Enzyme‐Inspired Chiral Secondary‐Phosphine‐Oxide Ligand with Dual Noncovalent Interactions for Asymmetric Hydrogenation

Inspired by the unique character of enzymes, we developed novel chiral SPO (secondary‐phosphine‐oxide) ligand (SPO‐Wudaphos) which can enter into both ion pair and H‐bond noncovalent interactions. The novel chiral SPO‐Wudaphos exhibited excellent results in the asymmetric hydrogenation of α‐methylene‐γ‐keto carboxylic acids, affording the chiral γ‐keto acids with up to over 99 % ee . A series of control experiments and DFT calculations were conducted to illustrate the critical roles of both the ion pair and H‐bond noncovalent interactions.     

Dynamic-to-Static Planar Chirality Conversion in Pillar[5]arenes Regulated by Guest Solvents or Amplified by Crystallization

Controlling dynamic chirality and memorizing the controlled chirality are important. Chirality memory has mainly been achieved using noncovalent interactions. However, in many cases, the memorized chirality arising from noncovalent interactions is erased by changing the conditions such as the solvent and temperature. In this study, the dynamic planar chirality of pillar[5]arenes was successfully converted into static planar chirality by introducing bulky groups through covalent bonds. Before introducing the bulky groups, pillar[5]arene with stereogenic carbon atoms at both rims existed as a pair of diastereomers, and thus showed planar chiral inversion that was dependent on the chain length of the guest solvent. The pS and pR forms, regulated by guest solvents, were both diastereomerically memorized by introducing bulky groups. Furthermore, the diastereomeric excess was amplified by crystallization of the pillar[5]arene. The subsequent introduction of bulky groups yielded pillar[5]arene with an excellent diastereomeric excess (95 % de).     

Bifunctional Ion Pair Catalysts from Chiral α‐Amino Acids

Asymmetric ion pair catalysis presents a powerful strategy for the construction of chiral molecules. However, the ion‐pair interactions are weakly directional and result in difficultly controlling the conformational constraint for high stereo‐ inductions. Based on the hydrogen bonding interactions, we have successfully designed and synthesized a new family of bifunctional ion pair catalysts derived from chiral amino acids via simple operations. With these chiral ammonium salts and phosphonium salts in hand, the enantioselective construction of C—C and C—X bonds was realized in our lab.     

Temperature‐Induced Chiroptical Changes in a Helical Poly(phenylacetylene) Bearing N,N‐Diisopropylaminomethyl Groups with Chiral Acids in Water

A stereoregular poly(phenylacetylene) bearing an N,N‐diisopropylaminomethyl group as the pendant (poly‐ 1 ) changed its structure into the prevailing one‐handed helical conformation upon complexation with optically active acids in water. The complexes exhibited induced circular dichroism (ICD) in the UV/Vis region of the polymer backbone. Poly‐ 1 is highly sensitive to the chirality of chiral acids and can detect a small enantiomeric imbalance in these acids, in particular, phenyl lactic acid in water. For example, a 0.005 % enantiomeric excess of phenyl lactic acid can be detected by CD spectroscopy. The observed ICD intensity and pattern of poly‐ 1 were dependent on the temperature and concentration of poly‐ 1 , probably due to aggregations of the polymer at high temperature as revealed by dynamic light scattering and AFM. On the basis of the temperature‐dependent ICD changes, the preferred chiral helical sense of poly‐ 1 was found to be controlled by noncovalent bonding interactions by using structurally different enantiomeric acids.     

Synthesis of chiral 5-aryltetrahydrofuran-2-ones via yeast bioreduction of γ-keto acids and their esters

Enantioselective reduction of γ-keto acids and related γ-keto esters with Saccharomyces cerevisiae (baker’s yeast) leads to the formation of the corresponding chiral 5-aryltetrahydrofuran-2-ones in satisfactory chemical and optical yields. Published in Zhurnal Organicheskoi Khimii, 2006, Vol. 42, No. 3, pp. 379–382. The text was submitted by the authors in English.     

