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Synlett 2007(19): 3011-3015  
DOI: 10.1055/s-2007-992353
LETTER
© Georg Thieme Verlag Stuttgart · New York

Mild and Stereoselective Friedel-Crafts Alkylation of Phenol Derivatives with Vinyloxiranes: A New Access to Cycloalkenobenzofurans

Ferruccio Bertolini, Valeria Di Bussolo, Paolo Crotti, Mauro Pineschi*
Dipartimento di Chimica Bioorganica e Biofarmacia, Università di Pisa, Via Bonanno 33, 56126 Pisa, Italy
Fax: +39(050)2219660; e-Mail: pineschi@farm.unipi.it;
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Publication History

Received 5 July 2007
Publication Date:
08 November 2007 (online)

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Abstract

The ring opening of vinyloxiranes with aryl borates under very mild and neutral conditions affords new hydroxyphenols with interesting levels of regio- and stereoselectivity. The subsequent Mitsunobu-type cyclodehydration proceeds with a good yield giving a new and easy access to cycloalkenobenzofurans.

Key words

Friedel-Crafts - vinyloxiranes - regioselectivity - stereoselectivity - fused-ring systems

    References and Notes

  • For recent examples, see:
  • 1a Kimura M. Mukai R. Tamaki T. Horino Y. Tamaru Y. J. Am. Chem. Soc.  2007,  129:  4122 
    CrossrefGoogle Scholar
  • 1b Brunner B. Stogaitis N. Lautens M. Org. Lett.  2006,  8:  3473 
    CrossrefGoogle Scholar
  • 1c Charrier N. Gravestock D. Zard SZ. Angew. Chem. Int. Ed.  2006,  45:  6520 
    CrossrefGoogle Scholar
  • 1d Restorp P. Somfai P. Eur. J. Org. Chem.  2005,  3946 ; and references cited therein
    CrossrefGoogle Scholar
  • For a review, see:
  • 2a Olah GA. Krishnamurti R. Prakash SGK. In Comprehensive Organic Synthesis   Vol. 3:  Trost BM. Fleming I. Pergamon Press; Oxford: 1991.  p.293 
    Article in Thieme ConnectGoogle Scholar
  • For recent examples, see:
  • 2b Bertolini F. Crotti P. Macchia F. Pineschi M. Tetrahedron Lett.  2006,  47:  61 
    Article in Thieme ConnectGoogle Scholar
  • 2c Prakash SGK. Linares-Palomino PJ. Glinton K. Chacko S. Rasul G. Mathew T. Olah GA. Synlett  2007,  1158 
    Article in Thieme ConnectGoogle Scholar
  • 3 Vinyloxiranes have been used in an intramolecular process to control a 7-endo-selective Friedel-Crafts-type cyclization. See: Nagumo S. Miyoshi I. Akita H. Kawahara N. Tetrahedron Lett.  2002,  43:  2223 
    CrossrefGoogle Scholar
  • 4a Taylor SK. Clark DL. Heinz KL. Schramm SB. Westermann CD. Barnell KK. J. Org. Chem.  1983,  48:  592 
    CrossrefGoogle Scholar
  • 4b

