Nitroaldol reaction in fluorous media: An important improvement of the chemoselective addition of aldehyde

Ytterbium perfluorooctanesulfonate [Yb(OPf)₃] catalyses the highly efficient Henry reaction in the presence of a catalytic amount of a novel perfluoroalkylated-pyridine as a ligand in a fluorous biphase system (FBS) composed of toluene and perfluorodecalin. An unprecedented chemoselective addition of aldehydes among various carbonyl compounds and the robustness of the catalytic system for recycling using by simple phase-separation were obtained.     

Switchable cholesterol recognition system with Diels–Alder reaction using molecular imprinting technique on self‐assembled monolayer

Molecular imprinting was conducted using a method to form a polymeric coating on a self‐assembled monolayer (SAM). This molecular imprinting system was able to obtain an on–off function using the Diels–Alder reaction. Cholesterol was used as a target compound and the SAM was formed using thiol compound on a gold plate. Epoxy resin was used to form the polymeric coating. Covalent bonding method was used in molecular imprinting. The formed molecular imprinting system recognized cholesterol better than analogs of cholesterol. Epoxy resin curing agent with furan group was synthesized to form the molecular imprinting system. Using the Diels–Alder reaction between the furan group and phenylmaleimide, this molecular imprinting system offers a switchable function. © 2019 Society of Chemical Industry     

Retro‐Diels–Alder Reactions of Masked Cyclopentadienones Catalyzed by Heterogeneous Brønsted Acids

The zeolite H‐Beta catalyzes the retro‐Diels–Alder reaction of a range of cyclopentadiene cyclo‐adducts at moderate temperatures and ambient pressure, in the presence of an active dienophile. The active catalyst was identified and optimum reaction conditions established after screening a range of zeolites in the retro‐Diels–Alder reaction of the cyclopentadiene adduct of cyclopentenone. Our results suggest that retro‐Diels–Alder reactions of tricyclodecadienones are catalyzed by Brønsted acids and the high catalytic performance of H‐Beta catalysts can be ascribed to the optimal balance between the number of acid sites and their strength as well as to the accessibility of these sites. The methodology was then applied to a series of alkyl derivatives of cyclopentadienylcyclopentenones to provide a viable alternative synthetic route to 4‐alkylcyclopentenones and the versatility of the approach was demonstrated by the successful cycloreversion of N‐cyclohexyl‐2‐azanorborn‐5‐ene.     

Mechanistic Insights into Transition Metal‐Catalysed Oxidation of a Hydroxamic Acid with in situ Diels–Alder Trapping of the Acyl Nitroso Derivative

New insights into the mechanism for the transition metal‐mediated oxidation of hydroxamic acids to give intermediate acyl nitroso species, with subsequent hetero‐Diels–Alder trapping are presented. The activation of triphenylphosphine‐ligated ruthenium‐salen complexes is examined, and evidence is presented for the ruthenium‐oxo species which are involved in the oxidative process of the hydroxamic acid. The observation of the lack of asymmetric induction involved in the intermolecular cycloaddition process involving the intermediate acyl nitrsoso species is explained, with the aid of comparing the ruthenium‐salen‐based systems with nitrosotoluene, and copper(I)/copper(II) BINAP‐based catalysis of nitrosopyridine complexes. This study demonstrates the importance of secondary coordination to achieve asymmetric induction in nitroso‐Diels–Alder reactions.     

Synthesis of Chiral Polyethers Containing Imidazolidinone Repeating Units and Application as Catalyst in Asymmetric Diels–Alder Reaction

In this study, enantiopure imidazolidinones containing two hydroxyphenyl groups were synthesized, and the Williamson synthesis of the chiral bisphenols thus prepared with dihalides afforded polyethers containing chiral imidazolidinone repeating units. These chiral imidazolidinone polyethers exhibited excellent catalytic activity in the asymmetric Diels–Alder reaction. With the use of these polymeric catalysts, enantioselectivities up to 99% were obtained, higher than those obtained by the corresponding monomeric imidazolidinone catalyst in homogeneous solution. The polymeric catalysts were found to be insoluble in commonly used organic solvents, and they could be repeatedly used without the loss of activity.

