chiral building blocks - acids

Preparation of Ethyl Diazoacetate

A solution containing 140g glycine ethyl ester hydrochloride (1mol) in 250ml water is placed in a 2L four- neck flask. 600 ml dichloromethane is added and the mixture is cooled to -5ºC under a nitrogen atmosphere. A solution containing 83g sodium nitrite in 250ml water is cooled to 0ºC and added with stirring to the reaction mixture. While keeping the reaction temperature below -9ºC, 95g 5% sulfuric acid is added dropwise to the reaction over a 3 minute period. After ten minutes addition stirring the reaction is transferred to a 2L separatory funnel while cold. The isolated yellow-greenish organic phase is poured into a cooled 1L 5% sodium carbonate solution, then placed into a separatory funnel and shaken. The isolated aqueous phase is extracted with 75ml dicholoromethane, dried over 15g anhydrous sodium sulfate, and concentrated under reduced pressure (350mmHg). Futher concentration at 20mmHg and a bath temperature of 35ºC gives 90 ~ 100g (79 ~ 80%) yellow oily substance.

The product is pure enough to be used for ordinary synthesizing purposes. It is explosive, and distillation under even reduced pressure is hazardous.

*Ethyl diazoacetate is explosive and very toxic. Wear protective gloves, protective goggles, protective mask, and use a safety screen. Work in a well ventilated fume hood.

Preparation of Diazomethane

From: http://www.tcieurope.eu/en/product/synthetic-chem/S026.shtml

A reaction and distillation apparatus is assembled by connecting an addition funnel and condensor to a 100ml long-neck distillation flask. Two in series receiving flasks are connected to the apparatus with the second flask containing an induction tube. A solution containing 6g potassium hydroxide in 10ml water, and a solution containing 35ml Carbitol (Diethylene glycol monoethyl ether) and 10ml of ether are placed in the distillation flask. 20 ~ 30ml ether is placed in the second receiving flask making sure the induction tube is immersed into the ether. Both receiving flasks are cooled to 0ºC. A solution containing p-toluenesulfonyl-N- methyl-N-nitrosamide (21.5g, 0.1mol) in 140ml ether is placed in the addition funnel. Heat the distillation flask to 70ºC in a warm water bath. As the ether begins to boil, start adding the p-toluenesulfonyl-N-methyl-N-nitrosamide solution dropwise over a 20 minute period. Swirl distillation flask from time to time. About 3g of diazomethane (0.07mol) is dissolved in ether distillate.
　The reagent should be used at once without storing it.
* Diazomethane is explosive and highly toxic. Wear protective gloves, protective goggles, protective mask and work in a well ventilated fume hood. Also place a safety shield in front of distillation apparatus. Diazomethane may explode upon contact with ground glass joints or other scratched glass surfaces, so avoid handling or preparing this compound with such surfaces. Ordinarily, diazomethane is used as a solution in ether.
*We have TMS diazomethane available. This reagent is analogous in reactivity to diazomethane, but less explosive and less toxic. Please consider using this reagent prior to preparing diazomethane.
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Note:
0. diazomethane is yellow colored, easy to know when to stop ether distillation.
1. the diazomethane distilled by this way contains water, if anhydrous diazomethane needed, KOH pellets can be added into the diazomethane ether solution and put in freezer overnit to get dry diazomethane.
2. TMS diazomethane can't replace diazomethane, although in most case, it is a good substitutuion.
3. dry diazomethane ether solution can be stored in freezer for a while (several days). when diazomethane decomposed, the yellow color will disappear.

Preparation of Cyclopentadiene

From: http://www.tcieurope.eu/en/product/synthetic-chem/S026.shtml

The reaction apparatus (Figure 1) is assembled by attaching a thermometer, Vigreaux distilling column and Liebig condenser to a 500ml two necked flask. The receiver is cooled by means of a refrigerants or freezing mixtures.
Dicyclopentadiene (195g) is placed in the two necked flask and heated to about 160ºC with an electric heating mantle or oil bath. Thermal decomposition begins at about 150ºC and distillates at 43 ~ 46ºC can be obtained (addition of iron powder expedites the thermal decomposition rate of Cyclopentadiene). Heating is applied slowly, because rapid temperature increases cause dicyclopentadiene to distill prior to undergoing thermal decomposition. In such a case, re-distillation allows narrow boiling-point distillates.
Cyclopentadiene dimerzes rapidly at room temperature and should be used immediately.

Di-n-butyltin Oxide

1. in sugar chemistry, equatorial OH of a cis-diol (6 membered sugar) can be selectively protected by BuSnO then benzylbromide/allylbromide in dmf.

2. axial OH of a cis-diol can be oxidized by (BuSnO/MeOH then BuSnOMe/Br2) to ketone selectively.

How to make beta anomer of sugar?

anomeric effect is effective when you have free -OH ( or ether protected) around the sugar ring.

So when you make a glycoside at the anomeric position, you will get a mixture of alpha and beta anomers.
Alghough alpha anomer is thermodynamically more stable, beta anomer formation is quicker.

how do you make beta anomer selectively?
one way is to protect the -OH on the sugar ring with ester (ex. acetate) which have small anomeric effect when you do reaction at anomeric position.