Optically active transition metal complexes. Part 119:New rhodium(I) complexes containing two different types of optically active ligands

The synthesis of novel rhodium(I) complexes containing two different chiral ligands is described. These ligands are on the one hand (−)-diop and on the other hand various optically active pyrroleimines, which derive from 1-phenylethylamine or 1-cyclohexylethylamine with an (R)- or (S)-configuration. The resulting (−)-diop–pyrrolylimine–rhodium(I) complexes are diastereomers and are expected to give different stereoselectivities in enantioselective catalysis (double stereoselection). In addition, the synthesis of novel rhodium(I) complexes containing 1,5-cyclooctadiene and various chiral pyrroleoxazoline ligands is described. All the complexes are used in the enantioselective hydrogenation of ketopantolactone (see following paper).     

Interaction between ketopantolactone and chirally modified Pt investigated by attenuated total reflection IR concentration modulation spectroscopy

The combination of ATR-IR and modulation spectroscopy allowed for the study of the interaction of ketopantolactone with Pt/Al2O3 films chirally modified by cinchonidine under hydrogenation conditions. The spectra reveal a significant influence of ketopantolactone on the adsorption of the modifier and indicate a N-H-O hydrogen bond between modifier and reactant. The latter was corroborated by a comparative study with N-methyl cinchonidine chloride modified Pt/Al2O3.     

Low-Waste Process for Preparing Ketopantolactone,with Electrochemical Recovery of Bromine

The process parameters of dehydrogenation of pantolactone with bromine in chloroform and the possibility of bromine recycling by electrolysis of hydrogen bromide formed in the synthesis of ketopantolactone were studied.     

Platinum-Catalyzed Asymmetric Hydrogenation: Spectroscopic Evidence for an O-H-O Hydrogen-Bond Interaction between Substrate and Modifier

The mighty cinchonidine: A diastereomeric surface complex in the asymmetric hydrogenation of ketopantolactone on chirally modified Pt is monitored by in?situ ATR-IR spectroscopy, in combination with modulation excitation spectroscopy and phase-sensitive detection. Cinchonidine bound to the surface with its quinoline ring is shown to induce the chiral environment through a C9?O???H???O?C interaction.     

Synthesis and application of a novel bisphosphine ligand, (−)-DIOCP,as an unsymmetrized diop to prove the general utility of new designing concept.

A new chiral bisphosphine-Rh complex (DIOCP-Rh) was found to show excellent catalytic activity and good enantioselectivity for the asymmetric hydrogenation of ketopantolactone proving the general utility of new designing concept.     

Separation of diastereomers of phosphinic pseudopeptides by capillary zone electrophoresis and reverse phase high‐performance liquid chromatography

Capillary zone electrophoresis (CZE) and reverse phase high‐performance liquid chromatography (RP‐HPLC) were used for separation of diastereomers of phosphinic pseudopeptides in achiral separation media. A set of phosphinic pseudopeptides, i. e. peptides with one peptide bond substituted by phosphinic acid moiety ‐PO₂^–‐CH₂‐ derived from the structure N‐Ac‐Val‐AlaB(‐CH₂)Leu‐His‐NH₂ synthesized as a mixture of four diastereomers was used. Separations of diastereomers by CZE were carried out in Tris‐phosphate background electrolytes in the pH range 1.1–3.2 and at least partial separation of the four diastereomers of each pseudopeptide was achieved. A routinely used RP‐HPLC method (C₁₈‐silica column and water/acetonitrile/trifluoroacetic acid mobile phase) was also capable of resolving the diastereomers. In addition, since individual diastereomers of majority of the pseudopeptides were isolated by RP‐HPLC it was possible to check the purity of these RP‐HPLC separated diastereomers and to compare the migration order of the diastereomers in CZE with their elution order in RP‐HPLC. The results obtained by CZE and RP‐HPLC demonstrate a complementarity of both methods in analysis and separation of phosphinic pseudopeptides including their diastereomers.     

