7-bromo-2-methylidene-3,4-dihydronaphthalen-1-one

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Anhydrous THF (200 mL) was added to a flame dried flask charged with anhydrous cerium (III) chloride (3.90 g, 15.8 mmol) under dry nitrogen. The mixture was vigorously stirred for 2 hours to provide an opaque suspension. The suspension was cooled to −78° C. Methyllithium (1.6 M in diethylether) (9.89 mL, 15.8 mmol) was added to the suspension of cerium(III) chloride to produce a bright yellow solution of methylcerium(III) dichloride. After stirring for 1 hour at −78° C., a solution of 7-bromo-2-methylene-3,4-dihydronaphthalen-1(2H)-one from step C1 (1.5 g, 6.33 mmol) in THF (20 mL) was added. The reaction mixture was allowed to stir for 30 min at −78° C., then it was poured into an Erlenmeyer flask charged with saturated aqueous ammonium chloride solution. The aqueous mixture was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified using silica gel column chromatography (10:1 Hex/EtOAc) to afford 7-bromo-1-methyl-2-methylene-1,2,3,4-tetrahydronaphthalen-1-ol (0.670 g, 2.66 mmol, 42% yield) as a clear viscous oil. 1H NMR (500 MHz, chloroform-d) δ 7.81 (d, J=2.0 Hz, 1H), 7.29 (dd, J=8.1, 2.1 Hz, 1H), 6.93 (d, J=8.1 Hz, 1H), 5.29-5.25 (m, 1H), 4.98 (d, J=1.2 Hz, 1H), 2.86-2.76 (m, 2H), 2.65-2.57 (m, 2H), 1.87-1.84 (m, 1H), 1.60 (s, 3H). to stir for 30 min at −78° C. it was poured into an Erlenmeyer flask The aqueous mixture was extracted with ethyl acetate The combined organic layers were washed with brine dried over sodium sulfate filtered concentrated in vacuo The residue was purified

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 7-bromo-3,4-dihydronaphthalen-1(2H)-one (2.00 g, 8.89 mmol) in THF (50 mL) was added to a mixture of N-methylanilinium trifluoroacetate (2.95 g, 13.3 mmol) and paraformaldehyde (1.20 g, 40.0 mmol) at rt. The resulting mixture was heated at reflux for 6 hours. The oil bath was removed and the mixture was allowed to cool to rt. Diethyl ether was added to the reaction mixture, which induced the separation of a red gum. The ethereal solution was decanted from the red gum into a separatory funnel and washed with half-saturated sodium bicarbonate solution. The red gum was triturated with diethyl ether, and the resulting ethereal solution was then used to extract the washing water. The combined organic layers were dried over magnesium sulfate. Filtration and concentration of the organic layer afforded a heavy red oil. The oil was purified using silica gel column chromatography (20:1 hexanes/EtOAc) to afford 7-bromo-2-methylene-3,4-dihydronaphthalen-1(2H)-one (0.850 g, 3.59 mmol, 40% yield) as a thick viscous yellow oil. 1H NMR (400 MHz, chloroform-d) δ 8.23 (d, J=2.0 Hz, 1H), 7.60 (dd, J=8.2, 2.1 Hz, 1H), 7.16 (d, J=8.3 Hz, 1H), 6.26 (q, J=1.3 Hz, 1H), 5.50 (q, J=1.7 Hz, 1H), 3.01-2.91 (m, 2H), 2.91-2.82 (m, 2H). The resulting mixture was heated at reflux for 6 hours The oil bath was removed Diethyl ether was added to the reaction mixture, which the separation of a red gum The ethereal solution was decanted from the red gum into a separatory funnel washed with half-saturated sodium bicarbonate solution The red gum was triturated with diethyl ether to extract the washing water The combined organic layers were dried over magnesium sulfate Filtration and concentration of the organic layer afforded a heavy red oil The oil was purified