反应 #67887

反应方程式

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

溶剂

ether

ether

ether

反应条件

后处理

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

实验过程

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%).

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