Synthesis of Polymer‐Supported Fesulphos Ligands and their Application in Asymmetric Catalysis

The synthesis of two Fesulphos‐based chiral ligands and their immobilization on a polystyrene support is described. These supported chiral ligands act as very efficient catalysts in 1,3‐dipolar cycloaddition and allylic substitution reactions providing the products with excellent enantioselectivities (91 to >99 % ee). Filtration of the catalyst from the reaction mixtures allows simple product isolation. The polymer‐supported Cu complex of chiral ligand PS‐ 8 can be recycled without further addition of a copper salt in 1,3‐dipolar cycloaddition reactions.     

A High‐Throughput Screening Approach for the Determination of Additive Effects in Organozinc Addition Reactions to Aldehydes

The effects of additives in phenylzinc addition reactions to an aldehyde have been studied using an automated high‐throughput screening approach. With 2‐bromobenzaldehyde as test substrate and N,N‐dibutylnorephedrine (dbne) as chiral ligand, an improvement of 20% ee over the catalyzed reaction in the absence of the additive was observed. The described results enable a novel access towards chiral diarylmethanols using commercially available substrates, reagents and ligands as well as fast, automated techniques.     

Synthesis of Substituted Mandelic Acid Derivatives via Enantioselective Hydrogenation: Homogeneous versus Heterogeneous Catalysis

An extensive screening of both homogeneous and heterogeneous catalysts was carried out for the enantioselective hydrogenation of p‐chlorophenylglyoxylic acid derivatives. For p‐chlorophenylglyoxylic amides only homogeneous Rh‐diphosphine complexes gave satisfactory results, ees up to 87% were observed for the cy‐oxo‐pronop ligand. For methyl p‐chlorophenylglyoxylate both a homogeneous as well as a heterogeneous catalyst performed with ees >90%. A Pt catalyst modified with cinchona derivatives achieved 93% ee for the (R)‐ and 87% ee for the (S)‐methyl p‐chloromandelate. A Ru‐MeObiphep catalyst also reached 93% ee with TONs up to 4000 and TOFs up to 210 h⁻¹. For all catalytic systems the effects of the metal, the nature of the chiral auxiliary and the solvent as well as of the reaction conditions were investigated. The homogeneous process was scaled up to the kg scale and the enantiomeric purity of the product was enhanced to >99% ee by two recrystallizations of the free p‐chlorophenylmandelic acid.     

Rhodium‐BisbenzodioxanPhos Complex‐Catalyzed Homogeneous Enantioselective Pauson–Khand‐Type Cyclization in Alcoholic Solvents

The chiral atropisomeric diphosphane ligand (S)‐BisbenzodioxanPhos was found to be highly effective in the co‐operative processeses of aldehyde decarbonylation and cascaded enantioselective Pauson–Khand‐type reactions. Various 1,6‐enynes were transformed to the corresponding bicyclic cyclopentenones in good yields and enantiomeric excesses (up to 96% ee). The attractive feature of this new Rh‐catalyzed homogeneous dual catalysis system is that the reaction can be performed in alcoholic solution.     

Enantioselective Synthesis of Chiral Homoallyl Alcohols and Homoallylamines by Nucleophilic Addition of an Allylboron Reagent Modified by a Polymer‐Supported Chiral Ligand

Crosslinked polymer‐supported chiral N‐sulfonylamino alcohols 5–8 have been prepared by suspension polymerization of enantiopure N‐sulfonylamino alcohol monomers 1–4 with styrene and divinylbenzene. Polymer‐supported chiral allylboron reagents were prepared from the polymeric chiral ligands. Enantioselective additions of the polymer‐supported allylboron reagents to aldehydes and N‐(trimethylsilyl)imines have been successfully carried out in the heterogeneous system. The corresponding optically active homoallyl alcohols and homoallylamines were obtained in high yields with high enantioselectivities (up to 95% ee) which are almost the same as those obtained from homogeneous analogues. The polymer‐supported chiral ligands used were recovered easily and can be reused without any loss of activity.     

Heterogeneous Catalytic Sulfimidation using Immobilized Cu(acac)2

The heterogeneous sulfimidation of various sulfides by microencapsulated copper(II) acetylacetonate, [MC‐Cu(acac)₂], and Cu(acac)₂ immobilized in ionic liquids using [N‐(p‐tolylsulfonyl)imino]phenyliodinane (PhINTs) as nitrene donor has been developed to afford the corresponding sulfimides in good to excellent yields. In the presence of a chiral bis(oxazoline) as ligand, asymmetric induction occurs to afford the chiral sulfimides (up to 50% ee). The ionic liquid containing the immobilized bis(oxazoline)‐copper catalyst can be reused for several cycles with consistent activity and enantioselectivity.     

