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Synlett 2008(8): 1179-1184  
DOI: 10.1055/s-2008-1072729
LETTER
© Georg Thieme Verlag Stuttgart · New York

Linearly Fused Dicyclobutabenzenes via Dual, Regioselective Cycloadditions of 1,4-Benzdiyne Equivalent and Ketene Silyl Acetals

Tetsu Arisawa, Toshiyuki Hamura, Hidehiro Uekusa, Takashi Matsumoto, Keisuke Suzuki*
Department of Chemistry, Tokyo Institute of Technology and SORST, Japan Science and Technology (JST) Agency, O-okayama, Meguro-ku, Tokyo 152-8551, Japan
Fax: +81(3)57342788; e-Mail: ksuzuki@chem.titech.ac.jp;
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Publication History

Received 16 February 2008
Publication Date:
16 April 2008 (online)

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Abstract

An efficient, flexible route to highly functionalized linearly fused dicyclobutabenzenes is described based on the dual, regioselective cycloaddition of benzyne and ketene silyl acetals.

Key words

benzyne - cycloaddition - dicyclobutabenzene - ketene silyl acetal - regioselectivity

    References and Notes

  • For preparation of linear dicyclobutabenzenes, see:
  • 1a Cava MP. Deana AA. Muth K. J. Am. Chem. Soc.  1960,  82:  2524 
    CrossrefGoogle Scholar
  • 1b Thummel RP. Nutakul W. J. Org. Chem.  1977,  42:  300 
    CrossrefGoogle Scholar
  • 1c Iyoda M. Yamauchi T. Oda M. J. Chem. Soc., Chem. Commun.  1986,  303 
    CrossrefGoogle Scholar
  • 1d Buchwald SL. Lucas EA. Dewan JC. J. Am. Chem. Soc.  1987,  109:  4396 
    CrossrefGoogle Scholar
  • 1e Moorthy JN. Venkatakrishnan P. Mal P. Venugopalan P. J. Org. Chem.  2003,  68:  327 
    CrossrefGoogle Scholar
  • For curved dicyclobutabenzenes, see:
  • 2a Giovannini E. Vuilleumier H. Helv. Chim. Acta  1977,  60:  1452 
    CrossrefGoogle Scholar
  • 2b Thummel RP. J. Am. Chem. Soc.  1976,  98:  628 
    CrossrefGoogle Scholar
  • 2c Maurin P. Ibrahim-Ouali M. Santelli M. Tetrahedron Lett.  2001,  42:  8147 
    CrossrefGoogle Scholar
  • 2d Hamura T. Ibusuki Y. Sato K. Matsumoto T. Osamura Y. Suzuki K. Org. Lett.  2003,  5:  3551 
    CrossrefGoogle Scholar
  • By exploiting benzyne-KSA [2+2]-cycloaddition chemistry, we recently reported a viable route to functionalized tricyclobutabenzenes. See:
  • 3a Hamura T. Ibusuki Y. Uekusa H. Matsumoto T. Suzuki K. J. Am. Chem. Soc.  2006,  128:  3534 
    CrossrefGoogle Scholar
  • 3b Hamura T. Ibusuki Y. Uekusa H. Matsumoto T. Siegel JS. Baldridge KK. Suzuki K. J. Am. Chem. Soc.  2006,  128:  10032 
    CrossrefGoogle Scholar
  • 4a Siegel JS. Angew. Chem., Int. Ed. Engl.  1994,  33:  1721 
    CrossrefGoogle Scholar
  • 4b Frank NL. Siegel JS. In Advances in Theoretically Interesting Molecules   Vol. 3:  Thummel RP. JAI Press; Greenwich USA: 1995.  p.209-260  
    CrossrefGoogle Scholar
  • For reviews on arynes, see:
  • 5a Hoffmann RW. Dehydrobenzene and Cycloalkynes   Academic; New York: 1967. 
    Google Scholar
  • 5b Kessar SV. In Comprehensive Organic Synthesis   Vol. 4:  Trost BM. Pergamon; Oxford UK: 1991.  p.483-515  
    Google Scholar
  • 6 Hamura T. Arisawa T. Matsumoto T. Suzuki K. Angew. Chem. Int. Ed.  2006,  45:  6842 
    CrossrefGoogle Scholar
  • For generation and trapping of 1,4-benzdiyne equivalents, see:
  • 7a Hart H. Ok D. J. Org. Chem.  1986,  51:  979 
    CrossrefGoogle Scholar
  • 7b Hart H. Lai C.-Y. Nwokogu G. Shamouilian S. Teuerstein A. Zlotogorski C. J. Am. Chem. Soc.  1980,  102:  6649 
    CrossrefGoogle Scholar
  • For other recent examples, see:
  • 7c Chen Y.-L. Sun J.-Q. Wei X. Wong W.-Y. Lee AWM. J. Org. Chem.  2004,  69:  7190 
    CrossrefGoogle Scholar
  • 7d Morton GE. Barrett AGM. J. Org. Chem.  2005,  70:  3525 
    CrossrefGoogle Scholar
  • 7e Schuster II. Craciun L. Ho DM. Pascal RA. Tetrahedron  2002,  58:  8875 
    CrossrefGoogle Scholar
  • 7f Duong HM. Bendikov M. Steiger D. Zhang Q. Sonmez G. Yamada J. Wudl F. Org. Lett.  2003,  5:  4433 
    CrossrefGoogle Scholar
  • 8a Hosoya T. Hasegawa T. Kuriyama Y. Matsumoto T. Suzuki K. Synlett  1995,  177 
    CrossrefGoogle Scholar
  • 8b Hosoya T. Hasegawa T. Kuriyama Y. Suzuki K. Tetrahedron Lett.  1995,  36:  3377 
    CrossrefGoogle Scholar
  • 8c Hosoya T. Hamura T. Kuriyama Y. Suzuki K. Synlett  2000,  520 
    CrossrefGoogle Scholar
  • 8d Hamura T. Hosoya T. Yamaguchi H. Kuriyama Y. Tanabe M. Miyamoto M. Yasui Y. Matsumoto T. Suzuki K. Helv. Chim. Acta  2002,  85:  3589 
    CrossrefGoogle Scholar
  • 8e Tsujiyama S. Suzuki K. Org. Synth.  2007,  84:  272 
    CrossrefGoogle Scholar
9

