Methylethers of cinchona alkaloids in Pt-catalyzed hydrogenation of ethyl pyruvate and ketopantolactone: Effect of stereochemical factors on the enantioselectivity

We studied the enantioselective hydrogenation of ethyl pyruvate (EP) and ketopantolactone (KPL) under mild experimental conditions (hydrogen pressure 1 bar, room temperature) on Pt-alumina catalyst modified with O-methyl derivatives of parent cinchona alkaloids (MeOCD, MeOCN, MeOQN, MeOQD) in two solvents with highly different polarities (AcOH, toluene). The best ee's were achieved (91–96%) using MeOCD and MeOQN modifiers in AcOH. Hydrogenation, especially in the presence of the chiral modifiers MeOCN and MeOQD in toluene proceeded with exceptionally low enantioselectivities (35–46% for EP and 2–4% for KPL) as compared to the already well-known Pt-MeOCD catalyst (ee%: 71–74 for EP, 38–48 for KPL). Results of the hydrogenations of the modifiers and studies on the hydrogenation of substrates using modifier mixtures suggested that the low ee are attributable to stereochemical reasons. Namely, it seems justified to suppose that the low ee observed is dependent on the various tilted adsorbed structures of the substrate and modifier 1:1 intermediate complex responsible for enantiodifferentiation.     

Effect of modifier structure in the enantioselective hydrogenation of 1-phenyl-1,2-propanedione

Three different modifiers, (-)-cinchonidine, 10,11-dihydrocinchonidine and (+)-cinchonine were investigated in the enantioselective hydrogenation of an unsymmetrical dione, 1-phenyl-1,2-propanedione, over a commercial Pt/Al₂O₃ catalyst. The catalytic activity, as well as the regio- and enantioselectivity in the hydroxyketones and diols formed were compared.     

Catalyst electronic polarizability and enantiomeric excess in asymmetric hydrogenation

In the classical rhodium-diphosphine complexes-catalyzed asymmetric hydrogenation of enamide substrates, examination on the role of catalyst electronic polarizability in the origin of enantioselectivity reveals its linear free energy relationship with the product enantiomeric ratio that is much more pronounced than analogous correlation with steric effect in the same systems. From a conceptually novel scenario, this work suggests that the often-overlooked chiral catalyst local polarizability property may function as a controlling force in enantioselection thus has important implication in rational catalyst design.     

Enantioselective hydrogenation of isophorone over Pd catalysts in the presence of(−)-dihydroapovincaminic acid ethyl ester: The effect of reduction method of Pd blacks on the enantiomeric excess

The enantioselective heterogeneous catalytic hydrogenation of isophorone in the presence of apovincaminic acid ethyl ester was investigated. Various Pd black catalysts differing in their preparation method were studied. The catalysts were characterized by different methods such as physical adsorption and chemisorption, SEM and XPS. An explanation was created for the different enantioselectivity of the catalysts being precipitated by different reducing agents.     

