Catalytic Asymmetric Synthesis of 3‐(α‐Hydroxy‐β‐carbonyl) Oxindoles by a ScIII‐Catalyzed Direct Aldol‐Type Reaction

A direct catalytic asymmetric aldol‐type reaction of 3‐substituted‐2‐oxindoles with glyoxal derivatives and ethyl trifluoropyruvate, catalyzed by a chiral N,N′‐dioxide–Sc(OTf)₃ (Tf=trifluoromethanesulfonyl) complex, has been developed that tolerates a wide range of substrates. The reaction proceeds in good yields and excellent enantioselectivities (up to 93 % yield, 99:1 diastereomeric ratio (dr), and >99 % enantiomeric excess (ee)) under mild conditions, to deliver 3‐(α‐hydroxy‐β‐carbonyl) oxindoles with vicinal quaternary–tertiary or quaternary–quaternary stereocenters. Even with 1 mol % catalyst loading or on scaleup (10 mmol of starting material), maintenance of ee was observed, which showed the potential value of the catalyst system. In studies probing the reaction mechanism, a positive nonlinear effect was observed and Sc^III‐based enolate intermediates were detected by using ESIMS. On the basis of the experimental results and previous reports, a possible catalytic cycle was assumed.     

Synthesis and Conformational Analysis of Hybrid α/β‐Dipeptides Incorporating S‐Glycosyl‐β2,2‐Amino Acids

We synthesized and carried out the conformational analysis of several hybrid dipeptides consisting of an α‐amino acid attached to a quaternary glyco‐β‐amino acid. In particular, we combined a S‐glycosylated β^2,2‐amino acid and two different types of α‐amino acid, namely, aliphatic (alanine) and aromatic (phenylalanine and tryptophan) in the sequence of hybrid α/β‐dipeptides. The key step in the synthesis involved the ring‐opening reaction of a chiral cyclic sulfamidate, inserted in the peptidic sequence, with a sulfur‐containing nucleophile by using 1‐thio‐β‐D ‐glucopyranose derivatives. This reaction of glycosylation occurred with inversion of configuration at the quaternary center. The conformational behavior in aqueous solution of the peptide backbone and the glycosidic linkage for all synthesized hybrid glycopeptides was analyzed by using a protocol that combined NMR experiments and molecular dynamics with time‐averaged restraints (MD‐tar). Interestingly, the presence of the sulfur heteroatom at the quaternary center of the β‐amino acid induced θ torsional angles close to 180° (anti). Notably, this value changed to 60° (gauche) when the peptidic sequence displayed aromatic α‐amino acids due to the presence of CH–π interactions between the phenyl or indole ring and the methyl groups of the β‐amino acid unit.     

Asymmetric Synthesis of Enantioenriched 2‐Aryl‐2,3‐Dihydrobenzofurans by a Lewis Acid Catalyzed Cyclopropanation/Intramolecular Rearrangement Sequence

A cyclopropanation/intramolecular rearrangement initiated by the Michael addition of in situ generated ortho‐quinone methides (o‐QMs) has been developed for the enantioselective synthesis of 2‐aryl‐2,3‐dihydrobenzofurans containing two consecutive stereogenic centers, including a quaternary carbon atom. In the presence of a chiral oxazaborolidinium ion catalyst, the reaction proceeded in excellent yields (up to 95 %) with excellent stereoselectivity (up to >99 ee, up to >20:1 d.r.).     

Pd/Cu‐Catalyzed Enantioselective Sequential Heck/Sonogashira Coupling: Asymmetric Synthesis of Oxindoles Containing Trifluoromethylated Quaternary Stereogenic Centers

An asymmetric palladium and copper co‐catalyzed Heck/Sonogashira reaction between o‐iodoacrylanilides and terminal alkynes to synthesize chiral oxindoles was developed. In particular, a wide range of CF₃‐substituted o‐iodoacrylanilides reacted with terminal alkynes, affording the corresponding chiral oxindoles containing trifluoromethylated quaternary stereogenic centers in high yields with excellent enantioselectivities (94–98 % ee). This asymmetric Heck/Sonogashira reaction provides a general approach to access oxindole derivatives containing quaternary stereogenic centers including CF₃‐substituted ones.     

