Alkylation carboxylic acid synthesis

H,6H-Purine, l,7-dimethyl-6-oxo-UV spectra, 5, 517 7H,8H-Purine, 8-oxo-UV spectra, 5, 517 Purinecarboxamides reactions, 5, 550, 551 Purinecarboxylic adds reactions, 5, 550 Purine-6-carboxylic acids synthesis, 5, 593 Purine-8-carboxylic acids synthesis, 5, 593 Purine nucleotides biosynthesis, 1, 87-88 Purine[9,8-a]quinolines, 5, 566 Purines, 5, 499-605 aldehydes reactions, 5, 549 synthesis, 5, 593 alkylation, 5, 505, 528-538 amination, 5, 541-542 anions... 

Fig. 13.42. Helmchen synthesis of enantiomerically pure a-alkylated carboxylic acids. The deprotonation of the propionic acid ester results in the "f "-enolate in the solvent THF and in the "Z"-enoLate in the solvent mixture THF/HHPA. In these projections, both enolates react preferentially from the front. The "f" -enolate results in a 97 3 mixture of 5- and fi-configured a-benzyl-propionic acid esters (X marks the chiral alkoxide group), while the "Z"-enolate results in a 5 95 mixture. Chromatographic separation and reduction of the C(=0)—Xc groups afford alcohol B with 100% ee from the " "-enolate and alcohol ent-B with 100% ee from the "Z"-enolate.

Fig. 13.43. Evans synthesis of enantiomerically pure a-alkylated carboxylic acids.

The alkylations of the oxazolidinone-containing amide enolate of Figure 13.43 occur with diastereoselectivities of 93 7 and > 99 1, respectively. The hydrogen peroxide-accelerated alkaline hydrolysis of these compounds occurs with complete retention of the previously established configuration at the a-stereocenter. To date, the Evans synthesis offers the most versatile access to enantiomerically pure a-alkylated carboxylic acids. 

Fig. 10.38. Evans synthesis of enantiomerically pure a-alkylated carboxylic acids. The amides are derived from oxazolidinones and yield Z -enolates with high stereoselectivity. The alkylating agent attacks in both cases from the side that is opposite to the side of the substituent highlighted in red.

This chiral auxiliary has been applied to the enantioselective synthesis of a-alkyl carboxylic acids such as (5 )-2-methyl-4-pentenoic acid. A retrosynthetic analysis of the carbon skeleton of 2-methyl-4-pentenoic acid suggests preparation by alkylation of the enolate of a propanoyl group with an allyl halide. 

The Asymmetric Synthesis of Nonracemic p-Alkyl Carboxylic Acids and ( -Substituted Cyclopentanones... 

G. W. Gribble, J. M. Jasinski, J. T. Pellicone, and J. A. Panetta. Reactions of sodium borohydride in acidic media VIII. A-alkylation of aliphatic secondary amines with carboxylic acids. Synthesis, 1978, 766. 

The palladium(II)-catalyzed olefin carbonylation reaction was first reported more than 30 years ago in studies by Stille and co-workers and James et al. The reaction of carbon monoxide with cis- and tra 5-but-2-ene in methanol in the presence of palladium(II)-chloride and copper(II)-chloride yielded threo- and eryt/zro-3-methoxy-2-methyl-butanoate, respectively. The transformation that was based on the well-known Wacker process for oxidation of ethylene into acetaldehyde in water " is now broadly defined as the Pd(II)-catalyzed oxycarbonylation of the unsaturated carbon-carbon bonds. This domino reaction includes oxypalladation of alkenes, migratory insertion of carbon monoxide, and alkoxylation. Since the development of this process, several transformations mediated by palladium(II) compounds have been described. The direct oxidative bisfunctionalization of alkenes represents a powerful transformation in the field of chemical synthesis. Palladium(II)-promoted carbonylation of alkenes in the presence of water/alcohol may lead to alkyl carboxylic acids (hydrocarboxylation), diesters [bis(aIkoxycarbonyla-tion)], (3-alkoxy carboxylic acids (alkoxy-carboxylation), or (3-alkoxy esters (alkoxy-carbonylation or alkoxy-alkoxy-carbonylation). Particularly attractive features of these multitransformation processes include the following ... 

Section 21 7 The malonic ester synthesis is related to the acetoacetic ester synthesis Alkyl halides (RX) are converted to carboxylic acids of the type RCH2COOH by reaction with the enolate ion derived from diethyl mal onate followed by saponification and decarboxylation... 

Malonic ester synthesis (Section 21 7) Synthetic method for the preparation of carboxylic acids involving alkylation of the enolate of diethyl malonate... 

Isoquinoline reacts with aliphatic carboxylic acids photolyticaHy or with a silver catalyst to give excellent yields of alkylation products by decarboxylation (155). This method is useful in the synthesis of 2-benzoyhsoquinolines bearing a variety of aromatic substituents in the 1-position (156). 

Azodne-3-carboxylic acid, 7V-alkyl-2-oxo-l,2,3,4-tetrahydro synthesis, 7, 662... 

Benzimidazole-2-carboxylic acid decarboxylation, 5, 435 Benzimidazole-3-carboxylic acid, 1-hydroxy-ethyl ester synthesis, 6, 407 Benzimidazoles acidity, 5, 50, 385, 386 acylation, 5, 71, 391, 402, 417 2V-alkyl-... 

Furan-2-carbonyl chloride, 5-alkyl-3,4-dichloro-synthesis, 4, 690 Furancarboxamides rotational isomerism, 4, 543 Furan-2-carboxylic acid, 5-acetylamino-ethyl ester reactions, 4, 647 Furan-2-carboxylic acid, amino-properties, 4, 708 Furan-2-carboxylic acid, 5-bromo-nitration, 4, 603, 711 Furan-2-carboxylic acid, 3-methyl-methyl ester bromination, 4, 604 Furan-2-carboxylic acid, 5-methyl-nitration, 4, 602... 

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