Pd-catalyzed Aerobic Oxidation Research Articles

The role of anagostic interactions in the Pd−Superoxo formation in aerobic Pd catalysed C–C coupling reaction: What do DFT computations reveal?

Aerobic oxidative CC coupling catalyzed by dimethyl PdII center (L–[Pd]) bearing tetradentate pyridinophane (N4) ligand L (L = N,N-dimethyl-2,11-diaza[3.3]-(2,6)pyridinophane) has been investigated using density functional theory (DFT) computations. In Pd-catalyzed aerobic oxidation processes, the interaction of dioxygen with PdII center is a crucial step. Computations reveal that the reactant dimethyl PdII complex L–[Pd] has anagostic interactions (4 × Pd···H ∼ 2.60 Å) in total agreement with reported experimental NMR downshift values and these interactions play a significant role in the formation of PdIII–Superoxo intermediate which is less probed. While oxygen approaches the reactant, PdII center becomes PdIII allowing axial amine coordination. This pushes two protons (Csp3–H) away from Pd center weakening the two anagostic interactions. The other two anagostic interactions are intact at long ranges and at closer distances they weaken facilitating Pd–O bonding. The formation of the PdIII center in the PdIII–Superoxo were confirmed by reported EPR measurements. To understand this process, this key step has been modelled. Calculations have been performed with fourteen different density functionals (M06L, B3LYP, PBE0, M06, M11 to name a few) and different basis sets both in gas phase and in solvent medium. It is found that the range separated functionals, particularly M11 functional describe the process accurately and this is attributed to their efficiency of handling electron correlation at different ranges by including different percentage of Hartree-Fock exchange. The role of anagostic interactions M⋯H (M = Ni, Pd and Pt) in metal–superoxo species bearing symmetric and asymmetric substituted N4 ligands have been investigated. These results clearly explain asymmetrically substituted N4 ligands assist the simultaneous creation of M–O bonds at medium ranges and the weakening of bis anagostic (repulsive) M∙∙∙H interactions at short ranges. These findings suggest that intermediate stabilization in CC coupling processes mediated by transition-metal catalysts containing N4 ligands depends critically on the strength of anagostic interactions.

Pd-Catalyzed aerobic oxidation of the sesquiterpene isolongifolene: A green and heterogeneous process

The oxidation of the sesquiterpene isolongifolene, catalyzed by Pd/SiO2 prepared through a conventional sol–gel method, resulted mainly in isolongifolen-9-one (65% selectivity), a compound which occupies a prominent place in perfume industry. In addition to the product obtained from the allylic oxidation of isolongifolene, the formation of other oxygenated products with potential industrial application (both total yield of 94%) was also observed. The system can be used for oxidation of other sesquiterpene, valencene. In this case, it was possible to obtain oxygenated products with up to 66% yield. The reactions occurred under mild conditions in a green and heterogeneous oxidation catalytic system. Pd (II) was used as a solo catalyst in the absence of co-oxidants. The catalyst can be easily recovered and re-used maintaining activity and selectivity.

Pd-Catalyzed Aerobic Oxidative Coupling of Thiophenes: Synergistic Benefits of Phenanthroline Dione and a Cu Cocatalyst.

Substituted bithiophenes are prominent fragments in functional organic materials, and they are ideally prepared via direct oxidative C-H/C-H coupling. Here, we report a novel PdII catalyst system, employing 1,10-phenanthroline-5,6-dione (phd) as the ancillary ligand, that enables aerobic oxidative homocoupling of 2-bromothiophenes and other related heterocycles. These observations represent the first use of phd to support Pd-catalyzed aerobic oxidation. The reaction also benefits from a Cu(OAc)2 cocatalyst, and mechanistic studies show that Cu promotes C-C coupling, implicating a role for CuII different from its conventional contribution to reoxidation of the Pd catalyst.