含有手性BINAP基团的共轭微孔聚合材料应用于喹啉高效不对称氢化反应

喹啉不对称氢化反应是不对称氢化研究的重点之一。其氢化产物四氢喹啉不仅是重要的有机合成中间体,同时也是自然界中生物碱的结构单元和生物活性化合物。周永贵研究组首次报道了手性(R)-MeO-Biphep/Ir体系成功用于喹啉的不对称催化,取得了非常好的反应结果。随后他们对喹啉底物进行了拓展,包括拥有特殊取代基的喹啉衍生物,均取得了良好的反应结果。后来多个研究组对该反应进行了深入研究并开发出了多个不同手性膦配体的Ir催化体系。虽然喹啉不对称氢化反应取得了很大的发展,但是该均相反应体系只能在高的反应催化剂用量下才能实现好的结果。进一步研究发现手性配体与金属Ir络合后形成反应活性物种,但后者可发生二聚或三聚,生成的产物是不具有催化活性的,从而导致了反应体系需要高的催化剂的用量。为此人们做了大量研究。范青华研究组通过对BINAP基团上嫁接大空间位阻的枝状分子合成了一系列新的手性BINAP配体,在与Ir络合后,表现出远高于均相催化剂的反应活性,且可循环利用。在该体系中,大位阻的枝状分子起到了阻隔活性物种二聚、三聚的作用,因而提高了反应活性。后来周永贵研究组也尝试通过改变有机配体的方法来实现高的反应活性。他们选择改变手性双膦配体上P原子所连接有机配体的空间位阻来实现对活性物种多聚的控制。实验同样取得了很好的反应效果。对于均相反应体系,我们只能通过这种改变有机配体空间位阻的方式来降低活性物种多聚的可能性,那么如何彻底阻止这种多聚呢？非均相体系给我们提供了很好的研究思路,但如何将非均相体系引入到喹啉不对称氢化反应体系当中成为了难点。
　　共轭微孔聚合物(CMPs)的发展使得手性催化体系很容易从均相转变到非均相。这种材料具有较高的比表面积和固定的开放孔道结构,可应用于非均相催化中。且制备相对容易。我们可以将手性双膦配体作为材料制备配体嫁接到CMPs材料当中。在这种材料当中,手性配体会以有序、空间分离的方式分布,在与Ir配合后应用于喹啉不对称氢化反应中,从而从根本上避免了活性物种多聚的可能因此反应活性提高。我们曾首次成功合成了一系列含有手性(R)-Binap基团的共轭微孔聚合材料-BINAP-CMPs,并将其用于β-酮酸酯的不对称氢化反应当中,取得了很好的催化效果。手性BINAP基团均匀、有序地分散于该材料中。我们尝试利用BINAP-CMPs固有的空间隔离效应,将其应用于喹啉的不对称氢化反应中,结果表明,在相同条件下,非均相BINAP-CMPs/Ir催化体系的TOF值是340 h–1,是均相BINAP/Ir体系(100 h–1)3倍,反应的对映体选择性与均相相当;另外该催化体系多循环利用次后仍可以保持高的反应活性。我们还发现材料结构性质对反应结果的影响很大,材料的比表面积和孔容更大反应结果更好。     

Host–guest interactions and their role in enantioselective hydrogenation of α-keto esters: An analysis of model systems

The interaction between cinchonidine and methyl pyruvate has been proposed as the key step leading to enantiodifferentiation in the enantioselective hydrogenation of α-ketoesters. In the present work, we employ ab initio MP2/6-31G(d) and MP2/6-31G(d,p) methods to carry out an analysis of the most relevant kind of interactions operating in representative model systems. These interactions are discussed in terms of orbital superposition and dipolar interaction. When approaching H₂CO to NH₃ at distances lower than 3.4 Å, orbital superposition is the predominant interaction, while at distances above 3.4 Å, both orbital superposition and dipolar interactions may contribute to stabilization, with a small prevalence of dipolar interactions. The stabilization energy at large distances (above 4.5 Å) is very small (about 0.5 kcal mol⁻¹), probably not enough to be responsible for the enantiodifferentiation process. Semiempirical calculations on the parent systems were also unable to reveal any special interaction which could be attributed to the enantiodifferentiation process.     

Role of the C3-substituted derivatives of cinchonidine in the enantioselective hydrogenation of ethyl pyruvate on Pt-alumina catalyst in AcOH

Summary The enantioselective hydrogenation of ethyl pyruvate (EtPy) was studied on Pt-alumina catalysts modified by C3-substituted cinchonidines (NC, A, B, C1, C2in Fig. 1) and for comparison by DHCDand MeO-DHCDin AcOH. The effect of the C3-substituent on the reaction rate and the enantioselectivity were examined. Using the Engelhard 4759 catalyst under mild experimental conditions (room temperature, hydrogen pressure 1 bar) such as DHCDthe (R)-ethyl lactate formed in excess (e.e.max: 79-91%)</o:p>     

Determination of enantiomeric excess and concentration of chiral compounds using a 1,8-diheteroarylnaphthalene-derived fluorosensor

Enantioselective fluorosensing using a rigid C₂-symmetric 1,8-diacridylnaphthalene N,N′-dioxide sensor allows accurate determination of both the enantiomeric composition and concentration of several analytes capable of chiral hydrogen bonding.     

