Direct Synthesis of Protected Arylacetaldehydes by Palladium-Tetra­phosphine-Catalyzed Arylation of Ethyleneglycol Vinylether

Abstract

Through the use of [PdCl(C₃H₅)]₂/cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl) cyclopentane as a catalyst, a range of aryl bromides undergo Heck reaction with ethyleneglycol vinylether to give regioselectively protected arylacetaldehydes in good yields. The β-arylation products were obtained in the range 93-98% selectivity with electron-poor aryl bromides. Furthermore, this catalyst can be used at low loading, even for reactions of sterically hindered aryl bromides. The arylvinyl ethers intermediates undergo subsequent ketalization to give the corresponding 2-benzyl-1,3-dioxolane derivatives.

palladium - catalysis - tetraphosphine - Heck reaction - aryl bromides - ethyleneglycol vinylether - arylacetaldehydes

References

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<A NAME="RG13104ST-23">23</A>

As a Typical Experiment: Synthesis of 2-(4-Acetyl-benzyl)-1,3-dioxolane(1d).
The reaction of 4-bromoacetophenone (0.199 g, 1 mmol), K₂CO₃ (0.276 g, 2 mmol) and ethylene glycol vinylether (0.176 g, 2 mmol) at 130 °C during 20 h in anhyd DMF (5 mL) in the presence of the Tedicyp-palladium complex (0.1 µmol) under argon affords the corresponding coupling product after extraction with Et₂O, separation, drying (MgSO₄), evaporation and filtration on silica gel (Et₂O-/pentane 1:4) in 87% (0.179 g) isolated yield. White solid, mp 55 °C. ¹H NMR (300 MHz, CDCl₃): δ = 7.90 (d, J = 8.1 Hz, 2 H, Ar), 7.36 (d, J = 8.1 Hz, 2 H, Ar), 5.08 (t, J = 5.1 Hz, 1 H, CH₂CH), 3.95-3.80 (m, 4 H, CH ₂CH ₂), 3.02 (d, J = 5.1 Hz, 2 H, CH ₂CH), 2.56 (s, 3 H, Me). ¹³C NMR (75 MHz, CDCl₃): δ = 197.8, 141.7, 135.6, 129.9, 128.3, 103.9, 65.0, 40.6, 26.5. MS: m/z calcd for C₁₂H₁₄O₃: 206; found: 206 (19%). Anal. Calcd for C₁₂H₁₄O₃: C, 69.88; H, 6.84. Found: C, 69.62; H, 6.63. Before purification, traces of 2-methyl-2-(4-acetylphenyl)-1,3-dioxolane(1e) were also observed: ¹H NMR (300 MHz, CDCl₃): δ = 7.91 (d, J = 8.3 Hz, 2 H, Ar), 7.55 (d, J = 8.3 Hz, 2 H, Ar), 4.03 (m, 2 H, CH ₂CH ₂), 3.75 (m, 2 H, CH ₂CH ₂), 2.57 (s, 3 H, Me), 1.62 (s, 3 H, Me).

<A NAME="RG13104ST-24">24</A>

All new compounds gave satisfactory ¹H NMR, ¹³C NMR and elemental analysis data.