A convenient method for the synthesis of fluorinated α-cyanoacetates via phase-transfer catalysis

A simple and convenient method for the synthesis of fluorinated α-cyanoacetate derivatives has been developed by using electrophilic fluorination of allyl and benzyl substituted α-cyanoacetates with N-fluorobenzensulfonimide (NFSI) as electrophilic fluorinating agent via phase transfer catalysis. The reaction is transition metal free and carried out in aqueous and mild reaction conditions in the presence of readily available tetra-N-butylammonium iodide (TBAI) as phase-transfer catalyst.     

A rapid method toward the synthesis of new substituted tetrahydro α-carbolines and α-carbolines

A rapid and efficient method for stereoselective synthesis of new substituted tetrahydro-α-carbolines using Diels-Alder reaction under microwave irradiation has been developed. Further, dehydrogenation of these adducts resulted in synthesis of new substituted α-carbolines.     

New method for the synthesis of α-chlorocinnamonitriles

A novel method for the preparation of nitriles of -chlorocinnamic acid from aldehydes and ketones was proposed. Transformation of carbonyl compounds into hydrazones followed by treatment of the reaction mixture with CCl₃CN in the presence of copper chloride(i) yields -chlorocinnamonitriles.     

Diphenylparabanic acid as a synthon for the synthesis of α-diketones and α-ketocarboxylic acids

Diphenylparabanic acid was found to react with >2 equiv of organolithiums at -78 °C to effectively give the corresponding symmetrical α-diketones. However, upon treatment with 1 equiv of organolithium, the parabanic acid gave mainly 5-substituted 5-hydroxyimidazolidine-2,4-diones. On the other hand, Grignard reagents were less reactive toward the parabanic acid at low temperature, and selectively gave the corresponding 5-hydroxyimidazolidine-2,4-diones even if more than 1 equiv of the reagents was used. A tandem process in which the parabanic acid was first reacted with a Grignard reagent and then reacted in one-pot with an organolithium effectively gave the unsymmetrical α-diketone. 5-Substituted 5-hydroxyimidazolidine-2,4-diones were useful as versatile precursors for preparing α-ketocarboxylic acids as well as unsymmetrical α-diketones.     

Convenient and efficient method for the synthesis of substituted quinolines via one-pot heteroannulation reaction of o-amino arylketones with α-methylene ketones under solvent-free conditions

A facile and practical approach to the synthesis of a wide range of functionalized quinolines was developed via a tandem heteroannulation reaction of o-aminoarylketones with diverse α-methylene ketones in high yields by using tetrabutylammonium peroxydisulfate as a versatile reagent (25?mol%) at ambient temperature under solvent-free conditions. This protocol was applied to the synthesis of drug-like molecules, which are key intermediates of alkaloid camptothecin.     

Development of methods for the synthesis of libraries of substituted maleimides and α,β-unsaturated-γ-butyrolactams

Synthetic methods for the preparation of maleimide and α,β-unsaturated-γ-butyrolactam compound collections are described. These routes take advantage of Pd cross-coupling and conjugate addition/elimination reactions to permit the facile production of bisaryl-maleimides, anilinoaryl-maleimides, and bisanilino-maleimides while allowing control over the synthesis of symmetrical or nonsymmetrical derivatives. Similarly, the chemistry developed allows for the generation of bisaryl substituted α,β-unsaturated-γ-butyrolactams. The scope and limitations of the approaches are presented.     

Alkylation of β-dicarbonyl compounds as a method for the production of functionally substituted dihydrofurans

The alkylation of some representatives of β-dicarbonyl compounds by 1,4-dibromo-2-butene and ethyl 2,3-dibromopropionate was investigated. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 514–518, April, 2009.     

Heterocyclization of β,γ-dichloro ketones as a method for the synthesis of furan derivatives

Dichloro ketones obtained from acyl chlorides and allyl or -methylallyl chloride undergo spontaneous cyclization to give 2-alkyl- and 2,4-dialkylfurans when they are heated; the intermediates in the case of 2,3-dichloropropene split out a molecule of hydrogen chloride to give 3,4-dichloro-2-butenones.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 313–319, March, 1992.     

Acylation of Meldrum’s acid with arylacetic acid imidazolides as a convenient method for the synthesis of 4-aryl-3-oxobutanoates

C-Acylation of Meldrum’s acid by (het)arylacetic acids in ethanol in the presence of 1,1′-carbonyldiimidazole leads to ethyl 4-(het)aryl-3-oxobutanoates in high yields.     