Remarkable Efficiency Improvement in the Preparation of Insoluble Polymer‐Bound (IPB) Enantioselective Catalytic Systems by the Use of Silicone Chemistry

The use of platinum‐catalyzed hydrosilylation chemistry of silicones greatly simplifies the preparation of bis‐oxazoline (box) ligands covalently bound to an insoluble polymeric support. The use of such immobilized chiral ligands in different copper‐catalyzed asymmetric transformations (carbonyl‐ene, Mukaiyama aldol and olefin cyclopropanation reactions) allows the attainment of high levels of enantioselectivity (91–99 % ee).     

Kinetics of Catalytic Ozonation of Methyl tert‐Butyl Ether in the Presence of Perfluorooctyl Alumina

In this work, the kinetics of heterogeneous ozonation of methyl tert‐butyl ether (MTBE) in the presence of perfluorooctyl alumina (PFOAL) catalysts is presented. Activity of the PFOAL catalysts in ozonation reactions of MTBE was studied in a batch reactor over the temperature range of 25 to 40 °C. The results show that PFOAL is an effective catalyst for enhancing the molecular mechanism of ozone reactions. For a catalyst concentration of 5 g/L, the contribution of the rate of heterogeneous catalytic reaction in the total reaction rate is about 50 %, 75 %, and 85 % at the reaction temperatures of 25 °C, 30 °C, and 40 °C, respectively. Kinetic studies showed that the chemical reaction of ozone and MTBE is the controlling step in this catalytic system. The quasi‐homogeneous kinetic model proved to be an appropriate approach in modeling the heterogeneous reaction of ozone with MTBE on PFOAL catalysts.     

Palladium on Carbon: An Efficient,Heterogeneous and Reusable Catalytic System for Carbonylative Synthesis of N‐Substituted Phthalimides

The application of palladium on carbon (Pd/C) as a heterogeneous recyclable catalyst was investigated for the double carbonylation of o‐dihaloarenes with amines providing excellent yield of N‐substituted phthalimides in shorter reaction time as compared to earlier reported homogeneous protocols. Furthermore, the scope of the developed protocol was applied for the synthesis N‐substituted phthalimides from o‐halobenzoates and o‐halobenzoic acid via a single step carbonylative cyclization reaction. The developed methodology describes an efficient one‐step approach for the synthesis of an important class of heterocycles and tolerates a wide variety of functional groups. It circumvents the use of phosphine ligands with an additional advantage of catalyst recyclability for up to eight consecutive cycles.     

Ferrocene‐Based Chiral Phosphine‐Triazines: A New Family of Highly Efficient P,N Ligands for Asymmetric Catalysis

The presence of the additional heterocyclic nitrogen atoms in chiral P,N ligands has an important influence on the asymmetric catalysis, and a clear trend was observed in the present research that the enantioselectivity and reactivity were significantly increased by raising the number of heterocyclic nitrogen atoms in these P,N ligands. Through finely tuning the number of heterocyclic nitrogen atoms, a new family of ferrocene‐based chiral phosphine‐triazine ligands with three heterocyclic nitrogen atoms has been developed and successfully applied in Pd‐catalyzed asymmetric allylic substitution. Up to 99% ee with 99% yield of allylic alkylation products and 94% ee of allylic amination products have been obtained by the use of ligand (R_c,S_p)‐ 1f with a 4,6‐diphenoxy‐1,3,5‐triazine moiety.     

Asymmetric 1,4‐Addition of Diethylzinc to Cyclic Enones Catalyzed by Cu(I)‐Chiral Sulfonamide‐Thiophosphoramide Ligands and Lithium Salts

The chiral sulfonamide‐thiophosphoramide ligand L1 , prepared from the reaction of (1R,2R)‐(−)‐1,2‐cyclohexanediamine with diphenylthiophosphoryl chloride and p‐toluenesulfonyl chloride, was used as a chiral ligand in Cu(MeCN)₄ClO₄‐promoted catalytic asymmetric addition of diethylzinc to cyclic enones using LiCl as an additive in which up to 90% ee can be realized under mild conditions within 0.5 h. This chiral ligand is stable and recoverable after usual work‐up and can be reused in the same catalytic asymmetric reaction. Moreover, it was found that this series of chiral ligands represents a type of S,O‐bidentate ligands on the basis of ¹H NMR, ³¹P NMR and ¹³C NMR spectroscopic investigations. The linear effect of ligand ee and product ee further revealed that the active species is a monomeric Cu(I) complex bearing a single ligand.     