Influence of halogenation on the properties of uracil and its noncovalent interactions with alkali metal ions. Threshold collision-induced dissociation and theoretical studies

The influence of halogenation on the properties of uracil and its noncovalent interactions with alkali metal ions is investigated both experimentally and theoretically. Bond dissociation energies of alkali metal ion-halouracil complexes, M+(XU), are determined using threshold collision-induced dissociation techniques in a guided ion beam mass spectrometer, where M+ = Li+, Na+, and K+ and XU = 5-fluorouracil, 5-chlorouracil, 6-chlorouracil, 5-bromouracil, and 5-iodouracil. The structures and theoretical bond dissociation energies of these complexes are determined from ab initio calculations. Theoretical calculations are also performed to examine the influence of halogenation on the acidities, proton affinities, and Watson-Crick base pairing energies. Halogenation of uracil is found to produce a decrease in the proton affinity, an increase in the alkali metal ion binding affinities, an increase in the acidity, and stabilization of the A::U base pair. In addition, alkali metal ion binding is expected to lead to an increase in the stability of nucleic acids by reducing the charge on the nucleic acid in a zwitterion effect as well as through additional noncovalent interactions between the alkali metal ion and the nucleobases.     

A family of single-isomer positively charged cyclodextrins as chiral selectors for capillary electrophoresis: mono-6A-butylammonium-6A-deoxy-beta-cyclodextrin tosylate

A novel single-isomer positively charged beta-cyclodextrin (beta-CD), mono-6(A)-butylammonium-6(A)-deoxy-beta-cyclodextrin tosylate (BuAM-beta-CD), has been synthesized, characterized, and used for the enantioseparations of alpha-hydroxy acids, carboxylic acids, and ampholytic analytes by capillary electrophoresis in acidic aqueous background electrolytes. The effective mobilities of all studied analytes decreased with increasing concentration of CD. Satisfactory resolutions were obtained for alpha-hydroxy acids over a wide range of chiral selector concentration. The optimum CD concentration was lower than 5 mM for the carboxylic acids, while higher than 20 mM for alpha-hydroxy acids. Inclusion complexation in combination with ion pair interaction seemed to account for the chiral discrimination process. The hydrogen bonding may provide secondary contribution for the chiral resolution of alpha-hydroxy acids. In addition, BuAM-beta-CD was further proved to be an effective chiral selector for anionic analytes by the baseline enantioseparation of a six-acid mixture within 20 min.     

Supramolecular helical mesomorphic polymers. Chiral induction through H-bonding

The work described here concerns a challenge of general interest in supramolecular chemistry: the achievement of chiral helical organizations with controlled structures. This work provides a strategy to obtain supramolecular polymers in which a chiral helical conformation has been induced by a noncovalent association, that is, through hydrogen bonding. Polycatenar 2,4,6-triarylamino-1,3,5-triazines, which organize into columnar mesophases and are susceptible to H-bonding interactions, were chosen as a starting point to build up the chiral supramolecular structure. The stacking of these mesogens has been forced to wind in a helical way by means of H-bond association with (R)-3-methyladipic acid, within the mesophase. The optically active columnar organization has been studied in depth by optical microscopy, differential scanning calorimetry (DSC), X-ray diffraction, and circular dichroism. Formation of stable complexes between the triazine units and (R)-3-methyladipic acid has also been investigated by means of NMR diffusion-ordered spectroscopy (DOSY) experiments in chloroform.     

Chiral ligand exchange countercurrent chromatography: Enantioseparation of amino acids

This work deals with the enantioseparation of α‐amino acids by chiral ligand exchange high‐speed countercurrent chromatography using N‐n‐dodecyl‐l ‐hydroxyproline as a chiral ligand and copper(II) as a transition metal ion. A biphasic solvent system composed of n‐hexane/n‐butanol/aqueous phase with different volume ratios was selected for each α‐amino acid. The enantioseparation conditions were optimized by enantioselective liquid–liquid extractions, in which the main influence factors, including type of chiral ligand, concentration of chiral ligand and transition metal ion, separation temperature, and pH of the aqueous phase, were investigated for racemic phenylalanine. Altogether, we tried to enantioseparate 15 racemic α‐amino acids by the analytical countercurrent chromatography, of which only five of them could be successfully enantioseparated. Different elution sequence for phenylalanine enantiomer was observed compared with traditional liquid chromatography and the proposed interactions between chiral ligand, transition metal ion (Cu²⁺), and enantiomer are discussed.     

Enantioselective Catalysis of the Intermolecular [2+2] Photocycloaddition between 2‐Pyridones and Acetylenedicarboxylates

Intermolecular [2+2] photocycloadditions represent the most versatile and widely applicable of photochemical reactions. For the first time, such intermolecular reactions have been carried out in a catalytic fashion using a chiral triplet sensitizer, with high enantioselectivity (up to 92 % ee). The low catalyst loading (2.5–5 mol %) underlines the high efficiency of the process both in terms of reaction acceleration and differentiation of the enantiotopic faces of the substrate. The substrate is anchored to the chiral catalyst through noncovalent interactions (hydrogen bonds), thus providing a chiral environment in which the enantioselective photocycloaddition proceeds. The densely functionalized products present numerous possibilities for further synthetic transformations.     

