From p-keto esters

The present chapter extends our study of carbanions to the enolate ions derived from esters Ester enolates are important reagents m synthetic organic chemistry The stabilized enolates derived from p keto esters are particularly useful... 

Although the synthesis of 3-isoxazolols from P-keto esters and hydroxylamine suffers from the formation of 5-isoxazolones as major products, treatment of acyl chlorides with Meldrum s acid 4 followed by aminolysis gave rise to p-keto hydroxamic acids 6 that cyclised to the corresponding 5-substituted 3-isoxazolols 7 without formation of any byproduct <00JOC1003>. Cyclisation of N-substituted salicylhydroxamic acids 9 under... 

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

FORMATION OFy-KETO ESTERS FROM p-KETO ESTERS ... 

Functionalised 2,3-dihydro-l,4-dioxins can be synthesised in a three step-sequence from P-keto esters. The key step is the insertion of a Rh-carbenoid derived from an a-diazo-p-keto ester into an 0-H bond of a 13-diol <99H(51)1073>. The reaction of 2-(l,4-dioxenyl)alkanols with silyl enol ethers yields 23-disubstituted 1,4-dioxanes. When 13-bis(trimethylsilyloxy)-cyclobut-l-ene is used, the expected cyclobutanone products are accompanied by a spirocyclopropane derivative <99TL863>. 1,4-Dioxane-monochloroborane 57 is a highly reactive hydroborating reagent <990L315>. 

P-Keto acids484 are easily decarboxylated, but such acids are usually prepared from p-keto esters, and the esters are easily decarboxylated themselves on hydrolysis without isolation of the acids.485 This decarboxylation of p-keto esters involving cleavage on the carboxyl side of the substituted methylene group (arrow) is carried out under acidic, neutral, or... 

Since we have already made compounds like 2 in chapter 25 from P-keto-esters, it makes sense to use the same strategy here. Addition of ethylene oxide 3 to the enolate of 5 gives the lactone 6 directly and treatment with HBr accomplishes decarboxylation and formation of the bromide 7 in one pot.1 Vogel2 uses the chloroketone to make 1 R=H in 82% yield by this method with NaOH for the base. 

Some new methods for the synthesis of the oxadiazole ring have been recently published. 1,2,4-Oxadiazoles can be easily obtained in a one-pot solvent-free process starting from P-keto esters 169 and amidoximes 170. The process is likely to go through an acyl ketene intermediate <07TL2231>. 

Feist-B6nary furan synthesis Synthesis of furans from p-keto esters and a-halogenated carbonyl compounds under basic conditions. 166... 

Lygo, B. Reaction of aziridines with dianions derived from p-keto esters application to the preparation of substituted pyrrolidines. Synlett 1993, 764-766. 

The reduction of imines/enamines 10j-10n/36j-36n generated from p keto esters can be regarded as an interesting method for the preparation of p amino acids. This approach has been extended to the reduction ofthe imines/enamines derived from a substituted P keto esters 37 (Scheme 4.4). In this case, the fast enamine imine equilibration 38 39 is the key point since imines 39 are chiral but racemic, so that... 

Durham TB, MiUer Ml (2003) Enantioselective synthesis of a-amino acids from N-tosyloxy P-lactams derived from P-keto esters. J Org Chem 68 27-34... 

An alternative route by the Danishefsky group was developed [142e-g] (Scheme 84). The aldol reaction of ethyl ketone 580, prepared from P-keto ester 579, with aldehyde 581 stereoselectively afforded 582 (dr = 5.4 1). After Troc protection followed by hydrolysis of the enol ether, Suzuki coupling with 583 followed by TBS deprotection gave the desired (12Z)-olefin 584. The Noyori reduction of the P-keto ester 584 gave 3a-alcohol with high stereoselectivity, which was converted into hydroxy carboxylic acid 585. Macrolactonization of 585 was accomplished by the Yamaguchi method, and subsequent deprotection and DMDO oxidation efficiently afforded epothilone B (5b). 

Dianions have been prepared from p-keto esters by double deprotonation using a number of strong bases including LDA. 

When this reaction is carried out on the parent diethyl malonate, acetic acid results, and the process is of no practical synthetic utility. As with the synthesis of ketones starting from P-keto esters, this process is far more usefiil when combined with the alkylation reaction. One or two alkylations of malonic ester give substituted diesters that can be hydrolyzed and decarboxylated to give carboxylic acids (Fig. 19.62). Substituted acetic acids are potential sources of esters, acid halides, and any other compound that can be made from a carboxylic acid. 

For the reductive removal of the sulphone group from adducts derived from P-keto-esters, higher yields were obtained by protection of the keto-group prior to reduction. 

SCHEME 9.12. Application of Michael adduct from p-keto esters for the (—)-tubifolidine synthesis. 

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