Synthesis and application of C2-symmetric diamino FERRIPHOS as ligands for enantioselective Rh-catalyzed preparation of chiral α-amino acids

C₂-Symmetrical ferrocenyl diamino diphosphines (diamino FERRIPHOS ligands) proved to be excellent ligands for the rhodium-catalyzed enantioselective reduction of methyl α-acetamidoacrylates. The straightforward synthesis, their air stability and the easy modification of their structure makes these ligands especially interesting for transition metal-catalyzed hydrogenations. α-Amino acids with enantioselectivities greater than 95% (and up to 99.3% ee) were obtained with no need of further recrystallization.     

Catalytic Strecker reaction: g-C3N4-anchored sulfonic acid organocatalyst for the synthesis of α-aminonitriles

Research on Chemical Intermediates - Efficient organocatalyst for enantioselective Strecker reaction was synthesized using g-C3N4 sheets (CN). CN-anchored sulfonic acid (CN-Bu-SO3H) was found to be...     

Performance of C1-symmetric chiral ammonium betaines as catalysts for the enantioselective Mannich-type reaction of α-nitrocarboxylates

The catalytic performance of C₁-symmetric chiral ammonium betaines in the enantioselective direct Mannich-type reaction of α-nitrocarboxylates with N-Boc imines has been investigated. The most effective catalyst structure has been identified; this provides a reliable synthetic route to a variety of enantiomerically enriched α-tetrasubstituted α,β-diamino acid derivatives.     

Stereoselective alkylation of C2-symmetric chiral N-phthaloylglycinamides in the preparation of enantiopure α-amino acids

The novel, chiral glycinamides (S,S)-3 and (S,S)-4 were prepared in good yields from C₂-symmetric chiral amines (S,S)-1 and (S,S)-2, respectively. Enolate formation and addition to methyl iodide and benzyl bromide proceeded in good yield and high diastereoselectivity, especially in the presence of LiCl or DMPU. Removal of the phthaloyl protecting group with hydrazine, followed by hydrolysis with 6N HCl, converted the benzylated product (S,S,S)-7 to enantiopure (S)-phenylalanine.     

Visual chiral recognition of mandelic acid and α-amino acid derivatives by enantioselective gel formation and precipitation

Novel chiral receptors based on l-phenylalanine and l-valine have been synthesized and their chiral recognition properties toward mandelic acid and N-tosyl α-amino acids are studied. The phenylalanine-based receptor undergoes enantioselective gel formation with R-mandelic acid and N-tosyl-d-valine, whereas the valine-linked receptor in their presence results in the formation of precipitates.     

Stereoselective alkylation of chiral glycine enolate synthons. The enantioselective synthesis of α-amino acid derivatives.

The highly stereoselective alkylation (% de=99.6 to 97.6) of a new chiral glycine enolate synthon derived from D-2-phenylglycinol is described. Deprotection of the alkylation adducts in a one-pot three-step procedure provides the ethyl ester hydrochloride salts of the corresponding α-amino acids with no attending racemization.     

Synthesis of novel chiral lipophilic pyridyl-containing β-amino alcohol ligands and enantioselective hydrolysis of α-amino acid esters by chiral metallomicelles

Seven novel chiral lipophilic pyridyl-containing β-amino alcohol ligands have been synthesized by coupling of 6-alkoxymethyl-2-chloromethylpyridine 3 with the corresponding chiral β-amino alcohols or l-cysteine. Their metal ion complexes have been investigated as catalysts for the enantioselective hydrolysis of N-protected α-amino acid esters in aqueous comicellar solution. The results indicate that the hydrophobic interactions between substrate and metallocatalyst, the rigidity of the ligand, the hydroxyl group of the ligand acting as a nucleophile for the transacylation process, and the micellar microenvironment are important factors for the activity and enantioselectivity. Large rate accelerations (up to three orders of magnitude) and moderate enantioselectivities (up to 7.81 (k_R/k_S)) employing 4a–Cu²⁺ have been observed.     

Silica-bonded S-sulfonic acid: an efficient and recyclable solid acid catalyst for the three-component synthesis of α-amino nitriles

Silica-bonded S-sulfonic acid (SBSSA) is employed as a recyclable catalyst for the synthesis of α-amino nitriles. These syntheses were performed via a one-pot three-component condensation of aldehydes, amines, and trimethylsilyl cyanide under mild reaction conditions at room temperature.     

