0-Keto esters cleavage

The addition of ethyl sodiomalonate to olefinic ketones followed by ring closure and /3-keto ester cleavage leads to 1,3-cyclohexanediones. The reaction has been applied to the formation of 2-alkyl-5-phenyl-1,3-cyclohexanediones and is typified by the preparation of 5,5-dimethyl-1,3-cyclohexanedione (85%). Other cyclizations for formation of four-and five-membered rings have been described. ... 

These substances, as well as the parent compound, are p-keto esters and undergo hydrol3rtio cleavage in two directions. One type of cleavage, ketonlc hydrolysis, is effected by the action of dilute caustic alkali in the cold, followed by acidification and boiling the free acetoacetic acid produced has a carboxyl and carbonyl group on the same carbon atom and therefore readily undergoes decarboxylation to yield a ketone, for example ... 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

Problem 23.12 As shown in Figure 23.5, the Claisen reaction is reversible. That is, a /3-keto ester can be cleaved by base into two fragments. Using curved arrows to indicate electron flow, show the mechanism by which this cleavage occurs. 

Step 4 of Figure 29.3 Chain Cleavage Acetyl CoA is split off from the chain in the final step of /3-oxidation, leaving an acyl CoA that is two carbon atoms shorter than the original. The reaction is catalyzed by /3-ketoacyl-CoA thiolase and is mechanistically the reverse of a Claisen condensation reaction (Section 23.7). In the forward direction, a Claisen condensation joins two esters together to form a /3-keto ester product. In the reverse direction, a retro-Claisen reaction splits a /3-keto ester (or /3-keto thioester) apart to form two esters (or two thioesters). 

Standard retrosynthetic manipulation of PGA2 (1) converts it to 5 (see Scheme 2). A conspicuous feature of the five-membered ring of intermediate 5 is the /(-keto ester moiety. Retrosynthetic cleavage of the indicated bond in 5 furnishes triester 6 as a potential precursor. Under basic conditions and in the synthetic direction, a Dieck-mann condensation4 could accomplish the formation of a bond between carbon atoms 9 and 10 in 6 to give intermediate 5. The action of sodium hydroxide on intermediate 5 could then accomplish saponification of both methyl esters, decarboxylation, and epi-merization adjacent to the ketone carbonyl to establish the necessary, and thermodynamically most stable, trans relationship between the two unsaturated side-chain appendages. 

The oxidation of aldehydes to carboxylic acids can proceed by a nucleophilic mechanism, but more often it does not. The reaction is considered in Chapter 14 (14-6). Basic cleavage of (3-keto esters and the haloform reaction could be considered at this point, but they are also electrophilic substitutions and are treated in Chapter 12 (12-41 and 12-42). 

Basic Cleavage of P-Keto Esters and p-Diketones Hydro-de-acylation... 

When P-keto esters are treated with concentrated base, cleavage occurs, but is on the keto side of the CR2 group (arrow) in contrast to the acid cleavage mentioned on page 810. The products are a carboxylic ester and the salt of an acid. However, the... 

The A-D-ring analog 30a,b (mixture of epimers) has been prepared from the epoxide 3a,b by base catalyzed epoxide cleavage, hydroxymethylenation, and O-alkylation of the butenolide unit using standard conditions. Hydroxymethylenation of keto-ester 7 followed by butenolide addition provided the A-D-ring analog 31. 

Simiraly, alkynones undergo arylative cyclization with arylboronic acids in the presence of a rhodium catalyst (Equation (49)).400 When acetylenic /3-keto esters are employed as shown in Equation (50), arylative cyclization (formation of cyclobutanols) and subsequent, facile acid-catalyzed bond cleavage take place to give <5-keto esters.401 Ring expansions of cyclic [3-keto esters are also possible according to this reaction. 

The diketone (225) underwent cleavage reaction by a catalytic amount of NaOMe in MeOH to give the keto-ester (226) 75). 

Dioxo-l,3-dioxanes ring-open under basic conditions. Cleavage of the 5,5-disubstituted derivatives in the presence of quininium or quinidinium alkoxides produces chiral malonic hemi-esters (ee 30-40%) in high yield [11]. The addition of cetyltrimethylammonium bromide promotes the base-catalysed cleavage of p-keto esters to form ketones under sonication [12]. 

The present case simply illustrates another utility of the ester cleavage reaction, i.e., the cleavage of a /3-keto ester with con-ccanitant decarboxylation under only slightly basic conditions. The method should be particularly applicable to systems which are prone to undergo reverse Claisen reactions. 

The reaction with /3-keto esters 660 has also been performed where the amidine component 661 was attached to a solid support, as shown by the synthesis of 2,4-pyrimidinediones 663 where oxidation of the thio linker of 662 was followed by hydrolytic cleavage from the solid support <2004ARK(v)349>. 

Based on our previous results on the nucleophilic alkenoylation of aldehydes via metallated a, 3-unsaturated aminonitriles [50], we now envisaged an enanti-oselective variant. Thus, the enantiopure a-aminonitriles 60 were metallated with LDA and by reaction with aldehydes the adducts 61 could be obtained. Subsequent cleavage of the aminonitrile function with silver nitrate led to the desired a -hydroxyenones 62 in overall yields of 29-80% and enantiomeric excesses ee of 50-69%. Alternatively, the conjugate addition of the lithiated aminonitrile 63 to t-butyl crotonate led to the y-keto ester 63 in 35% yield and an enantiomeric excess ee of >90% (Scheme 1.1.18). 

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