Oxalic acid catalyzed solvent-free one pot synthesis of coumarins

Oxalic acid was found to be an efficient catalyst for Pechmann condensation,which includes the reaction between phenols andβ-keto esters leading to formation of coumarin derivatives.The advantages of present methods are the use of cheap and easy available catalyst,solvent-free reaction conditions,better yields and shorter reaction time.     

Meglumine sulfate catalyzed solvent-free one-pot synthesis of coumarins under microwave and thermal conditions

A convenient method has been developed for the Pechmann reaction of phenols and β-keto esters catalyzed by meglumine sulfate. Solvent-free conditions, inexpensive catalyst, short reaction times, high yield, and ease of purification of the products are the advantages of this protocol. This novel catalytic system is expected to contribute to the development of more benign Pechmann condensation reactions of phenols with β-keto esters.     

Niobium(V) chloride-catalyzed C-H insertion reactions of α-diazoesters: synthesis of β-keto esters

Aldehydes react readily with ethyl diazoacetate in the presence of 5 mol% of NbCl₅ in dichloromethane to produce the corresponding β-keto esters in good yields with high selectivity. This method is very useful for the preparation of β-keto esters from both electron-rich as well as electron-deficient aromatic aldehydes under mild reaction conditions.     

A facile and efficient one-pot synthesis of thiirans by the reaction of benzoxazolyl β-ketosulfides with NaBH4/NaOH

Convenient and efficient procedures for thiirans have been developed via a one-pot reaction of benzoxazolyl β-ketosulfides with NaBH₄ and NaOH in MeOH and THF. The reaction is considered to proceed via the spiro intermediate by the ipso-addition of β-hydroxygroup, which is formed by the NaBH₄ reduction of β-keto group, to 2-position of benzoxazole group.     

A new method for the synthesis of N-protected β-amino-α-keto esters from fluoroalkanesulfonylazides and α-keto esters

In the presence of a secondary amine, treatment of α-keto esters with fluoroalkanesulfonyl azides at room temperature afforded N-sulfonyl protected β-amino-α-keto esters in good to excellent yields. This reaction provided a novel, direct and convenient access to N-sulfonyl protected β-amino-α-keto esters from α-keto esters and fluoroalkanesulfonyl azides under mild conditions. However, the reaction of fluoroalkanesulfonyl azides with β-ketoester enamines afforded two products: N-fluoroalkanesulfonyl amidines and diazoacetate. The reaction mechanism is discussed.     

α-Methylthiocarbonylation of Ketones. Generality and Regioselectivity

Over the past few years, there have been several methods documented for the preparation of β-keto thiolesters^2,3. However, most of these methods have limited synthetic applicability due to either the requirement of rather specific starting substrates³, or operational complexity, often coupled with unsatisfactory yields². A more promising procedure was briefly examined by Demuynck and Thuillier², who demonstrated the feasibility of β-keto thiolester formation by the reaction of an enolate ion with S,S'-dimethyl dithiocarbonate. Of the three simple acyclic ketones examined, products were obtained in moderate yields of 30–70%. In continuation of our investigation of the synthetic utility of β-keto thiolesters³ and efficient method of preparation was required. We have studied the α-methylthiocarbonylation process with special attention to its improvement, general applicability and regioslectivity.     

Dual-reagent organocatalysis with a phosphine and electron-deficient alkene: application to the Henry reaction

Triphenylphosphine in combination with methyl acrylate was found to be able to catalyze the Henry (nitroaldol) reaction of various aldehydes and α-keto esters to give the corresponding β-nitroalkanols in good to excellent yields, and a catalytic cycle involving a zwitterionic phosphine-alkene adduct was proposed for this dual-reagent organocatalysis according to the deuterium-labeling experiments with CD₃NO₂.     

以芳樟醇为手性源的β-羟基酸的不对称合成

以芳樟醇与乙酰乙酸乙酯进行酯交换反应,合成了具有手性的乙酰乙酸芳樟酯(β-酮酯),再用其与不同的格氏试剂反应,得到不对称β-羟基酸;产物分别经手性柱分析.结果表明,手性乙酰乙酸芳樟酯与格氏试剂的反应具有不同程度的立体选择性,产物为R-或S-构型过量的β-羟基酸,ee值最高达50%.     

InCl3-catalyzed efficient one-pot synthesis of 2-pyrrolo-3′-yloxindoles

An InCl₃-catalyzed one-pot synthesis of 2-pyrrolo-3′-yloxindoles was achieved via three-component reaction of 3-phenacylideneoxindole, β-keto ester, and ammonium acetate at reflux by a sequential Michael addition followed by Paal-Knorr condensation.     

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.     

A solvent-free synthesis of coumarins using a Wells-Dawson heteropolyacid as catalyst

Substituted coumarins are synthesized from phenols and β-ketoesters by the Pechmann reaction, using a Wells-Dawson heteropolyacid (H₆P₂W₁₈O₆₂·24H₂O) as catalyst by a solvent-free procedure. This one requires low reaction times, 130 °C temperature and as little as 1 mol % of Wells-Dawson acid, obtaining good to excellent yields of coumarins. The catalyst showed to be reusable with no differences in the yields. The results are compared with those of the reactions performed in toluene solution. The presented synthetic procedure is a convenient, clean and fast alternative for synthesizing 4-substituted coumarins (17 examples).     

