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

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.

alkyne - palladium - catalysis - cross-coupling

References

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6

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).