P-Hydroxycarboxylic acids

Table 13. Ring Extension of alicyclic P-hydroxycarboxylic acids by non-Kolbe electrolysis...

The scope of this quinine ester-catalyzed ketene addition reaction is promising. Optically pure a- and p-hydroxycarboxylic acids of either configuration can be prepared with facility. 

Transformation of the a- or P-hydroxycarboxylic acids into esters eliminates the acidic character of the racemate, thus one can avoid formation of the above mentioned unsoluble calcium salts. In the same time formation of a mixed calcium salt of DBTA and the racemic acid is impossible therefore coordination bonds should entirely replace it. 

Series of racemic a- and p-hydroxycarboxylic acid esters (4 and 5, Scheme 4) could be separated into their enantiomers via coordination complex formation but in these cases the acidic salt, (DBTA)2Ca had to be used as resolving agent. [23, 24]... 

Analytical Properties Resolution of a series of p-hydroxycarboxylic acids as f-butylamide derivatives Reference 43... 

P-Hydroxy carboxylic acids (12,3).2 This acetate on double deprotonation with LDA undergoes diastereoselective aldol reactions with aldehydes. The adducts are easily hydrolyzed to optically active P-hydroxycarboxylic acids with release of (R)-(+)-1,1,2-triphenyl-1,2-ethanediol, the precursor to 1. Optically pure acids can be obtained by crystallization of the salt with an optically active amine such as (S)-(—)-1 -pheny lethylamine. 

Dioxinones Obtained by Resolution or Prepared with a Chiral Auxiliary. 2-Phenyl-4//-1,3-dioxin-4-ones (15) derived from formylacetate or acetoacetate can be readily prepared in enantiopure form by preparative resolution " on cellulose triacetate. These have been used for Michael additions and hydrolysis to long-chain p-hydroxycarboxylic acids, for example the tride-canoic acid (16) from (/ )-(15a). The cuprate adducts formed with the methylphenyldioxinone (i f-flSb) can be hydrogenolyti-cally cleaved directly to p-branched p-hydroxy acids with benzyl protection of the hydroxy functional group see (17) in eq 9. ... 

This facial selectivity can also be utilized in alkylation reactions of the -hydroxy aldol products (138), so that overall a chiral propionate aldol unit is formed, as shown in Scheme 61. 79 xhe final products are syn-a-methyl-P-hydroxycarboxylic acids (139),... 

Peterson aikenation of carbonyl compounds with trimethylsilylmethoxymethyl carbanion (14) can also give enol ethers. An example is the reaction of (14) with adamantanone. Another method of alkene synthesis is the elimination of CO2 and H2O from a P-hydroxycarboxylic acid. If the carboxylic acid is substituted by an a-alkoxy group, the reaction can be used for the synthesis of enol ethers, as illustrated in Scheme 4. ... 

Synthetic approaches to fluorinated p-lactones (oxetane-2-ones) are very similar to oxetane synthesis. Usually p-lactones are prepared either by cycloaddition of ketenes to aldehydes or ketones or by cyclodehydration of p-hydroxycarboxylic acids. 

A suspension of Pd-C in ethyl acetate vigorously stirred under H2 until uptake of gas ceased, a soln. of /r 5-2-azidocyclohexanol and di- ert-butyl dicarbonate in the same solvent added, and the mixture stirred at room temp, under H2 for 19 h - product. Y 71%. Pre-saturation of the catalyst is important to prevent nitrile formation. F.e. incl. N-protected a-amino-p-hydroxycarboxylic acid esters and 2-acoxyamines, s. S. Saito et al.. Tetrahedron Letters 30, 837-8 (1989). 

Dialkylborinyl triflateslethyldiisopropylamine Stereospecific aldol-type condensation with a-alkoxycarboxylic acid esters under mild conditions 5> /f-a-Alkoxy-p-hydroxycarboxylic acid esters... 

P-Hydroxycarboxylic acids. Propionyldimethyl-/ r -butylsilane added dropwise at — 78° to a soln. of /-Pr2NLi in THF/hexane under N2, after stirring for 25 min benzaldehyde added in one portion, quenched after 2 min with aq. NH4CI, extracted, the crude adduct dissolved in methanol/30% H2O2/3 N NaOH, and the slurry stirred at room temp, for 20 min (2SR,3RS)-3-hydroxy-2-methyl-3-phenylpropionic acid. 

Unfortunately, the position of the equilibrium does not favor synthesis, which requires to push the reaction by employing either an excess of the donor glycine (which is difficult to separate from the product) or the acceptor aldehyde (which at high concentrations may deactive the enzyme). A recently developed protocol relies on pulling of the equilibrium by (irreversible) decarboxylation of the formed a-amino-p-hydroxycarboxylic acid catalyzed by a decarboxylase to yield the corresponding aminoalcohols as final products [1452]. 

Two impressive results are achieved with the aldehyde general formulae R CHO first, nearly exclusive formation of yn-isomers 14a-18a and second high optical purity of the prevailing diastereomers, as confirmed by 99-100 % e.e. of isolated a-substituted P-hydroxycarboxylic acids. Products 14a-18a and 14b-18b are in a diastereomeric relationship since both series retain the same configuration... 

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