Catalysts For Asymmetric Catalysis Research Articles

Application of chiral recyclable catalysts in asymmetric catalysis.

Chiral drugs hold a significant position within the contemporary pharmaceutical market, and the chiral catalysts play a crucial role in their synthesis. However, current chiral catalysts encounter challenges pertaining to their separation from products and the recycling process. The utilization of chiral recyclable catalysts not only reduces production costs but also aligns with the growing emphasis on environmentally-friendly chiral synthetic chemistry. These recyclable catalysts exhibit diverse carriers and distinct characteristics. Chemists employ the distinctive attributes of individual carriers to render them recyclable, thereby yielding time and cost savings. This review examines the asymmetric recyclable catalytic reactions reported between January 2017 and October 2023, categorizing them based on carrier solubility, and elucidates the loading techniques, catalytic impacts, recovery approaches, and recycling processes associated with these carriers.

Diastereo- and atroposelective synthesis of N-arylpyrroles enabled by light-induced phosphoric acid catalysis

The C−N axially chiral N-arylpyrrole motifs are privileged scaffolds in numerous biologically active molecules and natural products, as well as in chiral ligands/catalysts. Asymmetric synthesis of N-arylpyrroles, however, is still challenging, and the simultaneous creation of contiguous C−N axial and central chirality remains unknown. Herein, a diastereo- and atroposelective synthesis of N-arylpyrroles enabled by light-induced phosphoric acid catalysis has been developed. The key transformation is a one-pot, three-component oxo-diarylation reaction, which simultaneously creates a C−N axial chirality and a central quaternary stereogenic center. A broad range of unactivated alkynes were readily employed as a reaction partner in this transformation, and the N-arylpyrrole products are obtained in good yields, with excellent enantioselectivities and very good diastereoselectivities. Notably, the N-arylpyrrole skeletons represent interesting structural motifs that could be used as chiral ligands and catalysts in asymmetric catalysis.

Synthesis of planar chiral ferrocenes via enantioselective remote C-H activation.

Planar chiral ferrocenes are widely studied structures in asymmetric catalysis, materials science and medicinal chemistry. Although synthetic methods for 1,2-disubstituted planar chiral ferrocenes are well known, methods for the direct construction of 1,3-disubstituted planar chiral ferrocenes remain elusive. Here we report a modular platform for the construction of planar chirality in 1,3-disubstituted ferrocenes/ruthenocenes via an enantioselective relay remote C-H activation strategy. This method demonstrates a mechanism for remote enantiocontrol via enantiodetermining initial C‒H activation at the C2 position, enabled by a chiral mono-N-protected natural amino-acid ligand, and subsequent relay to the remote C3 position by a bridgehead-substituted norbornene mediator. A wide variety of 1,3-disubstituted planar chiral metallocenes are prepared with high enantioselectivity (96‒99% e.e.). The reaction shows good functional-group tolerance and high step-economy, and aryl iodides/bromides are compatible as coupling partners. The resulting metallocenes can be readily derivatized to yield planar chiral ligands and catalysts for asymmetric catalysis as well as building blocks for other applications.

Chiral Alkynyl‐Stabilized Ag/Cu Nanoclusters from Spontaneous Resolution

AbstractIntrinsically chiral metal nanoclusters with crystal structure are highly desirable to gain deep insights into chirality origin of chiral nanostructures and understand structure‐and‐property relationship of heterogeneous catalysts in asymmetric catalysis. Although several strategies including the use of chiral ligands and high‐performance liquid chromatography have been routinely employed to gain nanoclusters with inherent chirality, another simple methodology of spontaneous resolution remains largely unexplored. In this work, we report the isolation of homochiral Ag/Cu nanoclusters stabilized by alkynyl ligands from spontaneous self‐resolution, which represents a pioneering example in the realm of alkynyl‐protected metal nanoclusters. The cluster, with the formula of [Ag12Cu7(dppe)3(RC≡C)14]3+, has been prepared in one‐pot, with the high yield of 71%. Structural anatomy reveals that the metal architecture, metal‐ligand interface and ligand arrangement of the cluster all display chirality. The cluster features superatomic free electrons, implying its potential application in specific fields. This work not only offers strategic guidance for the simple synthesis of alkynyl‐protected metal nanoclusters with inherent chirality in an all‐achiral environment, but also displays the hierarchical chirality of cluster moieties at molecular level.

Atropisomers with Axial and Point Chirality: Synthesis and Applications.

