Crystalline Hetero‐Stereocomplexed Polycarbonates Produced from Amorphous Opposite Enantiomers Having Different Chemical Structures

Stereocomplexation is the stereoselective interaction between two opposite enantiomeric polymers through an interlocked orderly assembly. Most studies focus on the stereocomplex formation from the crystalline opposite enantiomers having the identical structure; nevertheless, rare examples were reported regarding the crystalline stereocomplexes from enantiomeric polymers having different chemical structures. Herein we show a strategy for polymer orderly assembly through the formation of crystalline hetero‐stereocomplexed polymeric materials by the cocrystallization of amorphous isotactic polycarbonates with different chemical structures and opposite configurations. The behaviors in the crystalline state are significantly different from that of the component enantiomeric polymers or their homo‐stereocomplexes. This study is expected to open up a new way to prepare various semicrystalline materials having a wide variety of physical properties and degradability.     

In Situ Mass Spectrometric and Kinetic Investigations of Soai's Asymmetric Autocatalysis

Chemical reactions that lead to a spontaneous symmetry breaking or amplification of the enantiomeric excess are of fundamental interest in explaining the formation of a homochiral world. An outstanding example is Soai's asymmetric autocatalysis, in which small enantiomeric excesses of the added product alcohol are amplified in the reaction of diisopropylzinc and pyrimidine-5-carbaldehydes. The exact mechanism is still in dispute due to complex reaction equilibria and elusive intermediates. In situ high-resolution mass spectrometric measurements, detailed kinetic analyses and doping with in situ reacting reaction mixtures show the transient formation of hemiacetal complexes, which can establish an autocatalytic cycle. We propose a mechanism that explains the autocatalytic amplification involving these hemiacetal complexes. Comprehensive kinetic experiments and modelling of the hemiacetal formation and the Soai reaction allow the precise prediction of the reaction progress, the enantiomeric excess as well as the enantiomeric excess dependent time shift in the induction period. Experimental structural data give insights into the privileged properties of the pyrimidyl units and the formation of diastereomeric structures leading to an efficient amplification of even minimal enantiomeric excesses, respectively.     

Enol ethers as substrates for efficient Z- and enantioselective ring-opening/cross-metathesis reactions promoted by stereogenic-at-Mo complexes: utility in chemical synthesis and mechanistic attributes

The first examples of catalytic enantioselective ring-opening/cross-metathesis (EROCM) reactions that involve enol ethers are reported. Specifically, we demonstrate that catalytic EROCM of several oxa- and azabicycles, cyclobutenes and a cyclopropene with an alkyl- or aryl-substituted enol ether proceed readily in the presence of a stereogenic-at-Mo monopyrrolide-monoaryloxide. In some instances, as little as 0.15 mol % of the catalytically active alkylidene is sufficient to promote complete conversion within 10 min. The desired products are formed in up to 90% yield and >99:1 enantiomeric ratio (er) with the disubstituted enol ether generated in >90% Z selectivity. The enol ether of the enantiomerically enriched products can be easily differentiated from the terminal alkene through a number of functionalization procedures that lead to the formation of useful intermediates for chemical synthesis (e.g., efficient acid hydrolysis to afford the enantiomerically enriched carboxaldehyde). In certain cases, enantioselectivity is strongly dependent on enol ether concentration: larger equivalents of the cross partner leads to the formation of products of high enantiomeric purity (versus near racemic products with one equivalent). The length of reaction time can be critical to product enantiomeric purity; high enantioselectivity in reactions that proceed to >98% conversion in as brief a reaction time as 30 s can be nearly entirely eroded within 30 min. Mechanistic rationale that accounts for the above characteristics of the catalytic process is provided.     

New enantiomeric polylactide-block-poly(butylene succinate)-block-polylactides: syntheses, characterization and in situ self-assembly

