Synlett 2017; 28(16): 2189-2193
DOI: 10.1055/s-0036-1588461
letter
© Georg Thieme Verlag Stuttgart · New York

Heat Versus Basic Conditions: Intramolecular Dehydro-Diels–Alder Reaction of 1-Indolyl-1,6-heptadiynes for the Selective Synthesis of Substituted Carbazoles

Takayuki Kudoh
Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan   eMail: sakakura@okayama-u.ac.jp
,
Syo Fujisawa
Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan   eMail: sakakura@okayama-u.ac.jp
,
Megumi Kitamura
Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan   eMail: sakakura@okayama-u.ac.jp
,
Akira Sakakura*
Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan   eMail: sakakura@okayama-u.ac.jp
› Institutsangaben
This project was supported in part by JSPS KAKENHI (26410120)
Weitere Informationen

Publikationsverlauf

Received: 01. Mai 2017

Accepted after revision: 19. Mai 2017

Publikationsdatum:
06. Juli 2017 (online)


Abstract

The intramolecular dehydro-Diels–Alder reaction of 1-indolyl-1,6-heptadiynes proceeds smoothly under rather mild heating conditions to give substituted carbazoles in moderate to good yields. The reaction of 7-aryl-1-indolyl-1,6-heptadiynes under heating gives the corresponding carbazoles chemoselectively in high yields, whereas the reaction under basic conditions gives naphthalenes as major products.

Supporting Information

 
  • References and Notes


    • For selected recent reviews, see:
    • 1a Tsutsumi LS. Gündisch D. Sun D. Curr. Top. Med. Chem. (Sharjah, United Arab Emirates) 2016; 16: 1290
    • 1b Sherer C. Snape TJ. Eur. J. Med. Chem. 2015; 97: 552
    • 1c Głuszyńska A. Eur. J. Med. Chem. 2015; 94: 405
    • 1d Bashir M. Bano A. Ijaz AS. Chaudhary BA. Molecules 2015; 20: 13496
    • 1e Li J. Grimsdale AC. Chem. Soc. Rev. 2010; 39: 2399

      For reviews, see:
    • 2a Sainsbury M. Synthesis 1977; 437
    • 2b Knölker H.-J. Synlett 1992; 371
    • 2c Knölker H.-J. Chem. Soc. Rev. 1999; 28: 151
    • 2d Knölker H.-J. Reddy KR. Chem. Rev. 2002; 102: 4303
    • 2e Fröhner W. Krahl MP. Reddy KR. Knölker H.-J. Heterocycles 2004; 63: 2393
    • 2f Knölker H.-J. Curr. Org. Synth. 2004; 1: 309
    • 2g Agarwal S. Cammerer S. Filali S. Fröhner W. Knoll J. Krahl MP. Reddy KR. Knölker H.-J. Curr. Org. Chem. 2005; 9: 1601
    • 2h Yaqub G. Hussain EA. Rehman MA. Mateen B. Asian J. Chem. 2009; 21: 2485
    • 2i Schmidt AW. Reddy KR. Knölker H.-J. Chem. Rev. 2012; 112: 3193
    • 2j Deng Y. Persson AK. Å. Bäckvall J.-E. Chem. Eur. J. 2012; 18: 11498
    • 2k Yoshikai N. Wei Y. Asian J. Org. Chem. 2013; 2: 466
    • 2l Alcaide B. Almendros P. Acc. Chem. Res. 2014; 47: 939

