Isolation, absolute configuration, and chiral crystallization of optically active seleninic acid

An optically pure seleninic acid was isolated as stable crystals for the first time by chiral crystallization. The relationship between the absolute configurations and the circular dichroism spectra of the enantiomers could be determined by X-ray crystallographic analysis.     

Synthesis of optically active oligomers consisting of chiral phosphorus atoms: capture of an intermediate between a polymer and a small molecule

We describe here the synthesis and properties of novel optically active oligophosphines. The effect of the number of chiral phosphorus atoms on thermal properties and conformations is documented. In this study, we captured an intermediate between a polymer and a small molecule. To the best of our knowledge, it is primarily observed that a small molecule transforms into a polymer via an amorphous small molecule during the process of the elongation of the oligomer main chain.     

Asymmetric synthesis of a chiral arsinophosphine via a metal template promoted asymmetric Diels-Alder reaction between diphenylvinylphosphine and 2-furyldiphenylarsine

The asymmetric Diels-Alder reaction between 2-furyldiphenylarsine and diphenylvinylphosphine was achieved stereospecifically by utilizing an organoplatinum reaction promoter containing the ortho-metalated (R)-(1-(dimethylamino) ethyl)-naphthalene as the chiral auxiliary. The optically pure (+)-As-P heterobidentate cycloadduct could be liberated from the template product by successive treatment with concentrated hydrochloric acid and aqueous potassium cyanide.     

Synthesis, structure, and catalytic activity of titanium(IV) and zirconium(IV) amides with chiral biphenyldiamine-based ligands

A new series of titanium(IV) and zirconium(IV) amides have been prepared from the reaction between M(NMe₂)₄ (M = Ti, Zr) and C₂-symmetric ligands, (R)-2,2′-bis(pyridin-2-ylmethylamino)-6,6′-dimethyl-1,1′-biphenyl (2H₂), (R)-2,2′-bis(pyrrol-2-ylmethyleneamino)-6,6′-dimethyl-1,1′-biphenyl (3H₂), (R)-2,2′-bis(diphenylphosphinoylamino)-6,6′-dimethyl-1,1′-biphenyl (4H₂), (R)-2,2′-bis(methanesulphonylamino)-6,6′-dimethyl-1,1′-biphenyl (5H₂), (R)-2,2′-bis(p-toluenesulphonylamino)-6,6′-dimethyl-1,1′-biphenyl (6H₂), and C₁-symmetric ligands, (R)-2-(diphenylthiophosphoramino)-2′-(dimethylamino)-6,6′-dimethyl-1,1′-biphenyl (7H) and (R)-2-(pyridin-2-ylamino)-2′-(dimethylamino)-6,6′-dimethyl-1,1′-biphenyl (8H), which are derived from (R)-2,2′-diamino-6,6′-dimethyl-1,1′-biphenyl. Treatment of M(NMe₂)₄ with 1 equiv. of N₄-ligand, 2H₂ or 3H₂ gives, after recrystallization from an n-hexane solution, the chiral zirconium amides (2)Zr(NMe₂)₂ (9), (3)Zr(NMe₂)₂ (11), and titanium amide (3)Ti(NMe₂)₂ (10), respectively, in good yields. Reaction of Zr(NMe₂)₄ with 1 equiv of diphenylphosphoramide 4H₂ affords the chiral zirconium amide (4)Zr(NMe₂)₂ (12) in 85% yield. Under similar reaction conditions, treatment of Ti(NMe₂)₄ with 1 equiv. of sulphonylamide ligand, 5H₂ or 6H₂ gives, after recrystallization from a toluene solution, the chiral titanium amides (5)Ti(NMe₂)₂·0.5C₇H₈ (13·0.5C₇H₈) and (6)Ti(NMe₂)₂ (15), respectively, in good yields, while reaction of Zr(NMe₂)₄ with 1 equiv. of 5H₂ or 6H₂ gives the bis-ligated complexes, (5)₂Zr (14) and (6)₂Zr (16). Treatment of M(NMe₂)₄ with 2 equiv. of diphenylthiophosphoramide ligand 7H or N₃-ligand 8H gives, after recrystallization from a benzene solution, the bis-ligated chiral zirconium amides (7)₂Zr(NMe₂)₂ (17) and (8)₂Zr(NMe₂)₂ (19), and bis-ligated chiral titanium amide (8)₂Ti(NMe₂)₂ (18), respectively, in good yields. All new compounds have been characterized by various spectroscopic techniques, and elemental analyses. The solid-state structures of complexes 10, 12, 13, and 17-19 have further been confirmed by X-ray diffraction analyses. The zirconium amides are active catalysts for the asymmetric hydroamination/cyclization of aminoalkenes, affording cyclic amines in good to excellent yields with moderate ee values, while the titanium amides are not.     

