Y Keto esters

In another procedure, acyl radicals derived from phenyl selenoesters ArCOSePh I by treatment of them with Bu3SnH) add to a,P-unsaturated esters and nitriles to give y-keto esters and y-keto nitriles, respectively. ... 

The y-keto nitriles shown in Table I were prepared by the cyanide-catalyzed procedure described here. This procedure is generally applicable to the synthesis of y-diketones, y-keto esters, and other y-keto nitriles. However, the addition of 2-furancarboxaldehyde is more difficult, and a somewhat modified procedure should be employed. Although the cyanide-catalyzed reaction is generally limited to aromatic and heterocyclic aldehydes, the addition of aliphatic aldehydes to various Michael acceptors may be accomplished in the presence of thioazolium ions, which are also effective catalysts for the additions. 

Importance of enol formation for y keto ester fluorination... 

For internal olefins, the Wacker oxidation is sometimes surprisingly regioselective. By using aqueous dioxane or THF, oxidation of P,y-unsaturated esters can be achieved selectively to generate y-keto-esters (Eq. 3.18).86 Under appropriate conditions, Wacker oxidation can be used very efficiently in transforming an olefin to a carbonyl compound. Thus, olefins become masked ketones. An example is its application in the synthesis of (+)-19-nortestosterone (3.11) carried out by Tsuji (Scheme 3.5).87... 

To date, only one example of a combination of a photochemically induced transformation with a transition metal-catalyzed reaction has been found in the literature. This hv/Pd°-promoted process allows the synthesis of five-membered cyclic y-keto esters 5-119 from 5-iodoalkenes 5-117 in the presence of CO and an alcohol 5-118 as a nucleophile (Scheme 5.24) [41]. The yields are high, and differently substituted iodoalkenes can be employed. 

Diverging results have been reported for the carbenoid reaction between alkyl diazoacetates and silyl enol ethers 49a-c. Whereas Reissig and coworkers 60) observed successful cyclopropanation with methyl diazoacetate/Cu(acac)2, Le Goaller and Pierre, in a note without experimental details u8), reported the isolation of 4-oxo-carboxylic esters for the copper-catalyzed decomposition of ethyl diazoacetate. According to this communication, both cyclopropane and ring-opened y-keto ester are obtained from 49 c but the cyclopropane suffers ring-opening under the reaction conditions. 

Mechanistically, the formation of the tricychc y-keto esters 231 can be rationalized in three different ways. Most probably, an intermolecular Michael addition of... 

In spite of the fact that the only a-protons with respect to the carbonyl group in the tricyclic y-keto esters 231 are at bridgehead positions and thus no real enolates can be formed [118], compounds 231 with R = OR could easily and selectively be deprotonated at C-7, and the resulting lithium derivative then substituted with various electrophiles (Scheme 66). 

Scheme 66. Deprotonation of the tricyclic y-keto esters 231 followed by trapping with an electrophile [108]...

Organolithium compounds add to the tricyclic y-keto ester 231 from the exo side to give the endo-alcohols 239 in moderate to excellent yields (Scheme 68) [108]. Treatment of the alcohols 239 with concentrated hydrochloric acid afford-... 

Scheme 67. Additions of the lithiated tricyclic y-keto ester 231 i to aldehydes and subsequent transformations of the products [108]...

FORMATION OF y-KETO ESTERS FROM p-KETO ESTERS METHYL 5.5-DIMETHYL-4-OXOHEXANOATE (Hexanoic acid, 5,5-dimethyl-4-oxo-, methyl ester)... 

A variety of methods have been reported for the preparation of y-keto esters. Although strategies in which the ketone and ester functionalities are assembled from different sources are frequently used, reactions that promote the insertion of a single methylene unit between the carbonyl functionalities of readily accessible (3-keto esters are very attractive. The formation and fragmentation of 2-carboxycyclopropyl alcohols have been central to this methodological development. ... 

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). 

The treatment of the mercurio ketone with palladium (II) in the presence of carbon monoxide and methanol, Eq. (27) results in the formation of a y-keto ester with incorporation of one molecule of carbon monoxide [8], The overall conversion of a siloxycyclopropane to the keto ester may be performed without isolation of the mercurio ketone. 

FORMATION OF y-KETO ESTERS FROM p-KETO ESTERS ... 

FROM a,a -DIBROMOKETONES AND ENAMINES 2,5-DI-METHYL-3-PHENYL-2-C Y CLOPENTEN-1 -ONE y-KETO-ESTER TO PREPARE CYCLIC DIKETONES 2-METHYL-1,3-CYCLOPENTANEDIONE, with the companion preparation y-KETOESTERS FROM ALDEHYDES VIA DIETHYL ARYLSUCCINATES 4-OXOHEXANOIC ACID ETHYL ESTER, which gives the procedure used to prepare the needed... 

This method has been applied to a,(i-unsaturated ketones, esters, and nitriles to give the corresponding 1,4-diketones, y-keto esters, and y-keto nitriles, respectively (see also 6-54). 

Acetoxylation of fS,y-unsaturated esters.3 / ,y-Unsaturated esters are oxidized by PdCI2-CuCl-02 to y-keto esters in 20 40% yield. Reaction of these esters with PdCl2 and KOAc and pentyl nitrite (oxidizes Pd(0)] under oxygen leads to y-aceloxy-a,/ -unsaturated esters (45- 55% yield). The double bond has the (reconfiguration (equation I). 

Pyrrolinones are best obtained by cyclizative condensation of y-keto esters with ammonia or a primary amine (reaction 195). Alternatively, the 2-pyrrolinones may be obtained by cyclization of preformed a-keto amides as shown in reaction (196) (71CC346). Preexisting lactones (2H- or 5H-furanones) also react with amines to give pyrrolinones (reaction 197). Jones and Bean give references to specific examples of these methods as well as to more specialized examples (B-77MI30610). 

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