      For reviews, see:
    • 3a Wessig P. Müller G. Chem. Rev. 2008; 108: 2051
    • 3b Li W. Zhou L. Zhang J. Chem. Eur. J. 2016; 22: 1558
    • 4a Garratt PJ. Neoh SB. J. Org. Chem. 1979; 44: 2667
    • 4b Cheng YS. P. Garratt PJ. Neoh SB. Rumjanek VH. Isr. J. Chem. 1985; 26: 101
    • 4c Braverman S. Duar Y. Segev D. Tetrahedron Lett. 1976; 17: 3181
    • 4d Zafrani Y. Gottlieb HE. Sprecher M. Braverman S. J. Org. Chem. 2005; 70: 10166
    • 4e Basak A. Das S. Mallick D. Jemmis ED. J. Am. Chem. Soc. 2009; 131: 15695
    • 4f Mondal S. Maji M. Basak A. Tetrahedron Lett. 2010; 52: 1183
    • 4g Mondal S. Mitra T. Mukherjee R. Addy PS. Basak A. Synlett 2012; 23: 2582
    • 4h Mondal S. Basak A. Jana S. Anoop A. Tetrahedron 2012; 68: 7202
    • 4i Mukherjee R. Mondal S. Basak A. Mallick D. Jemmis ED. Chem. Asian J. 2012; 7: 957
    • 4j Addy PS. Dutta S. Biradha K. Basak A. Tetrahedron Lett. 2012; 53: 19
    • 4k Mitra T. Das J. Maji M. Das R. Das UK. Chattaraj PK. Basak A. RSC Adv. 2013; 3: 19844
    • 4l Das J. Mukherjee R. Basak A. J. Org. Chem. 2014; 79: 3789
    • 5a Ishikawa T. Mizuta T. Hagiwara K. Aikawa T. Kudo T. Saito S. J. Org. Chem. 2003; 68: 3702
    • 5b Kudoh T. Mori T. Shirahama M. Yamada M. Ishikawa T. Saito S. Kobayashi H. J. Am. Chem. Soc. 2007; 129: 4939
    • 5c Kudoh T. Shishido A. Ikeda K. Saito S. Ishikawa T. Synlett 2013; 24: 1509
    • 6a Iwai I. Ide J. Chem. Pharm. Bull. 1964; 12: 1094
    • 6b Bartlett AJ. Laird T. Ollis WD. J. Chem. Soc., Perkin Trans. 1 1975; 1315
    • 7a Wessig P. Müller G. Herre R. Kühn A. Helv. Chim. Acta 2006; 89: 2694
    • 7b Brummond KM. Kocsis LS. Acc. Chem. Res. 2015; 48: 2320
  • 8 Johnson R. Chem. Rev. 1989; 89: 1111
  • 9 Sonogashira K. Tohda Y. Hagihara N. Tetrahedron Lett. 1975; 16: 4467
  • 10 See the Supporting Information for the syntheses of substrates 1, 4, 7, and 10.
  • 11 5-Benzyl-4-(4-methoxyphenyl)-3,5-dihydro-1H-furo[3,4-b]carbazole (2a) and 1-Benzyl-3-(6-methoxy-1,3-dihydronaphtho[2,3-c]furan-4-yl)-1H-indole (3a); Typical Procedure Hydroquinone (4.4 mg, 0.044 mmol) was added to a solution of diyne 1a (44 mg, 0.11 mmol) in degassed toluene (1 mL) in a 12 mL glass pressure vessel. The mixture was stirred at 100 °C for 80 h then cooled to r.t. The solvent was removed under reduced pressure, and the residue was purified by column chromatography [silica gel, toluene–EtOAc (10:1)] to give carbazole 2a and naphthalene 3a. 2a: Colorless solid; yield: 35.2 mg (0.086 mmol, 77%); mp 35.5 °C. 1H NMR (300 MHz, CDCl3): δ = 8.12 (d, J = 7.8 Hz, 1 H), 7.96 (s, 1 H), 7.4−7.1 (m, 6 H), 7.02 (d, J = 8.8 Hz, 2 H), 6.74 (d, J = 8.8 Hz, 2 H), 6.6–6.5 (m, 2 H), 5.33 (s, 2 H), 5.10 (s, 2 H), 4.88 (s, 2 H), 3.82 (s, 3 H). 3a: Colorless solid; yield: 7.3 mg (0.018 mmol, 16%); mp 66.9 °C. 1H NMR (300 MHz, CDCl3): δ = 7.78 (d, J = 8.9 Hz, 1 H), 7.63 (s, 1 H), 7.44 (d, J = 8.4 Hz, 1 H), 7.4−7.0 (m, 11 H), 5.47 (d, J = 16.0 Hz, 1 H), 5.42 (d, J = 16.0 Hz, 1 H), 5.29 (s, 2 H), 5.05 (s, 2 H), 3.60 (s, 3 H).
  • 12 When the reaction of 1a was conducted in degassed toluene in the absence of hydroquinone, 2a was obtained in 51% yield, along with 3a in 9% yield.
    • 13a Beesley RM. Ingold CK. Thorpe JF. J. Chem. Soc., Trans. 1915; 107: 1080
    • 13b Jung ME. Piizzi G. Chem. Rev. 2005; 105: 1735
    • 14a Yamazaki S. Org. Lett. 1999; 1: 2129
    • 14b Gudla V. Balamurugan R. J. Org. Chem. 2011; 76: 9919