Trimethyl borate → (alphaR)-2-Bromo-5-chloro-alpha-methylbenzenemethanol

Participants

Reaction Conditions

Reaction Steps

Trimethylborate (1.74 mL, 15.4 mmol) was added to a stirred solution of (S)-(−)-alpha,alpha-diphenyl-2-pyrrolidinemethanol (3.24 g, 12.8 mol) in tetrahydrofuran (350 mL) at room temperature. After 1.25 h, borane-methyl sulfide complex (70.4 mL of a 2M solution in tetrahydrofuran, 0.141 mol) was added slowly and a gentle effervesence was observed. The resulting solution was cooled to approximately 0° C. and a solution of 1-(2-bromo-5-chlorophenyl)ethanone (3-3) (30.0 g, 0.128 mmol) in tetrahydrofuran (150 mL) was then added uniformly over 1 h. After the addition, the resulting mixture was allowed to warm to ambient temperature and aged overnight. The reaction mixture was concentrated under reduced pressure to approximately one quarter of its original volume, poured into 1N hydrochloric acid and extracted three times with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (9% ethyl acetate/hexanes as eluent) afforded 3-4 as a colorless solid (25.8 g; 98:2 S/R enantiomeric ratio).

Provenance & Evidence