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Synlett 2003(1): 0029-0034
DOI: 10.1055/s-2003-36233
LETTER
© Georg Thieme Verlag Stuttgart · New York

An Alkyne Metathesis-Based Route to ortho-Dehydrobenzannulenes

Ognjen Š. Miljanić *, K. Peter C. Vollhardt, Glenn D. Whitener*
Center for New Directions in Organic Synthesis, Department of Chemistry, University of California at Berkeley and the Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720-1460, USA
Fax: +1(510)6435208; e-Mail: kpcv@uclink.berkeley.edu;
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Publication History

Received 11 November 2002
Publication Date:
18 December 2002 (online)

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Abstract

An application of alkyne metathesis to 1,2-di(prop-1-ynyl)arenes, producing dehydrobenzannulenes, is described. An efficient method for selective Sonogashira couplings of bromoiodoarenes under conditions of microwave irradiation is also reported.

Key words

alkyne metathesis - 1,2-di(prop-1-ynyl)arenes - dehydrobenzannulenes - microwave irradiation - Sonogashira coupling

    References

  • 1 Mortreux A. Blanchard M. J. Chem. Soc, Chem. Commun.  1974,  786 
    CrossrefGoogle Scholar
  • For recent references, see:
  • 2a Brizius G. Bunz UHF. Org. Lett.  2002,  4:  2829 
    Google Scholar
  • 2b Brizius G. Kroth S. Bunz UHF. Macromolecules  2002,  35:  5317 
    Google Scholar
  • 2c For reviews, see: Bunz UHF. Acc. Chem. Res.  2001,  34:  998 
    Google Scholar
  • 2d See also: Bunz UHF. Kloppenburg L. Angew. Chem. Int. Ed.  1999,  38:  478 
    Google Scholar
  • 2e For a pertinent example, see: Ge P.-H. Fu W. Herrmann WA. Herdtweck E. Campana C. Adams RA. Bunz UHF. Angew. Chem. Int. Ed.  2000,  39:  3607 
    Google Scholar
  • For selected references, see:
  • 3a Fürstner A. Mathes C. Grela K. Chem. Commun.  2002,  1057 
    Google Scholar
  • 3b Fürstner A. Stelzer F. Rumbo A. Krause H. Chem.-Eur. J.  2002,  8:  1856 
    Google Scholar
  • 3c Fürstner A. Mathes C. Lehmann CW. Chem.-Eur. J.  2001,  7:  5299 
    Google Scholar
  • 3d Fürstner A. Grela K. Mathes C. Lehmann CW. J. Am. Chem. Soc.  2000,  122:  11799 
    Google Scholar
  • 3e Fürstner A. Guth O. Rumbo A. Seidel G. J. Am. Chem. Soc.  1999,  121:  11108 
    Google Scholar
  • 3f Fürstner A. Mathes C. Lehmann CW. J. Am. Chem. Soc.  1999,  121:  9453 
    Google Scholar
  • 3g Fürstner A. Seidel G. Angew. Chem. Int. Ed.  1998,  37:  1734 
    Google Scholar
  • For reviews, see:
  • 4a Haley MM. Synlett  1998,  557 
    CrossrefGoogle Scholar
  • 4b Haley MM. Pak JJ. Brand SC. Top. Curr. Chem.  1999,  202:  81 
    CrossrefGoogle Scholar
  • 4c Haley MM. Wan WB. In Advances in Strained and Interesting Organic Molecules   Vol. 8:  Halton B. JAI Press; New York: 2000.  p.1 
    CrossrefGoogle Scholar
  • 4d Kennedy RD. Lloyd D. McNab H. J. Chem. Soc., Perkin Trans. 1  2002,  1601 
