Β-carbonyl Compounds Research Articles

A versatile core–shell hetero-nanostructure catalysed chemo-selective synthesis of β-enamino carbonyl compounds

A core–shell hetero-nanostructure has been developed and used for the enamination of β-carbonyl compounds.

Enantioselective biosynthesis of (R)-γ-hydroxy sulfides via a one-pot approach with ChKRED20

An efficient, and high enantioselective one-pot reaction for ChKRED20 (Ketoreductase20 from Chryseobacterium sp. CA49) for the conversion of thiols and unsaturated α, β-carbonyl compounds into γ-hydroxy sulfides was proposed. The reaction is carried out in water phase, where spontaneous thio-Michael addition is sufficient to provide substrates for enzyme reaction. The effects of aromatic thiophenol substituents on the biocatalytic process were investigated by molecular docking simulations. Eighteen γ-hydroxy sulfides of R-alcohols can be obtained by this green and sustainable approach with high enantioselectivity.

Copper-catalyzed enantioselective direct α-C-H amination of β-dicarbonyl derivatives with aryl hydroxylamines and mechanistic insights

We report a novel and efficient Cu-catalyzed direct asymmetric amination of tertiary β-carbonyl compounds using aryl hydroxylamine as electrophilic nitrogen donor. The process facilitates the convenient and direct synthesis of chiral α-amino carbonyl derivatives, without the need for any post-reaction manipulation. This method reveals an effective strategy for the synthesis of enantioenriched α-CH aminated derivatives which is hitherto challenging. The choice of the robust chiral indabox ligand was ascertained to be very crucial for the desired enantioselectivity in the contemporary transformation. The reaction mechanism is fully supported by ab initio electronic structure calculations. The reaction is facile, efficient and performs well at room temperature with an enantiomeric excess (ee) up to 93 %.

An efficient strategy to synthesis of β-carbonyl compounds by 1-pentyl-1,2,4-triazolium methanesulfonate

It is well known that applying green chemistry aspects for organic reactions would reduce the toxicity of chemicals and it reduces the amount of volatile organic solvents too. Thus we have developed a Bronsted acidic 1-pentyl-1,2–4-triazolium methanesulfonate as a room temperature ionic liquid for organic reactions as reaction medium. The same has been employed as organocatalyst for the synthesis of β-Carbonyl Compounds. The present papers reveal the significance of ionic liquids in optimization of reaction condition in terms of equivalence of reagents, impact of solvents and amount of catalyst, synthesis of library of halogen rich β-carbonyl compounds.

ОДНОРЕАКТОРНЫЙ МЕТОД СИНТЕЗА ПРОИЗВОДНЫХ 5-(ПИРАЗОЛ-1-ИЛ)-ТЕТРАЗОЛА ИЗ 5-АМИНОТЕТРАЗОЛА

Condensation reactions of 5-hydrazinotetrazole with malonic dialdehyde and acetylacetone are considered. 12 new derivatives of 5-(pyrazole-1-yl)tetrazoles were synthesized and characterized. Commercially available 5-aminotetrazole was oxidized by potassium permanganate in aqueous alkaline solution yielding 5,5'-azotetrazolate pentahydrate which was decomposed in acidic media to 5-hydrazinotetrazole. One-pot procedure is suggested to prepare the 5(pyrazole-1-yl)tetrazole derivatives from 5-aminotetrazole. According to introduced method after carrying out condensation with β-carbonyl compounds reaction mixture was treated by an equivalent amount of bromine. Target products were separated from the reaction mixture as corresponding 4-bromoderivatives of 5-(pyrazole-1-yl)tetrazoles. The presence of a bromine atom in structure of synthesized compounds greatly facilitates processes of their isolation, purification and further alkylation of tetrazole ring. Debromination was realized by hydrogenation over palladium catalyst by hydrogen at moderate pressure. For synthesis of 4-nitroderivatives of 5-(pyrazole-1-yl)tetrazoles nitration in system HNO 3 /H 2 SO 4 was used. 5-(4-amino-3,5-dimethylpyrazole-1-yl)tetrazole was prepared by the reduction of 5-(4-nitro-3,5-dimethylpyrazole-1-yl)tetrazole.

