配位子周辺部の修飾による新しい遷移金属錯体触媒の開発と触媒反応への応用

Use of homogeneous catalysis for fine chemical production is rapidly expanding. Advantages of its use are high chemo‐, regio‐, and enantioselectivity, which can be tuned by ligand design. Use of catalysis also leads to cleaner production processes. A third adavantage are the mild conditions that are often possible, which allows the application of homogeneous catalysis as a late step in a total synthesis. Often protective groups are unnecessary.While in the past homogeneous catalysis was mainly used for second‐generation processes of rather large products, it is now increasingly used in the first production processes. This is related to an increased availability of catalysts with sufficient rate and stability. In addition, high throughput experimentation allows rapid screening of these catalysts.While several hundred reactions are known that are catalyzed by homogeneous transition metal catalysts, only a limited number of these are applied for fine chemical production. They can be subdivided into four main classes: hydrogenation, carbon–carbon bond formation, carbon–heteroatom bond formation, and isomerization reactions. Important requirements are rate of the reaction, expressed as turnover frequency (TOF) and catalyst stability, expressed as turnover number (TON). Examples are given of many processes on scales varying from 1 to 10,000 ton/year.Recycle of catalysts is rarely practiced in fine chemical production, as the extra unit operations involved does not outweigh the gains of a reuse of the catalyst. Immobilization of homogeneous transition metal catalysts often leads to loss of activity and selectivity. In addition catalyst deactivation makes this an unattractive option. Emphasis is on the development of very fast catalysts. The metal is usually sent to the producer for reclaiming and refining. Two‐phase catalysis might be a viable option for catalyst recycle.Double digit growth is expected in the coming years for the application of homogeneous catalysis in the production of fine chemicals.

Luminescent palladium(0) complexes bearing N-heterocyclic carbene and phosphine ligands

The objectives of the work described in this dissertation were twofold: (1) to further improve the activity and selectivity of ruthenium-based olefin metathesis catalysts, and (2) to obtain a better understanding of how these catalysts operate. The first problem was addressed by varying the ligand sphere within the L2X2Ru=CHR framework. Chapter 2 explores the metathesis of directly functionalized olefins, such as 1,1-difluoroethylene and acrylonitrile. Detailed studies revealed that ruthenium alkylidene complexes react readily with these olefins but stop after a single turnover of the catalytic cycle. This effect is caused by electronically deactivating carbene substituents, which dramatically decrease the rate of phosphine dissociation from the metal center and thus prevent catalyst re-initiation. Chapter 3 describes complexes where the L ligands are phosphines, N-heterocyclic carbenes (NHCs), imidazoles, or pyridines, where the X ligands are chlorides, and where the carbene moiety is either benzylidene or a cyclic moiety. Improved catalytic activity and selectivity were achieved with complexes containing a combination of phosphine and NHC ligands. The reactivity and stability profiles of these species can be tuned through the stereoelectronic properties of the NHC. To facilitate the use of NHCs in organometallic applications, a synthetic route was developed that employs NHC adducts to protect the reactive carbene centers. Chapter 4 describes the reactions of ruthenium alkylidene complexes with alkynes. In the majority of cases, the metathesis polymerization of alkynes is unsuccessful because of competing reactions to form eta3-vinylcarbene and eta5-cyclopentadienyl derivatives. The eta3-vinylcarbene complexes are particularly interesting as models for the olefin-bound intermediate in the olefin metathesis catalytic cycle, and their structures demonstrate that it is possible for the chloride ligands to adopt a cis arrangement that places one of the chlorides trans to the L donor ligand. The studies in Chapter 5 explore the stereoelectronic properties of phosphine and NHC ligands and provide valuable insights about electronic structure and bonding. This information was obtained by a variety of techniques, including structure-activity studies, kinetics, x-ray crystallography, heteronuclear NMR, infrared spectroscopy, and gas-phase UV photoelectron spectroscopy.

Asymmetric Nickel-Catalyzed Reactions

Expanding catalytic environment to a nanosize is one of the most promising ways to improve performance of homogeneous catalysts. In this highlight review, recent development in homogeneous transition metal catalysts with well-defined nanosize ligands is overviewed. These systems realize efficient catalysts with remarkable enhancement of catalytic activity, suppression of metal aggregation, and unprecedented selectivity.