Synthesis of polyethers with unsymmetrical structures by the polyaddition of 3‐ethyl‐3‐(glycidyloxymethyl)oxetane with diacyl chlorides

Polyethers with unsymmetrical structures in the main chains and pendant chloromethyl groups were synthesized by the polyaddition of 3‐ethyl‐3‐(glycidyloxymethyl)oxetane (EGMO) with certain diacyl chlorides with quaternary onium salts or pyridine as catalysts. The unsymmetrical polyaddition of EGMO containing two different cyclic ether moieties such as oxirane and oxetane groups with terephthaloyl chloride proceeded smoothly in toluene at 90 °C for 6 h to give polymer 1 with a number‐average molecular weight (M_n) of 51,700 in a 93% yield when tetrabutylammonium bromide (TBAB) was used as a catalyst. The polyaddition also proceeded smoothly under the same conditions when other quaternary onium salts, such as tetrabutylammonium chloride, tetrabutylammonium iodide, tetrabutylphosphonium chloride, and tetrabutylphosphonium bromide, and pyridine were used as catalysts. However, without a catalyst no reaction occurred under the same reaction conditions. Polyadditions of EGMO with isophthaloyl chloride and adipoyl chloride gave polymer 2 (M_n = 28,700) and polymer 3 (M_n = 25,400) in 99 and 65% yields, respectively, under the same conditions. The chemical modification of the resulting polymer, polymer 1 , which contained reactive pendant chloromethyl groups, was also attempted with potassium 3‐phenyl‐2,5‐norbornadiene‐2‐carboxylate with TBAB as a phase‐transfer catalyst, and a polymer with 65 mol % pendant norbornadiene moieties was obtained. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 368–375, 2001     

Copper(I)‐Catalyzed Asymmetric [3+2]‐Cycloaddition of α‐Substituted Iminoesters with α‐Trifluoromethyl α,β‐Unsaturated Esters

Reported herein is an example of highly regio‐, diastereo‐ and enantioselective Cu(I)‐catalyzed intermolecular [3+2] cycloaddition reaction of α‐substituted iminoesters with α‐trifluoromethyl α,β‐unsaturated esters. This novel strategy provided a facile access to pyrrolidines with two skipped (aza)quaternary stereocenters including a CF₃ all‐carbon quaternary stereocenter. A broad substrate scope was observed and high yields (up to 94%) with excellent diastereoselectivity (up to >20 : 1 d.r.) and enantioselectivity (up to 98% ee) were obtained.     

Copper‐Catalyzed Intermolecular Asymmetric Propargylic Dearomatization of Indoles

The first copper‐catalyzed intermolecular dearomatization of indoles by an asymmetric propargylic substitution reaction was developed. This method provides a highly efficient synthesis of versatile furoindoline and pyrroloindoline derivatives containing a quaternary carbon stereogenic center and a terminal alkyne moiety with up to 86 % yield and 98 % ee.     

Solid‐phase incorporation of gaseous carbon dioxide into oxirane‐containing copolymers

Carbon dioxide was incorporated into poly(glycidyl methacrylate‐co‐methyl methacrylate) by a solid‐phase reaction, which transformed the pendent oxirane moieties into cyclic carbonate moieties, with quaternary ammonium halide catalysts. The incorporation of carbon dioxide into the copolymer led to soluble carbonate‐containing polymers, whereas the incorporation of carbon dioxide into the glycidyl methacrylate homopolymer produced an insoluble product. The copolymer composition, reaction temperature, and catalyst amount affected the incorporation efficiency and the side reaction that caused crosslinking. Effective incorporation was achieved under the following reaction conditions: the glycidyl methacrylate content was less than approximately 50%, the temperature was greater than the glass‐transition temperature, and the catalyst concentration was 1.5–6 mol %. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3812–3817, 2004     

Biologically active polymers. V. Synthesis and antimicrobial activity of modified poly(glycidyl methacrylate‐co‐2‐hydroxyethyl methacrylate) derivatives with quaternary ammonium and phosphonium salts

