Role of cations and confinement in asymmetric photochemistry: enantio- and diastereo-selective photocyclization of tropolone derivatives within zeolites

Asymmetric induction in photochemical reactions has been explored using the photochemistry of tropolones as a model. Three approaches have been examined: chiral inductor, chiral auxiliary and [chiral inductor + chiral auxiliary]. All three methods gave excellent asymmetric induction in zeolite and very little or zero induction in solution. Results presented on tropolones clearly illustrate the remarkable influence that a confined space studded with cations can have on asymmetric induction. Tropolone derivatives, upon irradiation undergo 4pi-electron electrocyclization to yield a bicyclic product and a rearranged product. Enantiomeric excess up to 68% has been achieved in the cyclized product. In systems where a chiral inductor has been covalently linked, diastereomeric excess as high as 88% has been achieved within a zeolite while the same system in solution gave 10%.     

Modeling and optimization of the chiral selectivity of basic analytes in chiral capillary electrophoresis with negatively charged cyclodextrins using electrochemical detection

A mathematical model concerning the separation selectivity of basic analytes in chiral capillary electrophoresis (CE) modified with negatively charged cyclodextrins (CDs) has been presented to describe the dependence of chiral selectivity on the buffer pH and the chiral selector concentration. The electrophoretic method to determine the parameters of the model has also been developed. The model has been tested with racemic epinephrine and isoproterenol as target analytes and sulfonated beta-CD as chiral selector. The agreements have been found between the calculated and the measured values. Some significant conclusions to optimize chiral CE separation have been derived from the model and proven by the experiments. Electrochemical detection was used to meet the requirement of the low introduced concentration of analytes.     

Synthesis of chiral building blocks for use in drug discovery

In the past decade there has been a significant growth in the sales of pharmaceutical drugs worldwide, but more importantly there has been a dramatic growth in the sales of single enantiomer drugs. The pharmaceutical industry has a rising demand for chiral intermediates and research reagents because of the continuing imperative to improve drug efficacy. This in turn impacts on researchers involved in preclinical discovery work. Besides traditional chiral pool and resolution of racemates as sources of chiral building blocks, many new synthetic methods including a great variety of catalytic reactions have been developed which facilitate the production of complex chiral drug candidates for clinical trials. The most ambitious technique is to synthesise homochiral compounds from non-chiral starting materials using chiral metal catalysts and related chemistry. Examples of the synthesis of chiral building blocks from achiral materials utilizing asymmetric hydrogenation and asymmetric epoxidation are presented.     

Construction of Supramolecular Chirality in Polymer Systems:Chiral Induction,Transfer and Application

Chirality,commonly found in organisms,biomolecules and nature such as L-amino acids and D-sugars,has been extensively studied in chemistry and biomedical science.Hence,the demand for simple and efficient construction of chiral structures,especially chiral polymers,has been rapidly growing due to their potential applications in chemosensors,asymmetric catalysis and biological materials.However,most chiral polymers reported are prepared directly from chiral monomers/chiral catalysts,the corresponding strategies usually involve tedious and expensive design and synthesis.Fortunately,chirality induction strategies (such as circularly polarized light,chiral solvation and chiral gelation etc.) have been known to be highly versatile and efficient in producing chirality from achiral polymers.In this feature article,the current research on chirality induction,transfer and application in achiral polymer systems is summarized.Furthermore,this article discusses some basic concepts,seminal studies,recent advances,the structural design principles,as well as perspectives in the construction and applications of chiral polymers derived from achiral monomers,with the hope to attract more interest from researchers and further advance the development of chiral chemistry.     

Phosphorus-bearing axially chiral biaryls by catalytic asymmetric cross-cyclotrimerization and a first application in asymmetric hydrosilylation

A novel and efficient, two-step route to axially chiral biaryls is demonstrated. In a direct asymmetric cross-cyclotrimerization in the presence of a chiral cobalt(I) catalyst, axially chiral biaryls bearing phosphoryl moieties have been prepared, and through indirect evidence the authors have been able to clarify the origin of the stereochemical induction and the nature of the central intermediate in the catalytic cycle. By subsequent reduction of the phosphoryl moiety to the corresponding phosphine, a very efficient and atom-economical approach to chiral systems has been developed. These chiral systems clearly have great potential use as axially chiral monodentate P- or bidentate P,O-ligands, as has been demonstrated by the employment of the novel NAPHEP as a new monodentate acting ligand in an asymmetric hydrosilylation reaction.     

