Bis(3,5‐dimethylphenyl)‐(S)‐pyrrolidin‐2‐ylmethanol: an Improved Organocatalyst for the Asymmetric Epoxidation of α,β‐Enones

The asymmetric epoxidation of α,β‐enones by the readily available bis(3,5‐dimethylphenyl)‐(S)‐pyrrolidin‐2‐ylmethanol and tert‐butyl hydroperoxide (TBHP) is described. Stereoelectronic substitution on the aryl moiety of diaryl‐2‐pyrrolidinemethanols was found to significantly affect the efficiency with respect to the previously reported (S)‐diphenyl‐2‐pyrrolidinemethanol. Improved reactivity and enantioselectivity were achieved with bis(3,5‐dimethylphenyl)‐(S)‐pyrrolidin‐2‐ylmethanol at reduced catalyst loading (20 mol %) with ees up to 94% for chalcone epoxides under mild reaction conditions, whereas (S)‐diphenyl‐2‐pyrrolidinemethanol afforded a maximum ee of 80%. Interestingly, the methodology is applicable to the epoxidation of more challenging aliphatic or enolizable enones with good control of the asymmetric induction (up to 87% ee).     

Asymmetric Michael Addition of 5 H‐Oxazol‐4‐ones to Vinyl Sulfones: Stereoselective Synthesis of Monofluorinated Analogs of 2‐Tertiary Hydroxyl‐3‐Methyl‐Substituted Carboxylic Acidl Derivatives

An asymmetric Michael addition of 5H‐oxazol‐4‐ones to vinyl sulfones has been developed. In the presence of 10 mol % of quinine‐based benzyl‐substituted thiourea as catalyst at 0 °C, the products could be obtained with excellent enantio‐ and diastereoselectivity (up to>99 % ee and>20:1 dr). 1.0 mol % of catalyst also produced the corresponding adducts with similar stereoselective results when the temperature was increased to 25 °C. The obtained adducts have been demonstrated as significant synthetic fragments to conveniently access the monofluorinated analogs of biologically important 2‐tertiary hydroxyl‐3‐methyl‐substituted carboxylic acid derivatives.

     

Atom Transfer Radical Polymerisation with an Immobilised [RuCl2(p-cymene)]2 Dimer

[RuCl₂(p-cymene)]₂ has been immobilized on silica and mesoporous MCM-41 and used as a catalyst for the atom transfer radical polymerisation (ATRP) of styrene, (methyl)methacrylate and acrylonitrile. The heterogeneous catalyst has a comparable activity as the homogeneous analogues and showed no significant loss of catalytic activity when reused.     

An Improved Catalyst for Iodine(I/III)‐Catalysed Intermolecular C?H Amination

1,2‐Diiodobenzene is presented as an efficient catalyst precursor for the intermolecular amination of arenes under homogeneous conditions. N‐Troc‐ and N‐phthalimido‐substituted methoxyamines serve as suitable nitrogen sources providing the corresponding aniline derivatives in up to 99% yield and with up to 66:1 regioselectivity. Key for this successful C N coupling protocol is the strained μ‐oxo‐bridged conformation of the bisiodine(III) catalyst, which induces unparalleled high reactivity.

     

L‐Prolinethioamides – Efficient Organocatalysts for the Direct Asymmetric Aldol Reaction

A series of novel L ‐proline derived thioamides has been synthesised. They have been evaluated as organocatalysts in the direct asymmetric aldol reaction for the first time. Thioamides exhibit catalytic ability higher than proline itself and the model aldol reaction of 4‐cyanobenzaldehyde with acetone proceeds well in the presence of 5 mol % of catalyst (ee up to 100%). Other aromatic aldehydes gave aldol products with high ees and moderate yields. Small changes in the catalyst's structure [e.g., N‐Bn versus N‐CH(CH₃)Ph] as well as the addition of an acid have a profound effect on their activity. The unexpected formation of the catalyst‐derived cyclic adducts was observed and their reactivity was established giving valuable insight into the course of the reaction.     

Trichloroisocyanuric Acid: A Convenient Oxidation Reagent for Phase‐Transfer Catalytic Epoxidation of Enones under Non‐Aqueous Conditions

Trichloroisocyanuric acid (TCCA) is a cheap, safe and readily available alternative to the commonly used hydrogen peroxide and hypochlorite for the phase‐transfer catalytic epoxidation of α,β‐enones under non‐aqueous conditions. A variety of chalcone derivatives give the corresponding epoxides with quantitative conversion and satisfactory yields in just a few hours under mild conditions. An asymmetric variant of the epoxidation can be carried out in the presence of chiral N‐anthracenylmethylcinchonidine bromide catalyst giving 73–93% ees and 76–94% yields.     

