Halide Anion Triggered Reactions of Michael Acceptors with Tropylium Ion

Tropylium bromide undergoes noncatalyzed, regioselective additions to a large variety of Michael acceptors. In this way, acrylic esters are converted into β‐bromo‐α‐cycloheptatrienylpropionic esters. The reactions are interpreted as nucleophilic attack of bromide ions at the electron‐deficient olefins and the approach of the tropylium ion to the incipient carbanion. Quantum chemical calculations were performed to elucidate the analogy to the amine‐ or phosphine‐catalyzed Rauhut–Currier reactions. Subsequent synthetic transformations of the bromo‐cycloheptatrienylated adducts are reported.     

Palladium-catalyzed reaction of allylic ammonium bromides with nucleophiles

The reactions of allylic triethylammonium bromides and dimethylsulfonium bromide with carbon nucleophiles were catalyzed by tetrakis(triphenylphosphine)palladium to afford olefinic esters and ketones.     

Influence of the fluoride ion on the aggregation and catalytic properties of micellar solutions of cetyltrimethylammonium bromide

The influence of the fluoride ion on the aggregation behavior and catalytic properties of neutral and alkaline aqueous solutions of cetyltrimethylammonium bromide in nucleophilic substitution reactions of phosphorus acid esters was studied by tensiometry, small-angle neutron scattering, and UV spectrophotometry. The critical micelle concentrations and the radii, aggregation numbers, and shape of micelles forming in these systems, as well as the kinetic parameters of the nucleophilic substitution reactions of phosphorus acid esters, were determined.     

A facile solution phase combinatorial synthesis of tetrasubstituted pyridines using the Bohlmann-Rahtz heteroannulation reaction

The solution phase combinatorial Bohlmann-Rahtz reaction gives highly functionalized pyridine libraries from enamino esters and alkynones in a single synthetic step. Good product ratios and library purities were obtained in reactions catalyzed by zinc(II) bromide, the acid-catalyzed heteroannulation procedure offering considerable improvements over traditional methodology.     

Kinetics and mechanism of phosphorylation of monoethanolamine in reversed micelles of a cationic surfactant

The reactions of monoethanolamine with 4-nitrophenyl esters of tetracoordinated phosphorus acids in chloroform in the presence of 2-hydroxyethyldimethylpentadecylammonium bromide were studied. The effective rate constants of the reactions are increased by more than two orders of magnitude in the presence of the micelle-forming cationic surfactant. The latter also favors the formation of the product ofO-phosphorylation of monoethanolamine and leads to the appearance of a new ionic form of the 4-nitrophenol-monoethanolamine complex. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 280–283, February, 1998.     

On the mechanism of the selenolactonization reaction with selenenyl halides

The mechanism of selenocyclization reactions of beta,gamma-unsaturated acids and their derivatives has been studied. The reactions of (E)-4-phenyl-3-butenoic acid 10 and its silyl and alkyl esters with benzeneselenenyl chloride (PhSeCl) and bromide (PhSeBr) have been examined by VT-NMR and in situ IR spectroscopic methods. Whereas the reactions of the acid 10 in the presence of a base were irreproducible and complicated, reactions of the silyl esters were clean and spontaneously and quantitatively afforded a chloroselenylation adduct at -70 degrees C as a single (Markovnikov) isomer. This adduct underwent three processes as the temperature was raised: (1) reversal to the starting materials, (2) isomerization to the anti-Markovnikov product, and (3) cyclization to the selenolactone 12. All of these processes are believed to proceed via a seleniranium ion the intermediacy of which was established by independent synthesis and spectroscopic identification. The reversible formation of chloro selenide adducts was unambiguously established by crossover experiments. The reaction of 10 with PhSeBr was found to be rapid but thermodynamically unfavorable at room temperature.     

Catalysis by ionic liquid: a simple, green and efficient procedure for the Michael addition of thiols and thiophosphate to conjugated alkenes in ionic liquid, [pmIm]Br

A room temperature ionic liquid, 1-pentyl-3-methylimidazolium bromide, [pmIm]Br efficiently catalyzes Michael addition of thiols and diethyl dithiophosphate to a variety of conjugated alkenes such as α,β-unsaturated carbonyl compounds, carboxylic esters, nitriles and chalcones without requiring any other organic solvent and catalyst. The ionic liquid can be recycled for subsequent reactions without any appreciable loss of efficiency.     

