Synthesis and properties of 4,4′-bipyridine based tetracationic carbazolophanes

The precyclophane derived from 3,6-bis(bromomethyl)-9-ethylcarbazole and 5 equiv of 4,4′-bipyridine underwent macrocyclization on quaternization with various dibromides including 3,6-bis(bromomethyl)-9-ethylcarbazole to give carbazole-paraquat, self-complementary, cyclophanes revealing distinct charge-transfer and electrostatic interactions. The macrocyclic carbazolophane 1 was also obtained by a one-pot quaternization technique using equimolar amounts of 3,6-bis(bromomethyl)-9-ethylcarbazole and 4,4′-bipyridine.     

Synthesis of chiral polymers containing thioetherified cinchonidinium repeating units and their application to asymmetric catalysis

A thiol-ene reaction of dithiol and two equivalents of cinchonidine afforded a thioetherified cinchonidine dimer. The dimer was treated with benzyl bromide to give a quaternary ammonium dimer. An ion exchange reaction of the cinchonidinium dimer and disodium disulfonate gave polymers containing chiral quaternary ammonium repeating units in their main-chain structures. Another type of chiral polymer was synthesized by quaternization polymerization. Repeated quaternization reactions between the thioetherified cinchonidine dimer and dihalides yielded chiral polymers containing cinchonidinium structures in their main chains. Both of these chiral polymers were successfully used as catalysts for the asymmetric alkylation of N-diphenylmethylene glycine tert-butyl ester. The chiral cinchonidinium polymers explored in this study showed excellent catalytic activity in asymmetric alkylation reactions and were reused several times without loss of activity.     

Synthesis of allylic thiocyanates and novel 1,3-thiazin-4-ones from 2-(bromomethyl)alkenoates and S-nucleophiles in aqueous medium

Allylic thiocyanates and novel heterocycles containing the 1,3-thiazin-4-one core are easily obtained in high yields and mild conditions by nucleophilic displacement of 2-(bromomethyl)alkenoates (derived from Morita-Baylis-Hillman adducts) with sulphur-centred nucleophiles in aqueous acetone at 25 °C. Treatment of allylic bromides with NaSCN gave the corresponding (Z)-2-(thiocyanomethyl)alkenoates, while the reaction with thiourea followed by a basic work-up selectively produced (5Z)-2-amino-5-arylidene-1,3-thiazin-4-ones. The structural assignments were confirmed by X-ray diffraction analysis.     

Platinum-catalyzed enantioselective hydrogenation of aryl-substituted trifluoroacetophenones

The hydrogenation of 2,2,2-trifluoroacetophenones with different aryl-substituents (CF₃, N(Me)₂ and Me) has been studied over Pt/Al₂O₃ modified by cinchonidine, its hydrochloride or O-methyl cinchonidine. Electron-withdrawing groups increased and electron-releasing groups decreased the rate and enantioselectivity of these reactions, although steric effects (with m- or p-substituents) were also critical. The 92% e.e. achieved in the hydrogenation of 2,2,2-trifluoroacetophenone is the highest value obtained so far in this reaction using any heterogeneous catalyst system.     

Organocatalytic desymmetrization of cyclic meso-anhydrides through enantioselective alcoholysis with functionalized primary nitroallylic alcohols

The direct organocatalytic desymmetrization of cyclic meso-anhydrides was achieved by alcoholysis with nitroallylic alcohols. The reaction between primary nitroallylic alcohols and cyclic meso-anhydrides catalyzed by cinchonidine derived thiourea organocatalyst II (10 mol %) proceeded smoothly. The corresponding hemiesters were obtained in high chemical yields with high to excellent levels of stereoselectivity (up to 90% yield and 99% ee). On the other hand, the reversal of enantioselectivity was observed when an amino cinchonidine derivative (III) was used as the organocatalyst under the similar reaction conditions. This demonstrated an example of activation of the nucelophilic component in the desymmetrization of cyclic meso-anhydrides.     

离子聚合物微球负载钯催化甲酸分解产氢

催化甲酸分解产氢是氢气储存和氢能利用的重要途径。以对乙烯基吡啶和1,3,5-三(溴甲基)-2,4,6-三甲基苯为原料,通过季胺化和聚合,制备了树枝状离子聚合物微球。负载Pd纳米粒子后用于催化甲酸分解产氢。微球的离子交换性能、含N特性以及分子内部空穴使制备的Pd 纳米粒子具有高分散性、小尺寸、均一粒径和优化的电子结构。考察了甲酸浓度和反应温度对产氢速率的影响。结果表明,在50℃、甲酸浓度为1 M、甲酸与钯摩尔比为200、甲酸与甲酸钠摩尔比为3的优化反应条件下,甲酸完全分解时间为30 min。催化剂使用4次后活性无明显下降。     