Axially Chiral Imidodiphosphoric Acid Catalyst for Asymmetric Sulfoxidation Reaction: Insights on Asymmetric Induction

Insights into chiral induction for an asymmetric sulfoxidation reaction involving a single oxygen atom transfer are gained through analyzing the stereocontrolling transition states. The fitting of the substrate into the chiral cavity of a new class of imidodiphosphoric Brønsted acids, as well as weak C H⋅⋅⋅π and C H⋅⋅⋅O noncovalent interactions, are identified as responsible for the observed chiral induction.     

Influence of thioketo substitution on the properties of uracil and its noncovalent interactions with alkali metal ions: threshold collision-induced dissociation and theoretical studies

Experimental and theoretical studies are carried out to determine the influence of thioketo substitution on the properties of uracil and its noncovalent interactions with alkali metal ions. Bond dissociation energies of alkali metal ion-thiouracil complexes, M(+)(SU), are determined using threshold collision-induced dissociation techniques in a guided ion beam mass spectrometer, where M(+) = Li(+), Na(+), and K(+) and SU = 2-thiouracil, 4-thiouracil, 2,4-dithiouracil, 5-methyl-2-thiouracil, and 6-methyl-2-thiouracil. Ab initio electronic structure calculations are performed to determine the structures and theoretical bond dissociation energies of these complexes and provide molecular constants necessary for thermodynamic analysis of the experimental data. Theoretical calculations are also performed to examine the influence of thioketo substitution on the acidities, proton affinities, and A::SU Watson-Crick base pairing energies. In general, thioketo substitution leads to an increase in both the proton affinity and the acidity of uracil. 2-Thio substitution generally results in an increase in the alkali metal ion binding affinities but has almost no affect on the stability of the A::SU base pair. In contrast, 4-thio substitution results in a decrease in the alkali metal ion binding affinities and a significant decrease in the stability of the A::SU base pair. In addition, alkali metal ion binding is expected to lead to an increase in the stability of both single-stranded and double-stranded nucleic acids by reducing the charge on the nucleic acid in a zwitterion effect as well as through additional noncovalent interactions between the alkali metal ion and the nucleobases.     

Synthesis of ionic liquids functionalized β-cyclodextrin-bonded chiral stationary phases and their applications in high-performance liquid chromatography

Four novel ILs functionalized β-cyclodextrins (β-CDs) were prepared by treating 6-tosyl-β-cyclodextrin with 1,2-dimethylimidazole or 1-amino-1,2,3-triazole, and bonded to silica gel to obtain chiral stationary phases (CSPs) to be used in high-performance liquid chromatography (HPLC). The separation performances of these CSPs were examined with 16 chiral aromatic alcohol derivatives and 2 racemic drugs in acetonitrile-based polar-organic mobile phase. Excellent enantioseparations were achieved for most of the analytes. The highest value of resolution factor calculated is 6.868. Comparison of the performance of 8a, 8b, 8c and 8d suggests that the positively charged imidazole group provides electrostatic interactions probably through strong H-bonding with the analytes, whereas the cationic triazole, which forms a weaker ion pair with its counter ion, is more capable of participating in ion-pairing interactions with acidic analytes. However, for compounds 12 and 13, which have larger molecular volumes than the other analytes, the interactions between analytes and both cationic imidazole and its counter ion of the selectors play an important role in the chiral resolution. Moreover, the high resolutions were found to depend on the properties of the cations and anions on the selectors in combination with the chiral recognition sites on the rim of the CD. The ionic strength in mobile phase affects the relative interactions between analytes and the chiral selector as well as between analytes and solvents.     

以芳樟醇为手性源的β-羟基酸的不对称合成

以芳樟醇与乙酰乙酸乙酯进行酯交换反应,合成了具有手性的乙酰乙酸芳樟酯(β-酮酯),再用其与不同的格氏试剂反应,得到不对称β-羟基酸;产物分别经手性柱分析.结果表明,手性乙酰乙酸芳樟酯与格氏试剂的反应具有不同程度的立体选择性,产物为R-或S-构型过量的β-羟基酸,ee值最高达50%.     