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.     

Enantiospecific synthesis of α-amino acid semialdehydes: a key step for the synthesis of unnatural unsaturated and saturated α-amino acids

The enantiospecific synthesis of unnatural unsaturated and saturated α-amino acids based on a Wittig type reaction is described. The versatile synthetic intermediates, l-glutamic and l-aspartic acid semialdehydes, are obtained from the corresponding N,N-di-Boc-diesters, by the selective reduction of the ω-ester with DIBAL^® under controlled conditions. The semialdehydes are chemically stable for a prolonged time and react with various phosphorous ylides, under controlled conditions, to produce the enantiomerically pure unsaturated α-amino acids in high yields. The method is equally applicable to homologated diesters obtained by the presented methodology providing unsaturated amino acids with variable unsaturated positions and geometries. The corresponding saturated products can be obtained by simple hydrogenation.     

C_2-symmetric BINOL-squaramide as efficient organocatalyst for the enantioselective α-amination of 1,3-dicarbonyl compounds with dialkyl azodicarboxylates

The asymmetric α-amination of 1,3-dicarbonyl compounds with dialkyl azodicarboxylates has been achieved by C2-symmetric BINOL-squaramide bearing multiple hydrogen bond donors to provide the desired products in excellent yields and enantioselectivities (up to 99% yield and 98% ee).     

Trifluoroethanol as a metal-free, homogeneous and recyclable medium for the efficient one-pot synthesis of α-amino nitriles and α-amino phosphonates

Trifluoroethanol is found to be an efficient and recyclable medium in promoting one-pot, three-component coupling reactions of aldehydes or ketones, amines and trimethylsilyl cyanide or trimethyl phosphite to afford the corresponding α-amino nitriles or α-amino phosphonates in high yields. This protocol does not require the use of an acid or base catalyst.     

Camphor-based oxazaphospholanes as chiral templates for the enantioselective synthesis of α-chlorophosphonic acids

Constrained camphor-derived oxazaphospholanes have provided an efficient entry for the preparation of enantiomerically enriched α-chlorophosphonic acids.     

Oxalic acid as a simple and efficient organocatalyst for three-component synthesis ofα-amino nitriles

A simple,efficient,and general method has been developed for the synthesis ofα-amino nitriles.Oxalic acid as a BrФnsted acid promotes the addition of TMSCN to various imines(generated in situ).     

Self-assembly of an organocatalyst for the enantioselective synthesis of Michael adducts and α-aminoxy alcohols in a nonpolar medium

A proline–thiourea host–guest complex is described as a self-assembled organocatalyst for the enantioselective Michael addition of aldehydes to nitroolefins and for the asymmetric α-aminoxylation of both aldehydes and ketones. The Michael adducts were obtained in good yields of up to 80%, high diastereoselectivities of up to 5:95, and high enantiomeric excesses of up to 98%. The optically active aminoxy alcohols were synthesized in 60–85% yields with 94–99% enantiomeric excesses after reduction of the α-oxidation products using NaBH₄.     

A highly enantioselective Diels-Alder reaction of 1,2-dihydropyridine using a simple β-amino alcohol organocatalyst for a practical synthetic methodology of oseltamivir intermediate

An easily prepared chiral amino alcohol catalyst was found to provide an efficient synthetic intermediate of oseltamivir with excellent chemical yield and enantioselectivity (up to 98% yield and up to 98% ee) in enantioselective Diels-Alder reactions of 1,2-dihydropylidines with acroleins.     

A new general, practical and enantioselective synthesis of α-amino acids

In recent years, considerable efforts have been expended to the development ofenantioselective synthesis of α-amino acids and the use of α-amino acids as chiralbuilding blocks for the synthesis of complex molecules. Numerous unnatural aminoacids which are often the characteristic units of biologically active peptides, have alsobeen discovered. Herein we describe a convenient and general access to natural andunnatural α-amino acids which are based on the use of the chiral building blocks,(S)-1a-e and (R)-1a-e from kinetic resolution of α-furfuryl amines (Scheme 1).