Olefin and Enyne Cross-Metathesis - A New Tool for the Synthesis of Alkenyl-substituted Azulenes

Agnieszka Mikus; Volodymyr Sashuk; Mariusz Kūdziorek; Cezary Samojowicz; Stanisaw Ostrowski; Karol Grela

doi:10.1055/s-2005-865242

LETTER

Olefin and Enyne Cross-Metathesis - A New Tool for the Synthesis of Alkenyl-substituted Azulenes

Agnieszka Mikus^b, Volodymyr Sashuk^a, Mariusz Kūdziorek^a, Cezary Samojowicz^a, Stanisaw Ostrowski*^a,b, Karol Grela*^a
^a Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, 01-224 Warszawa, Poland
Fax: +48(22)6326681; e-Mail: grela@icho.edu.pl;
^b Institute of Chemistry, University of Podlasie, ul. 3 Maja 54, 08-110 Siedlce, Poland
Fax: +48(25)6442045; e-Mail: stan@ap.siedlce.pl;

Abstract

Alle Artikel dieser Rubrik

Abstract

A selective synthesis of azulenes with an extended π-electron system by olefin and enyne cross-metathesis is described. Electron-enriched five-membered ring and electron-deficient seven-membered ring of the azulene moiety affected the reaction yield.

Key words

azulene derivatives - olefin and enyne metathesis - ruthenium complexes

Volltext

Referenzen

References

<A NAME="RG00905ST-1A">1a</A> Handbook of Conducting Polymers Skotheim TA. Elsenbaumer RL. Reynolds IR. Dekker; New York: 1998.

<A NAME="RG00905ST-1B">1b</A> Diederich F. Martin RE. Angew. Chem. Int. Ed. 1999, 38: 1350

<A NAME="RG00905ST-1C">1c</A> Scherf U. Müllen K. Synthesis 1992, 23

<A NAME="RG00905ST-1D">1d</A> Tour JM. Chem. Rev. 1996, 96: 537

<A NAME="RG00905ST-1E">1e</A> Nelson JC. Saven JG. Moore JS. Wolynes PG. Science (Washington, D.C.) 1997, 277: 1793

<A NAME="RG00905ST-1F">1f</A> Baum-garten M. Müllen K. Top. Curr. Chem. 1994, 169: 1

<A NAME="RG00905ST-2A">2a</A> Fabian KHH. Elwahy AHM. Hafner K. Tetrahedron Lett. 2000, 41: 2855

<A NAME="RG00905ST-2B">2b</A> Elwahy AHM. Hafner K. Tetrahedron Lett. 2000, 41: 2859

<A NAME="RG00905ST-2C">2c</A> Elwahy AHM. Hafner K. Tetrahedron Lett. 2000, 41: 4079

<A NAME="RG00905ST-3A">3a</A> Ito S. Inabe H. Okujima T. Morita N. Watanabe M. Imafuku K. Tetrahedron Lett. 2000, 41: 8343

<A NAME="RG00905ST-3B">3b</A> Elwahy AHM. Tetrahedron Lett. 2002, 43: 711

<A NAME="RG00905ST-3C">3c</A> Ito S. Nomura A. Morita N. Kabuto Ch. Kobayashi H. Maejima S. Fujimori K. Yasunami M. J. Org. Chem. 2002, 67: 7295

<A NAME="RG00905ST-3D">3d</A> Ito S. Inabe H. Morita N. Ohta K. Kitamura T. Imafuku K. J. Am. Chem. Soc. 2003, 125: 1669

<A NAME="RG00905ST-4A">4a</A> Corey EJ. Fuchs PL. Tetrahedron Lett. 1972, 3769

<A NAME="RG00905ST-4B">4b</A> Hünig S. Ort B. Liebigs Ann. Chem. 1984, 1905

<A NAME="RG00905ST-5A">5a</A> Schmitt S. Baumgarten M. Simon J. Hafner K. Angew. Chem. Int. Ed. 1998, 37: 1078

<A NAME="RG00905ST-5B">5b</A> Mkosza M. Kêdziorek M. Ostrowski S. Synthesis 2002, 2517

<A NAME="RG00905ST-5C">5c</A> Horino H. Asao T. Inoue N. Bull. Chem. Soc. Jpn. 1991, 64: 183

<A NAME="RG00905ST-5D">5d</A> Ito S. Okujima T. Morita N. J. Chem. Soc., Perkin Trans. 1 2002, 1896

<A NAME="RG00905ST-5E">5e</A> Crombie AL. Kane JL. Shea KM. Danheiser RL. J. Org. Chem. 2004, 69: 8652

<A NAME="RG00905ST-5F">5f</A> Ito S. Terazono T. Kubo T. Okujima T. Morita N. Murafuji T. Sugihara Y. Fujimori K. Kawakami J. Tajiri A. Tetrahedron 2004, 60: 5357

