Download PDF
Synlett 2008(20): 3208-3212  
DOI: 10.1055/s-0028-1087410
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Radical Clock for Reactions of Epoxy Derivatives Induced by Titanocene Chloride

A. Fernández-Mateos*, P. Herrero Teijón, R. Rabanedo Clemente, R. Rubio González
Departemeno de Química Orgánica, Facultad de C. Químicas, Universidad de Salamanca, Plaza de los Caídos 1-5, 37008 Salamanca, Spain
e-Mail: afmateos@usal.es;
Further Information

Publication History

Received 3 September 2008
Publication Date:
26 November 2008 (online)

    Permissions and Reprints All articles of this category

Abstract

A new radical clock based on pinene derivatives has been designed to measure the radical cyclization rate onto cyano and carbonyl groups and the radical elimination rate of OR and CN. In this system, the known rate constant of cyclobutylcarbinyl radical cleavage is used as the internal clock. At room temperature, the cyclization rate constants for 4-exo and 5-exo processes onto nitrile and aldehyde carbonyl groups are in the order of 107 to 108 s-¹. The radical elimination rate constants for CN, OH, OCHO, and OAc are in the order of 105 to 108 s-¹.

Key words

epoxides - titanium(III) - radical clock - titanocene chloride - epoxynitriles - epoxyaldehydes - epoxyketones - epoxyesters

