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DOI: 10.1055/s-2008-1072729
Linearly Fused Dicyclobutabenzenes via Dual, Regioselective Cycloadditions of 1,4-Benzdiyne Equivalent and Ketene Silyl Acetals
Publication History
Publication Date:
16 April 2008 (online)
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
- For preparation of linear dicyclobutabenzenes, see:
-
1a
Cava MP.Deana AA.Muth K. J. Am. Chem. Soc. 1960, 82: 2524 -
1b
Thummel RP.Nutakul W. J. Org. Chem. 1977, 42: 300 -
1c
Iyoda M.Yamauchi T.Oda M. J. Chem. Soc., Chem. Commun. 1986, 303 -
1d
Buchwald SL.Lucas EA.Dewan JC. J. Am. Chem. Soc. 1987, 109: 4396 -
1e
Moorthy JN.Venkatakrishnan P.Mal P.Venugopalan P. J. Org. Chem. 2003, 68: 327 - For curved dicyclobutabenzenes, see:
-
2a
Giovannini E.Vuilleumier H. Helv. Chim. Acta 1977, 60: 1452 -
2b
Thummel RP. J. Am. Chem. Soc. 1976, 98: 628 -
2c
Maurin P.Ibrahim-Ouali M.Santelli M. Tetrahedron Lett. 2001, 42: 8147 -
2d
Hamura T.Ibusuki Y.Sato K.Matsumoto T.Osamura Y.Suzuki K. Org. Lett. 2003, 5: 3551 - 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 -
3b
Hamura T.Ibusuki Y.Uekusa H.Matsumoto T.Siegel JS.Baldridge KK.Suzuki K. J. Am. Chem. Soc. 2006, 128: 10032 -
4a
Siegel JS. Angew. Chem., Int. Ed. Engl. 1994, 33: 1721 -
4b
Frank NL.Siegel JS. In Advances in Theoretically Interesting Molecules Vol. 3:Thummel RP. JAI Press; Greenwich USA: 1995. p.209-260 - For reviews on arynes, see:
-
5a
Hoffmann RW. Dehydrobenzene and Cycloalkynes Academic; New York: 1967. -
5b
Kessar SV. In Comprehensive Organic Synthesis Vol. 4:Trost BM. Pergamon; Oxford UK: 1991. p.483-515 - 6
Hamura T.Arisawa T.Matsumoto T.Suzuki K. Angew. Chem. Int. Ed. 2006, 45: 6842 - For generation and trapping of 1,4-benzdiyne equivalents, see:
-
7a
Hart H.Ok D. J. Org. Chem. 1986, 51: 979 -
7b
Hart H.Lai C.-Y.Nwokogu G.Shamouilian S.Teuerstein A.Zlotogorski C. J. Am. Chem. Soc. 1980, 102: 6649 - 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 -
7d
Morton GE.Barrett AGM. J. Org. Chem. 2005, 70: 3525 -
7e
Schuster II.Craciun L.Ho DM.Pascal RA. Tetrahedron 2002, 58: 8875 -
7f
Duong HM.Bendikov M.Steiger D.Zhang Q.Sonmez G.Yamada J.Wudl F. Org. Lett. 2003, 5: 4433 -
8a
Hosoya T.Hasegawa T.Kuriyama Y.Matsumoto T.Suzuki K. Synlett 1995, 177 -
8b
Hosoya T.Hasegawa T.Kuriyama Y.Suzuki K. Tetrahedron Lett. 1995, 36: 3377 -
8c
Hosoya T.Hamura T.Kuriyama Y.Suzuki K. Synlett 2000, 520 -
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 -
8e
Tsujiyama S.Suzuki K. Org. Synth. 2007, 84: 272
References and Notes
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.
10Typical 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.
11Crystallographic 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.