Complexation and hydrogenation of methionine-containing N-acetyle-dehydrodipeptides

The hydrogenation of the Fe^II complex ofN-Ac-Phe-(S)- or -(R)-Met over a Pd/C catalyst affords mainlyN-Ac-(R)-Phe-(S)-Met orN-Ac-(S)-Phe-(R)-Met, correspondingly. In the reaction of mixed dipeptide complexes with Ca^II and Fe^II the predominance of one of the diastereomers increases from 26 % (for complexes with Fe ions) to 38 %.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 545–546, March, 1994.The work was financially supported by the Russian Foundation for Basic Research (project No. 93-03-4646).     

Highly enantioselective hydrogenation of exocyclic double bond of N-tosyloxazolidinones catalyzed by a neutral rhodium complex and its synthetic applications

A highly enantioselective synthesis of optically active N-tosyl-4-alkyl-1,3-oxazolidin-2-ones based on the asymmetric hydrogenation of the trisubstituted exocyclic double bond of N-tosyl-4-alkylidene-1,3-oxazolidin-2-ones under the catalysis of neutral [Rh(COD)Cl]₂ (COD=1,5-cyclooctadiene) and (S)-(+)-DTBM-SEGPHOS was developed. The utility of this highly enantioselective reaction was exemplified by the synthesis of optically active amino acids, amino alcohols, and piperidine derivatives.     

The asymmetric hydrogenation of 2-phenethylacrylic acid as the key step for the enantioselective synthesis of Citralis Nitrile

A catalytic approach to the enantioselective synthesis of Citralis Nitrile^® (3-methyl-5-phenyl-pentanenitrile, a citrus-type odorant) is described. The key step is the transition-metal catalyzed asymmetric hydrogenation of 2-phenethylacrylic acid. Among the different catalysts tested, the most efficient appears to be the one formed by combining in situ [Ru(benzene)Cl₂]₂ with the atropisomeric diphosphine MeOBIPHEP and triethylamine, which allows us to obtain enantiomeric excesses up to 98% under mild conditions. Very good results (ees >80%) have also been obtained using iridium cationic complexes in combination with a phosphinooxazoline ligand.     

Effect of the substituent position on the enantioselective hydrogenation of methoxy-substituted 2,3-diphenylpropenoic acids over palladium catalyst

The enantioselective hydrogenation of mono and dimethoxy-substituted 2,3-diphenylpropenoic acids has been studied over cinchonidine modified supported Pd catalyst. The hydrogenation of the six monosubstituted methoxy derivatives of (E)-2,3-diphenylpropenoic acid showed that the position of the substituent has a decisive influence on the initial reaction rate and the enantioselectivity. High enantioselectivities, 86–90%, were obtained in the hydrogenation of mono-substituted derivatives with a favourable substituent position. The results were rationalized in terms of either the electronic or the steric effects of the methoxy substituent determined by its position. These suggestions were also applicable in interpreting the results obtained in the hydrogenation of substituted (Z)-2,3-diphenylpropenoic acids and selected dimethoxy (E)-2,3-diphenylpropenoic acids. The combined steric and electronic effects of the substituents on the α- and β-phenyl rings ensured the highest enantioselectivities, up to 92% ee, in the hydrogenation of (E)-2-(2-methoxyphenyl)-3-(4-methoxyphenyl)propenoic acid.     

Highly enantioselective Rh-catalyzed hydrogenations with heterocombinations of pentafluorobenzyl- and methoxybenzyl-derived binaphthyl phosphites

The Rh-catalyzed hydrogenations of dimethyl itaconate and methyl acetamido acrylate using selected heterocombinations of pentafluorobenzyl- and methoxybenzyl-derived binaphthyl phosphites proved to be highly enantioselective (ee 93-99%). In these selected cases the Rh-heterocomplexes, which were formed in a statistical amount (ca. 50% by ³¹P NMR), turned out to be more active and selective than the two homocomplexes.     