    References and Notes

  • 1a Curran DP. In Comprehensive Organic Synthesis   Vol. 4:  Trost BM. Fleming I. Paquette LA. Pergamon; Oxford: 1991.  Chap. 4.2.1.
    Google 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.307 
    Google Scholar
  • 1c Dhimane AL. Fensterbank L. Malacria M. In Radicals in Organic Synthesis   Vol. 2:  Renaud M. Sibi MP. Wiley-VCH; Weinheim: 2001. 
    Google Scholar
  • 2a Griller D. Ingold KU. Acc Chem. Res.  1980,  13:  317 
    Google Scholar
  • 2b Newcomb M. Tetrahedron  1993,  49:  1151 
    Google Scholar
  • 2c Newcomb M. In Radicals in Organic Synthesis   Vol. 1:  Renaud M. Sibi MP. Wiley-VCH; Weinheim: 2001.  p.317-336  
    Google Scholar
  • 3a Tsang R. Fraser-Reid B. J. Am. Chem. Soc.  1986,  108:  2116 
    Google Scholar
  • 3b Tsang R. Fraser-Reid B. J. Am. Chem. Soc.  1986,  108:  8102 
    Google Scholar
  • 3c Tsang R. Dickson JK. Pak H. Walton R. Fraser-Reid B. J. Am. Chem. Soc.  1987,  109:  3484 
    Google Scholar
  • 3d Fraser-Reid B. Vite GD. Yeung B.-WA. Tsang R. Tetrahedron Lett.  1988,  29:  1645 
    Google Scholar
  • 3e Dickson JKJr. Tsang R. Llera JM. Fraser-Reid B. J. Org. Chem.  1989,  54:  5350 
    Google Scholar
  • 3f Walton R. Fraser-Reid B. J. Am. Chem. Soc.  1991,  113:  5791 
    Google Scholar
  • 3g Paquette LA. Ra CS. Silvestri TW. Tetrahedron  1989,  45:  3099 
    Google Scholar
  • 3h Knapp S. Gibson FS. Choe YH. Tetrahedron Lett.  1990,  38:  5397 
    Google Scholar
  • 3i Knapp S. Gibson FS. J. Org. Chem.  1992,  57:  4802 
    Google Scholar
  • 3j Grissom JW. Klingberg D. J. Org. Chem.  1993,  58:  6559 
    Google Scholar
  • 3k Grissom JW. Klingberg D. Meyenburg S. Stallman BL. J. Org. Chem.  1994,  59:  7876 
    Google Scholar
  • 3l Clive DLJ. Postema MHD. J. Chem. Soc., Chem. Commun.  1993,  429 
    Google Scholar
  • 3m Jung ME. Choe SWT. Tetrahedron Lett.  1993,  34:  6247 
    Google Scholar
  • 3n Hays DS. Fu GC. J. Am. Chem. Soc.  1995,  117:  7283 
    Google Scholar
  • 3o Davin P. Fensterbank L. Malacria M. Tetrahedron Lett.  1998,  39:  833 
    Google Scholar
  • 3p Beckwith ALJ. Hay BP. J. Am. Chem. Soc.  1989,  111:  230 
    Google Scholar
  • 3q Beckwith ALJ. Hay BP. J. Am. Chem. Soc.  1989,  111:  2674 
    Google Scholar
  • 3r Beckwith ALJ. Raner KD. J. Org. Chem.  1992,  57:  4954 
    Google Scholar
  • 3s Bowman WR. Bridge CF. Brookes P. Tetrahedron Lett.  2000,  41:  8989 ; and references therein
    Google Scholar
  • 3t Fallis AG. Brinza IM. Tetrahedron  1997,  52:  17543 
    Google Scholar
  • 3u Curran DP. Liu W. Synlett  1999,  117 
    Google Scholar
  • 4a RajanBabu TV. Nugent WA. J. Am. Chem. Soc.  1994,  116:  986 
    Google Scholar
  • 4b RajanBabu TV. Nugent WA. J. Am. Chem. Soc.  1988,  110:  8561 
    Google Scholar
  • 4c Daasbjerg K. Svith H. Grimme S. Gerenkamp M. Muck-Lichtenfeld C. Gansäuer A. Barchuk A. Keller F. Angew. Chem. Int. Ed.  2006,  45:  2041 ; Angew. Chem. 2006, 118, 2095
    Google Scholar
  • 4d Gansäuer A. Bluhm H. Chem. Rev.  2000,  100:  2771 
    Google Scholar
  • 4e Gansäuer A. Lauterbach T. Narayan S. Angew. Chem. Int. Ed.  2003,  42:  5556 ; Angew. Chem. 2003, 115, 5714
    Google Scholar
  • 4f Barrero AF. Quilez del Moral JF. Sánchez EM. Arteaga JF. Eur. J. Org. Chem.  2006,  1627 
    Google Scholar
  • 4g Cuerva JM. Justicia J. Oller-López JL. Bazdi B. Oltra JE. Mini-Rev. Org. Chem.  2006,  3:  23 
    Google Scholar
  • 4h Gansäuer A. Bluhm H. Pierobon M. J. Am. Chem. Soc.  1998,  120:  12849 
    Google Scholar
  • 4i Cuerva JM. Justicia J. Oller-López JL. Oltra JE. Top. Curr. Chem.  2006,  264:  63 
    Google Scholar
  • 5a Fernández-Mateos A. Martín de la Nava EM. Pascual Coca G. Rubio González R. Org. Lett.  1999,  1:  607 
    Google Scholar
  • 5b Fernández-Mateos A. Mateos Burón L. Rabanedo Clemente R. Ramos Silvo AI. Rubio González R. Synlett  2004,  1011 
    Google Scholar
  • 5c Fernández-Mateos A. Martín de la Nava EM. Mateos Burón L. Rabanedo Clemente R. Rubio González R. Sanz González F. Synlett  2004,  2553 
    Google Scholar
  • 5d Fernández-Mateos A. Herrero Teijón P. Rabanedo Clemente R. Rubio González R. Tetrahedron Lett.  2006,  47:  7755 
    Google Scholar
  • 5e Fernández-Mateos A. Herrero Teijón P. Rabanedo Clemente R. Rubio González R. J. Org. Chem.  2007,  72:  9973 
    Google Scholar
  • 5f Fernández-Mateos A. Herrero Teijón P. Rabanedo Clemente R. Rubio González R. Synlett  2007,  2718 
    Google Scholar
  • 6a Beckwith ALJ. Moad G. J. Chem. Soc., Perkin Trans. 2  1980,  1083 
    Google Scholar
  • 6b Maillard B. Walton JC. J. Chem. Soc., Perkin Trans. 2  1985,  443 
    Google Scholar
  • 7a Il’ina IV. Volcho KP. Korchagina DV. Barkash VA. Salakhutdinov NF. Helv. Chim. Acta  2007,  90:  353 
    Google Scholar
  • 7b Il’ina IV. Volcho KP. Korchagina DV. Salakhutdinov NF. Barkash VA. Russ. J. Org. Chem.  2004,  40:  1483 
    Google Scholar
  • 9 Yamamoto Y. Matsumi D. Hattori R. Itoh K. J. Org. Chem.  1999,  64:  3224 
    CrossrefGoogle Scholar
  • 10 Cuerva JM. Campaña AG. Justicia J. Rosales A. Oller-López JL. Robles R. Cárdenas DJ. Buñuel E. Oltra JE. Angew. Chem.  2006,  118:  5522 
    Google Scholar
8

