Download PDF
Synlett 2003(5): 0609-0614
DOI: 10.1055/s-2003-38367
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Enyne Ring-rearrangement/Cross-metathesis Reactions of Cyclic Enones

Sonia Imhof, Siegfried Blechert*
Institut für Chemie, Technische Universität Berlin, Strasse des 17. Juni 135, 10623 Berlin, Germany
Fax: +49(30)31423619; e-Mail: blechert@chem.tu-berlin.de;
Further Information

Publication History

Received 27 December 2002
Publication Date:
28 March 2003 (online)

    Permissions and Reprints All articles of this category

Abstract

The use of efficient ring rearrangement metathesis reactions of cyclic enones involving cross-metathesis is reported. The resulting trienes from these reactions are substrates for intramolecular Diels-Alder cycloaddition reactions. Thus, the synthesis of highly stereoselective fused tricyclic products in four distinct steps is achieved.

Key words

ring-rearrangement - metathesis - Diels-Alder cycloaddition - enyne - enones

    References

  • For recent olefin metathesis reviews see:
  • 1a Trnka TM. Grubbs RH. Acc. Chem. Res.  2001,  34:  18 
    CrossrefGoogle Scholar
  • 1b Fürstner A. Angew. Chem. Int. Ed.  2000,  39:  3012 ; Angew. Chem. 2000, 112, 3140
    CrossrefGoogle Scholar
  • 1c Roy R. Das SK. Chem. Commun.  2000,  519 
    CrossrefGoogle Scholar
  • 1d Philips AJ. Abell AD. Aldrichimica Acta  1999,  32:  75 
    CrossrefGoogle Scholar
  • 1e Armstrong SK. J. Chem. Soc., Perkin Trans. 1  1998,  371 
    CrossrefGoogle Scholar
  • 1f Grubbs RH. Chang S. Tetrahedron  1998,  54:  4413 
    CrossrefGoogle Scholar
  • 1g Ivin KJ. J. Mol. Catal. A: Chem.  1998,  133:  1 
    CrossrefGoogle Scholar
  • 1h Alkene Metathesis in Organic Synthesis   Fürstner A. Springer; Berlin: 1998. 
    CrossrefGoogle Scholar
  • 1i Randall ML. Snapper ML. J. Mol. Catal. A: Chem.  1998,  133:  29 
    CrossrefGoogle Scholar
  • 1j Schuster M. Blechert S. Angew. Chem., Int. Ed. Engl.  1997,  36:  2036 ; Angew. Chem. 1997, 109, 2124
    CrossrefGoogle Scholar
  • 2a Randl S. Lukas N. Connon S. Blechert S. Adv. Synth. Catal.  2002,  344:  1 
    Google Scholar
  • 2b Ovaa H. Stapper C. van der Marel GA. Overkleeft HS. van Boom JH. Blechert S. Tetrahedron  2002,  58:  7503 
    Google Scholar
  • 2c Zaminer J. Stapper C. Blechert S. Tetrahedron Lett.  2002,  43:  6739 
    Google Scholar
  • 2d Stapper C. Blechert S. Eur. J. Org. Chem.  2002,  16:  2855 
    Google Scholar
  • 2e Stapper C. Blechert S. J. Org. Chem.  2002,  67:  6456 
    Google Scholar
  • 2f Buschmann N. Rückert A. Blechert S. J. Org. Chem.  2002,  67:  4325 
    Google Scholar
  • 2g Banti D. North M. Adv. Synth. Catal.  2002,  344:  694 
    Google Scholar
  • 2h Stragies R. Blechert S. J. Am. Chem. Soc.  2000,  122:  9584 
    Google Scholar
  • 2i Voigtmann U. Blechert S. Synthesis  2000,  893 
    Google Scholar
  • 2j Ovaa H. Stragies R. van der Marel GA. van Boom JH. Blechert S. Chem. Commun.  2000,  1501 
    Google Scholar
  • 2k Fürstner A. Szillat H. Stelzer F. J. Am. Chem. Soc.  2000,  122:  6785 
    Google Scholar
  • 2l Stragies R. Blechert S. Tetrahedron  1999,  55:  8179 
    Google Scholar
  • 2m Adams J. Ford JG. Stamatos PJ. Hoveyda AH. J. Org. Chem.  1999,  64:  9690 
    Google Scholar
  • 2n Fürstner A. Szillat H. Gabor B. Mynott R. J. Am. Chem. Soc.  1998,  120:  8305 
    Google Scholar
  • 2o Chatani N. Furukawa N. Sakurai H. Murai S. Organometallics  1996,  15:  901 
