Ethyl acetoacetate chiral reduction

Where there is a chiral centre adjacent to the ketone it may also influence the stereochemistry of the reduction. Thus the reduction of ethyl acetoacetate (10.8) by yeast has the stereochemical result shown in 10.9. 

In 1981 we started our works to employ ethyl (S)-3-hydroxybutanoate (B, Figure 4.35) as a chiral and nonracemic building block in pheromone synthesis. Reduction of ethyl acetoacetate (A) with fermenting baker s yeast gives (5)-B. Synthesis of (2S,6R,8S)-88 was executed as a part of this project (Figure 4.35).64,65... 

The 3(S)-hydroxybutanoate 141 obtained by bakers yeast reduction of ethyl acetoacetate was the starting material providing the required chirality at C37 (Scheme 18). Stereoselective alkylation, hydroxy group protection, and aldehyde formation at C35 gave the anti-product 142. Aldol condensation with vinylbor-... 

Hydroxy-esters. - Once again, most contributions to this area involve the synthesis of chiral hydroxy-esters. Almost complete enantioselectivity is achieved in the reduction of a-keto-esters to a-hydroxy-esters using Alpine-Borane (B-(3-pinanyl)-9-BBN) derived from either (+)- or (-)-a-pinene when the reactions are carried out at relatively high concentrations (>2M). Many other types of prochiral ketones are also reduced with excellent asymmetric inductions although 3-keto-esters may not be particularly suitable substrates as ethyl acetoacetate is reduced to ethyl 3-hydroxybutanoate with an enantiomeric excess of only... 

The alkyl esters of 3-hydroxybutanoic acid are a particularly useful group of compounds in organic synthesis because they are available in both chiral forms. Ethyl (5)-3-hydroxybutanoate, for example, may be prepared by the reduction of ethyl acetoacetate on the re side of the keto group with fermenting yeast and leads to an enantiomeric purity of about 85% which may be enriched further via a crystalline dinitrobenzoate. Synthesis of the R form was a little more difficult but could be achieved with 83-88% purity by the reduction of the acetoacetate with hydrogen in the presence of Raney nickel which had been treated with tartaric acid. " ... 

Exp. 28, "Chiral Reduction of Ethyl Acetoacetate" Exp. 29, Nitration of Aromatic Compounds Using a Recyclable Catalyst"... 

Chiral Reduction of Ethyl Acetoacetate Optical Purity Determination... 

In Experiment 28B (optional), you may use nuclear magnetic resonance spectroscopy to determine the relative amounts of (R) and (S) enantiomers produced in the chiral reduction of ethyl acetoacetate. This part of the experiment requires the use of a chiral shift reagent. 

Chiral gas chromatography will provide a direct measure of amounts of each stereoisomer present in your chiral ethyl 3-hydroxybutanoate sample. A Varian CP-3800 equipped with an Alltech Cyclosil B capillary column (30 m, 0.25-mm ID, 0.25 /xm) provides an excellent separation of (R) and (S)-enantiomers. Set the FID detector at 270°C and the injector temperature at 250°C, with a 50 1 split ratio. Set the column oven temperature at 90°C and hold at that temperature for 20 minutes. The helium flow rate is 1 mL/min. The compounds elute in the following order ethyl (S)-3-hydroxybutanoate (14.3 min) and the (R)-enantiomer (15.0 min). Any remaining ethyl acetoacetate present in the sample will produce a peak with a retention time of 14.1 minutes. Your observed retention times may vary from those given here, but the order of elution will be the same. Calculate the percentages of each of the enantiomers from the chiral gas chromatography results. Usually, about 92-94% of the (S)-enantiomer is obtained from the reduction. 

New techniques have been introduced in this edition. Chiral gas chromatography has been included in the analysis of the products obtained from the resolution of a-phenylethylamine (Experiment 30) and the products from the chiral reduction of ethyl acetoacetate (Experiment 28). A new method of obtaining boiling points using a temperature probe with a Vernier LabPro interface or digital thermometer has been introduced. 

The reaction of S-phenethylamine and ethyl acetoacetate led to 5.209 (ethyl 3-(N-phenethyl)but-2-enoate)S9.90 as seen in chapter one, section l.l.C.ii. Reduction of the double bond would give the ethyl 3-aminobutanoate derivative, and the presence of the chiral auxiliary would lead to asymmetric induction during that reduction. 

Hydroxy-esters.—Ethyl 5-3-hydroxybutanoate is obtained in 87% optical purity by the reduction of ethyl acetoacetate with Bakers yeast. " Two independent chiral synthesis of the leukotriene intermediates (46), R = CHO and R = CH2OH, have appeared. An effective large-scale conversion of arachidonic acid into 5-hydroxy-6-fran5-8,ll,14-cis-eicosatetraenoicacid (5)HETE, including its resolution, is also reported by Corey and Hashimoto. ... 

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