Enantiopure atropisomers have become increasingly important in asymmetric synthesis and catalysis, pharmaceutical science, and material science since the discovery of inherent features of axial chirality originating from rotational restriction. Despite the advances made in this field to date, it remains highly desirable to construct structurally diverse atropisomers with potentially useful functions. We propose superposition to match axial and point chirality as a potentially useful strategy to access structurally complex and diverse building blocks for organic synthesis and pharmaceutical science because merging atropisomeric backbones with one or more extra chiral elements can topologically broaden three-dimensional environments to create complex scaffolds with multiple tunable parameters. Over the past decade, we have successfully implemented a strategic design for the superposition of axial and point chirality to develop a series of enantiopure atropisomers and have utilized the synergistic functions of these molecules to enhance chirality transfer in various catalytic asymmetric transformations.In this Account, we present several novel atropisomers with superposed axial and point chirality developed in our laboratory. In our studies, this superposition strategy was used to design and synthesize both biaryl and non-biaryl atropisomers from commercially available chiral sources. Consequently, these atropisomers were used to demonstrate the importance of the synergetic functions of axial and point chirality in specific enantioselective reactions. For example, aromatic amide-derived atropisomers, simplified as Xing-Phos arrays, were broadly employed in Ag-catalyzed [3 + 2] cycloaddition by a series of reactions of aldiminoesters with activated alkenes and imines, as well as being used as chiral solvating agents for the discrimination of optically active mandelic acid derivatives. Considering the powerful potential of non-biaryl atropisomers for asymmetric catalysis, we also explored the transition-metal-catalyzed enantioselective construction of a novel backbone of non-biaryl atropisomers (Ar-alkene, Ar-N axis) bearing both axial and point chirality for the design and synthesis of chiral ligands and functional molecules.The studies presented herein are expected to stimulate further research efforts on the development of functional atropisomers by superposition of matching axial and point chirality. In addition to tunable electron and stereohindrance effects, the synergy between matching chiral elements of axial/point chirality and functional groups is proven to be a special function that cannot be ignored for promoting reactivity and chirality-transfer efficiency in enantioselective synthesis. Consequently, our novel types of scaffolds with superposed axial and point chirality that are capable of versatile coordination with various metal catalysts in asymmetric catalysis highlight the power of the superposition of matching axial and point chirality for the construction of synthetically useful atropisomers.

Conformational enantiodiscrimination for asymmetric construction of atropisomers

Molecular conformations induced by the rotation about single bonds play a crucial role in chemical transformations. Revealing the relationship between the conformations of chiral catalysts and the enantiodiscrimination is a formidable challenge due to the great difficulty in isolating the conformers. Herein, we report a chiral catalytic system composed of an achiral catalytically active unit and an axially chiral 1,1′-bi-2-naphthol (BINOL) unit which are connected via a C–O single bond. The two conformers of the catalyst induced by the rotation about the C–O bond, are determined via single-crystal X-ray diffraction and found to respectively lead to the formation of highly important axially chiral 1,1′-binaphthyl-2,2′-diamine (BINAM) and 2-amino-2′-hydroxy-1,1′-binaphthyl (NOBIN) derivatives in high yields (up to 98%), with excellent enantioselectivities (up to 98:2 e.r.) and opposite absolute configurations. The results highlight the importance of conformational dynamics of chiral catalysts in asymmetric catalysis.

Chiral Dienes: From Ligands to FLP Catalysts

Comprehensive SummaryOlefins are very easily accessible compounds which are both popular substrates in synthetic chemistry and good ligands in the organometallic complexes. This dual character makes olefins a rich source of chiral ligands and catalysts for asymmetric catalysis. Herein, we will briefly summarize our studies on the development of chiral diene ligands for transition‐metal catalyzed asymmetric reactions and chiral FLP catalysts for asymmetric metal‐free hydrogenations and hydrosilylations. Several acyclic chiral diene ligands as well as P/olefin and S/olefin hybrid ligands were developed for Rh or Pd‐catalyzed asymmetric reactions. With these ligands in hand, we further put forward a novel strategy for acquiring chiral FLP catalysts via the in situ hydroboration of chiral dienes with Piers’ borane. These catalysts proved to be highly effective for asymmetric metal‐free hydrogenations and hydrosilylations of imines, silyl enol ethers, ketones, and aromatic N‐heterocycles. What is the most favorite and original chemistry developed in your research group?The development of acyclic dienes both as chiral ligands and as precursors of chiral FLP catalysts.How do you get into this specific field? Could you please share some experiences with our readers?When I started my independent research in 2008, chiral olefins belong to one novel ligand type. We got into the field with the thought of the simpler the better. This experience further led us to step into FLP catalysis.What is the most important personality for scientific research?Courage and persistence of doing something unique.What are your hobbies?Walking and playing cards.How do you keep balance between research and family?Life is not only research, but also family. You believe it, the balance is there.What is your favorite journal(s)?My favorite journal is Organic Letters, in which authors can publish their work rapidly and readers can browse the progress of organic chemistry comprehensively.