Mechanism of the reaction of an NHC-coordinated palladium(II)-hydride with O2 in acetonitrile

PdII-hydride species are important intermediates in many Pd-catalyzed aerobic oxidation reactions, and their reaction with molecular oxygen has been the subject of considerable previous study. This investigation probes the reactivity of trans-[(IMes)2Pd(H)(OBz)] (IMes = 1,3-dimesitylimidazol-2-ylidene) with O2 in acetonitrile, a polar coordinating solvent that leads to substantial changes in the kinetic behavior of the reaction relative the previously reported reaction in benzene and other non-coordinating solvents. In acetonitrile, the benzoate ligand dissociates to form the solvent-coordinated complex trans-[(IMes)2Pd(H)(NCMe)][OBz]. Upon exposure to O2, this cationic PdII–H complex reacts to form the corresponding PdII-hydroperoxide complex trans-[(IMes)2Pd(OOH)(NCCD3)][OBz]. Kinetic studies of this reaction revealed a complex rate law, rate = k1k2[3][OBz]/(k−1[CD3CN] + k2[OBz]) + k3[3][OBz], which is rationalized by a mechanism involving two parallel pathways for rate-limiting deprotonation of the PdII–H species to generate the Pd0 complex, Pd(IMes)2. The latter complex undergoes rapid (kinetically invisible) reaction with O2 and BzOH to afford the PdII-hydroperoxide product. The results of this study are compared to observations from the previously reported reaction in benzene and discussed in the context of catalytic reactivity.

Selective C–O Bond Cleavage of Lignin Systems and Polymers Enabled by Sequential Palladium-Catalyzed Aerobic Oxidation and Visible-Light Photoredox Catalysis

Lignin, which is a highly cross-linked and irregular biopolymer, is nature’s most abundant source of aromatic compounds and constitutes an attractive renewable resource for the production of aromatic commodity chemicals. Herein, we demonstrate a practical and operationally simple two-step degradation approach involving Pd-catalyzed aerobic oxidation and visible-light photoredox-catalyzed reductive fragmentation for the chemoselective cleavage of the β-O-4 linkage—the predominant linkage in lignin—for the generation of lower-molecular-weight aromatic building blocks. The developed strategy affords the β-O-4 bond cleaved products with high chemoselectivity and in high yields, is amenable to continuous flow processing, operates at ambient temperature and pressure, and is moisture- and oxygen-tolerant.

Are Phosphines Viable Ligands for Pd-Catalyzed Aerobic Oxidation Reactions? Contrasting Insights from a Survey of Six Reactions

Phosphines are the broadest and most important class of ligands in homogeneous catalysis, but they are typically avoided in Pd-catalyzed aerobic oxidation reactions because of their susceptibility to oxidative degradation. Recent empirical reaction-development efforts have led to a growing number of Pd/phosphine catalyst systems for aerobic oxidative coupling reactions, but few of these studies have assessed the fate of the phosphine ligand. Here, we assess six different oxidative coupling reactions, including the homocoupling of boronic acids, amino- and alkoxycarbonylation reactions, intramolecular C–H annulation, and enantioselective Fujiwara–Moritani C–C coupling. The fate and role of the phosphine, analyzed by 31P NMR spectroscopy throughout the reaction time course in each case, varies in different reactions. In one case, the phosphine has an inhibitory effect and leads to lower selectivity relative to ligand-free conditions. In other cases, the phosphine ligands have a beneficial effect on the reac...

Synthesis and Characterization of Carboxylic Acids Bearing Poly(ethylene glycol) Chains

Carboxylic acids 1a and 1b bearing three poly(ethylene glycol) (PEG) chains and carboxylic acid 1c bearing one PEG chain were designed and synthesized. The carboxylic acids 1a–c were fully characterized by NMR and ESI-HRMS analyses. In a Pd-catalyzed aerobic oxidation of 1-phenylethanol, 1a and 1b worked well as carboxylate ligands.

Mechanistic Basis for Efficient, Site-Selective, Aerobic Catalytic Turnover in Pd-Catalyzed C-H Imidoylation of Heterocycle-Containing Molecules.