Antimicrobial copolymers bearing quaternary ammonium and phosphonium salts based on a copolymer of glycidyl methacrylate and 2‐hydroxyethyl methacrylate were synthesized. Poly(glycidyl methacrylate‐co‐2‐hydroxyethyl methacrylate) was modified for the introduction of chloromethyl groups by its reaction with chloroacetyl chloride. The chloroacetylated copolymer was modified for the production of quaternary ammonium or phosphonium salts. The antimicrobial activity of the obtained copolymers was studied against gram‐negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Shigella sp., and Salmonella typhae), gram‐positive bacteria (Bacillus subtilus and B. cereus), and the fungus Trichophyton rubrum by the cut‐plug method. The results showed that the three copolymers had high antimicrobial activity. A control experiment was carried out on the main polymer without ammonium or phosphonium groups. The copolymer bearing quaternary salt made from tributyl phosphine was the most effective copolymer against both gram‐negative and gram‐positive bacteria and the fungus T. rubrum. The diameters of the inhibition zones ranged between 20 and 60 mm after 24 h. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2384–2393, 2002     

Antibacterial poly(ethylene glycol) hydrogels from combined epoxy‐amine and thiol‐ene click reaction

Antibacterial hydrogels containing quaternary ammonium (QA) groups were prepared via a facile thiol‐ene “click” reaction using multifunctional poly(ethylene glycol) (PEG). The multifunctional PEG polymers were prepared by an epoxy‐amine ring opening reaction. The chemical and physical properties of the hydrogels could be tuned with different crosslinking structures and crosslinking densities. The antibacterial hydrogel structures prepared from PEG Pendant QA were less well‐defined than those from PEG Chain‐End QA. Furthermore, functionalization of the PEG‐type hydrogels with QA groups produced strong antibacterial abilities against Staphylococcus aureus, and therefore has the potential to be used as an anti‐infective material for biomedical devices. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 656–667     

Switchable thin‐film surface prepared via a simple grafting‐to method using a polystyrene‐b‐poly(2‐vinylpyridine) copolymer

A polystyrene‐b‐poly(2‐vinylpyridine) block copolymer containing a methylhydridosilane linking group was chemically grafted to an 8‐trichlorosilyloctene monolayer via a simple one‐step hydrosilylation reaction. The resulting Y‐shaped thin film exhibited a low grafting density, which was characteristic of the grafting‐to technique. To further reduce the miscibility of the two arms, methyl iodide was reacted with the poly(2‐vinylpyridine) block to produce quaternary ammonium groups. The surfaces before and after quaternization were both solvent‐switchable when subjected to block‐selective solvents. Tensiometry, ellipsometry, attenuated total reflection/Fourier transform infrared, and atomic force microscopy were used to characterize the properties and morphology of both unquaternized and quaternized samples. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5608–5617, 2006     

Diphenylprolinol Silyl Ether Catalyzed Asymmetric Michael Reaction of Nitroalkanes and β,β‐Disubstituted α,β‐Unsaturated Aldehydes for the Construction of All‐Carbon Quaternary Stereogenic Centers

The asymmetric Michael reaction of nitroalkanes and β,β‐disubstituted α,β‐unsaturated aldehydes was catalyzed by diphenylprolinol silyl ether to afford 1,4‐addition products with an all‐carbon quaternary stereogenic center with excellent enantioselectivity. The reaction is general for β‐substituents such as β‐aryl and β‐alkyl groups, and both nitromethane and nitroethane can be employed. The addition of nitroethane is considered a synthetic equivalent of the asymmetric Michael reaction of ethyl and acetyl substituents by means of radical denitration and Nef reaction, respectively. The short asymmetric synthesis of (S)‐ethosuximide with a quaternary carbon center was accomplished by using the present asymmetric Michael reaction as the key step. The reaction mechanism that involves the E/Z isomerization of α,β‐unsaturated aldehydes, the retro‐Michael reaction, and the different reactivity between nitromethane and nitroethane is discussed.     

