1,3-Dipolar cycloadditions of new 2,5-bifunctionalized five-membered cyclic nitrones

A new family of five-membered cyclic nitrones bearing functional groups at positions 2 and 5 were tested in 1,3-cycloadditions with various dipolarophiles. These reactions gave the corresponding cycloadducts as single diastereomers in high yields. The reaction scope was examined, 23 compounds were isolated and fully characterized. The comparison of the reactivity was carried out by a study of reaction conversions while different nitrones or dipolarophiles were used. In addition, the exceptional reactivity of nitrone bearing benzylamino group in position 2 was studied. The formation of the nitrone complex and evaluation of its reactivity in 1,3-DC is presented.     

Integrated electrochemical-chemical oxidation mediated by alkoxysulfonium ions

Generation of carbocations by the "cation pool" method followed by reaction with dimethyl sulfoxide (DMSO) gave the corresponding alkoxysulfonium ions. Alkoxysulfonium ions could also be generated by in situ DMSO trapping of electrochemically generated carbocations. The resulting alkoxysulfonium ions were transformed into carbonyl compounds by treatment with triethylamine. The present integrated electrochemical-chemical oxidation can be applied to the oxidation of diarylmethanes to diaryl ketones, toluenes to benzaldehydes, and aryl-substituted alkenes to 1,2-diketones. Moreover, the oxidation of unsaturated compounds bearing a nucleophilic group in an appropriate position gives cyclized carbonyl compounds.     

Chemoselective Oxidation of Alkenes by Metal-Organic Framework-Supported Copper Catalyst

Oxidation of alkenes to carbonyls or diols compounds is important in synthesizing fine chemicals and pharmaceutical intermediates. We report the synthesis and characterization of an aluminum metal-organic framework node-supported copper(II) chloride (DUT-5-CuCl), which is an efficient heterogeneous catalyst for the oxidation of alkenes using H₂O₂ as an oxidizing agent. Styrene and various substituted styrenes were transformed into the corresponding carbonyl compounds in excellent selectivity and yields. DUT-5-CuCl is tolerant with various functional groups and could be recycled and reused at least 5 times in the oxidation of α-methylstyrene. Unlike the oxidation of styrene derivatives, DUT-5-Cu catalyzed oxidation of aliphatic and cyclic alkenes produced 1,2-diols compounds selectively. The mechanism of the DUT-5-Cu catalyzed oxidation of styrene to benzaldehyde was investigated in detail by various experiments such as the determination of reaction intermediates and characterization of the catalyst after catalysis, and computational studies. This work highlights the importance of MOF-supported earth-abundant metal catalysts for oxidation reactions to produce fine chemicals.     

Radical Cyclization Reactions via Manganese(III) Acetate Leading to 2‐Thienyl‐Substituted Dihydrofuran Compounds

The 2‐thienyl‐substituted 4,5‐dihydrofuran derivatives 3 – 8 were obtained by the radical cyclization reaction of 1,3‐dicarbonyl compounds 1a – 1f with 2‐thienyl‐substituted conjugated alkenes 2a – 2e by using [Mn(OAc)₃] (Tables 1–5). In this study, reactions of 1,3‐dicarbonyl compounds 1a – 1e with alkenes 2a – 2c gave 4,5‐dihydrofuran derivatives 3 – 5 in high yields (Tables 1–3). Also the cyclic alkenes 2d and 2e gave the dihydrobenzofuran compounds, i.e., 6 and 7 in good yields (Table 4). Interestingly, the reaction of benzoylacetone (=1‐phenylbutane‐1,3‐dione; 1f ) with some alkenes gave two products due to generation of two stable carbocation intermediates (Table 5).     

