PDF herunterladen
Synlett 2003(7): 0955-0958
DOI: 10.1055/s-2003-39296
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Stereoselective Preparation of Homo- and Hetero-1,1-Dihalo-1-alkenes

Patrick Le Méneza, Jean-Daniel Brion*a, Jean-François Betzerb, Ange Pancrazib, Janick Ardisson*b
a CNRS-BIOCIS, Faculté de Pharmacie, Université de Châtenay-Malabry, 92296 Châtenay-Malabry, France
Fax: +33(146)835398;
b ‘Laboratoire de Synthèse Organique Sélective et Chimie Organométallique’, CNRS-UCP-ESCOM, UMR 8123, 13 Bd de l’Hautil, 95092 Cergy-Pontoise Cedex, France
Fax: +33(130)756015; e-Mail: janick.ardisson@chim.u-cergy.fr;
Weitere Informationen

Publikationsverlauf

Received 20 March 2003
Publikationsdatum:
20. Mai 2003 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik

Abstract

Metallate rearrangements performed on 5-lithio-2,3-dihydrofuran 1 gave access to several homo- and hetero-1,1-bimetallated (or pseudo) alkenes 3 upon exposure to a cyanocuprate and quench with an electrophilic reagent Ε X. After metal/halogen exchange, several homo- or hetero-1,1-dihalo-1-alkenes were prepared stereospecifically and in good yields.

Key words

metallate rearrangement - Kocienski reaction - cuprate reagent - halogen exchange - 1,1-dihalo-1-alkene

7

Le Ménez, P.; Brion, J.-D.; Lensen, N.; Chelain, E.; Pancrazi, A.; Ardisson, J. results to be published.

10

Preparation of Z -7: A solution of the 5-lithio-2,3-dihydro-furan derivative 1 (2.5 mmol) [9] in THF (4 mL) was added, via cannula, to the solution of the bis-(trimethylsilyl) dilithio-cyanocuprate [15] at -30 °C (2.75 mmol, 1.1 equiv) in THF-Et2O (6 mL/12 mL). The mixture was stirred at -5 °C to 0 °C for 1.5 h. The mixture was then cooled at -40 °C and Bu3SnCl (4 equiv) was added. The temperature was allowed to rise to 0 °C over 1 h, stirring was maintained for 4 h, while the temperature rose to 20 °C. The reaction mixture was poured into a solution of saturated aqueous NH4Cl/concentrated ammonia (4:1) at 0 °C and stirred for 30 min before extraction with diethyl ether. After purification by chromatography on silica gel compound Z -7 was obtained in 86% yield. IR (Neat): 3298, 2954, 2923, 2871, 1571, 1463, 1244, 1180, 1046, 960, 871, 830, 743, 685, 620, 591 cm-1. 1H NMR (200 MHz, CDCl3) δ 0.0 (s, 9 H), 0.88 (m, 15 H), 1.32 (m, 6 H + OH), 1.45 (m, 6 H), 2.45 (q, J = 6.5 Hz, 2 H), 3.69 (t, J = 6.5 Hz, 2 H), 6.72 (t, J = 6.5 Hz, 1 H, J H- 119 Sn = J H- 117 Sn = 170.0 Hz). 13C NMR (50 MHz, CDCl3) δ -0.3 (3 CH3), 11.3 (3 CH2, J C- 119 Sn = 318.0 Hz, J C- 117 Sn = 304.0 Hz), 13.6 (3 CH3), 27.4 (3 CH2, J C- 119 Sn = J C- 117 Sn = 58.0 Hz), 29.2 (3 CH2, J C- 119 Sn = J C- 117 Sn = 19.0 Hz), 42.4 (CH2, J C- 119 Sn = J C- 117 Sn = 57.5 Hz), 62.1 (CH2), 147.6 (C), 150.7 (CH, J C- 119 Sn = J C- 117 Sn = 20.0 Hz). MS (CI, CH4): for major 120Sn isotope, m/z 377, 311, 308, 306, 304, 252, 250, 248, 102.