Preparation and Reactions of Amino Acid Ester Sulfones as New Remote Asymmetrical Induced Reagents

The development of chiral auxiliary-controlled asymmetric synthesis has been receiving increasing interest in recent yearsfi,2] Various chiral auxiliary reagents have been observed[3] and a lot of results showed that variation of the chiral auxiliary could influence asymmetric induction. Recently, it has been reported the reaction of the aminated sulfones as a remote chiral auxiliary with α,β-unsaturated carbonyl compounds.[4] Here we would like to report the preparation of amino acid ester sulfones as new remote asymmetrical induced reagents and their reactions with α,β-unsaturated esters.     

Chiral quaternary phosphonium salts: a new class of organocatalysts

Phase-transfer catalysis has widely been used as a prime synthetic tool for both laboratory and industrial processes. During the last twenty years, asymmetric phase-transfer catalysis using chiral organocatalysts has attracted widespread interest. However, the scope of chiral phase-transfer catalysis has been limited mostly to the quaternary ammonium salts. As an emerging area, the recent developments in the application of quaternary phosphonium salts as chiral phase-transfer catalysts are discussed in this article.     

Supramolecular assembly of strongly chemisorbed size- and shape-defined chiral clusters: S- and R-alanine on Cu(110)

The bonding and self-assembly of a chirally organized monolayer of alanine on the Cu(110) surface has been investigated using reflection-absorption infrared spectroscopy, low-energy electron diffraction (LEED), and scanning tunneling microscopy (STM). This multitechnique approach has enabled an in-depth understanding of the hierarchy of chirality transfer: from a single adsorbed molecule, to size-defined chiral clusters, and then to an overall chiral assembly. The data have indicated that the alanine is in its anionic form, bound to the copper surface through the oxygens of the ionized carboxylate group and the nitrogen of the neutral amino group. Importantly, the methyl group is held away from the surface, resulting in direct chirality transfer into the footprint of the adsorbed alanine molecules, with the local adsorption motif for S-alanine being the mirror image of that created for R-alanine. STM has shown that S-alanine molecules self-organize to form size-defined chiral clusters of six or eight molecules at the surface, interspersed with chiral channels of bare metal. Together, these clusters and channels further self-assemble into a chiral array with one unique chiral domain sustained across the entire surface. A similar chiral assembly, but with the mirror organization, has been observed for R-alanine. Structural models for the individual clusters are proposed, and in conjunction with LEED data, overall models for these chiral phases of both S- and R-alanine have been constructed. Overall, this adsorption system has been found to be both strongly chemisorbed and capable of extensive intermolecular H-bonding, causing stresses that lead not only to the chiral self-organization of molecules but also to a specific self-organization of the empty chiral channels and spaces that intersperse the structure which, in turn, chirally assemble across macroscopic length scales to give a surface with global organizational chirality.     

Characteristic monomials with chirality fittingness for combinatorial enumeration of isomers with chiral and achiral ligands

A new method of combinatorial enumeration based on characteristic monomials with chirality fittingness (CM-CFs) has been proposed in order to enumerate isomers with chiral ligands as well as with achiral ones. The CM-CFs have been defined as monomials that consist of three kinds of dummy variables in light of the subduction of the Q-conjugacy representations for chiral and achiral cyclic groups. A procedure of calculating CM-CFs for cyclic groups and finite groups has been discribed so as to tabulate them as CM-CF tables. Then the CM-CF method has been applied to the enumeration of isomers with achiral ligands as well as chiral ones.     