The Preparation of O-Trifluoromethyl Carbohydrates

A simple method for the preparation of O-tri-fluoromethyl carbohydrate derivatives is reported. Carbohydrate derivatives bearing excellent leaving groups can react with tris(dimethylamino)sulfonium trifluoromethoxide (TAS+CF₃-O-) to afford trifluoro-methoxy-substituted compounds along with varying amounts of the corresponding deoxyfluoro products. Primary and secondary triflates afford the corresponding trifluoromethyl ethers. Displacement at a secondary center occurs with complete inversion of configuration. Glucosyl bromides react to form mixtures of trifluoromethyl glucosides and glucosyl fluorides.     

Spectres de masse de composes alleniques—I : Transposition de type McLafferty de groupes heteroatomiques et de phenyle sur le carbone allenique central

Mass spectra of allenic compounds substituted with a hydrocarbon chain bearing a heteroatomic group (hydroxy, alcoxy, halogen, dialkylamino) or a phenyl in the γ position exhibits a strong peak corresponding to the loss of C₂H₄ (28a.m.u.) from the molecular ion. This is commonly the base peak of the spectra and due to a McLafferty type transfer of the heteroatom or phenyl group to the central allenic carbon atom. The methyl group shows a lower migratory aptitude in such a process. This type of fragmentation involving the migration of heteroatomic groups is not observed in the spectra of γ-halogen and γ-hydroxyketones, alkenes, alkynes or arenes and seems to be characteristic of the allenic linkage. A nucleophilic attack by heteroatom group (or phenyl) on the central allenic carbon atom is proposed.     

A Convenient Method for the Synthesis of Alkenes from Vic-diols via Cyclic Sulfates with Magnesium Iodide

Reaction of cyclic sulfates of vic-diols with magnesium iodide in acetonitrile produced the corresponding olefins in excellent isolated yields at room temperature. Cyclic sulfates of trans-diols gave trans-alkenes exclusively. Cyclic sulfates of cis-diols gave a mixture of cis- and trans- alkenes. However, the cyclic sulfate of cyclic cis-diol afforded the corresponding cis-alkene only.     

Intramolecular hydroamination with homogeneous zinc catalysts: evaluation of substituent effects in N,N'-disubstituted aminotroponiminate zinc complexes

A series of symmetrical and unsymmetrical N,N'-disubstituted aminotroponimines (ATIHs) have been prepared. Substituents ranging from linear to cyclic alkyl groups, chelating ethers, and aryl groups were employed. The corresponding aminotroponiminate zinc complexes were then synthesized and characterized by a number of techniques, including by X-ray crystallography. Herein we report on the investigations into their activity in the intramolecular hydroamination of nonactivated alkenes. We also demonstrate that complexes bearing ligands with cyclic alkyl groups show superior activity in a number of selected reactions with functionalized aminoalkenes.     

Ruthenium- and platinum-catalyzed sequential reactions: selective synthesis of fused polycyclic compounds from propargylic alcohols and alkenes

A simple method for the preparation of fused polycyclic compounds by an intramolecular cyclization of propargylic alcohols bearing an alkene moiety at a suitable position has been developed, where the presence of both Ru and Pt catalysts promotes a sequence of catalytic cycles in the same medium. This sequential system can be applied to an intermolecular reaction between a propargylic alcohol and an alkene to obtain the corresponding bicyclo[3,1,0]hex-2-ene derivative. These sequential reactions provide a conceptually new type of cycloaddition system between propargylic alcohols and alkenes.     

Highly Fluorescent Flavins: Rational Molecular Design for Quenching Protection Based on Repulsive and Attractive Control of Molecular Alignment