    The drastic reaction conditions used in this work, allowed direct ring opening of the oxirane ring by the Lewis acid promoter and caused the resulting alcohols to undergo a further Friedel-Crafts alkylation to give diarylated products.
    Crossref
  • 5 For Friedel-Crafts reactions of a sulfonyl-substituted vinylic epoxide with various aromatics promoted by BF3·Et2O, see: Brandänge S. Bäckvall J.-E. Leijonmarck H. J. Chem. Soc., Perkin Trans. 1  2001,  2051 
    CrossrefGoogle Scholar
  • 6 For the reactions of methyl 4,5-epoxypentenoate with aryl ethers, see: Ono M. Tanikawa S. Suzuki K. Akita H. Tetrahedron  2004,  60:  10187 ; and references cited therein
    CrossrefGoogle Scholar
  • 7 Pineschi M. Bertolini F. Haak RM. Crotti P. Macchia F. Chem. Commun.  2005,  1426 
    CrossrefGoogle Scholar
  • 8 Tsuji Y. Toteva Garth HA. Richard JP. J. Am. Chem. Soc.  2003,  125:  15455 
    CrossrefGoogle Scholar
  • For the use of indium salts in Friedel-Crafts-type reactions of heteroarenes with epoxides, see:
  • 9a Yadav JS. Reddy BVS. Parimala G. Synlett  2002,  1143 
    CrossrefGoogle Scholar
  • 9b Bandini M. Cozzi PG. Melchiorre P. Umani-Ronchi A. J. Org. Chem.  2002,  67:  5386 
    CrossrefGoogle Scholar
  • For the synthesis of tetrahydrobenzofurans, see:
  • 10a Hosokawa T. Miyagi S. Murahashi S.-I. Sonoda A. J. Org. Chem.  1978,  43:  2752 
    CrossrefGoogle Scholar
  • 10b Guzzo PR. Buckle RN. Chou M. Dinn SR. Flaugh ME. Kiefer AD. Ryter KT. Sampognaro AJ. Tregay SW. Xu Y.-C.
    J. Org. Chem.  2003,  68:  770 
    CrossrefGoogle Scholar
  • 10c Yamashita M. Inaba T. Nagahama M. Shimizu T. Kosaka S. Kawasaki I. Ohta S. Org. Biomol. Chem.  2005,  3:  2296 
    CrossrefGoogle Scholar
  • 10d Crich D. Sannigrahi M. Tetrahedron  2002,  58:  3319 
    CrossrefGoogle Scholar
  • For the obtainment of hexahydrodibenzofurans, see:
  • 10e Liu Q. Han B. Zhang W. Yang L. Liu Z.-L. Yu W. Synlett  2005,  2248 
    CrossrefGoogle Scholar
  • 10f Kurono N. Honda E. Komatsu F. Orito K. Tokuda M. Tetrahedron  2004,  60:  1791 
    CrossrefGoogle Scholar
  • 10g Nguyen R.-V. Yao X. Li C.-J. Org. Lett.  2006,  8:  2397 
    CrossrefGoogle Scholar
  • 11a Clive DLJ. Daigneault S. J. Org. Chem.  1991,  56:  5285 
    CrossrefGoogle Scholar
  • 11b Trost BM. Tang W. Toste FD. J. Am. Chem. Soc.  2005,  127:  14785 
    CrossrefGoogle Scholar
  • 12 Aristoff PA. Harrison AW. Huber AM. Tetrahedron Lett.  1984,  25:  3955 
    CrossrefGoogle Scholar
  • 14 Brown CA. Krishnamurthy S. J. Org. Chem.  1978,  43:  2731 
    CrossrefGoogle Scholar
13

