Sodium ethoxide reaction with epoxides

An a ,/3-epoxycarboxylic ester (also called glycidic ester) 3 is formed upon reaction of a a-halo ester 2 with an aldehyde or ketone 1 in the presence of a base such as sodium ethoxide or sodium amide. Mechanistically it is a Knoevenagel-type reaction of the aldehyde or ketone 1 with the deprotonated a-halo ester to the a-halo alkoxide 4, followed by an intramolecular nucleophilic substitution reaction to give the epoxide 3 ... 

The benzylidene and p-chlorobenzyIidene triphenylarsorane ylides, when generated from sodium ethoxide in ethanol, react with a series of substituted benzaldehydes to give epoxides regardless of the nature of substituents present on the aromatic aldehyde (55, 97). However, the same ylides generated from sodium hydride in benzene (59), reacted with a series of aldehydes to give olefins. These observations clearly show that the base and solvent, in addition to the nature of substituent present on the ylidic carbanion, play an important role in dictating the exact path of the reaction. 

This isomerization reaction has been used in the synthesis of some norcarane derivatives. Thus treatment of the epoxide (4) of karahanaenone with sodium ethoxide in ethanol (reflux IS min.) yielded stereospecifically one bicyclic hydroxy ketone (S S-enrf( -hydroxy-3,3.6-trimethylnorcarane-2-onc) in over 80% yield. 

Initial studies of solvent effects, on the reactions of triarylarsonium benzoylylides with p-nitrobenzaldehyde in N, A-dimethylformamide, dimethyl sulphoxide or methanol, indicated little solvent effect in these cases" ", but later studies of the more finely balanced reactions of semi-stabilized ylides have provided examples of strong influences due to the effect of different base and solvent when the ylide is generated in the presence of a carbonyl compound ". Thus, when benzyltriphenylarsonium bromide or p-chloroben-zyltriphenylarsonium bromide were treated with sodium hydride in benzene in the presence of a variety of p-substituted benzaldehydes the products were alkenes, but if sodium ethoxide in ethanol was used the isolated products were epoxides ". Likewise, when triphenylarsonium benzylylide was generated by phenyllithium in the presence of either benzaldehyde or acetaldehyde, the preponderant product was the epoxide whereas use of sodium amide as base provided mostly the alkene . Similar results were obtained when an allyltriphenylarsonium salt was deprotonated using different hexamethyldisilaz-... 

Large scale epoxidation of 53 (50-100 g) with peracetic acid (33) consistently furnished the epoxides 54 and 55 in essentially quantitative yield. Treatment of the epoxides (40-100 g) with sodium ethoxide in refluxing ethanol provided allylic alcohol 56. Oxidation of 56 (0.50 mmol-0.50 mol) with the Jones reagent (13,34) consistently afforded enone 57 in yields of 95 or "Better. In large scale conversions of 53 to 57, the crude intermediate compounds 54, 55, and 56 were used directly in the subsequent reaction without further purification. Typically, for the three-step process, 57 is obtained in 95 yield, sufficiently pure for the next reaction. 

B.vi. Tbe Darzens Glycidic Ester Condensation. When an a-halo ester is treated with base and the resulting enolate anion condensed with a carbonyl derivative, the product is an alkoxide. This nucleophilic species can displace the halogen intramolecularly to produce an epoxide, which forms the basis of a classical reaction known as the Darzens glycidic ester condensation. 13S Reaction of ethyl a-chloroacetate and sodium ethoxide, in the presence of benzaldehyde. generated the usual alkoxide (221). Intramolecular displacement... 

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