An organocatalytic one-pot cascade incorporating the Achmatowicz reaction affording 3-pyrone derivatives.

The development of an organocatalytic one-pot cascade for the annulation of simple starting materials: α,β-unsaturated aldehydes, hydrogen peroxide, β-carbonyl compounds and NBS to furnish optically active 3-pyrones in good yield and with excellent enantioselectivity is presented. Further diversification of the obtained products is demonstrated by selective reductive transformations.

Mild Synthesis of Furans with a Quaternary Carbon Substituent at the 2-Position

Abstract The reaction of cis-4-oxopent-2-enal with β-carbonyl compounds in the presence of weak acids such as hexafluoroisopropyl alcohol was found to give furans with a quaternary carbon substituent at the 2-positon at room temperature or below. Reactivity was dependent on the identity of the substrates.

ChemInform Abstract: Substrate Range of the Titanium TADDOLate Catalyzed Asymmetric Fluorination of Activated Carbonyl Compounds

Abstract59 examples

Substrate Range of the Titanium TADDOLate Catalyzed Asymmetric Fluorination of Activated Carbonyl Compounds

AbstractThe substrate range of the [TiCl2(TADDOLate)] (TADDOL=α,α,α′,α′‐tetraaryl‐1,3‐dioxolane‐4,5‐dimethanol)‐catalyzed asymmetric α‐fluorination of activated β‐carbonyl compounds has been investigated. Optimal conditions for catalysis are characterized by using 5 mol‐% of TiCl2(naphthalen‐1‐yl)‐TADDOLate) as catalyst in a saturated (0.14 mol/l) MeCN solution of F‐TEDA (1‐(chloromethyl)‐4‐fluoro‐1,4‐diazoniabicyclo[2.2.2]octane bis‐[tetrafluoroborate]) at room temperature. A series of α‐methylated β‐keto esters (3‐oxobutanoates, 3‐oxopentanoates) with bulky benzyl ester groups (60–90% ee) or phenyl ester (67–88% ee) have been fluorinated readily, whereas α‐acyl lactones were also readily fluorinated, but gave lower inductions (13–46% ee). Double stereochemical differentiation in β‐keto esters with chiral ester groups raised the stereoselectivity to a diastereomeric ratio (dr) of up to 96.5 : 3.5. For the first time, β‐keto S‐thioesters were asymmetrically fluorinated (62–91.5% ee) and chlorinated (83% ee). Lower inductions were observed in fluorinations of 1,3‐diketones (up to 40% ee) and β‐keto amides (up to 59% ee). General strategies for preparing activated β‐carbonyl compounds as important model substrates for asymmetric catalytic α‐functionalizations are presented (>60 examples).

Efficient Synthesis of Functionalized Benzimidazoles and Perimidines: Ytterbium Chloride Catalyzed CC Bond Cleavage

AbstractAn efficient method is developed for the synthesis of functionalized benzimidazoles and perimidines by the condensation of aryl diamines with β‐carbonyl compounds catalyzed by ytterbium chloride. The reactions give good yields under mild conditions. A mechanism involving a lanthanide activated CC bond cleavage is proposed.

Catalytic Enantioselective Electrophilic Aminations of Acyclic α-Alkyl β-Carbonyl Nucleophilies.

Highly enantioselective aminations of acyclic α-alkyl β-keto thioesters and trifluoroethyl α-methyl α-cyanoacetate (12) with as low as 0.05 mol % of a bifunctional cinchona alkaloid catalyst were established. This ability to afford highly enantioselectivity for the amination of α-alkyl β-carbonyl compounds renders the 6'-OH cinchona alkaloid-catalyzed amination applicable for the enantioselective synthesis of acyclic chiral compounds bearing N-substituted quaternary stereocenters. The synthetic application of this reaction is illustrated in a concise asymmetric synthesis of α-methylserine, a key intermediate previously utilized in the total synthesis of a small molecule immunomodulator, conagenin.