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.     

Enantioselective Cyanosilylation of Ketones with Amino Acid/BINAP/Ruthenium(II)‐Lithium Phenoxide Catalyst Systems

Enantioselective reactions of simple ketones, α,α‐ and β,β‐dialkoxy ketones, and α‐alkoxy ketones with trimethylsilyl cyanide catalyzed by the bimetallic systems of amino acid/BINAP/ruthenium(II) complexes and lithium phenoxide have been studied [BINAP=2,2′‐bis(diphenylphosphino)‐1,1′‐binaphthyl]. The Ru(PhGly)₂(BINAP)‐lithium phenoxide system showed high enantioselectivity for the reaction of acetophenone derivatives to afford the cyanated products in up to 90% ee [PhGly=phenylglycinate]. For the cyanosilylation of dialkoxy ketones and α‐alkoxy ketones, the Ru(t‐Leu)₂(BINAP)‐lithium phenoxide system exhibited the best catalyst performance to produce the cyanohydrin derivatives in up to 99% ee and 98% ee, respectively [t‐Leu=tert‐leucinate]. The excellent catalytic activity resulted in complete conversion in the reaction with a substrate‐to‐catalyst molar ratio (S/C) of 10,000 in the best cases.     

New investigation of 1‐substituted imidazole derivatives as thermal latent catalysts for epoxy‐phenolic resins

Novel 1‐substituted imidazole derivatives ( 4 – 10 ) were synthesized by imidazole and the corresponding substituted reagents (chloromethylpivalate, diphenylphosphinicchloride, di‐tert‐butyldicarbonate, 1,1′‐oxalylchloride, pyrazine, phneylisocyanat, and p‐toluensulfonylchloride). Polymerization of diglycidyl ether of bisphenol A (DGEBA) with 1‐substituted imidazole derivatives, two commercial available catalysts (imidazole and 1‐cyanoethyl‐2‐ethyl‐4‐methylimidazole) and N‐benzylpyrazinium hexafluoroantimonate were investigated as model reactions of epoxy resin systems with respect to the thermal latency and storage stability of the catalysts. The catalytic activity of 1‐substituted imidazole derivatives 4 – 10 depended on the steric and withdrawing electronic effect of the substitution groups. To characterize the cure activation energy and the viscosity‐storage time, the order of thermally latent activity is 1‐tosylimidazole ( 6 ) > 1,1′‐oxalyldiimidazole ( 8 ) > N‐benzylpyrazinium hexafluoroantimonate (BPH, 3 ) > 1‐tritylimidazole ( 9 ) > N‐phenyl‐imidazole‐1‐carboxamide ( 5 ) > 3‐(diphenylphosphinoyl)imidazole ( 7 ) > tert‐butyl‐1H‐imidazole‐1‐carboxylate ( 4 ) > 1‐cyanoethyl‐2‐ethyl‐4‐methylimidazole (2E4MZ, 2 ) > 1‐[(pivalyloxy)methyl]imidazol ( 10 ) > imidazole ( 1 ). In comparison with commercially available catalysts imidazole ( 1 ) and 1‐cyanoethyl‐2‐ethyl‐4‐methylimidazole ( 2 ) and a cationic latent catalyst N‐benzylpyrazinium hexafluoroantimonate (BPH, 3 ) as the standard compounds, in addition to 1‐[(pivalyloxy)methyl]imidazole ( 10 ), the 1‐substituted imidazole derivatives ( 4 – 9 ) revealed better thermal latency. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

Synthesis of an Enantiocomplementary Catalyst of β‐Isocupreidine (β‐ICD) from Quinine

Compound 20 , a pseudoenantiomer of β‐isocupreidine (β‐ICD), was synthesized from quinine employing a Barton reaction of nitrosyl ester 13 and acid‐catalyzed cyclization of carbinol 18 as key steps. The Baylis–Hillman reaction of benzaldehyde, p‐nitrobenzaldehyde, and hydrocinnamaldehyde with 1,1,1,3,3,3‐hexafluoroisopropyl acrylate (HFIPA) using 20 as a chiral amine catalyst was found to give the corresponding S‐enriched adducts in high optical purity (>91% ee) in contrast to the β‐ICD‐catalyzed reaction which affords R‐enriched adducts. This result suggests that compound 20 can serve as an enantiocomplementary catalyst of β‐ICD in the asymmetric Baylis–Hillman reaction of aldehydes with HFIPA.     

