Α-keto Esters Research Articles

Oxone-Mediated Oxidative Cleavage of β-Keto Esters and 1,3-Diketones to α-Keto Esters and 1,2-Diketones in Aqueous Medium

A versatile and highly efficient method for the direct synthesis of α-keto esters and 1,2-diketones has been developed. This approach utilizes the oxidative cleavage of a variety of β-keto esters and 1,3-diketones mediated by an Oxone/aluminum trichloride system. The simple one-step oxidation reaction proceeded selectively in aqueous media to afford products in high yields, short reaction times, and environmentally benign conditions.

A Csp3–Csp3 Bond Forming Reductive Condensation of α-Keto Esters and Enolizable Carbon Pronucleophiles

The preparation of densely functionalized unsymmetrical 1,4-dicarbonyl structural motifs by a phosphorus(III)-mediated reductive condensation of α-keto esters and enolizable carbon pronucleophiles is described. The reaction, which is initiated by Kukhtin-Ramirez addition of commercially available tris(dimethylamino)phosphine to the α-keto ester substrate, proceeds rapidly under mild conditions.

Biomimetic Asymmetric 1,3-Dioplar Cycloaddition: Amino Acid Precursors in Biosynthesis Serve as Latent Azomethine Ylides

The first asymmetric catalytic biomimetic three-component 1,3-dipolar cycloaddition of α-keto esters and benzylamine with electron-deficient olefins, inspired by the transamination of α-keto acids involving pyridoxal phosphate (PLP)-dependent enzymes in biological systems, giving several families of structurally diverse pyrrolidine derivatives in high yields and excellent enantioselectivities (up to 99% ee) under mild conditions is described.

Asymmetric Synthesis of anti-β-Amino-α-Hydroxy Esters via Dynamic Kinetic Resolution of β-Amino-α-Keto Esters

A method for the asymmetric synthesis of enantioenriched anti-α-hydroxy-β-amino acid derivatives by enantioconvergent reduction of the corresponding racemic α-keto esters is presented. The requisite α-keto esters are prepared via Mannich addition of ethyl diazoacetate to imines followed by oxidation of the diazo group with Oxone. Implementation of a recently developed dynamic kinetic resolution of β-substituted-α-keto esters via Ru(II)-catalyzed asymmetric transfer hydrogenation provides the title motif in routinely high diastereo- and enantioselectivity.

Asymmetric hydrogenation of methyl pyruvate in the continuous gas phase using Supported Ionic Liquid Phase (SILP) catalysis

Based on the recently reported asymmetric hydrogenation of methyl acetoacetate in a continuous-flow, gas phase reaction using Supported Ionic Liquid Phase (SILP) catalysis, this study deals with the even more challenging asymmetric reduction of the α-keto ester methyl pyruvate. Different support materials, ligands and ionic liquids were screened to identify an optimized Ru-based SILP catalyst. With Ru-BINAP dissolved in the ionic liquids 3-hydroxypropylpyridinium bis(trifluoromethylsulfonyl)imide on silica 100, stable catalyst performance could be obtained for more than 50h time-on-stream. At 95°C and with a residence time in the reactor of less than 3s a stable product yield of 80–84% was obtained with moderate but stable enantiomeric excess of 26–30%.

ChemInform Abstract: A Tertiary Amine Catalyzed Carbocyclization Sequence to Furnish Spirocyclo Hexene Systems Having Vicinal Quaternary Stereocenters.

Two types of enolates can be formed stepwise from enolisable 1,3-dicarbonyl-substituted propene systems in the presence of catalytic amounts of 1,4-diazabicyclo[2.2.2]octane (DABCO) to accomplish a highly selective carbocyclization with β,γ-unsaturated α-keto esters, giving functionalized spiroketones with vicinal quaternary stereocenters.

ChemInform Abstract: Microwave‐Assisted Synthesis of Novel Imidazo[2,1‐b]thiazole Derivative Attached to Quinoxalinones.

AbstractVarious biologically important derivatives are prepared by reaction of α‐keto esters (I) with o‐phenylenediamines.

Diametric stereocontrol in dynamic catalytic reduction of racemic acyl phosphonates: divergence from α-keto ester congeners.

An unexpected dichotomy was observed in the Ru-catalyzed asymmetric transfer hydrogenation of acyl phosphonates: reduction proceeded from the opposite face relative to that observed in the analogous reduction of α-keto esters. The first highly selective catalytic hydrogenation of acyl phosphonates was utilized in the dynamic kinetic resolution of α-aryl acyl phosphonates, providing β-stereogenic α-hydroxy phosphonic acid derivatives.

Preparation of Chiral Hydroxy Esters Using Actinobacteria: Biocatalyst Activity of Marine-Derived <i>Micromonospora</i> and <i>Streptomyces</i> Strains

To research the potential ability of marine-derived actinomycetes to act as biocatalysts, 8 Micromonospora strains and 5 Streptomyces strains were screened. Two recommended media (227 and 1076 media) and 2 modified media (1076-25% and P-1076-25% media) for liquid culture of these marine-derived actinomycetes were tested. As a result, 2 Micromonospora strains (Micromonospora sp. NBRC107096 and 107097) cultured with the 1076-25% medium and 2 Streptomyces strains (Streptomyces tateyamensis NBRC105048 and Streptomyces sp. NBRC105896) cultured with P-1076-25% medium showed a good growth. The stereoselective reduction of α-keto esters using these 4 actinomycetes was tested. As a result, it was found that these strains had a reducing activity toward various α-keto esters. The introduction of L-glutamate or sucrose as an additive remarkably increased the conversion ratios in the reduction of substrates by the Micromonospora strain. Furthermore, in the presence of L-alanine, Streptomyces tateyamensis NBRC105048 reduced ethyl pyruvate, ethyl 2-oxobutanoate, ethyl 2-oxopentanoate, ethyl 2-oxohexanoate, and ethyl 3-methyl-2-oxobutyrate to the corresponding α-hydroxy ester with a high conversion ratio and with excellent enantiomeric excess. Thus, we found that these marine-derived actinomycetes have great potential to be used as biocatalysts for stereoselective reduction of carbonyl compounds.

