Near-Enantiopure Trimerization of 9-Ethynylphenanthrene on a Chiral Metal Surface

Enantioselectivity in heterogeneous catalysis strongly depends on the chirality transfer between catalyst surface and all reactants, intermediates, and the product along the reaction pathway. Herein we report the first enantioselective on-surface synthesis of molecular structures from an initial racemic mixture and without the need of enantiopure modifier molecules. The reaction consists of a trimerization via an unidentified bonding motif of prochiral 9-ethynylphenanthrene (9-EP) upon annealing to 500 K on the chiral Pd₃-terminated PdGa{111} surfaces into essentially enantiopure, homochiral 9-EP propellers. The observed behavior strongly contrasts the reaction of 9-EP on the chiral Pd₁-terminated PdGa{111} surfaces, where 9-EP monomers that are in nearly enantiopure configuration, dimerize without enantiomeric excess. Our findings demonstrate strong chiral recognition and a significant ensemble effect in the PdGa system, hence highlighting the huge potential of chiral intermetallic compounds for enantioselective synthesis and underlining the importance to control the catalytically active sites at the atomic level.     

Near‐Enantiopure Trimerization of 9‐Ethynylphenanthrene on a Chiral Metal Surface

Enantioselectivity in heterogeneous catalysis strongly depends on the chirality transfer between catalyst surface and all reactants, intermediates, and the product along the reaction pathway. Herein we report the first enantioselective on‐surface synthesis of molecular structures from an initial racemic mixture and without the need of enantiopure modifier molecules. The reaction consists of a trimerization via an unidentified bonding motif of prochiral 9‐ethynylphenanthrene (9‐EP) upon annealing to 500 K on the chiral Pd₃‐terminated PdGa{111} surfaces into essentially enantiopure, homochiral 9‐EP propellers. The observed behavior strongly contrasts the reaction of 9‐EP on the chiral Pd₁‐terminated PdGa{111} surfaces, where 9‐EP monomers that are in nearly enantiopure configuration, dimerize without enantiomeric excess. Our findings demonstrate strong chiral recognition and a significant ensemble effect in the PdGa system, hence highlighting the huge potential of chiral intermetallic compounds for enantioselective synthesis and underlining the importance to control the catalytically active sites at the atomic level.     

Highly Enantioselective Adsorption of Small Prochiral Molecules on a Chiral Intermetallic Compound

Intrinsically chiral surfaces of intermetallic compounds are shown to be novel materials for enantioselective processes. Their advantage is the significantly higher thermal and chemical stability, and therefore their extended application range for catalyzed chiral reactions compared to surfaces templated with chiral molecular modifiers or auxiliaries. On the Pd₁‐terminated PdGa(111) surface, room‐temperature adsorption of a small prochiral molecule (9‐ethynylphenanthrene) leads to exceptionally high enantiomeric excess ratios of up to 98 %. Our findings highlight the great potential of intrinsically chiral intermetallic compounds for the development of novel, enantioselective catalysts that can be operated at high temperatures and potentially also in harsh chemical environments.     

Enantioselective Crystallization of Chiral Inorganic Crystals of ϵ-Zn(OH)2 with Amino Acids

Many inorganic materials can form crystals, but little is known about their enantioselective crystallization. Herein, we report on the enantioselective crystallization of ϵ-Zn(OH)₂ (Wulfingite) chiral crystals by using amino acids. Crystals of ϵ-Zn(OH)₂ were crystallized from supersaturated sodium hydroxide and zinc nitrate aqueous solutions in the presence of l - or d -arginine. All of the chiral measurements, such as selective chiral adsorption by circular dichroism (CD), chiral chromatography, and polarimetry measurements, clearly show chiral discrimination during the crystallization of ϵ-Zn(OH)₂. In addition, a new method has been developed for identifying chirality in crystals by using electron paramagnetic resonance (EPR). Although the values of chiral induction of the ϵ-Zn(OH)₂ crystals obtained are somewhat low, these values are still significant because they demonstrate that enantioselectivity during the crystallization of chiral inorganic crystals with chiral additives can be achieved. The method can be applied to many chiral inorganic systems. Understanding and controlling the crystallization of chiral inorganic crystals is important for gaining knowledge on the interaction of chiral molecules with inorganic surfaces. This knowledge can lead to an understanding of basic scientific questions such as the evolution of homochirality in biomolecules and the development of chiral inorganic crystals for a variety of purposes such as asymmetric catalysis and optical applications.     