Reaction of Epoxides with Cp 2 TiCl A mixture of Cp2TiCl2 (3.3 mmol) and Zn (6.60 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 mmol) was dissolved in strictly deoxygenated THF (10 mL). The green TiIII solution was slowly added via cannula to the epoxide solution. After 30 min, an excess of sat. NaH2PO4 was added, and the mixture was stirred for 20 min. The product was extracted into Et2O, washed with sat. NaHCO3 and brine, dried (Na2SO4), and filtered. After removal of the solvent, the crude product was purified by flash chromatography.
Compound 10: diastereomeric mixture (60:40). IR: 3408, 2923, 1462, 1053 cm-¹. MS (EI): m/z (%) = 192 (14) [M+ - 18], 177 (7), 163 (3), 149 (12), 135 (17), 121 (16), 119 (25), 95 (31), 91 (82), 70 (65), 55 (100). HRMS (EI): m/z calcd for C13H22O2Na [M+ + Na]: 233.1517; found: 233.1514. ¹H NMR (400 MHz, CDCl3): δ (major isomer) = 0.94 (3 H, s), 1.10 (3 H, d, J = 7.2 Hz), 1.22 (3 H, s), 1.60-2.60 (7 H, m), 3.47 (1 H, dd, J 1 = 3.3 Hz, J 2 = 8.5 Hz), 3.51 (1 H, d, J = 9.1 Hz), 3.95 (1 H, dd, J 1 = 6.8 Hz, J 2 = 8.5 Hz), 4.22 (1 H, d, J = 9.1 Hz), 4.53 (1 H, dd, J 1 = 5.2 Hz, J 2 = 9.3 Hz) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 16.17 (CH3), 23.83 (CH3), 27.77 (CH3), 30.66 (CH2), 38.15 (C), 39.31 (CH2), 40.14 (CH), 41.77 (CH), 51.50 (CH), 55.05 (C), 64.65 (CH), 72.86 (CH2), 75.30 (CH2) ppm. ¹H NMR (400 MHz, CDCl3): δ (minor isomer) = 0.87 (3 H, d, J = 7.4 Hz), 0.88 (3 H, s), 1.21 (3 H, s), 1.60-2.90 (7 H, m), 3.31 (1 H, dd, J 1 = 3.7 Hz, J 2 = 8.4 Hz), 3.37 (1 H, d, J = 8.6 Hz), 3.77 (1 H, d, J = 8.6 Hz), 4.02 (1 H, dd, J 1 = 7.4 Hz, J 2 = 8.4 Hz), 4.28 (1 H, dd, J 1 = 5.3 Hz, J 2 = 9.3 Hz), ppm. ¹³C NMR (100 MHz, CDCl3): δ = 16.60 (CH3), 23.91 (CH3), 27.63 (CH3), 30.51 (CH2), 36.37 (CH), 38.15 (C), 38.68 (CH2), 39.46 (CH), 40.92 (CH), 55.32 (C), 72.69 (CH), 72.76 (CH2), 79.34 (CH2) ppm.
Compound 11: IR: 3400, 1645 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 1.76 (3 H, s), 1.80-2.50 (5 H, m), 4.01 (1 H, m), 4.03 (2 H, s), 4.29 (1 H, s), 4.73 (1 H, s), 4.75 (1 H, s), 5.19 (1 H, d, J = 10.4 Hz), 5.27 (1 H, d, J = 15.6 Hz), 5.87 (1 H, br s), 5.89 (1 H, m) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 20.87 (CH3), 30.86 (CH2), 30.15 (CH), 35.57 (CH2), 60.30 (CH), 71.38 (CH2), 74.45 (CH2), 109.03 (CH2), 117.24 (CH2), 129.49 (CH), 134.34 (CH), 134.94 (C), 149.01 (C) ppm. MS (EI): m/z (%) = 150 (22) [M+ - 58], 135 (20), 131 (13), 108 (69), 93 (68), 91 (100), 68 (79), 55 (98). HRMS (EI): m/z calcd for C13H20O2Na [M+ + Na]: 231.1355; found: 231.1353; [α]D ²0 -49.2 (c 1.3, CHCl3).
