Download PDF
Synlett 2004(14): 2553-2557  
DOI: 10.1055/s-2004-834824
LETTER
© Georg Thieme Verlag Stuttgart · New York

Effect of Tether Length on Ti(III)-Mediated Cyclization of Epoxyalkenes and Unsaturated Epoxyketones

A. Fernández-Mateos*a, L. Mateos Buróna, E. M. Martín de la Navaa, 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, Universidad de Salamanca, Plaza de los Caídos 1-5, 37008 Salamanca, Spain
Further Information

Publication History

Received 12 July 2004
Publication Date:
20 October 2004 (online)

    Permissions and Reprints All articles of this category

Abstract

The chemo- and regioselectivity of the radical cyclization induced by titanocene chloride of a series of epoxyalkenes and another of unsaturated epoxyketones are investigated. 5-Exo and 6-exo cyclizations are the main processes with epoxyalkenes. 3-Exo and 4-exo cyclizations onto the carbonyl group and 6-exo and 8-endo onto the carbon-carbon double bond are the preferred processes with epoxyenones. A tandem reaction, 6-exo onto C=C, followed by a 3-exo onto C=O, and a disfavored 5-endo cyclization onto C=C are reported.

Key words

radical cyclization - titanocene chloride - unsaturated epoxyketones - cyclobutanodiol - cyclooctanodiol

    References

  • 1a Curran DP. In Comprehensive Organic Synthesis   Vol. 4:  Trost BM. Fleming I. Paquette LA. Pergamon; Oxford: 1991.  p.815 
    CrossrefGoogle Scholar
  • 1b 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.308 
    CrossrefGoogle Scholar
  • 1c Beckwith ALJ. Hay BD. J. Am. Chem. Soc.  1989,  111:  230 
    CrossrefGoogle Scholar
  • 1d Beckwith ALJ. Hay BD. J. Am. Chem. Soc.  1989,  111:  2674 
    CrossrefGoogle Scholar
  • 1e Beckwith ALJ. Raner KD. J. Org. Chem.  1992,  57:  4954 
    CrossrefGoogle Scholar
  • 1f Beckwith ALJ. Tetrahedron  1981,  37:  3073 
    CrossrefGoogle Scholar
  • 2 Srikrishna A. In Radicals in Organic Synthesis   Vol. 2:  Renaud P. Sibi MP. Wiley-VCH; Weinheim: 2001.  p.151 
    Google Scholar
  • 3a Ishibashi H. Sato T. Ikeda M. Synthesis  2002,  695 
    CrossrefGoogle Scholar
  • 3b Chatgilialoglu C. Ferreri C. Guerra M. J. Am. Chem. Soc.  2002,  124:  10765 
    CrossrefGoogle Scholar
  • 4 Bailey WF. Longstaff SC. Org. Lett.  2002,  3:  2217 
    Google Scholar
  • 5 Fernández-Mateos A. Martín de la Nava E. Pascual Coca G. Ramos Silvo A. Rubio González R. Org. Lett.  1999,  1:  607 
    CrossrefGoogle Scholar
  • 6a RajanBabu TV. Nugent WA. J. Am. Chem. Soc.  1994,  116:  986 
    Google Scholar
  • 6b Nugent WA. RajanBabu TV. J. Am. Chem. Soc.  1988,  110:  8561 
    Google Scholar
  • 7a Gansäuer A. Bluhm H. Chem. Rev.  2000,  100:  2771 
    Google Scholar
  • 7b Gansäuer A. Lauterbach T. Narayan S. Angew. Chem. Int. Ed.  2003,  42:  5556 
    Google Scholar
  • 7c Gansäuer A. Rinker B. Pierobon M. Grimme S. Gerenkamp M. Mück-Lichtenfeld C. Angew. Chem. Int. Ed.  2003,  42:  3687 
    Google Scholar
  • 7d Gansäuer A. Pierobon M. Bluhm H. Synthesis  2001,  2500 
    Google Scholar
  • 7e Gansäuer A. Bluhm H. Pierobon M. J. Am. Chem. Soc.  1998,  120:  12849 
    Google Scholar
  • 8a Yamada H. Hasegawa T. Tanaka H. Takahashi T. Synlett  2001,  1935 
    CrossrefGoogle Scholar
  • 8b Fuse S. Hanochi M. Doi T. Takahashi T. Tetrahedron Lett.  2004,  45:  1961 
    CrossrefGoogle Scholar
  • 8c Barrero AF. Cuerva JM. Herrador MM. Valdivia MV. J. Org. Chem.  2001,  66:  4074 
    CrossrefGoogle Scholar
  • 8d Barrero AF. Oltra JE. Cuerva JM. Rosales A. J. Org. Chem.  2002,  67:  2566 
    CrossrefGoogle Scholar
  • 8e Barrero AF. Rosales A. Cuerva JM. Oltra JE. Org. Lett.  2003,  5:  1935 
    CrossrefGoogle Scholar
  • 8f Haïdour A. Oltra JE. Barrero AF. Cardenas DJ. Cuerva JM. Chem.-Eur. J.  2004,  10:  1778 
    CrossrefGoogle Scholar
  • 8g Ruano G. Grande M. Anaya J. J. Org. Chem.  2002,  67:  8243 
    CrossrefGoogle Scholar
  • 9x The epoxyalkenes 1-4 were obtained by a Wittig reaction of the aldehydes I (n = 0, 1, 2, 3) followed by selective epoxidation with mCPBA in CH2Cl2 at -30 °C. The starting aldehydes I (n = 0, 1, 2, 3) have been reported in the literature
  • 9a (i) For aldehydes I, n = 0, see: Geyde RN. Aura PC. Deck K. Can. J. Chem.  1971,  49:  1764 
    Google Scholar
  • 9b (ii) For aldehyde I, n = 1, see: Fernández-Mateos A. Lopéz Barba A. J. Org. Chem.  1995,  60:  3580 
    Google Scholar
  • 9c (iii) For aldehyde I, n = 2, see: Fernández-Mateos A. Pascual Coca G. Rubio González R. Tapia Hernández C. J. Org. Chem.  1996,  61:  9097 
    Google Scholar
  • 9d

