Application In Asymmetric Catalysis Research Articles

Betti base derived P-stereogenic phosphine-diamidophosphite ligands with a single atom spacer and their application in asymmetric catalysis

Small bite-angle P-chirogenic PNP ligands have been synthesized stereo-selectively and employed in Rh-catalyzed asymmetric hydrogenation and Pd-catalyzed asymmetric allylic substitution resulting in moderate to excellent enantioselectivities.

Palladium/Xiao-Phos-Catalyzed Kinetic Resolution of sec-Phosphine Oxides by P-Benzylation.

P-stereogenic tert- and sec-phosphines have wide applications in asymmetric catalysis, materials, and pharmaceutical chemistry, however, their practical synthesis still constitutes a significant challenge. Herein, a successful kinetic resolution of rac-secondary phosphine oxides via the enantioselective P-benzylation process catalyzed by the palladium/Xiao-Phos was designed. Both tert- and sec-phosphine oxides were delivered in good yield and excellent enantiopurity (selectivity factor up to 226.1). The appealing synthetic utilities are further demonstrated by the facile preparation of several valuable P-chiral compounds, precursors of bidentate ligands, as well as transition metal complexes.

Palladium/Xiao‐Phos‐Catalyzed Kinetic Resolution of sec‐Phosphine Oxides by P‐Benzylation

AbstractP‐stereogenic tert‐ and sec‐phosphines have wide applications in asymmetric catalysis, materials, and pharmaceutical chemistry, however, their practical synthesis still constitutes a significant challenge. Herein, a successful kinetic resolution of rac‐secondary phosphine oxides via the enantioselective P‐benzylation process catalyzed by the palladium/Xiao‐Phos was designed. Both tert‐ and sec‐phosphine oxides were delivered in good yield and excellent enantiopurity (selectivity factor up to 226.1). The appealing synthetic utilities are further demonstrated by the facile preparation of several valuable P‐chiral compounds, precursors of bidentate ligands, as well as transition metal complexes.

Carbene‐Catalyzed Enantioselective Hydrophosphination of α‐Bromoenals to Prepare Phosphine‐Containing Chiral Molecules

AbstractDisclosed herein is the first carbene‐organocatalyzed asymmetric addition of phosphine nucleophiles to the in situ generated α,β‐unsaturated acyl azolium intermediates. Our reaction enantioselectively constructs carbon–phosphine bonds and prepares chiral phosphines with high optical purities. The phosphine products are suitable for transforming to chiral ligands or catalysts with applications in asymmetric catalysis. The diarylalkyl or trialkyl phosphine products from our catalytic reactions, air‐sensitive and reactive in nature, can be trapped (and stored) in their sulfur‐oxidized form for operational simplicities.

Carbene-Catalyzed Enantioselective Hydrophosphination of α-Bromoenals to Prepare Phosphine-Containing Chiral Molecules.

Disclosed herein is the first carbene-organocatalyzed asymmetric addition of phosphine nucleophiles to the in situ generated α,β-unsaturated acyl azolium intermediates. Our reaction enantioselectively constructs carbon-phosphine bonds and prepares chiral phosphines with high optical purities. The phosphine products are suitable for transforming to chiral ligands or catalysts with applications in asymmetric catalysis. The diarylalkyl or trialkyl phosphine products from our catalytic reactions, air-sensitive and reactive in nature, can be trapped (and stored) in their sulfur-oxidized form for operational simplicities.

Phosphination of Phenol Derivatives and Applications to Divergent Synthesis of Phosphine Ligands.

We describe a general and efficient protocol for the synthesis of organophosphine compounds from phenols and phosphines (R2PH) via a metal-free C-O bond cleavage and C-P bond formation process. This approach exhibits broad substrate scope and excellent functional group tolerance. The synthetic utilities of this protocol were demonstrated by the synthesis of chiral ligands via the various transformations of cyano groups and their applications in asymmetric catalysis.

