O,O'-Di-p-toluoyl-(2R,3R)-tartaric acid as supramolecular resolving agent

O,O'-di-p-toluoyl-(2R,3R)-tartaric acid (DPTTA) was investigated as supramolecular complex (SMC) forming resolving agent with three racemic alcohols (menthol, 4-methyl-2-pentanol, trans-2-iodo-cyclohexanol) by preparative scale experiments and thermoanalytical measurements. Despite the very small structural difference (two methyl groups) between the O,O'-dibenzoyl-(2R,3R)-tartaric acid (DBTA) and DPTTA, their SMC forming properties with water and racemic alcohols is very different. While DBTA forms SMC with all the three investigated alcohols, DPTTA forms SMC only with trans-2-iodo-cyclohexanol. DPTTA binds the guest compound less strongly and the stoichiometry of the SMC is also different. The weaker interactions resulted in less effective optical resolutions. The results of these investigations remind us, that in optical resolutions during the chiral discrimination process the weaker interactions have a determining role, since DBTA and DPTTA have the possibility to form the same strong (O-H···O and N-H···O) hydrogen bond network. This revised version was published online in August 2006 with corrections to the Cover Date.     

Thermoanalytical Study of O,O'-Dibenzoyl-(2R,3R)-Tartaric Acid Supramolecular Compounds Part II. Investigation of the resolution of racemic alcohols

The resolution of three chiral alcohols with O,O'-dibenzoyl-(2R,3R)-tartaric acid (DBTA) via diastereoisomeric supramolecular compound formation was investigated with thermoanalytical methods. On the basis of TG measurements the DBTA:chiral alcohol molar ratio in the compounds is 1:1 which agrees with the results of single-crystal X-ray diffraction analysis. The DBTA – chiral alcohol supramolecular compounds have different supramolecular structure than the DBTA – achiral alcohol supramolecular compounds. The supramolecular compounds containing cyclohexanols have higher thermal stability than the compounds containing acyclic aliphatic alcohols. The amount of unreacted DBTA monohydrate in the solid phase can be determined both with DSC and with TG measurements. This revised version was published online in August 2006 with corrections to the Cover Date.     

Thermoanalytical Study of O,O'-Dibenzoyl-(2R,3R)-Tartaric Acid Supramolecular Compounds. Part I. Investigation of compounds with water, achiral alcohols and phenols

Thermal behaviour of O,O'-dibenzoyl-(2R,3R)-tartaric acid (DBTA), its monohydrate, and its potential supramolecular compounds with achiral alcohols and phenols were investigated with TG, DSC, EGD. The structural differences among the anhydrous DBTA, its monohydrate, and the supramolecular derivatives were investigated with X-ray powder diffraction. The thermal behaviour of DBTA-supramoleculars with isopropyl, tert-butyl, and 5-cyclohexyl alcohols is found to be similar to each other but essentially different from that of both DBTA and its monohydrate. On heating they melt and decompose between 60–180°C while they loose in one or two steps the bound alcohol. The thermal stability of the supramolecular compounds increases with the boiling point of the alcohol component. According to the X-ray powder diffraction patterns each supramolecular substance has different structure, that may also result in the different thermal stability of the compounds. The molar ratio of DBTA:achiral alcohol samples is 1:1.01–1:1.57 estimated from the corresponding mass losses. The XRD patterns of the prepared two DBTA-phenol materials are different from those of DBTA-achiral alcohol samples. The phenol compounds melt with slow mass losses and give an endothermic peak between 73–83°C but the melting point of the anhydrous DBTA cannot be observed. DBTA:phenol molar ratio is estimated to be 1:0.41 and 1:0.65 for phenol and 2-methylphenol, respectively. This revised version was published online in July 2006 with corrections to the Cover Date.     