    (iv) The aldehyde I, n = 3, was obtained from I, n = 2, by Wittig reaction with Ph3P=CHOCH3, followed by treatment with HClO4 (60%) in THF. All compounds synthesized are racemic, although only one enantiomer is depicted (Figure [3] ).
  • 9e

    The epoxyketones 6-9 were obtained by a three-step sequence from the aldehydes I, n = 0, 1, 2, 3: i) Grignard reaction with vinyl magnesium bromide, ii) oxidation with Dess-Martin reagent, and iii) epoxidation with mCPBA.
  • 9f The structure of epoxyketones 6-10, in which the oxiranic oxygen and the side chain is cis, is based on spectroscopic data and comparison with the epoxy compound described by K. Mori et al., whose structure was determined by X-ray. See: Mori K. Aki S. Kido M. Liebigs Ann. Chem.  1993,  83 
    Google Scholar
  • 12 Moisan L. Hardouin C. Rousseau B. Doris E. Tetrahedron Lett.  2001,  43:  2013 
    Google Scholar
  • 14 Yet L. Tetrahedron  1999,  55:  9349 
    CrossrefGoogle Scholar
  • 15 Beckwith AL. Schiesser CH. Tetrahedron  1985,  41:  3925 
    Google Scholar
10

General Procedure. A mixture of Cp2TiCl2 (2.2 mmol) and Zn (3.0 mmol) in strictly deoxygenated THF (4 mL) was stirred at r.t. until the red solution turned green. In a separate flask, the epoxy compound (1.0 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 H2O. After removal of the solvent, the crude product was purified by flash chromatography. All homolytic cleavages were absolutely selective and always afforded the tertiary radical.