    CrossrefGoogle Scholar
  • 4e Balaban AT. Banciu M. Ciorba V. Annulenes, Benzo-, Hetero-, Homo-Derivatives and Their Valence Isomers   Vol. 2:  CRC Press; Boca Raton: 1987.  p.146 
    CrossrefGoogle Scholar
  • 5 Youngs WJ. Tessier CA. Bradshaw JD. Chem. Rev.  1999,  99:  3153 
    CrossrefGoogle Scholar
  • For a review, see:
  • 6a Bunz UHF. Rubin Y. Tobe Y. Chem. Soc. Rev.  1999,  28:  107 
    CrossrefGoogle Scholar
  • 6b See also, inter alia: Narita N. Nagai S. Suzuki S. Phys. Rev. B: Condensed Matter Mater. Phys.  2002,  64:  245408 
    CrossrefGoogle Scholar
  • 6c Kehoe JM. Kiley JH. English JJ. Johnson CA. Petersen RC. Haley MM. Org. Lett.  2000,  2:  969 
    CrossrefGoogle Scholar
  • 6d Grima JN. Evans KE. Chem. Commun.  2000,  1531 
    CrossrefGoogle Scholar
  • 7a Boese R. Matzger AJ. Vollhardt KPC. J. Am. Chem. Soc.  1997,  119:  2052 
    CrossrefGoogle Scholar
  • 7b Dosa PI. Erben C. Iyer VS. Vollhardt KPC. Wasser IM. J. Am. Chem. Soc.  1999,  121:  10430 
    CrossrefGoogle Scholar
  • For selected recent references, see:
  • 8a Pak JJ. Weakley TJR. Haley MM. Lau DYK. Stoddart JF. Synthesis  2002,  1256 
    CrossrefGoogle Scholar
  • 8b Tobe Y. Utsumi N. Kawabata K. Nagano A. Adachi K. Araki S. Sonoda M. Hirose K. Naemura K. J. Am. Chem. Soc.  2002,  124:  5350 
    CrossrefGoogle Scholar
  • 8c Hosokawa Y. Kawase T. Oda M. Chem. Commun.  2001,  1948 
    CrossrefGoogle Scholar
  • 8d Nakamura K. Okubo H. Yamaguchi M. Org. Lett.  2001,  3:  1097 
    CrossrefGoogle Scholar
  • 8e Höger S. Enkelmann V. Bonrad K. Tschierske C. Angew. Chem. Int. Ed.  2000,  39:  2268 
    CrossrefGoogle Scholar
  • 8f See also: Moore JS. Acc. Chem. Res.  1997,  30:  402 
    CrossrefGoogle Scholar
  • 8g Zhang J. Pesak DJ. Ludwick JL. Moore JS. J. Am. Chem. Soc.  1994,  116:  4227 
    CrossrefGoogle Scholar
  • 8h Pickholz M. Stafström S. Chem. Phys.  2001,  270:  245 
    CrossrefGoogle Scholar
  • See, inter alia:
  • 9a Sarkar A. Pak JJ. Rayfield GW. Haley MM. J. Mater. Chem.  2001,  11:  2943 
    CrossrefGoogle Scholar
  • 9b Wan WB. Haley MM. J. Org. Chem.  2001,  66:  3893 
    CrossrefGoogle Scholar
  • 10 Eickmeier C. Junga H. Matzger AJ. Scherhag F. Shim M. Vollhardt KPC. Angew. Chem., Int. Ed. Engl.  1997,  36:  2103 
    CrossrefGoogle Scholar
  • Most of the starting iodoarenes are either commercially available (5a, 5h, 5k) or have been described previously:
  • 11a 5b, 5d: Kryska A. Skulski L. J. Chem. Res., Synop.  1999,  590 
    Google Scholar
  • 11b 5c: Lacour J. Monchaud D. Bernardinelli G. Favarger F. Org. Lett.  2001,  3:  1407 
    Google Scholar
  • 11c 5g: Nakayama J. Sakai A. Hoshino M. J. Org. Chem.  1984,  49:  5084 
    Google Scholar
  • 11d 5i: Mattern DL. J. Org. Chem.  1983,  48:  4772 
    Google Scholar
  • 11e 5j: Goldfinger MB. Crawford KB. Swager TM. J. Am. Chem. Soc.  1997,  119:  4578 
    Google Scholar
  • 11f

