基于(R)-1,1’-联萘硫脲的手性荧光受体: 合成与手性识别

Two chiral fluorescent receptors 1 and 2 based on (R)-1,1‘-binaphthylene-2,2‘-bisthiourea were synthesized, and their chiral recognition properties for enantiomeric mandelate anions were studied by fluorescence spectra and molecular modeling. Addition of the L- and D-mandelate anions caused considerable fluorescent increases in the fluorescent intensity of the host solution. The L-enantiomer can enhance the fluorescence intensity of 1 much more than the D-enantiomer can do, and 1 shows a better enantioselective recognition ability than 2.     

β‐Cyclodextrin Functionalized Nanoporous Graphene Oxides for Efficient Resolution of Asparagine Enantiomers

Efficient resolution of racemic mixture has long been an attractive but challenging subject since Pasteur separated tartrate enantiomers in 19^th century. Graphene oxide (GO) could be flexibly functionalized by using a variety of chiral host molecules and therefore, was expected to show excellent enantioselective resolution performance. However, this combination with efficient enantioselective resolution capability has been scarcely demonstrated. Here, nanoporous graphene oxides were produced and then covalently functionalized by using a chiral host material‐β‐cyclodextrin (β‐CD). This chiral GO displayed enantioselective affinity toward the l ‐enantiomers of amino acids. In particular, >99 % of l ‐asparagine (Asn) was captured in a racemic solution of Asn while the adsorption of d ‐enantiomer was not observed. This remarkable resolution performance was subsequently modelled by using an attach‐pull‐release dynamic method. We expect this preliminary concept could be expanded to other chiral host molecules and be employed to current membrane separation technologies and finally show practical use for many other racemates.     

Enantioselective Allylic Amination of Morita‐Baylis‐Hillman Acetates Catalyzed by Chiral Thiourea‐Phosphine

The enantioselective allylic amination of Morita‐Baylis‐Hillman acetates catalyzed by chiral cyclohexane‐based thiourea‐phosphine catalysts was investigated. In the presence of 20 mol% rosin‐derived thiourea‐phosphine 3j , the chiral amines were obtained in up to 88% yield and up to 85% ee.     

Combining Organocatalysis with Central‐to‐Axial Chirality Conversion: Atroposelective Hantzsch‐Type Synthesis of 4‐Arylpyridines

Suitably substituted enantioenriched 4‐aryl‐1,4‐dihydro‐pyridines prepared by an organocatalytic enantioselective Michael addition were oxidized with MnO₂ into axially chiral 4‐arylpyridines with central‐to‐axial chirality conversion. Moderate to complete percentages (cp) were observed, and a model for the conversion of chirality is discussed.     

Facile enantioseparation and recognition of mandelic acid and its derivatives in self‐assembly interaction with chiral ionic liquids

Mandelic acid and its derivatives are important medical intermediates in the pharmaceutical industry. Different stereoisomers exhibited distinct biological properties to human bodies. Given that, enantioselective recognition and separation of mandelic acid are of great importance. In this study, four novel different types of chiral ionic liquids bearing designed functional groups were synthesized and successful enantioselective precipitation with mandelic acid and its derivatives. That is, (R, R)‐chiral ionic liquid 1 can coprecipitated with S‐mandelic acid and its derivatives was observed. In addition, good correlation coefficient is achieved by using electrospray mass spectrum at negative ion pattern for quick analysis of the enantioselective precipitation, which could be served as a method of enantioselective recognition. The possible intermolecular interactions are established after systematical studies by NMR spectroscopy and DFT calculations.     

Enantioselective Trifluoromethylthiolating Lactonization Catalyzed by an Indane‐Based Chiral Sulfide

Enantioselective trifluoromethylthiolation, especially of alkenes, is a challenging task. In this work, we have developed an efficient approach for enantioselective trifluoromethylthiolating lactonization by designing an indane‐based bifunctional chiral sulfide catalyst and a shelf‐stable electrophilic SCF₃ reagent. The desired products were formed with diastereoselectivities of >99:1 and good to excellent enantioselectivities. The transformation represents the first enantioselective trifluoromethylthiolation of alkenes and the first enantioselective trifluoromethylthiolation that is enabled by a catalyst with a Lewis basic sulfur center.     

Lewis‐Base‐Mediated Diastereoselective Silylations of Alcohols: Synthesis of Silicon‐Stereogenic Dialkoxysilanes Controlled by Chiral Aryl BINMOLs

In the past years, stereoselective functionalizations of hydroxyl groups of alcohol substrates with chlorosilanes leading to silyl ether formation have evolved from a functional‐group protection to an enantioselective synthetic strategy. This work comprises a controlled desymmetrization of dichlorosilanes by using a family of structurally specific chiral diols, chiral 1,1′‐binaphthalene‐2‐α‐arylmethanol‐2′‐ol (Ar‐BINMOL). This process led to the facile construction of silicon‐stereogenic organosilicon compounds with high yields and good diastereoselectivities. In addition, the diasteroselective silylation of chiral diols might not only be of interest for the development of highly stereoselective nucleophilic silylation, but also shed light on the construction of novel chiral phosphine ligands bearing a silicon‐stereogenic center.     

