Reaction #7771

Reaction equation

NH4Cl

BF3 Et2O

(±)(1S*,2R*,4S*)-4-(benzyloxy)-1,2-epoxycyclohexane

1-Methanesulfonyl-4-methylsulfanyl-benzene

nBuLi

→

(±)(1R*,2R*,5S*)-5-benzyloxy-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexanol

Yield 80.3%

Solvents

THF

EtOAc

THF

Conditions

Workup

1. 1
   workup.ADDITIONAfter an addition 1 h at −78° C.
2. 2
   Temperaturethe solution was warmed to 0° C
3. 3
   workup.WAITAfter 2 h
4. 4
   Temperaturethe solution was cooled to −78° C.
5. 5
   TemperatureThe solution was warmed to rt
6. 6
   WashThe organic layer was washed with brine
7. 7
   Otherdried
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated

Procedure

1-Methanesulfonyl-4-methylsulfanyl-benzene (3.25 g) was dissolved in THF (50 mL) and cooled to −78° C. prior to the addition of 1.6 M nBuLi (10 mL). After 0.5 h, BF3-Et2O (2.04 mL) was added followed by (±)(1S*,2R*,4S*)-4-(benzyloxy)-1,2-epoxycyclohexane (2.19 g) (Chini et al. J. Org. Chem. 1990, 55, 4265) in THF (20 mL). After an addition 1 h at −78° C., the solution was warmed to 0° C. After 2 h, the solution was cooled to −78° C. and saturated NH4Cl solution (aq) was added. The solution was warmed to rt and EtOAc was added. The organic layer was washed with brine, dried, filtered, and concentrated. Flash chromatography of the resulting residue gave (±)(1R*,2R*,5S*)-5-benzyloxy-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexanol (3.5 g) as the major product: 1H NMR (CDCl3, δ ppm, 300 mHz) 1.41 (m, 2H), 1.59 (m, 1H), 1.95 (m, 1H), 2.05-2.35 (m, 2H), 2.54 (s, 3H), 2.96 (dd, 1H), 3.64 (m, 2H), 3.81 (s, 1H), 4.48 (m, 2H), 7.3 (m, 7H), 7.82 (d, 2H)

Source