Metal-free oxidative cross-coupling enabled practical synthesis of atropisomeric QUINOL and its derivatives

As an important platform molecule, atropisomeric QUINOL plays a crucial role in the development of chiral ligands and catalysts in asymmetric catalysis. However, efficient approaches towards QUINOL remain scarce, and the resulting high production costs greatly impede the related academic research as well as downstream industrial applications. Here we report a direct oxidative cross-coupling reaction between isoquinolines and 2-naphthols, providing a straightforward and scalable route to acquire the privileged QUINOL scaffolds in a metal-free manner. Moreover, a NHC-catalyzed kinetic resolution of QUINOL N-oxides with high selectivity factor is established to access two types of promising axially chiral Lewis base catalysts in optically pure forms. The utility of this methodology is further illustrated by facile transformations of the products into QUINAP, an iconic ligand in asymmetric catalysis.

Anisotropic nanomaterials for asymmetric synthesis.

The production of enantiopure chemicals is an essential part of modern chemical industry. Hence, the emergence of asymmetric catalysis led to dramatic changes in the procedures of chemical synthesis, and now it provides the most advantageous and economically executable solution for large-scale production of chiral chemicals. In recent years, nanostructures have emerged as potential materials for asymmetric synthesis. Indeed, on the one hand, nanomaterials offer great opportunities as catalysts in asymmetric catalysis, due to their tunable absorption, chirality, and unique energy transfer properties; on the other hand, the advantages of the larger surface area, increased number of unsaturated coordination centres, and more accessible active sites open prospects for catalyst encapsulation, partial or complete, in a nanoscale cavity, pore, pocket, or channel leading to alteration of the chemical reactivity through spatial confinement. This review focuses on anisotropic nanomaterials and considers the state-of-the-art progress in asymmetric synthesis catalysed by 1D, 2D and 3D nanostructures. The discussion comprises three main sections according to the nanostructure dimensionality. We analyze recent advances in materials and structure development, discuss the functional role of the nanomaterials in asymmetric synthesis, chirality, confinement effects, and reported enantioselectivity. Finally, the new opportunities and challenges of anisotropic 1D, 2D, and 3D nanomaterials in asymmetric synthesis, as well as the future prospects and current trends of the design and applications of these materials are analyzed in the Conclusions and outlook section.

Recent Advances of ChiraI Spiro Ligands and Their Catalysts in Asymmetric Catalysis

Recent Advances of ChiraI Spiro Ligands and Their Catalysts in Asymmetric Catalysis

Chiral Cobalt(II) Complex Catalyzed Asymmetric [2,3]-Sigmatropic Rearrangement of Allylic Selenides with α-Diazo Pyrazoleamides

Organoselenium compounds, due to their high structural diversity, special function, and biological activities, have drawn attention in synthetic chemistry. Herein, a novel example of chiral N,N′-di...

Enantioselective Access to Axial Biaryls via Ruthenium‐Catalyzed Hydrogen‐Transfer Reductive Amination

AbstractAxially chiral biaryls are widespread in natural products, and often utilized as chiral ligands or catalysts in asymmetric catalysis. Driven by the demand of efficient assembly of axial biaryls, we describe herein a novel atropoenantioselective synthesis of biaryls via a ruthenium catalyzed hydrogen‐transfer reductive amination and dynamic kinetic resolution process. This protocol enriches the diversity of axial biaryl amine‐alcohols bearing various substituents and functional groups.

Synthesis of Planar Chiral Ferrocenes via Transition-Metal-Catalyzed Direct C-H Bond Functionalization.

Ferrocenes are of great interest in the fields of materials science, organic synthesis, and biomedical research. Of particular significance is the fact that ferrocenes bearing planar chirality have been demonstrated to be highly efficient ligands or catalysts in asymmetric catalysis, some of which have been employed in the industrial synthesis of pharmaceuticals and agrochemicals. So far, the main methods for the synthesis of planar chiral ferrocenes involve diastereoselective directed ortho-metalation (DoM), enantioselective DoM, and chiral resolution. Despite the fact that these approaches are well developed and widely applied, the use of chiral auxiliaries or external stoichiometric chiral bases is required in most cases. Additionally, the practicality of these processes is hampered by the requirement of sensitive organometallic reagents, the poor compatibility with functional groups, and the low atom economy in some cases. Therefore, the development of highly efficient strategies to introduce planar chirality on the backbone of ferrocene that do not possess these limitations is highly desirable. Meanwhile, transition-metal-catalyzed asymmetric C-H bond functionalization reactions have attracted much attention over the past few years owing to their emerging potential for providing a straightforward approach for the preparation of chiral molecules. In addition to the majority of the work focusing on the installation of central chirality, methods for the catalytic asymmetric synthesis of planar chiral compounds via C-H bond functionalization have also been explored. In this Account, we summarize our recent efforts aimed at the development of novel methods to synthesize planar chiral compounds via asymmetric C-H bond functionalization and also highlight related achievements by other groups. First, we briefly introduce the precedent examples of diastereoselective and enantioselective synthesis of planar chiral ferrocenes. Subsequently, asymmetric syntheses of structurally diverse planar chiral ferrocenes via Pd [Pd(II), Pd(0)]-, Ir-, Rh-, Au-, and Pt-catalyzed C-H bond functionalization are described. These methods have impressive advantages over traditional approaches for the synthesis of functionalized planar chiral ferrocenes in terms of both step- and atom-economies. Notably, the products of these processes are easily transformed into a variety of new catalysts or ligands, which have been demonstrated to promote efficient asymmetric reactions. Moreover, DFT calculations have been conducted to explore the origin of the excellent enantioselectivity of Pd-catalyzed enantioselective C-H bond functionalization reactions. Progress made in the area of asymmetric C-H bond functionalization provides an effective platform for the design and synthesis of planar chiral ferrocenes.