Self-supported chiral catalysts for heterogeneous asymmetric catalysis

A conceptually new strategy for chiral catalyst immobilization, self-supported catalysts, in heterogeneous asymmetric catalysis is highlighted in the present article. Various homochiral metal-organic polymers with diverse structures have been designed and readily prepared through coordination assembly of modular polytypic/polyfunctional ligands and metal ions without using any supports. These polymers have been successfully employed as chiral catalysts in a variety of heterogeneous asymmetric ractions, including hydrogenation, epoxidation, sulfoxidation, carbonyl-ene reactions, diethylzinc addition, and Michael addition. The self-supported heterogeneous chiral catalysts showed activity and enanioselectivity comparable or even superior to those obtained with their corresponding homogeneous counterparts, and could be readily recovered and reused several times without significant loss of activity or enantioslectivity.     

Highly enantioselective asymmetric reduction of aromatic ketimines promoted by chiral enantiomerically pure sulfoxides as organocatalysts

Optically pure hetero-organic organocatalysts, bearing a hydroxy moiety, a stereogenic sulfinyl group and a chiral amine moiety, have revealed high catalytic activity in the asymmetric reduction of various N-aryl ketimines leading to the corresponding chiral amines. Desired products were formed in high chemical yields (up to 95%) and with ee’s up to 97%. The influence of particular stereogenic centres on the stereochemical outcome of the reduction reaction is discussed.     

An Ion‐Pair Immobilization Strategy in Rhodium‐Catalyzed Asymmetric Transfer Hydrogenation of Aromatic Ketones

A chiral diamine‐based homogeneous cationic rhodium catalyst was developed and two heterogeneous cationic rhodium catalysts were obtained via the encapsulation of the homogeneous cationic rhodium catalyst within Me‐SBA‐15 and Me‐SBA‐16. All these catalysts presented excellent catalytic activities and high enantioselectivities in ultrasound‐promoted asymmetric transfer hydrogenation of aromatic ketones and represent a successful use of the ion‐pair immobilization strategy. More importantly, the encapsulation of the cationic rhodium functionality within Me‐SBA‐16 had an obvious high recyclability, in which the recycled catalyst could be reused nine times without significantly affecting its enantioselectivity, showing good potential in industrial application.     

Aqueous Asymmetric Mukaiyama Aldol Reaction Catalyzed by Chiral Gallium Lewis Acid with Trost‐Type Semi‐Crown Ligands

The combination of Ga(OTf)₃ with chiral semi‐crown ligands ( 1a – e ) generates highly effective chiral gallium Lewis acid catalysts for aqueous asymmetric aldol reactions of aromatic silyl enol ethers with aldehydes. A ligand‐acceleration effect was observed. Water is essential for obtaining high diastereoselectivity and enantioselectivity. The p‐phenyl substituent in aromatic silyl enol ether ( 2 h ) plays an important role and increases the enantioselectivity up to 95% ee. Although aliphatic silyl enol ethers provided low enantioselectivities and silylketene acetal is easily hydrolyzed in aqueous alcohol, the aldol reactions of silylketene thioacetal ( 12 ) with aldehydes in the presence of gallium‐Lewis acid catalysts give the β‐hydroxy thioester with reasonable yields and high diastereo‐ (up to 99 : 1) and enantioselectivities (up to 96% ee).     