Asymmetric Catalysis. Part 149 [1]. Synthesis of New Chiral Tridentate Ligands for Enantioselective Catalysis

Summary. The synthesis of new chiral tridentate ligands is reported which coordinate transition metals in a meridional way. The ligands contain a pyridine ring, an oxazoline ring, and a strongly coordinating diphenylphosphanyl group. The methionine-derived ligand forms a copper complex, which has been studied by X-ray crystallography. The new ligands were tested in models of enantioselective catalyses, such as hydrogenation of ketopantolactone, hydrosilylation of acetophenone, and transfer hydrogenation of acetophenone.X-ray structure analysesReceived March 4, 2003; accepted March 4, 2003 Published online August 18, 2003     

Remarkably large remote-stereocenter-induced chromatographic differences: azulenyl 1,5-diols

A series of four new azulene-1,5-diol diastereomers were prepared and found to exhibit large differences (ΔR_f 0.22–0.46) in silica TLC mobilities despite having stereocenters four bonds apart. The stereoisomers were identified by X-ray crystallography, and in all cases the RR/SS diastereomers were less strongly retained than the RS/SR diastereomers. The crystal structures suggested that this is due to a conformational preference for the CF₃ groups to be nearly perpendicular to the plane of the azulene ring, which caused the dihedral angle between the OH groups to be larger (in the RR/SS diastereomers) or smaller (in the RS/SR diastereomers). The smaller dihedral angles allow the RS/SR diastereomers to simultaneously bind to a silica surface and thus be more strongly retained. Two similar benzene derivatives and several cycloalkanediols with more proximate stereocenters showed little or no difference in mobilities between diastereomers, though the NMR differences were greater. Thus, the azulene ring is an important factor in enforcing the conformational preferences, either through steric interactions with the 4/8 substituents (H or methyl) or its significant dipole moment, or both.     

Role of guiding groups in cinchona-modified platinum for controlling the sense of enantiodifferentiation in the hydrogenation of ketones

Systematic structural variations of cinchona-type modifiers used in the platinum-catalyzed hydrogenation of ketones give insight into the adsorption mode of the modifier and its interaction with the substrate on the platinum surface under truly in situ conditions. The performance of a new modifier, O-(2-pyridyl)-cinchonidine, is compared to that of O-phenyl-cinchonidine and cinchonidine (CD). In the hydrogenation of ethyl pyruvate, ketopantolactone, and 2-methoxyacetophenone, CD gives the (R)-alcohol in excess. Introduction of the bulky O-phenyl group favors the (S)-enantiomer, whereas upon replacement of the phenyl by a 2-pyridyl group the (R)-alcohol is again the major product. This finding is particularly striking, because the two ether groups have virtually identical van der Waals volumes. A catalytic study including the nonlinear behavior of modifier mixtures, and attenuated total reflection infrared spectroscopy of the solid-liquid interface in the presence of hydrogen, revealed the adsorption mode and strength of the modifiers on Pt. Theoretical calculations of the modifier-substrate interactions offered a feasible explanation for the different role of the bulky ether groups: repulsion by the phenoxy and attraction by the 2-pyridoxy groups. Simulation of the interaction of o-pyridoxy-CD with ketopantolactone on a model Pt surface suggests that formation of two N-H-O-type H-bonds--involving the quinuclidine and pyridine N atoms, and the two keto-carbonyls in the substrate--controls the adsorption of the substrate during hydrogen uptake. This mechanistic study demonstrates the potential of insertion of suitable substituents into CD and their influence on adsorption and stereocontrol on the platinum surface.     

Determination of enantiomeric excess and degree of hydrogenation in the enantioselective hydrogenation of ketopantolactone

Summary A new gas chromatographic method for the simultaneous determination of the degree of hydrogenation of ketopantolactone and the enantiomeric excess of pantolactone does not require any derivatisation.

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Bestimmung von Enantiomerenüberschuß und Hydriergrad bei der enantioselektiven Hydrierung von Ketopantolacton (Kurze Mitt.)

Zusammenfassung Zur Bestimmung des Hydriergrads von Ketopantolacton und des Enantiomerenüberschusses von Pantolacton wird ein neues gaschromatographisches Verfahren eingesetzt, das keine Derivatisierung erfordert.

     

Beiträge zur Chemie der Pyrrolpigmente, 48. Mitt.

2,3-Dihydrobilatrienes-abc substituted analogous to the natural chromophor of phytochrome may exhibit diastereomerism at the exocyclic double bond of the unsaturated lactam ring. Their properties are comparable to the previouslystudied bilatriene-abc diastereomers. At the exocyclic double bond of the saturated lactam ring however, diastereomers could only be prepared for thermodynamic reasons. The spectroscopic properties of the various diastereomers of five compounds were recorded and are discussed with respect to their utility in structural studies of the natural pigment system.     

