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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
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Publication History

Received 27 July 2007
Publication Date:
25 September 2007 (online)

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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

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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].