Cross‐Linked‐Polymer‐Supported N‐{2′‐[(Arylsulfonyl)amino][1,1′‐binaphthalen]‐2‐yl}prolinamide as Organocatalyst for the Direct Aldol Intermolecular Reaction under Solvent‐Free Conditions

A bottom‐up strategy was used for the synthesis of cross‐linked copolymers containing the organocatalyst N‐{(1R)‐2′‐{[(4‐ethylphenyl)sulfonyl]amino}[1,1′‐binaphthalen]‐2‐yl}‐D ‐prolinamide derived from 2 (Scheme 1). The polymer‐bound catalyst 5b containing 1% of divinylbenzene as cross‐linker showed higher catalyst activity in the aldol reaction between cyclohexanone and 4‐nitrobenzaldehyde than 5a and 5c . Remarkably, the reaction in the presence of 5b was carried out under solvent‐free, mild conditions, achieving up to 93% ee (Table 1). The polymer‐bound catalyst 5b was recovered by filtration and re‐used up to seven times without detrimental effects on the achieved diastereo‐ and enantioselectivities (Table 2). The catalytic procedure with polymer 5b was extended to the aldol reaction under solvent‐free conditions of other ketones, including functionalized ones, and different aromatic aldehydes (Table 3). In some cases, the addition of a small amount of H₂O was required to give the best results (up to 95% ee). Under these reaction conditions, the cross‐aldol reaction between aldehydes proceeded in moderate yield and diastereo‐ and enantioselectivity (Scheme 2).     

Highly Enantioselective Formation of α‐Allyl‐α‐Arylcyclopentanones via Pd‐Catalysed Decarboxylative Asymmetric Allylic Alkylation

A highly enantioselective Pd‐catalysed decarboxylative asymmetric allylic alkylation of cyclopentanone derived α‐aryl‐β‐keto esters employing the (R,R)‐ANDEN‐phenyl Trost ligand has been developed. The product (S)‐α‐allyl‐α‐arylcyclopentanones were obtained in excellent yields and enantioselectivities (up to >99.9 % ee). This represents one of the most highly enantioselective formations of an all‐carbon quaternary stereogenic center reported to date. This reaction was demonstrated on a 4.0 mmol scale without any deterioration of enantioselectivity and was exploited as the key enantioselective transformation in an asymmetric formal synthesis of the natural product (+)‐tanikolide.     

Synthesis and characterization of benzimidazolium‐functionalized polysulfones as anion‐exchange membranes

Anion‐exchange membranes containing pendant benzimidazolium groups were synthesized from polysulfone by chrolomethylation followed by nucleophilic substitution reaction with 1‐methylbenzimidazole. The structures of the polymers were characterized by ¹H‐NMR and FTIR analysis. The resulting membranes showed high thermal stability below 200 °C. The values of water uptake and swelling degree increased with the ion‐exchange capacity of the polymeric membrane. The ionic conductivity was measured by means of impedance spectroscopy in aqueous solution of potassium hydroxide (10^?4?10^?1 M). The results show not only a clear correlation between the membrane's electrochemical behavior with the electrolyte solution embedded in the membrane, but also with the degree of the polysulfone's chloromethylation.Thus, the ionic conductivity increased more than two orders of magnitude when the degree of chloromethylation increased from 40 to 140%. Benzimidazolium‐functionalized polysulfones exhibited better thermal, mechanical, and electrochemical properties than the widely used polymeric membranes containing quaternary ammonium groups. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2363–2373     

Catalytic Asymmetric Construction of Quaternary α‐Amino Acid Containing Pyrrolidines through 1,3‐Dipolar Cycloaddition of Azomethine Ylides to α‐Aminoacrylates

The first catalytic enantioselective 1,3‐dipolar cycloaddition of azomethine ylides to α‐aminoacrylate catalyzed by a AgOAc/ferrocenyl oxazolinylphosphine (FOXAP) system was developed, which exhibits excellent exo‐ and enantioselectivity (92–99 % ee). This process provides efficient access to useful 4‐aminopyrrolidine‐2,4‐dicarboxylic acid (APDC)‐like compounds containing a unique quaternary α‐amino acid unit.     

