4,4,6-trifluoro-2-hydroxy-3,4-dihydronaphthalen-1(2H)-one → (S)-4,4,6-Trifluoro-1-isopropyl-3,4-dihydronaphthalen-2(1H)-one

Participants

Reaction Conditions

Reaction Steps

A THF solution (3.75 mL) of methyl lithium (3.05 mL, 4.88 mmol) was cooled to −78° C. with a dry ice/acetone cooling bath. A hexanes solution of isopropyl magnesium chloride (1.44 mL, 2.68 mmol) was introduced by syringe. This mixture was allowed to age for one hour at this temperature. Then a THF solution (1.75 mL) of 4,4,6-trifluoro-2-hydroxy-3,4-dihydronaphthalen-1(2H)-one (0.263 mg, 1.22 mmol) was added to the cooled solution dropwise by syringe pump over one hour. The reaction was allowed to stir at −78° C. for 4 hours and then quenched by pouring into an aqueous solution of ammonium chloride, volatiles were removed and the mixture was re-dissolved in ethyl acetate. The aqueous phase was extracted with ethyl acetate (3×), dried over sodium sulfate, filtered and concentrated to give an orange oil. The desired product, 4,4,6-trifluoro-2-hydroxy-3,4-dihydronaphthalen-1(2H)-one, was purified with a gradient heptanes/ethyl acetate eluent system on silica gel by a ISCO companion system to give the desired product, 4,4,6-trifluoro-1-isopropyl-1,2,3,4-tetrahydronaphthalene-1,2-diol, as a colorless oil (0.189 g, 0.727 mmol, 60% yield). 1H NMR (400 MHz, CDCl3) δ: 7.65 (m, 1H), 7.34 (d, J=8 Hz, 1H), 7.19 (m, 1H), 4.32 (m, 1H), 2.69 (m, 2H), 1.96 (q, J=8 Hz, 1H) 0.98 (d, J=4 Hz, 1H) 0.93 (d, J=4 Hz, 1H). MS (ESI-, infusion) 259 [(M−H)−].

Provenance & Evidence