PDF herunterladen
Synlett 2007(17): 2718-2722  
DOI: 10.1055/s-2007-991057
LETTER
© Georg Thieme Verlag Stuttgart · New York

Stereoselective Radical Cascade Cyclizations of Unsaturated Epoxynitriles: Quadruple Radical Cyclization Terminated by a 4-exo Process onto Nitrile

A. Fernández-Mateos*a, P. Herrero Teijóna, R. Rabanedo Clementea, R. Rubio Gonzáleza, F. Sanz Gonzálezb
a Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad de Salamanca, Plaza de los Caídos 1-5, 37008 Salamanca, Spain
e-Mail: afmateos@usal.es;
b General X-ray Diffraction Service, Facultad de Ciencias Químicas, Universidad de Salamanca, Plaza de los Caídos 1-5, 37008 Salamanca, Spain
Weitere Informationen

Publikationsverlauf

Received 27 July 2007
Publikationsdatum:
25. September 2007 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik

Abstract

Radical cascade cyclizations of unsaturated epoxy­nitriles induced by titanocene chloride proceed in good yields and with excellent diastereoselectivities. From three to seven stereocenters were created by the reaction and a single isomeric product was obtained from most of the substrates examined. The relative configuration of the products is consistent with cyclization occurring via a chair-like transition state. The termination of the radical cascade reaction by 4-exo, 5-exo or 6-exo cyclization onto nitrile is remarkable.

Key words

radical cyclization - titanocene chloride - epoxynitriles - cascade reactions

    References and Notes

  • 1 Dhimane AL. Fensterbank L. Malacria M. In Radicals in Organic Synthesis   Vol. 2:  Renaud M. Sibi MP. Wiley-VCH; Weinheim: 2001.  p.350-382  
    Google Scholar
  • 2 Snider BB. Kiselgof JY. Foxman BM. J. Org. Chem.  1998,  63:  7945 ; and references cited therein
    Google Scholar
  • 3a Justicia J. Rosales A. Buñuel E. Oller-López JL. Valdivia M. Haïdour A. Oltra JE. Barrero AF. Cárdenas DJ. Cuerva JM. Chem. Eur. J.  2004,  10:  1778 
    Google Scholar
  • 3b Barrero AF. Quílez de Moral JF. Sánchez EM. Arteaga JF. Eur. J. Org. Chem.  2006,  1627 
    Google Scholar
  • 3c Cuerva JM. Justicia J. Oller-López JL. Bazdi B. Oltra JE. Mini-Rev. Org. Chem.  2006,  3:  23 
    Google Scholar
  • 4a RajanBabu TV. Nugent WA. J. Am. Chem. Soc.  1994,  116:  986 
    Google Scholar
  • 4b Gansäuer A. Bluhm H. Chem. Rev.  2000,  100:  2771 
    Google Scholar
  • 4c Gansäuer A. Lauterbach T. Narayan S. Angew. Chem. Int. Ed.  2003,  42:  5556 
    Google Scholar
  • 5a Bowman WR. Bridge CF. Brookes P. Tetrahedron Lett.  2000,  41:  8989 ; and references therein
    Google Scholar
  • 5b Fallis AG. Rinza IM. Tetrahedron  1997,  52:  17543 
    Google Scholar
  • 6 Fernández-Mateos A. Mateos Burón L. Rabanedo Clemente R. Ramos Silvo AI. Rubio González R. Synlett  2004,  1011 
    Artikel in Thieme ConnectGoogle Scholar
  • 7a Tsang T. Fraser-Reid B. J. Am. Chem. Soc.  1986,  108:  2116 
    CrossrefGoogle Scholar
  • 7b Barry B. Snider BB. Buckman BO. J. Org. Chem.  1992,  57:  322 
    CrossrefGoogle Scholar
  • 7c Crich D. Bowers AA. J. Org. Chem.  2006,  71:  3452 
    CrossrefGoogle Scholar
  • 8a

