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Synlett 2004(12): 2169-2171  
DOI: 10.1055/s-2004-830892
LETTER
© Georg Thieme Verlag Stuttgart · New York

Functionalization of 2-Alkylidenetetrahydrofurans and 2-Alkylidene­pyrrolidines by Palladium(0)-Catalyzed Cross-Coupling Reactions

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 23 February 2004
Publication Date:
05 August 2004 (online)

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Abstract

2-Alkylidenetetrahydrofurans and 2-alkylidenepyrrol­idines were efficiently functionalized by bromination of the exo­cyclic double bond and subsequent palladium-catalyzed cross-coupling reactions.

Key words

bromination - cross-coupling - palladium - pyrrolidines - tetrahydrofurans

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Typical Experimental Procedure for 3a: N-Bromo-succinimide (0.879 g, 4.9 mmol) was added to a CCl4 solution (40 mL) of 2a (0.700 g, 3.8 mmol) at r.t. The reaction mixture was stirred under reflux for 3 h. The reaction mixture was allowed to cool to r.t. and Et2O (20 mL) was added. The solution was filtered and the filtrate was concentrated in vacuo. The residue was purified by column chromatography (silica gel, n-hexane-EtOAc, 100:1 to 1:1) to give 3a as a colorless solid (0.732 g, 73%). 1H NMR (300 MHz, CDCl3): δ = 1.51 (s, 9 H, Ot-Bu), 2.21 (quint, J = 7.2 Hz, 2 H, CH2), 3.13 (t, J = 7.8 Hz, 2 H, CH2), 4.37 (t, J = 7.2 Hz, 2 H, OCH2). 13C NMR (150 MHz, CDCl3): δ = 25.10 (CH2), 28.46 (CH3), 32.54 (CH2), 72.83 (C-5), 81.65 (C), 85.80 (Br-C=C), 163.38 (O=C-O), 170.80 (O-C=C). IR (KBr): ν = 2975 (w, C-H), 1694 (s, C=C-O), 1613 (s, C=C-C=O), 1370 (m), 1295 (s), 1250 (w), 1243 (w), 1210 (m), 1170 (s), 1067 (s), 1039 (w), 1023 (w), 955 (w), 934 (w), 864 (w). MS (EI, 70 eV): m/z (%) = 263 (19)[M+], 206 (100), 190 (92), 162 (4) cm-1. The exact molecular mass m/z = 262.0205 ± 2 mD [M+] for C10H15O3Br was confirmed by HRMS (EI, 70 eV). Anal. Calcd for C10H15O3Br (263.131): C, 45.65; H, 5.75. Found: C, 45.38; H, 6.03. All products gave satisfactory spectroscopic and analytical and/or high-resolution mass data.

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Typical Experimental Procedure for 4a: Tetrakis(triphenylphosphine)palladium (0.20 g, 0.017 mmol) was added to a 1,4-dioxane solution (5 mL) of 3a (0.150 g, 0.57 mmol), K3PO4 (0.726 g, 3.42 mmol) and phenylboronic acid (0.209 g, 1.71 mmol) at r.t. The reaction mixture was stirred under reflux for 6 h. The solution was allowed to cool to r.t. and a sat. solution of NH4Cl (20 mL) was added. The solution was extracted with Et2O (4 × 30 mL). The combined organic layers 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 25:1) to give 4a as a slightly yellow solid (0.128 g, 87%). 1H NMR (300 MHz, CDCl3): δ = 1.44 (s, 9 H, Ot-Bu), 2.11 (quint, J = 7.2 Hz, 2 H, CH2), 3.21 (t, J = 7.8 Hz, 2 H, CH2), 4.17 (t, J = 6.9 Hz, 2 H, OCH2), 7.20-7.34 (m, 5 H, Ph). 13C NMR (75 MHz, CDCl3): δ = 24.36 (CH2), 28.46 (CH3), 31.74 (CH2), 71.92 (C-5), 79.83 (C), 106.37 (C=C-O), 126.35, 127.60, 130.60 (CH, Ph), 136.18 (C, Ph), 167.92 (O=C-O), 170.73 (O-C=O). IR (neat): ν = 3079 (w), 2974 (m), 2921 (w), 2907 (w, C-H), 1687 (s, C=C-O), 1608 (s, C=C-C=O), 1492 (m), 1474 (m), 1452 (m), 1420 (w), 1384 (m), 1368 (m), 1321 (m), 1301 (m), 1269 (m), 1251 (m), 1231 (m), 1157 (s), 1113 (m), 1063 (s), 1038 (s), 956 (m), 930 (m), 880 (w), 839 (m), 812 (m), 778 (m), 756 (m), 697 (m), 654 (w), 508 (w) cm-1. MS (EI, 70 eV): m/z (%) = 260 (23) [M+], 203 (100), 186 (79), 169 (4), 157 (1). The exact molecular mass m/z = 260.1412 ± 2 mD [M+] for C16H20O3 was confirmed by HRMS (EI, 70 eV).