Heterogeneous Chiral Catalysts Research Articles

Heterogeneous Asymmetric Hydrogenation of C═C and C═O Double Bonds

AbstractNowadays, heterogeneous catalysts play a crucial role in the field of asymmetric catalysis to produce enantiopure compounds for various applications. The unique properties of heterogeneous systems, such as high stability, reusability, or ease of separation, allow effective catalysis of asymmetric transformations and their further implementation in industrial processes. In this mini‐review, we address the recent trend in the synthesis of chiral heterogeneous catalysts and their subsequent application in asymmetric hydrogenation reactions. We focus on current advances in asymmetric hydrogenation reactions of C═C and C═O bonds due to their high relevance in the fine chemicals industry. Our main aim is to provide a short overview of this expanding field, its current challenges, and future perspectives.

Copper‐Catalyzed Simultaneous Dehydrogenation and Enantioselective Allylic Oxidation of Alkanes Using Chiral Heterogeneous Ligands to Produce Allylic Esters and Theoretical Investigation of the Mechanism

ABSTRACTA new asymmetric method for preparing chiral allylic esters from various unactivated alkanes through simultaneous dehydrogenation and enantioselective allylic oxidation in the presence of chiral heterogeneous oxazoline–based ligands is reported for the first time. For this purpose, chiral amino oxazoline ligands, synthesized from chiral amino alcohols and cyanogen bromide, were immobilized on modified MCM‐41 mesoporous silica. These chiral heterogeneous ligands were then characterized using Fourier‐transform infrared spectroscopy, thermogravimetric analysis, X‐ray diffraction, scanning electron microscopy, energy‐dispersive X‐ray spectroscopy, and Brunauer–Emmett–Teller and Barrett–Joyner–Halenda techniques. Finally, copper complexes of these ligands were employed in the synthesis of chiral allylic esters, achieving the best result with a 90% yield and 77% enantiomeric excess. Evaluation of the recyclability of the chiral heterogeneous catalysts revealed that they can be reused three times without a noticeable reduction in the results. In addition, the mechanism of formation of the chiral allylic esters was investigated using a density functional theory method.

Crystalline Olefin-Linked Chiral Covalent Organic Frameworks as a Platform for Asymmetric Catalysis.

The construction of olefin-linked chiral covalent organic frameworks (COFs) with high crystallinity is highly desirable while remains great challenge due to the poor reversibility of the formation reaction for the olefin linkages during the in situ structural self-healing process. Herein, we successfully synthesized two sets of enantiomeric olefin-linked COFs. The chiral catalytic groups are uniformly distributed on the pore walls of COFs, resulting in the full exposure of catalytic sites to the reactants in asymmetric catalysis. The as-prepared (R)/(S)-CCOF8 exhibits excellent catalytic performance with exceeding 99 % enantiomeric excess in the enantioselective electrophilic amination reaction. Moreover, the heterogeneous chiral catalysts are conveniently recycled and could maintain the performance after ten catalytic cycles. Our findings expand the scope to construct stable and crystalline chiral COFs for the asymmetric catalysis.

Crystalline Olefin‐Linked Chiral Covalent Organic Frameworks as a Platform for Asymmetric Catalysis

AbstractThe construction of olefin‐linked chiral covalent organic frameworks (COFs) with high crystallinity is highly desirable while remains great challenge due to the poor reversibility of the formation reaction for the olefin linkages during the in situ structural self‐healing process. Herein, we successfully synthesized two sets of enantiomeric olefin‐linked COFs. The chiral catalytic groups are uniformly distributed on the pore walls of COFs, resulting in the full exposure of catalytic sites to the reactants in asymmetric catalysis. The as‐prepared (R)/(S)‐CCOF8 exhibits excellent catalytic performance with exceeding 99 % enantiomeric excess in the enantioselective electrophilic amination reaction. Moreover, the heterogeneous chiral catalysts are conveniently recycled and could maintain the performance after ten catalytic cycles. Our findings expand the scope to construct stable and crystalline chiral COFs for the asymmetric catalysis.