Control of the catalytic effect of cetyltrimethylammonium bromide micelles by the addition of background electrolyte and nonionic surfactant

The variation of the microscopic properties (surface potential, micropolarity, etc.) of the interface of cetyltrimethylammonium bromide micelles upon the addition of a background electrolyte or the nonionic surfactant Triton X-100 decreases the rates of ion-molecular reactions, namely, alkaline hydrolysis of carboxylic acid esters and tetracoordinate phosphorus acid esters, and results in the shift of acid-base equilibria. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1933–1940, October, 2007.     

Development of a protocol for eight- and nine-membered ring synthesis in the annulation of sp(2),sp(3)-hybridized organic dihalides with keto esters

A protocol has been developed in which annulation reactions of various dihalides with keto esters can be carried out to provide entry to eight- and nine-membered carbocycles. In this process wherein one alkenyl- or aryl bromide and a tethered alkyl chloride comprise the organic dihalide, a selective metal-halogen exchange reaction between the sp(2)-hybridized bromide and an organolithium initiates the process. Transmetalation to an organoytterbium reagent generates a species that undergoes selective carbonyl addition to the ketone of the keto ester, creating a lactone intermediate. Subjection of the resulting chloroalkyl lactone to intramolecular reductive coupling with samarium(II) iodide completes the desired annulation.     

Synthesis of methyl 3-bromomethylbut-3-enoate and its reactions with aldehydes and tributylchlorostannane in the presence of zinc

Methyl 3-bromomethylbut-3-enoate smoothly reacted with prenal, β-ionylideneacetaldehyde, benzyloxyacetaldehyde, and tributylchlorostannane in the presence of zinc and aqueous ammonium chloride in tetrahydrofuran to give the corresponding δ-hydroxy-β-methylidenecarboxylic acid esters. In the absence of ammonium chloride, satisfactory yields of the products were obtained only in the reactions with prenal and benzyloxyacetaldehyde; these reactions involved lactonization of intermediate δ-hydroxy-β-methylidenecarboxylic acid esters, and the double carbon-carbon bond migrated to the conjugated position with the lactone carbonyl group. The condensation of β-ionylideneacetaldehyde with methyl 3-bromomethylbut-3-enoate was successfully used to obtain isotretinoin. Initial methyl 3-bromomethylbut-3-enoate was synthesized in a good yield from readily accessible ethyl 3,3-diethoxypropionate via cyclopropanation with ethylmagnesium bromide in the presence of titanium tetra(isopropoxide), oxidation of the acetal moiety to ester, and cleavage of the cyclopropane ring in intermediate methyl (1-methylsulfonyloxycyclopropyl)acetate.     

Reductive ethylation of homoallyl alcohols with a disubstituted double bond with ethylmagnesium bromide in the presence of titanium(IV) isopropoxide

Homoallyl and bishomoallyl alcohols with a disubstituted double bond treated with ethylmagnesium bromide in the presence of titanium(IV) isopropoxide are converted into the products of a reductive ethylation of the olefin fragment. Under similar conditions esters of β,γ-unsaturated carboxylic acids undergo a successive cyclopropanation of the ester group and reductive ethylation of the double carbon-carbon bond and yield 1-(3-ethylalkyl)cyclopropanols. The features of the observed reactions are explained in the framework of the carbometallation mechanism of the double carbon-carbon bond by the action of dialkoxytitanacyclopropane reagents.     