Aryl borates 1a,b were prepared from the corresponding commercially available phenols with BH3·SMe2,14 and were used immediately after their preparation.
Typical Procedure for the Preparation of Hydroxy-phenols (Entry 7, Table 1): Under an argon atmosphere, a solution of aryl borate 1b (705 mg, 1.5 mmol) in CH2Cl2 (1.0 mL) was added at -78 °C to a stirred solution of vinyloxirane 2a (96 mg, 1.0 mmol) in CH2Cl2 (0.5 mL). The mixture was allowed to react for 18 h at -78 °C, then quenched with brine (2.0 mL) and diluted with Et2O or CH2Cl2 (20 mL). Evaporation of the dried (MgSO4) organic solution afforded a crude reaction mixture which was purified by silica gel column chromatography eluting with hexanes-EtOAc (7:3), to give pure 2-[(1R*,6S*)-6-hydroxycyclohexen-2-yl]-3,5-dimethoxyphenol (4ab; 162 mg, 65%), as a light yellow oil; TLC (hexanes-EtOAc, 1:1): R f 0.36. 1H NMR (250 MHz, CDCl3): δ = 1.70-1.90 (m, 1 H), 2.05-2.18 (m, 1 H), 2.30-2.43 (m, 2 H), 2.50-2.67 (br s, 1 H, CHOH), 3.82 (s, 3 H), 3.83 (s, 3 H), 3.95-4.10 (m, 2 H), 5.67-5.83 (m, 2 H), 5.93-6.05 (m, 1 H), 6.10-6.25 (m, 1 H), 6.50-6.70 (br s, 1 H, ArOH). 13C NMR (62.5 MHz, CDCl3): δ = 24.6, 30.7, 40.6, 55.1, 55.6, 71.2, 91.5, 94.5, 106.1, 107.7, 128.8, 156.9, 159.2, 159.9.
2-[(1 R *,6 S *)-6-Hydroxycyclohexen-2-yl]-3,5-dimethyl-phenol (4aa): yield: 40%; solid; mp 119-122 °C; TLC (hexanes-EtOAc, 7:3): R f 0.20. 1H NMR (200 MHz, MeOD): δ = 1.56-1.86 (m, 2 H), 1.93-2.12 (m, 2 H), 2.17 (s, 3 H), 2.27 (s, 3 H), 3.62-3.89 (m, 1 H), 4.12-4.33 (m, 1 H), 5.45 (d, J = 9.8 Hz, 1 H), 5.56-5.71 (m, 1 H), 6.46 (s, 2 H). 13C NMR (50 MHz, MeOD): δ = 21.0, 21.2, 26.4, 33.4, 45.3, 71.1, 115.3, 124.2, 125.4, 126.0, 131.7, 137.6, 139.5, 157.1.
2-(1-Hydroxybut-3-en-2-yl)-3,5-dimethylphenol (6aa): yield: 54%; colorless oil; TLC (hexanes-EtOAc, 6:4): R f 0.31. 1H NMR (200 MHz, CDCl3): δ = 2.24 (s, 3 H), 2.28 (s, 3 H), 3.63 (br s, 1 H), 3.81-4.19 (m, 3 H), 5.04-5.24 (m, 2 H), 6.22 (ddd, J 1 = 16.6 Hz, J 2 = 10.4 Hz, J 3 = 5.3 Hz, 1 H), 6.58 (s, 1 H), 6.60 (s, 1 H), 8.26 (br s, 1 H). 13C NMR (50 MHz, CDCl3): δ = 20.7, 44.8, 65.1, 116.1, 116.5, 122.4, 123.6, 136.0, 137.6, 154.7.
2-(1-Hydroxybut-3-en-2-yl)-3,5-dimethoxyphenol (6ab): yield: 75%; colorless oil; TLC (hexanes-EtOAc, 8:2): R f 0.13. 1H NMR (200 MHz, CDCl3): δ = 3.73 (s, 6 H), 3.89 (dd, J 1 = 10.2 Hz, J 1 = 3.2 Hz, 1 H), 4.02-4.15 (m, 1 H), 4.16-4.28 (m, 1 H), 5.00-5.19 (m, 2 H), 6.03-6.12 (m, 2 H), 6.13-6.23 (m, 1 H). 13C NMR (500 MHz, CDCl3): δ = 40.0, 54.5, 55.7, 65.7, 91.2, 94.7, 108.0, 116.1, 136.7, 156.6, 158.6, 159.8.
( E )-2-(6-Hydroxynon-4-en-3-yl)-3,5-dimethoxyphenol (6bb): yield: 65%; colorless oil; TLC (hexanes-EtOAc, 7:3): R f 0.27. 1H NMR (250 MHz, CDCl3): δ = 0.79 (t, 3 H), 0.86 (t, J = 7.1 Hz, 3 H), 1.19-1.52 (m, 4 H), 1.62-1.82 (m, 2 H), 2.20 (br s, 1 H, CHOH), 3.69 (s, 3 H), 3.71 (s, 3 H), 3.74-3.89 (m, 1 H), 4.06-4.13 (m, 1 H), 5.55 (dd, J 1 = 16.3 Hz, J 2 = 6.7 Hz, 1 H), 5.98-6.18 (m, 3 H). 13C NMR (62.5 MHz, CDCl3): δ = 12.3, 13.9, 18.61, 25.49, 38.27, 39.31, 55.1, 55.6, 72.7, 91.4, 94.4, 110.2, 132.6, 134.4, 158.8, 159.1.
