Keto acids, esterification groups

Our first approach to 1 is based on a retrosynthetic analysis depicted in Fig (8). The crucial step to construct the cw-fused bicyclic ring skeleton of 1 is the intramolecular allylic amination of a cw-allylic carbonate 25. The paUadium-catalyzed allylation takes place with retention of the configuration [76] and requires the c/s-isomer 25 for the ring closure. Compound 25 may be derived from keto acid 24 through a sequence of reactions including esterification, O-methoxycarbonylation, removal of the Boc and benzylidene groups, dehydrative cyclization, reductive alkylation and ureido formation. The last five transformations are to be conducted in a successive manner, i.e., without isolation of the intermediates. The 4-carboxybutyl chain of 1 may be installed by the reaction of O-trimethylsilyl (TMS) cyanohydrin 23 with a di-Grignard... 

In the follow-up detailed report, Hudlicky s group (53) also described the synthesis of homoharringtonine from the unsaturated keto acid 151 (Scheme 23). Acid 151 was treated with formic acid in the presence of perchloric acid to provide the intermediate formylated derivative 163, which, on treatment with aqueous sodium hydroxide, produced hydroxy acid 164. Esterification of 164 with cephalotaxine yielded the cephalotaxyl ester 165, which underwent the Reformatsky reaction with methyl bro-... 

Compounds with keto groups often give more than one derivative on silylation, acylation or esterification because of the possibility of geometrical isomerism, and yields may be unsatisfactory. For oc-keto acids the fonna-... 

Preferential esterification. Startg. tricarboxylic acid and Amberlyst 15 in methanol stirred at room temp, for 10 h monomethyl ester. Y 80%. a,p-Unsatd. and ar. carboxyl groups were left unaffected the method failed with higher alcohols (/-PrOH /-BuOH). Under these mild conditions, a-epimerization, c/5-tra 5-rearrangement, and transesterification (of ethyl esters) are avoided, and keto and olefinic groups remain intact. F.e. inch methyl esters of bile acids s. M. Petrini et al., Synth. Commun. 18, 847-53 (1988). 

Keto acids containing an a-hydrogen atom on a carbon adjacent to the keto group are subject to keto-enol tautomerism. This applies to 2,3,4 and other 0X0 acids and results in the formation of two derivatives on esterification, the enol-ether and the free oxo compound. These separate on gas chromatography, making qualitative and quantitative work difficult. In addition, esterification of the free oxo acid with diazomethane and analogous... 

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