    Reaction of Epoxides with Cp 2 TiCl: A mixture of Cp2TiCl2 (3.3 mmol) and Zn (6.60 mmol) in strictly deoxy-genated THF (4 mL) was stirred at r.t. until the red solution turned green. In a separate flask, the epoxy compound (1 mmol) was dissolved in strictly deoxygenated THF (10 mL). The green Ti(III) solution was slowly added via cannula to the epoxide solution. After 30 min, an excess of sat. NaH2PO3 was added, and the mixture was stirred for 20 min. The product was extracted into Et2O and washed with sat. NaHCO3, and brine, dried (Na2SO4), and filtered. After removal of the solvent, the crude product was purified by flash chromatography.
    Crossref
  • 8b Yamamoto Y. Matsumi D. Hattori R. Itoh K. J. Org. Chem.  1999,  64:  3224 
    CrossrefGoogle Scholar
  • 9a Curran DP. In Comprehensive Organic Synthesis   Vol. 4:  Trost BM. Fleming I. Paquette LA. Pergamon; Oxford: 1991.  Chap. 4.2.1.
    Google Scholar
  • 9b Giese B. Kopping B. Göbel T. Thoma G. Dickhaut J. Kulicke KJ. Trach F. In Organic Reactions   Vol. 48:  Paquette LA. Wiley; New York: 1996.  p.307 
    Google Scholar
  • 10a Curran DP. Porter NA. Giese B. In Stereochemistry of Radical Reactions   VCH; Weinheim: 1995.  p.31-101  
    Google Scholar
  • 10b Spellmeyer DC. Houk KN. J. Org. Chem.  1987,  52:  959 
    Google Scholar
  • 12 Escher S. Giersch W. Ohloff G. Helv. Chim. Acta  1981,  64:  943 
    Google Scholar
  • 13 Hagiwara H. Uda H. J. Org. Chem.  1988,  53:  2308 
    CrossrefGoogle Scholar
  • 14 Deng WP. Zhong M. Guo XC. Kende AS. J. Org. Chem.  2003,  68:  7422 
    CrossrefPubMedGoogle Scholar
  • 15a Falck JR. Chandrasekhar S. Manna S. Chiu CCS. Mioskowski C. Wetzel I. J. Am. Chem. Soc.  1993,  115:  11606 
    CrossrefGoogle Scholar
  • 15b Abad A. Agullo C. Arno M. Cuñat AC. Meseguer B. Zaragoza RJ. J. Org. Chem.  1998,  63:  5100 
    CrossrefGoogle Scholar
  • 16 Ireland RE. Baldwin SW. Dawson DJ. Dawson MI. Dolfini JE. Newbould J. Johnson WS. Brown M. Crawford RJ. Hudrlik PF. Rasmussen GH. Schmiegel KK. J. Am. Chem. Soc.  1970,  92:  5743 
    CrossrefGoogle Scholar
  • 17 Takikawa H. Hirooka M. Sasaki M. Tetrahedron Lett.  2003,  44:  5235 
    CrossrefGoogle Scholar
  • 18a Fernández-Mateos A. Martín de la Nava EM. Pascual Coca G. Ramos Silvo A. Rubio González R. Org. Lett.  1999,  1:  607 
    Google Scholar
  • 18b Fernández-Mateos A. Mateos Burón L. Martín de la Nava EM. Rabanedo Clemente R. Rubio González R. Sanz González F. Synlett  2004,  2553 
    Google Scholar
  • 18c Cuerva JM. Campaña AG. Justicia J. Rosales A. Oller-López JL. Robles R. Cárdenas DJ. Buñuel E. Oltra JE. Angew. Chem. Int. Ed.  2006,  45:  5522 
    Google Scholar
  • 19a Lee-Ruff E. Mladenova G. Chem. Rev.  2003,  103:  1449 
    CrossrefGoogle Scholar
  • 19b Namyslo JC. Kaufmann DE. Chem. Rev.  2003,  103:  1485 
    CrossrefGoogle Scholar
  • 19c Bellus D. Ernst B. Angew. Chem., Int. Ed. Engl.  1988,  27:  797 
    CrossrefGoogle Scholar
  • 19d Snider BB. Chem. Rev.  1988,  88:  793 
    CrossrefGoogle Scholar
11

Crystallographic data for the structures 2a(dinitrobenzoate), 5a, and 8a(dinitrobenzoate) have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication nos. CCDC 646905, CCDC 646904, CCDC 646903, respectively. These data can be obtained free of charge from the CCDC via www.ccdc.cam.ac.uk/data_request/cif.