    Google Scholar
  • 2p Zuercher WJ. Hashimoto M. Grubbs RH. J. Am. Chem. Soc.  1996,  18:  6634 
    Google Scholar
  • 3a Kitamura T. Sato Y. Mori M. Chem. Commun.  2001,  1258 
    Google Scholar
  • 3b Mori M. Kitamura T. Sato Y. Synthesis  2001,  654 
    Google Scholar
  • 3c Stragies R. Voigtmann U. Blechert S. Tetrahedron Lett.  2000,  41:  5465 
    Google Scholar
  • 3d Mori M. Kitamura T. Sakakibara N. Sato Y. Org. Lett.  2000,  2:  543 
    Google Scholar
  • 3e Smulik JA. Diver ST. J. Org. Chem.  2000,  65:  1788 
    Google Scholar
  • 3f Smulik JA. Diver ST. Org. Lett.  2000,  2:  2271 
    Google Scholar
  • 3g Renaud J. Graf C.-D. Oberer L. Angew. Chem. Int. Ed.  2000,  39:  3101 
    Google Scholar
  • 3h Stragies R. Schuster M. Blechert S. Chem. Commun.  1999,  237 
    Google Scholar
  • 3i Schürer SC. Blechert S. Chem. Commun.  1999,  1203 
    Google Scholar
  • 3j Schürer SC. Blechert S. Tetrahedron Lett.  1999,  40:  1877 
    Google Scholar
  • 3k Schürer SC. Blechert S. Synlett  1999,  1879 
    Google Scholar
  • 3l Kinoshita A. Sakakibara N. Mori M. Tetrahedron  1999,  12388 
    Google Scholar
  • 3m Mori M. In Topics in Organometallic Chemistry   Vol. 1:  Fürstner A. Springer-Verlag; Berlin, Heidelberg: 1998.  p.133 
    Google Scholar
  • 3n Schürer SC. Blechert S. Synlett  1998,  166 
    Google Scholar
  • 3o Schuster M. Blechert S. Tetrahedron Lett.  1998,  39:  2295 
    Google Scholar
  • 3p Mori M. Sakakibara N. Kinoshita H. J. Org. Chem.  1998,  63:  6082 
    Google Scholar
  • 4a Kitamura T. Mori M. Org. Lett.  2001,  3:  1161 
    Article in Thieme ConnectGoogle Scholar
  • 4b Bentz D. Laschat S. Synthesis  2000,  12:  1766 
    Article in Thieme ConnectGoogle Scholar
  • 5a Schenck GO. Dunlap DE. Angew. Chem.  1956,  68:  248 
    CrossrefGoogle Scholar
  • 5b Laumen K. Reimerdes EH. Schneider M. Tetrahedron Lett.  1985,  26:  407 
    CrossrefGoogle Scholar
  • 5c Laumen K. Reimerdes EH. Schneider M. Tetrahedron Lett.  1985,  4:  407 
    CrossrefGoogle Scholar
  • 5d Kaneko C. Sugimoto A. Tanaka S. Synthesis  1974,  876 
    CrossrefGoogle Scholar
  • 5e Dirkzwanger H. Nienstad TJ. van Wijk AM. van Bekkum H. Recl. Trav. Chim. Pays-Bas  1973,  35 
    CrossrefGoogle Scholar
  • 5f Bis SJ. Whitaker DT. Johnson CR. Tetrahedron: Asymmetry  1993,  4:  875 
    CrossrefGoogle Scholar
  • 5g Johnson CR. Bis SJ. Tetrahedron Lett.  1992,  33:  7287 
    CrossrefGoogle Scholar
  • 5h Adam W. Bloodworth AJ. Eggelte HJ. Loveitt ME. Angew. Chem.  1978,  3:  216 
    CrossrefGoogle Scholar
  • 5i Mitsunobu O. Synthesis  1981,  1 
    CrossrefGoogle Scholar
  • 5j Dess DB. Martin JC. J. Am. Chem. Soc.  1991,  113:  7277 
    CrossrefGoogle Scholar
  • 6a Schwab P. Grubbs RH. Ziller JW. J. Am. Chem. Soc.  1996,  118:  100 
    Google Scholar
  • 6b Scholl M. Ding S. Lee CW. Grubbs RH. Org. Lett.  1999,  1:  953 
    Google Scholar
  • Other active NHC-based catalysts:
  • 7a Huang J. Stevens ED. Nolan SP. Petersen JL. J. Am. Chem. Soc.  1999,  121:  2674 
    Google Scholar
  • 7b Ackermann L. Fürstner A. Weskamp T. Kohl FJ. Herrmann WA. Tetrahedron Lett.  1999,  40:  4787 
    Google Scholar
  • 7c Scholl M. Trnka TM. Morgan JP. Grubbs RH. Tetrahedron Lett.  1999,  40:  2247 
    Google Scholar
  • 9a Kitamura T. Sato Y. Mori M. Chem. Commun.  2001,  1258 
    Google Scholar
  • 9b Kitamura T. Sato Y. Mori M. Adv. Synth. Catal.  2002,  344:  678 
    Google Scholar
  • 12a

