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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;
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Publication History

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

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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

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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).