A recently reported Pd-catalyzed method for oxidative imidoylation of C-H bonds exhibits unique features that have important implications for Pd-catalyzed aerobic oxidation catalysis: (1) The reaction tolerates heterocycles that commonly poison Pd catalysts. (2) The site selectivity of C-H activation is controlled by an N-methoxyamide group rather than a suitably positioned heterocycle. (3) A Pd0 source, Pd2(dba)3 (dba = dibenzylideneacetone), is superior to Pd(OAc)2 as a precatalyst, and other PdII sources are ineffective. (4) The reaction performs better with air, rather than pure O2. The present study elucidates the origin of these features. Kinetic, mechanistic, and in situ spectroscopic studies establish that PdII-mediated C-H activation is the turnover-limiting step. The tBuNC substrate is shown to coordinate more strongly to PdII than pyridine, thereby contributing to the lack of heterocycle catalyst poisoning. A well-defined PdII-peroxo complex is a competent intermediate that promotes substrate coordination via proton-coupled ligand exchange. The effectiveness of this substrate coordination step correlates with the basicity of the anionic ligands coordinated to PdII, and Pd0 catalyst precursors are most effective because they selectively afford the PdII-peroxo in situ. Finally, elevated O2 pressures are shown to contribute to background oxidation of the isonitrile, thereby explaining the improved performance of reactions conducted with air rather than 1 atm O2. These collective results explain the unique features of the aerobic C-H imidoylation of N-methoxybenzamides and have important implications for other Pd-catalyzed aerobic C-H oxidation reactions.

Detection of Palladium(I) in Aerobic Oxidation Catalysis.

Palladium(II)-catalyzed oxidation reactions exhibit broad utility in organic synthesis; however, they often feature high catalyst loading and low turnover numbers relative to non-oxidative cross-coupling reactions. Insights into the fate of the Pd catalyst during turnover could help to address this limitation. Herein, we report the identification and characterization of a dimeric PdI species in two prototypical Pd-catalyzed aerobic oxidation reactions: allylic C-H acetoxylation of terminal alkenes and intramolecular aza-Wacker cyclization. Both reactions employ 4,5-diazafluoren-9-one (DAF) as an ancillary ligand. The dimeric PdI complex, [PdI (μ-DAF)(OAc)]2 , which features two bridging DAF ligands and two terminal acetate ligands, has been characterized by several spectroscopic methods, as well as single-crystal X-ray crystallography. The origin of this PdI complex and its implications for catalytic reactivity are discussed.

Diazafluorenone-Promoted Oxidation Catalysis: Insights into the Role of Bidentate Ligands in Pd-Catalyzed Aerobic Aza-Wacker Reactions.

2,2'-Bipyridine (bpy), 1,10-phenanthroline (phen) and related bidentate ligands often inhibit homogeneous Pd-catalyzed aerobic oxidation reactions; however, certain derivatives, such as 4,5-diazafluoren-9-one (DAF), can promote catalysis. In order to gain insight into this divergent ligand behavior, eight different bpy- and phen-derived chelating ligands have been evaluated in Pd(OAc)2-catalyzed oxidative cyclization of (E)-4-hexenyltosylamide. Two of the ligands, DAF and 6,6'-dimethyl-2,2'-bipyridine (6,6'-Me2bpy), support efficient catalytic turnover, while the others strongly inhibit the reaction. DAF is especially effective and is the only ligand that exhibits "ligand-accelerated catalysis". Evidence suggests that the utility of DAF and 6,6'-Me2bpy originates from the ability of these ligands to access κ1-coordination modes via dissociation of one of the pyridyl rings. This hemilabile character is directly observed by NMR spectroscopy upon adding one equivalent of pyridine to solutions of 1:1 L/Pd(OAc)2 (L = DAF and 6,6'-Me2bpy), and is further supported by an X-ray crystal structure of Pd(py)(κ1-DAF)OAc2. DFT computational studies illuminate the influence of three different chelating ligands [DAF, 6,6'-Me2bpy, and 2,9-dimethyl-1,10-phenanthroline (2,9-Me2phen)] on the energetics of the aza-Wacker reaction pathway. The results show that DAF and 6,6'-Me2bpy destabilize the corresponding ground-state Pd(N~N)(OAc)2 complexes, while stabilizing the rate-limiting transition state for alkene insertion into a Pd-N bond. Interconversion between κ2- and κ1-coordination modes facilitate access to open coordination sites at the PdII center. The insights from these studies introduce new ligand concepts that could promote numerous other classes of Pd-catalyzed aerobic oxidation reaction.

ChemInform Abstract: Aerobic Oxidation at Benzylic Positions Catalyzed by a Simple Pd(OAc)2/Bis‐Triazole System.