Photoswitchable Chiral Organocatalysts: Photocontrol of Enantioselective Reactions

This study presents recent advances in photoswitchable chiral organocatalysts and their applications in the photomodulation of enantioselective reactions. Under irradiation with an appropriate wavelength of light, the E/Z-photoisomerization of the photoresponsive units on the catalysts leads to the control of the catalytic activity and/or selectivity of the enantioselective reactions. Additionally, this study elucidates the design, synthesis, and catalytic application of the fabricated azobenzene BINOL-based photoswitchable chiral phase-transfer catalysts. This account will provide insights into the appropriate design of a photoswitchable chiral organocatalyst that can achieve both good enantioselectivity and photocontrol.     

Enantioselective Reaction of 2H‐Azirines

2H‐Azirines are useful precursors for the synthesis of a variety of chiral aziridine and amine derivatives with a range of biological activities. Owing to the ring strain and the presence of a C=N double bond, 2H‐azirines are more reactive than other types of ketimine, and undergo a range of enantioselective reactions, including reduction and Diels–Alder reactions, as well as nucleophilic addition to the C=N double bond. Therefore, the enantioselective reactions of 2H‐azirines has become a hot topic, in particular within the last few years. In this Minireview, we focus on the enantioselective reactions of 2H‐azirines by using catalytic or stoichiometric amounts of chiral additives, the reaction mechanisms, and the applications of these reactions of 2H‐azirines and related compounds in organic synthesis.     

Dimeric & Polymeric Chiral Schiff Base Complexes and Supported BINOL Complexes as Potential Recyclable Catalysts in Asymmetric Kinetic Resolution and C–C Bond Formation Reactions

This review is based on dimeric and polymeric chiral Schiff base metal complexes and chiral BINOL supported metal complexes as potential recyclable catalysts for kinetic resolution of racemic and meso epoxide and asymmetric C–C bond formation reactions e.g., asymmetric addition of diethylzinc to aldehydes, enantioselective addition of phenylacetylene to aldehydes, asymmetric nitro-Aldol reactions and asymmetric cyanation reaction.     

The Electron Spin as a Chiral Reagent

We show that enantioselective reactions can be induced by the electron spin itself and that it is possible to replace a conventional enantiopure chemical reagent by spin‐polarized electrons that provide the chiral bias for enantioselective reactions. Three examples of enantioselective chemistry resulting from electron‐spin polarization are presented. One demonstrates the enantioselective association of a chiral molecule with an achiral self‐assembled monolayer film that is spin‐polarized, while the other two show that the chiral bias provided by the electron helicity can drive both reduction and oxidation in enantiospecific electrochemical reactions. In each case, the enantioselectivity does not result from enantiospecific interactions of the molecule with the ferromagnetic electrode but from the polarized spin that crosses the interface between the substrate and the molecule. Furthermore, the direction of the electron‐spin polarization defines the handedness of the enantioselectivity. This work demonstrates a new mechanism for realizing enantioselective chemistry.     

StereoPHIP: Stereoselective Parahydrogen-Induced Polarization

Parahydrogen-induced polarization (PHIP) followed by polarization transfer to ¹³C is a rapidly developing technique for the generation of ¹³C-hyperpolarized substrates. Chirality plays an essential role in living systems and differential metabolism of enantiomeric pairs of metabolic substrates is well documented. Inspired by asymmetric hydrogenation, here we report stereoPHIP, which involves the addition of parahydrogen to a prochiral substrate with a chiral catalyst followed by polarization transfer to ¹³C spins. We demonstrate that parahydrogen could be rapidly added to the prochiral precursor to both enantiomers of lactic acid (D and L), with both the (R,R) and (S,S) enantiomers of a chiral rhodium(I) catalyst to afford highly ¹³C-hyperpolarized (over 20 %) L- and D-lactate ester derivatives, respectively, with excellent stereoselectivity. We also show that the hyperpolarized ¹H signal decays obtained with the (R,R) and (S,S) catalysts were markedly different. StereoPHIP expands the scope of conventional PHIP to the production of ¹³C hyperpolarized chiral substrates with high stereoselectivity.     

Enantioselective C?C and C?H Bond Formation Mediated or Catalyzed by Chiral ebthi Complexes of Titanium and Zirconium

The development of catalytic processes that effect enantioselective bond formation under mild conditions is an important and challenging task in modern chemical synthesis. In this connection, chiral C₂-symmetric ansa-metallocenes (bridged metallocenes) have found notable applications as catalysts. This article discusses the chemistry of this class of chiral metallocene complexes with regard to their utility in catalytic and enantioselective C? C and C? H bond formation reactions. In addition, where applicable, a brief comparison with other related catalytic enantioselective processes is offered. Many of the reactions effected with high levels of enantioselectivity by catalytic amounts of these complexes are of great significance to the preparation of new materials and in the synthesis of therapeutic agents. For example, zirconocene complexes readily catalyze the enantioselective addition of alkylmagnesium halides to alkenes, and cationic zirconocene complexes may promote the highly stereoregulated copolymerization of terminal alkenes. Furthermore, the related chiral titanocenes are involved in an impressive range of useful asymmetric catalytic reactions, including the enantioselective hydrogenation of olefins and reduction of imines or ketones. This review attempts to bring together the practical aspects of the use of [(ebthi)M] complexes of Group 4 transition metals (catalyst synthesis and resolution), outline the manner in which the C₂-symmetric chiral ligands are believed to initiate stereoselective bond formation, and highlight the aspects of this chemistry that are less well understood and require further research.     