    1,2-Dibromo-4,5-diiodobenzene (5e) was prepared using the general procedure described for 5j. Compound 5e: White needles (33%), mp 173-175 °C. 1H NMR (400 MHz, CDCl3): δ = 8.03 (s, 2 H). 13C NMR (100 MHz, CDCl3): δ = 142.5, 125.4, 106.9. MS (EI, 70 eV): m/z (%) = 488 (100) [M+], 361 (32), 234 (17), 153 (8), 74 (20). IR (CS2): 2925, 1408, 1282, 1005, 877 cm-1. HRMS: Calcd for C6H2Br2I2: 487.6592. Found: 487.6596. Anal. Calcd for C6H2Br2I2:
    C, 14.78; H, 0.41. Found: C, 14.55; H, 0.43.
    1,4-Dibromo-2,3-diiodobenzene ( 5f): The first two steps followed the general procedure in ref. [11g] . Chloral hydrate (9.93 g, 60.0 mmol), 2,5-dibromoaniline (12.6 g, 50.0 mmol), hydroxylamine hydrochloride (5.21 g, 75.0 mmol), and Na2SO4 (60.0 g) were suspended in a mixture of H2O (300 mL) and EtOH (300 mL). The mixture was stirred and kept at reflux for 12 h. It was then concentrated by evaporation of the ethanol and poured onto crushed ice, which caused precipitation of a white solid. After 5 h at 0 °C, the suspension was filtered, and the crystals were air dried to yield 13.5 g (84%) of crude 2,5-dibromoisonitroso-acetanilide. This amount was then cyclized by heating at 100 °C in 86% H2SO4 for 15 min. The resulting dark red suspension was poured onto crushed ice to yield 5.98 g (47%) of 3,6-dibromoisatine as bright orange crystals, which were subsequently subjected to basic hydrolysis in aq H2O2to yield 2.72 g (47%) of off-white crystals of 3,6-dibromoanthranilic acid. [11h] Finally, 3,6-dibromoanthranilic acid was converted to 1,4-dibromo-2,3-diiodobenzene by employing the aprotic diazotization procedure in ref. [11i] After column chromatography(hexanes) the product was obtained as white crystals, 2.61 g (58%), mp 97-99 °C. 1H NMR (400 MHz, CDCl3): δ = 7.49 (s, 2 H). 13C NMR (100 MHz, CDCl3): δ = 132.8, 127.8, 117.4. MS (EI, 70 eV): m/z (%) = 488 (100) [M+], 361 (29), 234 (21), 153 (18), 74 (24). IR (CHCl3): 2920, 1396, 1150, 1002, 810 cm-1. HRMS: Calcd for C6H2Br2I2: 487.6592. Found: 487.6596. Anal. Calcd for C6H2Br2I2: C, 14.78; H, 0.41. Found: C, 14.74; H, 0.04.
    Google Scholar
  • 11g Garden SJ. Torres JC. Ferreira AA. Silva RB. Pinto AC. Tetrahedron Lett.  1997,  38:  1501 
    Google Scholar
  • 11h Lisowski V. Robba M. Rault S. J. Org. Chem.  2000,  65:  4193 
    Google Scholar
  • 11i Nakayama J. Sakai A. Hoshino M. J. Org. Chem.  1984,  49:  5084 
    Google Scholar
  • 13a Sonogashira K. In Metal-Catalyzed Cross-Coupling Reactions   Diederich F. Stang PJ. Wiley-VCH; New York: 1998.  p.Chap. 5 
    Google Scholar
  • 13b Sonogashira K. In Comprehensive Organic Synthesis   Vol. 3:  Trost BM. Pergamon; New York: 1991.  p.Chap. 2.4 
    Google Scholar
  • 14 A somewhat related application of microwaves in Sonogashira reactions is described in: Erdelyi M. Gogoll A. J. Org. Chem.  2001,  66:  4165 
    CrossrefGoogle Scholar
  • 15 Lidström P. Tierney J. Wathey B. Westman J. Tetrahedron  2001,  57:  9225 
    CrossrefGoogle Scholar
  • 17a Iyoda M. Vorasingha A. Kuwatani Y. Yoshida M. Tetrahedron Lett.  1998,  39:  4701 
    CrossrefGoogle Scholar
  • 17b Huynh C. Linstrumelle G. Tetrahedron  1988,  44:  6337 
    CrossrefGoogle Scholar
  • 18 Collman JP. Hegedus LS. Norton JR. Finke RG. Principles and Applications of Organotransition Metal Chemistry   University Science Books; Mill Valley: 1987.  p.Chap. 9 
    Google Scholar
  • 20 The spectral data are in good agreement with those in: Staab HA. Graf F. Chem. Ber.  1970,  103:  1107 
    CrossrefGoogle Scholar
  • 22 Srinivasan M. Sankararaman S. Dix I. Jones PG. Org. Lett.  2000,  2:  3849 
    CrossrefGoogle Scholar
  • 23a Alkorta I. Rozas I. Elguero J. Tetrahedron  2001,  57:  6043 
    CrossrefGoogle Scholar
  • 23b Jusélius J. Sundholm D. Phys. Chem.  2001,  3:  2433 
    CrossrefGoogle Scholar
  • 23c Godard C. Lepetit C. Chauvin R. Chem. Commun.  2000,  1833 
    CrossrefGoogle Scholar
  • 23d Wan WB. Kimball DB. Haley MM. Tetrahedron Lett.  1998,  39:  6795 
    CrossrefGoogle Scholar
  • 23e Matzger AJ. Vollhardt KPC. Tetrahedron Lett.  1998,  39:  6791 
    CrossrefGoogle Scholar
12

