Ligands In Transition Metal Catalysis Research Articles

Natural Chiral Ligand Strategy: Metal-Catalyzed Reactions with Ligands Prepared from Amino Acids and Peptides

Amino acids and peptides are readily available biomolecules and can function as chiral ligands for transition metal catalysis. An example is the copper complex catalyzed 1,4-addition of dialkylzinc to acyclic enones, which employs peptide ligands. This review provides a dataset of amino acids and peptides reported in the literature proving to be effective ligands for metal-centered catalysts. Several parameters were highlighted, including amino acid combination, metal atoms, carboxyl and amino protecting groups, modification of natural amino acids, and the mechanism of catalysis. Along with analyzing physical-chemical properties, the SMILES representation for each amino acid and/or peptide was generated and made available online, providing an easy-to-use means of training machine learning models. This review offers an opportunity for the development of more efficient peptide ligands for enantioselective metal-centered catalysts. The available online dataset is a reliable manually curated table, it enables the benchmark for comparison of new terminal functional groups. Moreover, the review provides insight into the structures of the more successful peptide ligands and can be used as the foundation for the development of the next generation of peptide-based chiral ligands.

Synthesis of Biheteroaryls by Pd-Catalyzed Homocoupling of Heteroaryl Bromides.

Symmetrical biheteroaryl compounds, such as bypyridines and bipyrazoles, are important ligands in transition-metal catalysis. They also serve as synthetic precursors of photo catalysts/sensitizers, bioactive agents, and energetic materials. To facilitate the concise synthesis of these useful structures, an efficient Pd-catalyzed homocoupling of heteroaryl bromides has been successfully established using the electron-rich and sterically hindered monophosphorus ligand BIDIME. The coupling protocol features a tandem Miyaura borylation/Suzuki coupling sequence and exhibits unprecedented tolerance of a wide range of heteroaryl bromides, providing a series of symmetrical biheteroaryls in moderate to good yields. Notably, the use of the corresponding polymeric ligand, PolyBIDIME, enabled the recycling of a palladium catalyst, demonstrating the potential of the homocoupling in practical applications.

Photocatalytic synthesis of 2,3-diamines from anilines and DIPEA via C–N bond cleavage and C–C bond formation

2,3-Diamines are skeleton structures widely found in natural products and drug molecules and can also be used as ligands in transition metal catalysis.

Pyrazolopyridine Ligands in Transition-Metal-Catalyzed C–C and C–Heteroatom Bond-Forming Reactions

AbstractPyrazole-substituted pyridines have emerged as versatile bidentate ligands in transition-metal catalysis, providing opportunities to fine-tune reactivity and selectivity beyond what conventional bipyridine ligands can achieve. This review focuses on two representative pyrazolopyridine ligands: 2-(1H-pyrazol-1-yl)pyridine (1-PzPy) and 2-(1H-pyrazol-3-yl)pyridine (3-PzPy). The 1-PzPy series, characterized by a pyrazole ring serving as a weakly coordinating Lewis basic ligand, offer flexibility in ligand binding. Alternatively, the 3-PzPy series provide both L2- and LX-type binding modes, functioning as hydrogen bond donors and σ-donors, respectively. The structural diversity of pyrazolopyridine ligands enables the development of various synthetic strategies, facilitating cross-coupling, cycloaddition, photocatalytic, and asymmetric reactions. This review highlights the roles of these ligands in advancing transition-metal-catalyzed C–C and C–heteroatom bond-forming reactions.1 Introduction2 Synthesis of Pyrazolopyridine Ligands3 Applications of 1-PzPy Ligands4 Applications of 3-PzPy Ligands5 Conclusion

Nondirected Pd-Catalyzed C–H Perdeuteration and meta-Selective Alkenylation of Arenes Enabled by Pyrazolopyridone Ligands