Unprecedented intense fluorescent emission was observed for a variety of flavin compounds bearing a perpendicular cyclic imide moiety at the C7 position of an isoalloxazine platform. A series of alloxan‐substituted flavins was prepared selectively by reduction of the corresponding N‐aryl‐2‐nitro‐5‐alkoxyanilines with zinc dust and subsequent reaction with alloxan monohydrate in the presence of boric acid. Analogues bearing oxazolidine‐2,4‐dione functionality were obtained on methylation of the alloxan‐substituted flavins with methyl iodide and subsequent rearrangement in the presence of an inorganic base. The flavin compounds exhibit intense white‐green fluorescent emission in the solution state under UV excitation at 298 K, with emission efficiencies Φ_{298 K} greater than 0.55 in CH₃CN, which are higher than the values for all reported flavin compounds under similar conditions. The highest Φ_{298 K} value of 0.70 was obtained in CH₃CN for isoalloxazine bearing C7‐alloxan and N10‐2,6‐diisopropylphenyl groups. The temperature dependence of the emission intensities indicates that the pronounced emission properties at 298 K are attributable to the highly heat resistant properties towards emission decay with increasing temperature. Mechanistic studies, including X‐ray diffraction analysis, revealed that the good emission properties and high heat resistance of the alloxan‐substituted flavins are due to a synergetic effect of the associative nature of the C7‐alloxan unit and the repulsive nature of the perpendicular bulky substituents at the C7 and N10 positions.     

Highly diastereoselective 7-endo radical cyclization of ethyl α-methylene-γ-(bromomethyl)dimethylsiloxycarboxylates

The 7-endo radical cyclization of (bromomethyl)dimethylsilyl ethers derived from ethyl γ-hydroxy-α-methylenecarboxylates bearing a bulky γ-substituent such as isopropyl, cyclohexyl, and tert-butyl groups in tetrahydrofuran gave preferentially cyclic silyl ethers bearing the ethoxycarbonyl group anti to the γ-substituents in high yields. Treatment of the cyclic silyl ethers with silica gel gave acyclic ethyl γ-hydroxy-α-[2-(hydroxydimethylsilyl)ethyl]carboxylates. The reduction of the cyclization products with DIBAL followed by Tamao oxidation gave the corresponding acyclic triols.     

Synthesis of highly substituted pyrrolidines via palladium-catalyzed cyclization of 5-vinyloxazolidinones and activated alkenes

N-Tosyl-5,5-divinyloxazolidin-2-one undergoes a palladium-catalyzed decarboxylative cyclization across a range of electrophilic alkenes to give the corresponding pyrrolidine derivatives bearing two contiguous quaternary centres. Alkenes bearing two electron-withdrawing groups are required; pyrrolidines were not formed from mono-activated alkenes. Bulky, electron-rich phosphines promote pyrrolidine formation with less highly electrophilic, doubly activated alkenes, and a dramatic improvement is observed in the presence of iodide.     

Gold(I)-catalyzed intermolecular hydroarylation of alkenes with indoles under thermal and microwave-assisted conditions

An efficient method for intermolecular hydroarylation of aryl and aliphatic alkenes with indoles using a combination of [(PR(3))AuCl]/AgOTf as catalyst under thermal and microwave-assisted conditions has been developed. The gold(I)-catalyzed reactions of indoles with aryl alkenes were achieved in toluene at 85 degrees C over a reaction time of 1-3 h with 2 mol% of [(PR(3))AuCl]/AgOTf as catalyst. This method works for a variety of styrenes bearing electron-deficient, electron-rich, and sterically bulky substituents to give the corresponding products in good to high yields (60-95%). Under microwave irradiation, coupling of unactivated aliphatic alkenes with indoles gave the corresponding adducts in up to 90% yield. Selective hydroarylation of terminal C=C bond of conjugated dienes with indoles gave good product yields (62-81%). On the basis of deuterium-labeling experiments, a reaction mechanism involving nucleophilic attack of Au(I)-coordinated alkenes by indoles is proposed.     