Effect of the Orientation of Amide Linkage Groups on the Enantioselectivity of Two Related Synthetic Polymeric Chiral Stationary Phases

Two new synthetic polymeric chiral stationary phases (CSPs) based on trans-(1S,2S)-cyclohexanedicarboxylic acid bis-4-vinylphenylamide (I) and trans-N,N′-(1R,2R)-cyclohexanediyl-bis-4-ethenylbenzamide (II) monomers were prepared and evaluated by normal phase high performance liquid chromatography (HPLC) and supercritical fluid chromatography (SFC). A variety of chiral compounds were separated on these two new CSPs. The different orientation of the amide groups in the two CSPs resulted in a striking difference in the enantioselectivity properties of these two CSPs. Their differences in enantioselectivity with HPLC and SFC were compared.     

Enantioselective Reduction of Prochiral Ketones Using a Reagent Prepared from Lithium Aluminium Hydride, (+)Threo-1,16-Dibenzyloxy, 7(R),8(R)-Dihydroxy Hexadecane and Alcohol

Asymmetric reduction of prochiral ketones to optically active chiral secondary alcohols was achieved using a reagent prepared by modifying lithium aluminium hydride with a chiral auxiliary, (+)threo-1,16-dibenzyloxy,7,8-dihydroxy hexadecane and various additive alcohols. (+)threo-1,16-dibenzyloxy,7(R),8(R)-dihydroxy hexadecane was prepared from (+)threo-9(R),10(R),16-trihydroxy hexadecanoic acid. Alcohols such as CH₃(CH₂)_n-OH of different chain length (n = 0–11) and (R)-hydnocarpic alcohol were used. Complex prepared from (+)threo-1,16-dibenzyloxy,7(R),8(R)-dihydroxy hexadecane, LAH and (R)-hydnocarpic alcohol reduced acetophenone in moderate enantioselectivity (maximum of 70% ee). Various arylalkylketones were reduced with the same complex.     

Synthesis and Evaluation of a Synthetic Polymeric Chiral Stationary Phase for LC Based on the N, N′-[(1R,2R)-1,2-Diphenyl-1,2-Ethanediyl]bis-2-Propenamide Monomer

A synthetic polymeric chiral stationary phase for liquid chromatography based on N, N′-[(1R,2R)-1,2-diphenyl-1,2-ethanediyl]bis-2-propenamide monomer was prepared via a simple solution initiated radical polymerization. This stable chiral stationary phase showed enantioselectivities for a large number of racemates in polar organic and normal phase modes and high sample loading ability. However, none of the generated data has been optimized in terms of column performance. Different enantioselectivities were observed on this new chiral stationary phase compared with the commercial polymeric chiral stationary phase based on N-(2-acryloylamino-(1R,2R)-cyclohexyl)-acrylamine monomer. Consequently, these two chiral stationary phases are considered complementary to one another. Furthermore they utilize the same mobile phase and optimization procedures. This polymeric chiral stationary phase appears to be useful for preparative separations since high amounts of analyte can be injected without loosing enantioselectivity.     

Asymmetric [2,3]-Wittig rearrangement of the dienolates of chiral secondary alcohol-substituted β-pyrrolidinyl-γ-allyloxyl-α,β-unsaturated esters: total synthesis of (+)-eldanolide

The asymmetric [2,3]-Wittig rearrangement of the dienolates of various chiral β-pyrrolidinyl-γ-allyloxyl-α,β-unsaturated esters was investigated using different chiral secondary alcohol substitutions. When (1S,2R,4R)-2-hydroxy-7,7-dimethylbicyclo[2,2,1]heptane-1-carboxylic acid diisopropylamide was used as chiral auxiliary, it provided the best enantioselectivity in the rearrangement. When various γ-allyloxy substitutions underwent temperature and additive studies, 1,1-dimethylpropenoxy substitution was found to give the best enantioselectivity. The methodology was applied to the total synthesis of (+)-eldanolide.     

