Dimethyl Sulfoxide → (1R,2R,4R,5S)-4-bromo-2-(2-bromophenyl)-6-oxabicyclo[3.2.1]octan-7-one

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Reaction Steps

Bromotrimethylsilane (1.96 mL, 15.1 mmol) was added dropwise to a 0° C. solution of dimethyl sulfoxide (1.10 mL, 15.5 mmol) in chloroform (15 mL) with stirring at this temperature for 30 minutes. (−)-(1R,6R)-6-(2-bromophenyl)cyclohex-3-ene-1-carboxylic acid (4.24 g, 15.1 mmol; prepared in 93% ee, [α]D=62° (c=1.0, CHCl3), by resolution of the racemic Diels-Alder adduct between 1,3-butadiene and 2-bromocinnamic acid [see Morn, R.; Manuel, C.; Mazmanian, C. Eur. J. Med. Chem. 1976, 11, 493-499]with (R)-phenethyl amine) was added as a solid with stirring at rt for 1 h prior to the addition of diisopropylethylamine (2.65 mL, 15.2 mmol) at 0° C. followed by reflux for 24 hours. The reaction vessel contents were then cooled to rt, diluted with ethyl acetate and washed in succession with water, 5% HCl, water and brine, and the organic phase was dried over sodium sulfate. Concentration in vacuo afforded (1R,2R,4R,5S)-4-bromo-2-(2-bromophenyl)-6-oxabicyclo[3.2.1]octan-7-one as an oily solid.

Provenance & Evidence