Amplifying enantioselectivity in asymmetric transformations using heterogeneous chiral single-rhodium-site catalyst with sustained catalytic activity

Rhodium-catalyzed asymmetric reactions have played a pivotal role in the synthesis of functional chiral molecules. However, the ambiguous mechanism involving several plausible catalytically active species, the potential for catalyst deactivation and the need for constant reusability remain key challenges. Heterogeneous chiral Rh catalysts are highly desirable, but their performance has been hampered by low density and stability of catalytically active sites. Herein, we have devised a versatile methodology for fabricating highly efficient and robust chiral heterogeneous single-Rh-site catalysts by direct polymerization. The successful anchoring of single Rh-ligand species, the amplification of enantioselective inductive ability and the uniform distribution of atomic Rh sites within the resulting polymer matrix are identified as crucial factors contributing to their exceptional catalytic performance via comprehensive characterization and controlled experiments. In contrast to the corresponding homogeneous analogues, these chiral single-Rhodium-site catalysts exhibit outstanding performance, yielding enhanced enantioselectivity and broad applicability, even accommodating various functional groups. Remarkably, these results are achieved with just half catalyst dosage. Furthermore, their industrial potential is demonstrated through successful utilization in continuous flow processes and robust batch recycling. In future, we aim to expand the horizons of heterogeneous chiral single-metal-site catalysis, and bring us a step closer to practical asymmetric synthesis.

Enantioselective recognition, synthesis, and separation of pharmaceutical compounds at chiral metallic surfaces.

The development of new pharmaceutical compounds is challenging because most of them are based on enantiopure chiral molecules, which exhibit unique properties for therapy. However, the synthesis of pharmaceutical compounds in the absence of a chiral environment naturally leads to a racemic mixture. Thus, to control their synthesis, an asymmetric environment is required, and chiral homogeneous catalysts are typically used to synthesize enantiopure pharmaceutical compounds (EPC). Nevertheless, homogeneous catalysts are difficult to recover after the reaction, generating additional problems and costs in practical processes. Thus, the development of chiral heterogeneous catalysts is a timely topic. In a more general context, such chiral materials cannot only be used for synthesis, but also to recognize and separate enantiomers. In the frame of these different challenges, we give in this review a short introduction to strategies to extrinsically and intrinsically modify heterogeneous metal matrixes for the enantioselective synthesis, recognition, and separation of chiral pharmaceutical compounds.

Continuous-Flow Enantioselective Hydrogenative Enyne Cyclization with Chiral Heterogeneous Rh Catalysts

Continuous-Flow Enantioselective Hydrogenative Enyne Cyclization with Chiral Heterogeneous Rh Catalysts

Continuous-Flow Enantioselective Hydroacylations under Heterogeneous Chiral Rhodium Catalysts.

Transition metal-catalyzed enantioselective C-H bond functionalizations have become efficient methods for the synthesis of complex optically active molecules. Heterogeneous catalysts for this chemistry remain largely unexplored despite the advantages they offer in terms of ease of separation and reuse of catalysts. Herein, we report the development of heterogeneous chiral Rh catalysts for continuous-flow enantioselective hydroacylations. Heterogeneous catalysts could be prepared simply by mixing supports and Rh complexes. The prepared catalysts exhibited excellent activity and enantioselectivity affording optically active ketones in quantitative yields with 99 % ee's. Under the optimized reaction conditions, a turnover number >300 was achieved without the leaching of Rh species. The catalysts exhibited a wide substrate scope and in sequential-flow reactions with other heterogeneous catalysts, the syntheses of biologically active molecules and functional materials were demonstrated.

