Synlett 2004(12): 2175-2179  
DOI: 10.1055/s-2004-831310
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© Georg Thieme Verlag Stuttgart · New York

Highly Efficient p-Toluenesulfonic Acid-Catalyzed Alcohol Addition or Hydration of Unsymmetrical Arylalkynes

Nathanaël Olivi, Emmanuel Thomas, Jean-François Peyrat, Mouâd Alami*, Jean-Daniel Brion
Laboratoire de Chimie Thérapeutique, BioCIS - CNRS (UMR 8076), Université Paris Sud XI, Faculté de Pharmacie, rue J. B. Clément 92296 Châtenay-Malabry Cedex, France
Fax: +33(1)46835828; e-Mail: mouad.alami@cep.u-psud.fr;
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Publikationsverlauf

Received 4 May 2004
Publikationsdatum:
26. August 2004 (online)

Abstract

Under a catalytic amount of PTSA in aqueous or alcoholic media, activated unsymmetrical arylalkynes 1 undergo regioselective water or alcohol addition to afford successfully carbonyl compounds 2 in good to excellent yields. This new environmentally metal-free procedure, which afforded only Markovnikov adducts, is characterized by the mildness of acidic conditions and the excellent regio- and chemoselectivity.

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Typical Procedure for the PTSA-Catalyzed Hydration of Unsymmetrical Arylalkynes: To a stirred solution of 1a (162 mg, 1 mmol) in 2 mL of absolute EtOH, was added pTSA monohydrate (38 mg, 0.2 mmol). The mixture was heated at reflux for 5 h, diluted with H2O and extracted with EtOAc. The combined organic layer was washed with brine and dried over anhydrous Na2SO4. After removal of the solvent under vacuo, the crude product was purified by column chromatography on silica gel (CH2Cl2) to afford 196 mg (94%) of 2b as a yellow oil. 3-Ethoxy-1-(4-methoxy-phenyl)propan-1-one (2b): 1H NMR (270 MHz, CDCl3): δ = 7.89 (2 H, d, J = 8.9 Hz), 6.87 (2 H, d, J = 8.9 Hz), 3.79 (2 H, t, J = 6.8 Hz), 3.78 (3 H, s), 3.47 (2 H, q, J = 7.0 Hz), 3.14 (2 H, t, J = 6.7 Hz), 1.14 (3 H, t, J = 7.0 Hz). 13C NMR (67.5 MHz, CDCl3): δ = 196.7, 163.3, 130.2, 130.0, 113.5, 66.3, 65.8, 55.2, 38.4, 14.9. 1-(4-Aminophenyl)-6-hydroxyhexan-1-one (2f): 1H NMR (270 MHz, CD3OD): δ = 7.75 (2 H, d, J = 8.8 Hz), 6.63 (2 H, d, J = 8.8 Hz), 3.55 (2 H, t, J = 6.4 Hz), 2.87 (2 H, t, J = 7.6 Hz), 1.80-1.20 (6 H, m). 13C NMR (67.5 MHz, CD3OD): δ = 201.5, 153.6, 132.1, 126.8, 114.3, 62.3, 38.6, 33.5, 26.7, 26.1. 1-(2-Methoxyphenyl)hexan-1-one (2k): 1H NMR (270 MHz, CDCl3): δ = 7.61 (1 H, dd, J = 7.6 Hz, J = 1.8 Hz), 7.45-7.30 (1 H, m), 7.00-6.85 (2 H, m), 3.84 (3 H, s), 2.92 (2 H, t, J = 7.5 Hz), 1.75-1.55 (2 H, m), 1.35-1.25 (4 H, m), 0.87 (3 H, t, J = 6.9 Hz). 13C NMR (67.5 MHz, CDCl3): δ = 202.9, 158.1, 132.8, 129.9, 128.7, 120.4, 111.4, 55.2, 43.5, 31.4, 23.9, 22.3, 13.7.