Synthesis of stable azomethine ylides by the rearrangement of 1,3-dipolar cycloadducts of 3,4-dihydroisoquinoline-2-oxides with DMAD

1-Aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines were prepared according to a one-pot procedure involving the reaction of 2-(3,4-dimethoxyphenyl)-ethylamine with aromatic aldehydes in TFA at reflux. The tetrahydroisoquinolines were treated with H₂O₂-WO₄²⁻ in methanol at room temperature to give the corresponding 3,4-dihydroisoquinoline-2-oxides. Treatment of these cyclic nitrones with DMAD in toluene at room temperature gave the corresponding isoxazolo[3,2-a]isoquinolines. These compounds were heated in toluene at reflux to give the corresponding ylides in high yields (Method A). The effect of the substituents on the rate of the rearrangement of such compounds prompted us to discuss a new mechanism involving consecutive C-C bond heterolysis and 1,3-sigmatropic shift. A one-pot reaction involving the treatment of the nitrones with equimolar amounts of DMAD in refluxing toluene also gave the ylides (Method B). The structures of the prepared compounds were elucidated by spectral means and elemental analyses.     

Synthesis of trivalent phosphorus derivatives by light-induced dibromophosphination of akenes

Light-induced dibromophosphination of alkenes was studied. Dehydrobromination of the synthesized bromoalkylphosphonous dibromides gave the corresponding dibromophosphinoalkenes which were converted into alkenylphosphonous acids and their cyclic esters, benzo[1,3,2]dioxaphospholes.     

Synthesis of fused tricyclic gamma-lactones mediated by manganese(III) acetate

Exposure of cyclic alkenes bearing a carboxylic acid and a malonate group to manganese(III) acetate and an appropriate copper(II) salt provides the corresponding tricyclic gamma-lactones in good yield.     

Electroreductive intramolecular coupling of aliphatic cyclic imides with ketones and O-methyloximes

The electroreductive intramolecular coupling of aliphatic cyclic imides with ketones in isopropanol gave five- and six-membered cyclized products. Similarly, the electroreductive intramolecular coupling of aliphatic cyclic imides with O-methyloximes afforded five-, six-, and seven-membered cyclized products. These reactions provide a useful method to synthesize azabicyclo[n.m.0] compounds. The bicyclic products were stereoselectively transformed to the corresponding deoxylated compounds by reduction with NaB(CN)H₃ or Et₃SiH/BF₃·Et₂O.     

Highly Enantioselective Iridium‐Catalyzed Hydrogenation of Cyclic Enamides

The MaxPHOX–Ir catalyst system provided the highest selectivity ever reported for the reduction of cyclic enamides derived from α‐ and β‐tetralones. This result indicates that iridium catalysts are also proficient in reducing alkenes bearing metal‐coordinating groups. In the present system, selectivity was pressure‐dependent: In most cases, a decrease in the H₂ pressure to 3 bar resulted in an increase in enantioselectivity. Moreover, the process can be carried out in environmentally friendly solvents, such as methanol and ethyl acetate, with no loss of selectivity.     

Highly Selective Allylborations of Aldehydes Using α,α‐Disubstituted Allylic Pinacol Boronic Esters

α,α‐Disubstituted allylic pinacol boronic esters undergo highly selective allylborations of aldehydes to give tetrasubstituted homoallylic alcohols with exceptional levels of anti‐Z‐selectivity (>20:1). The scope of the reaction includes both acyclic and cyclic allylic boronic esters which lead to acyclic and exocyclic tetrasubstituted homoallylic alcohols. The use of β‐borylated allylic boronic esters gave fully substituted alkenes bearing a boronic ester which underwent further cross‐coupling enabling a highly modular and stereoselective approach to the synthesis of diaryl tetrasubstituted alkenes. Computational analysis revealed the origin of the remarkable selectivity observed.     

Synthesis of conjugated γ- and δ-lactones from aldehydes and ketones via a vinylation(allylation)-ring closing metathesis-oxidation sequence

Nucleophilic C-vinylation and C-allylation of aldehydes and ketones followed by O-allylation of the obtained carbinols gave the corresponding allyl or homoallyl ethers, respectively. Ring-closing metathesis of these compounds afforded in many cases cyclic ethers (dihydrofurans and dihydropyrans, respectively) bearing disubstituted and trisubstituted CC bonds. These were then subjected to allylic oxidation to yield conjugated γ- and δ-lactones. Reasons for the observed failures are presented and discussed.