Structural determination of a zinc reagent from ethyl 3-bromodifluoromethyl-3-benzyloxyacrylate and its reactions with aldehydes

The reactivity of ethyl 3-bromodifluoromethyl-3-benzyloxyacrylate as a novel gem-difluoromethylene synthon was investigated. ¹⁹F NMR spectra of its zinc reagent in THF and DMF indicate unambiguously that the active species exists as the γ-carbon metallated form. Moreover, promoted by zinc or TDAE, a complete control of the addition reaction mode (α or γ) of this acrylate with aldehydes can be accomplished.     

Tandem three-component reaction of aldehyde, alkyl acrylate, and amide using ethyl diphenylphosphine as organocatalyst

It is the first time that a chemoselective EtPPh₂-catalyzed three-component reaction of aromatic aldehyde, alkyl acrylate, and phthalimide or methyl toluenesulfonamide has been achieved. A variety of highly functional adducts can be generated efficiently in one step within 1-72 h in 38-93% yields. The reaction mechanism is proposed to undergo Morita-Baylis-Hillman reactions of aryl-substituted aldehydes and alkyl acrylates followed by Michael additions of amides. Our studies indicated that, in combination of EtPPh₂, alkyl acrylate also catalyzed this process.     

Practical synthesis of gem-difluorides from cyclohexanone: Synthesis of gem-bistrifluoroacetates and their reactions with fluoride nucleophiles

Formation of ketone acylals bearing trihaloacetoxy groups and their nucleophilic geminal disubstitution by fluoride ions were investigated. Cyclohexanone reacted with trifluoroacetic anhydride without catalyst to give gem-bistrifluoroacetates via a concerted bimolecular reaction. Treatment with hydrogen fluoride under mild conditions efficiently yielded the corresponding gem-difluorides. In this reaction process, trifluoroacetic acid was recovered and converted to trifluoroacetic anhydride using P₂O₅. Since gem-difluorides were derived from ketones, HF and P₂O₅, this constitutes a practical synthesis of gem-difluorides.     

Acid catalyzed reactions of α,β-unsaturated aldehydes and ethyl diazoacetate

The formation of cyclopropanes from α,β-unsaturated aldehydes and diazo compounds has been a rather challenging goal due to the extremely reactive aldehyde starter. Herein, our group reports the first formation of ethyl 2-formyl-1-cyclopropanecarboxylate in 100% yield from the acid catalyzed reaction between acrolein and ethyl diazoacetate (EDA).     

Phenyl trifluorovinyl sulfide: a radical acceptor for preparation of gem-difluoromethylene compounds

Phenyl trifluorovinyl sulfide was prepared from the reaction of trifluorovinyllithium and S-phenyl benzenethiosulfonate. The fluorinated olefin showed reactivity with alkyl radicals generated from halogen-abstraction from alkyl halides. Reactions with alkyl halides required tris(trimethylsilyl)silane as a chain transfer reagent to improve selectivity of the products. Initiation of radical reaction was effected by thermal decomposition of AIBN. Oxidation of the thioether products gave the corresponding sulfoxides, which were successively converted into α,α-difluoroalkanecarboxylic acid thiol esters by Pummerer reaction.     

Sulfinatodehalogenation reactions of gem-aryl disubstituted methylenecyclopropanes with perfluoroiodoalkanes

Sulfinatodehalogenation reaction of gem-aryl disubstituted methylenecyclopropanes (MCPs) 1 with perfluoroiodoalkanes produces the corresponding ring-opened products 4-iodo-1,1-diaryl-2-perfluorobutyl-but-1-enes 2, rearranged products 1,2-dihydronaphthalenes 3, and addition products 1-perfluoroalkyl-1-(diarylmethyl)cyclopropanes 4 in the presence of sodium dithionite in moderate yields through a radical process under mild conditions. The major product 2 is derived from radical ring-opening reaction of MCPs 1.     

Synthetic studies of venturicidins: stereoselective synthesis of the C15-C27 segment based on two types of stereospecific epoxide opening reactions

The C15-C27 segment of venturicidins was stereoselectively synthesized by using two types of stereospecific methyl substitution reactions of epoxides and subsequent stereocontrolled methylation reactions of lactone derivatives as the key steps.     

A novel four-component reaction of diethylamine, an aromatic aldehyde and an alkyl isocyanide with dialkyl acetylenedicarboxylates in the presence of silica gel: an efficient route for the regio- and stereoselective synthesis of sterically congested alkenes

The 1:1 intermediate generated by the addition of an isocyanide to a dialkyl acetylenedicarboxylate is trapped by the iminium ion intermediate that forms from the reaction between an aromatic aldehyde and diethylamine. The reactions were completed in the presence of silica gel powder. The product dialkyl 2-[(alkylamino)carbonyl]-3-[(Z)-1-(diethylamino)-1-arylmethylidene]succinates, were produced in acceptable yields. The reactions are completely regio- and stereoselective.     

