Reaction #67887

Reaction equation

tert-butyl-lithium

(R)-2-(3-(benzyloxy)benzyl)-4-(tert-butyldimethylsilyloxy)cyclopent-2-enone

copper cyanide

methyllithium

(S)-tert-butyl(1-iodooctan-3-yloxy)dimethylsilane

→

(2R,3R,4R)-2-(3-(benzyloxy)benzyl)-4-tert-butyldimethylsilyoxy-3-((S)-3-tert-butyldimethylsilyoxyoctyl)cyclopentanone

Solvents

ether

ether

ether

Conditions

Workup

1. 1
   TemperatureA 25 ml two-necked flask was flame
2. 2
   Otherdried
3. 3
   Temperatureto be cooled
4. 4
   workup.ADDITIONadded to the reaction flask
5. 5
   OtherThe reaction was quenched with 40 ml saturated ammonium chloride (aq)
6. 6
   workup.ADDITIONcontaining 0.4 ml ammonium hydroxide
7. 7
   Otherseparated
8. 8
   Extractionthe aqueous layer was extracted with ethyl acetate
9. 9
   Dryingdried over anhydrous magnesium sulfate
10. 10
    FiltrationThe solid was filtered off
11. 11
    OtherThe solvent was evaporated off under vacuum
12. 12
    OtherThe crude product was purified by chromatography on silica gel using
13. 13
    workup.ADDITIONa mixture of hexane and ethyl acetate as a gradient eluent

Procedure

A 25 ml two-necked flask was flame dried and allowed to be cooled. (S)-tert-butyl(1-iodooctan-3-yloxy)dimethylsilane (1.18 g, 3.2 mmol) and 11.8 L ether were added to the reaction flask, followed by dropwise addition of tert-butyl-lithium (3.75 ml, 1.7M in pentane) at −70° C. A homogenous solution of copper cyanide (0.29 g, 3.2 mmol) and methyllithium (1.6 ml, 2M in ether) in 5.8 ml ether was cooled from room temperature to −70° C. and added to the reaction flask while stirring for 30 minutes. Then, a solution of (R)-2-(3-(benzyloxy)benzyl)-4-(tert-butyldimethylsilyloxy)cyclopent-2-enone (0.65 g, 1.6 mmol) in 6.5 ml ether at −70° C. was added to the reaction mixture for 30 minutes. The reaction was quenched with 40 ml saturated ammonium chloride (aq) containing 0.4 ml ammonium hydroxide. The reaction mixture was phase separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined and dried over anhydrous magnesium sulfate. The solid was filtered off. The solvent was evaporated off under vacuum. The crude product was purified by chromatography on silica gel using a mixture of hexane and ethyl acetate as a gradient eluent. Yield of the titled compound was 1.1 g (85%).

Source