Access to P‐ and Axially Chiral Biaryl Phosphine Oxides by Enantioselective CpxIrIII‐Catalyzed C−H Arylations

An enantioselective C?H arylation of phosphine oxides with o‐quinone diazides catalyzed by an iridium(III) complex bearing an atropchiral cyclopentadienyl (Cp^x) ligand and phthaloyl tert‐leucine as co‐catalyst is reported. The method allows access to a) P‐chiral biaryl phosphine oxides, b) atropo‐enantioselective construction of sterically demanding biaryl backbones, and also c) selective assembly of axial and P‐chiral compounds in excellent yields and diastereo‐ and enantioselectivities. Enantiospecific reductions provide monodentate chiral phosphorus(III) compounds having structures and biaryl backbones with proven importance as ligands in asymmetric catalysis.     

Enantioselective Allylic Oxidation of Olefins Using Chiral Quinolinyl‐oxazoline Copper Complex Catalysts

Copper complexes of chiral quinolinyl‐oxazoline have been studied as the catalysts for enantioselective allylic oxidation of cycloalkenes with tert‐butyl perbenzoate. Using 5 mol% of these chiral catalysts, optical active allylic benzoates were obtained in moderate enantiomeric excesses. CuOTf prepared in situ, CuClO₄ and CuPF₆ were found to be good precatalysts in acetone.     

Chiral (S)‐(+) 1‐Substituted Aryl‐4‐(1‐phenyl) Ethylformamido‐5‐amino‐1,2,3‐triazole: A New Class of Chiral Ligands for the Silver(I)‐Promoted Enantioselective Allylation of Aldehydes

Some novel chiral ligands, (S)‐(+) 1‐substituted aryl‐4‐(1‐phenyl) ethylformamido‐5‐amino‐1,2,3‐triazoles, were prepared starting from 1‐substituted aryl‐4‐ethoxycarbonyl‐5‐amino‐1,2,3‐triazoles and other reagents. They were used as catalytic chiral ligands in the silver (I)‐promoted enantioselective allylation reaction of aldehydes with allyltributyltin.     

Chiral Phosphoric Acid Catalyzed Asymmetric Synthesis of Hetero‐triarylmethanes from Racemic Indolyl Alcohols

The direct enantioselective 1,4‐ and 1,8‐arylations of 7‐methide‐7H‐indoles and 6‐methide‐6H‐indoles, respectively, generated in situ from diarylmethanols, with electron‐rich arenes as nucleophiles, has been achieved in the presence of chiral phosphoric acids (CPAs). These two remote activation protocols provide an efficient approach for the construction of diverse hetero‐triarylmethanes in high yields (up to 97 %) and with excellent enantioselectivities (up to 96 %). Mechanistically inspired experiments tentatively indicate that the catalytic enantioselective 1,4‐addition as well as the formal S_N1 substitution could proceed efficiently in the similar catalytic systems. Furthermore, the modification of the catalytic system and diarylmethanol structure successfully deviates the reactivity toward a remote, highly enantioselective 1,8‐arylation reaction. This flexible activation mode and novel reactivity of diarylmethanols expand the synthetic potential of chiral phosphoric acids.     

Chiral soluble polymers and microspheres for enantioselective crystallization

A series of chiral polymers based on poly(N‐acryl) amino acids was synthesized using a convergent synthetic approach. These chiral polymers have been used as chiral additives to induce enantioselective crystallization of racemic or conglomerate amino acids in solutions. These polymeric additives showed strong capabilities to enhance highly enantioselective resolution during the crystallization of amino acids. In addition, these polymers caused unusual modifications of amino acid crystal morphologies. Furthermore, spherical microparticles of those same chiral polymers were also shown active in similar chiral discriminations during amino acid crystallizations occurring on microparticle surfaces. Our study demonstrates the high potential of chiral polymers and microparticles to resolve amino acids throughout crystallization processes. High enantiomeric excesses in one targeted enantiomer of amino acids can also be maximized via time‐dependent kinetic control of crystallizations. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 3009–3017, 2006     

A Chiral Nitrogen Ligand for Enantioselective,Iridium‐Catalyzed Silylation of Aromatic C−H Bonds

Iridium catalysts containing dative nitrogen ligands are highly active for the borylation and silylation of C−H bonds, but chiral analogs of these catalysts for enantioselective silylation reactions have not been developed. We report a new chiral pyridinyloxazoline ligand for enantioselective, intramolecular silylation of symmetrical diarylmethoxy diethylsilanes. Regioselective and enantioselective silylation of unsymmetrical substrates was also achieved in the presence of this newly developed system. Preliminary mechanistic studies imply that C−H bond cleavage is irreversible, but not the rate‐determining step.     

