The reaction of α-stannylmethyllithium with esters

Ketonic compounds were prepared from esters using α-stannylmethyllithium as the reagent.     

An expedient synthesis of α,α-difluoro-β-hydroxy ketones via decarboxylative aldol reaction of α,α-difluoro-β-keto acids with aldehydes

A novel decarboxylative aldol reaction of α,α-difluoro-β-keto acids with aldehydes in the absence of any base and metal catalysts has been developed. This reaction provides a highly convenient and efficient method for the synthesis of structurally diverse α,α-difluoro-β-hydroxy ketones in good to excellent yields.     

Regiospecific synthesis of α-chloro- and α-fluoro-1,2-diones

α-Chloro-1,2-diones and α-fluoro-1,2-diones were prepared from the corresponding α-chloroaldimines by a sequence of reactions involving cyanation to α-cyanoenamines, α-halogenation to form α-chloro- or α-fluoroimidoyl cyanides and addition of organolithium reagents across the nitrile moiety, followed by acidic hydrolysis. All steps are straightforward and occur without side reactions finally leading to regiospecifically chlorinated and fluorinated 1,2-diones in good yields.     

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.     

An alternative synthesis of β-pyrrolic acetylene-substituted porphyrins

A modified Horner-Emmons condensation reaction has been employed in the synthesis of acetylene-substituted porphyrins at the β-pyrrolic position. This technique was shown to have many advantages over the typically employed Sonogashira coupling method, including negating the requirement for a brominated porphyrin starting material. The electronic spectra of 2-(4′-carboxyphenyl)ethynyl-5,10,15,20-tetraphenylporphyrinato zinc(II) showed a red shift compared to the double bond equivalent, 4-(trans-2′-(2″-(5″,10″,15″,20″-tetraphenylporphyrinato zinc(II)yl))ethen-1′-yl)-1-benzoic acid. Comparison of the X-ray structures of 2-((4′-formyl)phenyl)ethynyl-5,10,15,20-tetraphenylporphyrinato zinc(II) and its analogue 4-(trans-2′-(2″-(5″,10″,15″,20″-tetraphenylporphyrinato copper(II)yl))ethen-1′-yl)-1-benzaldehyde showed an unexpected decrease in planarity in the analogue with the triple bond as opposed to that with the double bond.     

One-stage procedure of synthesis of highly reactive α-chloro-β-ketoacetals. 4-chloropyrazoles from α-chloro-β-ketodimethoxyacetals

Conditions were developed where the reaction of alkyl 1,2-dichlorovinyl ketones with alcohols and 1,2-dihydroxybenzenes led to the formation of the corresponding open-chain and cyclic α-chloro-β-ketoacetals. The reaction of α-chloro-β-alkylketodimethoxyacetals with alkyl-, benzyl-, and arylhydrazines resulted in 1,3-substituted 4-chloropyrazoles in 70–90% yields demonstrating that primarily formed 2,2-dimethoxy-1-chloroethyl alkyl ketones hydrazones underwent heterocyclization.     

The Ugi reaction with CF3-carbonyl compounds: effective synthesis of α-trifluoromethyl amino acid derivatives

The Ugi reaction with CF₃-carbonyl compounds is described in detail. The method is efficient for the multicomponent preparation of α-trifluoromethyl (Tfm) amino acids, α-Tfm containing dipeptides, and iminodicarboxylic acids. In addition, the first protected CF₃-opine derivative was prepared. The scope, limitations, and stereochemistry of the approach are discussed.     