Typical Experimental Procedure for the Symmetrical Dual Benzyne Cycloaddition: To a mixture of bissulfonate 1 (98.0 mg, 0.145 mmol) and KSA 2b (113 mg, 0.517 mmol) in Et2O (2.0 mL) was added n-BuLi (0.58 M in hexane, 0.54 mL, 0.31 mmol) at -78 °C. After 5 min, the reaction was stopped by adding H2O and the products were extracted with EtOAc (3 ×). The combined organic extracts were washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by PTLC (hexane-CH2Cl2-Et2O, 3:1:1) to afford the less polar cycloadduct 4a (25.6 mg, 32.8%) and the more polar cycloadduct 4b (25.6 mg, 32.8%). 4a: R f 0.57 (hexane-EtOAc, 4:1). 1H NMR (acetone-d 6): δ = -0.05 (s, 6 H), 0.00 (s, 6 H), 0.92 (s, 18 H), 3.40 (s, 6 H), 3.53 (s, 6 H), 4.05 (s, 3 H), 4.77 (s, 2 H), 6.99 (s, 1 H). 13C NMR (acetone-d 6): δ = -3.8, -3.1, 19.0, 26.3, 52.2, 57.7, 59.3, 86.6, 105.0, 112.6, 133.2, 148.5, 149.9. IR (neat): 2951, 2930, 2857, 1601, 1473, 1423, 1348, 1296, 1243, 1231, 1179, 1138, 1118, 1069, 970, 935, 834, 809, 778 cm-1. Anal. Calcd for C27H48O7Si2: C, 59.96; H, 8.95. Found: C, 59.76; H, 9.25. 4b: R f 0.49 (hexane-EtOAc, 4:1). 1H NMR (acetone-d 6): δ = -0.02 (s, 6 H), 0.04 (s, 6 H), 0.92 (s, 18 H), 3.41 (s, 6 H), 3.53 (s, 6 H), 4.06 (s, 3 H), 4.73 (s, 2 H), 6.99 (s, 1 H). 13C NMR (acetone-d 6): δ = -3.5, -2.9, 19.1, 26.4, 52.1, 57.6, 59.2, 86.3, 105.3, 112.9, 133.2, 148.4, 149.7. IR (neat): 2930, 2856, 1599, 1473, 1422, 1340, 1297, 1251, 1177, 1119, 1069, 967, 955, 897, 780 cm-1. Anal. Calcd for C27H48O7Si2: C, 59.96; H, 8.95. Found: C, 60.20; H, 9.19. Chiral HPLC analysis [DAICEL, CHIRALPAK® OD-H, φ = 0.46 cm × 25 cm, hexane-i-PrOH, 95:5] of 4a showed two peaks, proving the structure with C 2 symmetry.