An efficient catalyst system for the Pd-catalyzed aerobic oxidation of benzylic positions has been developed. The combination of palladium(II) acetate and 3,5-bis((1H-1,2,4-triazol-1-yl)methyl)benzoate ligand allows the selective oxidation at carbon adjacent to arene rings (primary and secondary benzylic alcohols, and other benzyl compounds) to provide the corresponding carbonyl and carboxy derivatives, employing molecular oxygen as oxidizing agent and a very low metal loading (10−5 mol%).

Bimetallic PdCu Nanoparticle Catalyst Supported on Hydrotalcite for Selective Aerobic Oxidation of Benzyl Alcohol

ABSTRACTTo decrease the amount of precious metal usage for Pd-catalyzed aerobic alcohol oxidation, various amount of Cu-contained Pd bimetallic nanoparticle-supported solid base hydrotalcite catalyst (PdxCuy-PVP/HTs) were prepared and applied for aerobic benzyl alcohol oxidation. It was found that the addition of Cu atoms into Pd in the range of 0-40% provided a similar or a little superior activity to that of Pd100-PVP catalyst, whereas a large quantity of co-existence Cu (>40%) gradually decreased their activity of the catalyst. The aerobic benzyl alcohol oxidation over Pd80Cu20-PVP/HT served 77% yield and 95% selectivity towards benzaldehyde at 313 K for 5 h in toluene under O2 flow. X-ray adsorption spectroscopy (XAS) studies and scanning transmission electron microscopy-high angle annuar dark field (STEM-HAADF) with energy dispersive X-ray spectroscopy (EDS) analyses suggested that Cu atoms doping into Pd(0) NP influenced not only localized nanostructure but also oxidation state around Pd atoms. We suggested that substitution of precious metal with small amount of transition metals such as Cu lead to geometric/electronic changes in active sites would be one of nice strategies for reducing the cost for the catalyst in the oxidation process.

Synthesis of 2-Aminobenzoxazoles and 3-Aminobenzoxazines via Palladium-Catalyzed Aerobic Oxidation of o-Aminophenols with Isocyanides

A Pd-catalyzed aerobic oxidation of o-aminophenols and isocyanides for the synthesis of 2-aminobenzoxazoles and 3-aminobenzoxazines has been achieved in an air atmosphere. The procedure constructs 2-aminobenzoxazoles and 3-aminobenzoxazines with moderate to excellent yields and a broad substrate scope. Apart from experimental simplicity, this methodology has the advantages of mild reaction conditions and easily accessible starting materials. Furthermore, the utility of this method has also been successfully applied to the synthesis of other types of useful nitrogen heterocycles.

Palladium‐Catalyzed N‐Alkylation of Amides and Amines with Alcohols Employing the Aerobic Relay Race Methodology

AbstractPossibly because homogeneous palladium catalysts are not typical borrowing hydrogen catalysts and ligands are thus ineffective in catalyst activation under conventional anaerobic conditions, they had not been used in the N‐alkylation reactions of amines/amides with alcohols in the past. By employing the aerobic relay race methodology with Pd‐catalyzed aerobic alcohol oxidation being a more effective protocol for alcohol activation, ligand‐free homogeneous palladiums are successfully used as active catalysts in the dehydrative N‐alkylation reactions, giving high yields and selectivities of the alkylated amides and amines. Mechanistic studies implied that the reaction most probably proceeds via the novel relay race mechanism we recently discovered and proposed.

ChemInform Abstract: Palladium‐Assisted Multicomponent Cyclization of Aromatic Aldehydes, Arylamines and Terminal Olefins under Molecular Oxygen: An Assembly of 1,4‐Dihydropyridines.

The palladium-assisted one-pot three-component reactions of aldehydes, amines and olefins proceeded smoothly to give 2,6-unsubstituted 1,4-dihydropyridines (1,4-DHPs) using molecular oxygen as a sole oxidant. It also provides efficient Pd-catalyzed aerobic oxidation access to the anti-Markovnikov oxidative amination products of olefins from primary aromatic amines and alkenes. The method is atom-efficient, using cheap and easily available starting materials and an environmentally benign oxidant.