20

Data for 1a: IR: ν = 3466, 2245 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.84 (3 H, s), 0.88 (3 H, s), 1.13 (3 H, s), 1.53 (1 H, m), 1.70 (2 H, t, J = 7.2 Hz), 2.10 (1 H, m), 2.21 (2 H, br s), 3.87 (1 H, dd, J 1 = 6.4 Hz, J 2 = 8.2 Hz) ppm. 13C NMR (100 MHz, CDCl3): δ = 17.4 (CH3), 22.0 (CH3), 22.3 (CH3), 27.0 (CH2), 29.9 (CH2), 34.4 (CH2), 44.2 (C), 46.2 (C), 80.6 (CH), 119.2 (C) ppm. MS (EI): m/z (%) = 167 (4) [M+], 150 (6), 139 (7), 126 (60), 108 (56), 96 (25), 86 (98), 71 (100). ESI-HRMS: m/z calcd for C10H17NO: 167.1310; found: 167.1315 [M+].
Data for 1b: IR: ν = 3475, 2249 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.88 (3 H, s), 0.89 (3 H, s), 1.08 (3 H, s), 1.57 (2 H, m), 1.87 (1 H, m), 2.16 (1 H, m), 2.27 (1 H, d, J = 16.7 Hz), 2.68 (1 H, d, J = 16.7 Hz), 3.92 (1 H, m) ppm. 13C NMR (100 MHz, CDCl3): δ = 16.8 (CH3), 22.2 (CH3), 22.7 (CH3), 26.6 (CH2), 30.1 (CH2), 34.6 (CH2), 44.0 (C), 46.5 (C), 80.8 (CH), 119.4 (C) ppm. MS (EI): m/z (%) = 167 (3) [M+], 126 (60), 108 (54), 86 (96), 71 (100). ESI-HRMS: m/z calcd for C10H17NO: 167.1310; found: 167.1319 [M+].

21

Data for 2a: colourless oil. IR: ν = 3491, 1765 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.98 (3 H, s), 1.06 (3 H, s), 1.25 (3 H, s), 1.28 (1 H, m), 1.65-1.90 (4 H, m), 2.14 (1 H, td, J 1 = 4.2 Hz, J 2 = 13.9 Hz), 2.71 (1 H, dd, J 1 = 8.8 Hz, J 2 = 16.3 Hz), 3.64 (2 H, m) ppm. 13C NMR (100 MHz, CDCl3): δ = 20.9 (CH3), 21.5 (CH2), 24.2 (CH3), 24.4 (CH2), 28.9 (CH3), 32.82 (C), 41.0 (CH), 47.0 (CH2), 58.1 (C), 74.3 (CH), 212.0 (C) ppm. MS (EI): m/z (%) = 182 (2) [M+], 167 (3), 139 (10), 122 (38), 107 (17), 96 (100), 81 (28), 69 (19). ESI-HRMS: m/z calcd for C11H18O2: 182.1307; found: 182.1311 [M+].
Data for 2b: viscous oil. 1H NMR (400 MHz, CDCl3): δ = 1.03 (6 H, s), 1.22 (3 H, s), 1.40-2.00 (5 H, m), 2.70 (1 H, dd, J 1 = 8.8 Hz, J 2 = 16.4 Hz), 3.14 (1 H, dd, J 1 = 10.4 Hz, J 2 = 16.4 Hz), 3.67 (1 H, m) ppm. 13C NMR (100 MHz, CDCl3): δ = 20.6 (CH3), 21.3 (CH3), 25.1 (CH3), 26.8 (CH2), 29.2 (CH2), 34.4 (C), 44.6 (CH2), 45.0 (CH), 58.9 (C), 74.4 (CH), 209.9 (C) ppm. MS (EI): m/z (%) = 182 (2) [M+], 165 (3), 139 (11), 122 (40), 107 (20), 96 (100), 81 (30), 71 (18). ESI-HRMS: m/z calcd for C11H18O2: 182.1307; found: 182.1301 [M+].

