3-Arylpropanoate Esters through the Palladium-Catalyzed Reaction of Aryl Halides with Acrolein Diethyl Acetal

Abstract

The reaction of aryl halides with acrolein diethyl acetal in the presence of Pd(OAc)₂, n-Bu₃N, and n-Bu₄NCl in DMF at 90 °C affords ethyl 3-arylpropanoates. A variety of functional groups are tolerated in the aryl halides, including ether, aldehyde, ketone, ester, nitrile, and nitro groups. ortho-Substituents do not hamper the reaction. 3-Arylpropanoate esters were isolated in good to excellent yields with many neutral, electron-rich and electron-poor aryl iodides and electron-poor aryl bromide. Neutral and electron-rich aryl bromides gave the desired ester in moderate yields.

Key words

palladium - alkenes - esters - aryl halides - Heck reaction

References

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6

Typical Procedure for the Preparation of Ethyl 3-Arylpropanoates ( 5). To a solution of 2-iodo-4-nitrotoluene (0.132 g, 0.501 mmol), acrolein diethylacetal (0.229 mL, 1.50 mmol), n-Bu₄NCl (0.139 g, 0.50 mmol), n-Bu₃N (0.238 mL, 1.00 mmol) in 2.0 mL of DMF, Pd(OAc)₂ (0.003 g, 0.015 mmol) was added. The mixture was warmed at 90 °C and stirred for 1 h. After cooling, the reaction mixture was diluted with 2 N HCl and extracted with Et₂O. The organic layer was dried over Na₂SO₄ and concentrated under reduced pressure. The residue was purified by chromatography (n-hexane/EtOAc 85/15 v/v) to give 0.109 g of 5z (92% yield) as an oil. IR (KBr): 1733, 1521, 1348 cm^-1. ¹H NMR (CDCl₃): δ = 8.01 (d, J ₁ = 2.3 Hz, 1 H), 7.95 (dd, J ₁ = 8.3 Hz, J ₂ = 2.4 Hz, 1 H), 7.28 (d, J = 8.3 Hz, 1 H), 4.14 (q, J ₁ = 7.1 Hz, 2 H), 3.01 (t, J ₁ = 7.5 Hz, 2 H), 2.64 (t, J ₁ = 7.5 Hz, 2 H), 2.42 (s, 3 H), 1.24 (t, J ₁ = 7.1 Hz, 3 H). ¹³C NMR (CDCl₃): δ = 172.3, 146.5, 144.2, 140.3, 131.0, 123.2, 121.4, 60.7, 33.9, 28.0, 19.6, 14.1. MS: m/z (%) = 237 (55) [M⁺], 192 (70), 191 (53), 164 (78), 150 (100), 91(95). Anal. Calcd for C₁₂H₁₅NO₄: C, 70.65; H, 6.37; N, 5.90. Found: C, 70.61; H, 6.34; N, 5.95.

7

Compound 6i was prepared according to the ref. [2] , omitting treatment with HCl.

8

Diiodobenzene (0.5 mmol), acrolein diethyl acetal (3 mmol), Pd(OAc)₂ (6 mol%), n-Bu₃N (2 mmol), n-Bu₄NCl (1.5 mmol), DMF (1 mL).
3-[2-(2-Ethoxycarbonyl-ethyl)-phenyl]-propionic Acid Ethyl Ester ( 8a). Oil. IR (neat): 1734 cm^-1. ¹H NMR (CDCl₃): δ = 7.17 (s, 4 H), 4.15 (q, J ₁ = 7.1 Hz, 4 H), 2.99 (t, J = 7.7 Hz, 4 H), 2.62 (t, J ₁ = 7.7 Hz, 4 H), 1.26 (t, J ₁ = 7.1, Hz, 6 H). ¹³C NMR (CDCl₃): δ = 172.9, 138.4, 129.1, 126.7, 60.6, 35.4, 27.6, 14.3. MS: m/z (%) = 278 (16) [M⁺], 233 (34), 186 (90), 158 (100), 144 (34), 130 (64), 117 (91). Anal Calcd for C₁₆H₂₂O₄: C, 69.04; H, 7.97. Found: C, 69.11; H, 7.94.
3-[4-(2-Ethoxycarbonyl-ethyl)-phenyl]-propionic Acid Ethyl Ester ( 8b). Mp 65-66 °C. IR (KBr): 1725 cm^-1. ¹H NMR (CDCl₃): δ = 7.13 (s, 4 H), 4.13 (q, J ₁ = 7.2 Hz, 4 H), 2.92 (t, J = 8.0 Hz, 4 H), 2.60 (t, J ₁ = 8.0 Hz, 4 H), 1.25 (t, J ₁ = 7.2, Hz, 6 H). ¹³C NMR (CDCl₃): δ = 173.0, 138.5, 128.5, 60.5, 36.0, 30.6, 14.3. MS: m/z (%) = 278 (24) [M⁺], 233 (10), 204 (60), 190 (27), 159 (16), 130 (57), 117 (100). Anal. Calcd for C₁₆H₂₂O₄: C, 69.04; H, 7.97. Found: C, 69.09; H, 7.93.