Contrary to most platinum-based anti-cancer agents which target DNA, coordination of N-heterocyclic carbene (NHC) ligands to cyclometalated platinum(II) complexes confers these luminescent complexes to other cellular target(s). The strong Pt–Ccarbene bond(s) renders the platinum(II) complexes to display unique photophysical properties and enhanced stability against biological reduction and ligand exchange reactions. The platinum complexes described in this work are highly cytotoxic and display high specificity to cancerous cells. Among them, [(C^N^N)PtII(N,N′-nBu2NHC)]PF6 (1a, where HC^N^N = 6-phenyl-2,2′-bipyridine) with a lipophilic carbon chain on the carbene ligand induces apoptosis in cancer cells, demonstrates an enhancing synergistic effect with cisplatin in vitro, and displays potent in vivo activities using nude mice models. As this complex is strongly emissive, its cellular localization can be traced using emission microscopy. In contrast to common platinum-based anti-cancer agents, 1a does not accumulate in the vicinity of DNA but preferentially accumulates in cytoplasmic structures including sites where active survivin, an inhibitor of apoptosis (IAP), is located. In vitro, 1a significantly inhibits the expression of survivin, activates poly(ADP-ribose) polymerase (PARP) and induces apoptosis in cancer cells. Given the ease of structural modification of NHC ligand to alter the overall biological activities, these [(C^N^N)PtII(NHC)]+ complexes having unique photophysical properties provide an entry to a new class of potential anti-cancer drug leads.

Owing to the importance of amine/amide derivatives in all fields of chemistry, and also the green and environmentally benign features of using alcohols as alkylating reagents, the relatively high atom economic dehydrative N-alkylation reactions of amines/amides with alcohols through hydrogen autotransfer processes have received much attention and have developed rapidly in recent decades. Various efficient homogeneous and heterogeneous transition metal catalysts, nano materials, electrochemical methods, biomimetic methods, asymmetric N-alkylation reactions, aerobic oxidative methods, and even certain transition metal-free, catalyst-free, or autocatalyzed methods, have also been developed in recent years. With a brief introduction to the background and developments in this area of research, this chapter focuses mainly on recent progress and technical and conceptual advances contributing to the development of this research in the last decade. In addition to mainstream research on homogeneous and heterogeneous transition metal-catalyzed reactions, possible mechanistic routes for hydrogen transfer and alcohol activation, which are key processes in N-alkylation reactions but seldom discussed in the past, the recent reports on computational mechanistic studies of the N-alkylation reactions, and the newly emerged N-alkylation methods based on novel alcohol activation protocols such as air-promoted reactions and transition metal-free methods, are also reviewed in this chapter. Problems and bottlenecks that remained to be solved in the field, and promising new research that deserves greater future attention and effort, are also reviewed and discussed.

A recently developed metal-organic framework (MOF) catalyst for the dimerization of ethylene has a combination of selectivity and activity that surpasses that of commercial homogeneous catalysts, which have dominated this important industrial process for nearly 50 years. The uniform catalytic sites available in MOFs provide a unique opportunity to directly study reaction mechanisms in heterogeneous catalysts, a problem typically intractable due to the multiplicity of coordination environments found in many solid catalysts. In this work, we use a combination of isotopic labeling studies, mechanistic probes, and DFT calculations to demonstrate that Ni-MFU-4l operates via the Cossee-Arlman mechanism, which has also been implicated in homogeneous late transition metal catalysts. These studies demonstrate that metal nodes in MOFs mimic homogeneous catalysts not just functionally, but also mechanistically. They provide a blueprint for the development of advanced heterogeneous catalysts with similar degrees of tunability to their homogeneous counterparts.

We report electron-donor and steric properties of a diverse group of representative N-heterocyclic carbene (NHC) ligands quantified with the help of DFT calculations. This study afforded the conventional TEP data (Tolman electronic parameter = νCO (A1) of Ni(CO)3(NHC)), which allowed ranking 76 NHC ligands in order of increasing donor power. The TEP data reveal several general trends concerning the influence of NHC ring size, substitution, and annulation. The calculations also provided reaction enthalpies for CO elimination from the Ni(CO)3(NHC) complexes and formation of the 16-electron Ni(CO)2(NHC) species. This reaction is largely under steric control, which allowed defining a new steric descriptor for NHC ligands, r ("repulsiveness") = 10 × (7.568 − 0.003172TEP − 0.0446ΔH), ranging from 0.0 for the smallest (ImNH2) to 8.0 for the most repulsive carbene (ImNAd2) of this work. Ni(CO)3L and Os(H2)Cl2(CO)L2 complexes eliminate CO and H2, respectively, more readily with L = NHC vs PR3 ligands. Apparently, even relatively small NHC ligands are very sterically demanding, and this property of N-heterocyclic carbenes may play a major role in coordination chemistry and catalysis.

