Iron-Catalyzed C−C Bond Formation via Chelation-Assisted C−H Activation

This review provides a brief overview of iron-catalyzed C−C bond forming reactions via heteroatom-assisted C−H bond activation, which have been extensively developed in the last decade. Three major types of reactions are discussed, namely, (1) C−H activation/C−C coupling using organometallic reagents under oxidative conditions, (2) C−H activation/C−C coupling using organic electrophiles under redox-neutral conditions, and (3) C−H activation/C−C coupling using unsaturated hydrocarbons under redox-neutral or oxidative conditions.     

High-Valent Iron-Oxo and -Nitrido Complexes: Bonding and Reactivity

Multiple-bonded iron-oxo and -nitrido species have been identified or proposed as key intermediates in a range of important chemical transformations. The reported model complexes feature various coordination geometries and distinct electronic structures, and therefore exhibit diverse reactivity. The present contribution highlights the synergy from both experimental and theoretical standpoints to elucidate their different bonding situations and delineate their common mechanistic features in hydrogen-atom abstraction processes. Our analysis reveals that a radical centered on the abstracting atom E (E=O, N), which is generated via homolysis of covalent Fe−E bonds upon approaching the transition state, is an intrinsic C−H cleaving agent. The iron-oxo species is predicted to be more reactive than its nitride congener, in general, because the O−H bond formed in the H-atom transfer process is often stronger than the corresponding N−H bond.     

Visible Light instead of Transition Metal: Electron Donor Acceptor Complex Enabled Cross-Coupling of Aryl Halides with Active Methylene Compounds

An arylation of anions of active methylene compounds with aryl halides provides an access to synthetically versatile α-arylated 1,3-diketones, β-keto esters, β-keto nitriles, β-cyano esters, etc. Previously, these C−C cross-coupling reactions have been accomplished only using transition metal-based catalysts. Herein, we demonstrate that these arylations can be successfully realized under catalyst-free conditions employing the electron donor-acceptor (EDA) complex photoactivation strategy. The protocol was further optimized for a semi-one pot synthesis of indole derivatives via an intramolecular C−C coupling.     

Catalytically Active Iron(IV)oxo Species Based on a Bis(pyridinyl)phenanthrolinylmethane

Starting from the mononuclear iron(II) complex [Fe(MeCPy₂Phen)(MeCN)₂]²⁺, a non-heme Fe(IV)oxo complex [Fe^IV(MeCPy₂Phen)O]²⁺ was synthesized via oxidation with meta-chloroperoxybenzoic acid (mCPBA). The Fe(IV)oxo complex was characterized using UV/Vis spectroscopy, Mößbauer spectroscopy and CSI mass spectrometry. The ability of this species to oxidize C−H bonds was tested with cyclohexane and adamantane as model substrates. For cyclohexane, an alcohol-to-ketone ratio (A/K) of 6.1 and efficiencies up to 55 were obtained. In case of adamantane, the ratio of tertiary over secondary products (3°/2°) is 38. In combination, this indicates the iron(IV)oxo complex being the catalytically active species.     

High-valent iron(IV)-oxo complexes of heme and non-heme ligands in oxygenation reactions

High-valent iron(IV)-oxo species have been implicated as the key reactive intermediates in the catalytic cycles of dioxygen activation by heme and non-heme iron enzymes. Our understanding of the enzymatic reactions has improved greatly via investigation of spectroscopic and chemical properties of heme and non-heme iron(IV)-oxo complexes. In this Account, reactivities of synthetic iron(IV)-oxo porphyrin pi-cation radicals and mononuclear non-heme iron(IV)-oxo complexes in oxygenation reactions have been discussed as chemical models of cytochrome P450 and non-heme iron enzymes. These results demonstrate how mechanistic developments in biomimetic research can help our understanding of dioxygen activation and oxygen atom transfer reactions in nature.     

Selective C−H Functionalizations by Electrochemical Reactions with Palladium Catalysts

Efficient, selective, transition-metal-catalyzed C−H functionalizations have been widely studied and are recognized as atom- and step-economical tools in organic synthesis. During the past two decades, a variety of catalytic reactions involving C−H bond cleavage have been developed. In this review, we briefly survey studies dealing with transition-metal-catalyzed efficient and selective C−H functionalization by electrochemical reactions.     