The development of ligands and the elucidation of their roles in the catalytic cycle are key to achieving high efficiency and selectivity in nondirected transition-metal-catalyzed C–H functionalization. In particular, careful ligand design can enable the functionalization of previously inaccessible substrate positions, which can lead to regiodivergent transformations of common reactants. In this study, a series of pyrazolopyridone (PzPyOH) ligands that can be easily prepared in a single step was developed for the Pd-catalyzed perdeuteration and meta-selective alkenylation of arenes. In this system, the 2-pyridone moiety was incorporated to function as an internal base, facilitating C–H cleavage and rendering C–H activation reversible, even at challenging sp2 C–H bonds, thus enabling perdeuteration. In addition, the reversible activation of the C–H bonds implies that site selectivity is determined during the migratory insertion step in the alkenylation reaction, thereby preferentially functionalizing the meta-positions rather than the typically more reactive ortho- and para-positions of anisole derivatives. Further, the electronic and structural properties of the pyrazole moiety provide flexibility in the ligand binding to Pd, enabling the facile coordination of an alkene coupling partner during alkenylation. In this process, the hydrogen bonding between pyridone and acetate ligands was crucial to stabilize intermediates, allowing for different types of binding modes, including L,L- and L,X-type bidentate and monodentate binding. Kinetic and computational studies support the proposed mechanisms for perdeuteration and alkenylation, and the findings reveal crucial factors in the design of ligands for Pd-catalyzed C–H functionalization, which will be useful for further development of pyrazole- and pyridone-containing ligands in transition metal catalysis.

Speciation and Structures in Pt Surface Sites Stabilized by N-Heterocyclic Carbene Ligands Revealed by Dynamic Nuclear Polarization Enhanced Indirectly Detected 195Pt NMR Spectroscopic Signatures and Fingerprint Analysis.

N-Heterocyclic carbenes (NHCs) are widely used ligands in transition metal catalysis. Notably, they are increasingly encountered in heterogeneous systems. While a detailed knowledge of the possibly multiple metal environments would be essential to understand the activity of metal-NHC-based heterogeneous catalysts, only a few techniques currently have the ability to describe with atomic-resolution structures dispersed on a solid support. Here, we introduce a new dynamic nuclear polarization (DNP) surface-enhanced solid-state nuclear magnetic resonance (NMR) approach that, in combination with advanced density functional theory (DFT) calculations, allows the structure characterization of isolated silica-supported Pt-NHC sites. Notably, we demonstrate that the signal amplification provided by DNP in combination with fast magic angle spinning enables the implementation of sensitive 13C-195Pt correlation experiments. By exploiting 1J(13C-195Pt) couplings, 2D NMR spectra were acquired, revealing two types of Pt sites. For each of them, 1J(13C-195Pt) value was determined as well as 195Pt chemical shift tensor parameters. To interpret the NMR data, DFT calculations were performed on an extensive library of molecular Pt-NHC complexes. While one surface site was identified as a bis-NHC compound, the second site most likely contains a bidentate 1,5-cyclooctadiene ligand, pointing to various parallel grafting mechanisms. The methodology described here represents a new step forward in the atomic-level description of catalytically relevant surface metal-NHC complexes. In particular, it opens up innovative avenues for exploiting the spectral signature of platinum, one of the most widely used transition metals in catalysis, but whose use for solid-state NMR remains difficult. Our results also highlight the sensitivity of 195Pt NMR parameters to slight structural changes.

Sparteine Family: Privileged Chiral Ligands in Transition Metal Catalysis

Abstract: Chiral ligands are the footstones for asymmetric synthesis, constructing the enantioenriched molecules that are widely used in material and medicinal sciences. Naturally occurring compounds, such as proline analogues and cinchona alkaloids, are widely used as privileged ligands in asymmetric synthesis. Sparteine, a natural alkaloid firstly reported in 1968, was also employed in asymmetric synthesis, albeit with less satisfactory results. In this perspective, transition metal-involved asymmetric transformations using sparteine or family members as ligands are overviewed and discussed. The design and perspective of ligands with similar skeleton are also proposed.