Enantioselective Construction of Axially Chiral Amino Sulfide Vinyl Arenes by Chiral Sulfide‐Catalyzed Electrophilic Carbothiolation of Alkynes

The enantioselective construction of axially chiral compounds by electrophilic carbothiolation of alkynes is disclosed for the first time. This enantioselective transformation is enabled by the use of a Ts‐protected bifunctional sulfide catalyst and Ms‐protected ortho‐alkynylaryl amines (Ts=tosyl; Ms=mesyl). Both electrophilic arylthiolating and electrophilic trifluoromethylthiolating reagents are suitable for this reaction. The obtained products of axially chiral vinyl–aryl amino sulfides can be easily converted into biaryl amino sulfides, biaryl amino sulfoxides, biaryl amines, vinyl–aryl amines, and other valuable difunctionalized compounds.     

Asymmetric catalytic epoxidation of enones by chiral binaphthol‐derived lanthanum catalyst

Asymmetric epoxidation of chalcone catalyzed by chiral (5)‐6, 6′‐diphenyl‐BINOL‐lanthanum complex affords the corresponding epoxychalcone with excellent yields as well as the good enantioselective excesses of 93%. The influences of solvent, the temperature, the structure of the chiral ligand, as well as the substrate on the stereochemistry were discussed.     

Asymmetric [2,3]‐Wittig Rearrangement of Oxygenated Allyl Benzyl Ethers in the Presence of a Chiral di‐tBu‐bis(oxazoline) Ligand: A Novel Synthetic Approach to THF Lignans

We have accomplished highly enantioselective [2,3]‐Wittig rearrangements of functionalized allyl benzyl ethers in the presence of a chiral di‐tBu‐bis(oxazoline) ligand. In various oxygenated benzylic ethers, the reactions proceeded with excellent diastereo‐ and enantioselectivities, although the presence of a methoxy substituent at the ortho‐position on the benzyl group drastically decreased the enantioselectivity. Conversely, o‐ethyl and o‐phenyl substituents had no significant effect on the selectivity. We found that the C2‐substituent of the allylic moiety played an important role in producing high enantioselectivity. Highly enantioselective [2,3]‐Wittig rearrangement in the presence of catalytic amounts of the chiral ligands is also described.     

Synthesis of Novel 1,4‐Bissulfonamide Ligands for Enantioselective Addition of Diethylzinc to Aldehydes

Several novel chiral sulfonamide ligands based on (1R,2S,4R,5S)‐1,4‐diamino‐2,5‐dimethylcyclohexane skeleton have been synthesized and their application in the enantioselective addition of diethylzinc to aldehydes was investigated in the presence of Ti(OⁱPr)₄. The effect of ligands, temperature and the loading amount of ligands was studied. Under optimized conditions, enantioselective addition of diethylzinc with various aryl aldehydes and aliphatic aldehydes proceeded smoothly and afforded chiral secondary alcohols in up to 88% ee.     

Enantioselective Synthesis of Isoquinolines: Merging Chiral‐Phosphine and Gold Catalysis

The highly enantioselective synthesis of dihydroisoquinoline derivatives from aromatic sulfonated imines tethered with an alkyne moiety, through a one‐pot asymmetric relay catalysis of chiral‐phosphine and gold catalysts, is reported. Enantiomerically enriched dihydroisoquinoline derivatives were afforded in good yields and good‐to‐excellent ee values under mild conditions, based on the asymmetric aza‐Morita‐Baylis–Hillman reaction. Dihydroisoquinoline derivatives containing two chiral centers were also synthesized through further transformations.     

Chiral N,N′‐Dioxide‐Organocatalyzed Regio‐, Diastereo‐ and Enantioselective Michael Addition–Alkylation Reaction

A highly regio‐, diastereo‐ and enantioselective Michael addition–alkylation reaction between α‐substituted cyano ketones and (Z)‐bromonitrostyrenes has been realized by using a chiral N,N′‐dioxide as organocatalyst. A variety of substrates performed well in this reaction, and the corresponding multifunctionalized chiral 2,3‐dihydrofurans were obtained in up to 95 % yield with 95:5 dr and 93 % ee.     

Rhodium(III)/Amine Synergistically Catalyzed Enantioselective Alkylation of Aldehydes with α,β‐Unsaturated 2‐Acyl Imidazoles

A synergistic catalysis combination of chiral‐at‐metal rhodium complex and amine catalyst was developed for enantioselective alkylation of aldehydes with α,β‐unsaturated 2‐acyl imidazoles. The corresponding adducts were obtained in good yields with excellent enantioselectivities (up to 99% ee).