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

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.

Key words

unsymmetrical arylalkyne - hydration - PTSA - ketone - alcohol addition - water

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7

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.