Hybrid cycloolefin ligands for palladium–olefin cooperative catalysis

The engineering of molecular catalysts in homogeneous catalysis enables new catalytic modes, which leads to efficient synthetic transformations. In this regard, the design of ligands for transition metal catalysis has played a major role. In transition metal catalysed reactions, olefins can serve as steering ligands by tuning the electronic and steric nature of the metal centre. Here we report unstrained olefin ligands that bear a P or S coordination site for use in the Pd-catalysed Catellani reaction. This olefin ligand shows a covalent catalytic function and enables an efficient ipso,ortho-difunctionalization of iodoarenes. Mechanistic analysis reveals a reversible covalent bonding between the substrate and the cycloolefin unit of the ligand, which forms key organopalladium intermediates to enable a new reactivity. Our results demonstrate a design concept that employs hybrid cycloolefin ligands as a covalent catalytic module, which opens up possibilities for further cooperative catalysis with other transition metal–olefin hybrids. Taking inspiration from palladium–norbornene cooperative catalysis, Catellani-type reactions are now performed using a hybrid olefin ligand with a P or S coordination site. This olefin ligand enables efficient ipso,ortho-difunctionalization of iodoarenes. Mechanistic studies show the formation of organopalladium intermediates that comprise both the substrate and the hybrid olefin ligand.

Development of novel syntheses of organophosphorus compounds: from a simple P-C bond formation to phosphacycles

Organophosphorus compounds play several essential roles in organic chemistry, such as valuable ligands in transition metal catalysis and functional materials. We have developed versatile organophosphine syntheses via Pd-catalyzed P-C cross-coupling reactions in the course of our study using silylphosphines. Up to three aryl groups can be selectively incorporated into the same phosphorus atom in a stepwise manner. In addition, we found the formation of phosphorus-ylide containing phosphacycles, λ5-phosphinines, during the extension of silylphosphine chemistry.

Primary Alcohols via Nickel Pentacarboxycyclopentadienyl Diamide Catalyzed Hydrosilylation of Terminal Epoxides.

The efficient and regioselective hydrosilylation of epoxides co-catalyzed by a pentacarboxycyclopentadienyl (PCCP) diamide nickel complex and Lewis acid is reported. This method allows for the reductive opening of terminal, monosubstituted epoxides to form unbranched, primary alcohols. A range of substrates including both terminal and nonterminal epoxides are shown to work, and a mechanistic rationale is provided. This work represents the first use of a PCCP derivative as a ligand for transition-metal catalysis.

Enantiopure planar chiral [2.2]paracyclophanes: Synthesis and applications in asymmetric organocatalysis

This short review focuses on enantiopure planar chiral [2.2]paracyclophanes (pCps), a fascinating class of molecules that possess an unusual three-dimensional core and intriguing physicochemical properties. In the first part of the review, different synthetic strategies for preparing optically active pCps are described. Although classical resolution methods based on the synthesis and separation of diastereoisomeric products still dominate the field, recent advances involving the kinetic resolution of racemic compounds and the desymmetrization of meso derivatives open up new possibilities to access enantiopure key intermediates on synthetically useful scales. Due to their advantageous properties including high configurational and chemical stability, [2.2]paracyclophanes are increasingly employed in various research fields, ranging from stereoselective synthesis to material sciences. The applications of [2.2]paracyclophanes in asymmetric organocatalysis are described in the second part of the review. While historically enantiopure pCps have been mainly employed by organic chemists as chiral ligands in transition-metal catalysis, these compounds can also be used as efficient catalysts in metal-free reactions and may inspire the development of new transformations in the near future.

Synthesis of α-chiral phosphine sulfides via non-covalent organocatalysis

Despite rapid advances in phosphine-containing compound as a privileged ligand for transition metal catalysis, synthesis and coordination chemistry are underexplored for the phosphine sulfide analogs. In this article, we report the enantioselective phospha-Michael addition reaction that leads to α-chiral phosphine sulfide. An independent hydrogen-bonding co-catalyst is found essential to high enantioselectivity (up to 98% yield and 95% enantiomeric excess [ee]). Divergent derivatizations under mild conditions are also attempted for the generic phosphine and phosphine oxide compounds, further emphasizing the bridge role of phosphine sulfide. An X-ray diffraction structure of κ 3 -NNS palladium complex also authenticates the coordination ability of p = S moiety. Combination of NHC and hydrogen bonding donor catalysis α-Chiral phosphine sulfides Downstream derivatizations κ 3 -NNS palladium complex In an effort to diversify the family of phosphine ligands, Li et al. report the orchestration of NHC catalysis and an H-bond donor as a straightforward synthetic strategy to yield α-chiral phosphine sulfides. Preliminary results for downstream derivatization and metal chelation further demonstrate the applications for p = S ligands.