An efficient chiral porous catalyst support – Hypercrosslinked amino acid polymer

The application of asymmetric catalysis in industrial processes is limited by the high cost of chiral ligands and the difficulty associated with recovering precious metal catalysts. Here, based on a FeCl3-catalyzed Friedel–Crafts alkylation reaction, an aromatic amino acid was crosslinked with 4,4′-bis(chloromethyl)-1,1′-biphenyl to produce a novel porous chiral catalyst support, hypercrosslinked amino acid polymer (HCP-AA). Subsequently, metal catalysts were loaded on HCP-AA through the coordination of the metal ion with amino acid residues to generate heterogeneous asymmetric catalysts, HCP-AA-M. The resulting catalysts were characterized by scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy. The HCP-AA-M samples were employed to catalyze the heterogeneous asymmetric reaction, and they achieved high enantioselectivities (up to 99% ee). Meanwhile, the catalysts could be readily recovered through filtration, and they exhibited good recycling performances. The results suggested that the utilization of inexpensive amino acids as raw materials for producing porous chiral supports for recyclable high-performance asymmetric catalysts is an effective strategy.

Towards Data‐Driven Design of Asymmetric Hydrogenation of Olefins: Database and Hierarchical Learning

AbstractAsymmetric hydrogenation of olefins is one of the most powerful asymmetric transformations in molecular synthesis. Although several privileged catalyst scaffolds are available, the catalyst development for asymmetric hydrogenation is still a time‐ and resource‐consuming process due to the lack of predictive catalyst design strategy. Targeting the data‐driven design of asymmetric catalysis, we herein report the development of a standardized database that contains the detailed information of over 12000 literature asymmetric hydrogenations of olefins. This database provides a valuable platform for the machine learning applications in asymmetric catalysis. Based on this database, we developed a hierarchical learning approach to achieve predictive machine leaning model using only dozens of enantioselectivity data with the target olefin, which offers a useful solution for the few‐shot learning problem and will facilitate the reaction optimization with new olefin substrate in catalysis screening.

Towards Data-Driven Design of Asymmetric Hydrogenation of Olefins: Database and Hierarchical Learning.

Asymmetric hydrogenation of olefins is one of the most powerful asymmetric transformations in molecular synthesis. Although several privileged catalyst scaffolds are available, the catalyst development for asymmetric hydrogenation is still a time- and resource-consuming process due to the lack of predictive catalyst design strategy. Targeting the data-driven design of asymmetric catalysis, we herein report the development of a standardized database that contains the detailed information of over 12000 literature asymmetric hydrogenations of olefins. This database provides a valuable platform for the machine learning applications in asymmetric catalysis. Based on this database, we developed a hierarchical learning approach to achieve predictive machine leaning model using only dozens of enantioselectivity data with the target olefin, which offers a useful solution for the few-shot learning problem and will facilitate the reaction optimization with new olefin substrate in catalysis screening.

Ni-Catalyzed Asymmetric Hydrophosphination of Unactivated Alkynes.

The practical synthesis of P-stereogenic tertiary phosphines, which have wide applications in asymmetric catalysis, materials, and pharmaceutical chemistry, represents a significant challenge. A regio- and enantioselective hydrophosphination using cheap and ubiquitous alkynes catalyzed by a nickel complex was designed, in which the toxic and air-sensitive secondary phosphines were prepared in situ from bench-stable secondary phosphine oxides. This methodology has been demonstrated with unprecedented substrate scope and functional group compatibility to afford electronically and structurally diversified P(III) compounds. The products could be easily converted into various precursors of bidentate ligands and organocatalysts, as well as a variety of transition-metal complexes containing both P- and metal-stereogenic centers.

Ex situ nucleation and growth study of the pure silica HPM-1 zeolite

In this manuscript, we reveal some insights into the nucleation and growth mechanism of pure silica zeolite HPM-1. This chiral material has attracted interest from academic and industrial researchers due to its potential for application in asymmetric catalysis and the separation of racemic products. We investigate four samples synthesized with different crystallization times and characterize them by X-ray diffraction, infrared spectroscopy, electron microscopy and small-angle X-ray scattering (SAXS). We propose a four-step synthesis mechanism based on the different populations of nanoparticles and the porous surface intermediate that is observed. We demonstrate that this synthesis follows a nonclassical mechanism of zeolitic nucleation and growth.