Continuous‐Flow Enantioselective Hydroacylations under Heterogeneous Chiral Rhodium Catalysts

AbstractTransition metal‐catalyzed enantioselective C−H bond functionalizations have become efficient methods for the synthesis of complex optically active molecules. Heterogeneous catalysts for this chemistry remain largely unexplored despite the advantages they offer in terms of ease of separation and reuse of catalysts. Herein, we report the development of heterogeneous chiral Rh catalysts for continuous‐flow enantioselective hydroacylations. Heterogeneous catalysts could be prepared simply by mixing supports and Rh complexes. The prepared catalysts exhibited excellent activity and enantioselectivity affording optically active ketones in quantitative yields with 99 % ee's. Under the optimized reaction conditions, a turnover number >300 was achieved without the leaching of Rh species. The catalysts exhibited a wide substrate scope and in sequential‐flow reactions with other heterogeneous catalysts, the syntheses of biologically active molecules and functional materials were demonstrated.

Polymer-Supported Chiral Heterogeneous Copper Catalyst for Asymmetric Conjugate Addition of Ketones and Imines under Batch and Flow

Enantioselective conjugate addition reactions are powerful methods in synthesizing optically active molecules. Procedures that employ chiral homogeneous catalysts have been developed extensively, but ones that use chiral heterogeneous catalysts are less explored and remain a challenge. Here we report a polymer-supported chiral heterogeneous copper catalyst that demonstrated high reactivity and enantioselectivity in asymmetric conjugate addition reactions of both ketones and imines. It was found that reduced steric hindrance inside the micro catalytic environment and a 1:1 ligand to metal ratio was crucial for the high efficiency and reusability of the chiral heterogeneous catalyst. Various α,β-unsaturated carbonyl substrates, including pharmaceutical intermediates and natural products, could be transformed in high yields with high enantioselectivities. Successful application of this methodology in a continuous flow fashion further broadened its usage in dealing with sensitive organozinc reagents. In addition, production was successfully scaled up under the flow condition.

Primary amine–thiourea grafted graphene–based heterogeneous chiral catalysts for highly enantioselective Michael additions

Heterogeneous asymmetric catalysis based on earth-abundant carbon materials put together the advantages for the ease of separation, simple regeneration, and high stability of solid catalysts as well as acts as low-cost, environmentally friendly metal-free alternative to the metal-based catalysts. Two new bifunctional carbocatalysts [(S,S) and (R,R) GO-PATU] were prepared by anchoring enantiomerically pure organosilanes bearing primary amine and thiourea groups to the graphene oxide (GO) skeleton covalently via silane coupling reaction. The surface modification of GO was analyzed by a combination of Fourier-transform infrared spectroscopy (FT-IR), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and transmission electron spectroscopy (TEM) techniques. The catalytic performances of graphene-based materials were investigated in the asymmetric Michael addition reactions of α,α-disubstituted-aldehydes to nitrostyrenes and N-substituted-maleimides. The effects of solvents and Brønsted basic or acidic additives were evaluated using both catalysts and good yields (up to 85%) and stereoselectivities (up to 95% ee) were obtained in dichloromethane at room temperature in the presence of l- and d-camphorsulfonic acid. Besides, recycling and reusing studies of the catalysts were successfully performed.

Heterogeneous Enantioselective Hydrogenation of Ketones by 2-Amino-2′-hydroxy-1,1′-binaphthyl-Modified CeO2-Supported Ir Nanoclusters