Isomerization of Ferrocenyl Phosphinites to Phosphane-oxides and retro-Phospha-Brook Rearrangement

Ferrocene-containing phosphorus derivatives are important as ligands in transition-metal catalysis. We have investigated the synthesis of ferrocene-based phosphanes from corresponding phosphinites via retro-phospha-Brook rearrangement. Ferrocenyl phosphinites isomerize to thermodynamically more stable phosphine oxides. Interestingly, retro-phospha-Brook rearrangement proceeds on the adjacent phenyl ring with the assistance of the ferrocenyl moiety. DFT calculations provided insight into the reaction mechanisms of these transformations. Isomerization probably proceeds intramolecularly with the participation of developing charge stabilization with iron´s d-orbitals. BH3 complexation seems to favor the phosphinite structure as was evidenced by 31P-11B scalar coupling. Retro-phospha-Brook rearrangement also likely proceeds as intramolecular migration of the phosphanyl group from oxygen to carbon, from both BH3 complexes and the uncomplexed starting material.

An electrochemical perspective on the roles of ligands in the merger of transition-metal catalysis and electrochemistry

A perspective on the roles of ligands in transition-metal catalysis under electrochemical conditions is provided.

Liquid fuel synthesis via CO2 hydrogenation by coupling homogeneous and heterogeneous catalysis

Summary Synthesis of liquid fuel (C5+ hydrocarbons) via CO2 hydrogenation generally involves cascade catalysis of reverse water gas shift (RWGS) and Fischer-Tropsch synthesis (FTS) reactions over heterogeneous catalysts. Because of thermodynamic limitations of the cascade reactions, the reported heterogeneous catalysts usually suffer from high temperature (above 300°C) and low selectivity. Here, we report the liquid fuel production from CO2 hydrogenation by coupling homogeneous RuCl3 and heterogeneous Ru0 catalysts, which proceeded at the lowest temperature reported so far (180°C) and reached the highest C5+ selectivity to date (71.1%). The TOF of the CO2 hydrogenation reached 9.5 h−1, which is comparable with that of the reported Ru0 catalyzed FTS reaction using syngas. Detailed study indicates that synergy of homogeneous and heterogeneous catalysis is the key for the outstanding performance.

Electrosynthesis of 3,3\u2032,5,5\u2019-Tetramethyl-2,2\u2032-biphenol in Flow

3,3′,5,5’-Tetramethyl-2,2′-biphenol is well known as an outstanding building block for ligands in transition-metal catalysis and is therefore of particular industrial interest. The electro-organic method is a powerful, sustainable, and efficient alternative to conventional synthetic approaches to obtain symmetric and non-symmetric biphenols. Here, we report the successive scale-up of the dehydrogenative anodic homocoupling of 2,4-dimethylphenol (4) from laboratory scale to the technically relevant scale in highly modular narrow gap flow electrolysis cells. The electrosynthesis was optimized in a manner that allows it to be easily adopted to different scales such as laboratory, semitechnical and technical scale. This includes not only the synthesis itself and its optimization but also a work-up strategy of the desired biphenols for larger scale. Furthermore, the challenges such as side reactions, heat development and gas evolution that arose during optimization are also discussed in detail. We have succeeded in obtaining yields of up to 62% of the desired biphenol.

Axially Chiral 1,1'‐Binaphthyl‐2‐Carboxylic Acid (BINA‐Cox) as Ligands for Titanium‐Catalyzed Asymmetric Hydroalkoxylation

Axially chiral, enantiopure 1,1'‐binaphthyl‐2‐carboxylic acids (BINA‐Cox) have recently been introduced as chiral ligands for transition metal catalysis. Together with equimolar, co‐catalytic amounts of Ti(OiPr)4 and water they form an in situ catalyst that performs the asymmetric catalytic hydroalkoxylation of 2‐allylphenols to 2‐methylcoumarans at high temperature (240 °C, microwave heating). The synthesis of reference ligand 2'‐MeO‐BINA‐Cox (L1) has been optimized and performed at molar scale. Synthetic routes have been developed to access a variety of substituted BINA‐Cox ligands (>30 examples), which have been tested for ligand effects on the reference asymmetric cyclization of 2‐allylphenol. The substrate range of asymmetric catalytic hydroalkoxylation has been explored through systematic substrate structure variations to define scope and limitations of the titanium‐catalyzed process. The new substrates 2‐(1‐vinylcycloalkyl)phenols (1j, 1k), 2‐(2‐vinylphenyl)propan‐2‐ol (1t), and 2'‐vinyl‐[1,1'‐biphenyl]‐2‐ol (1u) are shown to undergo asymmetric catalytic cyclization to benzodihydrofurans and benzo[c]chromene, respectively.