Visible-light-promoted oxidative difunctionalization of alkenes with sulfonyl chlorides to access β-keto sulfones under aerobic conditions

A mild, practical and efficient strategy to prepare β-keto sulfones has been developed by visible light promoted reactions. This reaction involves Ir(ppy)₂(dtbbpy)PF₆ catalyzed direct funcationalization of alkenes with sulfonyl chlorides under mild conditions. Air was used as oxidant without any additives. The transformation affords the corresponding products in moderate to high yields.     

FeCl3 catalysed two consecutive aminomethylation at the α-position of the β-dicarbonyl compounds: an easy access to hexahydropyrimidines and its spiro analogues

Multicomponent synthesis of 1,3-diaryl-hexahydropyrimidines by a one-pot reaction of 1,3-dicarbonyl compounds, amines and formaldehyde catalysed by FeCl₃ in dichloromethane at room temperature (25-30 °C) has been reported. Double amino methylation occurs at the α-position of the 1,3-dicabonyl compounds/β-keto esters. The same methodology leads to spiro compounds with indane-1,3-dione. In this reaction, six molecules condense in one pot to form six new covalent bonds, thus, creating high atom economy. This is the first report of the synthesis of the substituted hexahydropyrimidines involving β-keto esters and its spiro analogues with indane-1,3-dione.     

Differentiation effect of solvents on the keto-enol equilibrium of heterocyclic β-dicarbonyl compounds

The differentiation effect of a solvent on the equilibrium of five- and six-membered heterocyclic β-keto esters and β-diketones containing =O, =S, =SO, =NR, =NRHC1, and -S-C(R)₂-S-fragments and, for comparison, on the equilibrium of aliphatic and carbocyclic β-keto esters and β-diketones was studied. The differentiating effect of a solvent is explained by different kinds of solvation of the heteroatomic fragments in the ketone and enol forms of heterocyclic β-dicarbonyl compounds.     

Asymmetric 1,4-addition of β-keto esters to cyclic enones catalyzed by Ru amido complexes

Well-defined Ru amido complexes effected asymmetric Michael addition of β-keto esters to 2-cyclopenten-1-one to give quantitatively the corresponding Michael adducts with excellent ee although with a 1:1 diastereomer ratio. The stereochemical outcome of the reaction was significantly influenced by the structures of the catalysts and the structures of the β-keto esters; the ee value reaching up to 97%.     

Visible-light-induced direct oxysulfonylation of alkynes with sulfonyl chlorides and HCl

A mild, practical and efficient strategy to prepare β-keto sulfones has been developed by visible-light-induced reactions. This reaction involved Ir(dtbbpy)(ppy)₂PF₆-catalyzed direct functionalization of alkynes with sulfonyl chloride and HCl using air as the oxidant. HCl not only acted as a hydrogen source in the proton transfer process, but also played a vital role in the reaction process.     

Fe(HSO4)3·SiO2 as an efficient,heterogeneous and recyclable catalyst for the synthesis of bis-(β-enaminones) and bis-(β-enamino esters)

Fe(HSO₄)₃·SiO₂ is used to catalyze the condensation of β-diketones and β-keto esters with aromatic and aliphatic diamines in solvent-free conditions at room temperature. This afforded the corresponding bis-(β-enaminones) and bis-(β-enamino esters) in very good to excellent yields. Short reaction times, easy work-up procedure, and reusability of the catalyst are the merits of this study.     

Synthesis of the C18–C26 tetrahydrofuran-containing fragment of amphidinolide C congeners via tandem asymmetric dihydroxylation and SN2 cyclization

The C18–C26 fragment of amphidinolide C congeners has been synthesized starting from methyl acetoacetate in 14 steps in >17.0% overall yield. The C20 stereogenic center was secured by asymmetric hydrogenation of a β-keto ester and the configuration at both C23 and C24 was introduced by asymmetric dihydroxylation (AD). The trans-2,5-disubstituted tetrahydrofuran ring was assembled via the tandem AD–S_N2 sequence. The latter protocol could be employed for accessing the corresponding cis-2,5-disubstituted tetrahydrofuran rings from the same alkene substrates simply by choosing a suitable AD ligand. Moreover, functional group compatibility was observed for the Ru(II)-catalyzed hydrogenation of β-keto esters and the Pd(0)–Cu(I)-catalyzed Sonogashira cross-coupling reaction. These findings should be valuable for general synthetic design and application.     

Copper-bipyridine-catalyzed enantioselective α-amination of β-keto esters

The Cu(OTf)₂-bipyridine-catalyzed, enantioselective, direct α-amination of β-keto esters and β-diketones with diethyl azodicarboxylate (DEAD) has been studied. Exceptionally high enantioselectivities of up to 99% ee were found for 1-indanone-based β-keto esters in particular even for substrates and reagents carrying conventional ester groups such as methyl and ethyl.     

Stereoselective synthesis of syn β-hydroxy cycloalkane carboxylates: transfer hydrogenation of cyclic β-keto esters via dynamic kinetic resolution

The transfer hydrogenation of bicyclic and monocyclic β-keto esters using HCO₂H/Et₃N as the hydrogen source and TsDPEN-based Ru(II) catalysts proceeds with dynamic kinetic resolution to afford the corresponding cyclic β-hydroxy esters with moderate to excellent levels of diastereo- and enantioselectivities. The mild reaction conditions used make possible to preserve in most cases the syn relative configuration of the products, providing a complementary tool to known approaches to the synthesis of anti isomers.