10

Typical Procedure for the Unsymmetrical Dual benzyne Cycloaddition: To a mixture of bissulfonate 1 (181 mg, 0.267 mmol) and KSA 2c (93.3 mg, 0.376 mmol) in Et2O (2.5 mL) was added n-BuLi (0.56 M in hexane, 0.56 mL, 0.31 mmol) at -95 °C. After 5 min, KSA 2a (171 mg, 0.845 mmol) in Et2O (0.5 mL) was added to the reaction mixture at -95 °C, to which was slowly added n-BuLi (0.56 M in hexane, 0.55 mL, 0.31 mmol) at -78 °C. After 5 min, the reaction was stopped by adding H2O. The products were extracted with EtOAc (3 ×) and the combined organic extracts were washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by silica gel flash chromatography (hexane-acetone, 99:1) to afford the less polar cycloadduct 8a (40.9 mg, 27.6%) and the more polar adduct 8b (41.4 mg, 27.9%). Data for biscycloadduct 8a: R f 0.69 (hexane-CH2Cl2-Et2O, 8:1:1). 1H NMR (acetone-d 6): δ = -0.03 (s, 3 H), 0.00 (s, 3 H), 0.08 (s, 3 H), 0.12 (s, 3 H), 0.90 (s, 9 H), 0.91 (s, 9 H), 1.18 (t, J = 7.0 Hz, 3 H), 3.24 (d, J = 14.0 Hz, 1 H), 3.38 (s, 3 H), 3.43-3.66 (m, 2 H), 3.42 (s, 3 H), 3.45 (s, 3 H), 3.56 (d, J = 14.0 Hz, 1 H), 4.06 (s, 3 H), 6.84 (s, 1 H). 13C NMR (acetone-d 6): δ = -4.0, -3.8, -3.5, -3.0, 15.7, 18.5, 19.1, 26.1, 26.3, 46.0, 51.3, 51.6, 52.9, 59.0, 60.4, 102.8, 107.4, 109.4, 111.1, 132.7, 133.6, 145.7, 148.3, 149.5. IR (neat): 2956, 2931, 1606, 1584, 1473, 1426, 1302, 1247, 1233, 1179, 1150, 1106, 1075, 938, 837, 779, 677 cm-1. Anal. Calcd for C28H50O7Si2: C, 60.61; H, 9.08. Found: C, 60.84; H, 9.29. 8b: mp 63.3-64.6 °C (hexane); R f 0.54 (hexane-CH2Cl2-Et2O, 8:1:1). 1H NMR (acetone-d 6): δ = -0.01 (s, 3 H), 0.02 (s, 3 H), 0.08 (s, 3 H), 0.14 (s, 3 H), 0.90 (s, 9 H), 0.91 (s, 9 H), 1.19 (t, J = 7.0 Hz, 3 H), 3.27 (d, J = 13.7 Hz, 1 H), 3.38 (s, 3 H), 3.42 (s, 3 H), 3.45 (s, 3 H), 3.46-3.55 (m, 1 H), 3.54 (d, J = 13.7 Hz, 1 H), 3.67-3.83 (m, 1 H), 4.07 (s, 3 H), 6.83 (s, 1 H). 13C NMR (acetone-d 6): δ = -3.9, -3.7, -3.5, -3.0, 15.7, 18.5, 19.1, 26.1, 26.3, 45.9, 51.3, 51.6, 52.9, 58.9, 60.5, 102.6, 107.4, 109.4, 111.0, 132.7, 133.8, 145.6, 148.2, 149.4. IR (ATR): 2930, 2856, 1605, 1585, 1472, 1424, 1301, 1248, 1227, 1182, 1105, 1073, 1020, 938, 835, 800, 779, 679 cm-1. Anal. Calcd for C28H50O7Si2: C, 60.61; H, 9.08. Found: C, 60.40; H, 8.99.

11

Crystallographic data for 8b: C28H50O7Si2, MW = 554.86, colorless crystal, 0.31 × 0.30 × 0.26 mm, triclinic, space group P1, Z = 2, T = 93 K, a = 9.4852(14) Å, b = 13.1137(16) Å, c = 14.1070(18) Å, V = 1602.6(4) Å3, λ(Mo-Kα) = 0.71073 Å, µ = 0.150 mm-1. Intensity data were collected on a Bruker SMART 1000 diffractometer. The structure was solved by direct methods and refined by the full-matrix least-squares on F ² (SHELX97). A total of 15175 reflections were measured and 7242 were independent. Final R1 = 0.0334, wR2 = 0.0889 [6830 refs; I > 2s(I)], and GOF = 1.035 (for all data, R1 = 0.0353, wR2 = 0.0906). CCDC 676618 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html or from the Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44 (1223)336033; email: deposit@ccdc.cam.ac.uk.