Salt-Free Enantioselective Iridium-Catalyzed Allylic Alkylations

Previous systems involving iridium-catalyzed allylic alkylations with β-carbonyl compounds require the use of the corresponding ­alkali-metal salt. The authors report iridium complexes of several phosphorus amidite ligands activated by the base TBD [1,5,7-triazabicyclo[4.4.0]dec-5-ene] which accommodate neutral β-carbonyl compounds. Further, the authors illustrate the utility of this method by providing a key intermediate in Stork’s quinine synthesis, the Ta­niguchi lactone, in high enantiomeric purity. Additionally, the catalytic system is applied to the intramolecular cyclization of 6 to yield cyclopropane 7 in high ee.

Reaction kinetics and biological action in barley of mono-functional methanesulfonic esters

1. As a background for studies of the action mechanisms of biological alkylating agents a number of methanesulfonic esters were investigated with respect to rates of hydrolysis and reaction with different nucleophiles, mostly at 20°, 25° and 37°. 2. The reaction patterns of monofunctional alkylating agents (AA) of the kind studied were characterized in terms of (a) reaction mechanism (S N1 or S N2); (b) the S wain-S cott (61,64) substrate constant s describing the dependence of bimolecular rate constant on nucleophilicity n of the receptor molecule; (c) the absolute reaction rates and their temperature dependence which are accurately described by activation energy E A (≈ activation enthalpy, Δ H*) and activation entropy Δ S*, the latter parameter giving, in addition, information about the reaction mechanism. 3. In the series of unsubstituted alkyl esters studied, which mostly react according to S N2, branching on the α-carbon, as in iPMS, gives predominantly S N1 type reaction. The strong steric hindrance of S N2 reaction provoked by β-branching, as in iBMS and NeoMS, leads to the appearance of an S N1 type behaviour at low n, e.g. in hydrolysis. Of substituents studied, β-hydroxy and β-methoxy decrease reactivity, without considerable influence on s. β-Positioned carbonyl gives very high values of s (i.e. gives a character of “SH inhibitors”) to the compounds, with a strong retardation of reaction rate at low n. In certain cases abnormally high rates of reaction with the hydroxyl ion are encountered. Thus β-OH (as in HOEMS) leads to 1,2-epoxide formation in rapid OH − catalyzed reaction; β-carbonyl compounds exhibit a strongly OH − dependent hydrolysis. 4. In barley kernels the toxic action of the AA is in most instances reconcilable with alkylation at n ≈ 5·1, which corresponds to cysteine ester at pH 7, whereas genetic effects apparently are caused by alkylation of centres with n = 2·5–3, corresponding to primary phosphate and DNA. Kernels are therefore presumably killed by protein alkylation, e.g. leading to enzyme inactivation, whereas mutation (including sterility) is probably induced by DNA alkylation. Exceptions are the α-branched esters, indicated to kill by genetic mechanisms, and β-branched esters which are also more toxic than expected from kinetic data, however, for unknown reasons. iPMS (low s) induces mutation in a linear function of dose, whereas EMS and other esters of medium s exhibit an exponential dose response curve, possibly through simultaneous alkylation of DNA and protein, e.g. impairing repair enzyme function. The slight sterility induced by β-carbonyl esters implies that protein alkylation alone may provoke a certain genetic damage. 5. Experiments imply that, for a deeper understanding of the biological action of AA, the following factors should also be considered: (a) secondary reactions after alkylation of, e.g. DNA (especially important for chromosomal aberrations) and protein; (b) lipid/water partition; (c) steric factors on the side of AA as well as the receptor molecule.