A,p-Epoxy acids

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. 

The method is a modification of one used by Barton and McCombie.8 Reduction of ketones.9 Ketones can be reduced to alcohols by Bu3SnH in the presence of either AIBN or a Lewis acid, but this reaction is limited to unhindered ketones. However, even sterically hindered ketones, such as f-butyl methyl ketone, can be reduced under high pressure (10 kbar) in the absence of a catalyst. This method is particularly useful in the case of cyclopropyl and a,p-epoxy ketones, which are reduced to the corresponding alcohols. Reduction of these ketones with Bu3SnH under radical conditions results in ring-opened products. 

Sterically hindered ketones were more difficult to reduce with tin hydrides but reduction at high pressure (1 GPa) without radical or Lewis acid catalyst in methanol at 55 °C was effective.Reduction of the very hindered ketone (92) did not occur at atmospheric pressure but proceeded usefully at high pressure (equation 25). The absence of radical intermediates allowed even a,P-epoxy and cyclopropyl ketones such as (93) to be reduced in high yield, largely without cleavage of the strained ring (equation 26). Under conventional AIBN-initiated conditions radical-mediated processes predominated. 

The reaction has also been carried out on a-hydroxy ketones and on a,p-epoxy ketones, which give p-hydroxy acids.The fact that an epoxide gives a reaction analogous to a halide indicates that the oxygen and halogen are leaving groups in a nucleophihc substitution step. 

Diastereomerically enriched P-hydroxy silanes are also accessible from a,P-epoxy silanes and reaction of these with organocuprate reagents. The epoxy silanes are synthesized by epoxidation of (E)- or (Z)-vinylsilanes with m-chloroperbenzoic acid. The required (Z)- and ( )-vinylsilanes can be obtained by hydroboration-protonolysis of 1-trimethylsilyl-l-alkynes or by hydrosilylation of 1-alkynes, respectively. 

Griffin, C.E., and Ranieri, R.L., Acid-catalyzed rearrangements of dimethyl a,P,P-triaryl-a,P-epoxy-ethylphosphonates. Phosphorus, 6, 161, 1976. 

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. 

Eschenmoser a,p-epoxy ketone cleavage (2,419-422 3,293). In the synthesis of a prostanoid, Corey and Sachdev encountered a case where the Eschenmoser cleavage reaction with p-toluenesulfonylhydrazine gave a very complex mixture from which none of the desired acetylenic aldehyde could be isolated. They then found that cleavage could be effected with 2,4-dinitrobenzenesulfonyl-hydrazine in CH2CI2 or THF at 0-25°. Pyridine, sodium carbonate, or sodium bicarbonate can be used as catalysts. The yield can sometimes be improved by addition of ethyl isocyanate to scavenge the sulfinic acid formed in the fragmentation. This modified procedure was shown to be effective in five cases. 

Reductions. Aldehydes, ketones, acid chlorides, carboxylic acids, and N-Boc amino acids are reduced to the corresponding alcohols, generally in excellent yields. The reduction of a,P-epoxy ketones gives alcohols without affecting the heterocycle. ... 

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... 

Synonyms cas 77-83-8 C-ie aldehyde EMPG a-p-EPOXY-p-METHYLHYDROCINNAMIC acid, ethyl ester ETHYLa,p-EPOXY-p-METHYLHYDROCINNAMATE ETHYL 2,3-EP0XY-3-METHYL-3-PHENYLPR0PI0NATE ETHYL ESTEROf 2,3-EPOXY-3-PHENYLBUTANOIC ACID FRAESEOL 3-METHYL-3-PHENYLGLYCIDIC ACID ETHYL ESTER STRAWBERRY ALDEHYDE... 

The lessons learned from the abortive experiments in Scheme 12 were invaluable to Kozikowski and co-workers in developing a slate of do s and dont s for the final strategy (Scheme 13). Most notably, it transpired that the a,P-epoxy lactone C16 (c.f. C9, Scheme 12) underwent classical reductive elimination with zinc in acetic acid to give the P-hydroxy lactone C17, and cyclohexylidenation, followed by oxidation then led to the actinobolin skeleton in CIS. Final processing to give actinobolin hydrochloride now proved to be uneventful. 

Epoxidation of oleic and linoleic acid was readily achieved by treatment with the acetonitrile complex of hypofluorous acid (55). Phase-transfer-catalyzed biphasic epoxidation of unsaturated triglycerides was accomplished with ethylmethyldioxirane in 2-butanone (56). The enantioselective formation of an a,P-epoxy alcohol by reaction of methyl 13()S)-hydroperoxy-18 2(9Z,llfi) with titanium isopropoxide has been reported (57). An immobilized form of Candida antartica on acrylic resin (Novozyme 435) was used to catalyze the perhydrolysis and the interesterification of esters. Unsaturated alcohols were converted with an ester in the presence of hydrogen peroxide to esters of epoxidized alcohols (e.g., epoxystearylbutyrate) directly (58). Homoallyl ethers were obtained from olefinic fatty esters by the ethylaluminium-in-duced reactions with dimethyl acetals of formaldehyde, acetaldehyde, isobutyralde-hyde, and pivaldehyde (59). Reaction of 18 2(9Z, 12Z) with 50% BF3-methanol gave monomethoxy and dimethoxy derivatives (60). A bulky phosphite-modified rhodium catalyst was developed for the hydroformylation of methyl 18 1 (9Z)and 18 1(9 ), which furnished mixtures of formylstearate and diformylstearate (61). 

Synonyms Aldehyde C-16 Aldehyde C-16 pure C-16 aldehyde EMPG a-p-Epoxy-p-methylhydrocinnamic acid, ethyl ester Ethyl a,p-epoxy-p-methylhydrocinnamate ... 

Oxiranecarboxylic acids 41 (glycidic acids) can be converted into a,P epoxy diazomethyl ketones 42 via mixed anhydrides. It was found that photolysis of these compounds in the presence of alcohols gave yhyunsaturated esters 44. It is thought that nucleophilic attack of the alcohol on the ketene 43 results in epoxide ring opening. The E olefin isomer is predominately formed, although small quantities of Z esters are also isolated (< 10%). Conveniently non-racemic, chiral substrates are readily prepared via Sharpless asymmetric epoxidation of allylic alcohol 39, followed by... 

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