Addition reactions of pendant epoxide group in poly(glycidyl methacrylate) with various active esters

Addition reactions of pendant epoxide groups in poly(glycidyl methacrylate) (PGMA) with various active esters such as 1-benzotriazolyl benzoate, S-(2-benzoxazolyl) thiobenzoate, S-(2-benzothiazolyl) thiobenzoate, 4-nitrophenyl benzoate (4NPB), and S-phenyl thiobenzoate (PTB) were carried out using quaternary salts as catalysts. The reactions of PGMA with those active esters proceeded in diglyme at 100°C for 24 h quantitatively without the formation of 2-hydroxyl pendant groups in the polymer when 10 mol % of tetraethylammonium bromide was used as a catalyst. Furthermore, it was found that the respective quaternary salts have higher catalytic activity than tertiary amines in the reaction of PGMA with the active esters, and the reaction of PGMA with 4NPB gave the corresponding polymer with the highest conversion by addition of tetrabutylammonium bromide as a catalyst, while tetraethylammonium chloride showed the highest activity for the reaction of PGMA with PTB. In addition, the rate of reaction of PGMA with 4NPB was proportional to third order kinetics of the epoxide concentration, the ester concentration and the catalyst concentration as follows: ?d[Epoxide]/dt = ?[Ester]/dt = k₃[Epoxide] [Ester] [Catalyst].     

Aqueous hydroxide as a base for palladium-catalyzed amination of aryl chlorides and bromides

The amination of aryl halides in the presence of inexpensive and air-stable alkali metal hydroxide bases and Pd[P(t-Bu)3]2 as catalyst gave arylamines in high yields. The reactions were conducted with a catalytic amount of cetyltrimethylammonium bromide as phase-transfer agent and either aqueous hydroxide or solid hydroxide in the presence of water. This combination of alkali metal hydroxide base, H2O, and the ammonium salt performed as well as NaO-t-Bu in the amination of p-chlorotoluene with dibutylamine. Hydroxide base was suitable for reactions of a wide range of aryl chlorides and bromides with aliphatic and aromatic amines. Some functional groups that were intolerant of tert-butoxide base, such as esters, enolizable ketones, nitriles, and nitro groups, were tolerated by the combination of hydroxide base, H2O, and cetyltrimethylammonium bromide in toluene solvent.     

Development of Asymmetric Reactions Catalyzed by Chiral Organotin‐Alkoxide Reagents

Asymmetric catalysis under almost‐neutral reaction conditions is key for the efficient synthesis of optically active polar molecules. We have developed catalytic enantioselective reactions of acyclic or cyclic alkenyl esters by using an (S)‐BINOL‐derived chiral tin‐dibromide reagent that possesses a bulky aryl group at the 3 or 3′ position as the chiral pre‐catalyst in the presence of a sodium alkoxide and an alcohol, in which a chiral tin alkoxide bromide is generated in situ and recycled with the assistance of an alcohol. In this Personal Account, we describe three types of asymmetric transformation that proceed through a chiral tin enolate: 1) The asymmetric aldol reaction of alkenyl esters or unsaturated lactones with aldehydes or isatins; 2) the asymmetric three‐component Mannich‐type reaction of alkenyl esters and related cycloaddition reactions; and 3) the asymmetric N‐nitroso aldol reaction of unsaturated lactones with nitrosoarenes.     

Supramolecular systems based on aminomethylated calix[4]resorcinarene and a cationic surfactant: Catalysts of the hydrolysis of esters of phosphorus acids

Kinetics of alkaline hydrolysis of 4-nitrophenyl esters of tetracoordinated phosphorus acids in micellar solutions of aminomethylated calix[4]resorcinarene containing sulfonatoethylene groups on the lower rim of the macrocycle, 4-aza-1-hexadecyl-azoniabicyclo[2.2.2]octane bromide and their mixtures was investigated spectrophotometrically. It is established that the catalytic effect of aggregates depends on the concentration of calixarene and surfactants, pH, presence of lanthanum salt and reaches more than two orders of magnitude. The parameters of the catalyzed reactions and their dependence on the composition are determined.     