Direct Catalytic Asymmetric Aldol Reaction of an α‐Azido Amide

A direct aldol reaction of an α‐azido 7‐azaindolinylamide, promoted by a Cu‐based cooperative catalyst, is documented. Aromatic aldehydes bearing an ortho substituent exhibited diastereodivergency depending on the nature of the chiral ligands used. Smooth reactions with ynals highlighted the broad substrate scope. A vicinal azido alcohol unit in the product allowed direct access to the corresponding aziridine and facile hydrolysis of the 7‐azaindolinylamide moiety furnished enantioenriched β‐hydroxy‐α‐azido carboxylic acid derivatives.     

Oxazoline‐Based Organocatalyst for Enantioselective Strecker Reactions: A Protocol for the Synthesis of Levamisole

A chiral oxazoline‐based organocatalyst has been found to efficiently catalyze asymmetric Strecker reactions of various aromatic and aliphatic N‐benzhydrylimines with trimethylsilyl cyanide (TMSCN) as a cyanide source at ?20 °C to give α‐aminonitriles in high yield (96 %) with excellent chiral induction (up to 98 % ee). DFT calculations have been performed to rationalize the enantioselective formation of the product with the organocatalyst in these reactions. The organocatalyst has been characterized by single‐crystal X‐ray diffraction analysis, as well as by other analytical methods. This protocol has been extended to the synthesis of the pharmaceutically important drug molecule levamisole in high yield and with high enantioselectivity.     

Enantioselective Nucleophilic Aromatic Substitution with Small‐Molecule Chiral Selectors

Small‐molecule rationally designed chiral selectors have been shown to influence the stereochemical outcome of a variety of organic transformations. For instance, in a recent report, we demonstrated that a chiral selector (in conjunction with an achiral phase‐transfer catalyst) could selectively inhibit one enantiomer of electron‐deficient aromatic amides from forming Meisenheimer adducts (Scheme 2). We now extend this methodology to performing enantioselective nucleophilic aromatic substitutions. Initial studies involved biphasic kinetic resolutions with a chiral selector in conjunction with an achiral phase‐transfer catalyst (Scheme 3). The results are consistent with previous data taken for biphasic reactions (e.g., Scheme 1) where the chiral selector effectively shields the more highly complexed enantiomer from reaction. With neutral nucleophiles such as amines, the enantioselective nucleophilic aromatic substitutions can also be conducted in single‐phase systems. Several examples are given.     

New development in the enantioselective ring opening of meso-epoxides by various chloride ion silicon sources catalyzed by an o-methoxyaryldiazaphosphonamide Lewis base

New developments in the enantioselective ring opening of meso-epoxides catalyzed by a chiral Lewis base have been achieved using various chloride ion silicon sources. Thus, the use of TMSCl led to enantioselectivities varying from 6 to 98% ee depending on the nature of the considered epoxide.     

Rhodium(II)‐Catalyzed Inter‐ and Intramolecular Cyclopropanations with Diazo Compounds and Phenyliodonium Ylides: Synthesis and Chiral Analysis

Different classes of cyclopropanes derived from Meldrum's acid (=2,2‐dimethyl‐1,3‐dioxane‐4,6‐dione; 4 ), dimethyl malonate ( 5 ), 2‐diazo‐3‐(silyloxy)but‐3‐enoate 16 , 2‐diazo‐3,3,3‐trifluoropropanoate 18 , diazo(triethylsilyl)acetate 24a , and diazo(dimethylphenylsilyl)acetate 24b were prepared via dirhodium(II)‐catalyzed intermolecular cyclopropanation of a set of olefins 3 (Schemes 1 and 4–6). The reactions proceeded with either diazo‐free phenyliodonium ylides or diazo compounds affording the desired cyclopropane derivatives in either racemic or enantiomer‐enriched forms. The intramolecular cyclopropanation of allyl diazo(triethylsilyl)acetates 28, 30 , and 33 were carried out in the presence of the chiral dirhodium(II) catalyst [Rh₂{(S)‐nttl)₄}] ( 9 ) in toluene to afford the corresponding cyclopropane derivatives 29, 31 and 34 with up to 37% ee (Scheme 7). An efficient enantioselective chiral separation method based on enantioselective GC and HPLC was developed. The method provides information about the chemical yields of the cyclopropane derivatives, enantioselectivity, substrate specifity, and catalytic activity of the chiral catalysts used in the inter‐ and intramolecular cyclopropanation reactions and avoids time‐consuming workup procedures.     