In situ self-assemblies of new biodegradable triblock PLLA-b-PBS-b-PLLA and PDLA-b-PBS-b-PDLA have been investigated in acetonitrile solution. At first, two series of PLLA-b-PBS-b-PLLA and PDLA-b-PBS-b-PDLA, respectively denoted as the P and Q triblock copolyester series, were prepared with fixed PBS block ((overline) M(n,NMR) = 6.9 kDa) and diverse enantiomeric PLLA/PDLA blocks. Further, their chemical structures and thermal properties were characterized by means of titration, nuclear magnetic resonance spectroscopy (NMR), gel permeation chromatography (GPC), polarimeter, wide-angle X-ray diffraction (WAXD) and thermal analytical instruments. When mixing the synthesized enantiomeric copolyester pairs denoted as P(1)/Q(1) - P(8)/Q(8) in acetonitrile solution at 60 degrees C, in situ self-assemblies were found to happen for the P(4)/Q(4) to P(8)/Q(8) pairs, bearing longer enantiomeric PLA block lengths. DSC and WAXD analysis of the self-assembled microparticles demonstrated that PLLA/PDLA racemic crystals were formed for the P(5)/Q(5) - P(8)/Q(8) systems, as evidenced by their melting points over 200 degrees C, and a new X-ray diffraction peak detected at 2theta = 11.8 degrees . Moreover, morphological studies by scanning electron microscopy (SEM) indicated the formation of disk- or platelet-like microparticles. It was noted that the diameters of the microparticles self-assembled in situ decreased from 1.28-1.50 mum down to 480-660 nm, through tailoring the enantiomeric PLA block length. Other factors, such as a central PBS block, the enantiomeric block length and the preparation conditions were suggested to play important roles in the in situ self-assembly of these enantiomeric triblock copolyesters. These results provide a facile way to self-assemble hydrophobic, biodegradable microparticles, through tuning the important van der Waals stereocomplexation interactions between two enantiomeric blocks in solution.     

Self-sorting in rodlike micelles of chiral bisurea bolaamphiphiles

We have demonstrated the formation of segregated enantiomeric dynamic rods in water, from the self-sorting of chiral trans-1,2-bisureido cyclohexane-based bolaamphiphiles. Fluorescence probes have been used to investigate the self-sorting through forming exciplex and FRET.     

"Click" post-synthetic modification of metal-organic frameworks with chiral functional adduct for heterogeneous asymmetric catalysis

Two enantiomeric Zn-MOFs, having l- or d-proline chiral functionality, were achieved through in situ click reactions by modifying two opposite chiral adducts within the same pre-assembled achiral MOFs, respectively. Both of them exhibited remarkable catalytic activities in the relative asymmetric aldol reactions, and led to the formation of opposite enantiomorphs. The significant advantage of this approach not only includes the conversion of chemically and thermally robust MOFs into enantiomeric chiral material having catalytically active sites, but also involves the potential applications in asymmetric transformations with desirable chiralities of a special enantiomorph.     

Horeau's Coupling of Enantiomers Revisited. The Reversible Coupling of Enantiomers to Form Diastereoisomers in Kinetically Labile Metal Complexes

Pairs of enantiomeric molecules (??,??) of a substrate of unknown, but incomplete enantiomeric purity may be coupled to each other through labile coordination to a metal center M. This results in the formation of an equilibrium mixture of diastereoisomeric complexes, viz. meso-L_nM????(=m) and a pair of enantiomers L_nM???? and L_nM????(= e), where L is an achiral auxiliary ligand. General expressions are presented for determining the ratio of enantiomers [??]₀/[??]₀ from experimental parameters, which may be obtained from NMR measurements. Effects of diastereoselectivity are specifically considered. Limiting cases (nearly pure or nearly racemic substrates, very high or no diastereoselectivity, very large or no excess of free substrate) are discussed. The cases of additional diastereoisomerism owing to different coordination geometries and of the formation of complexes with more than two substrate molecules per metal center are also investigated. The results presented can not only be used for determining the enantiomeric excess but also for designing optimal strategies for the successive resolution of partly enriched samples.     

Supercritical fluid extraction: a novel method for the resolution of tetramisole

A new resolution method, based on the selective distribution of enantiomers between a chiral solid and an achiral supercritical fluid phase, is reported. The chiral solid phase is formed from the optically active dicarboxylic acid derivative, (2R,3R)-O,O′-dibenzoyltartaric acid, and the racemic base (tetramisole). A new method is also described for the enrichment of enantiomeric mixtures which have an enantiomeric ratio other than 1:1. This is based on the partial salt formation of the enantiomeric mixture with an achiral substance, which is then followed by supercritical fluid extraction of the free enantiomer. The extract has an enantiomeric composition which is different from the starting mixture. The method is applied to an enantiomeric mixture of tetramisole with hydrochloric acid.     

Azithromycin as a new chiral selector in capillary electrophoresis

In capillary electrophoresis (CE), separation of enantiomers of a chiral compound can be achieved through the chiral interactions and/or complex formation between the chiral selector and the enantiomeric analytes on leaving their diastereomeric forms with different stability constants and hence different mobilities. A great number of chiral selectors have been employed in CE and among them macrocyclic antibiotics exhibited excellent enantioselective properties towards a wide number of racemic compounds. The use of azithromycin (AZM) as a chiral selector has not been reported previously. This work reports the use of AZM as a chiral selector for the enantiomeric separations of five chiral drugs and one amino acid (tryptophan) in CE. The enantioseparation is carried out using polar organic mixtures of acetonitrile (ACN), methanol (MeOH), acetic acid and triethylamine as run buffer. The influences of the chiral selector concentration, ACN/MeOH ratio, applied voltage and capillary temperature on enantioseparation are investigated. The results show that AZM is a viable chiral selector in CE for the enantioseparation of the type of chiral drugs investigated.     