     

Chiral Phosphoric Acid‐Catalyzed Enantioselective Three‐ Component Aza‐Diels–Alder Reactions of Aminopyrroles and Aminopyrazoles

A highly stereoselective three‐component Povarov reaction, catalyzed by (R)‐ and (S)‐BINOL hydrogen phosphate, was achieved for the first time with aminopyrroles and aminopyrazoles as 2‐azadiene precursors. A variety of aldehydes, enecarbamates, amino‐substituted azines participated in the reaction to afford the tetrahydropyrrolopyridines and tetrahydropyrazolopyridines in good yields with excellent diatereo‐ and enantioselectivities. A stereochemical model is proposed to account for the observed absolute stereochemistry.

     

Copolymerization of a bisanthracene compound with bismaleimides by Diels–Alder cycloaddition

Four new polymers have been synthesized via succesive Diels–Alder cycloadditions of a bisdiene compound bearing two anthracene groups and four bisdienophiles, all containing bismaleimide functions. The polycondensation reaction was performed in N,N‐dimethylacetamide at 120 °C leading to polymers soluble in polar solvents having molecular weights lower than 6000 g mol^?1. © 2001 Society of Chemical Industry     

Bio‐orthogonal Fluorescent Labelling of Biopolymers through Inverse‐Electron‐Demand Diels–Alder Reactions

Bio‐orthogonal labelling schemes based on inverse‐electron‐demand Diels–Alder (IEDDA) cycloaddition have attracted much attention in chemical biology recently. The appealing features of this reaction, such as the fast reaction kinetics, fully bio‐orthogonal nature and high selectivity, have helped chemical biologists gain deeper understanding of biochemical processes at the molecular level. Listing the components and discussing the possibilities and limitations of these reagents, we provide a recent snapshot of the field of IEDDA‐based biomolecular manipulation with special focus on fluorescent modulation approaches through the use of bio‐orthogonalized building blocks. At the end, we discuss challenges that need to be addressed for further developments in order to overcome recent limitations and to enable researchers to answer biomolecular questions in more detail.     

Recycling Chiral Imidazolidin‐4‐one Catalyst for Asymmetric Diels–Alder Reactions: Screening of Various Ionic Liquids

Various imidazolium ionic liquids such as [Bmim]PF₆, [Bmim]SbF₆, [Bmim]OTf and [Bmim]BF₄ were screened for recycling an organic catalyst [(5S)‐5‐benzyl‐2,2,3‐trimethylimidazolidin‐4‐one ( 1 )] for asymmetric Diels–Alder reactions. Good yields and enantioselectivies (up to 85% yield and 93% ee) were obtained from reactions in [Bmim]PF₆ or [Bmim]SbF₆. However, reactions in [Bmim]OTf or [Bmim]BF₄ gave racemic products in low yields. Isolation of the products by simple extraction using diethyl ether allowed recycling of the ionic liquid containing the immobilized catalyst in subsequent reactions without significant decrease of yields and enantioselectivities.     

High Regioselective Diels–‐Alder Reaction of Myrcene with Acrolein Catalyzed by Zinc‐Containing Ionic Liquids

The ambient zinc‐containing ionic liquids, MX‐ZnCl₂, functioning as both Lewis acid catalyst and green solvent, are employed for a high regioselective Diels–Alder reaction of myrcene with acrolein for the first time, where MX is either 1‐butyl‐3‐methylimidazolium chloride (BmimCl), 1‐ethyl‐3‐methylimidazolium bromide (EmimBr), N‐butylpyridinium bromide (BPyBr), or N‐ethylpyridinium bromide (EtPyBr). Compared with the analogous reaction performed over a ZnCl₂ catalyst in the conventional solvent dichloromethane, higher regioselectivity of the ‘para’ cycloadduct and excellent yield were achieved at shorter reaction time in these ionic liquids with optimized molar compositions of MX and ZnCl₂. These moisture‐insensitive ionic liquids can be easily separated from reaction products after simple washing with hexane, allowing their reuse with no obvious loss in activity.     

Recyclable Copper Catalysts Based on Imidazolium‐Tagged Bis(oxazolines): A Marked Enhancement in Rate and Enantioselectivity for Diels–Alder Reactions in Ionic Liquid

