Sense Of Enantioselectivity Research Articles

Controlling the Sense of Enantioselection on Surfaces by Conformational Changes of Adsorbed Modifiers

Controlling the Sense of Enantioselection on Surfaces by Conformational Changes of Adsorbed Modifiers

Directed Catalytic Asymmetric Olefin Metathesis. Selectivity Control by Enoate and Ynoate Groups in Ru-Catalyzed Asymmetric Ring-Opening/Cross-Metathesis

A new concept in catalytic asymmetric olefin metathesis is introduced: a nonreacting enoate or ynoate group can be used to alter and significantly enhance the enantioselectivity. Catalytic asymmetric ring-opening/cross-metathesis (AROM/CM) processes proceed in ≤30% ee with non-styrenyl cross partners. However, with olefin partners bearing an enoate or ynoate group (1,6-diene or 1,6-enyne), catalytic AROM/CM affords the desired products in up to 98% ee, with the opposite sense of enantioselectivity versus reactions with styrene or aliphatic cross partners. This new method, for the first time, extends the scope of effective metal-catalyzed AROM/CM to reactions of non-styrenyl alkenes and cyclopropenes, a diverse and readily available set of substrates, and that of Ru-catalyzed asymmetric olefin metathesis to include processes that bear all-carbon quaternary stereogenic centers.

Inversion of enantioselectivity for the hydrogenation of ethyl pyruvate in the gas-phase over Pt/SiO 2 modified with derivatives of hydroquinidine

Ethyl pyruvate was hydrogenated as a gas-phase reactant over 2.5% Pt/SiO 2 premodified with hydroquinidine 4-chlorobenzoate at two concentrations (0.85 and 8.5 mM g −1 cat). The sense of enantioselectivity changed as a function of the modifier concentration. At low modifier concentrations, the ( S)-lactate is the preferred product, and at higher concentrations, ( R)-lactate is favoured. The lower concentration yielded an enantiomeric excess (ee) of 15% ( S)-ethyl lactate in contrast to 17% ( R)-lactate for the higher concentration. A range of hydroquinidine and hydroquinine derivatives were evaluated at these concentrations; the results suggest that the carbonyl group of the ester linkage at the C(9) position was required to promote the observed inversion of enantioselectivity. In a subsequent set of experiments, Bi 3+ was adsorbed onto the Pt/SiO 2 catalyst before the premodification step; these ions are considered to adsorb preferentially on high-energy surface sites (e.g., corner sites or step edges). Increasing Bi 3+ concentration decreased the degree of inversion until the effect was lost. On the basis of high-resolution electron microscopy (HREM) comparisons of these Pt/SiO 2 and Bi–Pt/SiO 2 catalysts, the inversion effect is discussed in terms of the interaction of the substrate and modifier with the catalyst surface.

Cyclodextrin Derivatives as Chiral Supramolecular Receptors for Enantioselective Sensing

In view of the chiral nature of many bio-molecules (and all bio-macromolecules),most of therapeutically active compounds which target these molecules need to be chiraland “good handed” to be effective. In addition to asymmetric synthetic and separationmethodologies, enantioselective chemical sensors, able to distinguish between twoenantiomers of the same molecule, are of relevance. In order to design these sensing tools,two major classes of enantioselective layers have been developed. The first is based onmolecularly imprinted polymers which are produced (polymerized) in the presence of theirtarget, thus the polymeric material keep in “memory” the size and the shape of this moleculeand the system could be used for sensing (not reviewed here). The second approach makesuse of sensitive layers containing chiral macrocyclic receptors able of stereoselectivemolecular recognition; these receptors are mainly based on cyclodextrins. In thiscontribution, are reviewed achievements in the use of native or chemically modifiedcyclodextrins for chiral sensing purposes (at interfaces). Potentialities of other chiralmacrocycles based on calixarenes, calix-resorcinarenes or crown-ethers as supramolecularreceptors for enantioselective sensing are discussed.

C9-O-substituted derivatives of cinchona alkaloids as chiral modifiers in the Orito-reaction: Effects of structure of modifiers on sense of enantioselectivity

The effect of the structure of C9-O-substituted cinchona alkaloids as chiral modifiers of Pt on the enantioselectivity of the Pt-alumina-catalyzed hydrogenation of ethyl pyruvate under mild experimental conditions (room temperature, hydrogen pressure of 1 bar, mainly toluene and tetrahydrofurane as solvents) was investigated. Although C9-O-substituted bulky chiral modifiers also have the open3 conformation, which is a prerequisite of high ee, the ee values observed were still low and even opposite to that expected. Based on the experimental data of a great variety of experiments (ESI-ion-trap-MS, modifier mixtures, selective hydrogenation of chiral modifiers, computational studies) the inversion can explain by tilted adsorption of chiral modifier, namely by a conformational change in the adsorbed chiral modifier and reactant 1:1 intermediate complex.