Novel tandem reactions of ethyl acetoacetate with aromatic aldehydes: product- and stereo-selective formation of highly functionalised cyclohexanones

The five-component tandem reaction of ethyl acetoacetate with aromatic aldehydes in the presence of pyrrolidine affords t(3),t(5)-diaryl-t(4)-[(E)-3-aryl-2-propenonyl]-r(2)-ethoxycarbonylcyclohexanones stereoselectively in good yields presumably via a tandem Knoevenagel condensation-Michael addition-condensation via enamine-deethoxycarbonylation-Michael addition sequence. The same reactants in the presence of DBU led to the formation of t(3)-aryl-r(2),c(4)-bisethoxycarbonyl-c(5)-hydroxy-t(5)-methylcyclohexanones in excellent yields via a tandem Knoevenagel condensation-Michael addition-aldol reaction sequence.     

Similarities and differences of epoxide, aldehyde and peroxide initiators for Cp2TiCl-catalyzed styrene living radical polymerizations

Cp₂TiCl is the first example of a single electron transfer (SET) agent that both provides initiating radicals from three different types of functionalities (i.e. radical ring opening of epoxides and reduction of aldehydes and peroxides) and doubles as mediator for the living radical polymerization of styrene (St) by reversibly endcapping the growing polymer chains. An initiator (I) comparison was performed using 1,4-butanediol diglycidyl ether (BDE), benzaldehyde (BA) and benzoyl peroxide (BPO) as models. The investigation of the effect of reaction variables was carried out over a wide range of experimental conditions ([Cp₂TiCl₂]/[I] = 0.5/1-4/1; [Zn]/[Cp₂TiCl₂] = 0.5/1-3/1, [St]/[I] = 50/1-400/1 and T = 60-130 °C) to reveal living polymerization features such as a linear dependence of molecular weight on conversion and narrow molecular weight distribution (M_w/M_n) for each initiator class. However, progressively lower polydispersities and larger initiator efficiencies are obtained with increasing the [Cp₂TiCl₂]/[I] and [Zn]/[Cp₂TiCl₂] ratios and with decreasing temperature. Accordingly, optimum conditions correspond to [St]/[I]/[Cp₂TiCl₂]/[Zn] = [50-200]/[1]/[2-3]/[4-6] at 70-90 °C. By contrast to peroxides, aldehydes and the more reactive epoxides provide alcohol end groups useful in block or graft copolymers synthesis.     

Kinetics of photocrosslinking reactions of a DCPA/EA matrix in the presence of thiols and acrylates

The crosslinking efficiency and kinetics of a solid acrylic copolymer DCPA/EA (dicyclopentenyl acrylate/ethyl acrylate) matrix were investigated in the presence of pentaerythritol tetrakis (2-mercaptoacetate) (PETMP) or pentaerythritol tri- and tetraacrylates used as multifunctional crosslinking agents. The reaction of thiol and acrylate addition was sensitized by benzophenone (BP). The crosslinking efficiency of the DCPA/EA—BP—PETMP copolymer system, illuminated at high wavelengths (λ > 310 nm), was compared with that of the DCPA/EA matrix alone and the 2-component system copolymer DCPA/EA–BP. The concentrations of photosensitizer and crosslinking agent were varied from 1 to 10 mass %. The kinetics of tetrafunctional thiol addition and cyclopentene (pendant group of the DCPA/EA matrix) disappearance was followed through Fourier transform infrared (FTIR) and by determining the gel content. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35 : 2333–2345, 1997     

Dodecatungestophosphoric acid (H3PW12O40) as a solid green BrØnsted acid catalyzes high yielding and efficient trimethylcyanosylilation reactions of aldehydes and ketones by trimethylsilyl cyanide

An efficient solvent-free method is described for the addition of TMSCN to carbonyl groups employing dodecatungestophosphoric acid (H₃PW₁₂O₄₀) as a heterogeneous and environmentally benign catalyst. By this method, aromatic, aliphatic, cyclic and heterocyclic aldehydes and ketones are converted into their corresponding cyanotrimethylsilyl ethers in excellent yields (89-98%) in short reaction times (<10 min).     

Expeditious, large scale preparation of ethyl (R)-5-methyl-3-oxo octanoate via a cross Claisen reaction between N-acyl oxazolidinone derivatives and the magnesium enolate of potassium ethyl malonate

A new and efficient method for the direct conversion of N-acyl oxazolidinones to a β-keto ester is disclosed. The one-pot transformation is effected by the utilization of an excess of Lewis acid along with base and potassium ethyl malonate. This methodology has been applied to the large scale preparation of ethyl (R)-5-methyl-3-oxooctanoate.     