Preparation and evaluation of a new synthetic polymeric chiral stationary phase for HPLC based on the trans-9,10-dihydro-9,10-ethanoanthracene-(11S,12S)-11,12-dicarboxylic acid bis-4-vinylphenylamide monomer

A new synthetic polymeric chiral stationary phase for liquid chromatography was prepared via free-radical-initiated polymerization of trans-9,10-dihydro-9,10-ethanoanthracene-(11S,12S)-11,12-dicarboxylic acid bis-4-vinylphenylamide. The new polymeric chiral stationary phase (CSP) showed enantioselectivity for many chiral compounds in multiple mobile phases. High stability and sample capacities were observed on this polymeric chiral stationary phase. Mobile phase components and additives affected chiral separation greatly. This new synthetic chiral stationary phase is complementary to two other related commercially available CSPs: the P-CAP and P-CAP-DP columns. Interactions between the chiral stationary phase and analytes that lead to retention and chiral recognition include hydrogen bonding, dipolar, and π–π interactions. Repulsive (steric) interactions also contribute to chiral recognition. Figure LC chromatograms showing the analytical (blue) and preparative (red) separations of N-(3,5-dinitrobenzoylleucine) enantiomers on a new synthetic polymeric chiral stationary phase     

Chiral differentiation of some cyclic β‐amino acids by kinetic and fixed ligand methods

Differentiation of β ‐amino acid enantiomers with two chiral centres was investigated by kinetic method with trimeric metal‐bound complexes. Four enantiomeric pairs of β ‐amino acids were studied: cis‐(1R,2S)‐, cis‐(1S,2R)‐, trans‐(1R,2R)‐ and trans‐(1S,2S)‐2‐aminocyclopentanecarboxylic acids (cyclopentane β ‐amino acids), and cis‐(1R,2S)‐, cis‐(1S,2R)‐, trans‐(1R,2R)‐, and trans‐(1S,2S)‐2‐aminocyclohexanecarboxylic acids (cyclohexane β ‐amino acids). The results showed that the choice of metal ion (Cu²⁺, Ni²⁺) and chiral reference compound (α‐ and β ‐amino acids) had an effect on the enantioselectivity. Especially, aromaticity of the reference compound was noted to enhance the enantioselectivity. The fixed‐ligand kinetic method, a modification of the kinetic method, was then applied to the same β ‐amino acids, with dipeptides used as fixed ligands. With this method, dipeptide containing an aromatic side chain enhanced the enantioselectivity. Copyright © 2009 John Wiley & Sons, Ltd.     

Cyclodextrins as chiral stationary phases in capillary gas chromatography. Part VI: Octakis (2,3,6-tri-O-pentyl)-γ-cyclodextrin

Perpentylated γ-cyclodextrin is a very hydrophobic liquid which exhibits enantioselectivity toward a number of non-polar chiral substrates including the saturated hydrocarbons cis- and trans-pinane, β-chiral olefins, iron(O) tricarbonyl complexes of prochiral olefins and 3,3,8,8-tetramethyl-trans-cyclooctene, a compound with planar chirality.     

On the Enantioselectivity of Transition Metal‐Catalyzed 1,3‐Cycloadditions of 2‐Diazocyclohexane‐1,3‐diones

The formal 1,3‐cycloaddition of 2‐diazocyclohexane‐1,3‐diones 1a –1 d to acyclic and cyclic enol ethers in the presence of Rh^II‐catalysts to afford dihydrofurans has been investigated. Reaction with a cis/trans mixture of 1‐ethoxyprop‐1‐ene ( 13a ) yielded the dihydrofuran 14a with a cis/trans ratio of 85 : 15, while that with (Z)‐1‐ethoxy‐3,3,3‐trifluoroprop‐1‐ene ( 13b ) gave the cis‐product 14b exclusively. The stereochemical outcome of the reaction is consistent with a concerted rather than stepwise mechanism for cycloaddition. The asymmetric cycloaddition of 2‐diazocyclohexane‐1,3‐dione ( 1a ) or 2‐diazodimedone (=2‐diazo‐5,5‐dimethylcyclohexane‐1,3‐dione; 1b ) to furan and dihydrofuran was investigated with a representative selection of chiral, nonracemic Rh^II catalysts, but no significant enantioselectivity was observed, and the reported enantioselective cycloadditions of these diazo compounds could not be reproduced. The absence of enantioselectivity in the cycloadditions of 2‐diazocyclohexane‐1,3‐diones is tentatively explained in terms of the Hammond postulate. The transition state for the cycloaddition occurs early on the reaction coordinate owing to the high reactivity of the intermediate metallocarbene. An early transition state is associated with low selectivity. In contrast, the transition state for transfer of stabilized metallocarbenes occurs later, and the reactions exhibit higher selectivity.     