(4 S* ,5 S* , E )-Ethyl 5-Hydroxy-4-(2-hydroxy-4,6-dimethylphenyl)oct-2-enoate (6cb): yield: 40%; colorless oil; TLC (hexanes-EtOAc, 7:3): R f 0.19. 1H NMR (200 MHz, CDCl3): δ = 0. 93 (t, J = 7.1 Hz, 3 H), 1.25 (t, J = 5.7 Hz, 3 H), 1.33-1.74 (m, 4 H), 3.52 (br s, 1 H, CHOH), 3.74 (s, 6 H), 3.95-4.30 (m, 4 H), 5.78 (d, J = 15.8 Hz, 1 H), 6.04 (s, 1 H), 6.11 (s, 1 H), 7.38 (dd, J 1 = 15.8 Hz, J 2 = 7.2 Hz, 1 H), 9.22 (br s, 1 H). 13C NMR (50 MHz, CDCl3): δ = 13.7, 14.1, 19.0, 38.1, 42.3, 55.1, 55.7, 60.3, 75.4, 91.0, 94.8, 108.0, 123.1, 145.2, 156.8, 158.2, 160.1, 167.0.
(1 S* ,2 R* )-2-(2-Hydroxy-4,6-dimethoxyphenyl)cyclo-hept-3-enol (4bb): yield: 58% [obtained as an inseparable mixture with 7% of the corresponding (1S*,2S*)-stereoisomer]; TLC (hexanes-EtOAc, 7:3): R f 0.16. 1H NMR (200 MHz, CDCl3): δ = 1.40-2.42 (m, 6 H), 3.70 (s, 3 H), 3.74 (s, 3 H), 3.93-4.17 (m, 2 H), 5.50-5.61 (m, 1 H), 5.77-5.95 (m, 1 H), 6.01 (d, J = 2.3 Hz, 1 H), (6.06 d, J = 2.3 Hz, 1 H), 6.94-7.03 (br s, 1 H, ArOH). 13C NMR (50 MHz, CDCl3): δ = 24.7, 27.8, 39.8, 43.3, 55.1, 55.6, 71.1, 91.2, 94.4, 109.0, 132.1, 133.0, 156.3, 159.5, 159.7. Typical Procedure for the Preparation of 2,3-Dihydro-benzofuranes via Mitsunobu Cyclodehydration (Scheme 2): Triphenylphosphine (262.3 mg, 1.0 mmol) and diethyl-azodicarboxylate (118 µL, 0.75 mmol) were added to a stirred solution of hydroxyphenol 4ab (125 mg, 0.5 mmol) in anhyd THF (2.0 mL) under argon. The reaction was followed by TLC up to complete consumption of the starting hydroxyphenol and the solvent was removed in vacuo. The crude reaction mixture was purified by silica gel column chromatography to give pure (4aR*,9bR*)-7,9-dimethoxy-3,4,4a,9b-tetrahydrodibenzo[b,d]furan (7ab; 94 mg, 81%) as a light yellow oil. 1H NMR (200 MHz, CDCl3): δ = 1.75-2.31 (m, 4 H), 3.75 (s, 3 H), 3.79 (s, 3 H), 3.81-3.88 (m, 1 H), 4.93-5.05 (m, 1 H), 5.73-5.95 (m, 2 H), 6.00 (d, J = 2.0 Hz, 1 H), 6.05 (d, J = 2.0 Hz, 1 H). 13C NMR (50 MHz, CDCl3): δ = 19.2, 25.1, 39.0, 55.1, 55.4, 82.3, 88.7, 91.0, 110.1, 126.0, 126.7, 156.7, 161.1, 161.5.
(4a R *,9b R *)-7,9-Dimethyl-3,4,4a,9b-tetrahydro-dibenzo[ b , d ]furan (7aa): yield: 83%; colorless oil; TLC (hexanes-Et2O, 9:1): R f 0.51. 1H NMR (200 MHz, CDCl3): δ = 1.75-2.12 (m, 2 H), 2.19-2.30 (m, 2 H), 2.27 (s, 3 H), 2.30 (s, 3 H), 3.77 (br d, J = 6.9 Hz, 1 H), 4.94-5.00 (m, 1 H), 5.68-5.95 (m, 2 H), 6.48 (s, 1 H), 6.50 (s, 1 H). 13C NMR (50 MHz, CDCl3): δ = 18.3, 19.0, 21.4, 24.9, 40.1, 81.3, 108.0, 122.6, 125.1, 126.9, 127.8, 134.0, 138.2.
(5a R *,10a R *)-1,3-Dimethoxy-6,7,8,10a-tetrahydro-5a H -benzo[ d ]cyclohepta[ b ]furan (7bb): yield: 80% (obtained as an inseparable mixture with 10% of the corresponding trans stereoisomer); light yellow oil; TLC (hexanes-EtOAc, 9:1): R f 0.38. 1H NMR (200 MHz, CDCl3): δ = 1.55-1.75 (m, 2 H), 1.92-2.07 (m, 2 H), 2.09-2.22 (m, 2 H), 3.76 (s, 3 H), 3.80 (s, 3 H), 4.25 (d, J = 9.8 Hz, 1 H), 4.88 (ddd, J 1 = 4.5 Hz, J 2 = 9.8 Hz, 1 H), 5.62-5.68 (m, 2 H), 6.00-6.05 (m, 2 H). 13C NMR (50 MHz, CDCl3): δ = 19.4, 26.7, 28.7, 42.4, 55.3, 55.5, 85.5, 88.1, 91.1, 127.6, 129.7, 159.0, 160.3, 160.7.
(5a S *,11a S *, Z )-1,3-Dimethoxy-5a,6,7,8,11a-hexa-hydrobenzo[ b ]cycloocta[ d ]furan (7cb): yield: (70%); light yellow oil; TLC (hexanes-EtOAc, 9:1): R f 0.45. 1H NMR (200 MHz, CDCl3): δ = 0.95-2.25 (m, 8 H), 3.72 (s, 3 H), 3.76 (s, 3 H), 4.10-4.26 (m, 1 H), 4.50-4.67 (m, 1 H), 5.11 (dd, J 1 = 10.6 Hz, J 2 = 7.0 Hz, 1 H), 5.68-5.88 (m, 1 H), 6.00 (s, 2 H). 13C NMR (50 MHz, CDCl3): δ = 26.6, 26.7, 28.2, 29.2, 40.4, 55.5 (2 × C), 88.3, 91.3, 91.5, 11.8, 130.5, 133.3, 156.7, 160.5, 161.6.