A Molten n-Bu₄NOAc/n-Bu₄NBr Mixture as an Efficient Medium for the Stereoselective Synthesis of (E)- and (Z)-3,3-Diarylacrylates

Abstract

The palladium-catalyzed reaction of neutral, slightly electron-rich and slightly electron-poor aryl iodides with methyl cinnamate in a molten n-Bu₄NOAc/n-Bu₄NBr 2:1.5 mixture provides a highly stereoselective route to (E)-3,3-diarylacrylates. Phosphine-free Pd(OAc)₂ is employed as precursor of Pd(0) species. The reaction of a variety of methyl 3-arylacrylates with phenyl iodide under the same reaction conditions affords stereoselectively the corresponding (Z)-isomers. The catalyst system can be recycled several times.

Heck reaction - stereoselectivity - molten salts - palladium - aryl halides

References

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See for examples:

5a Himmelsbach F, Austel V, Linz G, Pieper H, Guth B, Mueller T, and Weisenberger J. inventors; Eur Pat. EP  587,134.  ; Chem. Abstr. 1995, 122, 81372k

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11

The stereochemistry of vinylic substitution products obtained via our model reaction was established by NOE experiments on pure isomers. That of the other vinylic substitution derivatives has been assigned based on these data.

12

Interestingly, methyl 3-(p-methoxyphenyl)-3-phenylacrylate and methyl cinnamate were recovered in only 30 and 20% yield, respectively, when they were separately subjected to n-Bu₄NOAc at 100 °C for 7 h omitting all the other reactants. The corresponding acids were isolated in 70 and 67% yield.

13

A typical procedure for the preparation of 3 is as follows:
to a stirred solution of methyl cinnamate (0.104 g, 0.641 mmol), p-iodoanisole (0.225 g, 0.962 mmol), tetrabutylammonium acetate (0.387 g, 1.284 mmol) and tetrabutylammonium bromide (0.310 g, 0.962 mmol) at 100 °C under argon, palladium diacetate (0.007 g, 0.032 mmol) was added. The mixture was stirred at the same temperature for 3 h. Then it was diluted with ethyl acetate, washed with water, dried over Na₂SO₄, and evaporated under vacuum. The residue was chromatographed on silica gel eluting with n-hexane/ethyl acetate (92/8 v/v) to afford 0.134 g (78%) of methyl 3-(p-methoxyphenyl)-3-phenylacrylate (E:Z > 99:1). A sample was further purified through preparative HPLC to give pure methyl (E)-3-(p-methoxyphenyl)-3-phenylacrylate: Mp 70-71 °C; IR (KBr): 1724 cm^-1; ¹H NMR: δ = 7.43-7.38 (m, 3 H), 7.30-7.20 (m, 4 H), 6.89-6.82 (m, 2 H), 6.35 (s, 1 H), 3.82 (s, 3 H), 3.62 (s, 3 H); ¹³C NMR: δ = 166.6, 160.9, 156.9, 139.1, 133.1, 129.8, 129.1, 128.1, 127.9, 114.7, 113.8, 55.4, 51.2; MS: m/z (relative intensity) = 268(100) [M⁺], 237(81), 165(47), 135(36). Anal. Calcd for C₁₇H₁₆O₃: C, 76.12; H, 6.01. Found: C, 76.01; H, 6.12.

Selected NMR and MS data for (Z)-3-(p-methoxyphenyl)-3-phenylacrylate: ¹H NMR: δ = 7.36-7.29 (m, 5 H), 7.20-7.15 (m, 2 H), 6.94-6.89 (m, 2 H), 6.29 (s, 1 H), 3.85 (s, 3 H), 3.65 (s, 3 H); ¹³C NMR: δ = 166.6, 159.8, 157.1, 141.5, 130.9, 130.8, 129.4, 128.6, 128.3, 116.2, 113.2, 55.2, 51.2; Anal. Calcd for C₁₇H₁₆O₃: C, 76.15; H, 6.02. MS: m/z (relative intensity)= 268(100) [M⁺], 237(77), 165(53), 135(30).

14

A typical procedure for the preparation of cinnamate esters is as follows: to a solution of methyl acrylate (422 µL, 4.68 mmol), p-iodoanisole (365 mg, 1.56 mmol), and Et₃N (653 µL, 4.68 mmol) in DMF (2 mL) Pd(OAc)₂ (7 mg, 0.03 mmol) was added. The solution was stirred at 80 °C for 24 h under argon. After cooling, the reaction mixture was diluted with ethyl acetate, washed with water, dried over Na₂SO₄, and evaporated under vacuum. The residue was chromatographed on silica gel eluting with n-hexane/ethyl acetate (90/10 v/v) to afford 279 mg (93% yield) of methyl 3-(p-methoxyphenyl)acrylate: Mp 87-88 °C; IR (KBr): 1717 cm^-1; ¹H NMR: δ = 7.64 (d, 1 H, J = 15.94 Hz), 7.50-7.43 (m, 2 H), 6.92-6.86 (m, 2 H), 6.30 (d, 1 H, J = 16 Hz), 3.83 (s, 3 H), 3.79 (s, 3 H); ¹³C NMR: δ = 167.8, 161.4, 144.5, 129.7, 127.1, 115.3, 114.3, 55.4, 51.6; MS: m/z (relative intensity) = 192(73) [M⁺], 161(100), 133(27). Anal. Calcd for C₁₁H₁₂O₃: C, 68.74; H, 6.29. Found: C, 68.60; H, 6.37.

15

Recycles were carried out by extracting the reaction mixture with diethyl ether and adding n-Bu₄OAc to the mixture of the remaining ammonium salts to restore the proper amount of acetate anions (during the vinylic substitution reaction acetate anions are converted into acetic acid, which is lost in the extraction).

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