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Synlett 2004(12): 2172-2174  
DOI: 10.1055/s-2004-830893
LETTER
© Georg Thieme Verlag Stuttgart · New York

Reaction of 2-Alkylidenetetrahydrofurans with Boron Tribromide: Chemo- and Regioselective Synthesis of 6-Bromo-3-oxoalkanoates by ­Application of a ‘Cyclization-Ring-Opening’ Strategy

Esen Bellur, Peter Langer*
Institut für Chemie und Biochemie, Ernst-Moritz-Arndt-Universität Greifswald, Soldmannstrasse 16, 17487 Greifswald, Germany
e-Mail: peter.langer@uni-greifswald.de;
Further Information

Publication History

Received 17 May 2004
Publication Date:
05 August 2004 (online)

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Abstract

6-Bromo-3-oxoalkanoates, benzofurans and 1,7-dibromoheptan-4-ones were chemo- and regioselectively prepared by ­reaction of 2-alkylidenetetrahydrofurans with boron tribromide.

Key words

boron tribromide - domino reactions - nucleophilic substitution - halogenation - tetrahydrofurans

    References

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8

Typical Experimental Procedure for 2h: To a CH2Cl2 solution (5 mL) of 3h (0.130 g, 0.5 mmol) was added BBr3 (0.525 g, 2.1 mmol) at 0 °C. The reaction mixture was allowed to warm to 20 °C during 12 h. Water (2 mL) was added and the solution was stirred for 3 h at 20 °C. The solvent was removed in vacuo and the residue was purified by column chromatography (silica gel, n-hexane-EtOAc, 30:1 to 1:1) to give 2h as a brownish solid (0.118 g, 72%). The product mainly resides in the keto tautomeric form (keto-enol = 10:1). 1H NMR (300 MHz, CDCl3): δ = 2.09 (quint, J = 6.6 Hz, 2 H, CH2), 2.68 (t, J = 6.9 Hz, 2 H, CH2), 3.35 (t, J = 6.9 Hz, 2 H, CH2-Br), 3.76 (s, 3 H, OCH3), 4.70 (s, 1 H, CH), 5.65 (br, 1 H, OH), 6.83 (d, J = 8.7 Hz, 2 H, Ar), 7.20 (d, J = 8.7 Hz, 2 H, Ar), 13.03 (br, 1 H, enol from, OH). 13C NMR (75 MHz, CDCl3): δ = 26.33, 32.69 (CH2), 39.44 (CH2-Br), 52.76 (OCH3), 63.92 (CH), 103.92 (C=C-O, enol), 115.96 (CH), 123.71 (C), 130.55 (CH), 156.08 (C), 169.64 (O=C-O), 175.04 (O-C=C, enol), 203.55 (C=O). IR (KBr): 3396 (m, OH), 3184 (w), 2957 (w, C-H), 1735 (s, O=C-O), 1703 (s, C=O), 1614 (w), 1594 (w), 1516 (s), 1439 (m), 1359 (m), 1335 (w), 1302 (w), 1274 (m), 1249 (m), 1213 (s), 1161 (m), 1095 (w), 991 (w), 832 (w), 557 (w), 528 (w) cm-1. MS (EI, 70 eV): m/z (%) = 315 (1) [M+], 284 (14), 234 (5), 203 (1), 175 (5), 165 (85), 150 (29), 118 (3), 109 (100), 106 (55). Anal. Calcd for C13H15O4Br (315.163): C, 49.54; H, 4.80. Found: C, 49.63; H, 5.03. All products gave satisfactory spectroscopic and analytical and/or high-resolution mass data.

11

Typical Experimental Procedure for 5: To a CH2Cl2 solution (10 mL) of 4 (0.150 g, 0.6 mmol) was added BBr3 (0.605 g, 2.4 mmol) at 0 °C. The reaction mixture was allowed to warm to 20 °C and was stirred for 24 h. Water (15 mL) was slowly added to the reaction mixture and the organic layer was separated. The aqueous layer was extracted with EtOAc (4 × 30 mL). The combined organic extracts were dried (Na2SO4), filtered and the filtrate was concentrated in vacuo. The residue was purified by chromatography (silica gel, n-hexane-EtOAc, 100:1 to 1:1) to give 5 (0.163 g, 92%) as a yellow oil. 1H NMR (300 MHz, CDCl3): δ = 2.34 (quint, J = 7.2 Hz, 2 H, CH2), 3.35 (t, J = 7.5 Hz, 2 H, CH2), 3.47 (t, J = 6.9 Hz, 2 H, CH2-Br), 3.95 (s, 3 H, OCH3), 7.28-7.33 (m, 2 H, 2 × CH), 7.42-7.45 (m, 1 H, CH), 7.95-7.98 (m, 1 H, CH). 13C NMR (75 MHz, CDCl3): δ = 26.83, 30.80 (CH2), 32.41 (CH2-Br), 51.44 (OCH3), 109.17 (C=C-O), 110.88, 121.87, 123.86, 124.58 (CH), 125.82, 153.62 (C), 164.52 (O=C-O), 165.17 (O-C=C). IR (neat): 2952 (m, C-H), 1714 (s, O=C-O), 1593 (s), 1478 (m), 1451 (s), 1437 (s), 1386 (m), 1342 (w), 1284 (m), 1235 (s), 1174 (s), 1127 (w), 1106 (m), 1073 (s), 1010 (w), 959 (w), 935 (w), 861 (w), 790 (m), 752 (s) cm-1. MS (EI, 70 eV): m/z (%) = 297 (38) [M+], 266 (7), 217 (16), 203 (10), 188 (100), 174 (5), 170 (29), 158 (47), 144 (4). Anal. Calcd for C13H13O3Br (297.148): C, 52.55; H, 4.41. Found: C, 52.84; H, 4.74.