Rhodium-catalyzed cross-coupling reaction of arylboronates and diazoesters and tandem alkylation reaction for the synthesis of quaternary α,α-heterodiaryl carboxylic esters

A rhodium-catalyzed one-pot three-component coupling reaction was developed for the synthesis of quaternary α,α-heterodiaryl carboxylic esters. This reaction involves cross-coupling of the arylrhodium(I) complexes with α-aryldiazoacetates to form oxa-π-allylrhodium complexes. With KOtBu and alkyl halides, tandem alkylation of the allyl complex occurs to form a quaternary stereocenter at the carbenic carbon.     

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.     

Aza-Michael reaction as an efficient method for the synthesis of first representatives of β-azahetaryl-β-diphenylphosphorylalkanones

Aza-Michael reaction of (E)-4-(diphenylphosphoryl)but-3-en-2-one (1) with a number of mono-and bicyclic nitrogen heterocycles proceeds regioselectively in the absence of catalysts with the formation of corresponding β-azahetaryl β-diphenylphosphoryl ketones; in the case of imidazole, the presence of chiral organic catalysts allows one to increase the yields of the adducts and to obtain them in enantiomerically enriched form.

     

Investigating the reaction mechanism and organocatalytic synthesis of α,α'-dihydroxy ketones

A biomimetic TK one-pot reaction using hydroxypyruvate and aldehydes to generate α,α'-dihydroxy ketones in water has recently been described. To investigate this tertiary-amine mediated reaction mechanism two approaches were used. Firstly, (13)C labelled lithium hydroxypyruvate was synthesised and used to establish where hydroxypyruvate is incorporated in the product. In separate experiments reaction intermediates were also successfully intercepted and structurally identified using ESI-MS with tandem mass spectrometry ESI-MS/MS. These studies indicated that two mechanisms appear to be operating, one involving the addition of the tertiary amine catalyst to hydroxypyruvate, the other an aldol-based mechanism. Since the first mechanism may enable facial stereodifferentiation in the addition of intermediates to the aldehyde, a preliminary study on the use of chiral catalysts was performed and the first asymmetric organocatalytic synthesis of α,α'-dihydroxy ketones in aqueous media achieved, in up to 50% ee, using a quinine ether catalyst.     

Efficient synthesis of syn-α-alkoxy epoxide via a diastereoselective Darzens reaction

A highly diastereoselective Darzens reaction was developed by using a MEM- or TBDPS-protected α-hydroxy aldehyde with di-tert-butyl bromomalonate. This method effectively provides a syn-α-alkoxy epoxide, and a possible reaction mechanism was proposed to explain the high syn selectivity.     

Magnesium-methanol as a simple convenient reducing agent for α,β -unsaturated esters

Various α, β -unsaturated esters undergo double bond reduction by magnesium in methanol to give the corresponding saturated ones in almost quantitative yields.     

The chemistry of α,β-ditosyloxyketones: new and convenient route for the synthesis of 1,4,5-trisubstituted pyrazoles from α,β-chalcone ditosylates

The reaction of α,β-chalcone ditosylates with various reagents such as phenylhydrazine hydrochloride, semicarbazide hydrochloride and thiosemicarbazide in suitable conditions leads to 1,2-aryl shift, thereby providing a novel route for the synthesis of 1,4,5-trisubstituted pyrazoles.     

A stereoselective synthesis of an α-substituted α-amino acid as a substructure for the construction of myriocin

A synthetic route to the protected quaternary α-amino acid 2 with a hydroxylated side chain has been achieved. The key transformations are the diastereoselective substrate-controlled epoxidation of allylic alcohol 4; a highly stereoselective oxidation–reduction protocol, and the excellent regioselective isomerization of the oxazolidinone ring to give an oxazinanone skeleton in derivative 3. The carboxylic acid 2 obtained represents the polar substructure, which is present in myriocin 1.     

Superbase promoted synthesis of dienamides as useful intermediates for the synthesis of α-ketoamides, γ-lactams and cyclic imino ethers

Alkoxydienamides 2 have been synthesized exploiting the reactivity of α,β-unsaturated acetals 1 with isocyanates in the presence of Schlosser's superbase LIC-KOR. In a mild acidic medium, 2 can then be promptly converted both into α-ketoamides 3 and into substituted 2-pyrrolidinones 4 or imino ethers 5 by choosing the appropriate experimental conditions.