O2insertion into a palladium(ii)-hydride bond: Observation of mechanistic crossover between HX-reductive-elimination and hydrogen-atom-abstraction pathways

The reaction of molecular oxygen with palladium(II)–hydrides is a key step in Pd-catalyzed aerobic oxidation reactions, and the mechanism of such reactions has been the focus of considerable investigation and debate. Here we describe the reaction of O2 with a series of electronically varied PdII–H complexes of the type trans-(IMes)2Pd(H)(O2CAr), with different para-substituted benzoates as the ArCO2− ligand. Analysis of the oxygenation rates of these complexes revealed a non-linear Hammett plot, and further kinetic studies demonstrated that reaction of O2 with the most electron-rich para-methoxybenzoate derivative proceeds via two parallel mechanisms, one initiated by rate-limiting reductive elimination of the carboxylic acid (HXRE) and the other involving hydrogen-atom abstraction by O2 (HAA). DFT computational studies support these conclusions and reveal that the preferred mechanism for the O2insertion reaction changes from HAA to HXRE as the para substituent on the benzoate ligand shifts from electron-donating to electron-withdrawing.

Palladium-assisted multicomponent cyclization of aromatic aldehydes, arylamines and terminal olefins under molecular oxygen: an assembly of 1,4-dihydropyridines

The palladium-assisted one-pot three-component reactions of aldehydes, amines and olefins proceeded smoothly to give 2,6-unsubstituted 1,4-dihydropyridines (1,4-DHPs) using molecular oxygen as a sole oxidant. It also provides efficient Pd-catalyzed aerobic oxidation access to the anti-Markovnikov oxidative amination products of olefins from primary aromatic amines and alkenes. The method is atom-efficient, using cheap and easily available starting materials and an environmentally benign oxidant.

Palladium-Catalyzed Hydroarylation of 1,3-Dienes with Boronic Esters via Reductive Formation of π-Allyl Palladium Intermediates under Oxidative Conditions

A palladium-catalyzed reductive cross-coupling of 1,3-dienes with boronic esters in which a pi-allyl Pd species is generated directly from a 1,3-diene via a Pd-catalyzed aerobic alcohol oxidation is reported. Both the scope of the process and the origin of a highly selective 1,2-addition are discussed.

Electronic Structural Comparison of the Reactions of Dioxygen and Alkenes with Nitrogen-Chelated Palladium(0)

The reaction of molecular oxygen with palladium(0) centers is a key step in Pd-catalyzed aerobic oxidation reactions. The present study provides a density functional theory (DFT) computational analysis of the mechanism and electronic structural features of the reversible, associative exchange between O(2) and ethylene at an ethylenediamine (en)-coordinated palladium(0) center. Salient features of the mechanism include: (1) the near thermoneutrality of the O(2)-alkene exchange reaction, consistent with experimentally observed reversible exchange between O(2) and alkenes at well-defined Pd centers, (2) end-on activation of triplet O(2) at an apical site of the trigonal Pd(0) center, resulting in formation of a Pd(I)(η(1)-superoxide) species, (3) rearrangement of the Pd(I)(η(1)-superoxide) species into a pseudo-octahedral (en)Pd(η(2)-O(2))(η(2)-C(2)H(4)) species with concomitant crossing from the triplet to singlet energy surfaces, and (4) release of alkene from an axial face of (en)Pd(II)(η(2)-peroxo) with a geometry in which the alkene leaves with an end-on trajectory (involving an interaction of the Pd d(z(2)) and alkene π* orbitals). This study highlights the similar reactivity and reaction pathways of alkenes and O(2) with an electron-rich metal center, despite the different ground-state electronic configurations of these molecules (closed-shell singlet and open-shell triplet, respectively).

Development of safe and scalable continuous-flow methods for palladium-catalyzed aerobic oxidation reactions

The synthetic scope and utility of Pd-catalyzed aerobic oxidation reactions has advanced significantly over the past decade, and these reactions have potential to address important green-chemistry challenges in the pharmaceutical industry. This potential has been unrealized, however, because safety concerns and process constraints hinder large-scale applications of this chemistry. These limitations are addressed by the development of a continuous-flow tube reactor, which has been demonstrated on several scales in the aerobic oxidation of alcohols. Use of a dilute oxygen gas source (8% O(2) in N(2)) ensures that the oxygen/organic mixture never enters the explosive regime, and efficient gas-liquid mixing in the reactor minimizes decomposition of the homogeneous catalyst into inactive Pd metal. These results provide the basis for large-scale implementation of palladium-catalyzed (and other) aerobic oxidation reactions for pharmaceutical synthesis.