Hydroxy-amides, from addition

Not surprinsingly, the aldol addition of the lithium enolates derived from these systems proved to be unsatisfactory. However, the derived zirkonium enolates in these and related systems have proven to be exceptional 176). The amides (171) and (172), each of which is readily derived from (S)-proline and (S)-valine respectively, exhibit good stereoselectivity with a range of aldehydes. The optical purity of the P-hydroxy amides (173) was very good (>95% e.e.). However, this method has a limitation which has been associated with the acidic conditions that are required to hydrolize these chiral amides (173) to their derived carboxylic acids (174). While... 

There are several types of chiral derivatizing reagents commonly used depending on the functional group involved. For amines, the formation of an amide from reaction with an acyl halide [147,148], chloroformate reaction to form a carbamate [149], and reaction with isocyanate to form the corresponding urea are common reactions [150]. Carboxyl groups can be effectively esterified with chiral alcohols [151-153]. Isocynates have been used as reagents for enantiomer separation of amino acids, iV-methylamino acids, and 3-hydroxy acids [154]. In addition to the above-mentioned reactions, many others have been used in the formation of derivatives for use on a variety of packed and capillary columns. For a more comprehensive list, refer to References 155-159. 

Hydration of cyanohydrins.1 The cyanohydrins derived from aldehydes undergo hydration when treated with borax in water at 80° to give a-hydroxy amides in 65-85% yield. In some cases addition of a trace of KCN can increase the yield. 

Bredereck and Schmotzer (1044), from diaminomaleonitrile (DAMN hydrogen cyanide tetramer) and oxalyl chloride, prepared 2,3-dicyano-5,6-dihydroxy-pyrazine but Stetten and Fox (1049) could not prepare 23-diamino-5-hydroxy-pyrazine from glycine amide and oxamide. Section 11.3 lists preparations from a, -diamino or a, -diimino compounds and reagents other than a,0-dicarbonyl compounds (384) with additional data (1050) and oxidation of 23-dichloro-quinoxaline with hot aqueous potassium permanganate gave 23-dicarboxy-5,6-dihydroxypyrazine (1051). 

In Eq. (14), Yoda et al. [50] studied the preparation of optically active lactones, with three contiguous stereogenic centers, from imides with two stereogenic centers. The precursor chiral imide was easily prepared from tartaric acid. Silylation of the 2,3-diol and addition of lipophilic Grignard reagents to the imide gave the ( -hydroxy amide. The authors are investigating the stereochemical consequences of their work. 

Among other enantioselective alkylations, a series of 3-aminopyrrolidine lithium amides (67 derived from 4-hydroxy-L-proline) have been used to induce high ee% in the addition of alkyllithiums to various aldehydes. Structure-activity relationships are identified, and the role of a second chiral centre (in the R group) in determining the stereochemistry of the product is discussed. 

The latter, on reaction with methylamine yielded via the P-epoxide 373, the trans-a aminoalcohol 374, which was N-acylated to the amide 375. Acid-catalysed dehydration of the tertiary alcohol 375, led to the olefin 375, from which the key radical precursor, the chlorothioether377 was secured in quantitative yield by reaction with N-chlorosuccinimide. In keeping with the earlier results recorded for structurally related compounds, 377 on heating in the presence of ruthenium dichloride and triphenylphosphine also underwent a 5-exo radical addition to generate the cyclohexyl radical 378 which recaptured the chlorine atom to furnish the a-chloro-c/5-hydroindolone 379. Oxidation of thioether 379 gave the corresponding sulfoxide 380, which on successive treatment with trifluoroacetic anhydride and aqueous bicarbonate led to the chloro-a-ketoamide 381. The olefin 382 resulting from base induced dehydrochlorination of 381, was reduced to the hydroxy-amine 383, which was obtained as the sole diastereoisomer... 

Enantiopure amide derivatives (64) of -unsaturated a-hydroxy acids have been made by addition of a vinylsilane, R2R1C=(4ISiMe3, to /V-phcnylglyoxamide.181 The reaction is catalysed by scandium(III) triflate complexed to a C2-symmetric PYBOX ligand derived from (f )-norephedrine. 

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