Glycidic esters, 3-substituted

The glycidic esters are of interest primarily because upon hydrolysis aud decarboxylation they aflFord aldehydes (if ClCHjCOOEt is used) or ketones (if substituted chloroacetic esters- ClCHRCOOEt are employed) having a higher carbon content than the original aldehyde or ketone. Thus (I) gives o-phenyl-propionaldehyde or hydratropaldehyde (II) ... 

Recendy, Darzens reaction was investigated for its synthetic applicability to the condensation of substituted cyclohexanes and optically active a-chloroesters (derived from (-)-phenylmenthol). In this report, it was found that reaction between chloroester 44 and cyclohexanone 43 provided an 84% yield with 78 22 selectivity for the axial glycidic ester 45 over equatorial glycidic ester 46 both having the R configuration at the epoxide stereocenter. 

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 ... 

Epoxides also participate in the Ritter reaction with nitriles. An investigation of the ring opening of several alkyl-substituted glycidic esters and amides 181 showed that this transformation occurs with inversion and is completely regiospecific. ° Esters appeared to be somewhat more reactive than amides. However, phenyl-substituted glycidic esters and amides 184 are almost totally nonstereoselective. In addition, the oxazolines 186 are isolated in low yield due to the propensity of intermediate 185 to generate an aldehyde byproduct 187 (Scheme 8.53). 

Loss straightforward are results secured with aryl-substituted glycidic esters. Difficult to reconcile with the Parker-Isaacs model, for instance, are the reactions (Kqs. 029 and 630) of ethyl 3>penta-methylene glyojdate111 -l115-uz0 and ethyl 3-p-anisylgIyeid te.1128... 

Isomerization of substituted styrene oxides allows the synthesis of aldehydes in high yields726 [Eq. (5.275)]. Cycloalkene oxides do not react under these conditions, whereas 2,2,3-trimethyloxirane gives isopropyl methyl ketone (85% yield). Isomerization of oxiranes to carbonyl compounds is mechanistically similar to the pinacol rearrangement involving either the formation of an intermediate carbocation or a concerted mechanism may also be operative. Glycidic esters are transformed to a-hydroxy-/3,y-unsaturated esters in the presence of Nafion-H727 [Eq. (5.276)]. 

However, these conditions have not been applied to other epoxides. Catalysis by the boron trifluoride -diethyl ether complex is very useful for the ring opening of cyano-substituted epoxides " and glycidic esters see the formation of and Table 14. This is demonstrated by the regioselective opening of the epoxide ring in 2,3-dimethyloxirane-2-carbonitrile to provide 3-fluoro-2-hydroxy-2.3-dimcthylbutanonitrile... 

Table 17 indicates some limitations of the amine hydrofluorides in the reaction with glycidic esters. In the least-substituted case (entry 1) the yield is low. On the other hand, the fully substituted glycidic esters (entries 8 and 9) do not react at all with the amine hydrofluoride, probably due to steric hindrance. This type of epoxide gives better results with other fluorination reagents, e.g. they can be opened to the fluorohydrins in good yield with hydrogen fluoride in the presence of the boron trifluoride-diethyl ether complex (sec Section 1.1.4.3.2.1.2.).37... 

When NaY was further applied to the ring opening of a glycidic ester, which is susceptible to polymerization, a -substituted a-hydroxy ester (6a) was exclusively obtained without polymerization because NaY is not a very strong acidic or basic catalyst (Table VII). 

Baures, P. W., Eggleston, D. S., Flisak, J. R., Gombatz, K., Lantos, I., Mendelson, W., Remich, J. J. An efficient asymmetric synthesis of substituted phenyl glycidic esters. Tetrahedron Lett. 1990, 31, 6501-6504. 

Subtle differences in acidity can sometimes be used to discriminate between two hydroxyl functions (Scheme 58). In these cases, p-nitrobenzenesulfonyl chloride appears to be the reagent of choice. Not only does it display improved chem-oselectivity for the most acidic hydroxyl function, but it also acts as a better leaving group. This strategy was employed to prepare, inter alia, substituted a-ami-no acids 225 [127a],glycidic esters 226 [127a] and chloramphenicol 227 [139]. 

The reaction of a-halo esters with carbonyl compounds in the presence of sodium ethoxide leads to 2-(ethoxycarbonyl)oxiranes (Darzens 1904). They are known as glycidic esters. In the first step, the a-halo ester is deprotonated by the base to the corresponding carbanion. This nucleophile adds to the carbonyl compound in a rate-determining step. Finally, the halogen atom is intramolecularly substituted, e.g. ... 

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