A, P-epoxy esters

Condensations of aldehydes or ketones with a-halo esters give a,P-epoxy esters. This is called the Dar2ens condensation. 

Darzens glycidic ester condensation generally involves the condensation of an aldehyde or ketone 2 with the enolate of an a-halo ester 1 which leads to an a,P-epoxy ester (a glycidic ester) (3). Thus the reaction adds two carbons to the electrophile however, the reaction has been primarily developed as a one-carbon homologation method. That is, subsequent to the condensation, the ester is saponified and decarboxylation ensues to give the corresponding aldehyde or ketone 5.2... 

Magnesium iodide reacts with a,p-epoxy esters to form p-iodo-a-hydroxy esters selectively (200 1). The regioselectivity is attributed to favorable chelation of the iodohydrin. These products are reduced by Bu,SnH to hydroxy esters in 75-95% overall yields with retention of the original configuration at the a-position. 

The Darzens Reaction is the condensation of a carbonyl compound with an a-halo ester in the presence of a base to form an a,p epoxy ester. 

In the past, Darzens methodology was primarily used for the synthesis of aldehydes and ketones, as a homologation reaction without any consideration of stereocontrol in the epoxide formation. For this sequence, saponification of the a,P-epoxy ester followed by decarboxylation gives the substituted carbonyl compound ... 

Inanaga also studied the reduction of a,p-epoxy esters with Sml2 and found that a strong chelating agent such as dimethylaminoethanol (DMAE) or TMEDA was required to obtain high regioselectivity (Scheme 4.30).34... 

Aldol reactions. Aldol products are obtained in good yields from reaction of ketones with glyoxylic acid monohydrate with assistance of ultrasound irradiation. Substrate-control (by 1,3- + 1,5-asynmietric induction) of the aldol reaction involving y-amino-a-ketoesters under solvent-free conditions is very effective.- With lithium dicyclohexylamide and InCl, the reaction of esters with aldehydes furnishes P-hydroxy esters, and that of a-bromo esters affords a,p-epoxy esters." These are typical Reformatsky and Darzens reaction products, respectively. 

Nemoto T, Ohshima T, Shibasaki M. Catalytic asymmetric synthesis of a,p-epoxy esters, aldehydes, amides, and -y,8-epoxy p-keto esters unique reactivity of a,p-unsaturated carboxylic acid imidazolides. J. Am. Chem. Soc. 2001 123 (38) 9474-9475. 

The use of an ester as an anion-stabilizing group for a lithiated epoxide was demonstrated by Eisch and Galle (Table 5.5, Entry 11). This strategy has been extended to a,P-epoxy-y-butyrolactone 191, which could be deprotonated with LDA and trapped in situ with chlorotrimethylsilane to give 192, which was used in a total synthesis of epolactaene (Scheme 5.45) [69], The use of a lactone rather than a... 

Aldehydes and ketones condense with a-halo esters in the presence of bases to give ot,p-epoxy esters, called glycidic esters. This is called the Darzens condensation. The reaction consists of an initial Knoevenagel-type reaction (16-41), followed by an internal Sn2 reaction (10-13) ° ... 

In 2004, Bode and Rovis independently and concurrently reported the catalytic coupling of reducible aldehydes and alcohols. This mode of reactivity is most closely related to the work published by Wallach, who generated dichloroacetic acid from chloral under cyanide catalysis in aqueous media [108]. Bode and coworkers reported the catalytic, diastereoselective synthesis of P-hydroxy esters from a,P-epoxy aldehydes using thiazolium pre-catalyst 173 Eq. 16a [109]. MeOH, EtOH, and BnOH are effective nucleophiles providing upwards of >10 1 diastere-oselectivity. Aziridinylaldehyde 174 has also been shown to provide the desired iV-tosyl-P-aminoester 175 in 53% yield Eq. 16b. 

EPOXY-3-ISOPROPOXYPROP. NE see IPDOOO 4-(l,2-EPOXY-l-METHYLETHYL)-l-METHYL-7-OXABICYCLO(4.1.0)HEPTANE see LF 000 a-P-EPOXY-P-METHYLHYDROCINNAMICACID, ETHYL ESTER see ENCOOO... 

A modification of the asymmetric bromolactonization leads to optically active a,p-epoxy aldehydes (18). Treatment of the bromolactone (14) with Sodium Methoxide results in the formation of the epimeric epoxy ester (17) in a ratio of 2 1 (eq 7). 

Hydroxyketones are versatile intermediates in the synthesis of pharmaceutical intermediates and heterocyclic molecules. a-Aryl hydroxyketones have been prepared by reaction of aryl aldehydes with 1,4-dioxane followed by reduction with lithium aluminum hydride (LAH) and by the selective LAH reduction of a-silyloxy a,P-unsaturated esters." WissneC has shown that treatment of acid chlorides with tris(trimethylsilyloxy)ethylene affords alkyl and aryl hydroxymethyl ketones. 1-Hydroxy-3-phenyl-2-propanone (3) has been generated by the osmium-catalyzed oxidation of phenylpropene and by the palladium-catalyzed rearrangement of phenyl epoxy alcohoP both in 62% yield. 

In order to craft the lactone ring, 38 was oxidized to 40 under Swem conditions in a prelude to intramolecular 1,4-addition of the hemiacetal anion [20] formed via nucleophilic attack by methoxide ion at the aldehyde site. With the availability of acetal 41, it became necessary to consider carefully whether to elaborate the epoxy lactone segment in advance of, or subsequent to, introduction of the a,p-unsaturated ester subunit. Since the latter option was considered more workable, 41 was transformed into the enol triflate and subjected to palladium(II) catalyzed methoxycarbonylation [21]. This methodology allowed for proper homologation of 42 to 43, and subsequent conversion to 44, in totally regiocontrolled fashion. 

Ph P)4Pd catalyzes removal of the R SO, group from aryl perfluorosulfonates and the transformation of 7,8-epoxy-a, 3-unsaturated esters " to 8-hydroxy-a,P-unsaturated esters by the borane-dimethylamine complex. 

This reaction involves the condensation of an aldehyde or ketone with an a-halo ester in the presence of a basic condensing agent (sodium ethoxide, sodamide, finely divided sodium or potassium teri.-butoxide) to give a glycidic (or p-epoxy) ester. Thus acetophenone and ethyl chloroacetate yield phenyl-methyl glycidic ester (I) ... 

Heterocycle openings. a,p-Epoxy silanes fiimish P-hydroxy silanes due to the attack of cuprate reagents at the a-carbon. The regioselectivity for the reaction of methyl ( J-4,5-epoxypent-2-enoate with arylcopper is dependent on the presence or absence of BF,. The S 2 pathway giving the a-aryl esters becomes significant with the added Lewis acid. The Sf 2 products are observed in the reaction of epoxy vinyl sulfoxides with... 

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