Highly regio- and stereocontrolled SN2′ reactions of gem-difluorinated vinyloxiranes with monoalkylcopper reagents

Reaction of gem-difluorinated vinyloxiranes with RCu(X)Li allowed us to introduce the R group regioselectively at the fluorine-attached terminal carbon atom in an S_N2′ manner to afford (E)-allylic alcohols exclusively, while homoallylic alcohols with anti stereochemical relationship were found to be obtained selectively from higher-ordered cuprates derived from CuCl and RMgBr in a ratio of 1:3.     

Synthetic applications of the nickel-catalyzed cyclization of alkynes combined with addition reactions in a domino process

Carbonickelations of alkynes and functionalization of the resulting vinylnickel moiety have been performed efficiently in a nickel-catalyzed domino cyclization-condensation process. This reaction, which does not require the preparation of any other organometallic reagent, proceeds only by exo-dig cyclization. This convenient and mild method constitutes a one-pot synthesis of substituted dihydrobenzofurans, chromans, isochromans, indoles, or indanes. Theses valuable products are generally obtained in good yields and high stereoselectivity. They are shown to be useful synthons for rapid access to functionalized polycyclic skeletons.     

gem-Difluoromethylation of α- and γ-ketoesters: preparation of gem-difluorinated α-hydroxyesters and γ-butyrolactones

PhSCF₂SiMe₃ has been demonstrated as difluoromethyl carbanion synthon (⁻CF₂H). It reacts chemoselectively with α- and γ-ketoesters at the keto group in the presence of a catalytic amount of TBAF in THF to give the corresponding α-hydroxy ester adducts as well as γ-gem-difluorophenylsulfanylmethylated-γ-butyrolactones in good yields. Reductive cleavage of the phenylsulfanyl group of these products employing Bu₃SnH/AIBN gives the corresponding gem-difluoromethylated α-hydroxyesters and γ-butyrolactones in good yields.     

Boron-mediated aldol reactions of ethyl α-(N,N)-dibenzylamino ketones: control of enolisation geometry and aldehyde π-facial selectivity

The boron-mediated aldol reactions of a range of chiral α-(N,N)-dibenzylamino ketones with aldehydes can be controlled to provide stereodefined adducts. Complementary induction can be achieved with ^cHex₂BCl/Me₂NEt leading to preferential formation of the 1,2-anti-2,4-syn adducts, while Bu₂BOTf/ⁱPr₂NEt provides 1,2-syn-2,4-anti adducts.     

Reactions of ethyl methylsulfonylpyruvate and its sodium salt with a mixture of aromatic aldehyde and arylamine

The reactions of ethyl methylsulfonylpyruvate and its sodium salt with a mixture of aromatic aldehyde and arylamine afforded 1,5-diaryl-3-hydroxy-4-methylsulfonyl-3-pyrrolin-2-ones. The spatial structure of 1,5-diphenyl-3-hydroxy-4-methylsulfonyl-3-pyrrolin-2-one was established by X-ray diffraction analysis.     

Zinc(II) perchlorate as a new and highly efficient catalyst for formation of aldehyde 1,1-diacetate at room temperature and under solvent-free conditions

Zinc(II) perchlorate efficiently catalysed the conversion of aromatic, heteroaromatic, and aliphatic aldehydes to 1,1-diacetates under solvent-free conditions at room temperature. It was compatible with other functional groups (e.g., ether, ester, nitro, and cyano) likely to interfere by complex formation with the catalyst. Other anhydrides such as isobutyric, pivalic, and benzoic anhydrides afforded the corresponding 1,1-dicarboxylates and established the generality. The reaction rate was influenced by the steric and electronic nature of the anhydride. The rate of 1,1-dicarboxylate formation was found to follow the order Ac₂O > (i-PrCO)₂O > (t-BuCO)₂O > (PhCO)₂O and no 1,1-dicarboxylate formation took place with (ClCH₂CO)₂O, and (F₃CO)₂O. During inter- and intra-molecular competition between a ketone and an aldehyde group with Ac₂O, 1,1-diacetate formation took place exclusively with the aldehyde group. An 88:12 selectivity was observed for 1,1-diacetate formation in favour of 1-naphthaldehyde during competition with 2-methoxy-1-naphthaldehyde.     

Regioselective and regiospecific reactions of ethyl ortho-(dimethylaminovinylazoloazinylcarboxylates with hydrazine

Selectivity of reactions of ethyl 4-[(E)-2(dimethylamino)vinyl]pyrazolo[5,1-c]-[1,2,4]triazino-3-ylcarboxylates and ethyl 7-[(E)-2-(dimethylamino)vinyl][1,2,4]triazolo[1,5]pyrimidine-6-ylcarboxylates with hydrazine in various solvents was studied. The formation of a pyridone cycle proceeds regiospecifically in dimethyl formamide or dimethyl acetamide. A regioselective cyclization resulting in fused 1,2-diazepines occurs in acetic or propionic acid.