Optically Active Hybrid Materials Constructed from Helically Substituted Polyacetylenes

Functional materials derived from synthetic helical polymers are attracting increasing interest. Helically substituted polyacetylenes (HSPAs) are especially interesting as typical artificial helical polymers. In recent years, we designed and prepared a series of functional materials based on HSPAs and inorganic materials. The target is to establish some novel hybrid materials that combine the superior properties of both. The examined inorganic materials include silica, graphene, and magnetic Fe₃O₄ nanoparticles. Such new functional materials hold great promise and are expected to find practical applications, for instance, as chiral absorbents, chiral sensors, chiral selectors for inducing enantioselective crystallization, chiral catalysts towards asymmetric catalysis, and chiral carriers for enantioselective release. The Personal Account summarizes our major achievements in preparing optically active hybrid materials. We hope it will speed up progress in chiral‐related research areas.     

Enhanced Circularly Polarized Luminescence from Reorganized Chiral Emitters on the Skeleton of a Zeolitic Imidazolate Framework

A chiral zeolitic imidazolate framework (ZIF) showing circularly polarized luminescence (CPL) has been successfully constructed by blending binapthyl‐derived chiral emitters with ZIF‐8 rhombic dodecahedron nanoparticles. This approach solves a major trade‐off in CPL‐active materials: the large luminescence dissymmetry factor (g_lum) always suffers from suppression of luminescence efficiency. Compared to the optical properties of chiral emitters, the obtained chiral ZIF nanomaterials showed an enhanced fluorescence efficiency while the |g_lum| value is significantly amplified by one order of magnitude. Additionally, enantioselective fluorescence sensing in response to α‐hydroxycarboxylic acids has been enhanced in chiral ZIFs. Reorganization and conjunction of chiral emitters to the skeleton of ZIF nanoparticles can greatly improve both the luminescence quantum yield and circularly polarization, which facilitates the design of more efficient chiroptical materials.     

Synthesis and Applications of Functionalized Magnetic Nanomaterials in Enantioseparation

Efficient enantioselective separation is a challenging task due to the identical physical and chemical properties of enantiomers. Functionalized magnetic nanomaterials modified with chiral ligands on their surface possess both magnetic property and chiral recognition ability, and have demonstrated great potential in chiral discrimination. This review summarizes the applications of magnetic nanomaterials modified with various chiral selectors (e.g., β-cyclodextrins, polymers, proteins, amino acids and cellulose) in enantioselective separation. After proper preparation and modification, these functionalized magnetic nanomaterials are effective for enantioseparation. Therefore, enantioseparations based on functionalized magnetic nanomaterials are convenient, economical and effective.     

New P,N-ferrocenyl ligands for rhodium-catalyzed hydroboration and palladium-catalyzed allylic alkylation

A set of nine new chiral P,N-ferrocenyl ligands for metal-catalyzed enantioselective reactions has been prepared. The rhodium-catalyzed hydroboration of styrene with catechol borane proceeded with high regioselectivity (up to 97:3) or with high enantioselectivity (up to 92% ee) depending on the catalyst. Good results were also obtained in the palladium-catalyzed asymmetric alkylation of 1,3-diphenylallylic systems (up to 94% ee).     

Highly enantioselective discrimination of amino acids using copper deposition on a gold electrode modified with homocysteine monolayer

An extremely enhanced enantioselectivity was achieved for the detection of enantiomers of alanine (Ala), leucine (Leu), and 3,4-dihydroxyphenylalanine (DOPA) based on the voltammograms for the deposition of Cu from Cu complexes of the amino acids at an Au electrode modified with a self-assembled monolayer (SAM) of l-homocysteine (Hcy). The enantioselective current density peak for the Cu deposition was found to change with increasing number of potential cycles after the addition of Cu(II), and the highest enantioselectivity was observed immediately after the addition of Cu(II). Besides, enantioselectivity was not observed with proline, whose five-membered ring contains the nitrogen atom of a secondary amino group, while some amino acids with a primary amine group such as Ala, Leu, and DOPA exhibited enantioselectivity. These results suggest that the chiral ligand exchange reaction at the l-Hcy SAM-modified Au electrode, namely, the enantioselective formation of diastereomeric complexes of Cu(II) with target enantiomers and l-Hcy self-assembled on the Au electrode, plays an important role in the chiral discrimination based on the Cu deposition.