Neutral Chiral Tetrakis-Iodo-Triazole Halogen-Bond Donor for Chiral Recognition and Enantioselective Catalysis

Halogen bonding represents a powerful tool in the field of noncovalent interactions. However, applications in enantioselective recognition and catalysis remain almost nonexistent, due in part to the distinct features of halogen bonds, including long covalent and noncovalent bond distances and high directionality. Herein, this work presents a novel chiral tetrakis-iodo-triazole structure as a neutral halogen bond donor for both chiral anion-recognition and enantioinduction in ion-pair organocatalysis. NMR-titration studies revealed significant differences in anion affinity between the halogen bonding receptor and its hydrogen bonding parent. Selective recognition of chiral dicarboxylates and asymmetric induction in a benchmark organocatalytic reaction were demonstrated using the halogen bond donor. Inversions in the absolute sense of chiral recognition, enantioselectivity, and chiroptical properties relative to the related hydrogen donor were observed. Computational modeling suggested that these effects were the result of distinct anion-binding modes for the halogen- versus hydrogen-bond donors.     

Organocatalytic Synthesis of Chiral Halogenated Compounds

This account summarizes our recent efforts in the enantioselective organocatalytic synthesis of chiral halogenated compounds. The enantioselective α-halogenation of aldehydes, decarboxylative chlorination of β-keto acids, and enantioselective C−C bond formation at the trifluoromethylated prochiral carbon to yield the corresponding organohalides with chlorinated, fluorinated, or trifluoromethylated chiral stereogenic centers are discussed. We applied common organocatalysts, such as Jørgensen-Hayashi catalyst and cinchona alkaloid-derivatived catalyst, and developed novel chiral amine catalysts for these reactions. This account also discusses stereospecific derivatizations of the resulting chiral halogenated compounds via nucleophilic substitution. Thus, we synthesized many novel chiral compounds that have not been reported, even as racemates.     

Enantioselective Organocatalytic Cascade Approach to Different Classes of Benzofused Acetals

A novel enantioselective organocatalytic strategy is presented for the synthesis of tetrahydrofurobenzofuran and methanobenzodioxepine natural product core structures. The strategy is based on a pair of divergent reaction pathways in which hydroxyarenes react with γ‐keto‐α,β‐unsaturated aldehydes, catalyzed by a chiral secondary amine. One reaction pathway, which leads to chiral 5,5‐fused acetals with two stereocenters—the tetrahydrofurobenzofuran scaffolds—proceeds in moderate yields and up to 96 % ee. The other reaction pathway provides 5,6‐bridged methanobenzodioxepine scaffolds with three stereocenters in moderate to good yields and up to 95 % ee. The reaction is remarkable as it can proceed with catalyst loadings as low as 0.25 mol %, providing one of the highest known turnover numbers in iminium ion catalysis. Furthermore, the hemiacetal tetrahydrofurobenzofuran can undergo functionalizations including reduction, oxidation, and allylation. Finally, the effects involved in the substrate control for the divergent pathways, based on both experimental and computational studies, have been investigated. A model involving steric, electronic and stereoelectronic interactions is discussed to rationalize the observed selectivities.     

Electronic structural studies of pyrrolidinium-based ionic liquids for electrochemical application

Electrochemical stability and noncovalent interactions escorting the cyclic ammonium-based ionic liquids composed of N-alkyl-substituted N-methyl pyrrolidinium (P_yr1R) (R = methyl, ethyl, propyl, butyl, pentyl, hexyl) cations and four anions hexafluorophosphate (PF₆), tetrafluoroborate (BF₄), bis(trifluoromethylsulfonyl-imide (TFSI), and trifluoromethane sulfonate (TFO) have been analyzed using the density functional theory. Electronic structures, electrochemical window, frontier orbital energy difference (HOMO-LUMO gap), binding energies, vibrational spectra of these ion pairs were characterized. It has been established that ion pair formation is largely reigned by C H⋯F interactions between anionic fluorine for BF₄⁻ and PF₆⁻ anions and C H⋯O interactions between anionic oxygen for TFSI and TFO anions and pyrrolidinic proton, methyl, or alkyl group protons of the cations. The effect of alkyl chain length and pairing anions of the alkyl substituted N-methyl pyrrolidinium-based ionic liquids on the electrochemical window was investigated. The results revealed that the HOMO energy of pairing anions is the key factor to decide the electrochemical window. Further quantification of noncovalent interactions in terms of electrostatic and hydrogen bonding interactions has been brought out employing a novel method with the aid of Mulliken and Merz-Singh-Kollman charges, prevailed in pyrrolidinium-based ionic liquids.