Unexpected Inversion in Enantioselectivity in the Hydrogenation N-acetyl Dehydrophenylalanine Methyl Ester using Cinchona-Modified Pd/Al2O3 catalyst

The enantioselective hydrogenation of N-acetyl dehydrophenylalanine methyl ester (NADPME) to N-acetyl phenylalanine methyl ester is investigated using cinchona-modified Pd/Al2O3 catalysts. The catalyst was prepared using deposition-reduction and was evaluated for the reaction using methanol as solvent with various cinchonine alkaloid/NADPME molar ratios. Enantioselectivity was sensitive to this ratio. For cinchonine at low cinchonine:NADPME molar ratios the S-N-acetyl phenylalanine methyl ester was formed with low enantioselection, and as the cinchonine:NADPME ratio was increased the reaction became less enantioselective. In the extreme the solubility of cinchonine limited the extent of the experimental conditions that could be explored. As expected cinchonidine modified Pd/Al2O3 initially gave R-N-acetyl phenylalanine methyl ester, again with low enantioselection. However, as the cinchonidine:NADPME molar ratio was increased the reaction initially became racemic and then was selective to the formation of S-N-acetyl phenylalanine methyl ester. This unexpected inversion in the sense of enantioselection was observed in a range of solvents.

Breaking the C3-Symmetry of Chiral Tripodal Oxazolines: Enantio-Discrimination of Chiral Organoammonium Ions

[structure: see text] A phenylglycinol-derived tripodal oxazoline with C1-symmetry (C1-PhBTO) was synthesized, and its enantioselective recognition behavior toward alpha-chiral primary organoammonium ions was studied. The C1-PhBTO receptor showed higher selectivity with an opposite sense of enantio-discrimination compared to other C1-symmetric analogues examined but lower selectivity with the same sense of enantioselection compared to its C3-symmetric analogue. Binding studies indicated that the C1-symmetric receptors, particularly C1-PhBTO, interact with the guests in a 2:1 host-guest complex mode in stark contrast to its C3-symmetric analogues.

Pd-catalyzed asymmetric allylic alkylation using furanoside diphosphinite ligands

We have tested furanoside diphosphinite ligands 7 and 8, derived from inexpensive d-(+)-xylose, in the Pd-catalyzed allylic alkylation of two substrates with different steric properties. Enantiomeric excesses of up to 31% with good activities were obtained in the Pd-catalyzed allylic alkylation of substrate rac-1,3-diphenyl-3-acetoxyprop-1-ene 9 with dimethylmalonate as nucleophile. Our results show that the absolute configuration at carbon C-3 of the carbohydrate backbone controlled the sense of enantioselectivity. Models for asymmetric induction are discussed based on the absolute stereochemistry of the product.

Evidence for the importance of conformational equilibria in Rh-diphosphine complexes for the enantioselection in Rh-catalyzed asymmetric hydrogenation

The conformations of the chelate cycles in the X-ray structures of norbornadiene- and cyclooctadiene-rhodium complexes of ( R, R)-1,2-bis[( o-methylphenyl)phenylphosphino]ethane are dramatically different. Nevertheless, they demonstrate the same sense of enantioselection in asymmetric hydrogenation of dehydroamino acids.

First Enantio‐Flexible Fluorination Reaction Using Metal‐Bis(oxazoline) Complexes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

The Mechanism of Stereoselection in Rh‐Catalyzed Asymmetric Hydrogenation: A General Approach for Predicting the Sense of Enantioselectivity

AbstractFor Abstract see ChemInform Abstract in Full Text.

Enantioselective Sensing of Chiral Carboxylic Acids

A chiral 1,8-diacridylnaphthalene-derived fluorosensor has been prepared and used for enantioselective sensing of a broad variety of chiral carboxylic acids including amino acids, aliphatic acids, arylalkanoic acids, and halogenated carboxylic acids. Fluorescence titration experiments in acetonitrile gave linear Stern-Volmer plots for 1:1 and 1:2 complexes and enantioselectivities up to 4.5.

On the mechanism of stereoselection in Rh-catalyzed asymmetric hydrogenation: a general approach for predicting the sense of enantioselectivity.

This account brings together the recent experimental and computational data on the mechanism of Rh-catalyzed asymmetric hydrogenation of activated double bonds. Two alternative reaction pathways (unsaturated and dihydride) are compared. It is suggested that the differences in these mechanisms are not primarily important for stereoselection, since they join in a single pathway before stereoselection occurs. This approach was used to rationalize the present discrepancies in the prediction of the sense of enantioselection for the P-stereogenic ligands and the ligands with backbone chirality.

Synthesis of New Chiral Aryl Diphosphite Ligands Derived from Pyranoside Backbone of Monosacharides and Their Application in Copper‐Catalyzed Asymmetric Conjugate Addition of Diethylzinc to Cyclic Enones

AbstractNew chiral aryl diphosphite ligands based on the pyranoside backbones of glucose and galactose were prepared. These ligands were tested in the Cu‐catalyzed asymmetric conjugate addition of diethylzinc to cyclic enones with up to 88% ee. The stereoselectivity was found to be dependent on the ring size of the substrate as well as the ligand and copper source. The enantioselectivity depends on the absolute configuration of the C‐4 stereogenic center of the ligand backbone, while the sense of enantioselectivity is mainly controlled by the configuration of the binaphthyl phosphite moieties.

