The effect of benzyl amine on the efficiency of the base-catalyzed transamination of α-keto esters

This paper describes the effect of benzyl amine on the base-catalyzed transamination of α-keto esters. Among various benzyl amines examined, o-HOC₆H₄CH₂NH₂ was found to be highly effective for the reaction, affording a wide variety of α-amino esters in good yields. The o-OH group of the benzyl amine facilitates the transamination process likely via H-bond. Moderate enantiomeric excess was obtained for α-amino ester when a quinine derived catalyst was used.     

Lewis acid-catalyzed one-pot sequential reaction for the synthesis of α-halogenated β-keto esters

A Lewis acid-catalyzed one-pot sequential transformation of β-keto esters, aromatic aldehydes, and NCS/NBS was reported. The reaction proceeds by way of Knoevenagel condensation/Nazarov cyclization/halogenation to give α-chloro- and α-bromo-β-keto esters in moderate yields with high diastereoselectivities. However, several aromatic aldehydes with electron-withdrawing substituents afforded unexpected α,β′-dichloro-β-keto esters in good to high yields.     

Studies on the reaction of α-imino esters with organometallic compounds

Benzylzinc reagent reacted with α-imino ester (2) at the α-carbon exclusively, though other organometallic reagents such as Mg. Al, Cu, Tl, and B derivatives reacted at the nitrogen atom. Use of the (S)-amine as a chiral auxiliary of 2 created the R chirality at the imino carbon. Very high chiral Induction was realized In the reaction of prenylzinc reagent wlih α-imino 8-(-)phenylmenthyl ester (10). The reaction of 2 with heteroatom substituted allylic organometalic compounds (15) gave the corresponding α-heterostom substituted amino acid derivatives (16). Here again, the allylic zinc reagent gave the adduct in higher yield than the corresponding Tl, Al, and B reagents.     

A highly diastereoselective decarboxylative mannich reaction of β-keto acids with optically active N-sulfinyl α-imino esters

A range of protected γ-oxo-α-amino esters have been prepared in a highly regio- and stereoselective manner through the decarboxylative Mannich reaction of β-keto acids with optically active N-tert-butanesulfinyl α-imino esters in the presence of 3 mol % La(OTf)(3) or 5 mol % Y(OTf)(3) at 20 °C. Preliminary mechanistic studies indicate that the reaction proceeds through imine addition followed by decarboxylation.     

SPANamine derivatives in the catalytic asymmetric α-fluorination of β-keto esters

The use of C₂-symmetric enantiopure nitrogen ligands in the asymmetric catalytic α-fluorination of β-ketoesters is described. SPANamine 1 in the presence of nickel salts gives up to 63% ee in the fluorination of tert-butyl 2-oxocyclopentanecarboxylate with N-fluorosuccinimide (NFSI). The same enantioselectivity is obtained when SPANamine 1 is used as an organocatalyst, although the reaction is much slower.     

CO2 deactivation of supported amines: does the nature of amine matter?

Adsorption of CO(2) was investigated on a series of primary, secondary, and tertiary monoamine-grafted pore-expanded mesoporous MCM-41 silicas, referred to as pMONO, sMONO, and tMONO, respectively. The pMONO adsorbent showed the highest CO(2) adsorption capacity, followed by sMONO, whereas tMONO exhibited hardly any CO(2) uptake. As for the stability in the presence of dry CO(2), we showed in a previous contribution [J. Am. Chem. Soc.2010, 132, 6312-6314] that amine-supported materials deactivate in the presence of dry CO(2) via the formation of urea linkages. Here, we showed that only primary amines suffered extensive loss in CO(2) uptake, whereas secondary and tertiary amines were stable even at temperature as high as 200 °C. The difference in the stability of primary vs secondary and tertiary amines was associated with the occurrence of isocyanate as intermediate species toward the formation of urea groups, since only primary amines can be precursors to isocyanate in the presence of CO(2). However, using a grafted propyldiethylenetriamine containing both primary and secondary amines, we demonstrated that while primary amines gave rise to isocyanate, the latter can react with either primary or secondary amines to generate di- and trisubstituted ureas, leading to deactivation of secondary amines as well.     

Organocatalytic asymmetric aldol reaction of hydroxyacetone with β,γ-unsaturated α-keto esters: facile access to chiral tertiary alcohols

An efficient direct asymmetric aldol reaction between hydroxyacetone and β,γ-unsaturated α-keto esters has been successfully developed. In the presence of 9-amino-9-deoxy-epi-cinchonine and trifluoroacetic acid, the direct aldol reaction of O-protected hydroxyacetone proceeded in a highly enantioselective manner, affording the desired adducts containing a chiral tertiary alcohol in high yields and with excellent enantioselectivities. The aldol products obtained are valuable precursors for the synthesis of 2-substituted glycerol derivatives.     

Thiourea-catalyzed asymmetric domino Michael-cyclization reaction of 3-isothiocyanato oxindoles with β,γ-unsaturated α-keto esters for the synthesis of spirocyclic oxindoles

A reaction between 3-isothiocyanato oxindoles and β,γ-unsaturated α-keto esters catalyzed by a chiral thiourea organocatalyst via a domino Michael-cyclization process is described, which delivers a range of biologically important 2′-thioxospiro[indoline-3,4′-oxazolidin]-2-one compounds in high yields with good diastereo- and enantioselectivities (up to 99% yield, >99:1 dr, >99% ee). Moreover, two of 2′-thioxospiro[indoline-3,4′-oxazolidin]-2-one compounds were found to significantly behave in anti-inflammatory activities in a preliminary biological evaluation.     