Azetidines and their applications in asymmetric catalysis

Abstract Since the early 1990s asymmetric catalytic applications of chiral, azetidine-derived, ligands and organocatalysts have been developed and utilised to engender asymmetry in reactions including Friedel-Crafts alkylations, Henry reactions and Michael-type reactions. This review surveys the effective synthetic opportunities presented by chiral azetidines in asymmetric catalysis. In order to benchmark, contrast and evaluate these asymmetric azetidine-containing catalysts, comparisons with aziridine- and pyrrolidine-containing analogues are drawn.

Chiral Cyclopentadienyl Ligands: Design, Syntheses, and Applications in Asymmetric Catalysis.

The creation of new chiral ligands capable of providing high stereocontrol in metal-catalyzed reactions is crucial in modern organic synthesis. The production of bioactive molecules as single enantiomers is increasingly required, and asymmetric catalysis with metal complexes constitutes one of the most efficient synthetic strategies to access optically active compounds. Herein we offer a historical overview on the development of chiral derivatives of the ubiquitous cyclopentadienyl ligand (CpX ), and detail their successful application in a broad range of metal-catalyzed transformations. Those include the functionalization of challenging C-H bonds and beyond, giving access to an extensive catalogue of valuable chiral molecules. A critical comparison of the existing ligand families, their design, synthesis, and complexation to different metals is also provided. In addition, future research directions are discussed to further enhance the performance and application of CpX ligands in enantioselective catalysis.

Chiral Cyclopentadienyl Ligands: Design, Syntheses, and Applications in Asymmetric Catalysis

AbstractThe creation of new chiral ligands capable of providing high stereocontrol in metal‐catalyzed reactions is crucial in modern organic synthesis. The production of bioactive molecules as single enantiomers is increasingly required, and asymmetric catalysis with metal complexes constitutes one of the most efficient synthetic strategies to access optically active compounds. Herein we offer a historical overview on the development of chiral derivatives of the ubiquitous cyclopentadienyl ligand (CpX), and detail their successful application in a broad range of metal‐catalyzed transformations. Those include the functionalization of challenging C−H bonds and beyond, giving access to an extensive catalogue of valuable chiral molecules. A critical comparison of the existing ligand families, their design, synthesis, and complexation to different metals is also provided. In addition, future research directions are discussed to further enhance the performance and application of CpXligands in enantioselective catalysis.

Catalytic Asymmetric Synthesis of P-Stereogenic Phosphines: Beyond Precious Metals

AbstractMetal-catalyzed asymmetric synthesis of P-stereogenic phosphines is a potentially useful approach to a class of chiral ligands with valuable applications in asymmetric catalysis. We introduced this idea with chiral platinum and palladium catalysts, exploiting rapid pyramidal inversion in diastereomeric metal–phosphido complexes (ML*(PRR′)) to control phosphorus stereochemistry. This Account summarizes our attempts to develop related synthetic methods using earth-abundant metals, especially copper, in which weaker metal–ligand bonds and faster substitution processes were expected to result in more active catalysts. Indeed, precious metals were not required. Without any transition metals at all, we exploited related P-epimerization processes to prepare enantiomerically pure phosphiranes and secondary phosphine oxides (SPOs) from commercially available chiral epoxides.1 Introduction2 Copper-Catalyzed Phosphine Alkylation3 Copper-Catalyzed Tandem Phosphine Alkylation/Arylation4 Nickel-Catalyzed Phosphine Alkylation5 Proton-Mediated P-Epimerization in Synthesis of Chiral Phosphiranes6 Diastereoselective Synthesis of P-Stereogenic Secondary Phosphine Oxides (SPOs) from (+)-Limonene Oxide7 Conclusions

Galantamine derivatives: Synthesis, NMR study, DFT calculations and application in asymmetric catalysis