22

Data for 3a: viscous oil: IR: ν = 3457, 1734 cm-1. H NMR (400 MHz, CDCl3): δ = 0.93 (3 H, s), 1.00 (3 H, s), 1.04 (3 H, s), 1.33 (1 H, m), 1.60-1.90 (5 H, m), 2.14 (1 H, dt, J 1 = 8.9 Hz, J 2 = 19.3 Hz), 2.47 (1 H, dd, J 1 = 8.8 Hz, J 2 = 19.3 Hz), 3.30 (1 H, dd, J 1 = 4.5 Hz, J 2 = 11.3 Hz) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.7 (2 CH3), 18.4 (CH2), 27.3 (CH3), 27.8 (CH2), 30.2 (CH2), 36.0 (CH2), 38.9 (C), 47.8 (C), 53.1 (CH), 79.2 (CH), 219.9 (C) ppm. MS (EI): m/z (%) = 196 (92) [M+], 178 (19), 134 (67), 96 (100), 81 (54), 69 (79). ESI-HRMS: m/z calcd for C12H20O2: 196.1463; found: 196.1453 [M+].

23

Data for 4a: colourless oil. IR: ν = 3447, 1699 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.90 (3 H, s), 1.02 (3 H, s), 1.12 (1 H, m), 1.15 (3 H, s), 1.50-2.15 (9 H, m), 2.20 (1 H, m), 2.56 (1 H, dt, J 1 = 7.0 Hz, J 2 = 13.9 Hz), 3.20 (1 H, dd, J 1 = 4.4 Hz, J 2 = 11.2 Hz) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.7 (CH3), 18.5 (CH3), 20.7 (CH2), 26.2 (CH2), 26.9 (CH2), 27.9 (CH3), 31.2 (CH2), 37.4 (CH2), 39.7 (C), 48.6 (C), 52.5 (CH), 78.1 (CH), 215.1 (C) ppm. MS (EI): m/z (%) = 210 (35), 192 (24), 177 (11), 121 (55), 107 (30), 95 (41), 82 (82), 69 (100). ESI-HRMS: m/z calcd for C13H22O2: 210.1620; found: 210.1628 [M+].

24

Data for 5a: white solid; mp137-139 °C. IR: ν = 3449, 1763 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.89 (3 H, s), 0.93 (3 H, s), 0.99 (3 H, s), 1.05 (1 H, m), 1.20 (3 H, s), 1.38 (2 H, m), 1.40-1.80 (5 H, m), 1.93 (2 H, m), 2.98 (2 H, m), 3.27 (1 H, m) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.1 (CH3), 17.2 (CH2), 17.9 (CH3), 23.6 (CH3), 24.8 (CH2), 37.3 (CH2), 27.8 (CH3), 33.6 (C), 39.1 (C), 41.9 (CH2), 44.0 (CH2), 47.0 (2CH), 61.2 (C) 79.1 (CH), 214.0 (C) ppm. MS (EI): m/z (%) = 208 (11) [M+ - 42], 190 (51), 175 (100), 147 (49), 120 (53), 105 (50), 95 (44), 81 (48), 69 (50), 55 (70). ESI-HRMS: m/z calcd for C16H34N2O2: 268.2271; found: 268.2253 [M+ + NH4].