Enantioselective addition of phenyl and alkyl acetylenes to imines catalyzed by chiral Cu(I) complexes

The stereoselective addition of phenyl acetylene and alkyl acetylenes to imines, catalyzed by chiral bis-imines-Cu(I) complexes was studied. A very simple experimental procedure allowed to obtain at room temperature optically active propargyl amines in very good yields and enantioselectivity up to 81%.     

Synthesis of some new chiral bifunctional o-hydroxyarylphosphonodiamides and their application as ligands in Ti(IV) complex catalyzed asymmetric silylcyanation of aromatic aldehydes

Some new chiral bifunctional o-hydroxyarylphosphonodiamides were synthesized starting from (+)-cis-1,2,2-trimethylcyclopentane-1,3-diamine and the absolute configuration of the phosphorus atom was determined by X-ray diffraction analysis. Excellent enantioselectivity (up to 98% ee) was achieved in asymmetric silylcyanation of aromatic aldehydes using a chiral titanium complex formed in situ from Ti(OⁱPr)₄ and o-hydroxyarylphosphonodiamide as the catalyst.     

Synthesis of novel well-defined chain-end-functionalized polystyrenes with dendritic chiral ephedrine moieties and their applications as highly enantioselective diethylzinc addition to N-diphenylphosphinoyl arylimines

A series of novel well-defined chain-end-functionalized polystyrenes having 2, 4, 8, and 16 chiral ephedrine moieties dendritically distributed at their hyperbranched chain-ends were quantitatively synthesized. Their well-defined architectures were fully confirmed by elemental analysis, FTIR, SEC as well as by ¹H and ¹³C NMR spectroscopies. These polymers were precisely controlled in the molecular weight and molecular weight distribution as well as well-defined in chain-end-functionalities. These dendritic chiral polymers serve as highly enantioselective chiral ligands in the enantioselective addition of diethylzinc to a series of N-diphenylphosphinoyl arylimines. Among them, chiral dendrimer having eight ephedrine moieties at the chain-ends afforded the corresponding enantiomerically enriched phosphinoylamides in good to high yields with enantioselectivities up to 93% ee. The obtained enantioselectivities are comparable with those obtained by using N-benzylephedrine and its corresponding copolymer as chiral ligands.     

Reversed-phase high-performance liquid chromatographic separation of diastereomers of (R,S)-mexiletine prepared by microwave irradiation with four new chiral derivatizing reagents based on trichloro-s-triazine having amino acids as chiral auxiliaries and 10 others having amino acid amides

A new series of chiral derivatizing reagents (CDRs) consisting of four dichloro-s-triazine reagents was synthesized by nucleophilic substitution of one chlorine atom in trichloro-s-triazine with amino acids, namely L-Leu, D-Phg, L-Val and L-Ala as chiral auxiliaries. Two other sets of CDRs consisting of four dichloro-s-triazine (DCT) and six monochloro-s-triazine (MCT) reagents were also prepared by nucleophilic substitution of chlorine atom(s) with different amino acid amides as chiral auxiliaries in trichloro-s-triazine and its 6-methoxy derivative, respectively. These 14 CDRs were used for the synthesis of diastereomers of (R,S)-mexiletine under microwave irradiation (i.e. 60s and 90 s at 85% power (of 800 W) using DCT and MCT reagents, respectively), which were resolved by reversed-phase high-performance liquid chromatography using C18 column and gradient eluting mixtures of methanol with aqueous trifluoroacetic acid (TFA) with UV detection at 230 nm. The resolution (R(s)), difference between retention times of resolved diastereomers (Δt) and retention factors (k) obtained for the three sets of diastereomers were compared among themselves and among the three groups. Explanations have been offered for longer retention times and better resolution of diastereomers prepared with DCT reagents in comparison of their MCT counterparts and, for the influence of hydrophobicity of the side chain R of the amino acid in the CDRs on retention times and resolution. The newly synthesized CDRs were observed to be superior as compared to their amide counterparts in terms of providing better resolution and cost effectiveness. The method was validated for limit of detection, linearity, accuracy and precision.     