Compound 13a1: IR: 3451, 2928, 2899, 1761, 1252, 1042 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 0.96 (3 H, s), 1.13 (1 H, d, J = 10.2 Hz), 1.21 (3 H, s), 1.64 (2 H, m), 1.94 (1 H, m), 2.24 (1 H, t, J = 5.7 Hz), 2.33 (1 H, m), 2.56 (2 H, m), 2.70 (1 H, m), 3.03 (1 H, m), 4.59 (1 H, dd, J 1 = 9.3 Hz, J 2 = 4.9 Hz) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 18.56 (CH2), 23.35 (CH3), 27.07 (CH3), 29.82 (CH2), 38.35 (CH2), 38.53 (C), 40.44 (CH), 41.63 (CH2), 50.24 (CH), 62.53 (CH), 75.80 (C), 212.49 (C) ppm. MS (EI): m/z (%) = 179 (2) [M+ - 15], 161 (2), 134 (4), 133 (17), 119 (26), 105 (100), 91 (96), 77 (30), 67 (28), 55 (68). HRMS (EI): m/z calcd for C12H18O2Na [M+ + Na]: 217.1199; found: 217.1206; [α]D ²0
-10.1 (c 1.4, CHCl3).
Compound 13a2: IR: ν = 3451, 2928, 2894, 1765, 1217 cm-¹. ¹H NMR (200 MHz, CDCl3): δ = 0.87 (3 H, s), 1.20 (1 H, d, J = 10.1 Hz), 1.28 (3 H, s), 1.50-2.40 (6 H, m), 2.54 (1 H, m), 3.01 (2 H, t, J = 8.9 Hz), 4.38 (1 H, dd, J 1 = 9.1 Hz, J 2 = 3.7 Hz) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 22.65 (CH3), 26.59 (CH3), 27.16 (CH2), 27.88 (CH2), 39.16 (CH2), 39.65 (C), 39.80 (CH), 42.98 (CH2), 48.56 (CH), 53.40 (C), 70.61 (CH), 213.39 (C) ppm. MS (EI): m/z (%) = 179 (3) [M+ - 15], 151 (3), 134 (6), 133 (24), 119 (26), 105 (100), 91 (80), 77 (40), 67 (42), 55 (89). HRMS (EI): m/z calcd for C12H18O2Na [M+ + Na]: 217.1199; found: 217.1195; [α]D ²0 +40.7. (c 1.9, CHCl3).
Compound 14a: IR: ν = 3455, 2920, 2249, 1645, 1441, 1217, 1053 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 1.62 (1 H, dt, J 1 = 4.0 Hz, J 2 = 13.3 Hz), 1.73 (3 H, s), 1.90 (4 H, m), 2.10-2.60 (4 H, m), 4.09 (1 H, br s), 4.72 (1 H, s), 4.75 (1 H, s), 5.73 (1 H, m) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 16.71 (CH2), 20.82 (CH3), 30.47 (CH2), 30.81 (CH2), 35.04 (CH), 36.85 (CH2), 66.90 (CH), 109.37 (CH2), 119.73 (C), 128.03 (CH), 134.77 (C), 148.52 (C) ppm. MS (EI): m/z (%) = 173 (6) [M+ - 18], 158 (6), 131 (9), 117 (22), 105 (21), 91 (100), 77 (23), 65 (22), 51 (23); HRMS (EI): m/z calcd for C12H17NONa [M+ + Na]:214.1208; found: 214.1205.