In a search of effective ligands for asymmetric catalysis (−)-galantamine has been selected as a complex chiral framework for the synthesis of four novel diphenylphosphino-benzenecarboxamides. Their application in Pd-catalyzed asymmetric allylic alkylation proceeded with excellent conversion and moderate enantioselectivity due to the conformational flexibility of the galantamine derived compounds. To get insights into their molecular structure and conformational behaviour in solution a combination of experimental NMR methods and theoretical DFT calculations has been employed. The ligands exist as four conformers due to restricted rotation around the amide bond and due to flexibility of the 2,3,4,5-tetrahydro-1H-azepine ring. The experimentally measured barriers of C–N rotation (17.1 ÷ 17.7 kcal/mol) are higher than the barriers of observed exchange process in azepine ring (13.7 ÷ 14.0 kcal/mol). Their BOC precursors exist in solution as two conformers due to restricted rotation around the carbamate C–N bond. The experimentally measured barrier is lower than the amide barriers in ligands (16.1 ÷ 16.5 kcal/mol).

Ion-Pairing Chirality Transfer in Atropisomeric Biaryl-Centered Gold Clusters

The stereocontrol of chiral metal clusters and nanoclusters has become a focus of interest in metal cluster chemistry due to their promising applications in asymmetric catalysis. Despite being a ge...

Diaza-Crown Ether-Bridged Chiral Diphosphoramidite Ligands: Synthesis and Applications in Asymmetric Catalysis.

A small library of diaza-crown ether-bridged chiral diphosphoramidite ligands was prepared. In the rhodium-catalyzed asymmetric hydrogenation and hydroformylation reactions, these ligands exhibited distinct properties in catalytic activity and/or enantioselectivity. Hydrogenated products with opposite absolute configurations could be obtained in high yields with excellent ee values by utilizing (S,S)-L1 and (S,S)-L3, respectively. Meanwhile, the addition of alkali metal cations caused variations in catalytic outcomes, showing the supramolecular tunability of these Rh/diphosphoramidite catalytic systems.

A Chiral Organic-inorganic Hybrid Crystal Constructed by Self-assembly of Achiral Azobispyridium Cations

Chiral crystals have particular interest due to their application in asymmetric catalysis, ferroelectrics, and nonlinear optics. A novel molecule, 2,2′-azobis (5-methylpyridine) ([abmpy]) was synthesized and utilized to prepare organic-inorganic hybrid crystals with anions of ZnCl42−, BiI52−, Sb2Cl82−, ZnBr42− and SnCl62−, respectively. The packing mode of [abmpyH2] cations was tuned by these anions. [abmpyH2] cations stacked in helical arrangement in [abmpyH2]ZnCl4 crystal which resulted in a chiral space group of C222, while the other four compounds crystallize in centrosymmetric point groups. The absolute structures of [abmpyH2]ZnCl4 crystals were confirmed by single-crystal X-ray using the Flack parameter method, and positive and negative Cotton effect could also be found in the CD spectra for the two enantiomers of [abmpyH2]ZnCl4 crystals. Besides, the nonlinear effect was observed for this chiral crystal.

Coinage Metal Complexes of Chiral N‐Heterocyclic Carbene Ligands: Syntheses and Applications in Asymmetric Catalysis

AbstractChiral N‐heterocyclic carbenes (NHCs) have become ligands of choice due to their remarkable catalytic activity in organic transformation reactions. Combining the chiral NHC ligand family and coinage metals became a productive area of research. The organometallic chemistry of coinage metals with the chiral N‐heterocyclic carbene (NHC) ligands is reviewed, with a special emphasis on the synthesis, characterization and possible applications obtained. Significant sections are devoted to the various recently developed coinage metal‐chiral NHC complexes and a detailed comparison of their activities which aims to rationalize the structure–activity relationships. Various methods of preparations of coinage metal‐chiral NHC complexes along with some typical examples of reactivity and mechanisms are covered. Cu‐chiral NHC complexes involved in conjugated additions, allylic substitutions, boration of alkenes, hydrosilylation of ketones and formation of alkenes are covered, along with some remarkable examples and reactivity of Ag‐chiral NHC complexes. Finally, applications of Au‐chiral NHC complexes in the asymmetric cyclization of ester‐functionalized 1,6‐enynes, 1,6‐enyneamines and substituted propargyloxymethanes are also reviewed.magnified image