手性邻二醇－－（2S，3R）－1，2，3－丁三醇－1－对甲苯磺酸酯的不对称合成

以（E）－2－丁烯－1－醇为原料经不对称环氧化反应合成2，3－环氧醇（1） 。该环氧醇的对甲苯磺酸酯对映选择性酸水解开环制备手性邻二醇（2）(95％ee)。     

Chiral Cooperativity: The Effect of Distant Chiral Centers in Ferrocenylamine Ligands upon Enantioselectivity in the Gold(I)-Catalyzed Aldol Reaction

Long-range chiral cooperativity in enantiomerically pure ferrocenylamine ligands containing both planar and multiple centers of chirality (multiple stereogenic C-atoms) was demonstrated in the Au^I-catalyzed reaction of aldehydes and isocyanoesters. Synthetic methodology was developed for the synthesis of ferrocenylamine ligands with two and three chiral centers of known absolute configuration in the C-side chain in addition to the planar chirality of the molecule. The diastereo- and enantioselectivity of the Au^I-catalyzed formation of the trans- and cis-dihydrooxazoles 5 and 6 , respectively, from benzaldehyde ( 1 ) and methyl isocyanoacetate ( 2 ) depend upon the sequence of chirality (absolute configuration of the chiral centers) in the side chain of the ferrocenylamine ligands. Particularly significant effects were observed upon the enantioselectivity for the minor cis-dihydrooxazole 6 , for which, in certain cases, resulted in a change in the enantiomeric dihydrooxazole 6 produced in excess with a change in the absolute configuration of a distant chiral center. Significant effects upon diastereo- and enantioselectivity were observed when chiral ferrocenylamine ligands containing free OH groups were utilized. Using ligands containing a free OH group gave 6 with an absolute configuration opposite to that produced by the corresponding ester and carbamate derivatives. The possible mechanisms for the transmission of chiral information in the proposed stereoselective transition state (TS) was discussed, including both the formation of a stereogenic N-atom and steric effects based upon Newman's rule of six.     

Optically-active polyurethanes containing coumarin dimer component: Synthesis,characterization, and chiral recognition ability

Optically-active polyurethanes ( 2a-2c ) were prepared by polyaddition reaction of diamide ( 1a, 1b ) and diester ( 1c ) derivatives of chiral coumarin dimer with 4,4′-diphenylmethane diisocyanate (MDI) in chloroform and methyl ethyl ketone, respectively. The inherent viscosity of the polyurethanes are between 0.13 and 0.21 dL/g in N,N-dimethylacetamide (DMAc) at 30°C. Treated silica gels were absorbed with ca. 25 wt % of the polyurethanes, and packed as chiral stationary phases for direct optical resolution of 16 racemates with aromatic groups by high-performance liquid chromatography (HPLC). Polyurethanes 2a and 2b , obtained from diamide derivatives, show efficient resolution ability to some of the racemates (α = 1.06-1.79), especially the atropic ( R5 ) and trans ( R6-R9 ) isomers. The recognition ability of the polyurethanes can be attributed to the simultaneous aromatic stacking and hydrogen-bonding interactions with racemates. © 1992 John Wiley & Sons, Inc.     

Enantioselective addition of diethylzinc to aryl aldehydes catalyzed by novel chiral imino alcohol ligands

The enantioselective alkylation of aryl aldehydes by diethylzinc in the presence of catalytic amounts of several novel chiral imino alcohol ligands, synthesized from the reaction of (R)-2-amino-1-butanol with aromatic aldehydes, was studied. The influence of temperature and ligand structure was investigated and enantioselectivity up to 81% was obtained.     

