4-Methylbenzaldehyde → (R)-Phenyl(p-tolyl)methanol

Participants

Reaction Conditions

Reaction Steps

To a toluene (4.0 mL) solution of phenylboronic acid (0.24 g, 2 mmol) was added diethylzinc (6.0 mL, 6 mmol 1.0 M in hexanes). The mixture was heated at 60° C. overnight and was then cooled to ambient temperature. The mixed zinc solution was transferred to another flask containing (1S,2R,4R)-1,2-bis((7,7-dimethyl-2-morpholinobicyclo[2.2.1]heptan-1-yl)methyl)disulfane (IIIa) (51 mg, 0.1 mmol) via syringe. After 10 minutes at ambient temperature, the mixture was cooled to 0° C. and neat p-tolualdehyde (108 μL, 1 mmol) was added dropwise. The reaction was stirred at 0° C. for 24 hours and was quenched by slow addition of sat. aq. NH4Cl (3 mL) and subsequent dilution with DCM (25 mL) and 1 N aq. HCl (30 mL). After layer separation, the aqueous solution was washed twice with DCM (20 mL). The DCM layers were combined, dried over Na2SO4, and concentrated to give a yellow oil which was purified by silica gel column chromatography (1:6 ethyl acetate:n-heptane) to give (R)-phenyl-p-tolyl-methanol as a white solid (0.147 g; 74% yield; 95.9% e.e.). The optical purity was determined by normal phase HPLC using a Chiralcel OD-H chiral column (eluted with isocratic 10:90 IPA/hexane, with 0.5 mL/minute flow rate; monitoring at 254 nm).

Provenance & Evidence