C−H Amination via Nitrene Transfer Catalyzed by Mononuclear Non-Heme Iron-Dependent Enzymes

Expanding the reaction scope of natural metalloenzymes can provide new opportunities for biocatalysis. Mononuclear non-heme iron-dependent enzymes represent a large class of biological catalysts involved in the biosynthesis of natural products and catabolism of xenobiotics, among other processes. Here, we report that several members of this enzyme family, including Rieske dioxygenases as well as α-ketoglutarate-dependent dioxygenases and halogenases, are able to catalyze the intramolecular C−H amination of a sulfonyl azide substrate, thereby exhibiting a promiscuous nitrene transfer reactivity. One of these enzymes, naphthalene dioxygenase (NDO), was further engineered resulting in several active site variants that function as C−H aminases. Furthermore, this enzyme could be applied to execute this non-native transformation on a gram scale in a bioreactor, thus demonstrating its potential for synthetic applications. These studies highlight the functional versatility of non-heme iron-dependent enzymes and pave the way to their further investigation and development as promising biocatalysts for non-native metal-catalyzed transformations.     

Dioxygen activation at non-heme iron: insights from rapid kinetic studies

One of the common biochemical pathways of binding and activation of dioxygen involves non-heme iron centers. The enzyme cycles usually start with an iron(II) or diiron(II) state and traverse via several intermediates (detected or postulated) such as (di)iron(III)-superoxo, (di)iron(III)-(hydro)peroxo, iron(III)iron(IV)-oxo, and (di)iron(IV)-oxo species, some of which are responsible for substrate oxidation. In this Account, we present results of kinetic and mechanistic studies of dioxygen binding and activation reactions of model inorganic iron compounds. The number of iron centers, their coordination number, and the steric and electronic properties of the ligands were varied in several series of well-characterized complexes that provided reactive manifolds modeling the function of native non-heme iron enzymes. Time-resolved cryogenic stopped-flow spectrophotometry permitted the identification of kinetically competent intermediates in these systems. Inner-sphere mechanisms dominated the chemistry of dioxygen binding, intermediate transformations, and substrate oxidation as most of these processes were controlled by the rates of ligand substitution at the iron centers.     

Oxoiron(V) Complexes of Relevance in Oxidation Catalysis of Organic Substrates

The selective oxidation of alkane and olefin moieties are reactions of fundamental importance in both chemical synthesis and biology. Nature efficiently catalyzes the oxidation of hydrocarbons using iron-dependent enzymes, which operate through the mediation of oxoiron(IV) or oxoiron(V) species. In the quest for chemo, regio and stereoselective transformations akin to those taking place in nature, bioinspired iron catalysts have been developed and understanding their mechanism of action has become a particularly relevant area of research. While a prominent advance in the preparation and characterization of oxoiron(IV) species has been accomplished, oxoiron(V) species remain exceedingly rare, presumably because the high reactivity that makes them particularly interesting also makes them difficult to observe. This review summarizes the advances in the field, focusing in synthetic systems for which the oxoiron(V) species relevant in these transformations have been directly detected and spetroscopically characterized.     

Biosynthesis of the Fungal Organophosphonate Fosfonochlorin Involves an Iron(II) and 2-(Oxo)glutarate Dependent Oxacyclase

The fungal metabolite Fosfonochlorin features a chloroacetyl moiety that is unusual within known phosphonate natural product biochemistry. Putative biosynthetic genes encoding Fosfonochlorin in Fusarium and Talaromyces spp. were investigated through reactions of encoded enzymes with synthetic substrates and isotope labelling studies. We show that the early biosynthetic steps for Fosfonochlorin involve the reduction of phosphonoacetaldehyde to form 2-hydroxyethylphosphonic acid, followed by oxidative intramolecular cyclization of the resulting alcohol to form (S)-epoxyethylphosphonic acid. The latter reaction is catalyzed by FfnD, a rare example of a non-heme iron/2-(oxo)glutarate dependent oxacyclase. In contrast, FfnD behaves as a more typical oxygenase with ethylphosphonic acid, producing (S)-1-hydroxyethylphosphonic acid. FfnD thus represents a new example of a ferryl generating enzyme that can suppress the typical oxygen rebound reaction that follows abstraction of a substrate hydrogen by a ferryl oxygen, thereby directing the substrate radical towards a fate other than hydroxylation.     