Synthesis of binuclear rhodacarboranes from 1,4-and 1,3-C6H4(CH2-9-C2H2B9H9-7,8-nido]2 2− dianions and (Ph3P)3RhCl

1,4- and 1,3-C₆H₄(CH₂-9-C₂H₂B₉H₉-7,8-nido]₂ ^2? dianions obtained fromnido-7,8-dicarbollide ion and 1,4-bis(bromomethyl)- and 1,3-bis(bromomethyl)benzenes react with (Ph₃P)₃RhCl to give binuclear rhodacarboranes, 1,4- and 1,3-[3,3-(Ph₃P)₂-3-H-3,1,2-RhC₂B₉H₁₀-4-CH₂]₂C₆H4.     

Highly substituted cyclohexanes: strong proximity effects influence synthetic access to 1,3,5-tris(bromomethyl)-1,3,5-trialkylcyclohexanes (alkyl = methyl, n-propyl)

1,3,5-Tris(bromomethyl)-1,3,5-trialkylcyclohexanes (alkyl = methyl, n-propyl) were prepared. These are the first examples of 1,3,5-tris(halomethyl)-1,3,5-trialkylcyclohexanes. One synthetic method directly converted the corresponding triols with PPh₃Br₂, where an excess of the bromination reagent and high temperature (175 °C) were required. Stoichiometric use of PPh₃Br₂ under mild conditions, successfully employed for the synthesis of the parent tris(bromomethyl)cyclohexane, did not lead to the desired tribromides but rather to cyclic ethers. Proximity effects triggered by the 1,3,5-alkyl groups strongly influence the reactivity of such highly substituted cyclohexanes. An alternative synthetic access to the tris(bromomethyl) compounds was also developed, using 1,3,5-tris(triflatomethyl)-1,3,5-trialkylcyclohexanes (triflato = F₃CSO₃) as synthetic intermediates. An X-ray crystal structure of 1,3,5-tris(bromomethyl)-1,3,5-trimethylcyclohexane was obtained.     

Synthesis of new derivatives of 1,5,9,13-tetraaza[16]annulene using 2-substituted vinamidinium salts

New 7,15-dibromo-, 7,15-di(bromomethyl)-, and 7,15-di[4-(bromomethyl)phenyl]-1,5,9,13-tetraaza[16]annulene derivatives are synthesized via the condensation reaction of 2-substituted vinamidinium salts [2-substituted 3-(dimethylamino)-N,N-dimethyl-2-propen-1-aminium salts] with 1,8-diaminonaphthalene in acetonitrile/acetic acid. The ultraviolet spectral behavior of these compounds is examined in DMSO.     

Enantioselective phenylacetylene addition to aldehydes induced by Cinchona alkaloids

Enantioselective addition of phenylacetylene to various aldehydes was studied in the presence of inexpensive and commercially available Cinchona alkaloids. A maximum of 85% ee was obtained using cinchonidine in the presence of Ti(OⁱPr)₄.     

New photochromic polymers

New photochromic polymers were synthesized by quaternization of amino groups of N-methyldiethanolamine polyterephthalate with a mixture of bis(2,5-dimethyl-4-chloromethyl-3-thienyl)-1,3-dioxol-2-one and p-or m-xylylene dichloride. The spectral-kinetic studies of coatings based on the obtained polymers showed that these coatings have photochromic properties, the efficiency of which decreases with an increase in the sample thickness.     

Highly enantioselective allylic alkylation of 5H-oxazol-4-ones with Morita-Baylis-Hillman carbonates

An organocatalytic enantioselective allylic alkylation of 5H-oxazol-4-ones with Morita-Baylis-Hillman carbonates has been developed. With 10?mol% of commercially available cinchonidine, a wide range of substituted 5H-oxazol-4-one derivatives were constructed in good-to-excellent yields with high diastereo- and enantioselectivities. The allylic alkylation adducts obtained are valuable precursors for the synthesis of chiral α-alkyl α-hydroxycarboxylic acid derivatives, which represent a series of versatile building blocks in many biologically active compounds.     

Asymmetric synthesis of α-amino acids using polymer-supported Cinchona alkaloid-derived ammonium salts as chiral phase-transfer catalysts

Cinchonidine and cinchonine have been N-alkylated with Merrifield resin and employed as chiral phase-transfer catalysts for the enantioselective alkylation of enolates from N-(diphenylmethylene)glycine esters with activated electrophiles (up to 90% ee). The use of the polymer-supported cinchonidine ammonium salt afforded the corresponding (S)-isomers, whereas the (R)-isomers were obtained using related cinchonine-supported polymers.     