General reviews on olefin metathesis reaction and catalysts:

<A NAME="RG00905ST-6A">6a</A> Schrock RR. Hoveyda AH. Angew. Chem. Int. Ed. 2003, 42: 4592

<A NAME="RG00905ST-6B">6b</A> Trnka TM. Grubbs RH. Acc. Chem. Res. 2001, 34: 18

<A NAME="RG00905ST-6C">6c</A> Schuster M. Blechert S. Angew. Chem., Int. Ed. Engl. 1997, 36: 2037

<A NAME="RG00905ST-6D">6d</A> Dragutan V. Dragutan I. Balaban AT. Platinum Met. Rev. 2001, 45: 155

<A NAME="RG00905ST-7A">7a</A> For a review on catalyst 1b and its variations see: Hoveyda AH. Gillingham DG. Van Veldhuizen JJ. Kataoka O. Garber SB. Kingsbury JS. Harrity JPA. Org. Biomol. Chem. 2004, 2: 1

<A NAME="RG00905ST-7B">7b</A> Grela K. Harutyunyan S. Michrowska A. Angew. Chem. Int. Ed. 2002, 41: 4038

<A NAME="RG00905ST-7C">7c</A> Michrowska A. Bujok R. Harutyunyan S. Sashuk V. Dolgonos G. Grela K. J. Am. Chem. Soc. 2004, 126: 9318

<A NAME="RG00905ST-7D">7d</A> Harutyunyan S. Michrowska A. Grela K. In Catalysts for Fine Chemical Synthesis Vol. 3: Roberts SM. Whittall J. Mather P. McCormack P. Wiley-Interscience; New York: 2004. Chap. 9.1. p.169-173

<A NAME="RG00905ST-8A">8a</A> Ostrowski S. Mikus A. Mol. Diversity 2003, 6: 315

<A NAME="RG00905ST-8B">8b</A> Honda T. Namiki H. Kaneda K. Mizutani H. Org. Lett. 2004, 6: 87

<A NAME="RG00905ST-8C">8c</A> Honda T. Namiki H. Watanabe M. Mizutani H. Tetrahedron Lett. 2004, 45: 5211

<A NAME="RG00905ST-8D">8d</A> Stellfeld T. Bhatt U. Kalesse M. Org. Lett. 2004, 6: 3889

<A NAME="RG00905ST-8E">8e</A> inventors; WO 2004/089974A1. For a recent application in synthesis of hepatitis C antiviral agent BILN 2061 see: ; Boehringer Ingelheim International GmbH

<A NAME="RG00905ST-9">9</A> For the definition of olefins types I-IV see: Chatterjee AK. Choi T.-L. Sanders DP. Grubbs RH. J. Am. Chem. Soc. 2003, 125: 11360

Mkosza, M.; Kêdziorek, M.; Hafner, K.; Ostrowski, S. Eur. J. Org. Chem., in preparation.

<A NAME="RG00905ST-11A">11a</A> Kinoshita A. Sakakibara N. Mori M. J. Am. Chem. Soc. 1997, 119: 12388

<A NAME="RG00905ST-11B">11b</A> For general reviews on enyne metathesis see: Diver ST. Giessert AJ. Chem. Rev. 2004, 104: 1317

<A NAME="RG00905ST-11C">11c</A> Poulsen CS. Madsen R. Synthesis 2003, 1

<A NAME="RG00905ST-11D">11d</A> Sémeril D. Bruneau C. Dixneuf PH. Adv. Synth. Catal. 2002, 344: 585

For reviews on cross-metathesis see:

<A NAME="RG00905ST-12A">12a</A> Vernall AJ. Abell AD. Aldrichimica Acta 2003, 36: 93

<A NAME="RG00905ST-12B">12b</A> Blechert S. Connon SJ. Angew. Chem. Int. Ed. 2003, 42: 1900

<A NAME="RG00905ST-12C">12c</A> For an application of styrene CM to a commercial product see: Pederson RL. Fellows IM. Ung TA. Ishihara H. Hajela SP. Adv. Synth. Catal. 2002, 344: 728

<A NAME="RG00905ST-12D">12d</A> For styrene CM as alternative to Heck and other cross-coupling reactions see: Chatterjee AK. Toste FD. Choi T.-L. Grubbs RH. Adv. Synth. Catal. 2002, 344: 634

These substrates were prepared either from (1-propynyl)- azulenes via Lindlar reduction (2b → 3a, 2e → 3c) or from the corresponding iodo-derivative via Stille coupling (3b): Sashuk, V. PhD Dissertation, in preparation.

