; yellow oil. IR (KBr): 3047, 2934, 2871, 2693, 1728, 1612, 1513, 1458 cm–1. 1H NMR (300 MHz, C6D6): δ = 9.46 (s, 1 H), 8.59 (d, J = 8.2 Hz, 1 H), 7.52 (d, J = 7.5 Hz, 1 H), 7.42 (m, 1 H), 7.34 (m, 1 H), 7.12 (d, J = 8.0 Hz, 2 H), 7.05 (d, J = 8.0 Hz, 2 H), 4.10 (q, J = 7.1 Hz, 2 H), 3.56 (m, 1 H), 3.39 (m, 2 H), 3.22 (m, 1 H), 2.21 (s, 3 H), 2.17 (m, 1 H), 1.92 (m, 2 H), 1.84 (m, 1 H), 1.60 (m, 1 H), 1.47 (m, 1 H), 1.01 (t, J = 7.1 Hz, 3 H). 13C NMR (75.45 MHz, C6D6): δ = 203.8 (CH), 152.0 (Cq), 138.6 (Cq), 137.2 (Cq), 136.9 (Cq), 134.3 (Cq), 129.7 (CH), 129.5 (Cq), 128.8 (CH), 124.4 (CH), 123.3 (CH), 119.2 (CH), 118.7 (Cq), 116.4 (CH), 62.9 (CH2), 62.4 (Cq), 44.4 (CH), 39.1 (CH), 30.1 (CH2), 29.4 (CH2), 24.5 (CH2), 24.3 (CH2), 21.1 (Me), 14.3 (Me). MS (ESI, +): m/z (%) = 402 (100) [M + 1]+. Anal. Calcd for C26H27NO3 (401.50): C, 77.78; H, 6.78; N, 3.49. Found: C, 77.75; H, 6.69; N, 3.43. 3a: yield: 30.3%; yellow solid; mp 130–131 °C. IR (KBr): 3052, 2942, 2871, 2699, 1735, 1615, 1514, 1475 cm–1. 1H NMR (300 MHz, C6D6): δ = 9.68 (s, 1 H), 8.60 (d, J = 8.1 Hz, 1 H), 7.51 (d, J = 7.5 Hz, 1 H), 7.43 (m, 1 H), 7.36 (m, 1 H), 7.19 (d, J = 7.8 Hz, 2 H), 7.01 (d, J = 7.8 Hz, 2 H), 4.05 (q, J = 7.1 Hz, 2 H), 3.81 (dd, J = 18.4, 9.6 Hz, 1 H), 3.53 (dd, J = 18.4, 5.5 Hz, 1 H), 3.43 (m, 1 H), 3.08 (dd, J = 9.6, 5.5 Hz, 1 H), 2.35 (m, 1 H), 2.18 (s, 3 H), 1.96 (m, 1 H), 1.75 (m, 3 H), 1.58 (m, 1 H), 0.97 (t, J = 7.1 Hz, 3 H). 13C NMR (75.45 MHz, C6D6): δ = 203.0 (CH), 152.0 (Cq), 139.1 (Cq), 137.2 (Cq), 136.8 (Cq), 134.5 (Cq), 129.9 (Cq), 129.6 (CH), 129.5 (CH), 124.5 (CH), 123.3 (CH), 119.0 (CH), 118.9 (Cq), 116.5 (CH), 62.8 (CH2), 60.0 (Cq), 44.8 (CH), 39.3 (CH), 32.3 (CH2), 31.0 (CH2), 30.3 (CH2), 24.0 (CH2), 21.1 (Me), 14.2 (Me). MS (ESI, +): m/z (%) = 402 (100) [M + 1]+. Anal. Calcd for C26H27NO3 (401.50): C, 77.78; H, 6.78; N, 3.49. Found: C, 77.62; H, 6.83; N, 3.47. General Procedure, Method B: To a nitrogen-flushed solution of 1a–e (1.00 mmol) and 2a,c,d,e (1.5 mmol) in toluene (6 mL) was added BF3·OEt2 (15 mol%) at –20 °C and, unless otherwise detailed, the mixture was stirred at the same temperature for the stated time. The solvent was then removed in vacuo and the residue was purified by flash silica gel chromatography. 