25

Data for 6a: colourless oil. IR: ν = 3461, 1728 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.81 (3 H, s), 0.95 (3 H, s), 0.98 (3 H, s), 0.99 (3 H, s), 1.00-1.30 (3 H, m), 1.40-1.80 (9 H, m), 2.07 (1 H, td, J 1 = 8.9 Hz, J 2 = 19.2 Hz), 2.42 (1 H, dd, J 1 = 8.8 Hz, J 2 = 16.3 Hz), 3.22 (2 H, dd, J 1 = 5.2 Hz, J 2 = 10.8 Hz) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.1 (CH3), 16.4 (CH3), 16.8 (CH3), 18.0 (CH2), 18.3 (CH2), 26.8 (CH2), 28.1 (CH3), 33.2 (CH2), 35.6 (CH2), 37.3 (CH2), 38.8 (C), 48.1 (C), 53.3 (C) 55.9 (CH), 58.2 (CH), 78.2 (CH), 220.7 (C) ppm. MS (EI): m/z (%) = 264 (25) [M+], 231 (10), 213 (23), 203 (12), 187 (27), 175 (19), 152 (12), 135 (27), 121 (21), 107 (29), 95 (26), 81 (30), 67 (100), 55 (80). ESI-HRMS: m/z calcd for C17H28ONa: 287.1981; found: 287.1977 [M+ + Na].

26

Data for 7a: colourless oil. IR: ν = 3455, 1701 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.79 (3 H, s), 0.94 (3 H, s), 0.98 (3 H, s), 1.14 (3 H, s), 1.25 (2 H, m), 1.20-1.80 (12 H, m), 2.00-2.20 (2 H, m), 2.31 (1 H, t, J = 7.2 Hz), 2.54 (1 H, td, J 1 = 13.9 Hz, J 2 = 6.9 Hz), 3.18 (1 H, dd, J 1 = 5.2 Hz, J 2 = 11.2 Hz) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.3 (CH3), 16.4 (CH3), 17.6 (CH2), 19.7 (CH3), 19.9 (CH2), 26.1 (CH2), 27.1 (CH2), 29.9 (CH3), 34.5 (CH2), 37.5 (CH2), 38.2 (C), 38.3 (CH2), 38.8 (C), 49.0 (C), 54.9 (CH), 57.7 (CH), 78.5 (CH), 215.7 (C) ppm. MS (EI): m/z (%) = 278 (11) [M+], 263 (8), 245 (5), 227 (6), 207 (30), 189 (27), 175 (6), 161 (7), 135 (27), 121 (39), 107 (29), 95 (36), 81 (41), 67 (69), 55 (100). ESI-HRMS: m/z calcd for C18H30O2Na: 301.2138; found: 301.2139 [M+ + Na].

27

Data for 8a: colourless oil: IR: ν = 3345, 1767 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.79 (3 H, s), 0.92 (3 H, s), 0.94 (3 H, s), 0.80-1.00 (2 H, m), 0.99 (3 H, s), 1.19 (3 H, s), 1.10-1.90 (13 H, m), 2.99 (2 H, m), 3.22 (1 H, dd, J 1 = 4.6 Hz, J 2 = 11.2 Hz) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.5 (CH3), 15.7 (CH3), 16.5 (CH2), 18.4 (CH2), 19.1 (CH3), 22.9 (CH3), 24.5 (CH2), 27.1 (CH2), 28.0 (CH3), 33.9 (C), 37.5 (C), 38.1 (CH2), 38.8 (C), 44.1 (CH2), 45.9 (CH2), 47.4 (CH), 51.9 (CH), 55.1 (CH), 61.3 (C), 78.8 (CH), 214.6 (C) ppm. MS (EI): m/z (%) = 281 (2) [M+ - 37], 244 (2), 207 (4), 189 (2), 174 (2), 161 (3), 136 (11), 121 (9), 107 (8), 95 (15), 81 (56), 69 (100), 55 (19). HRMS (ESI): m/z calcd for C21H34O2Na: 341.2451; found: 341.2463 [M+ + Na].