Compound 16a1: IR: ν = 3439, 2929, 1455, 1260, 1052 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 0.90 (3 H, s), 1.21 (3 H, s), 1.66 (4 H, m), 1.90 (1 H, m), 1.98 (1 H, t, J = 5.8 Hz), 2.10-2.60 (4 H, m), 3.93 (1 H, t, J = 6.1 Hz), 4.68 (1 H, dd, J 1 = 9.2 Hz, J 2 = 5.4 Hz) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 22.62 (CH2), 23.16 (CH3), 27.49 (CH3), 27.85 (CH2), 29.90 (CH2), 38.35 (CH2, C), 40.76 (CH), 53.12 (CH, C), 62.02 (CH), 74.68 (CH) ppm. MS (EI): m/z (%) = 177 (3) [M+ - 19], 163 (3), 149 (13), 134 (14), 121 (3), 108 (35), 92 (72), 91 (100), 67 (23), 55 (23). HRMS (EI): m/z calcd for C12H20O2Na [M+ + Na]: 219.1356; found: 219.1338. Mp 146-150 ˚C; [α]D ²0 -7.4 (c 0.6, CHCl3).
Compound 16a2: IR: n = 3445, 2929, 1453, 1260, 1051 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 0.81 (3 H, s), 1.29 (3 H, s), 1.44 (2 H, m), 1.60-1.90 (4 H, m), 2.09 (1 H, m), 2.34 (2 H, m), 2.46 (1 H, m), 3.94 (1 H, d, J = 8.2 Hz), 4.69 (1 H, dd, J 1 = 10.4 Hz, J 2 = 10.4 Hz) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 23.04 (CH3), 26.44 (CH2), 27.00 (CH3, CH2), 27.71 (CH2), 38.81 (CH2), 39.50 (CH), 39.54 (C), 43.99 (CH), 55.52 (C), 69.39 (CH), 71.48 (CH) ppm. MS (EI):
m/z (%) = 163 (3) [M+ - 33], 163 (2), 149 (1), 134 (10), 121 (4), 117 (27), 92 (51), 91 (100), 70 (23), 55 (43). HRMS (EI): m/z calcd for C12H20O2Na [M+ + Na]: 219.1356; found: 219.1344. Mp 166-168 ˚C; [α]D ²0 +33.5 (c 0.7, CHCl3).
Compound 17c: IR: 3383, 2923, 2858, 1729, 1469, 1391, 1372 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 0.89 (3 H, d, J = 6.6 Hz), 0.91 (3 H, d, J = 6.6 Hz), 1.20-2.20 (12 H, m), 2.44 (2 H, t, J = 8.9 Hz), 4.05 (1 H, br s), 5.56 (1 H, m), 9.77 (1 H, s) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 19.45 (CH3), 19.89 (CH3), 21.78 (CH2), 27.55 (CH2), 28.99 (CH2), 31.94 (CH), 33.99 (CH2), 34.06 (CH), 35.48 (CH2), 43.71 (CH2), 67.13 (CH), 125.69 (CH), 137.92 (C), 202.57 (CH) ppm. MS (EI): m/z (%) = 206 (9) [M+ - 18], 188 (3), 163 (9), 153 (13), 145 (33), 121 (12), 117 (29), 93 (35), 91 (100), 67 (67), 55 (90). HRMS (EI): m/z calcd for C14H24O2Na [M+ + Na]: 247.1674; found: 247.1681; [α]D ²0 -51.9 (c 2.1, CHCl3).
Compound 20d: IR: 3407, 2927, 1729, 1457, 1247, 1040 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 1.73 (3 H, s), 1.50-2.40 (5 H, m), 2.07 (3 H, s), 4.20 (1 H, br s), 4.51 (1 H, d, J = 6.2 Hz), 4.72 (1 H, s), 4.73 (1 H, d, J = 6.2 Hz), 4.75 (1 H, s), 5.94 (1 H, br s) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 20.78 (CH3), 20.94 (CH3), 30.80 (CH2), 34.99 (CH), 35.99 (CH2), 64.78 (CH), 66.58 (CH2), 109.27 (CH2), 130.74 (CH), 133.76 (C), 148.61 (C), 171.11 (C) ppm. MS (EI): m/z (%) = 192 (2) [M+ - 18], 167 (1), 150 (25), 132 (20), 117 (96), 91 (100), 68 (50), 53 (70). HRMS (EI): m/z calcd for C12H18O3Na [M+ + Na]: 233.1148; found: 233.1161; [α]D ²0
-108.5 (c 0.3, CHCl3).