Transfer Hydrogenation of Carbonyl Groups, Imines andN‐Heterocycles Catalyzed by Simple, Bipyridine‐Based MnIComplexes

AbstractUtilization of hydroxy‐substituted bipyridine ligands in transition metal catalysis mimicking [Fe]‐hydrogenase has been shown to be a promising approach in developing new catalysts for hydrogenation. For example, MnIcomplexes with 6,6′‐dihydroxy‐2,2′‐bipyridine ligand have been previously shown to be active catalysts for CO2hydrogenation. In this work, simple bipyridine‐based Mn catalysts were developed that act as active catalysts for transfer hydrogenation of ketones, aldehydes and imines. For the first time, Mn‐catalyzed transfer hydrogenation ofN‐heterocycles was reported. The highest catalytic activity among complexes with variously substituted ligands was observed for the complex bearing two OH groups in bipyridine. Deuterium labeling experiments suggest a monohydride pathway.

New Aspects of Recently Developed Rhodium(N‐Heterocyclic Carbene)‐Catalyzed Organic Transformations

AbstractN‐Heterocyclic carbene (NHC) compounds have attracted significant attention as ligands for transition metal catalysis and organometallic complexes. Over the last two decades, among the various transition metals, ruthenium‐NHC‐type metathesis catalysts and palladium‐NHC‐based cross‐coupling catalysts have been extensively studied and developed. Recently, however, there has been a resurgence in developing NHC complexes of group 9 metals (Co, Rh, and Ir) for their use in organic transformations. This review specifically focuses on the advances in rhodium‐NHC catalysts. From the classical NHC ligands to the most recently developed CAAC (cyclic alkyl amino carbene)‐type ligands, the impact of using NHC ligands for increasing activity and enhancing selectivity across multiple reactions is discussed. We address the recent achievements in Rh(NHC) catalysis, which include (i) reactions involving rhodium hydride species, (ii) cross‐coupling reactions, (iii) bond cleavage reactions, and (iv) reduction reactions. Mechanistic insights based on the active catalytic species and a discussion about harnessing their unique reactivity for the future development of rhodium catalysis are given.magnified image

Synthesis and characterization of ruthenium (II) complex incorporating ether functionalized bis- N-heterocyclic carbene ligand

Abstract NHCs have become common ligands in organometallic chemistry due to their unique properties. These NHC compounds have emerged as an extremely useful class of ligands for transition-metal catalysis. During the past decade, the use of NHC ligands derived from imidazolium ions has emerged as an alternative to phoshine ligands in the design of new organometallic compounds and catalysts. The strong σ-donating ability of NHCs leads to high stability of their metal complexes toward heat, moisture and air. Recently, much effort has been devoted to the synthesis of functionalized NHC ligands and their metal complexes. Metal complexes containing mono or polydentate NHC ligands are known to be active catalysts for a number of organic transformations. NHCs (type A), generated by the abstraction of the proton at C-2 of an imidazolium salt by a suitable base, show unique coordination properties such as particularly strong σ -donor but poor ᴨ-acceptor abilities. The interest in those nucleophilic carbene ligands that introduction of sterically demanding groups R (adamantly) in A enables the isolation and crystallization of the free imidazol-2-ylidene carbine. The bulky groups R provide steric protection from dimerization and carbene degradation pathways. NHCs bound to metal complex fragments (type B) are significantly less reactive than Schrock and Fischer carbenes. . The present review surveys different classes of Ru–NHCs and their applications as efficient catalysts (or precatalysts) in several types of fundamental organic processes e.g. hydrogenation, hydrogen transfer, isomerization, cycloisomerization, cyclopropanation, hydrosilylation, allylation and deallylation, enol-ester synthesis, heterocycle synthesis, C–C alkyne coupling, Kharasch addition and ATRP. Ruthenium compounds are their relatively low toxicity, which makes them ideal for the catalytic synthesis.