Site-Selective Pyridination of Benzylic and Allylic C−H bonds via Radical-Radical Cross-Coupling

Herein, we report a modular photocatalytic platform for the site-selective pyridination of saturated hydrocarbon compounds employing organic photoredox catalysis to forge new carbon-carbon bonds. The site-selective C−H pyridination could couple benzylic/allylic C−H bonds with pyridylphosphonium salts, which installed directly and regioselectively from C−H heteroarenes through a radical-radical cross coupling mechanism. This synthetic methodology could tolerate a variety of functional groups, complex heteroarenes, even late-stage functionalization of pharmaceuticals selectively.     

Iron and Single Electron Transfer: All is in the Ligand

This account describes some advances we have made in the field of iron catalysis. Two types of reactivity have been uncovered. Based on the use of an iron(II) precatalyst in the presence of NaBH₄, the first one consists in a SET which can be useful for the reductive dehalogenation of iodide and bromide derivatives. Switching to the non-innocent bis-iminopyridine ligands promotes a previously undescribed Csp²−H activation reaction leading to biaryl derivatives. First clues into the intricate nature of the mechanism were obtained and suggested that the redox-active bis-iminopyridine ligand acts as an electron reservoir. The resulting buildup of electron density triggers the C−H bond breaking. All these findings are discussed in light of the existing literature and perspectives are given.     

Eccentricities in Spectroscopy and Reactivity of Non-Heme Metal Intermediates Contained in Bispidine Scaffolds

Ligand framework in a metal complex has a pivotal role to play in orchestrating the spectroscopic and reactivity parameters. High-valent non-heme metal intermediates are known to be crucial species in the catalytic cycles of several metalloenzymes. Among the plethora of a variety of ligand frameworks employed in bioinorganic chemistry, the bispidine molecular scaffold is unique and privileged. In this review, we intend to discuss the overwhelming effects of the bispidine ligand scaffold in tuning the spectroscopic signatures and reactivity parameters of non-heme metal intermediates. The basic skeleton constituting a fused and rigid bicyclic diamine framework with its tentacles tethered to C2, C4, N3 and N7 provides tuneable features to both the primary and secondary coordination spheres. Therefore, the bispidine framework offers a handle to optimize the balance of rigidity and flexibility in a coordination molecule which is thereby important in understanding the rich but surprising results in the reactivity of metal intermediates contained in these scaffolds. Herein, we summarize the significant developments in different types of oxidation reactions of reactive metal intermediates stabilized in bispidine ligands and noted their mechanistic details.     

Electronic structure and reactivity of three-coordinate iron complexes

[Reaction: see text]. The identity and oxidation state of the metal in a coordination compound are typically thought to be the most important determinants of its reactivity. However, the coordination number (the number of bonds to the metal) can be equally influential. This Account describes iron complexes with a coordination number of only three, which differ greatly from iron complexes with octahedral (six-coordinate) geometries with respect to their magnetism, electronic structure, preference for ligands, and reactivity. Three-coordinate complexes with a trigonal-planar geometry are accessible using bulky, anionic, bidentate ligands (beta-diketiminates) that steer a monodentate ligand into the plane of their two nitrogen donors. This strategy has led to a variety of three-coordinate iron complexes in which iron is in the +1, +2, and +3 oxidation states. Systematic studies on the electronic structures of these complexes have been useful in interpreting their properties. The iron ions are generally high spin, with singly occupied orbitals available for pi interactions with ligands. Trends in sigma-bonding show that iron(II) complexes favor electronegative ligands (O, N donors) over electropositive ligands (hydride). The combination of electrostatic sigma-bonding and the availability of pi-interactions stabilizes iron(II) fluoride and oxo complexes. The same factors destabilize iron(II) hydride complexes, which are reactive enough to add the hydrogen atom to unsaturated organic molecules and to take part in radical reactions. Iron(I) complexes use strong pi-backbonding to transfer charge from iron into coordinated alkynes and N 2, whereas iron(III) accepts charge from a pi-donating imido ligand. Though the imidoiron(III) complex is stabilized by pi-bonding in the trigonal-planar geometry, addition of pyridine as a fourth donor weakens the pi-bonding, which enables abstraction of H atoms from hydrocarbons. The unusual bonding and reactivity patterns of three-coordinate iron compounds may lead to new catalysts for oxidation and reduction reactions and may be used by nature in transient intermediates of nitrogenase enzymes.     