    The geometries of the reactants, products and transition states were optimised using the AM1 semi-empirical method as implemented in Gaussian 98.12b Single point calculations were performed using these geometries with the resolution-of-identity method and the BP86 density functional, as implemented in Turbomol.12c The TZV basis sets of Ahlrichs [12d] were used for all atoms with polarisation functions for the heavy atoms. It was found that the relative activation energy of 16a, 17a and 18a was 72 kJmol-1, 47 kJmol-1 and 61 kJmol-1 respectively. This supports the argument that shorter chain lengths results in a less accessible transition state.
  • 12b Frisch MJ. Trucks GW. Schlegel HB. Scuseria GE. Robb MA. Cheeseman JR. Zakrzewski VG. Montgomery JA. Stratmann RE. Burant JC. Dapprich S. Millam JM. Daniels AD. Kudin KN. Strain MC. Farkas O. Tomasi J. Barone V. Cossi M. Cammi R. Mennucci B. Pomelli C. Adamo C. Clifford S. Ochterski J. Petersson GA. Ayala PY. Cui Q. Morokuma K. Malick DK. Rabuck AD. Raghavachari K. Foresman JB. Cioslowski J. Ortiz JV. Baboul AG. Stefanov BB. Liu G. Liashenko A. Piskorz P. Komaromi I. Gomperts R. Martin RL. Fox DJ. Keith T. Al-Laham MA. Peng CY. Nanayakkara A. Gonzalez C. Challacombe M. Gill PMW. Johnson BG. Chen W. Wong MW. Andres JL. Head-Gordon M. Replogle ES. Pople JA. Gaussian 98 (Revision A.9)   Gaussian, Inc.; Pittsburgh PA: 1998. 
    Google Scholar
  • 12c Ahlrichs R. Bär M. Häser M. Horn H. Kölmel C. Chem. Phys. Lett.  1998,  162 
    Google Scholar
  • 12d Schafer A. Huber C. Ahlrichs R. J. Chem. Phys.  1994,  100:  5829 
    Google Scholar
8

In a 10 mL flask a solution of 11 (25 mg, 0.075 mmol) and catalyst 15 (6.4 mg, 10 mol%) in CH2Cl2 (0.05 molar) under N2 was cooled with liquid nitrogen. To this cooled solution, 50 mL of CH2CH2 was added, which condensed rapidly and the sealed flask was stirred at 80 °C for 2 h. After the addition of an excess of ethyl vinyl ether the reaction mixture was stirred for an additional 60 h at 80 °C. The solvent was removed in vacuo and the residue was purified by flash column chromatography on silica gel (hexane/MTBE 2:1) to yield 14.9 mg of 17b (55%) as a light yellow oil.

10

The configuration of 18b was determinated by X-ray crystallography.

