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Synlett 2002(2): 0328-0330
DOI: 10.1055/s-2002-19769
LETTER
© Georg Thieme Verlag Stuttgart · New York

In Situ Generation of 1-Propyne: A Useful Introduction of 1-Propyne on Unsaturated Halogenated Compounds through the Sonogashira Reaction

Estelle Abraham, Jean Suffert*
Laboratoire de Pharmacochimie de la Communication Cellulaire (UMR 7081 CNRS/ULP), Faculté de Pharmacie, 74 route du Rhin 67401 Illkirch-Cedex, France
Fax: +33(390)244310; e-Mail: jeansu@aspirine.u-strasbg.fr;
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Publication History

Received 6 November 2001
Publication Date:
02 February 2007 (online)

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Abstract

Reaction of (E/Z)-1-bromopropene with exactly 1.42 equivalents of nBuLi followed by addition of water produces in situ a THF solution of propyne. Addition of a vinylic or aromatic halogenated substrates, Pd(PPh3)2Cl2, CuI and an amine to this solution give high yield of the corresponding coupling product bearing a propyne moiety. This practical procedure avoids the use of expensive and inflammable propyne gas which need a special apparatus for bubbling it into the reaction flask.

Key words

alkyne - palladium - catalysis - cross-coupling

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Representative Procedure (Table, Entry 2):
[2,2-Dimethyl-5-(2-pent-1-en-3-ynyl-phenyl)-[1,3]dioxolan -4-ylethynyl]-trimethyl-silane: A solution of nBuLi (1.8 mL, 1.54 M in hexane, 2.73 mmol, 2.2 equiv) was slowly added to a cooled solution of (Z/E)-1-bromopropene (0.233 g, 1.92 mmol, 1.55 equiv) in anhydrous THF (2.5 mL) under argon. This solution was stirred at -78 °C during 2 hours. H2O (0.05 mL, 2.73 mmol, 2.2 equiv) was then added in one portion at -78 °C via syringe and the reaction mixture warmed to 0 °C. The halogenated substrate (0.470 g, 1.24 mmol, 1 equiv) dissolved in THF (2 mL) was added via syringe to the propyne solution, followed by Pd(Ph3P)2Cl2 (43.5 mg, 0.062 mmol, 0.05 equiv), CuI (23.6 mg, 0.124 mmol, 0.1 equiv) and iPr2NH (2.2 mL). The temperature was raised to 20 °C and the reaction followed by TLC. Then the reaction was quenched with 20 mL of a saturated NH4Cl in water and extracted with the appropriate solvent (3 × 10 mL). The organic phase was dried over Na2SO4, decolored by charcoal, filtered and the solvent was removed under reduce pressure. The crude propynylated product was purified by flash chromatography (1:99, ether-hexane) on silica gel to give the desired compound (0.418 g 98%). 1H NMR (200 MHz, CDCl3) δ 0.21 (s, 9 H, Si(CH3)3); 1.61 (s, 3 H,); 1.62 (s, 3 H); 2.01 (d, 3 H, J = 2.4 Hz); 4.38 (d, 1 H, J = 7.9 Hz); 5.38 (d, 1 H, J = 7.9 Hz); 6.05 (dq, 1 H, J trans = 16 Hz, 5 J = 2.4 Hz); 7.25-7.38 (m, 2 H, arom. H); 7.47 (d, 1 H, J trans = 16 Hz); 7.43-7.57 (m, 2 H, arom. H). 13C NMR (50 MHz, CDCl3): δ 0.44 [Si(CH3)3]; 4.5, 26.3, 26.8, 73.1, 79.2, 79.4, 88.5, 93.3, 100.8, 110.4, 111.5, 125.6, 126.2, 128.4, 128.5, 134.0, 135.6, 137.2. IR (CHCl3, cm-1) 3668 (w); 3026 (m, CH); 2991 (m, CH); 2962 (s); 2918 (m); 2217 (m); 2177 (m, C≡C); 1600 (m); 1453 (m); 1383 (w); 1255 (w); 1210 (w); 1163 (w); 1100 (w); 1052 (w); 990 (w); 956 (m).