Off/on Switching of Electric Current as a Strategy for One-Pot Synthesis of Bromoarylpyridines by Cross-Coupling/ C−H Bromination

An “OFF/ON” electric current switching protocol was developed as a new strategy for one-pot organic synthesis. Suzuki-Miyaura coupling of 2-bromopyridines with arylboronic acids in an electrochemical cell was performed without applying an electric current, and subsequently, the Pd-catalyzed electrochemical C−H bromination was conducted using the already-present Pd catalyst to obtain 2-(2-bromoaryl)pyridines as products. The one-pot synthesis of bromoarenes can also be achieved without adding an external Br source in the second step. Furthermore, an OFF/ON/OFF two-times switching protocol also realized the formation of an N-containing teraryl derivative.     

N‐Heterocyclic Carbene Ligands and Iron: An Effective Association for Catalysis

Although iron has been known and widely used in coordination and organometallic chemistry for decades and N‐heterocyclic carbenes (NHCs) have also been used for about half a century, their combination surprisingly did not become a hot topic in chemistry until this last decade. This review presents several recent and stimulating developments in homogeneous catalysis done mainly using iron/NHC‐based catalysts. Of particular interest are the roles of iron/NHC complexes in cross‐coupling Kochi reactions, C C bond formation reactions and hydrofunctionalization, and more particularly in hydrosilylation. Our review summarizes the key developments in these fields.     

Nickel-Catalyzed Benzylation of C−H Bonds in Aromatic Amides with Benzyltrimethylammonium Halides

Nickel-catalyzed benzylation reactions of C−H bonds in aromatic amides with benzyltrimethylammonium halides are developed by using a 5-chloro-8-aminoquinoline derivative as a bidentate directing group. Benzylation occurs selectively at the ortho-C−H bonds in aromatic amides, and no methylation was detected. The presence of a 5-chloro-8-aminoquinoline moiety is essential for the success of this reaction, in which a variety of functional groups can be tolerated.     

碳酸钠促进选择性非催化还原脱硝的动力学模型与模拟

Abstract The detailed kinetic model of selective non-catalytic reduction （SNCR） of nitric oxide, including so-dium species reactions, was deyeloped on the basis of recent studies on thermal DeNOx mechanism, NOxOUTmechanism and promotion mechanism of Na2CO3. The model was validated by comparison with several experi-mental findings, thus providing an effective tool for the primary and promoted SNCR process simulation. Experimental and simulated results show part-per-million level of sodium carbonate enhances NO removal efficiency andextend the effective SNCR temperature range in comparison with use of a nitrogen agent alone. The kinetic modeling, sensitivity and rate-of-production analysis suggest that the performance improvement can be explained as ho-mogeneous sodium species reactions producing more reactive OH radicals. The net result of sodium species reac-tions is conversion of H2O and inactive HO2 radicals into reactive OH radicals, i.e. H2O＋HO2=3OH, which enhances the SNCR performance of nitrogen agents by mainly increasing the production rate of NH2 radicals. More-over, N2O and CO are eliminated diversely via the reactions Na＋N20=NaO＋N2, NaO＋CO=Na＋CO2 andNaO2＋CO =NaO＋CO2, in.the pro.moted SNCR process, especially in the NOxOUT process.     

Group 9 Transition Metal-Catalyzed C−H Halogenations

The high importance of organic halides as synthetic precursors has led to the development of milder and environmentally benign methods for their synthesis. In this regard, transition metal catalyzed C−H activation has emerged as one of the most promising methods for the synthesis of organic halides with high atom economy and excellent stereo- and regio-control. Despite the dominance of palladium and copper catalysts in the field of C−H halogenation reactions, iridium-, rhodium- and cobalt-complexes have also recently been employed as highly efficient catalysts for the formation of carbon-halogen bonds. This review describes the current state of the art in the field of C−H halogenation reactions using group nine transition metal (Co, Rh, Ir) catalysts.     

Electrochemical Ruthenium-Catalysed Directed C−H Functionalization of Arenes with Boron Reagents

Ortho-directed electrochemical C−H functionalization of aromatics with boron-based coupling partners has been achieved under ruthenium catalysis through an oxidatively induced reductive elimination mechanism. Our method provides a single set of conditions delivering C−H arylation, alkenylation and methylation, yielding ortho-functionalized products with good functional group tolerance, including examples of late-stage functionalization in synthetically useful yields. By harnessing electricity as a ‘green’ oxidant, this method circumvents the need for stoichiometric quantities of chemical oxidants, enhancing our sustainability metrics.