First Enantio-Flexible Fluorination Reaction Using Metal-Bis(oxazoline) Complexes

The first examples of an elective sense of enantioselectivity in enantioselective fluorination reaction using (S,S)-bis(oxazoline)-Ph complexed with Cu(II) or Ni(II) are described.

Towards phase-transfer catalysts with a chiral anion: inducing asymmetry in the reactions of cations

The ability of chiral anions, for example bis[1,1′-bi-2-naphtholato]borate, to induce asymmetry in the reactions of prochiral cations was investigated. Ion-pairing of a borate anion with an aziridinium ion was demonstrated by NMR spectroscopy. The addition of N-methyl indole to an iminium ion (benzylidenedimethylammonium) and the ring-opening of an aziridinium ion (1,2-diphenyl-3-azonia-spiro[2.4]heptane) with benzylamine were studied. Low, but significant, (<15%) enantioselectivities were induced in the formation of the diamine benzyl-(1′,2′-diphenyl-2-pyrrolidin-1-yl-ethyl)-amine. The counterion of the additive was found to have a remarkable effect on the yield and the sense of enantioselectivity of these reactions.

A chiral molecular square with metallo-corners for enantioselective sensing.

A family of chiral molecular squares based on fac-Re(CO)3Cl metallocorners and enantiopure atropisomeric bipyridine bridging ligands (L1-4) have been synthesized in high yields by refluxing ClRe(CO)5 and L1-4 in 1:1 molar ratio. These novel chiral metallocycles have been characterized by 1H and 13C{1H} NMR, UV-vis, luminescence, and circular dichroism (CD) spectroscopies, FAB mass spectrometry, and microanalysis. Molecular square 4 which contains four 1,1'-bi-2-naphthol functionalities exhibits interesting enantioselective luminescence quenching by 2-amino-1-propanol. This research illustrates the potential of generating novel functional materials based on supramolecular chemistry.

On the Orientation of Quinoline on Pd{111}: Implications for Heterogeneous Enantioselective Hydrogenation

The adsorption geometry of quinoid species at platinum and palladium surfaces is relevant to an understanding of enantioselective catalytic hydrogenation. Accordingly, quinoline multilayers and monolayers on Pd{111} have been characterized by XPS and the adsorption geometry within the monolayer determined by NEXAFS at 295 K and 360 K. The molecule lies approximately flat (α < 18° ± 5°), bound to the Pd{111} surface predominantly via the aromatic π-system. This adsorption geometry remains unaffected upon heating to 360 K, and the adsorbed layer does not exhibit long range order under any conditions. Comparison with the corresponding results for Pt{111} indicates that the different intrinsic rates and the reversal in the sense of enantioselectivity observed for pyruvate hydrogenation on palladium catalysts relative to platinum is unlikely to originate in either significantly different modifier adsorption geometries or spatial distributions in the two cases. In addition, it now seems less likely that the collapse in enantioselectivity observed beyond ∼320 K on quinoid-modified palladium catalysts originates in a change in the adsorption geometry of the anchoring moiety of the chiral modifier.

Highly enantioselective Rh-catalyzed hydrogenation based on phosphine-phosphite ligands derived from carbohydrates.

A new class of efficient catalysts was developed for the asymmetric hydrogenation of alpha,beta-unsaturated carboxylic acid derivatives by synthesizing a series of novel phosphine-phosphite ligands (4a-d) derived from readily available D-(+)-xylose. Excellent enantioselectivities (> 99%) were achieved under very mild reaction conditions (1 bar H(2) and 20 degrees C). Varying the biphenyl substituents in the phosphite moiety greatly affected the enantioselectivity in the hydrogenation reactions. The results also indicate that the sense of enantioselectivity is mainly controlled by the configuration of the phosphite moiety. (31)P[(1)H] NMR and kinetic studies on intermediates of the catalytic cycle show that the [Rh(P(1)-P(2))(enamide)]BF(4) species is the resting state and that the rate dependence is first order in rhodium and hydrogen pressure and zero order in enamide concentration.

Origin of Enantioreversal in the Rhodium-Catalyzed Asymmetric Hydrogenation of Prochiral Enamides and the Effect of the α-Substituent

The enantioselectivity of prochiral enamide hydrogenation depends on the structure of the enamide, with particular sensitivity to the nature of the α-substituent. Recently, Burk has reported a spectacular example of structure sensitivity for [Rh(DuPHOS)]+-catalyzed enamide hydrogenations: although enamides containing either carboxyl or tert-butyl α-substituents hydrogenate to ≥99% enantiomeric excess, the sense of enantioselection for the two substrate classes is reversed. Why should the magnitude and sense of enantioselectivity depend so strongly on the enamide α-substituent? We report the application of QM/MM (ONIOM) computations to address this long-standing issue in asymmetric catalysis. Specifically, we demonstrate that computational methods reproduce the α-substituent effect in enamide hydrogenation catalysis and probe how the interaction of the enamide CC bond and the catalyst varies with the structure of the substrate. The picture that emerges emphasizes the complex confluence of both electronic ...