Α-branched Carboxylic Acids Research Articles

Deoxygenative α-alkylation and α-arylation of 1,2-dicarbonyls.

Construction of C–C bonds at the α-carbon is a challenging but synthetically indispensable approach to α-branched carbonyl motifs that are widely represented among drugs, natural products, and synthetic intermediates. Here, we describe a simple approach to generation of boron enolates in the absence of strong bases that allows for introduction of both α-alkyl and α-aryl groups in a reaction of readily accessible 1,2-dicarbonyls and organoboranes. Obviation of unselective, strongly basic and nucleophilic reagents permits carrying out the reaction in the presence of electrophiles that intercept the intermediate boron enolates, resulting in two new α-C–C bonds in a tricomponent process.

Deracemizing α-Branched Carboxylic Acids by Catalytic Asymmetric Protonation of Bis-Silyl Ketene Acetals with Water or Methanol.

We report a highly enantioselective catalytic protonation of bis-silyl ketene acetals. Our method delivers α-branched carboxylic acids, including nonsteroidal anti-inflammatory arylpropionic acids such as Ibuprofen, in high enantiomeric purity and high yields. The process can be incorporated in an overall deracemization of α-branched carboxylic acids, involving a double deprotonation and silylation followed by the catalytic asymmetric protonation.

Difluoromethylation of Carboxylic Acids via the Addition of Difluorinated Phosphorus Ylide to Acyl Chlorides.

A one-step protocol for the difluoromethylation of carboxylic acids is described. The reaction involves the interaction of intermediate acyl chlorides with in situ generated difluorinated phosphorus ylide Ph3P═CF2. Aromatic acids can be selectively transformed within one step either to bis-difluoromethylated alcohols or to difluorinated ketones depending on the particular reaction conditions. For bulky α-branched carboxylic acids, only ketones are produced.

Design and synthesis of a new polymer-supported Evans-type oxazolidinone: an efficient chiral auxiliary in the solid-phase asymmetric alkylation reactions

Wang resin-supported Evans' chiral auxiliary ( 23 ) was designed based on a novel polymer-anchoring strategy, which utilizes the 5-position of the oxazolidinone ring, and its new synthetic route applicable to multi-gram preparation in just a day was developed. Solid-phase Evans' asymmetric alkylation on 23 -derived N-acylimide resin and following lithium hydroperoxide-mediated chemoselective hydrolysis afforded the corresponding α-branched carboxylic acids in desired high stereoselectivities (up to 97% ee) and moderate to good overall yield (up to 70%, for 3 steps), which were comparable to those of the conventional solution-phase methods. Furthermore, recovery and recycling of the polymer-supported chiral auxiliary were successfully achieved without decreasing the stereoselectivity of the product. Therefore, this is the first successful example that the solid-phase Evans' asymmetric enolate-alkylation was efficiently performed on the solid-support, and it is concluded that the connection to the solid-support via the 5-position of the oxazolidinone ring is an ideal strategy in the solid-phase Evans' chiral auxiliary.

Carbonylation of branched olefins in the presence of BF3�H2O and ethyl formate at atmospheric pressure

The carbonylation of branched olefins using ethyl formate occurs in one stage at atmospheric pressure in the presence of BF3·H2O as catalyst with the production of the ethyl esters ofα, α-branched carboxylic acids in yields up to 50–70%.

N-acyl derivatives of chiral amines as novel, readily prepared phases for the separation of optical isomers by gas chromatography

The results reported demonstrate that it suffices for a chiral stationary phase to contain an amide group and an asymmetric carbon atom, attached to the nitrogen atom [RCONHCH(CH 3)R′], in order to show selectivity in its interaction with the enantiomers of amides such as N-trifluoroacetylamines, N-trifluoroacetylamino acid esters and α-methyl- and α-phenylcarboxylic acid amides. The best efficiency is obtained when R′ is aromatic, particularly α-naphthyl, as in N-lauroyl- S-α-(1-naphthyl)ethylamine. The highest resolution factors were found for aromatic solutes, such as N-trifluoroacetyl-α-phenylethylamine and α-phenylbutyric acid amides, which could be resolved readily on packed columns. The enantiomers of α-branched carboxylic acids were separated for the first time by gas chromatography. Based on the packing arrangement in the crystalline form of the N-acetyl homologue of N-lauroyl- S-α-(1-naphthyl)ethylamine, a mechanism for the resolution is proposed. It is assumed that the mode of association found in the solid state is at least partially retained in the melt through a network of hydrogen bonds. The mechanism proposed is developed with particular reference to the aromatic solute-solvent systems. It is suggested that the solute is intercalated (“sandwiched”) between two solvent molecules. Arguments, based on X-ray data, are given to explain the selectivity observed.

Analysis of some β-branched primary alcohols and α-branched carboxylic acids by combined capillary gas chromatography and mass spectrometry

The application of a combined system of capillary chromatography and mass spectrometry for the separation and identification of C 6-C 10 β-branched primary alcohols and C 11-C 17 and C 19 α-branched carboxylic acids as their methyl esters is described. The retention indices were measured of α-branched carboxylic acid methyl esters and β-branched alcohols on polyphenyl ether and polypropylene glycol, respectively.