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Synlett 2007(8): 1279-1283  
DOI: 10.1055/s-2007-980337
LETTER
© Georg Thieme Verlag Stuttgart · New York

Microwave-Assisted Copper-Catalyzed Sonogashira Reaction in PEG Solvent

Evelina Colacino, Latifa Daïch, Jean Martinez, Frédéric Lamaty*
Institut des Biomolécules Max Mousseron (IBMM), CNRS-Université Montpellier I et II, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France
Fax: +33(467)144866; e-Mail: frederic.lamaty@univ-montp2.fr;
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Publication History

Received 17 January 2007
Publication Date:
08 May 2007 (online)

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Abstract

A catalytic system composed of copper salt, potassium carbonate and appropriate poly(ethylene glycol) (PEG; liquid or solid, various molecular weight: 300< MW <3400) was developed to perform a Sonogashira arylation under microwave activation. In the presence of copper(I) iodide, various substituted diphenyl­acetylenes could be synthesized.

Key words

Sonogashira coupling - microwave - arylation - copper - poly(ethylene glycol)

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Copper-Catalyzed Sonogashira Reaction of 4-Iodoanisole (1g) with Phenylacetylene (2): Microwave-assisted reactions were performed with a Biotage Initiator 60 EXP® instrument. Temperature was measured with an IR sensor on the outer surface of the reaction vial. In a typical experiment, to a mixture of CuI (0.0043 g, 0.023 mmol, 0.1 equiv), finely powdered K2CO3 (0.047 g, 0.34 mmol, 1.5 equiv) and PEG3400-OH (0.25 g) were added 4-iodoanisole (1b; 0.053 g, 0.23 mmol, 1.0 equiv) and phenylacetylene (2; 0.046 g, 0.46 mmol, 2.0 equiv). The resulting mixture was heated by microwave irradiation at 220 °C (initial power 400 W) for 30 min. After cooling, the reaction mixture was solubilized in CH2Cl2 and precipitated in Et2O. Filtration and evaporation afforded 1-(4-methoxyphenyl)-2-phenylethyne (3b) in 58% yield (measured by 1H NMR using CH2Br2 as an internal standard). HPLC analysis did not detect the presence of by-products. The precipitate was reused in a similar reaction with finely powdered K2CO3 (0.047 g, 0.34 mmol, 1.5 equiv), 4-iodoanisole (0.053 g, 0.23 mmol, 1.0 equiv) and phenylacetylene (0.046 g, 0.46 mmol, 2.0 equiv) to give 1-(4-methoxyphenyl)-2-phenylethyne (3b) in 88% yield (measured by 1H NMR using CH2Br2 as internal standard). When PEG550-monomethylether was the solvent of choice, the workup was achieved by adding cyclohexane (0.5 mL) to the reactor containing the crude, and the supernatant was recovered and evaporated, affording 1-(4-methoxyphenyl)-2-phenylethyne (3g) in 44% yield (measured by 1H NMR using CH2Br2 as an internal standard). The lower phase was reused in a similar reaction with finely powdered K2CO3 (0.047 g, 0.34 mmol, 1.5 equiv), 4-iodoanisole (0.053 g, 0.23 mmol, 1.0 equiv) and phenylacetylene (0.046 g, 0.46 mmol, 2.0 equiv) to give 1-(4-methoxyphenyl)-2-phenylethyne (3b) in 100% yield (measured by 1H NMR using CH2Br2 as an internal standard); TLC [cyclohexane-Et2O (50:50), λ = 254 nm]: R f = 0.66; mp 58-61 °C; HPLC (λ = 214 nm): t R = 14.253 min. IR (CCl4): 2210 (w), 1500 (s), 1435 (m), 1242 (s), 1168 (m), 1030 (s), 825 (s) cm-1. 1H NMR (CDCl3, Me4Si): δ = 7.46-7.53 (m, 4 H), 7.32-7.34 (m, 3 H), 6.87 (d, J = 8.8 Hz, 2 H), 3.83 (s, 3 H). 13C NMR (CDCl3, Me4Si): δ = 159.61, 113.06, 131.46, 128.32, 127.94, 123.59, 115.37, 114.00, 89.36, 88.06, 55.32. MS (ESI+): m/z = 435 [(2 × M + H2O) + H]+, 417 [2 × M + H]+, 209 [M + H]+. HRMS: m/z calcd for C15H12O: 208.0888; found: 208.0882.