Determination of the enantiomeric excess of ferroelectric liquid crystals derived from three natural amino acids

The synthesis and 1H NMR spectra are presented for diastereoisomeric esters based on chiral alpha-chloro acids which are derived from natural available alpha-amino acids (L-valine, L-leucine and L-isoleucine) and commonly employed for the synthesis of ferroelectric liquid crystals possessing a high spontaneous polarization. Partial racemization is established as occurring within the formation of the chiral alpha-chloro acids and their esterification procedure. The enantiomeric excess exceeds 90% for L-isoleucine and L-valine derivatives, whereas an enantiomeric excess of 60% is found for L-leucine derivatives. On the basis of existing data in the literature, the differences in the spontaneous polarization of these derivatives is discussed with regard to the determined enantiomeric excess and their conformational freedom affecting the average lateral dipole moment of a single molecule.     

Enantiomeric separation of halocarboxylic acids by capillary gas chromatography

The direct determination of the enantiomeric purity of halocarboxylic acids is described. The method used involves gas chromatographic separation of the corresponding tert-butylamides on deactivated glass or fused-silica capillaries coated with Chirasil-Val. Both the influence of the amide moiety on enantiomeric resolution and tailing, and the racemization during formation of the amide derivatives were studied.     

Chiral enrichment of serine via formation,dissociation, and soft-landing of octameric cluster ions

Chiral enrichment of serine is achieved in experiments that involve formation of serine octamers starting from non-racemic serine solutions. Serine octamers were generated by means of electrospray and sonic spray ionization of aqueous solutions of d(3)-L-serine (108 Da) and D-serine (105 Da) having different molar ratios of enantiomers. A cyclic process involving the formation of chirally-enriched octameric cluster ions and their dissociation, viz. Ser(1) --> Ser(8) --> Ser(1), allows serine monomers to be regenerated with increased enantiomeric excess as shown in two types of experiments: (1) Chiral enrichment in serine was observed in MS/MS/MS experiments in a quadrupole ion trap in which the entire distribution of serine octamers formed from non-racemic solutions was isolated, collisionally activated, and fragmented. Monomeric serine was regenerated with increased enantiomeric excess upon dissociation of octamers when compared with the enantiomeric composition of the original solution. (2) Chiral enrichment was observed in the products of soft-landing of mass-selected protonated serine octamers. These ions were generated by means of electrospray or sonic spray ionization, mass selected, and collected on a gold surface using ion soft-landing. Chiral enrichment of the soft-landed serine was established by redissolving the recovered material and comparing the intensities of protonated molecular ions of d(3)-L-serine and D-serine after APCI-MS analysis. Both of these experiments showed comparable results, suggesting that formation of serine octamers depends only on the enantiomeric composition of the serine solution and that the magnitude of the chiral preference is intrinsic to octamers formed from solutions of given chiral composition.     

Steric and electronic effects in the resolution of enantiomeric amides on a commercially available Pirkle-type high-performance liquid chromatographic chiral stationary phase

The steric and electronic effects in the resolution of enantiomeric amides on a commercially available (R)-N-(3,5-dinitrobenzoyl)phenylglycine chiral stationary phase (CSP) have been investigated. Several homologous series of enantiomeric amides were synthesized from alkyl and aromatic amines and from alkyl and aromatic acids. The results of the study indicate that chiral recognition is based on the formation of diastereomeric solute-CSP complexes that are due to attractive interactions located on a single bond in both the solute and CSP and on steric interactions within the complexes. The magnitude of the chiral resolution appears to depend on the steric bulk at the chiral center. In addition, when the amides synthesized from chiral amines were chromatographed, the (R)-enantiomers eluted first, whereas the opposite elution order was found for the amides synthesized from enantiomeric carboxylic acids. Thus, the amide moiety not only provides the sites of attractive interaction between the solute and CSP, but also influences the spatial orientation of the two molecules, thereby affecting the relative stabilities of the two diastereomeric complexes and determining the enantiomeric elution order.     