Modification of supported noble metals with chiral modifiers is a promising strategy for the design of effective heterogeneous chiral catalysts. The chiral compounds are generally introduced on the surface of noble metals, often leading to low enantioselectivity and to low activity. Herein, a unique heterogeneous chiral catalyst where a chiral modifier is introduced at the interface between the metal cluster and the support is presented. Modification of CeO2-supported Ir nanoclusters with 2-amino-2′-hydroxy-1,1′-binaphthyl (NOBIN) as a chiral modifier provided a heterogeneous chiral catalyst where NOBIN is introduced at the interface between Ir nanoclusters and the CeO2 support. The heterogeneous chiral catalyst enabled the asymmetric hydrogenation of acetophenone to provide 1-phenylethanol with moderate enantiomeric excess (ee) (up to 53%). The catalyst characterizations showed that about 1 nm Ir metal nanoclusters are formed on CeO2, and density functional theory calculations presented that NOBIN is adsorbed onto Ir nanoclusters and CeO2 at the NH2 and OH groups, respectively, constructing the asymmetric reaction field among NOBIN, Ir nanoclusters, and CeO2.

Chiral Heterogeneous Scandium Lewis Acid Catalysts for Continuous-Flow Enantioselective Friedel-Crafts Carbon-Carbon Bond-Forming Reactions.

While continuous-flow reactions with chiral heterogeneous catalysts provide a highly efficient method to synthesize optically active compounds, chiral heterogeneous Lewis acid catalysis has been less extensively explored. We have developed the first example of chiral heterogeneous Sc catalysts, which demonstrated excellent activity and selectivity for continuous-flow enantioselective Friedel-Crafts reactions of isatins with indoles. Noncovalent interactions between chiral Sc complexes and heteropoly acid-anchored amine-functionalized SiO2 as support were utilized for the synthesis. The heteropoly acid was found to be crucial for the preparation, activity, and selectivity of the catalysts. The chiral ligand could be easily tuned without chemical modification and the continuous-flow synthesis of a biologically active compound was achieved.

Chiral Heterogeneous Scandium Lewis Acid Catalysts for Continuous‐Flow Enantioselective Friedel–Crafts Carbon–Carbon Bond‐Forming Reactions

AbstractWhile continuous‐flow reactions with chiral heterogeneous catalysts provide a highly efficient method to synthesize optically active compounds, chiral heterogeneous Lewis acid catalysis has been less extensively explored. We have developed the first example of chiral heterogeneous Sc catalysts, which demonstrated excellent activity and selectivity for continuous‐flow enantioselective Friedel–Crafts reactions of isatins with indoles. Noncovalent interactions between chiral Sc complexes and heteropoly acid‐anchored amine‐functionalized SiO2 as support were utilized for the synthesis. The heteropoly acid was found to be crucial for the preparation, activity, and selectivity of the catalysts. The chiral ligand could be easily tuned without chemical modification and the continuous‐flow synthesis of a biologically active compound was achieved.

Machine‐Assisted Preparation of a Chiral Diamine Ligand Library and In Silico Screening Using Ab Initio Structural Parameters for Heterogeneous Chiral Catalysts

AbstractA ligand library containing 31 chiral diamines was synthesized using a flow‐based semiautomatic reductive amination system. These ligands were evaluated in a continuous‐flow asymmetric 1,4‐addition reaction with a heterogeneous Ni catalyst. Based on the experimental results of ab initio DFT calculations, a prediction model for enantioselectivities was successfully constructed. Furthermore, virtual screening of possible ligands was conducted to identify promising structures, which showed good enantioselectivities in experiments.magnified image

L-cysteine-functionalized CuPt: A chiral electrode for the asymmetric electroreduction of aromatic ketones

The heterogeneous chiral catalyst L-cysteine-CuPt prepared by the bonding between the natural and inexpensive L-cysteine and CuPt obtained by a simple method in a green process exceled in this work. L-cysteine showed strong chemisorption through the bonding of the sulfhydryl group with the CuPt, so it could be firmly present on the surface of the alloy. Detailed surface analysis were carried out on the as-prepared L-cysteine-CuPt which was further applied to catalyze the asymmetric electroreduction of aromatic ketones. (R)-α-(trifluoromethyl) benzyl alcohol with 73% yield and 43% ee was obtained on the L-cysteine-CuPt cathode under the optimized electrolytic reaction conditions. In addition to owning the activity capable of efficiently catalyzing the substrate to produce optically active products, the L-cysteine-CuPt also exhibited strong stability such that the catalytic results did not significantly change on it after repeated use.