Enantioselective Catalytic Aldehyde α‐Alkylation/Semipinacol Rearrangement: Construction of α‐Quaternary‐δ‐Carbonyl Cycloketones and Total Synthesis of (+)‐Cerapicol

An enantioselective aldehyde α‐alkylation/semipinacol rearrangement was achieved through organo‐SOMO catalysis. The catalytically generated enamine radical cation serves as a carbon radical electrophile that can stereoselectively add to the alkene of an allylic alcohol and initiate ensuing ring‐expansion of cyclopropanol or cyclobutanol. This tandem reaction enables the production of a wide range of nonracemic functionalizable α‐quaternary‐δ‐carbonyl cycloketones in high yields and excellent enantioselectivity from simple aldehydes and allylic alcohols. As a key step, the intramolecular reaction was also successfully applied in the asymmetric total synthesis of (+)‐cerapicol.     

Functional Ionic Liquids Promoted Double Michael Reaction of Benzofuran‐3‐one or 1‐Indone and Symmetric Dienones: Construction of Spiro[benzofuran‐2,1’‐cyclohexane]‐3‐one or Spiro[cyclohexane‐1,2’‐indene]‐1’,4(3’H)‐dione Derivatives

The double Michael reactions between benzofuran‐3‐one or 1‐indone and symmetric dienones in the presence of catalytic ionic liquids were successfully developed and spiro[benzofuran‐2,1’‐cyclohexane]‐3‐one or spiro[cyclohexane‐1,2’‐indene]‐1’,4(3’H )‐dione derivatives containing a spiro quaternary stereogenic center, which widely exist in biologically active products and building blocks in organic synthesis, were obtained in excellent yields (up to 99%). This catalytic system was also extended to the double Michael reaction of less reactive 1‐indone and the desired products were also obtained in 31%‐62% yields. The catalytic system was highly active and efficient for a broad of substrates under mild conditions.     

Electrophilic Cyanation of Boron Enolates: Efficient Access to Various β‐Ketonitrile Derivatives

The highly efficient electrophilic cyanation of boron enolates using readily available cyanating reagents, N‐cyano‐N‐phenyl‐p‐toluenesulfonamide (NCTS) and p‐toluenesulfonyl cyanide (TsCN), is reported. Various β‐ketonitriles were prepared by this new protocol, which has a remarkably broad substrate scope compared to existing methods. The present method also allowed efficient synthesis of β‐ketonitriles containing a quaternary α‐carbon center. In addition, a preliminary result with the use of a chiral boron enolate for the enantioselective cyanation reaction is described.     

Synthesis of poly[(2‐oxo‐1,3‐dioxolane‐ 4‐yl)methyl methacrylate‐co‐styrene] by addition reaction of carbon dioxide and its compatibility with poly(methyl methacrylate) or poly(vinyl chloride)

We investigated the chemical fixation of carbon dioxide (CO ₂) to a copolymer bearing epoxide and the application of the cyclic carbonate group containing copolymer to polymer blends. In the synthesis of poly[(2‐oxo‐1,3‐dioxolane‐4‐yl)methyl methacrylate‐co‐styrene] [poly(DOMA‐co‐St)] from the addition of CO ₂ to poly(glycidyl methacrylate‐co‐styrene) [poly(GMA‐co‐St)], quaternary ammonium salts showed good catalytic activity at mild reaction conditions. The CO ₂ addition reaction followed pseudo first‐order kinetics with the concentration of poly(GMA‐co‐St). In order to expand the applications of the CO ₂ fixed copolymer, polymer blends of this copolymer with poly(methyl methacrylate) (PMMA) or poly(vinyl chloride) (PVC) were cast from N,N′‐dimethylformamide (DMF) solution. Miscibility of blends of poly(DOMA‐co‐St) with PMMA or PVC have been investigated both by differential scanning calorimetry (DSC) and visual inspection of the blends, and the blends were miscible over the whole composition ranges. The miscibility behaviors were also discussed in terms of FT‐IR spectra. Copyright © 2002 John Wiley & Sons, Ltd.