Synthesis of dendrimer-supported ferrocenylmethyl aziridino alcohol ligands and their application in asymmetric catalysis

Dendrimer-supported ferrocenylmethyl aziridino alcohols have been developed and applied as efficient, recoverable and recyclable catalysts in asymmetric catalysis.

Recent Advances in Transition-Metal-Catalyzed Enantioselective Syntheses of Planar Chiral Ferrocenes

Planar chiral ferrocene derivatives have been proved to be effective ligands and catalysts in asymmetric catalysis. The study toward enantioselective synthesis of planar chiral ferrocenes became one of the high hot spots. In this paper, the recent advance in transition-metal-catalyzed menthods for the syntheses of planar chiral ferrocenes is reviewed.

ChemInform Abstract: (R)‐(+)‐Binol‐Functionalized Mesoporous Organosilica as a Highly Efficient Pre‐Chiral Catalyst for Asymmetric Catalysis.

AbstractThe cocondensation of Mom‐protected 6,6′‐bis(3‐trimethoxysilylpropyl)‐(R)‐BINOL with 1,2‐bis(trimethoxysilyl)ethane (BTME) in an acidic medium using the P123 surfactant as the template affords mesoporous organosilicas (MOS) with bridging ethane and (R)‐BINOL in the framework and an ordered 2D hexagonal mesostructure.

(R)‐(+)‐Binol‐Functionalized Mesoporous Organosilica as a Highly Efficient Pre‐Chiral Catalyst for Asymmetric Catalysis

(R)-(+)-Binol-functionalized chiral periodic mesoporous organosilicas (PMOs) with different framework compositions were successfully synthesized by cocondensation of (R)-2,2'-di(methoxymethyl)oxy-6,6'-di(1-propyltrimethoxysilyl)-1,1'-binaphthyl (BSBinol) with 1,2-bis(trimethoxysilyl)ethane (BTME) and tetramethoxysilane (TMOS) using triblock copolymer P123 as a template in acidic solution. The mixture of BTME and BSBinol can result in a highly ordered mesostructure in an acidic medium but the mesoporous materials synthesized using a mixture of TMOS and BSBinol can only be obtained in a weak acidic buffer solution. All the materials are efficient catalysts (coordinated with Ti) for asymmetric addition of diethylzinc to aldehydes. The chiral PMO with ethane and (R)-(+)-Binol in the framework exhibits an enantioselectivity as high as 90% with a turnover frequency (TOF) of 104 h(-1), which is even higher than the homogeneous (R)-(+)-Binol catalyst (83% ee with TOF of 96 h(-1)) using toluene as solvent under similar conditions. This work demonstrates the positive effect of the rigid pore wall in increasing the enantioselectivity of the chiral PMOs.

Synthesis and characterization of mesoporous zirconium phosphonates: A novel supported cinchona alkaloid catalysts in asymmetric catalysis

In this paper, cinchonidine (CD) with the different arm lengths ( n = 2–6) was covalently immobolized onto the backbone of zirconium phosphonate to afford a series of mesoporous zirconium phosphonates ( 4a – e ) for the first time. It was found that zirconium phosphonates ( 4a – e ) were conglomerated with the globular aggregates with the diameters of about 100–150 nm and possessed the surface areas of 20.8–36.2 m 2 g −1 , pore volumes of 0.219–0.498 cc g −1 and average pore sizes of 11.7–41.5 Å. The TEM images of 4a – e in organic solvent showed that these materials were easily swollen into the filiform structure with the length about several micrometers and thickness about 30–50 nm. In the field of the asymmetric catalysis, the preliminarily enantioselective addition of diethylzinc to various aldehydes catalyzed by 4a – e (35–62%e.e. in the 68–92% yield) was carried out and can be reused ten times without loss in the yield and enantiomeric excess.