Silica gel-immobilised chiral 1,2-benzenedisulfonimide: a Brønsted acid heterogeneous catalyst for enantioselective multicomponent Passerini reaction

A chiral heterogeneous catalyst derivative of (−)-4,5-dimethyl-3,6-bis(1-naphthyl)-1,2-benzenedisulfonimide is proven here to be efficient in a three-component asymmetric Passerini protocol, carried out in a deep eutectic solvent. Reaction conditions are mild and green, while enantioselectivity is excellent. The catalyst was easily recovered and reused with no decrease in its catalytic activity.

Recyclable and reusable chiral α, α-L-diaryl prolinol heterogeneous catalyst grafting to UiO-67 for enantioselective hydration/aldol/oxa-Diels Alder domino reaction

α,α-L-Diaryl prolinol was first introduced into a highly stable porous MOF, UiO-67, via the immobilization of a chiral prolinol side chain into 4,4′-biphenyldicarboxylic acid through a five-step process, to construct a chiral heterogeneous catalyst. The catalyst exhibited high yield (up to 88%) and excellent stereoselectivities (up to >4:1 dr, > 80% ee) for the enantioselective hydration/aldol/oxa-Diels Alder domino reactions, as well as good reusability with recycle use for three times without significant loss of activity. To our knowledge, this is the first report of chiral MOFs as heterogeneous catalysts for asymmetric domino reactions.

Synthesis, characterization and catalytic performance in enantioselective reactions by mesoporous silica materials functionalized with chiral thiourea-amine ligand

Chiral heterogeneous catalysts have been synthesized by grafting of silyl derivatives of (1R, 2R)- or (1S, 2S)-1,2-diphenylethane-1,2-diamine on SBA-15 mesoporous support. The mesoporous material SBA-15 and so-prepared chiral heterogeneous catalysts were characterized by a combination of different techniques such as X-ray diffractometry (XRD), Fourier transform infrared (FT-IR), thermogravimetric analysis (TGA), field emission scanning electron microscopy (FESEM), and Brunauer–Emmett–Teller (BET) surface area. Results showed that (1R, 2R)- and (1S, 2S)-1,2-diphenylethane-1,2-diamine were successively immobilized on SBA-15 mesoporous support. Chiral heterogeneous catalysts and their homogenous counterparts were tested in enantioselective transfer hydrogenation of aromatic ketones and enantioselective Michael addition of acetylacetone to β-nitroolefin derivatives. The catalysts demonstrated notably high catalytic conversions (up to 99%) with moderate enantiomeric excess (up to 30% ee) for the heterogeneous enantioselective transfer hydrogenation. The catalytic performances for enantioselective Michael reaction showed excellent activities (up to 99%) with poor enantioselectivities. Particularly, the chiral heterogeneous catalysts could be readily recycled for Michael reaction and reused in three consecutive catalytic experiments with no loss of catalytic efficacies.

A Nickel‐Bisdiamine Porous Organic Polymer as Heterogeneous Chiral Catalyst for Asymmetric Michael Addition to Aliphatic Nitroalkenes

AbstractWe report a polystyrene‐incorporated chiral nickel(II)‐bisdiamine complex, which is accessible on gram‐scale. This metal complex functions as a heterogeneous catalyst for the enantioselective Michael addition between malonates and aliphatic nitroalkenes, and it provides yields and enantioselectivities on par with homogeneous catalysts. Good functional group tolerance is reported for this reaction. Upon recycling, the catalyst achieves significantly higher TONs than previously reported. We demonstrate scalability to multigram‐scale, compatibility with continuous flow production (4.43 gram), and application to the synthesis of the blockbuster drug Pregabalin. Finally, a new tandem reaction is disclosed.magnified image