13

Preparation of Z -9, E -10 and E -11 derivatives:
A solution of the 5-lithio-2,3-dihydrofuran derivative 1 (2.5 mmol) in THF (4 mL) was added, via cannula, to the solution of the bis-[(tributyl)stannyl] dilithiocyanocuprate [9] at -30 °C (2.75 mmol, 1.1 equiv) in THF-Et2O (6 mL/12 mL). The mixture was stirred at -5°C to 0 °C for 1.5 h 30. The mixture was then cooled at -40 °C and a THF solution (1-2 mL) of the quenching agent, NIS, NBS or NCS (4.0 equiv), was added. The temperature was allowed to rise to 0 °C for 1 h, stirring was maintained for 4 h, with temperature going up to 20 °C. The reaction mixture was poured into a solution of saturated aqueous NH4Cl/concentrated ammonia (4:1) at 0 °C and stirred for 30 min before extraction with diethyl ether. The Z -9 compound was obtained in 75% yield. IR (Neat): 3324, 2950, 2920, 2870, 2850, 1594, 1461, 1376, 1180, 1044, 907, 733, 690, 664, 597 cm-1. 1H NMR (200 MHz, CDCl3) δ 0.85 (t, J = 8.0 Hz, 6 H), 0.96 (t, J = 8.0 Hz, 9 H), 1.30 (m, 6 H), 1.48 (m, 1 H, OH), 2.45 (q, J = 6.5 Hz, 2 H), 3.69 (t, J = 6.5 Hz, 2 H), 6.14 (t, J = 6.5 Hz, 1 H, J H- 119 Sn = J H- 117 Sn = 42.0 Hz). 13C NMR (50 MHz, CDCl3) δ 11.1 (3 CH2, J C- 119 Sn = 348.0 Hz, J C- 117 Sn = 332.0 Hz), 13.6 (3 CH3), 27.2 (3 CH2, J C- 119 Sn = J C- 117 Sn = 60.0 Hz), 28.6 (3 CH2, J C- 119 Sn = J C- 117 Sn = 20.0 Hz), 42.6 (CH2, J C- 119 Sn = J C- 117 Sn = 32.0 Hz), 60.9 (CH2), 110.0 (C), 145.2 (CH, J C- 119 Sn = J C- 117 Sn = 20.0 Hz). MS (CI, CH4): for major 120Sn isotope, m/z 377, 322, 307, 252. Anal. calcd for C16H33IOSn: C, 39.46; H, 6.83; I, 26.06; O, 3.29; Sn 24.37; Found: C, 39.88; H, 7.09.

14

Selected NMR spectroscopic data
Z -12: 1H NMR (200 MHz, CDCl3) δ 2.22 (q, J = 6.5 Hz, 2 H), 3.63 (t, J = 6.5 Hz, 2 H), 6.51 (t, J = 6.5 Hz, 1 H). 13C NMR (50 MHz, CDCl3) δ 40.4 (CH2), 55.5 (C), 59.9 (CH2), 143.5 (CH). E -13: 1H NMR (200 MHz, CDCl3) δ 2.37 (q, J = 7.0 Hz, 2 H), 3.72 (t, J = 7.0 Hz, 2 H), 6.90 (t, J = 7.0 Hz, 1 H). 13C NMR (50 MHz, CDCl3) δ 37.8 (CH2), 51.0 (C), 60.3 (CH2), 143.7 (CH).
14 : 1H NMR (200 MHz, CDCl3) δ 1.8 (s, 1 H), 2.44 (q, J = 6.5 Hz, 2 H), 3.76 (t, J = 6.5 Hz, 2 H), 6.48 (t, J = 6.5 Hz, 1 H). 13C NMR (50 MHz, CDCl3) δ 36.2 (CH2), 60.3 (CH2), 90.5 (C), 135.1 (CH).
E -15: 1H NMR (200 MHz, CDCl3) δ 2.43 (q, J = 7.0 Hz, 2 H), 3.69 (t, J = 7.0 Hz, 2 H), 6.51 (t, J = 7.0 Hz, 1 H). 13C NMR (50 MHz, CDCl3) δ 34.9 (CH2), 60.5 (CH2), 68.5 (C), 140.3 (CH).
Z -16: 1H NMR (200 MHz, CDCl3) δ 2.34 (q, J = 7.0 Hz, 2 H), 3.73 (t, J = 7.0 Hz, 2 H), 6.18 (t, J = 7.0 Hz, 1 H). 13C NMR (50 MHz, CDCl3) δ 39.2 (CH2), 60.4 (CH2), 75.7 (C), 137.3 (CH).