Catalytic asymmetric synthesis of α-(trifluoromethyl)benzylamine via cinchonidine derived base-catalyzed biomimetic 1,3-proton shift reaction

Here we describe catalytic asymmetric synthesis of α-(trifluoromethyl)benzylamine (1) via biomimetic transamination using chiral base. Imine 4 was isomerized to Schiff base 5 using 50 mol.% of cinchonidine derivatives as a catalyst in chloroform, methanol or acetonitrile. In the case of cinchonidine 6 as a catalyst, the reaction conducted in chloroform allowed for 79% conversion of the starting imine 4 in 52 days. The product imine 5 was obtained of (R) absolute configuration in 35% ee as individual compound without any byproducts. The catalyst 6 can be recovered (>95%) by adding n-hexane to the reaction mixture followed by a simple filtration.     

Expanding the scope of the indium-promoted allylation reaction: 4-(bromomethyl)-1,3-dioxol-2-one as a synthetic equivalent of a 3-arylhydroxyacetone enolate

Cyclic enol carbonates of type 2, obtained via the indium-promoted allylation of aldehydes with 4-(bromomethyl)-1,3-dioxol-2-one, undergo Heck reaction with aryl iodides in the presence of silver trifluoroacetate, to give the corresponding arylated products. Thus, 4-(bromomethyl)-1,3-dioxol-2-one can be considered as a synthetic equivalent of 3-arylhydroxyacetone enolate.     

Reduction of 5-(bromomethyl)-1-pyrrolinium bromides to 2-(bromomethyl)pyrrolidines and their transformation into piperidin-3-ones through an unprecedented ring expansion-oxidation protocol

3,3-Dialkyl-5-(bromomethyl)-1-pyrrolinium bromides, prepared via bromocyclization of N-(2,2-dialkyl-4-pentenylidene)amines by means of bromine in dichloromethane, were reduced to 4,4-dialkyl-2-(bromomethyl)pyrrolidines for the first time using borane dimethyl sulfide in dichloromethane. Furthermore, the latter 2-(bromomethyl)pyrrolidines were transformed into the corresponding piperidin-3-ones through an unprecedented ring expansion-oxidation protocol in dimethylsulfoxide in the presence of potassium carbonate. Reduction of 5,5-dialkylpiperidin-3-ones by means of sodium borohydride in methanol afforded 5,5-dialkyl-3-hydroxypiperidines in good yields.     

Concise and highly efficient approach to three key pyrimidine precursors for rosuvastatin synthesis

We report the synthesis of 5-formyl-, 5-(hydroxymethyl)-, and 5-(bromomethyl) substituted N-[4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl]-N-methylmethanesulfonamide. The presented synthetic approach is based on highly efficient three step preparation of functionalized 5-methylpyrimidine. The methyl group is selectively brominated by NBS with irradiation into the bromomethyl derivative, which is then transformed into the hydroxymethyl or formyl groups in nearly quantitative yields. This approach is superior to the existing methodologies for the preparation of the key pyrimidine precursors used in the synthesis of rosuvastatin since no metal catalysis and no cryogenic reaction conditions are involved.     

Diastereoselective cycloaddition of chiral 1-acryloyl-2-imidazolidinone and o-quinodimethane generated by reduction of 1,2-bis(bromomethyl)benzene with zinc

The reduction of 1,2-bis(bromomethyl)benzene with zinc powder followed by cycloaddition with the chiral dienophile (4R,5S)-1-acryloyl-3,4-dimethyl-5-phenyl-2-imidazolidinone in the presence of BF₃·Et₂O under ultrasound irradiation gave the corresponding Diels–Alder cycloadduct in high yield (90%) and high diastereoselectivity (R:S = 87:13).     

Simple access to 2-methylalk-2-enoates and insect pheromones by zinc-promoted reduction of Baylis-Hillman-derived allylic bromides

(E)-2-Methylacrylates are prepared in good yield and high stereoselectivity by zinc-promoted reduction of 2-(bromomethyl)alkenoates derived from Baylis-Hillman adducts. Synthesis of the male ant pheromone (E)-2,4-dimethyl-2-hexenoic acid was performed using this simple methodology.     

Synthesis of unsymmetrical hydroxybenzylphenols containing isobornyl fragments

4-(Bromomethyl)-2,6-diisobornylphenol was synthesized from 2,6-diisobornyl-4-methylphenol through intermediate 4-bromo-2,6-diisobornyl-4-methylcyclohexa-2,5-dien-1-one. Reactions of 4-(bromomethyl)-2,6-diisobornylphenol with 2,6- and 2,4-dialkylphenols gave new 4-(hydroxybenzyl)phenol derivatives containing bulky tert-butyl and isobornyl substituents.