Efficient construction of a chiral all-carbon quaternary center by asymmetric 1,4-addition and its application to total synthesis of (+)-bakuchiol

The conjugate addition of lithium divinylcuprate to (4S,2′E)-3-(6′-TBDPS-3′-methylhex-2′-enoyl)-4-phenyloxazolidin-2-one proceeded efficiently to create a chiral all-carbon quaternary center with a high diastereoselectivity (R:S = 95:5). The absolute configuration of the newly generated chiral center was confirmed by applying this methodology to the total synthesis of (+)-bakuchiol.     

Enantioselective determination of (R)‐ and (S)‐lansoprazole in human plasma by chiral liquid chromatography with mass spectrometry and its application to a stereoselective pharmacokinetic study

A simple and enantioselective method was developed and validated for the simultaneous determination of (R)‐ and (S)‐lansoprazole in human plasma by chiral liquid chromatography with tandem mass spectrometry. Lansoprazole enantiomers and internal standard (esomeprazole) were extracted from plasma using acetonitrile as protein precipitating agent. Baseline chiral separation was achieved within 9.0 min on a Chiralpak IC column (150 mm × 4.6 mm, 5 μm) with the column temperature of 30°C. The mobile phase consisted of 10 mM ammonium acetate solution containing 0.05% acetic acid/acetonitrile (50:50, v/v). The mass spectrometric analysis was performed using a QTrap 5500 mass spectrometer coupled with an electrospray ionization source in positive ion mode. The multiple reactions monitoring transitions of m/z 370.1→252.1 and 346.1→198.1 were used to quantify lansoprazole enantiomers and esomeprazole, respectively. For each enantiomer, no apparent matrix effect was found, the calibration curve was linear over 5.00–3000 ng/mL, the intra‐ and inter‐day precisions were below 10.0%, and the accuracy was –3.8 to 3.3%. Analytes were stable during the study. No chiral inversion was observed during sample storage, preparation procedure and analysis. The method was applied to the stereoselective pharmacokinetic studies in human after intravenous administration of dexlansoprazole or racemic lansoprazole.     

Asymmetric ring cleavage reaction with a combination of optically active cycloalkane-1,2-diol and Lewis acid: application to formal synthesis of (−)-alloyohimbane and approach to construction of adjacent chiral quaternary centers

Asymmetric ring cleavage reaction of meso-carbobicyclic ketones by a combination of benzaldehyde, chiral cycloalkane-1,2-diol, and Lewis acid gave optically active styrenyl esters of 26-69% ee in moderate yield. The ring cleavage reaction could be applied to the construction of adjacent chiral quaternary carbons, and also to the formal synthesis of natural alkaloid (−)-alloyohimbane.     

Application of a 1H δ‐resolved 2D NMR experiment to the visualization of enantiomers in chiral environment,using sample spatial encoding and selective echoes

We present the application of a 2D broadband homodecoupled proton NMR experiment to the visualization of enantiomers. In a chiral environment, the existence of diastereoisomeric intermolecular interactions can yield—generally slight—variations of proton chemical shifts from one enantiomer to another. We show that this approach, which relies on a spatial encoding of the NMR sample, is particularly well suited to the analysis of enantiomeric mixtures, since it allows, within one single 2D experiment, to detect subtle chemical shift differences between enantiomers, even in the presence of several couplings. This sequence, which uses semiselective radio‐frequency (rf) pulses combined to a z‐field gradient pulse, produces different selective echoes in various parts of the sample. The resulting homonuclear decoupling provides an original δ‐resolved spectrum along the diagonal of the 2D map where it becomes possible to probe the chiral differentiation process through every proton site where the resulting variation in the chemical shift is detectable. We discuss the advantages and drawbacks of this approach, regarding other experiments which provide homodecoupled proton spectra. This methodology is applied to the observation of enantiomers of (1) ( ± )2‐methyl‐isoborneol coordinated to europium (III) tris[3‐(trifluoromethyl‐hydroxymethylene)‐(+)‐camphorate] in isotropic solution, and (2) ( ± )3‐butyn‐2‐ol dissolved in a chiral liquid‐crystal solvent, in order to show the robustness of this pulse sequence for a wide range of chiral samples. Copyright © 2009 John Wiley & Sons, Ltd.     

The ruthenium catalyzed formation of chiral dihydropyrrolones from α,β-unsaturated imines: extending the reaction to terminal alkenes and investigating the formation of pyrroles as side-products

The reaction of α,β-unsaturated imines derived from cinnamaldehyde with CO and various alkenes produces chiral 1,3-dihydropyrrolone derivatives. As a byproduct the formation of 2,3-disubstituted pyrroles is observed in every reaction. If the imines are reacted with ethylene only, products with an ethyl group at C-3 of the imine chain are formed. The implications of these findings on the reaction mechanism are discussed.