General Procedure for Propynylations: To a 150 mL Schlenk flask, equipped with a Teflon-coated magnetic stirring bar, were added the diiodoarene (1.67 mmol), PdCl2(PPh3)2 (177 mg, 0.25 mmol), CuI (32 mg, 0.17 mmol), and Et3N (7.50 mL). The flask was then evacuated and filled with propyne gas up to 1.5 atm (approx. 10 mmol, 3 equiv) of pressure. Depending on the system, the reaction mixture was stirred for 22-96 h, at either room or elevated temperatures (Table [1] ). The reaction mixture was then diluted with ether, washed with two portions of aq NH4Cl, and dried over MgSO4. Solvent was removed in vacuo and the resulting crude product purified by Kugelrohr distillation, sublimation, or chromatography.

16

General Procedure for Microwave-Assisted Propynylations: A heavy-walled Smith process vial was charged with a magnetic stirring bar, Et3N (0.9 mL), DMF (0.1 mL), PdCl2(PPh3)2 (19.6 mg, 0.028 mmol), CuI (5.4 mg, 0.028 mmol), and the dibromodiiodobenzene (0.113 mmol). The vial was sealed, evacuated, and filled with propyne through a Teflon septum up to 2.5 atm pressure. It was then irradiated in a Smith Synthesizer single-mode microwave cavity, producing continuous radiation at 2450 MHz. The resulting solution was immediately filtered through a short plug of silica gel (hexanes/ethyl acetate) to remove the catalyst and the crude product further purified by column chromatography on silica gel (hexanes).

19

General Procedure for (Me3CO)3WCCMe3-Mediated Alkyne Metathesis: A 25 mL Schlenk flask was charged, under the atmosphere of nitrogen, with the respective propynylated arene (0.20-0.35 mmol), (Me3CO)3WCCMe3 (20-40 mol%), and toluene (20 mL). The solution was stirred at 80 °C for 8-96 h (Table [2] ). After the reaction was complete, solvent was removed in vacuo, and the residue was subjected to flash chromatography on silica, eluting with hexane/ethyl acetate. Compound 1e: Brown crystals, showing green fluorescence, mp 292-300 °C(dec). 1H NMR (400 MHz, CDCl3): δ = 7.56 (s). MS (EI, 70 eV): m/z (%) = 774 (100)[M+], 695 (29), 614 (19). IR (CHCl3): 2933, 2255, 1464, 1274, 1154 cm-1. The compound decomposed upon standing for one week. Compound 2: Pale yellow crystals, showing green fluorescence, mp 310-315 °C(dec). 1H NMR (400 MHz, CDCl3): δ = 8.05 (br t, 2 H, J = 1.5 Hz), 7.59 (dd, 4 H, J 1 = 3.3 Hz, J 2 = 5.7 Hz), 7.54 (dd, 4 H, J 1 = 1.6 Hz, J 2 = 7.9 Hz), 7.38 (t, 2 H, J = 8.0 Hz), 7.32 (dd, 4 H, J 1 = 3.4 Hz, J 2 = 5.8 Hz). MS (EI, 70 eV): m/z (%) = 401(31) [M + H]+, 400(100) [M+], 199(11). HRMS: Calcd for C32H16: 400.1252. Found: 400.1248. UV/Vis (CH2Cl2): λmax (lg ) = 265 (4.03), 272 (4.05), 278 (4.11), 280 (4.10), 317 (3.62), 341 (3.26) nm. IR (CHCl3): 2920, 2219, 1468, 1212,
892 cm-1. Selected spectral data for 3: 1H NMR (400 MHz, CDCl3): δ = 7.44 (AA′ m, 8 H), 7.34 (s, 2 H), 7.19 (BB′ m, 8 H). MS (EI, 70 eV): m/z (%) = 524 (10) [M + 2H]+, 523 (42) [M + H]+, 522 (100) [M+], 261 (25) [M2+]. HRMS: Calcd for C42H18: 522.1408. Found: 522.1428.

21

The spectral data are in good agreement with those in ref. [17a]

24

Details of the crystal structure determination (deposition number CCDC 192630) may be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [Fax: +44(1223)336033; E-mail: deposit@ccdc.cam.ac.uk].