4-Bromophenetole → di-isopropyl (2R,3S)-2-[(2E)-3-(4-ethoxyphenyl)-2-propenyl]-3-hydroxybutanedioate

Participants

Reaction Steps

To a solution of diisopropyl (2R,3S)-2-allyl-3-hydroxybutanedioate (3.0 g; 11.6 mmol; 1.0 eq.) and DIEA (3.86 mL; 28.9 mmol; 2.4 eq.) in CH3CN (30.0 mL) was added 4-bromophenetole (2.0 mL; 13.9 mmol; 1.2 eq.). To this solution was added a mixture of tri-o-tolylphosphine (0.35 g; 1.16 mmol; 0.1 eq.) and palladium(II) acetate (0.03 g; 0.12 mmol; 0.01 eq.) in CH3CN (3.0 mL) which was sonicated before the addition to the reaction mixture. The reaction was stirred under argon at reflux for 2.5 h, cooled to RT and the solvents were evaporated under reduce pressure. The resulting residue was then taken up in EtOAc and washed with an aqueous saturated solution of NaCl. Evaporation of the solvent gave an oil (4.3 g). Purification by chromatography (SiO2, gradient from 20/80 EtOAc/c-hex to 100/0 EtOAc/c-hex) gave the title product as a colorless oil (4.41 g, 100%). M+(ESI): 379.3. 1H NMR (CDCl3, 300 MHz) δ 7.14 (d, J=8.6 Hz, 2H), 6.70 (d, J=8.6 Hz, 2H), 6.46 (d, J=15.6 Hz, 1H), 6.00-5.86 (m, 1H), 5.05-4.83 (m, 2H), 4.13 (dd, J=7.0 Hz, J=3.0 Hz, 1H), 3.90 (q, J=7.0 Hz, 2H), 3.10 (d, J=7.2 Hz, 1H), 2.89-2.78 (m, 1H), 2.70-2.55 (m, 1H), 2.52-2.35 (m, 1H), 1.27 (t, J=7.0 Hz, 3H), 1.22-1.00 (m, 12H).

Provenance & Evidence