Enantioselective Synthesis of Complex Fused Heterocycles through Chiral Phosphoric Acid Catalyzed Intramolecular Inverse-Electron-Demand Aza-Diels–Alder Reactions

A stable asymmetric intramolecular Povarov reaction has been established to provide an efficient method to access structurally diverse trans,trans-trisubstituted tetrahydrochromeno[4,3-b]quinolines in high stereoselectivities of up to >99:1 diastereomeric ratio and 99 % enantiomeric excess, without any purification step. Additionally, to facilitate large-scale application of this method, a low catalyst loading protocol was employed, 0.2 mol % chiral phosphoric acid, which provided the cycloadducts without any loss in yield and enantioselectivity. Theoretical studies revealed that the reaction occurred through a sequential Mannich reaction and an intramolecular Friedel–Crafts reaction, wherein the phosphoric acid acted as a bifunctional catalyst to activate the para-phenolic dienophile and N-2-hydroxy-2-azadiene simultaneously.     

盐酸(R)-沙丁胺醇的不对称合成

研究了一种化学不对称合成盐酸(R)-沙丁胺醇的方法. 以自制的手性龙脑基β-二酮铁络合物为催化剂催化起始原料3-乙酰氧基甲基-4-乙酰氧基苯乙烯(1)的不对称环氧化, 得到(R)-3-乙酰氧基甲基-4-乙酰氧基苯基环氧乙烷(2), 这一步的化学收率和光学收率都较高. 然后环氧化合物2与叔丁胺发生开环反应, 再与盐酸成盐即制得盐酸(R)-沙丁胺醇. 合成盐酸(R)-沙丁胺醇只需两步, 总收率为68%. 还考察了反应温度、催化剂种类、催化剂的量等因素对3-乙酰氧基甲基-4-乙酰氧基苯乙烯(1)的不对称环氧化的化学产率和光学收率的影响.     

Synthesis of polymer microspheres functionalized with chiral ligand by precipitation polymerization and their application to asymmetric transfer hydrogenation

Monodisperse, crosslinked poly(divinylbenzene) and poly(methacrylic acid‐co‐ethylene glycol dimethacrylate) microspheres with (1R,2R)‐N¹‐toluenesulfonyl‐1,2‐diphenylethylene‐1,2‐diamine ((R,R)‐TsDPEN) moiety were successfully prepared by precipitation polymerization. Introduction site of the (R,R)‐TsDPEN moiety into the polymer microspheres could be controlled by changing the order of addition of the corresponding monomers. The functionalized polymer microspheres were applied to asymmetric transfer hydrogenation of ketone and imine. Polymer microsphere‐supported chiral catalysts showed good reactivity and enantioselectivity in the catalytic asymmetric transfer hydrogenations. Chiral secondary alcohol was quantitatively obtained with 94% ee in the asymmetric transfer hydrogenation of acetophenone in water. We also found that introduction site of the chiral catalyst and hydrophobicity of the microspheres, as well as degree of the crosslinking, affected the yield and enantioselectivity of chiral product in this reaction. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3340–3349, 2010     

Asymmetric Hydrogenation of Azaindoles: Chemo‐ and Enantioselective Reduction of Fused Aromatic Ring Systems Consisting of Two Heteroarenes

High enantioselectivity was achieved for the hydrogenation of azaindoles by using the chiral catalyst, which was prepared from [Ru(η³‐methallyl)₂(cod)] and a trans‐chelating bis(phosphine) ligand (PhTRAP). The dearomative reaction exclusively occurred on the five‐membered ring, thus giving the corresponding azaindolines with up to 97:3 enantiomer ratio.     

Enantiomerically Pure Cyclic trans-1,2-Diols,Diamines, and Amino Alcohols by Intramolecular Pinacol Coupling of Planar Chiral Mono-Cr(CO)3 Complexes of Biaryls

Without any formation of stereoisomers , the intramolecular pinacol cyclization of 1 —planar chiral mono-Cr(CO)₃ complexes of 1,1′-biphenyls with carbonyl functionalities at the 2- and 2′-positions—with samarium diiodide gives cyclic trans-1,2-diols 2 . Upon exposure to sunlight, the chromium-complexed diols 2 produce optically pure chromium-free trans-diols 3 . Similarly, the corresponding enantiomerically pure trans-1,2-diamines and amino alcohols are obtained from the planar chiral chromium complexes of biphenyls with diimino or keto-imino functionalities. R¹=H, OMe; R²=H, Me; R³=H, Me.