PSEUDOROTATION IN MONOCYCLIC OXYPHOSPHORANES WHICH CONTAIN CHIRAL CENTERS

Abstract

Phenylbis[2-methyl-1-butoxy]phosphine has been allowed to react with butanedione to produce 2,2-bis[2-methyl-1-butoxy]-2-phenyl-4,5-dimethyl-1,3,2-dioxaphophol-4-ene. This material is a mixture of three diastereomers. It has been reported that 2,2-bis[tetrahydrofurfuyloxy]-2-phenyl-4,5-dimethyl-1,3,2-dioxaphosphol-4-ene is a mixture of only two diastereomers. The present work suggest that two of the diastereomers of the tetrahydrofurfuryloxy compound interconvert via hexacoordinated zwitterionic intermediates which involve addition of the oxygen of the tetrahydrofuran ring to phosphorus.     

A Novel Synthesis of 3-O-Allyl-4, 5, 6-tri-O-benzyl-1-O-（p-methoxybenzyl）-D-myo-inositol

Highly efficient synthesis of the entitled compound was achieved from a readily available myo-inositol derivative. The key step involved a desymmetrization with ( )-camphor dimethyl ketal to give two diastereomers. The two diastereomers could be used to synthesize the same compound by changing the orders to introduce the protective groups.     

High yielding synthesis of 3a-hydroxypyrrolo[2,3-b]indoline dipeptide methyl esters: synthons for expedient introduction of the hydroxypyrroloindoline moiety into larger peptide-based natural products and for the creation of tryptathionine bridges

This work describes a rapid and high yielding oxidation of 14 tryptophanylated amino acid methyl esters to the corresponding 3a-hydroxypyrrolo[2,3-b]indoline (Hpi) amino acids with generally facile separation of syn-cis and anti-cis diastereomers. Structural X-ray diffraction data are presented for both diastereomers of Tr-Hpi-Gly-OMe, which allow for a putative assignment of the other 13 pairs of diastereomers reported herein, based on correlations with 1H NMR chemical shifts. Selective and high yielding deprotection at either the N or C terminus is described, allowing the Hpi motif to be introduced efficiently into potential targets with minimal protecting group manipulation. Two tripeptides containing Hpi and cysteine were prepared and treated with acid in the Savige-Fontana reaction to produce a cyclic tryptathionine linkage, characteristic of both amatoxins and phallotoxins.     

Separation and determination of diastereomers of lambda-cyhalothrin by normal phase-liquid chromatography using a CN column.

A simple and rapid normal-phase liquid-chromatographic method for the separation and determination of diastereomers of lambda-cyhalothrin using a CN column and detection at UV-230 nm has been developed. This method has the advantage of totally resolving each of the diastereomers from impurities, such as meta-phenoxy benzaldehyde, cyhalothric acid and cyhalothric acid chloride, of technical and formulated materials, allowing one to monitor the low-temperature conversion of diastereomers of lambda-cyhalothrin for process development.     

Synthesis of fluorescent label, DBD-beta-proline, and the resolution efficiency for chiral amines by reversed-phase chromatography

DBD-d(and l)-beta-proline, new fluorescent chiral derivatization reagents, were synthesized from the reaction of 4-(N,N-dimethylaminosulfonyl)-7- fl uoro-2,1,3-benzoxadiazole (DBD-F) with beta-proline. The racemic mixture synthesized was separated by a chiral stationary phase (CSP) column, Chiralpak AD-H, with n-hexane-EtOH-TFA-diethylamine (70:30:0.1:0.1) as the mobile phase. The dl-forms were decided according to the results obtained from a circular dichroism (CD) detector after separation by the CSP column. The fractionated enantiomers reacted with chiral amine to produce a couple of diastereomers. The labeling proceeded in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and pyridine as the activation reagents. The reaction conditions were mild and no racemization occurred during the diastereomer formation. The resulting diastereomers fluoresced at around 570 nm (excitation at around 460 nm). Good linearity of the calibration curves was obtained in the range 1-75 pmol and the detection limits on chromatogram were less than 1 pmol. The separability of the diastereomers was compared with the diastereomers derived from DBD-d(or l)-proline. The resolution values (Rs) obtained from the diastereomers of three chiral amines with DBD-d(or l)-beta-proline were higher than those derived from DBD-d(or l)-proline, e.g. dl-phenylalanine methylester (dl-PAME), 2.23 vs 1.37; (R)(S)-1-phenylethylamine [(R)(S)-PEA], 2.09 vs 1.13; and (R)(S)-1-(1-naphthyl)ethylamines [(R)(S)-NEA], 5.19 vs 1.23. The results suggest that the position of COOH group on pyrrolidine moiety in the structures is one of the important factors for the efficient separation of a couple of the diastereomers.     