Nickel-catalyzed reductive coupling reaction of monofluoroalkyl triflates with alkyl carboxylic acids toward the synthesis of α-alkyl-α-fluoro-alkylketones

The synthesis methods of α-fluoro-arylketones were well-established through electrophilic/nucleophilic fluorination and transition metal catalyzed cross-coupling. However, due to the site selectivity and substrate restriction, only a few cases have been developed to afford α-alkyl-α-fluoro-alkylketones. Herein, we report a general and efficient method of preparing diverse α-alkyl-α-fluoro-alkylketones via nickel-catalyzed reductive coupling reaction of monofluoroalkyl triflates with low-cost industrial raw material alkyl carboxylic acids. These transformations demonstrate high efficiency, mild conditions, and excellent functional group compatibility. This strategy provides a general and efficient method for the synthesis of α-alkyl-α-fluoro-alkylketones.     

Nucleophilic replacement of p-(1-chloro-2,2,2-trifluoroethyl)phenols: novel synthesis of β-trifluoromethyl-tyrosine

Three para-(1-chloro-2,2,2-trifluoroethyl)phenols 2a-c were prepared by selective α-chlorination of the corresponding alcohols 1a-c. Substitution of 2a by active methylene compound 4 proceeds smoothly in the presence of an appropriate base at room temperature, giving substituted products 5-9 in good yields. On the basis of this finding, both the important β-trifluoromethyl-tyrosine 15 and its derivatives have been successfully synthesized.     

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.     

The reaction of benzothiazolyl substituted α-phosphorylmethyl sulfoxides with several amines

We have examined the reactivities of α-phosphorylmethyl benzothiazolyl sulfoxides in the thermolyses and in the presence of several amines, such as aniline, benzylamine, piperidine, morpholine, and pyrrolidine. Thermolyses of the derivatives in the presence of 2,3-dimethyl-1,3-butadiene afforded 2-phosphoryl substituted 4,5-dimethyl-3,6-dihydro-2H-thiopyran S-oxide. In the reaction with amines, the complex product mixture, which contains α-phosphorylmethyl benzothiazolyl sulfides (2 and 5), α-phosphorylmethyl disulfides (15 and 16), and 2-amino substituted benzothiazole 14 was found to be formed besides the target phosphinecarbothioamides. Several mechanistic studies were performed to elucidate the formation mechanism, particularly for deoxygenated products from the starting sulfoxides, i.e., 2 and 5 from 3 and 6, respectively.     

The condensation reaction of methylphosphonic acid with α,ω-diethoxydimethylsiloxanes

Russian Chemical Bulletin -     

Reaction of adenine with an α-chlorooxetane: An approach to the synthesis of oxetane nucleosides

The reaction of adenine with 3,5-anhydro-5R-chloro-1,2-O- isopropylidenexylofuranose, a stable α-chlorooxetane, gives a mixture of the two epimers of 5-[9-adenyl]-3,5-anhydro- 1,2-O-isopropylidenexylofuranose; the structure of 5R-[9- adenyl)-3,5-anhydro-1,2-O-isopropylidenexylofuranose was established by X-ray crystallography.     

The NHCs-mediated cross-coupling of aromatic aldehydes with benzyl halides: synthesis of α-aryl ketones

A new NHCs-mediated synthetic method was found to produce α-aryl ketones in 22-63% yields in one-pot process from the corresponding aromatic aldehydes and benzyl halides. This method is the first example of the NHCs-mediated intermolecular nucleophilic acylation of aromatic aldehydes with benzyl halides.     

Reaction of α-chloro-β-oxobutanal with indole derivatives

The reactions of 2-methylindole and 2-methylindol-3-yldiphenylphosphine with α-chloro-β-oxobutanal was studied.     

An expedient and short synthesis of chiral α-hydrazinoesters: synthesis and conformational analysis of 1:1 [α/α-Nα-hydrazino]mers

Different α-hydrazinoesters with high optical purity have been obtained in large scale via an S_N2 protocol. A coupling reaction with a natural amino acid leads to the corresponding dimers, which have been oligomerized in order to obtain the 1:1 [α/α-N^α-hydrazino]mer series. Conformational studies show that these mixed oligomers are self-organized in solution via a succession of γ-turn and hydrazinoturn whatever the absolute configuration of the chiral carbons.