Asymmetric synthesis of 1,3-oxathiolan-5-one derivatives through dynamic covalent kinetic resolution

The asymmetric synthesis of 1,3-oxathiolan-5-one derivatives through an enzyme-catalyzed, dynamic covalent kinetic resolution strategy is presented. Dynamic hemithioacetal formation combined with intramolecular, lipase-catalyzed lactonization resulted in good conversions with moderate to good enantiomeric excess (ee) for the final products. The process was evaluated for different lipase preparations, solvents, bases, and reaction temperatures, where lipase B from Candida antarctica (CAL-B) proved most efficient. The substrate scope was furthermore explored for a range of aldehyde structures, together with the potential access to nucleoside analog inhibitor core structures.     

Carbon-carbon bond-forming enantioselective synthesis of chiral organosilicon compounds by rhodium/chiral diene-catalyzed asymmetric 1,4-addition reaction

[reaction: see text] A new synthetic method for chiral organosilicon compounds through a rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to beta-silyl alpha,beta-unsaturated carbonyl compounds has been developed. By employing (R,R)-Bn-bod* as a ligand, a range of arylboronic acids can be coupled with these substrates in very high enantiomeric excess. The resulting beta-silyl 1,4-adducts can be converted to beta-hydroxy carbonyl compounds or allylsilanes while retaining their stereochemical information.     

二乙酰酒石酸酐柱前手性衍生化反相高效液相色谱法拆分心得安对映体

以（Ｒ，Ｒ）－Ｏ，Ｏ－二乙酰基酒石酸酐作柱前手性衍生化试剂，用ＯＤＳ柱拆分了心得安对映体，探讨了衍生化反应条件，研究了ＰＨ及流动相组成对色谱保留行为的影响，发现心得安的两种非对映异构体衍生物的荧光响应有显著差别，对心得安对映体的半制备色谱拆分规律作了新的探讨，确定用Ｓｈｉｍ－ｐａｃｋＣＬＣ－ＯＤＳ柱进行半制备色谱拆分的最佳条件，得到的光学异构体纯度在９９％以上。     

Self-assembly of copper(II) ion-mediated nanotube and its supramolecular chiral catalytic behavior

Self-assembly of several low-molecular-weight L-glutamic acid-based gelators, which individually formed helical nanotube or nanofiber structures, was investigated in the presence of Cu(2+) ion. It was found that, when Cu(2+) was added into the system, the self-assembly manner changed significantly. Only in the case of bolaamphiphilic glutamic acid, N,N'-hexadecanedioyl-di-L-glutamic acid (L-HDGA), were the hydrogel formation as well as the nanotube structures maintained. The addition of Cu(2+) ion caused a transition from monolayer nanotube of L-HDGA to a multilayer nanotube with the thickness of the tubular wall about 10 nm. For the other amphiphiles, the gel was destroyed and nanofiber structures were mainly formed. The formed Cu(2+)-containing nanostructures can function as an asymmetric catalyst for Diels-Alder cycloaddition between cyclopentadiene and aza-chalcone. In comparison with the other Cu(2+)-containing nanostructures, the Cu(2+)-mediated nanotube structure showed not only accelerated reaction rate, but enhanced enantiomeric selectivity. It was suggested that, through the Cu(2+) mediated nanotube formation, the substrate molecules could be anchored on the nanotube surfaces and produced a stereochemically favored alignment. When adducts reacted with the substrate, both the enantiomeric selectivity and the reaction rate were increased. Since the Cu(2+)-mediated nanotube can be fabricated easily and in large amount, the work opened a new way to perform efficient chiral catalysis through the supramolecular gel.     

The separation of racemic crystals into enantiomers by chiral block copolymers

A series of chiral double hydrophilic block copolymers (DHBCs) was synthesized and employed as additives in the crystallization of calcium tartrate tetrahydrate (CaT). We found that appropriate polymers can slow down the formation of the thermodynamically most stable racemic crystals as well as the formation of one of the pure enantiomeric crystals so that chiral separation by crystallization occurs even when racemic crystals can be formed. In addition, the presence of DHBCs results in major modifications of crystal morphology, creating unusual morphologies of higher complexity. Our study demonstrates the potential application of chiral DHBCs in the control of chirality throughout crystallization, in particular for racemic crystal systems, and also shows that enantiomeric excess of one enantiomer can be maximized by the kinetic control of crystallization.     

Reactive extraction of enantiomers of 1,2-amino alcohols via stereoselective thermodynamic and kinetic processes

(R)-amino alcohol with an enantiomeric excess of >95% was resolved by reactive extraction processes from 2 equiv of racemic alcohol using a chiral receptor 2 as an enantioselective extractant. One resolution cycle is composed of three extractions: a stereoselective reversible imine formation, a stereoselective irreversible imine hydrolysis, and the recovery of 2 and enantiomeric amino alcohols.