Trimethyl borate → (2Z)-3-(8-Chloro-4-isopropyl-7-methoxy-2,2-dimethyl-2H-chromen-6-yl)-but-2-en-1-ol

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Reaction Steps

To a solution of 6-bromo-8-chloro-4-isopropyl-7-methoxy-2,2-dimethyl-2H-chromene (Compound 19, 334 mg, 0.97 mmol) in THF (25 mL) at −78° C. tert-butyllithium (1.7 M in pentane, 1.1 mL, 1.93 mmol) was added dropwise. After stirring for 30 min, trimethyl borate (0.2 mL, 1.93 mmol) was added. The reaction mixture was slowly warmed to room temperature and stirred for 2 h. The reaction mixture was quenched with a saturated solution of NH4Cl and extracted with diethyl ether. The combined organic layers were washed with water and brine, dried (MgSO4), filtered and concentrated under reduced pressure. The crude boronic acid was treated with 3-iodo-but-2E-en-1-ol (334 mg, 1.93 mmol), 2 M sodium carbonate (2 mL), and tetrakis(triphenylphosphine)palladium (0) (30 mg) in toluene (101 mL) and methanol (1 mL). The reaction mixture was degassed via bubbling argon for 5 min. After heating to 100° C. for 6 h, the black solution was cooled to room temperature and quenched with a saturated solution of NH4Cl and extracted with diethyl ether. The combined organic layers were washed with water and brine, dried (MgSO4), filtered and concentrated under reduced pressure. Purification of the residue by flash chromatography (silica gel, 5% to 20% ethyl acetate in hexanes) gave rise to the title compound as a brown oil.

Provenance & Evidence