Reaction Steps
To a suspension of ethyltriphenylphosphonium bromide (5.24 g, 14.1 mmol) in dry THF (50 mL), n-BuLi (4.8 mL, 12 mmol, 2.5M in hexane) was added within 10 min. The reaction mixture was stirred at rt for 1 h and then cooled to 0° C. A solution of β-ketoester 6a (981 mg, 3.0 mmol) in dry THF (10 mL) was added dropwise over a period of 15 min. The resulting mixture was allowed to warm to rt and stirred for an additional 3 h. The reaction was quenched with water, the THF was removed by rotary evaporation, and the aqueous residue was extracted with ethyl acetate. The extracts were washed with brine, dried, and concentrated. Flash chromatography (5% and then 10% ethyl acetate in hexane) gave 864 mg of the Z olefmation product. To a solution of this olefin (864 mg, 2.55 mmol) in dry toluene (10 mL) were added azobis(isobutyronitrile) (418 mg, 2.55 mmol) and thiophenol (0.52 mL, 5.1 mmol). The resulting solution was heated at 85° C. for 24 h. The toluene was removed by rotary evaporation, MeOH (4 mL), THF (2 mL), and 20% NaOH (2 mL) were added, and the resulting mixture was refluxed for 24 h. THF and MeOH were removed by rotary evaporation, and the aqueous residue was adjusted to a pH of ~7 with 6M HCl. Extraction with ethyl acetate, drying, and concentration gave the crude acid which was further purified by column chromatography (10% and then 80% ethyl acetate in hexanes) to afford 583 mg (60% overall) of the acid 7a as a mixture of diastereoisomers. Crystallization from acetone/hexane afforded 204 mg (21% overall) of the pure major isomer: IR (KBr) 3300-2500, 1703, 1271, 1031 cm-1 ; 1H NMR δ7.29 (d, 1H, J=8.5 Hz), 6.61 (d, 1H, J=8.5 Hz), 6.02 (m, 1H), 5.46 (m, 2H), 5.16 m, 2H), 3.93 (s, 3H), 3.50 (d, 1H, J=4.7 Hz), 2.97 (m, 2H), 2.70 (m, 1H), 2.16 (m, 2H), 1.75 (d, 3H) J=6.7 Hz), 1.55 (s, 3H); 13C NMR δ180.0, 162.7, 155.8, 137.9, 137.7, 134.5, 132.3, 128.8, 125.0, 117.0, 116.1, 108.7, 54.7, 53.3, 48.9, 45.4, 38.7, 35.6, 22.7, 13.6.