NMR spectra were recorded with a Varian GEMINI-200 spectrometer operating at 200 MHz for ¹H NMR and 50 MHz for ¹³C NMR. Coupling constants J are expressed in Hz. Mass spectra were measured with an AMD 604 (AMD Intectra GmbH, Germany) spectrometer (EI method). IR spectra were measured with Perkin-Elmer Spectrum 2000 FT-IR spectrometer. TLC analysis was performed on aluminium foil plates pre-coated with silica gel (60F 254, Merck). Silica gel, 230-400 mesh (Merck AG), was used for column chromatography.

Typical procedure for enyne metathesis with ethylene: A pressure tube (50 mL) was thoroughly flushed with argon and charged with a solution of an azulene derivative 2d (30 mg, 0.097 mmol) and the catalyst 1c (ca. 15 mol%) in anhydrous CH₂Cl₂ (4 mL). The tube was immersed in liquid nitrogen (ca. -190 °C) and gaseous ethylene was delivered to the tube through rubber septa. Once accumulation of ethylene had occurred, the tube was sealed and the reaction mixture was allowed to reach room temperature. The mixture was stirred under the ethylene gas atmosphere (12 atm) for approximately 44 h. Then it was recooled in liquid nitrogen and the tube was opened. The mixture was allowed to reach room temperature under a stream of argon. The residue was concentrated under reduced pressure and purified by column chromatography (eluent: CHCl₃) to give the product 5d as a dark-green solid (blue-green in CHCl₃ solution); yield: 15.0 mg (46%); mp 79-81°C. ¹H NMR (CDCl₃, 200 MHz): d = 8.24 (d, J = 10.8 Hz, 2 H), 7.77 (s, 1 H), 7.24 (d, J = 10.8 Hz, 2 H), 6.64 (dd, J = 17.5,10.9 Hz, 1 H, H-vinyl), 5.46-5.03 (m, 4 H, H-vinyl). ¹³C NMR (CDCl₃, 50 MHz): d = 139.0, 137.9, 135.7, 135.6, 135.0, 127.3, 125.0, 119.1, 118.4, 102.8. MS (EI): m/z (%) = 341 (1), 340 (9), 339 (3), 338 (19), 337 (2), 336 (10) [isotopic M^+·], 310 (5), 260 (1), 259 (6), 258 (6), 257 (6), 256 (5), 179 (16), 178 (100), 177 (18), 176 (20), 175 (2), 153 (1), 152 (11), 151 (10), 150 (15), 149 (3), 126 (3), 125 (4), 124 (2), 123 (1), 89 (10), 88 (8), 87 (3), 76 (11), 75 (10). HR-MS (EI): m/z calcd for C₁₄H₁₀ ⁷⁹Br₂, 335.9149; found, 335.9151. Anal. Calcd for C₁₄H₁₀Br₂ (338.04): C, 49.74; H, 2.98. Found: C, 50.67; H, 3.49.

Typical procedure for CM with olefins 4b-e. ( E )-3-(6-Azulenyl)-2-propenyl acetate ( 6c): To a mixture of 3c (21 mg. 0.125 mmol) and olefin 4d (43 mg, 0.250 mmol) in anhydrous CH₂Cl₂ (6 mL) a solution of 1c (8.4 mg, 10 mol%) in CH₂Cl₂ (1 mL) was added. The resulting mixture was stirred at 45 °C for 24 h under argon. The solvent was removed under reduced pressure. Flash chromatography (eluent: cyclohexane-EtOAc, 8:2) of the crude dark residue gave 19 mg of 6c (56%) as a dark-blue solid. IR (KBr): 1741, 1735, 1574, 1516, 1477, 1398, 1341, 1243, 1105, 1077, 1026, 961, 860, 782, 759 cm^-1. ¹H NMR (CDCl₃, 200 MHz): δ = 8.28 (d, J = 10.6 Hz, 2 H), 7.85 (apparent t, J = 3.7 Hz, 1 H), 7.35 (d, J = 3.7 Hz, 2 H), 7.27 (d, J = 10.6 Hz, 2 H), 6.84 (d, J = 16.0 Hz, 1 H), 6.48 (dt, J = 16.0, 6.3 Hz, 1 H), 4.80 (dd, J = 6.3, 1.4 Hz, 2 H), 2.14 (s, 3 H, CH₃). ¹³C NMR (CDCl₃, 50 MHz): δ = 170.7 (C=O), 144.4, 139.3, 138.0, 137.0, 135.5, 126.9, 121.6, 118.5, 64.8 (CH₂), 21.0 (CH₃). MS (EI): m/z (%) = 227 (17), 226 (100) [isotopic M^+·], 184 (26), 177 (25), 176 (33), 166 (29), 165 (77), 155 (52), 153 (20), 152 (31), 128 (19), 43 (58); HR-MS (EI): m/z calcd for C₁₅H₁₄O₂, 226.0994; found, 226.0999.