Organometallic chemistry of bis(N-heterocyclic carbene) ligands containing a heteroarene spacer

Conceptual study of co-product separation from catalyst-rich recycle streams in thermomorphic multiphase systems by OSN

Piano-stool iron complexes with N-heterocyclic carbene (NHC) ligands have shown high potential in the activation and conversion of C═O bonds in aldehydes, ketones, and esters. Here we demonstrate the expansion of this activity to the functionalization of CO2 with amines to form N-formamide products in the presence of a silane (PhSiH3). This synthetically valuable utilization of CO2 as C1-synthon is catalyzed by iron complexes containing a variety of different NHC ligands. Structural variations of the NHC ligands did not reveal any correlation with catalytic activity, with imidazole and triazole-derived NHCs reaching similar conversions. However, the use of BF4– as counterion in cationic complexes, and also incorporating a Cp* instead of a Cp spectator ligand led to a marked decrease in catalytic activity. While NHC iron complexes reach mediocre activity (about 50% conversion at 5% catalyst loading in 24 h), the corresponding imidazolium and triazolium carboxylates as precursors of free carbenes display excellent catalytic activity with essentially full conversion after 1 h at 1 mol % loading. Experiments at variable iron complex loading as well as carbene trapping experiments with S8 together with spectroscopic investigations demonstrated a high stability of the Fe–CNHC bond during catalysis and lend strong support to a NHC iron unit as catalytically active species rather than free NHC resulting from Fe–NHC dissociation, even though free NHCs are excellent catalysts for this reaction. Optimized of reaction conditions, in particular the addition of another equivalent of silane allowed to reach high conversions of piperidine and CO2 to N-formylpiperidine using a triazolylidene iron complex as catalyst precursor.

Despite significant advances in manufacturing atomically precise gold nanoclusters protected by various ligands, there is a limited understanding of the thermal stability dynamics and electronic properties of ligand effects. We conducted ab initio molecular dynamics (AIMD) simulations on the well-characterized [Au13(NHCMe)9Cl3]2+ nanocluster and its counterpart [Au13(PMe3)9Cl3]2+ cluster to evaluate the thermal stability induced by N-heterocyclic carbene (NHC) and phosphine ligands. The result shows that under vacuum conditions, [Au13(PMe3)9Cl3]2+ is more stable than [Au13(NHCMe)9Cl3]2+, and both lead to metal nucleation decomposition, breaking into the Au12 fragment and L-Au-Cl (L = NHCMe or PMe3) complexes eventually. The optical and electronic properties of these two clusters change significantly due to ligand alteration. Furthermore, we have designed a novel [Au13(NHCMe)(PMe3)8Cl3]2+ cluster coprotected by NHC and phosphine ligands, displaying higher thermal stability than the homoligand protected [Au13(NHCMe)9Cl3]2+ and [Au13(PMe3)9Cl3]2+. Our hypothetical species are an interesting model for nanostructured materials, facilitating the experimental exploration of cluster synthesis and catalytic applications.

(Imido)vanadium(V)−alkyl, alkylidene complexes containing an N-heterocyclic carbene (NHC) ligand, V(CHSiMe3)(NR)(CH2SiMe3)(NHC) [R = 1-adamantyl (Ad) or 2,6-Me2C6H3 (Ar), NHC = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene], have been prepared from the trialkyl analogues, V(NR)(CH2SiMe3)3, by α-hydrogen elimination in C6D6 in the presence of NHC. The V−C(NHC) bond distance [2.172(2) A] in V(CHSiMe3)(NAd)(CH2SiMe3)(NHC) is much longer than the V−C(alkylidene) [1.829 A] and the V−C(alkyl) [2.069 A] distances, indicating that NHC plays an important role in the stabilization of the high-oxidation-state vanadium(V)−alkylidene as a neutral carbene ligand.

Chiral gold complexes have been applied in homogeneous catalytic reactions since 1986, in some cases with high enantioselectivity. Acyclic diaminocarbene (ADC) ligands are acyclic analogues of N-heterocyclic carbenes (NHCs) that have larger N-CCarbene-N angles and stronger donating ability. ADCs have been developed as alternatives to phosphine and NHC ligands in homogeneous gold catalysis. In 2012, a new series of chiral gold(I) ADCs were first developed by Slaughter's group and were shown to give remarkable enantioselectivities in some reactions. Because of the hindered rotation of the N-CCarbene bonds of ADC, chiral ADC substituents can easily get close to the metal center in some conformations, although two rotameric structures are formed if the chiral amine is nonsymmetric. The selective of specific ADC conformations was the initial focus of this study. Formational selectivity of one diastereomer of an ADC ligand during synthesis was examines by measuring the relative rates of diastereomer formation in a 1H NMR kinetic study. The potential for converting multiple conformational isomers of ADCs into a single conformation, or at least a simpler mixture, was examined. This study used the analogy that anti- isomer has electronic and structural similarity with urea/thiourea, raising the possibility that 1,8-naphthyridine can be used to favor certain conformations through a self-assembled hydrogen-bonding complex. Gold(I) is a soft carbophilic Lewis acid able to active C-C π bonds to nucleophilic attack, and ADC-gold complexes are potentially useful in this regard. Therefore, biaryl gold(I) ADC complexes were examine with silver salt additives in catalytic 1,6-enyne cyclization reaction. A detailed study found that the counteranion affects the regioselectivities of these reactions more than substituents on the ancillary ADC ligands.