Hydroxycarboxylic acid catalysts

Lewis acid-promoted asymmetric addition of dialkylzincs to aldehydes is also an acceptable procedure for the preparation of chiral secondary alcohol. Various chiral titanium complexes are highly enantioselective catalysts [4]. C2-Symmet-ric disulfonamide, chiral diol (TADDOL) derived from tartaric acid, and chiral thiophosphoramidate are efficient chiral ligands. C2-Symmetric chiral diol 10, readily prepared from 1-indene by Brown s asymmetric hydroboration, is also a good chiral source (Scheme 2) [17], Even a simple a-hydroxycarboxylic acid 11 can achieve a good enantioselectivity [18]. 

The carboxyl group seems to activate epoxides slightly toward nucleophilic attack by amines, and in the absence of catalysts most 2,3-epoxycarboxylic acids react with amines to yield 2-amino-3-hydroxycarboxylic acids [346-348], This regioselectivity can, however, be overridden by complex formation with Ti(OiPr)4 (Scheme4.77). 

A-Alkyl-4-boronopyridinium halides such as 31 catalyze the esterification of a-hydroxycarboxylic acids <20050L5047>. When the quaternized iV-alkyl group is attached to a polystyrene resin, the supported iV-alkyl-4-boronopyridinium salt 32 serves as a catalyst in amide formation reactions. These catalysts are thermally stable and easily recovered and recycled <20050L5043>. 

Intramolecular condensation of co-hydroxycarboxylic acids is a standard method to prepare lactones. Acid catalysts or more elaborate mediators are usually required as well as continuous removal of water. Transition-metal-catalyzed cyclocarbonylation of unsaturated alcohols is a fascinating alternative, which proceeds under neutral conditions [26]. Intramolecular hydroesterification of... 

Another level of refinement regarding in situ acyl group activations is reached when the activated hydroxycarboxylic acid A is converted with additionally added para-(dimethylamino)pyridine, Steglich s catalyst, in an equilibrium reaction into the cor-... 

This procedure offers a convenient method for the esterification of carboxylic acids with alcohols2 and thiols2 under mild conditions. Its success depends on the high efficiency of 4-dialkylaminopyridines as nucleophilic catalysts 1n group transfer reactions. The esterification proceeds without the need of a preformed, activated carboxylic acid derivative, at room temperature, under nonacidic, mildly basic conditions. In addition to dichloromethane other aprotic solvents of comparable polarity such as diethyl ether, tetrahydrofuran, and acetonitrile can be used. The reaction can be applied to a wide variety of acids and alcohols, including polyols,2 6 a-hydroxycarboxylic acid esters,7 and even very acid labile... 

Hydrocyanation of aldehydes opens access to the synthetically valuable cyanohydrins, precursors for hydroxycarboxylic acids, a-hydroxyketones and /S-ami-noalcohols. Applying the principles of homogeneous catalysis to this reaction it is possible to obtain cyanohydrins in the optically active form, depending on how well the catalyst-ligand system is adapted to the substrate. 

The following cases should be distinguished caramelization in the presence of (a) an inorganic acid, (b) an organic acid as the catalyst, and (c) either a-, y-, or < hydroxycarboxylic acid as the catalyst. In the last case, such acids may form lactides or lactones, respectively, under the caramelization conditions. Our preliminary results suggested that such acids participate in the formation of secondary aromas similarly to 0 -amino acids. This problem will be discussed separately in the section devoted to certain food aromas in which carbohydrates are involved. In either case when organic acids are... 

Aromatic hydroxycarboxylic acids, especially salicylic acid, have a wide range of applications, for example, as valuable raw materials and intermediates in the production of pharmaceutical chemicals. Originally, salicylic acid was synthesized by the Kolbe-Schmitt reaction [57], which consists of two steps (1) the synthesis and purification of alkali metal phenoxides and (2) carboxylation (Scheme 4.4). Another possible synthetic method is via the attack of a trichloromethyl cation (generated by a copper catalyst from carbon tetrachloride) on the phenoxide anion, followed by hydrolysis of the C—Cl bonds with concentrated sodium hydroxide, because it is fairly difficult to replace an aromatic hydrogen with carboxyl functionality [58]. 

The first results showed that optically active amino acids are not very effective as modifiers and showed that the most effective modifiers are hydroxycarboxylic acids, such as tartaric and malic acids. Also, it was found that the treatment of Raney Ni catalysts with these modifying solutions diminished the catalytic activity for the hydrogenation of the C=0 bonds in beta-keto esters but not for the hydrogenation of C=C bonds in olefinic substrates (Scheme 4.1.). 

Using cinchonidine as a modifier of Pt-alumina catalysts, the reaction resulted in the formation of products with preponderances of one enantiomer of the resulting 2-hydroxycarboxylic acid or ester of (R)- configuration. But in many papers devoted to this process there is some confusion in the assignment of configuration to the optically active acid (or ester) Even the same... 

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). 

The bienzymatic approach was also used for the synthesis of a-alkyl-a-hydroxycarboxylic acids from ketones and cyanide. The conversion of ketones by HnLs is problematic because the reaction equilibrium is mainly on the side of the ketones and therefore these substrates are generally not quantitatively converted by HnLs ]68, 69]. Therefore, the presence of a second enzyme, such as a nitrilase, results in the establishment of an efficient cascade reaction. The feasibility of this biotransformation was demonstrated for the conversion of acetophenone plus cyanide at acidic pH-values by the recombinant whole-cell catalysts which simultaneously produced the nitrilase from P.Jluorescens EBC191 and the MeHnL. These cells converted acetophenone plus cyanide almost quantitatively to (S)-atroIactate (and (S)-atrolactamide) [61]. 

These catalysts are useful in the reactions of both primary and secondary amines with various carboxylic acids (Equation 10). Catalytic amidation of optically active aliphatic a-hydroxycarboxylic acids with benzylamine proceeds with no measurable loss (<2%) of enantiomeric purity under reflux conditions in toluene. Most amino acids are barely soluble in non-aqueous solvents. Nevertheless, their lactams can be prepared by the present technique under heterogeneous conditions. For example, when 6-aminocaproic acid and 1 mol% of the boron catalyst 3.4,5-FjC5H2B OH)2 are suspended in refluxing xylene, the solid slowly dissolves and caprolactam is formed in 93% yield. 

The hydration of C-C multiple bonds is a reaction with prevalent industrial interest due to the usefulness of the products as chemical intermediates. The wool-Pd complex is an economical and highly active catalyst for hydration of olefins. It is very stable and can be reused several times without any remarkable change in the catalytic activity [73, 74]. In particular, to convert alkenes to the corresponding alcohols in excellent enantioselectivity, a new biopolymer-metal complex constituted of wool-supported palladium-iron or palladium-cobalt was prepared and used, such as allylamine to amino-2-propanoI, acrylonitrile to lactonitrile and unsaturated acids to a-hydroxycarboxylic acids [75-77]. The same catalytic system was also used for hydration of substituted styrenes to produce chiral benzyl alcohols. The simple and cleaner procedure, mild reaction conditions, high stability and recovery rate of catalyst made these catalytic systems an attractive and useful alternative to the existing methods (Scheme 37). 

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