Asymmetric catalysis. Part 128: Diastereomeric rhodium(I) complexes in the enantioselective hydrogenation of ketopantolactone

In the hydrogenation of ketopantolactone, new rhodium complexes bearing (R,R)-diop and various bidentate chiral N,N′ co-ligands with (R)- or (S)-configuration were used. On the one hand, the N,N′ co-ligands consist of pyrroleimines, which derive from (R)- and (S)-1-phenylethylamine, (R)- and (S)-1-cyclohexylethylamine (and benzylamine), and on the other hand of pyrroleoxazolines and pyridineimines. Stereoselectivities of 31–33% ee for (R)-pantolactone were achieved using related compounds (RR-R) and (RR-S), respectively, with no double stereoselectivity being observed. It is assumed that during catalysis the pyrroleimines bind in a monodentate way at the sixth coordination site of the rhodium atom by the pyrrole nitrogen with the imine nitrogen carrying the different chiral substituents far away from the rhodium atom. Monodentate deltacyclane phosphanes, chloro ligands or solvent molecules, bound at the sixth coordination site of the catalyst, led to widely differing enantioselectivities in the ketopantolactone hydrogenation.     

Application of [BoPhoz Rh] catalysts in the asymmetric hydrogenation of a pyridyl benzothiophene alkene

The asymmetric hydrogenation of a pyridyl benzothiophene alkene has been successfully accomplished using [BoPhoz Rh] catalysts. By tailoring the steric properties of the BoPhoz ligand, the ee of the product could be increased from just 12% to 90%. This research further expands the substrate scope of the conventional class of functionalized alkenes amenable to catalytic asymmetric hydrogenation.     

Macrocyclic antibiotics as chiral selectors in the design of enantioselective, potentiometric membrane electrodes for the determination of S-flurbiprofen

Construction of three novel enantioselective, potentiometric membrane electrodes based on carbon paste impregnated with different macrocyclic antibiotics vancomycin and teicoplanin as chiral selectors are described. The solutions for the construction of electrodes were prepared in phosphate buffer pH 4 for the vancomycin-based electrode (VCM), pH 6 and pH 6/40% acetonitrile solutions for teicoplanin-based electrodes, TCP I and II, respectively. The proposed electrodes were applied in the assay of S-flurbiprofen raw material and its pharmaceutical formulation by use of direct potentiometry, VCM electrode exhibiting the best enantioselectivity. The surfaces of the electrodes are easily renewable by simply polishing on an alumina paper.     

Iridium-catalyzed asymmetric hydrogenation of imines in supercritical carbon dioxide using phosphite-type ligands

A series of chiral phosphite-type ligands has been evaluated in the iridium-catalyzed asymmetric hydrogenation of acyclic arylimines in supercritical CO₂. High reactivities (100% conversion in 50-120 min) and enantioselectivities (up to 95%) were obtained.     

Unusual deactivation in the asymmetric hydrogenation of itaconic acid

The formation of unusual Rh(III) substrate complexes from [Rh(DIPAMP)(MeOH)₂]BF₄ and itaconic acid has been detected which leads to the deactivation of the catalyst. The influence of different parameters on the formation of such complexes, namely substrate concentration, reaction time, temperature, acidic and basic additives, was investigated with different NMR methods. Two different Rh(III) substrate complexes are formed whose ratio is strongly dependent on substrate concentration and reaction time. The pH value of the solution shows a strong influence on the chemical shifts of the ³¹P NMR signals of such complexes. A catalyst-mediated esterification of itaconic acid in methanol was detected. Extended investigations provide detailed ¹H, ¹³C and ³¹P NMR data for the Rh(III) complexes and information about their stability in solution.     

Effect of pretreatment of the catalyst and catalyst-modifier system in the enantioselective hydrogenation of isophorone

The effects of the preliminary hydrogenation, the variation of the addition sequence of the components and that of the sonochemical treatment were investigated in enantioselective hydrogenation of isophorone over Pd black catalyst in the presence of chiral modifiers. This revised version was published online in June 2006 with corrections to the Cover Date.