A-Ketocarboxylic acid derivs

Thermal degradation prior to ionization can cause decarbonylation or decarboxylation of the analyte. Decarbonylation, for example, is observed from a-ketocarboxylic acids and a-ketocarboxylic acid esters, whereas decarboxylation is typical behavior of P-oxocarboxylic acids such as malonic acid and its derivatives and di-, tri-, or polycarboxylic acids. 

Use of a /3-ketocarboxylic acid derivative may circumvent this problem (8-ketocarboxylic acid derivatives react with esters of a-amino carboxylic acids to give (Y) a-aminonitriles afford (Z) in a condensation step. 

An ethereal soln. of the startg. enamine and triethylamine added at -20 to -10° to phosgene, the resulting triethylamine hydrochloride removed by filtration, and the filtrate treated dropwise at -20 to -10° with methanol and triethylamine methyl a-phenyl-/ -pyrrolidinoacrylate. Y 78%. - The reaction of enamines with phosgene occurs under mild conditions and provides reactive intermediates for the synthesis of / -ketocarboxylic acid derivs. and heterocyclics. F. e. and reactions s. A. Halleux and H. G. Viehe, Soc. (C) 1970, 881. 

Sometimes the products of carbonyl compounds silylation are not TMS-enols, but bis-TMS derivatives of hydrated carbonyls, RR C = 0 RR C(OH)2 RR C(OTMS)2. More unpredictable products can be formed during silylation of a-ketocarboxylic acids. For example, ketomalonic acid (II) besides the normal bis-JMS ester gives an unusual TMS derivative of the enol-hydrate form (see Fig. 7). 

The Petasis method involves the use of organoboron compounds to produce a side chain on a Mannich product derived from the imine condensation product between an amine and an a-ketocarboxylic acid. Thus, as shown in Scheme 12.64, as an example of this three-component reaction, when the styrylboronic acid derived from the reaction of phenylacetylene with catecholborane was allowed to react with glyoxylic acid (CHOCO2H) and (5)-2-phenylglycinol, a single diastereomer was isolated, which gave an enantiomerically pure (7 )-homophenylalanine hydrochloride on reduction. This procedure is limited only by the availability of the components. 

The considerations that (Z), as a vinylogous amide, may undergo hydrolysis to (Y) whereas (Y) and (Z), being derivatives of /3-ketocarboxylic acids, can be subjected to acid cleavage suggest starting with (Z) itself as a general synthetic approach (Scheme 2). 

The use of the y-(trimethylsiloxy)nitrile derivatives (190) as a route to 1,4-bifunctional units is exemplified in a convenient synthesis of jasmonoid compounds. The addition of the Grignard reagent to the cyano group as the homologation step results in the keto alcohol (191) after subsequent hydration. The -y-ketocarboxylic acid (192) obtained from the... 

Of the five-membered heterocyclic ring derivatives, 0,0-diethyl-0-(3-methylpyrazolyl-5) phosphorothioate (51), introduced under the name Pyrazo-thion , is an insecticide with strong systemic action. The development of this compound was a further important result of the research program carried out by the research workers of the Geigy Co. on the phosphorus esters of enolisable heterocyclic compounds obtained from j -ketocarboxylic acid esters (Gysin and Margot, 1952). 

Amino Acids and Peptides. - Wasserman s method of one-carbon homologation of carboxylic acids to give a-ketocarboxylates involves reaction with cyanomethylenetriphenyl-phosphorane followed by ozone (Scheme 24) and has been used as a key step in a chemo-enzymatic synthesis of isotopically labelled L-valine, L-isoleucine, and o/fo-isoleucine. Alkylation of the carbanion derived from the imino-substituted methylphosphonate diphenyl ester (186) with indol-3-ylmethyl bromide followed by appropriate deprotection has been used to prepare the phosphonate analogue (187) of tryptophan (Scheme 25). The deprotected analogue (188) and derived peptides show activity as inhibitors of chymotrypsin. Two approaches to solid phase Wadsworth-Enunons reactions which have applications in combinatorial chemistry have been reported. In one diethylphosphonoacetamide is bound to PEG-PAL resin via a peptide link, while... 

Although outside the scope of this section, the concurrent development of the Pd-catalyzed allylation of /3-ketocarboxylic acids via the formation and decomposition of allyl /3-ketocarboxylates is noteworthy (Sects. V.2.1.1 and V.2.1.2). The mechanism shown in Scheme 4, which involves (i) oxidative addition of allyl /3-ketocarboxylates, (ii) decarboxylation, and (iii) intermolecular enolate allylation was proposed and experimentally supportedUnfortunately, a-allylation with y-disubstituted allyl derivatives, such as geranyl carboxylates, proceeds in low yields, and there are some indications that the reaction may lack some specificity features, for example, stereospecificity of the allylic moiety. 

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