Imidazolium‐tagged bis(oxazolines) have been prepared and used as chiral ligands in the copper(II )‐catalysed Diels–Alder reaction of N‐acryloyl‐ and N‐crotonoyloxazolidinones with cyclopentadiene and 1,3‐cyclohexadiene in the ionic liquid 1‐ethyl‐3‐methylimidazolium bis[(trifluoromethyl)sulfonyl]imide, [emim][NTf₂]. A significant and substantial enhancement in the rate and enantioselectivity was achieved in [emim][NTf₂] compared with dichloromethane. For example, complete conversion and enantioselectivities up to 95 % were obtained for the reaction between N‐acryloyloxazolidinone and cyclopentadiene within 2 min in [emim][NTf₂] whereas the corresponding reaction in dichloromethane required 60 min to reach completion and gave an ee of only 16 %. The enhanced rates obtained in the ionic liquid enabled a catalyst loading as low as 0.5 mol % to give complete conversion within 2 min while retaining the same level of enantioselectivity. The imidazolium‐tagged catalysts can be recycled ten times without any loss in activity or enantioselectivity and showed much higher affinity for the ionic liquid phase during the recycle procedure than the analogous uncharged ligand.     

Ionic Liquid Effect on the Reversal of Configuration for the Magnesium(II) and Copper(II) Bis(oxazoline)‐Catalysed Enantioselective Diels–Alder Reaction

Ionic liquids have been used to support a range of magnesium‐ and copper‐based bis(oxazoline) complexes for the enantioselective Diels–Alder reaction between N‐acryloyloxazolidinone and cyclopentadiene. Compared with reaction performed in dichloromethane or diethyl ether, an enhancement in ee is observed with a large increase in reaction rate. In addition, for non‐sterically hindered bis(oxazoline) ligands, that is, phenyl functionalised ligands, a reversal in configuration is found in the ionic liquid, 1‐ethyl‐3‐methylimidazolium bis[(trifluoromethanesulfonyl)imide], compared with molecular solvents. Supported ionic liquid phase catalysts have also been developed using surface‐modified silica which show good reactivity and enantioselectivity for the case of the magnesium‐based bis(oxazoline) complexes. Poor ees and conversion were observed for the analogous copper‐based systems. Some drop in ee was found on supporting the catalyst due a drop in the rate of reaction and, therefore, an increase in the contribution from the uncatalysed achiral reaction.     

Higher‐Order Human Telomeric G‐Quadruplex DNA Metalloenzymes Enhance Enantioselectivity in the Diels–Alder Reaction

Short human telomeric (HT) DNA sequences form single G‐quadruplex (G₄) units and exhibit structure‐based stereocontrol for a series of reactions. However, for more biologically relevant higher‐order HT G₄‐DNAs (beyond a single G₄ unit), the catalytic performances are unknown. Here, we found that higher‐order HT G₄‐DNA copper metalloenzymes (two or three G₄ units) afford remarkably higher enantioselectivity (>90 % ee) and a five‐ to sixfold rate increase, compared to a single G₄ unit, for the Diels–Alder reaction. Electron paramagnetic resonance (EPR) and enzymatic kinetic studies revealed that the distinct catalytic function between single and higher‐order G₄‐DNA copper metalloenzymes can be attributed to different Cu^II coordination environments and substrate specificity. Our finding suggests that, like protein enzymes and ribozymes, higher‐order structural organization is crucial for G₄‐DNA‐based catalysis.     

Impact of Carbon Dioxide Pressurization on Liquid Phase Organic Reactions: A Case Study on Heck and Diels–Alder Reactions

Heck coupling reactions of methyl acrylate with various aryl bromides have been investigated using a Pd/TPP catalyst in toluene under pressurized CO₂ conditions up to 13 MPa. Although CO₂ is not a reactant, the pressurization of the reaction liquid phase with CO₂ has positive and negative impacts on the rate of Heck coupling depending on the structures of the substrates examined. In the case of either 2‐bromoacetophenone or 2‐bromocinnamate, the conversion has a maximum at a CO₂ pressure of about 3 MPa; for the former, it is much larger by a factor of 3 compared with that under ambient pressure. For 2‐bromobenzene, in contrast, the conversion is minimized at a similar CO₂ pressure, being half compared with that at ambient pressure. In the other substrates, including the other isomers of these three aryl bromides, the conversion simply decreases or does not change so much with the CO₂ pressure. To examine the factors responsible for the effects of CO₂ pressurization, the phase behavior and the molecular interactions with dense phase CO₂ have also been studied by visual observation and in situ high pressure FT‐IR spectroscopy. In addition, impact of CO₂ pressurization was also studied for the Diels–Alder reactions of isoprene with a few dienophiles like methyl acrylate, methyl vinyl ketone, and acrolein in the same solvent, toluene, but a heterogeneous silica‐alumina catalyst was used (the reaction system was liquid‐solid biphasic). When the CO₂ pressure is raised, the conversion monotonously decreases for the three dienophiles; however, the product selectivity changes with the pressure, in particular for acrolein. The FT‐IR spectroscopic measurements suggest that its reactivity is altered by interactions with CO₂ molecules under pressurized conditions.     

