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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
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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
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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

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  • 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.