A novel approach for enantioseparation as applied to (RS)‐etodolac from pharmaceutical formulations: LC MS and density functional theory support for confirmation of diastereomers so separated

In the present studies formation of diastereomers of (RS)‐etodolac was confirmed using LC‐MS when [M + H]⁺ or [M]⁺ were recorded for the diastereomers. The lowest energy optimized structures of two diastereomers were drawn, which confirmed the three‐dimensional geometry of the diastereomers. This supports the optimized analytical separation conditions. In addition, separation of diastereomers was successful using a C₁₈ column and a binary mixture of methanol and triethyl ammonium phosphate buffer of pH 4.5 (80:20, v/v) as mobile phase at a flow rate of 1 mL min^?1 and UV detection at 223 nm. The separation method was validated as per International Conference on Harmonization guidelines. (RS)‐Etodolac was isolated from commercial tablets and purified and characterized to be used as racemic standard. Three pairs of diastereomers were synthesized using enantiomerically pure amines, namely, (R)‐(+)‐α‐methyl benzyl amine, (S)‐(?)‐α,4‐dimethylbenzylamine and (R)‐(?)‐1‐cyclohexylethylamine. Derivatization reactions were carried out under conditions of stirring at room temperature (30 °C for 2 h) as well as under microwave irradiation (MWI), and the two types of diastereomers were compared. Reaction conditions for derivatization were optimized with respect to mole ratio of chiral derivatizing agent and (RS)‐etodolac and MWI time. No racemization was observed throughout the study. Copyright © 2015 John Wiley & Sons, Ltd.     

Synthesis and ring-opening metathesis of tetraalkoxy-substituted [2.2]paracyclophane-1,9-dienes

Tetraalkoxy-substituted [2.2]paracyclophane-1,9-dienes can be prepared in three steps from dithia[3.3]paracyclophanes. A mixture of pseudo-geminal and pseudo-ortho diastereomers is produced and the pure compounds can be separated by fractional crystallization. The solid state structures of these diastereomers reveal strongly distorted aromatic rings consistent with high levels of ring strain. Reaction of these diastereomers with the second generation Grubbs catalyst shows that only the pseudo-geminal isomer can be ring opened to give cis,trans-distrylbenzenes. The origin of this selectivity is discussed and the photoisomerization of the as-formed cis,trans-product to the all trans isomer is demonstrated.     

Diastereoselective reduction of α-pyrazolidinyl ketones

The conditions were found for the diastereoselective reduction of racemic ketones of the pyrazolidine series to alcohols. The latter compounds were preparatively isolated and characterized. The reduction of ketones with sodium borohydride on the surface of an adsorbent without a solvent affords predominantly one group of diastereomers, whereas the reduction with lithium tri-tert-butoxyaluminohydride in solution gives rise to another group of diastereomers.     

Selective adsorption and reactivity of dipeptide stereoisomers in clay mineral suspension

Preferential adsorption of dipeptide diastereomers (dialanine, Val-Ala) on clay mineral surfaces was observed. Significantly higher adsorption of dipeptides composed from only one type of enantiomer of amino acid units in comparison to those containing both L- and D-type of amino acid units in their molecules, was experimentally proven. This selectivity was explained in terms of different hydrophobic properties of diastereomers, which are probably controlled by intramolecular interactions between nonpolar and polar parts of dipeptide molecules affected by their stereochemistry. A significantly higher reactivity of stereoisomers composed from the same type of amino acid enantiomers to form amide bonds was proven as well. Theoretical study could distinguish different properties of the diastereomers. The results of the calculations indicate possible effects of molecular stability in the stereoselectivity during the adsorption and reactions of Ala(2) diastereomers.