Enantioselective synthesis of α-amino acids in chiral reverse micelles

Through alkylation of ethyl 2-phthalimidoacetate in chiral reverse micelles formed from chiral surfactants, followed by hydrazinolysis and hydrolysis of the resulting products, optically active α-amino acids were synthesized. The highest enantioselectivity was 59.5%. Meanwhile, we have found that the asymmetric induction depends on the reaction temperature, the alkyl chain length of surfactant and the strucure of the surfactants.     

Metal-free decarboxylative acylation of isoquinolines using α-keto acids in water

An efficient method for acylation of isoquinolines has been developed using α-ketoacids under metal- and additive-free conditions in water. The protocol involves C(sp²)H functionalization of isoquinolines providing an easy access to C1-benzoylated isoquinolines, which constitute the core structure of a number of biological active compounds and serve as key intermediate in the synthesis of many alkaloids.     

Absolute asymmetric synthesis of tertiary α-amino acids

Frozen: the spontaneous crystallization of an achiral compound in a chiral conformation is used as the unique source of chirality in an absolute asymmetric synthesis of tertiary amino acids. The dynamic axial chirality of tertiary aromatic amides is frozen in a crystal and is responsible for the stereoselectivity of the deprotonation/alkylation. α-Amino acid derivatives are synthesized in up to 96 % ee.     

One-pot efficient synthesis of aryl α-keto esters from aryl-ketones

A novel one-pot synthesis of aryl α-keto esters was developed through oxidation of aryl-ketones using selenium dioxide, esterification accompanied by ketalization, and hydrolysis. Both aromatics and heteroaromatics gave good yields by this one-pot method.     

Asymmetric synthesis of α,β-substituted γ-amino acids via conjugate addition

The first conjugate addition reaction of organocuprates to N-enoyl oxazolidinone where a N-protected γ-nitrogen atom and an α-methyl group are present into α, β-unsaturated system is described. This reaction gave anti-products in moderate yields and high diastereomeric ratios. The anti-products have two contiguous stereogenic centers, one formed by the conjugate addition reaction and the other by a diastereoselective protonation reaction. The removal of chiral oxazolidinone moiety and N-deprotection of amino group furnished chiral α, β-disubstituted γ-amino acids.     

A catalyst-free synthesis of α-aminophosphonates in glycerol

A simple and efficient method is described using glycerol as a solvent in the catalyst-free synthesis of α-aminophosphonates in high purity. Products are prepared by the Kabachnik–Fields reaction from amines, phosphites, and carbonyl compounds. The method does not require a toxic catalyst.     

Facile synthesis of α-hydroxy carboxylic acids from the corresponding α-amino acids

An effective and improved procedure is developed for the synthesis of α-hydroxy carboxylic acids by treatment of the corresponding protonated α-amino acid with tert-butyl nitrite in 1,4-dioxane–water. The amino moiety must be protonated and located α to a carboxylic acid function in order to undergo initial diazotization and successive hydroxylation, since neither β-amino acids nor acid derivatives such as esters and amides undergo hydroxylations. The method is successfully applied for the synthesis of 18 proteinogenic amino acids.     

A protocol for an asymmetric synthesis of γ-amino acids

A new and practical method for the asymmetric synthesis of γ-amino acids from β,γ-butenolides by an in situ esterification, condensation, and reduction in a one-pot procedure is described. This method is quite general for the preparation of both enantiomers of aryl or aliphatic γ-amino acids in high yields. These γ-amino-acid derivatives were also shown to be versatile synthetic intermediates for further transformations by their conversion to γ-lactams, δ-amino alcohols, and hydrolysis products in high yields with no racemization.     

Asymmetric synthesis of β-amino acids through application of chiral sulfoxide

This paper describes asymmetric synthesis of β-aminophenylpropionic acid through application of a homochiral sulfoxide auxiliary. High kinetically controlled (3R,2S,R_S)-diastereoselectivity (−60°C) is achieved during addition of the lithium enolate of tert-butyl (+)-(R)-p-toluenesulfinylacetate to substituted N-(benzylidene)toluene-4-sulfonamides 2a–2d. The reductive cleavage of adduct 3a with sodium amalgam yielded tert-butyl 3-(toluene-4-sulfonamido)-3-phenylpropionate 5a, which was subjected to ester hydrolysis and subsequent detosylation with sodium in liquid ammonia to yield (S)-β-aminophenylpropionic acid in good yield and high 91% e.e.     

A modular synthesis of dithiocarbamate pendant unnatural α-amino acids

Unnatural α-amino acids containing dithiocarbamate side chains were synthesized by a one-pot reaction of in situ generated dithiocarbamate anions with sulfamidates. A wide range of these anions participated in the highly regio- and stereo-selective ring opening of sulfamidates to produce the corresponding dithiocarbamate pendant α-amino acids in high yields.     

Oxidative decarboxylation of α-amino acids with coenzyme PQQ

Oxidative decarboxylation of α-phenylglycine with coenzyme pqq was performed catalytically in the presence of CTAB under mild conditions to give benzaldehyde and benzoic acid.     

Enantioselectivity of the reaction of α-amino acids with sodium azide and triethyl orthoformate in the synthesis of tetrazoles

Russian Journal of Organic Chemistry -     

Enantioselective synthesis of α-stereogenic γ-keto esters via formal umpolung

A feasible method has been developed for the enantioselective synthesis of α-stereogenic γ-keto esters. By employing nitro(phenylsulfonyl)methane as an acyl anion equivalent, the integrated Michael addition reaction-oxidative methanolysis protocol allows the preparation of various γ-keto esters with high optical purities.     

Asymmetric synthesis of α-amino acids by reduction of N-tert-butanesulfinyl ketimine esters

A highly regio- and diastereoselective reduction of various N-tert-butanesulfinyl ketimine esters with L-Selectride resulting in the formation of α-amino acids is reported. This method is quite general and also practical for the preparation of both enantiomers of aryl or aliphatic α-amino acids in high yields.     

Enantiopure synthesis of side chain-modified α-amino acids and 5-cis-alkylprolines

A short, concise synthesis of enantiopure, side chain-modified α-amino acids such as 4-oxo-L-norvaline, 6-oxo-L-homonorleucine, and 5-cis-alkyl prolines is described. Knoevenagel condensation of l-aminocarboxylate-derived β-ketoesters with aldehydes followed by reductive decarboxylation results in unnatural α-amino acids in good yield. A fluorescent amino acid is synthesized using a similar protocol. These studies show that aminocarboxylate-derived β-ketoesters are very useful intermediates and the method employed is both general and practical for the preparation of γ(δ)-oxo α-amino acids and alkylprolines.     

Novel approach to the synthesis of aliphatic and aromatic α-keto acids

A new practical and efficient synthesis of α-keto acids was accomplished starting from the synthon 1,4-diacetylpiperazine-2,5-dione. The synthesis encompasses both aromatic and aliphatic substrates proving to be versatile and innovative with excellent carbon economy and recycling of the glycine by-product.