11

The relative configuration of the newly created stereocenters has been assigned by spectroscopic data and H-C correlation, except for structures 7b, 8a, and 10b, whose crystallographic data have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication numbers CCDC 234516, 2345517 and 234515, respectively. Spectroscopic data of three selected compounds: 1-(2-Hydroxy-1,5,5-trimethylbicyclo[4.1.0]hept-7-yl)-propan-2-one ( 5a). IR (film) ν = 3430, 2902, 1715, 1040 cm-1. 1H NMR (CDCl3) δ = 0.39 (1 H, d, J = 5.9 Hz), 0.87 (3 H, s), 0.90 (1 H, m), 1.00 (3 H, s), 1.01 (3 H, s), 0.90-1.30 (4 H, m), 2.13 (3 H, s), 2.13 (1 H, m), 2.79 (1 H, dd, J = 4.2, J′ = 18.8 Hz), 3.81 (1 H, t, J = 6.2 Hz) ppm. 13C NMR (CDCl3) δ = 16.29 (CH), 19.69 (CH3), 26.83 (C), 27.01 (CH2), 27.93 (C), 28.38 (CH3), 29.48 (CH3), 31.38 (CH3), 33.39 (CH2), 39.54 (CH), 42.91 (CH2), 71.96 (CH-O), 210.06 (C=O) ppm. MS (EI): m/z (%) = 210 (19) [M+], 177 (9), 153 (53), 97 (100), 71 (95). HRMS (IE): m/z calcd for C13H22O2 [M+]: 210.1619. Found: 210.1620.
7-Hydroxy-1,4,4,7a-tetramethyloctahydroinden-2-one ( 7c). IR (film) ν = 3453, 2955, 1732, 1051 cm-1. 1H NMR (CDCl3) δ = 0.81 (3 H, s), 0.90 (3 H, s), 0.94 (3 H, s), 1.09 (3 H, d, J = 6.9 Hz), 1.20-1.70 (4 H, m), 1.52 (1 H, dd, J = 7.7 Hz, J′ = 14 Hz), 2.05 (2 H, m), 2.18 (1 H, dd, J = 7.7 Hz, J′ = 18 Hz), 3.60 (1 H, dd, J = 5.2 Hz, J′ = 10.3 Hz) ppm. 13C NMR (CDCl3) δ = 8.58 (CH3), 9.54 (CH3), 20.62 (CH3), 29.32 (CH2), 31.48 (C), 32.75 (CH3), 35.17 (CH2), 39.79 (CH2), 46.75 (C), 52.01 (CH), 59.23 (CH), 79.91 (CH-O), 217.59 (C=O) ppm. MS (EI): m/z (%) = 210 (41) [M+], 177 (10), 139 (67), 110 (54), 95 (100), 69 (48), 55 (51). HRMS (IE): m/z calcd for C13H22O2 [M+]: 210.1620. Found: 210.1623.
Acetic Acid 4,4,10a-Trimethyl-8-oxododecahydrobenzo-cycloocten-1-yl Ester ( 9b). IR (film) ν = 2953, 1734, 1697, 1244 cm-1. 1H NMR (CDCl3) δ = 0.80 (3 H, s), 0.83 (3 H, s), 0.92 (3 H, s), 1.20-1.70 (11 H, m), 2.04 (3 H, s), 2.25 (2 H, m), 2.66 (2 H, m), 4.78 (1 H, dd, J = 5.6 Hz, J′ = 10 Hz) ppm. 13C NMR (CDCl3) δ = 17.60 (CH3), 21.12 (CH3), 21.27 (CH3), 24.10 (CH2), 25.43 (CH2), 31.25 (CH2), 31.70 (CH2), 31.85 (CH3), 34.81 (C), 38.72 (CH2), 40.41 (CH2), 40.56 (CH2), 41.15 (C), 49.74 (CH), 74.22 (CH-O), 170.30 (C=O), 216.62 (C=O) ppm. MS (EI): m/z (%) = 220 (9) [M+ - 60], 205 (16), 187 (9), 150 (17), 135 (11), 109 (25), 95 (30), 81 (13), 67 (41), 55 (100),(54), 55 (100). HRMS (IE): m/z calcd for C17HO3 [M+]: 280.2038. Found: 280.2033.

13

The diastereomer the 6 afforded exclusively bicyclic diol 6a′ in 70% yield (Scheme [6] ).