农药甲霜灵对映体的高效液相色谱分离及手性拆分热力学研究

以正己烷 异丙醇为流动相 ,在纤维素 三 (3 ,5 二甲基苯基氨基甲酸酯 ) (CDMPC)涂敷型手性固定相上 ,对农药甲霜灵外消旋体进行了拆分 ,考察了流动相组成、柱温等对甲霜灵对映体的保留和分离的影响 ;对甲霜灵R、S对映体与固定相之间的保留和分离的热力学机理进行了讨论     

Enantioselective Synthesis of Chiral Oxime Ethers: Desymmetrization and Dynamic Kinetic Resolution of Substituted Cyclohexanones

Axially chiral cyclohexylidene oxime ethers exhibit unique chirality because of the restricted rotation of C=N. The first catalytic enantioselective synthesis of novel axially chiral cyclohexylidene oximes has been developed by catalytic desymmetrization of 4‐substituted cyclohexanones with O‐arylhydroxylamines and is catalyzed by a chiral BINOL‐derived strontium phosphate with excellent yields and good enantioselectivities. In addition, chiral BINOL‐derived phosphoric acid catalyzed dynamic kinetic resolution of α‐substituted cyclohexanones has been performed and yields versatile intermediates in high yields and enantioselectivities.     

Chiral cyclohexane based fluorescent chemosensors for enantiomeric discrimination of aspartate

Some new chiral cyclohexyl based fluorescent anion receptors have been synthesized and their absolute configuration has been determined by using circular dichroism (CD). Complexation experiments have been carried out with several dicarboxylates, and stoichiometries and complexation constants for the corresponding complexes have been determined. The chiral discrimination ability of these ligands for chiral dicarboxylates has been studied and the best results have been obtained with TMA aspartate.     

Application of chiral ionic liquids in the copper catalyzed enantioselective 1,4-addition of diethylzinc to enones

Copper catalyzed enantioselective addition of diethylzinc to various enones has been achieved in the presence of a new class of chiral ionic liquid (ChirILs) derived from α-pinene. This first study on the application of ChirILs for the title reaction shows that the chiral reaction medium has a significant influence on chiral induction.     

Tripodal borate ligands from tris(dimethylamino)borane: the first synthesis of a chiral tris(methimazolyl)borate ligand, and the crystal structure of a single diastereomer pseudo-C3-symmetric Ru(II) complex

The activation of tris(dimethylamino)borane towards reaction with a chiral methimazole by N-methylimidazole has been used to prepare the first example of a chiral tris(methimazolyl)borate ligand. Coordination of this neutral ligand to Ru(II) has been achieved by reaction with [(p-cymene)RuCl(2)](2) to provide a single diastereomer complex in which the chirality of the methimazolyl substituents dictate the chirality of the bicyclo[3.3.3]cage formed by the ligand on coordination to the metal. The alternative approach to chiral tris(methimazolyl)borate ligands involving the introduction of a chiral group onto the boron atom has been explored by replacing N-methylimidazole in the above reaction by chiral oxazolines as activating bases in reaction with simple methimazole. However, although the B(NMe(2))(3) is activated to reaction with methimazole by these oxazolines, an intramolecular oxazoline ring-opening by a coordinated methimazolyl sulfur occurs and prevents the successful synthesis of these ligands.     

Friedl?nder synthesis of chiral alkyl-substituted 1,10-phenanthrolines.

The synthetic scope of the Friedl?nder condensation in the preparation of chiral alkyl-substituted 1,10-phenanthrolines has been investigated. A range of chiral [x,y-b]-cycloalkeno-condensed phenanthrolines has been prepared in one step from steroidal or other cyclic ketones from the chiral pool and 8-amino-7-quinolinecarbaldehyde (1) via base-catalyzed condensation. Phenanthroline derivatives are formed in good yields with unhindered ketones, but the reaction proceeds even with sterically congested substrates such as camphor, albeit in low yield. The utility of the Friedl?nder condensation has been extended to the synthesis of chiral 3-alkyl-substituted phenanthrolines from monoalkyl-substituted acetaldehydes.     

Catalytic enantioselective allylation at the activated benzylic position of prochiral aryl cyano esters: access to quaternary stereogenic centers

Palladium catalyzed asymmetric allylic alkylation of prochiral aryl cyano esters has been carried out in the presence of various chiral ligands. The base and additives have been varied and allowed to produce the allyl derivative presenting a highly functionalized quaternary stereogenic center. The chiral pocket ligands of Trost appears the most appropriate to produce the desired chiral derivative.     