Phosphoramidite Ligands Based on Simple 1,2‐Diols: Synthesis,Use in Copper‐Catalyzed Asymmetric Additions,and Achirotopic Stereogenic Phosphorus Centres

Phosphoramidite ligands are widely used in catalysis and normally constructed from large C₂‐symmetrical diols such as BINOL or TADDOL. We report here on new ligands based on a set of simple diols that had been previously overlooked. Ligands based on (S,S)‐trans‐cyclohexanediol and (R,R)‐(+)‐1,2‐diphenyl‐1,2‐ethanediol, in combination with both chiral and achiral amines, were tested in 3 different copper‐catalyzed asymmetric reactions and up to 89% ee was observed. A different ligand gave the best results in each reaction examined. Using meso‐cis‐cyclohexanediol and meso‐cis‐diphenyl‐1,2‐ethanediol with a chiral non‐racemic amine gave diastereomeric ligands bearing achirotopic stereogenic phosphorus atoms which were characterized with the assistance of X‐ray crystallography and variable temperature NMR studies. This work provides a new set of ligands that may be useful in some asymmetric reactions when phosphoramidites based on BINOL and TADDOL are ineffective. We also identify a novel stereochemical feature of phosphoramidites that may be useful in asymmetric catalysis and ligand design.

     

Catalytic Asymmetric Heterogeneous Aziridination of Styrene Using CuHY/bis(oxazoline): Comments on the Factors Controlling Enantioselectivity

The copper-catalyzed aziridination of styrene is described using both heterogeneous, copper-exchanged zeolite HY, and homogeneous, copper (II) triflate catalysts using both [N-(p-tolylsulfonyl)imino]phenyliodinane (PhI=NTs) and [N-(p-nosylsulfonyl)imino]phenyliodinane (PhI=NNs) as nitrene donors. The key differences observed for the two catalysts when modified by chiral bis(oxazoline) ligands are discussed in detail. In particular, the heterogeneously catalyzed asymmetric reaction can give much higher enantioselection than the comparable homogeneously catalyzed reaction. The structure of the bis(oxazoline) ligand is the critical factor, and bis(oxazoline) ligands that are ineffective with the homogeneous catalysts are highly effective for the Cu²⁺ cation constrained within the zeolite micropores. The consequences of this observation for the design of chiral ligands for asymmetric heterogeneous catalysis are discussed. The effect of the degree of styrene conversion on the enantioselectivity is described in detail using PhI=NNs as a nitrene donor. The reaction shows a significant enhancement in ee with conversion at 25°C, and the possible origin of this effect is discussed.     

Identification of Suitable Ligands for a Transition Metal‐Catalyzed Reaction: Screening of a Modular Ligand Library in the Enantioselective Hydroboration of Styrene

Based on a general modular synthetic scheme, a variety of chiral bidentate P/P‐, P/S‐, P/N‐, and P/Se‐ligands is accessible in an efficient divergent manner starting from phenol or naphthol derived backbone systems. A library of 20 selected ligands was tested in the Rh‐catalyzed asymmetric hydroboration of styrene to give 1‐phenylethanol in up to 91% ee after oxidative work‐up. It was demonstrated that small variations of the ligand structures lead to pronounced, unpredictable differences in the performance of the in situ generated rhodium complexes. The modular approach should be applicable for the identification and optimization of suitable ligands for other transition metal‐catalyzed transformations with comparably low effort.     

Effect of pore size on the performance of mesoporous material supported chiral Mn(III) salen complex for the epoxidation of unfunctionalized olefins

A series of mesoporous MCM-41 and MCM-48 materials with different pore sizes were synthesized and used as supports to immobilize chiral Mn(III) salen complex. The heterogeneous catalysts were characterized by XRD, FT-IR, DR UV–vis, and N₂ sorption, and the results indicated the successful immobilization of chiral Mn(III) salen complex. The confinement effect of pore size on the catalytic performance of the heterogeneous catalysts was studied for the asymmetric epoxidation of unfunctionalized olefins with m-chloroperoxybenzoic acid as an oxidant. It was found that the conversions and enantiomeric excess (ee) values were closely correlated with the pore sizes of parent supports. The catalysts immobilized on the large-pore mesoporous supports exhibited higher conversions, and for the catalysts immobilized on MCM-41 materials, the ee values improved with increasing pore size. However, for the MCM-48 material-supported catalysts, the compatible pore size of the support with the substrate was beneficial for obtaining higher enantioselectivity in olefin epoxidation.     

Highly Enantioselective Catalytic Alkynylation of Ketones – A Convenient Approach to Optically Active Propargylic Alcohols

The development of highly enantioselective catalysts involving Cu(OTf)₂ and chiral camphorsulfonamides for the alkynylation of ketone is described. The influences of Lewis acids, reaction conditions and chiral ligands on the outcome of the reaction are discussed. The best enantioselectivity (up to 97 % ee) was obtained in the alkynylation of 2′‐chloroacetophenone. The scope of the reaction is also examined.