Direct synthesis of α-thio aromatic acids from aromatic amino acids

Modified amino acids are useful synthetic components in both chemistry and biology. Here we describe a simple, scalable two-step procedure to generate α-thio aromatic acids from aromatic amino acids with yields of up to 96%. Diazotization and α-lactone mediated bromination efficiently form the α-bromo acid with retention of configuration. Thiol substitution with mild reagents such as sodium hydrosulfide or sodium trithiocarbonate provides the inverted, free α-thio acid. The mildly acidic soft nucleophile can then be utilized in many synthetic applications.     

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.     

Electrochemical synthesis of α,α-dihaloacetophenones from terminal alkyne derivatives

By virtue of electrochemistry, a series of α,α-dihaloacetophenones were easily obtained with good to excellent yields. This electrochemical procedure was taken in a divided cell with constant current in aqueous media. The reaction can be carried out smoothly at room temperature under metal and oxidant free condition, which provides an eco-friendly synthesis for the α,α-dihaloacetophenone derivatives.     

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.     

The synthesis of ω-thienylalkane acids from ω-chloroalkane acids

Summary We have worked out a preparative method for the synthesis of -thienylalkane acids by acylation of thiophene with -chloroalkane acid chlorides followed by conversion of the resulting -chloroalkyl(2-thienyl)ketones into the corresponding acids by reaction with sodium malonic ester or potassium cyanide, and reduction of the resulting products with their simultaneous hydrolysis.Here and later we mean -(2-thienyl)alkne acids.We take this opportunity to thank R. Kh. Freidlina, A. A. Beér, and M. A. Besprozvannii for giving us enough -chloroalkane acids.     

Regiospecific synthesis of α-chloro- and α-fluoro-1,2-diones

α-Chloro-1,2-diones and α-fluoro-1,2-diones were prepared from the corresponding α-chloroaldimines by a sequence of reactions involving cyanation to α-cyanoenamines, α-halogenation to form α-chloro- or α-fluoroimidoyl cyanides and addition of organolithium reagents across the nitrile moiety, followed by acidic hydrolysis. All steps are straightforward and occur without side reactions finally leading to regiospecifically chlorinated and fluorinated 1,2-diones in good yields.     

Direct asymmetric synthesis of α-deuterated α-amino acid derivatives from the parent α-amino acids via memory of chirality

A method for asymmeyric α-deuteration of α-amino acid derivatives has been developed by a memory of chirality (MOC) strategy. The α-deuterated α-amino acid derivatives with 88–93% D were obtained in 60–98% ee in retention of the configuration (7 examples). The characterisrtic feature of the present procedure is that asymmeric induction was achieved by employing the parent amino acid derivatives as a sole source of chirality without the use of any external chiral souces.     

Copper-catalyzed synthesis of α-ketothioamides from ketones

In this paper, the conversion of acetophenone to α-ketothioamide was reported in the presence of CuI as the catalyst and S₈/DMF as the coupling partners. The presence of both KF and NaOH was found to be necessary to achieve the high yield of the product. Propiophenone and butyrophenone also reacted in the presence of phenylboronic acid as an additive. Willgerodt-Kindler products were not observed in these reactions.     

Copper-mediated synthesis of N,N''''-diarylhydrazines from boronic acids

N,N0-Diarylhydrazines have been prepared via the reaction of N-Boc-aryl hydrazines with boronic acids mediated by copper acetate. This mild reaction condition tolerates the presence of a variety of functional groups.     

Highly regio- and syn-diastereoselective synthesis of 4-hydroxy-1,2-alkadienylcarbamates from α-titanatedl 2-alkynylcarbamates and aldehydes1,2

$\text{N}$,$\text{N-}$Diisopropyl 2-alkynyl carbamates 9 are deprotonated by $\text{n}$-butyllithium to form lithium compounds 10. After exchange of the cation, titanium reagents 13 add highly diastereoselective to aldehydes with formation of the title compounds 14. In contrast to metallated 2-alkynyl ethers, the reagents 10 and 13 exhibit high γ-regioselectivity in carbonyl addition reactions, due to the chelating carbamoyl group. The $\text{syn}$-configuration of 14 was deduced from the crystal structure of the urethane derivative 21.     

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.     

Polymeric chiral phase-transfer catalysts derived from cinchona alkaloids for enantioselective synthesis of α-amino acids

A series of dimeric/trimeric chiral quaternary ammonium salts derived from cinchona alkaloids were designed as efficient and practical chiral phase-transfer catalysts (PTCs). Presented are the details on the development of the dimeric PTCs for the synthesis of optically active α-amino acid derivatives and the optimization of the reaction variables suitable for the dimeric PTCs. The 1,3-phenyl- and the 2,7-naphthyl-linked dimeric PTCs showed excellent catalytic capability on the reactivity and enantioselectivity in the catalytic phase-transfer alkylation of N-(diphenylmethylene)glycine tert-butyl ester (1). A variety of α-amino acid derivatives were obtained with high enantiopurities using the dimeric PTCs, especially the 2,7-naphthyl-dimer 41, in a very practical manner.     

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.     

One-pot gram-scale synthesis of γ-hydroxybutenolides through catalyst-free annulation of α-amino acids with α-keto acids in water

A one-pot gram-scale synthetic route for the preparation of γ-hydroxybutenolides via catalyst-free annulation of α-amino acids with α-keto acids in water is reported. The method shows many advantages such as readily available starting materials, mild reaction conditions, operational simplicity, acceptable yields, and requiring no extra catalysts or additions. Furthermore, the method is innocuous to the environment, also is valuable to industry.     

Chiron based synthesis of isocoumarins: reactivity of α-substituted carboxylic acids

The asymmetric synthesis of a novel (S)-isocoumarin has been attempted in a single step by the coupling of homophthalic acid with (S)-N-protected amino acids and α-chloroacids at high temperature by exploiting a chiral pool methodology. The coupling of homophthalic acid with N-protected (S)-amino acids gave exclusion of the carboxyl/alkyl group. However, coupling of homophthalic acid with α-chloroacids afforded asymmetric isocoumarins in high yield.