Second Generation CaSH (Camphor Sulfonyl Hydrazine) Organocatalysis. Asymmetric Diels–Alder Reactions and Isolation of the Catalytic Intermediate

In one step, the well known chiral auxiliary, Oppolzer’s camphor sultam, is turned into the new generation camphor sulfonyl hydrazine (CaSH II) organocatalyst. With the primary hydrazine functionality external to the tricyclic structure, CaSH II is active towards ketone substrates in asymmetric Diels–Alder reactions. The iminium intermediate of the catalytic cycle was isolated. When it was put back into the solution reaction system, the same level of yield and stereoselectivity was observed. Based on these observations, we argue that organocatlyst is actually an in situ chiral auxiliary.     

Separation of cation–anion mixture using micellar-enhanced ultrafiltration in a mixed micellar system

Aqueous solution containing copper (cation) and potassium permanganate (anion) was treated by ultrafiltration using mixed micellar system comprising of sodium dodecyl sulfate and cetylpyridinium chloride. Simultaneous separation characteristics of both cation and anion, as well as permeate flux were studied for various operating conditions, namely, transmembrane pressure drop and cross-flow rate. The study was carried over a wide concentration range of both solutes. In the mixture, copper concentration was in the range from 0.05 to 4.0 kg/m³ and that of potassium permanganate was 0.05 to 0.25 kg/m³. Retention of copper was in the range of 90–100% and that of potassium permanganate was 96–99%. Permeate flux was found to be less in the mixed micellar system compared to single surfactant system. A four step chemical treatment process was proposed to recover and reuse the surfactants.     

Hafnium Chloride Tetrahydrofuran Complex‐Catalyzed Diels–Alder Cycloadditions of 3‐Ethoxycarbonylcoumarins with 1,3‐Dienes under Solvent‐Free Conditions

Hafnium chloride tetrahydrofuran complex (HfCl₄⋅2 THF) is an efficient catalyst for the Diels–Alder cycloadditions of 3‐ethoxycarbonylcoumarins 1a – c and 1,3‐butadienes 2x – z under solvent‐free conditions furnishing the corresponding cycloadducts in excellent yields. This salt is an air stable Lewis acid and therefore the reactions can be performed in air atmosphere making the procedure simple to be carried out.     

Activity of horseradish peroxidase in aqueous and reverse micelles and back‐extraction from reverse‐micellar phases

Studies on the activity of the enzyme horseradish peroxidase (HRP) have been carried out in micellar as well as reverse‐micellar media. The activity of the enzyme was studied in the presence of different classes of surfactants – ionic as well as non‐ionic. In aqueous media, the activity of the enzyme varied depending on whether the concentration of the surfactant used was above or below the critical micellar concentration (CMC). The enzyme was also studied in reverse‐micellar systems. HRP was introduced into the reverse micellar phase by the injection method and its activity within the reverse micelles was determined. The effect of water to surfactant ratio (W_o) on activity within reverse micelles was studied, and an almost two‐fold increase in activity was seen when the enzyme was encapsulated within reverse micelles of aqueous phase fractional hold‐up (?) of 0.0072 (v/v) consisting of sodium bis‐(2‐ethylhexyl) sulfosuccinate (AOT) in isooctane at a W_o of 20. The activity of HRP was measured over a wide range of AOT concentrations having different W_o values. Back‐extraction of HRP from these reverse micelles was carried out at varying ionic strengths of phosphate buffer. Back extraction was found to be highest at pH 7.0 in 40 mol m^?3 phosphate buffer and 100 mol m^?3 sodium chloride. © 2001 Society of Chemical Industry     

N,N′‐Dioxide/Zinc Bis(trifluoromethylsulfonyl)imide Complex Catalyzed Enantioselective Diels–Alder Reaction of Cyclopentadiene with Alkynones

An N,N′‐dioxide/zinc bis(trifluoromethylsulfonyl)imide complex has been developed as an efficient catalyst for the highly enantioselective Diels–Alder reaction of cyclopentadiene with alkynones. Various 2‐acyl substituted norbornadiene derivatives were obtained in moderate to high yields (up to 99 %) with good enantiomeric excesses (up to 95 %).