11

After following conversion in these reactions by 1H NMR spectroscopy, it was found that 16a-19a decompose steadily to numerous unidentifiable products under the reaction conditions, in the case of the reaction of 10, 12 and 13, levels of 16a, 18a and 19a were typically in the range of 20-40% after 2 h, whereas 11 had undergone quantitative conversion at this time. In an attempt to enhance the yield, temperature ranges (between r.t. and 120 °C) were used as well as a Lewis acid (e.g. MeAlCl2) that was added at the beginning of the reaction and after 2 h, but proved to be unsuccessful. It is noteworthy that 16b-19b are perfectly stable and show no signs of decomposition even after extended reaction times.

13

In an attempt to improve stability, the possibility of employing reduced allyl alcohol analogues (protected as silylethers) was briefly investigated. While in the case of analogues of 11 these species proved stable and gave reasonable yields of RRM adduct (pre-cycloaddition) in accordance with ref. 4a, higher homologues were unreactive and offered no advantages over their oxidised counterparts 12 and 13.

14

To a solution of 11 (60.0 mg, 0.180 mmol) and 26 (56.1 mg, 0.540 mmol) in CH2Cl2 (0.05 molar) under N2 was added catalyst 15 (15.2 mg, 10 mol%) and the reaction was stirred at 55 °C for 3 h. To this solution was added an excess of ethyl vinyl ether. After the solvent was removed, the residue was purified by flash column chromatography on silica gel (hexane/MTBE 10:1) to yield 86.0 mg of triene 29 (93%) as a light yellow oil. 29 (24 mg, 0.0467 mmol) was solved
in toluene (2 mL) and heated to 150 °C for 4 h in a sealed tube to yield after purifying by flash column chromato-graphy on silica gel (hexane/MTBE 4/1) 20.4 mg of 34 (85%) as a white waxy product.
1H NMR (500 MHz, CDCl3): δ (ppm) = 8.41-8.39 (d, J = 8.9 Hz, 2 H), 8.08-8.06 (d, J = 8.8 Hz, 2 H), 7.25-7.19 (m, 6 H), 7.06-7.00 (d, J = 6.9 Hz, 2 H), 6.99-6.98 (d, J = 7.2 Hz, 2 H), 6.10 (br, 1 H), 4.33-4.31 (dd, J = 13.4 Hz, J = 1.2 Hz, 1 H), 4.22-4.18 (ddd, J = 8.7 Hz, J = 6.4 Hz, J = 6.4 Hz, 1 H), 4.06-4.02 (ddd, J = 13.5 Hz, J = 1.8 Hz, J = 1.8 Hz, 1 H), 3.92-3.91 (dd, J = 2.9 Hz, J = 2.9 Hz, 1 H), 3.66 (br, 1 H), 2.75-2.73 (ddd, J = 8.7 Hz, J = 8.7 Hz, J = 0.5 Hz, 1 H), 2.58-2.57 (dd, J = 7.4 Hz, J = 3.2 Hz, 1 H), 2.46-2.40 (m, 1 H), 2.30-2.24 (m, 2 H), 2.10-2.06 (m, 1 H). 13C NMR (125 MHz, CDCl3): δ (ppm) = 206.68 (C), 150.38 (C), 144.73 (C), 144.20 (C), 143.30 (C), 136.05 (C), 128.80 (CH ¥ 2), 128.75 (CH ¥ 2), 128.30 (CH ¥ 2), 127.90 (CH ¥ 2), 127.34 (CH ¥ 2), 126.81 (CH), 126.67 (CH), 124.96 (CH), 124.65 (CH ¥ 2), 58.72 (CH), 51.61 (CH2), 49.84 (CH), 45.60 (CH), 44.44 (CH), 37.81 (CH), 35.63 (CH2), 27.52 (CH2). IR (ATR): ν (cm-1) = 3103, 3060, 2926, 2867, 1713, 1529, 1349, 1168, 1091, 737. MS (EI, 100 °C): m/z (%) = 514 [M+], 355, 328, 182, 168, 141, 115, 91. HRMS calcd for C29H26N2O5S [M+]: 514.1562. Found: 514.1567.