Enantiomeric separation of chiral peptide nucleic acid monomers by capillary electrophoresis with charged cyclodextrins

Direct chiral separation of chiral peptide nucleic acid (PNA) monomers has been achieved for the first time by capillary electrophoresis (CE) with charged cyclodextrins as chiral selectors added to the electrophoretic buffer. Selectively modified 6-deoxy-6-N-histamino-beta-cyclodextrin and sulfobutyl ether-beta-CD were successfully used as chiral selectors for the enantiomeric separation of chiral monomers based on different aminoethylamino acids bearing thymine or adenine as nucleobases. Chiral separations were obtained at low selector concentrations (1-3 mM) with good enantioselectivity and resolution factors. Separations were optimized as a function of pH in order to exploit the effect of the electrostatic interactions between the oppositely charged selector and selectand. The method has been applied to the analysis of the enantiomeric excess of chiral monomers used for the solid phase synthesis of chiral PNA oligomers. CE chiral analysis showed that a very high enantiomeric purity was generally achieved in the synthesis of all monomers, except for histidine and aspartic acid based monomers in which ca. 10% of the "wrong" enantiomer was always present.     

Double stereodifferentiation in the "acetate-type" aldol reaction with garner's aldehyde. Stereocontrolled synthesis of polyhydroxylated gamma-amino carbonyl compounds

[reaction: see text] The aldol reaction of acetamide enolates with protected chiral alpha-amino-beta-hydroxy aldehyde 1 (Garner's aldehyde) has been performed in a stereocontrolled way under double stereodifferentiation conditions using pseudoephedrine as the additional chiral information source attached to the enolate reagent. In addition, the obtained adduct has been transformed into other valuable chiral building blocks such as gamma-amino-beta,delta-dihydroxy acids, esters, and ketones.     

金属催化的不对称氢化反应研究进展与展望

手性过渡金属络合物催化的不对称氢化反应是合成光学活性化合物的重要方法. 本文从手性配体及手性催化剂、不对称催化新反应、新方法和新策略三个方面简要评述新世纪以来过渡金属催化的不对称氢化反应研究领域的新进展. 从新世纪初至今, 手性单磷配体得到了复兴, 出现了如MonoPhos、SiPhos、DpenPhos等高效单齿亚磷酰胺酯配体; 磷原子手性(P-手性)配体也得到了快速发展, 如BenzP*、ZhanPhos、TriFer等已成为新的高效手性双膦配体; 螺环骨架手性配体成为新世纪手性配体设计合成的亮点, 除了SiPhos、SIPHOX、SpinPHOX等高效手性螺环配体外, 手性螺环吡啶胺基磷配体SpiroPAP的铱催化剂成为目前最高效的分子催化剂. 不对称催化氢化新反应研究也取得了突破, 如非保护烯胺、杂芳环化合物及N-H亚胺的氢化等反应都实现了高对映选择性. 自组装手性催化剂、树枝状手性催化剂、铁磁性纳米负载的可回收手性催化剂, 以及“混合”配体手性催化剂等新方法和新策略也在不对称催化氢化反应中得到了应用. 然而, 手性过渡金属络合物催化的不对称氢化研究仍然充满挑战, 也期待新的突破.     

Synthesis of 1,3-aminonaphthols by diastereoselective Betti-type aminoalkylation of dihydroxy naphthalenes; diastereoselectivity,absolute configuration,and application

Dihydroxy naphthalenes have been applied in Betti-type solventless condensation between aldehydes and (S)-phenylethylamine as a chiral auxiliary. A series of chiral 1,3-aminonaphthols has been synthesized and isolated in diastereoisomerically pure form. The absolute configurations of the aminonaphthols synthesized have been determined by means of advanced NMR experiments and confirmed by X-ray crystallography. The new chiral aminonaphthols have been tested as pre-catalysts for the addition of diethyl zinc and alkynyl-Zn-reagents to aldehydes with enantioselectivities of up to 98% ee.