Reusable Chiral Dicationic Chromium(III) Salen Catalysts for Aminolytic Kinetic Resolution of trans‐Epoxides

A series of new recyclable chiral dicationic chromium(III) salen complexes 1 – 10 bearing different substituents, viz., hydrogen, methyl, tert‐butyl, triphenylphosphinomethyl, triethylaminomethyl, methylimidazolium, methylpyridinium, methyl‐N,N‐dimethylpyridinium at the 3,3′‐ and 5,5′‐ positions of the salen unit with (1S,2S)‐(+)‐1,2‐diaminocyclohexane, (1S,2S)‐(−)‐1,2‐diphenyl‐1,2‐diaminoethane, and (S)‐(−)‐1,1′‐binaphthyl‐2,2′‐diamine collars have been synthesized and characterized by various physico‐chemical methods. These complexes were used as catalysts for the highly enantioselective aminolytic kinetic resolution of racemic trans‐epoxides with different anilines as nucleophiles at room temperature. With the use of catalyst 3 , anti‐β‐amino alcohols were obtained in excellent yields (>99% with respect to the nucleophile) and enantioselectivities (ee>99%) with the concomitant recovery of corresponding epoxides in high optical purity (ee up to >99%) and quantitative yields in 12 h. The catalyst 3 is recyclable in the aminolytic kinetic resolution process and worked well up to six cycles with retention of enantioselectivity.     

Highly Enantioselective Copper‐Phosphoramidite‐Catalyzed Conjugate Addition of Dialkylzinc Reagents to Acyclic α,β‐Unsaturated Imides

A new and practical way to introduce an alkyl fragment in the β‐position of aliphatic carboxylic acid derivatives with high enantioselectivities by the use of a commercially available chiral ligand is reported. N‐Acylpyrrolidinones, as simple derivatives of an α,β‐unsaturated carboxylic acid, were found to be the substrates of choice featuring good reactivity and high enantioselectivities (up to >99% ee).     

Selectivity engineering in the O‐ versus C‐alkylation of p‐cresol with cyclohexene over sulfated zirconia

Solid acids are more widely used as heterogeneous catalysts, because they are eco‐friendly. This paper reports the results for the Friedel‐Crafts alkylation of p‐cresol with cyclohexene using solid acids sulfated zirconia, 20% w/w dodecatungstophosphoric acid (DTP) supported on K10 clay and ZnCl₂/K10 (Clayzic). This reaction gave substantial amount of 1‐cyclohexyloxy‐4‐methyl benzene (O‐alkylated product) and 4‐cyclo‐hexyl‐4‐methyl phenol (C‐alkylated product). Both products are of commercial importance as perfume and insecticide respectively. Sulfated zirconia catalyst was shown to be better than others studied in terms of activity and selectivity to the O‐alkylated product. The kinetics were studied with sulfated zirconia as catalyst where the rate determining step was the surface reaction between chemisorbed cyclohexene and p‐cresol from the liquid phase within pores according to the Eley‐Rideal mechanism. The production of O‐alkylated p‐cresol is favoured at lower temperatures and C‐alkylated product at higher temperatures. The best operating temperature is 353 K. The activation energies for O‐ and C‐alkylation are 72.68 and 118.28 kj/mol, respectively.     

Immobilized Co/Rh Heterobimetallic Nanoparticle‐Catalyzed Pauson–Khand‐Type Reaction

Co/Rh heterobimetallic nanoparticles were prepared from cobalt‐rhodium carbonyl clusters [Co₂Rh₂(CO)₁₂ and Co₃Rh(CO)₁₂] and immobilized on charcoal. HR‐TEM revealed that the size of the heterobimetallic nanoparticles was ca. 2 nm and ICP‐AES analysis showed a 2 : 2 and a 3 : 1 cobalt‐rhodium stoichiometry (Co₂Rh₂ and Co₃Rh₁) in the heterobimetallic nanoparticles. The Co/Rh heterobimetallic nanoparticles immobilized on charcoal were used as a catalyst in the Pauson–Khand‐type reaction under 1 atm of CO. The catalytic reactivity was highly dependent upon the ratio of Co : Rh with the highest reactivity being observed when the ratio was 2 : 2 (Co₂Rh₂). The Co₂Rh₂ immobilized catalyst is quite an effective catalyst for intra‐ and intermolecular Pauson–Khand‐type reactions. When the immobilized Co₂Rh₂ catalyst was used as a catalyst in the Pauson–Khand‐type reaction in the presence of an aldehyde instead of carbon monoxide, the catalytic system was highly efficient. When the reaction was carried out in the presence of chiral diphosphines, ee values up to 87% were observed. The catalytic system can be reused at least five times in the presence of chiral diphosphines without loss of catalytic activity and enantioselectivity. The addition of Hg(0), a known heterogeneous catalyst poison, completely inhibits further catalysis. Thus, an environmentally friendly and sustainable process was developed.     