Transition-metal,organic solvent and base free α-hydroxylation of β-keto esters and β-keto amides with peroxides in water

Without employing any transition metal, organic solvent and base, a facile, economical and environmentally friendly strategy has been developed for the α-hydroxylation of β-keto esters and β-keto amides with peroxides via radical cross-coupling reaction in water under open-air conditions. This protocol allows a convenient access to various α-hydroxy-β-keto esters and α-hydroxy-β-keto amides with up to 92% yield (34 examples). Moreover, the reaction was successfully scaled up to gram quantity and mechanistic studies showed the radical pathway was involved in this hydroxylation.     

Highly enantioselective aldol reaction of acetone with β,γ-unsaturated α-keto esters promoted by simple chiral primary-tertiary diamine catalysts

A series of primary-tertiary diamine catalysts were successfully applied to promote the enantioselective aldol reaction of acetone with β,γ-unsaturated α-keto esters in excellent yields (up to 99%) and enantioselectivities (up to 96% ee).     

Bifunctional cinchona alkaloids-catalyzed asymmetric [4+2] cycloaddition reaction of β,γ-unsaturated α-keto esters with oxazolones

A highly enantioselective [4+2] cycloaddition reaction of β,γ-unsaturated α-keto esters with oxazolones was realized with readily available cinchona alkaloids as the catalysts. Using this reaction, a series of highly functionalized δ-lactones with adjacent α-quaternary-β-tertiary stereocenters were obtained in high yields (up to 97%) and with good-to-excellent enantioselectivities (up to 97% ee).     

Copper-catalyzed Pummerer type reaction of α-thio aryl/heteroarylacetates: Synthesis of aryl/heteroaryl α-keto esters

A copper catalyzed Pummerer type reaction of α-thio aryl/heteroarylacetates is described for the first time. This transformation represents a new route to synthesize α-keto esters, which are important intermediates for pharmaceuticals and organic synthesis. The reaction proceeds via in situ generation of a thionium ion that undergoes hydrolysis to furnish α-keto esters in synthetically viable yields (up to 82%).     

Organocatalytic conjugate addition of α-nitroacetates to β,γ-unsaturated α-keto esters and subsequent decarboxylation: synthesis of optically active δ-nitro-α-keto esters

Organocatalytic asymmetric conjugate addition of tert-butyl nitroacetates to β,γ-unsaturated α-keto esters has been developed. The subsequent in situ hydrolysis-decarboxylation of the adducts provided 5-nitro-2-oxopentanoates. A pyrrolidine-based thiourea-tertiary amine was identified as the best catalyst. A number of γ-aryl, γ-alkyl, and γ-heteroaryl β,γ-unsaturated α-keto esters and α-substituted tert-butyl nitroacetates were examined in the transformation. Generally 5-nitro-2-oxopentanoates were obtained in good yields (up to 97%) and enantioselectivities (up to 94% ee). The products were readily transformed to chiral proline derivatives by catalytic hydrogenation.     

Photoinduced Reaction of α-Bromoacetophenone with Thiosulfonate: Synthesis of β-Keto Thiosulfone

A photoinduced synthesis of β-keto thiosulfone/β-keto selenosulfone by the reaction of α-bromoacetophenone with thiosulfonate/selenosulfonate under metal-free and visible light irradiation conditions is developed. Two C−S bonds or one C−S bond and one C−Se bond were constructed simultaneously.     

The reaction of carbohydrate-derived alkoxyaldehydes with methoxycarbonylmethylenetriphenylphosphorane: stereoselective synthesis of β-unsaturated esters

The reaction of several carbohydrate-derive alkoxyaldehydes with methoxycarbonylmethylenetriphenylphosphorane afford α, β-unsaturated esters with Z-stereoselectivity. The stereoselectivity depends on the substrate stucture and the nature of the solvent used.     

Enantioselective photodeconjugation of α,β-unsaturated esters: Effect of the nature of the chiral agent

A synergism exists between the effect of the amino and hydroxy groups of chiral amino alcohols on the enantiomeric excess of the photodeconjugation of α,β-unsaturated esters.     

A novel oxidative ring-opening reaction of isoxazolidines: syntheses of β-amino ketones and β-amino acid esters from secondary amines

A novel oxidative ring-opening reaction of isoxazolidines upon treatment with an electrophile and subsequently with a basegives β-amino ketones and β-amino acid esters highly efficiently.     

Lewis acid-promoted reaction of β,γ-unsaturated α,α-dimethoxy esters with silyl nucleophiles

The Lewis acid-promoted reaction of β,γ-unsaturated α,α-dimethoxy esters, which are easily prepared by the acetalization of β,γ-unsaturated α-keto esters, with silyl nucleophiles is presented. By employing trimethylsilyl enolate and allyltrimethylsilane as nucleophiles, the BF₃-promoted reactions of a series of β,γ-unsaturated α,α-dimethoxy esters bearing aromatic and aliphatic substituents proceeded at the γ-position in an SN2′ manner to furnish γ-substituted α,β-unsaturated α-methoxy esters in good yields with high regioselectivity. In contrast, the reaction using trimethylsilyl cyanide predominantly occurred at the α-position, and the reaction of silyl hydride resulted in a mixture of α- and γ-regioisomers in favor of the γ-substitution products.     

Tetramic acids and indole derivatives from amino acid β-keto esters. Fine-tuning the conditions of the key Cu-catalyzed reaction

1,3,5-Trisubstituted tetramic acids and 2,3-disubstituted indole derivatives were prepared from β-keto esters derived from amino acids by their reaction with iodophenyl-2-trifluoroacetylamine under Cu-catalysis. Both heterocyclic systems were generated from the same starting materials by choice of the appropriate reaction conditions.