4d: yield: 7.6%; yellow solid; mp 167–168 °C. IR (KBr): 3027, 2925, 2854, 2747, 1733, 1722, 1612, 1512, 1492 cm–1. 1H NMR (300 MHz, CDCl3): δ = 9.62 (s, 1 H), 8.16 (d, J = 8.3 Hz, 1 H), 7.35 (m, 5 H), 7.28 (m, 1 H), 7.19 (d, J = 8.2 Hz, 2 H), 7.14 (d, J = 8.2 Hz, 2 H), 7.07 (m, 1 H), 6.76 (d, J = 7.7 Hz, 1 H), 4.62 (d, J = 5.8 Hz, 1 H), 4.50 (q, J = 7.1 Hz, 2 H), 4.48 (d, J = 9.5 Hz, 1 H), 4.31 (d, J = 9.5 Hz, 1 H), 4.06 (d, J = 5.8 Hz, 1 H), 3.61 (m, 1 H), 3.48 (m, 2 H), 2.38 (s, 3 H), 1.49 (t, J = 7.1 Hz, 3 H). 13C NMR (75.45 MHz, CDCl3): δ = 204.6 (CH), 152.3 (Cq), 140.6 (Cq), 137.8 (Cq), 136.7 (Cq), 136.5 (Cq), 134.4 (Cq), 130.0 (CH), 129.0 (CH), 128.9 (CH), 128.8 (Cq), 128.6 (CH), 128.1 (CH), 124.6 (CH), 123.2 (CH), 119.5 (CH), 117.5 (Cq), 115.9 (CH), 90.3 (CH), 69.1 (CH2), 63.6 (CH2), 62.8 (Cq), 47.3 (CH), 44.6 (CH), 29.1 (CH2), 21.4 (Me), 14.8 (Me). MS (ESI, +): m/z (%) = 502 (100) [M + Na]+. Anal. Calcd for C31H29NO4 (479.31): C, 77.64; H, 6.10; N, 2.92. Found: C, 77.56; H, 5.97; N, 3.07. 3d: yield: 68.4%; yellow solid; mp 186–187 °C. IR (KBr): 3031, 2918, 2852, 2737, 1733, 1513, 1492 cm–1. 1H NMR (300 MHz, CDCl3): δ = 9.85 (s, 1 H), 8.10 (d, J = 8.4 Hz, 1 H), 7.42 (m, 5 H), 7.23 (m, 5 H), 6.85 (m, 1 H), 5.98 (d, J = 7.8 Hz, 1 H), 4.95 (d, J = 8.7 Hz, 1 H), 4.52 (d, J = 9.7 Hz, 1 H), 4.50 (q, J = 7.1 Hz, 2 H), 4.15 (d, J = 9.7 Hz, 1 H), 3.75 (d, J = 8.7 Hz, 1 H), 3.72 (m, 3 H), 2.36 (s, 3 H), 1.47 (t, J = 7.1 Hz, 3 H). 13C NMR (75.45 MHz, CDCl3): δ = 201.1 (CH), 152.2 (Cq), 140.9 (Cq), 137.7 (Cq), 137.2 (Cq), 136.4 (Cq), 135.6 (Cq), 129.9 (CH), 129.7 (CH), 129.1 (CH), 129.1 (CH), 128.9 (Cq), 127.9 (CH), 124.4 (CH), 122.9 (CH), 119.7 (CH), 113.7 (CH), 115.7 (Cq), 87.9 (CH), 72.0 (CH2), 63.5 (CH2), 60.9 (Cq), 49.6 (CH), 43.8 (CH), 31.1 (CH2), 21.4 (Me), 14.8 (Me). MS (ESI, +): m/z (%) = 502 (100) [M + Na]+. Anal. Calcd for C31H29NO4 (479.31): C, 77.64; H, 6.10; N, 2.92. Found: C, 77.49; H, 6.03; N, 3.12.
    • 13a Atarashi S, Choi J.-K, Ha D.-C, Hart DJ, Kuzmich D, Lee C.-S, Ramesh S, Wu SC. J. Am. Chem. Soc. 1997; 119: 6226
      Crossref
    • 13b Hart DJ, Wu SC. Heterocycles 1993; 35: 135
      Crossref
    • 13c Miller FM, Lohr RA. J. Org. Chem. 1978; 43: 3388
      Crossref