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Synlett 2005(17): 2603-2606  
DOI: 10.1055/s-2005-917093
LETTER
© Georg Thieme Verlag Stuttgart · New York

Cyclization Reactions of Vinyl Radicals via 1,6-H-Atom Transfer: Facile Access to 2,3-Disubstituted Dihydrobenzofurans

Hechun Lin, Andreas Schall, Oliver Reiser*
Institute of Organic Chemistry, University of Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany
Fax: +49(941)9434121; e-Mail: Oliver.Reiser@chemie.uni-regensburg.de;
Further Information

Publication History

Received 26 July 2005
Publication Date:
05 October 2005 (online)

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Abstract

A new method for the synthesis of 2,3-disubstituted dihydrobenzofurans is reported making use of radical formation via translocation by 1,6-hydrogen atom transfer and subsequent 5-exo-trig cyclization.

Key words

dihydrobenzofurans - radicals - hydrogen transfer - ring-closure - radical reactions

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General Procedure for the Radical Cyclizations of Vinyl Bromides. To a refluxing solution of vinyl bromide (0.5 mmol) and AIBN (11 mg, 0.065 mmol) in benzene (7 mL) was added Bu3SnH (264 µL, 1.0 mmol) and AIBN (11 mg, 0.065 mmol) in 10 mL benzene via a syringe pump within 3 h (3.5 mL/h). After refluxing the reaction mixture for one additional hour, the solvent was removed, and to the residue was added DBU (1.5 mmol) in 10 mL of Et2O to remove the tin halides, followed by titration with 0.1 M iodide solution and filtration of the solution through silica.18 The crude product was purified by column chromatography on silica (EtOAc-hexane in an appropriate ratio) to give the benzofurane product.

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Representative Spectroscopic Data. Compound 5c: trans/cis 67:33 (GC); colorless oil. IR (NaCl): 1195, 1496, 1621, 1732, 2982 cm-1. cis-Isomer: 1H NMR (300 MHz, CDCl3): δ = 1.26 (t, 3 H, J = 6.9 Hz, CH3), 2.47-2.63 (m, 2 H, CH2), 3.74 (s, 3 H, CH3), 3.88-3.99 (m, 1 H, CH), 4.18 (q, 2 H, J = 7.2 Hz, CH2), 5.18-5.33 (br, 3 H, CH, CH2), 5.83-5.96 (m, 1 H, CH), 6.68-6.76 (br, 3 H, 3 CH). 13C NMR (300 MHz, CDCl3): δ = 14.2 (CH3), 35.5 (CH2), 41.8 (CH), 55.7 (CH3), 60.7 (CH2), 86.4 (CH), 109.7 (CH), 110.7 (CH), 113.5 (CH), 119.0 (CH2), 130.7 (C), 133.0 (CH), 152.9 (C), 154.3 (C), 172.0 (C). trans-Isomer: 1H NMR (300 MHz, CDCl3): δ = 1.28 (t, 3 H, J = 6.9 Hz, CH3), 2.56-2.76 (m, 2 H, CH2), 3.55-3.61 (m, 1 H, CH), 3.74 (s, 3 H, CH3), 4.18 (q, 2 H, J = 7.2 Hz, CH2), 4.76-4.84 (m, 1 H, CH), 5.30-5.48 (m, 2 H, CH2), 5.91-6.07 (m, 1 H, CH), 6.68-6.76 (br, 3 H, 3 CH). 13C NMR (300 MHz, CDCl3): δ = 14.2 (CH3), 38.9 (CH2), 44.8 (CH), 56.0 (CH3), 60.8 (CH2), 89.1 (CH), 109.7 (CH), 110.8 (CH), 113.7 (CH), 117.1 (CH2), 129.8 (C), 136.5 (CH), 153.1 (C), 154.3 (C), 171.5 (C). MS (EI): m/z (relative intensity) = 262 (97) [M+], 187 (15), 174 (100), 157 (12), 147 (7), 115 (17), 91 (26), 77 (21). HRMS: m/z calcd for C15H18O4 [M+]: 262.1205; found: 262.1207. Anal. Calcd for C15H18O4: C, 68.68; H, 6.92. Found: C, 68.45; H, 6.41.
Compound cis-13: colorless oil. IR (NaCl): 1197, 1477, 1597, 1734, 2982 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.27 (t, 3 H, J = 7.2 Hz, CH3), 1.30 (t, 3 H, J = 7.2 Hz, CH3), 2.55-2.70 (m, 2 H, CH2), 4.10-4.36 (br, 5 H, CH, 2 CH2), 5.27 (d, 1 H, J = 9.0 Hz, CH), 6.84-6.94 (br, 2 H, 2 CH), 7.10-7.21 (br, 2 H, 2 CH). 13C NMR (300 MHz, CDCl3): δ = 14.2 (2 CH3), 35.8 (CH2), 40.8 (CH), 60.9 (CH2), 61.5 (CH2), 82.5 (CH), 110.1 (CH), 121.4 (CH), 124.3 (CH), 128.0 (C), 129.1 (CH), 158.7 (C), 169.1 (C), 171.2 (C). MS (EI): m/z (relative intensity) = 278 (20) [M+], 232 (8), 204 (49), 191 (48), 131 (100), 118 (17), 91 (9), 77 (10). HRMS: m/z calcd for C15H18O5 [M+]: 278.1154; found: 278.1156.
Compound trans-13: colorless oil. IR (NaCl): 1197, 1477, 1597, 1734, 2982 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.26 (t, 3 H, J = 7.2 Hz, CH3), 1.30 (t, 3 H, J = 7.2 Hz, CH3), 2.73-2.80 (m, 2 H, CH2), 3.98-4.10 (m, 1 H, CH), 4.18 (t, 2 H, J = 7.2 Hz, CH2), 4.27 (t, 2 H, J = 7.2 Hz, CH2), 4.93 (d, 1 H, J = 5.7 Hz, CH), 6.86-6.95 (br, 2 H, 2 CH), 7.12-7.22 (br, 2 H, 2CH). 13C NMR (300 MHz, CDCl3): δ = 14.2 (2 CH3), 39.7 (CH2), 42.9 (CH), 60.9 (CH2), 61.7 (CH2), 84.1 (CH), 110.1 (CH), 121.4 (CH), 124.3 (CH), 127.6 (C), 129.1 (CH), 158.8 (C), 170.5 (C), 171.0 (C). MS (EI): m/z (relative intensity) = 278 (7) [M+], 232 (10), 204 (23), 191 (98), 131 (100), 118 (19), 91 (12), 77 (12). HRMS: m/z calcd for C15H18O5 [M+]: 278.1154; found: 278.1153.