Reaction of perfluoroalkanesulfonyl halide: 3. The reactions of perfluoroalkanesulfonyl bromide with α, β-unsaturated esters and chemical conversions of the products

The reactions of perfluoroalkanesulfonyl bromide with α, β-unsaturated esters were studied in detail. The reaction products were further converted to a series of perfluoroalkyl-substituted α, β-unsaturated acids or esters, α-amino acids and γ-lactones. A peculiar peak (M+15) was found to appear in the mass spectra of some perfluoroalkyl-substituted methyl esters. It was interpreted to be the result of a CH₃ group transfer to the molecular ion. Magnetic nonequivalence was observed in the ¹⁹F NMR spectra of CF₂ group linked to CH₂ in compounds 2f, g and 3f, g which showed a typical AB pattern, and was attributed to the effect of steric hindrance.     

A highly diastereoselective synthesis of (E)-B-2-(1-cyclopropyl-1-alkenyl)-1,3,2-dioxaborinanes. Isolation and oxidation to alkyl cyclopropyl ketones

A convenient, novel synthesis of alkyl cyclopropyl ketones based on Z-1-bromo-1-alkenylboronate esters is developed. α-Bromo-(Z)-1-alkenylboronate esters readily available from literature procedures smoothly undergo a reaction with cyclopropylmagnesium bromide in tetrahydrofuran to provide the corresponding ‘ate’ complexes. These ‘ate’ complexes undergo intramolecular nucleophilic substitution reactions to provide the corresponding (E)-1-alkenylboronate esters containing cylcopropyl moiety for the first time in good isolated yields (68-82%). The carbon skeleton present in these intermediates is confirmed by oxidation with hydrogen peroxide and sodium acetate to afford the corresponding alkyl cyclopropyl ketones in good yields (72-85%).     

Functionalized enamines—XXXII : Reaction of β-amino-α, β-unsaturated esters and amides with benzyl and cinnamyl bromides

Reactions of β-aminoacrylic esters (1–c) and amides (1d–o) with benzyl bromide 2 and cinnamyl bromide 3 give products which are dependent both upon the nature of the amine component of the enamine and, in the case of the amides, upon the amine from which the amide is derived. The β-enamino esters react with benzyl bromide to yield predominantly dialkylated products in the case of the pyrrolidine ester 1a. Reactions of the same esters with cinnamyl bromide yield mixtures of cinnamyl and 2-phenylpropenyl-substituted formylacetic esters. The enamino amides 1d–f react to yield the expected alkylated derivatives. The anilides 1i–o exhibit nucleophilic reactivity at the aniline nitrogen. A mechanism leading to the observed products is proposed.     

Evidence of enhanced reactivity of DAAP nucleophiles toward dephosphorylation and deacylation reactions in cationic gemini micellar media

4,4'-(Dialkylamino)pyridine (DAAP)-based compounds 1-4 catalytically cleave hydrophobic organophosphate and carboxylate esters in various host micellar aggregates at mildly alkaline pH. The role of the micellar reaction medium in such esterolytic reactions has been carefully examined in this work. The cationic gemini surfactant based micellar aggregates provide more than 1 order of magnitude better reaction medium for the above reactions than their conventional single-chain, single-charge, cationic cetyl trimethylammonium bromide (CTABr) micelles. The catalytic turnover behavior of DAAP nucleophiles in the presence of excess substrates is also retained in gemini micellar media.     

Reactivity and enantioselectivity in the reactions of scalemic stereogenic alpha-(N-carbamoyl)alkylcuprates

Stereogenic 2-(N-carbamoyl)pyrrolidinylcuprates prepared from scalemic (i.e., enantioenriched) N-Boc-2-lithiopyrrolidine and THF soluble CuCN.2LiCl react with vinyl iodides, vinyl triflates, beta-iodo-alpha,beta-enoates, propargyl mesylates, and allyl bromide to afford the substitution products with excellent enantioselectivity. Excellent enantiomeric ratios are obtained in the conjugate addition reactions with methyl vinyl ketone while low enantiomeric ratios can be achieved with acrylate esters using HMPA/TMSCl activation. Enantiomeric ratios vary with substrate substitution patterns and the observed enantioselectivities appear to be more a function of cuprate-electrophile reactivities than of the reaction type (e.g., substitution, conjugate addition). Low enantiomeric ratios are obtained with the alpha-(N-carbamoyl)benzylcuprates. The lithium-copper transmetalation and cuprate vinylation reactions proceed with retention of configuration.