Catalytic highly asymmetric 1,5(6)-selective cyclization reaction of α-hydroxyimino cyclic ketones: direct approach to ring-fused hydroxyimino dihydropyrans

Herein, we have disclosed a catalytic asymmetric 1,5(6)-selective Michael/cyclization reaction of α-hydroxyimino cyclic ketones with γ,β-unsaturated α-keto esters. Unlike the previous catalytic strategies, this reaction provides a convenient 1,5(6)-selective asymmetric pathway to access synthetically useful ring-fused dihydropyrans. In general, high levels of yield, enantio- and diastereoselectivity (up to 99% yield, >99% ee and >20 : 1 dr) were obtained.

A tertiary amine catalyzed carbocyclization sequence to furnish spirocyclo hexene systems having vicinal quaternary stereocenters

Two types of enolates can be formed stepwise from enolisable 1,3-dicarbonyl-substituted propene systems in the presence of catalytic amounts of 1,4-diazabicyclo[2.2.2]octane (DABCO) to accomplish a highly selective carbocyclization with β,γ-unsaturated α-keto esters, giving functionalized spiroketones with vicinal quaternary stereocenters.

Reactions of organolithiums with dialkyl oxalates. A flow microreactor approach to synthesis of functionalized α-keto esters

Reactions of functionalized aryllithiums with dialkyl oxalates were achieved using a flow microreactor to obtain α-keto esters with high selectivity by virtue of fast 1 : 1 micromixing.

P-chirogenic organocatalysts: application to the aza-Morita–Baylis–Hillman (aza-MBH) reaction of ketimines

The P-chirogenic organocatalysts were found to promote the enantioselective aza-Morita-Baylis-Hillman reaction of ketimines derived from acyclic α-keto esters. In the P-chirogenic organocatalyzed aza-MBH reactions, α,α-disubstituted α-amino acid derivatives were obtained in high yields with high enantioselectivities (up to 97% ee).

α-ケトエステルのバイオミメティックトランスアミノ化反応

The development of biomimetic reactions is one of the major challenges for synthetic chemists, because mimicking these complicated reactions in the laboratory by simple catalytic systems is difficult to achieve in general. Vitamine B6-dependent aminotransferase-catalyzed transamination of α-keto acids from pyridoxamine is an important process to generate α-amino acids in nature. In this review, recent progresses on the biomimetic transamination of α-keto esters are described.

Asymmetric Vinylogous Aldol Reaction via H-Bond-Directing Dienamine Catalysis

The enantioselective direct vinylogous aldol reaction of 3-methyl 2-cyclohexen-1-one with α-keto esters has been developed. The key to success was the design of a bifunctional primary amine-thiourea catalyst that can combine H-bond-directing activation and dienamine catalysis. The simultaneous dual activation of the two reacting partners results in high reactivity while securing high levels of stereocontrol.

Asymmetric synthesis of diverse glycolic acid scaffolds via dynamic kinetic resolution of α-keto esters.

The dynamic kinetic resolution of α-keto esters via asymmetric transfer hydrogenation has been developed as a technique for the highly stereoselective construction of structurally diverse β-substituted-α-hydroxy carboxylic acid derivatives. Through the development of a privileged m-terphenylsulfonamide for (arene)RuCl(monosulfonamide) complexes with a high affinity for selective α-keto ester reduction, excellent levels of chemo-, diastereo-, and enantiocontrol can be realized in the reduction of β-aryl- and β-chloro-α-keto esters.

Palladium-Catalyzed Asymmetric Formal [3+2] Cycloaddition of Vinyl Cyclopropanes and β,γ-Unsaturated α-Keto Esters: An Effective Route to Highly Functionalized Cyclopentanes

Palladium-catalyzed asymmetric formal [3+2] cycloaddition of vinyl cyclopropanes and β,γ-unsaturated α-keto esters proceeded smoothly in the presence of chiral imidazoline–phosphine ligands to give the corresponding highly functionalized cyclopentanes in good yields along with high diastereo- and enantioselectivities under mild conditions.

An Efficient Asymmetric Biomimetic Transamination of α-Keto Esters to Chiral α-Amino Esters

An efficient asymmetric biomimetic transamination of α-keto esters with quinine derivatives as chiral bases was described. A wide variety of α-amino esters containing various functional groups can be synthesized in high yield and enantioselectivity.

ChemInform Abstract: Enantioselective Direct Aldol Reaction of α‐Keto Esters Catalyzed by (Sa)‐Binam‐D‐prolinamide under Quasi Solvent‐Free Conditions.

(Sa)-Binam-D-prolinamide (20 mol%), instead of (Sa)-binam-L-prolinamide, in combination with chloroacetic acid (100 mol%) is an efficient organocatalyst for the direct aldol reaction between α-keto esters as electrophiles and alkyl and α-functionalised ketones, under quasi solvent-free conditions, providing access to highly functionalised chiral quaternary γ-keto α-hydroxyesters with up to 92% ee.

A Nonmetal Approach to α‐Heterofunctionalized Carbonyl Derivatives by Formal Reductive XH Insertion

Keeping it organic: A direct synthesis of α-alkoxy and α-amino ester derivatives by direct reductive coupling of widely available, stable α-keto esters and protic pronucleophiles is described (see scheme; X = OR, NR(2)). The method serves as a convenient nonmetal alternative to X-H insertion by diazo decomposition.