Enzymes in Organic Chemistry, 11:[1] Hydrolase‐Catalyzed Resolution of α‐ and β‐Hydroxyphosphonates and Synthesis of Chiral,Non‐Racemic β‐Aminophosphonic Acids

The enantioselective acylation of racemic diisopropyl α‐ and β‐hydroxyphosphonates by hydrolases in t‐butyl methyl ether with isopropenyl acetate as acyl donor is limited by the narrow substrate specificity of the enzymes. High enantiomeric excesses (up to 99%) were obtained for the acetates of (S)‐diisopropyl 1‐hydroxy‐(2‐thienyl)methyl‐, 1‐hydroxyethyl‐ and 1‐hydroxyhexylphosphonate and (R)‐diisopropyl 2‐hydroxypropylphosphonate. The hydrolysis of a variety of β‐chloroacetoxyphosphonates by the lipase from Candida cylindracea and protease subtilisin in a biphasic system gives (S)‐β‐hydroxyphosphonates (ee 51–92%) enantioselectively. (S)‐2‐Phenyl‐2‐hydroxyethyl‐ and (S)‐3‐methyl‐2‐hydroxybutylphosphonates (ee 96% and 99%, respectively) were transformed into (R)‐2‐aminophosphonic acids of the same ee.     

Efficient Heterogeneous Asymmetric Catalysis of the Mukaiyama Aldol Reaction by Silica‐ and Ionic Liquid‐Supported Lewis Acid Copper(II) Complexes of Bis(oxazolines)

Lewis acid complexes based on copper(II) and an imidazolium‐tagged bis(oxazoline) have been used to catalyse the asymmetric Mukaiyama aldol reaction between methyl pyruvate and 1‐methoxy‐1‐trimethylsilyloxypropene under homogeneous and heterogeneous conditions. Although the ees obtained in ionic liquid were similar to those found in dichloromethane, there was a significant rate enhancement in the ionic liquid with reactions typically reaching completion within 2 min compared with only 55 % conversion after 60 min in dichloromethane. However, this rate enhancement was offset by lower chemoselectivity in ionic liquids due to the formation of 3‐hydroxy‐1,3‐diphenylbutan‐1‐one as a by‐product. Supporting the catalyst on silica or an imidazolium‐modified silica using the ionic liquid or in an ionic liquid‐diethyl ether system completely suppressed the formation of this by‐product without reducing the enantioselectivity. Although the heterogeneous systems were characterised by a drop in catalytic activity the system could be recycled up to five times without any loss in conversion or 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.     

Catalytic Asymmetric Total Synthesis of the Muscarinic Receptor Antagonist (R)‐Tolterodine

A convenient and high yielding method for the preparation of (R)‐tolterodine, utilizing a catalytic asymmetric Me‐CBS reduction was developed. Highly enantioenriched ( R)‐6‐methyl‐4‐phenyl‐3,4‐dihydrochromen‐2‐one (94% ee) was recrystallized to yield practically enantiopure material (ee >99%) and converted to (R)‐tolterodine in a four‐step procedure. The configuration of the crucial stereocenter was preserved during the synthesis and the obtained product was identified by chiral HPLC to be the (R)‐tolterodine enantiomer.     

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.     

A General and Practical Palladium‐Catalyzed Direct α‐Arylation of Amides with Aryl Halides

An efficient system for the direct catalytic intermolecular α‐arylation of acetamide derivatives with aryl bromides and chlorides is presented. The palladium catalyst is supported by Kwong’s indole‐based phosphine ligand and provides monoarylated amides in up to 95% yield. Excellent chemoselectivities (>10:1) in the mono‐ and diarylation with aryl bromides were achieved by careful selection of bases, solvents, and stoichiometry. Under the coupling conditions, the weakly acidic α‐protons of amides (pK_a up to 35) were reversibly depotonated by lithium tert‐butoxide (LiO‐t‐Bu), sodium tert‐butoxide (NaO‐t‐Bu) or sodium bis(trimethylsilyl)amide [NaN(SiMe₃)₂].