A Pd(OAc)₂-Mediated One-Pot Synthesis of Trisubstituted Alkenes via Michael Addition of a Stabilized Ylide to Baylis-Hillman Adducts [1]

Abstract

A simple and efficient stereoselective synthesis of Z- and E-isomers of trisubstituted alkenes has been developed by treating Baylis-Hillman (BH) acetates with palladium acetate and the ­stabilized ylide (ethoxycarbonylmethylene)triphenylphosphorane. ­Several ethyl acrylate and acrylonitrile-derived BH acetates were used as substrates, which yielded the corresponding trisubstituted alkenes stereoselectively in good yields.

Key words

Baylis-Hillman adducts - palladium acetate - E- and Z-trisubstituted alkenes - stabilized ylide

1

IICT communication No: 060602.

References and Notes

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1

IICT communication No: 060602.

10

Typical Experimental Procedure: To a solution of the Baylis-Hillman acetate (0.0016 mol) in anhyd benzene (8 mL) were added(ethoxycarbonylmethylene)triphenylphos-phorane (0.0016 mol) and Pd(OAc)₂ (6 mol%) and the solution was heated to reflux for 10-13 h (monitored by TLC). After completion of the reaction, H₂O (2 mL) was added to the reaction mixture, which was extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with H₂O and brine, dried over anhyd Na₂SO₄, concentrated in vacuo and the crude product was purified by flash column chromatography. The yields of the trisubstituted alkenes are given in the Table [1] .
Spectroscopic data for selected compounds are given as follows: Compound 1a: ¹H NMR (200 MHz, CDCl₃): δ = 7.70 (s, 1 H), 7.30-7.41 (m, 5 H), 4.28 (q, J = 6.9 Hz, 2 H), 4.11 (q, J = 6.9 Hz, 2 H), 2.85-2.88 (m, 2 H), 2.51-2.56 (m, 2 H), 1.40 (t, J = 6.9 Hz, 3 H), 1.27 (t, J = 6.9 Hz, 3 H). IR (KBr): 1730, 1709, 1250, 1095 cm^-1. ESI-MS: m/z = 299 [M + Na]⁺. Compound 2a: ¹H NMR (300 MHz, CDCl₃): δ = 7.69 (s, 1 H), 7.25 (d, J = 7.5 Hz, 2 H), 7.18 (d, J = 8.3 Hz, 2 H), 4.26 (q, J = 7.5 Hz, 2 H), 4.11 (q, J = 6.8 Hz, 2 H), 2.81-2.87 (m, 2 H), 2.48-2.54 (m, 2 H), 2.37 (s, 3 H), 1.35 (t, J = 6.8 Hz, 3 H), 1.25 (t, J = 7.5 Hz, 3 H). IR (KBr): 1737, 1710, 1250, 1050 cm^-1. ESI-MS: m/z = 313 [M + Na]⁺. Compound 6a: ¹H NMR (300 MHz, CDCl₃): δ = 7.62 (s, 1 H), 7.53-7.59 (m, 1 H), 7.46-7.50 (m, 1 H), 7.28-7.35 (m, 2 H), 4.28 (q, J = 7.5 Hz, 2 H), 4.11 (q, J = 6.8 Hz, 2 H), 2.81-2.83 (m, 2 H), 2.50-2.55 (m, 2 H), 1.37 (t, J = 7.5 Hz, 3 H), 1.26 (t, J = 6.8 Hz, 3 H). IR (KBr): 2961, 1715, 1711, 1260, 1252, 1072, 1028 cm^-1. ESI-MS: m/z = 355 [M + H]⁺, 379 [M + Na + H]⁺. Compound 7a: ¹H NMR (200 MHz, CDCl₃): δ = 7.48-7.87 (m, 5 H), 7.16 (s, 1 H), 4.16 (q, J = 6.9 Hz, 2 H), 2.60-2.81 (m, 4 H), 1.26 (t, J = 6.9 Hz, 3 H). IR (KBr): 2978, 2208, 1732, 1225 cm^-1. ESI-MS: m/z = 252 [M + Na]⁺. Compound 8a: ¹H NMR (200 MHz, CDCl₃): δ = 7.73-7.74 (m, 2 H), 7.52 (d, J = 7.6 Hz, 1 H), 7.26-7.33 (m, 1 H), 6.92 (s, 1 H), 4.15 (q, J = 6.8 Hz, 2 H), 2.60-2.76 (m, 4 H), 1.27 (t, J = 6.8 Hz, 3 H). IR (KBr): 2980, 2218, 1733, 1618, 1375, 1218 cm^-1. ESI-MS: m/z = 330 [M + Na]⁺, 332 [M + Na + 2 × H⁺]. Compound 9a: ¹H NMR (400 MHz, CDCl₃): δ = 7.59 (d, J = 7.8 Hz, 2 H), 7.19-7.29 (m, 2 H), 6.96 (s, 1 H), 4.15 (q, J = 7.0 Hz, 2 H), 2.70-2.83 (m, 2 H), 2.63-2.67 (m, 2 H), 2.41 (s, 3 H), 1.27 (t, J = 7.0 Hz, 3 H). IR (KBr): 2982, 2209, 1734, 1617, 1375, 1184 cm^-1. ESI-MS: m/z = 244 [M + H]⁺, 266 [M + Na]⁺.