Enantioselective Palladium‐Catalyzed Insertion of α‐Aryl‐α‐diazoacetates into the OH Bonds of Phenols

A palladium‐catalyzed asymmetric O? H insertion reaction was developed. Palladium complexes with chiral spiro bisoxazoline ligands promoted the insertion of α‐aryl‐α‐diazoacetates into the O? H bond of phenols with high yield and excellent enantioselectivity under mild reaction conditions. This palladium‐catalyzed asymmetric O? H insertion reaction provided an efficient and highly enantioselective method for the preparation of synthetically useful optically active α‐aryl‐α‐aryloxyacetates.     

Redox‐Active NOx Ligands in Palladium‐Mediated Processes

This Minireview highlights the redox and non‐innocent behavior of NO_x ligands (x=1, 2, or 3) in selected Pd‐mediated processes, for example, alkene and aromatic oxidation processes. A focus is placed on mechanistic understanding and linking recent transformations, such as C? H bond activation/functionalization and Wacker oxidation, with previous work on the functionalization of aromatics and alkenes by Pd^II salts.     

Iron‐Carbonyl‐Catalyzed Redox‐Neutral [4+2] Annulation of N−H Imines and Internal Alkynes by C−H Bond Activation

Stoichiometric C?H bond activation of arenes mediated by iron carbonyls was reported by Pauson as early as in 1965, yet the catalytic C?H transformations have not been developed. Herein, an iron‐catalyzed annulation of N?H imines and internal alkynes to furnish cis‐3,4‐dihydroisoquinolines is described, and represents the first iron‐carbonyl‐catalyzed C?H activation reaction of arenes. Remarkablely, this is also the first redox‐neutral [4+2] annulation of imines and alkynes proceeding by C?H activation. The reaction also features only cis stereoselectivity and excellent atom economy as neither base, nor external ligand, nor additive is required. Experimental and theoretical studies reveal an oxidative addition mechanism for C?H bond activation to afford a dinuclear ferracycle and a synergetic diiron‐promoted H‐transfer to the alkyne as the turnover‐determining step.     

Non‐coordinating‐Anion‐Directed Reversal of Activation Site: Selective C−H Bond Activation of N‐Aryl Rings

An Rh‐catalyzed selective C?H bond activation of diaryl‐substituted anilides is described. In an attempt to achieve C?H activation of C‐aryl rings, we unexpectedly obtained an N‐aryl ring product under non‐coordinating anion conditions, whereas the C‐aryl ring product was obtained in the absence of a non‐coordinating anion. This methodology has proved to be an excellent means of tuning and adjusting selective C?H bond activation of C‐aryl and N‐aryl rings. The approach has been rationalized by mechanistic studies and theoretical calculations. In addition, it has been found and verified that the catalytic activity of the rhodium catalyst is obviously improved by non‐coordinating anions, which provides an efficient strategy for obtaining a highly chemoselective catalyst. Mechanistic experiments also unequivocally ruled out the possibility of a so‐called “silver effect” in this transformation involving silver.     

Gold‐Catalyzed 1,2‐Diarylation of Alkenes

Herein, we disclose the gold‐catalyzed 1,2‐diarylation of alkenes through the interplay of ligand‐enabled Au^I/Au^III catalysis with the idiosyncratic π‐activation mode of gold complexes. Unlike the classical migratory‐insertion‐based approach to 1,2‐diarylation, the present approach not only circumvents the formation of direct Ar?Ar′ coupling and Heck‐type side products but more intriguingly demonstrates reactivity and selectivity complementary to those of previously known metal catalysis (Pd, Ni, or Cu). Detailed investigations to underpin the mechanistic scenario revealed oxidative addition of aryl iodides to an Au^I complex to be the rate‐limiting step owing to the non‐innocent nature of the aryl alkene.     

Three‐Way Cooperativity in d8 Metal Complexes with Ligands Displaying Chemical and Redox Non‐Innocence

Reversible proton‐ and electron‐transfer steps are crucial for various chemical transformations. The electron‐reservoir behavior of redox non‐innocent ligands and the proton‐reservoir behavior of chemically non‐innocent ligands can be cooperatively utilized for substrate bond activation. Although site‐decoupled proton‐ and electron‐transfer steps are often found in enzymatic systems, generating model metal complexes with these properties remains challenging. To tackle this issue, we present herein complexes [(cod_?H)M(μ‐L^2?) M (cod_?H)] (M=Pt^II, [ 1 ] or Pd^II, [ 2 ], cod=1,5‐cyclooctadiene, H₂L=2,5‐di‐[2,6‐(diisopropyl)anilino]‐1,4‐benzoquinone), in which cod acts as a proton reservoir, and L^2? as an electron reservoir. Protonation of [ 2 ] leads to an unusual tetranuclear complex. However, [ 1 ] can be stepwise reversibly protonated with up to two protons on the cod_?H ligands, and the protonated forms can be stepwise reversibly reduced with up to two electrons on the L^2? ligand. The doubly protonated form of [ 1 ] is also shown to react with OMe^? leading to an activation of the cod ligands. The site‐decoupled proton and electron reservoir sources work in tandem in a three‐way cooperative process that results in the transfer of two electrons and two protons to a substrate leading to its double reduction and protonation. These results will possibly provide new insights into developing catalysts for multiple proton‐ and electron‐transfer reactions by using metal complexes of non‐innocent ligands.     

Manganese‐Catalyzed Dehydrogenative [4+2] Annulation of NH Imines and Alkynes by CH/NH Activation

Described herein is a manganese‐catalyzed dehydrogenative [4+2] annulation of N? H imines and alkynes, a reaction providing highly atom‐economical access to diverse isoquinolines. This transformation represents the first example of manganese‐catalyzed C? H activation of imines; the stoichiometric variant of the cyclomanganation was reported in 1971. The redox neutral reaction produces H₂ as the major byproduct and eliminates the need for any oxidants, external ligands, or additives, thus standing out from known isoquinoline synthesis by transition‐metal‐catalyzed C? H activation. Mechanistic studies revealed the five‐membered manganacycle and manganese hydride species as key reaction intermediates in the catalytic cycle.     

Mononuclear Nonheme High‐Spin (S=2) versus Intermediate‐Spin (S=1) Iron(IV)–Oxo Complexes in Oxidation Reactions

Mononuclear nonheme high‐spin (S=2) iron(IV)–oxo species have been identified as the key intermediates responsible for the C?H bond activation of organic substrates in nonheme iron enzymatic reactions. Herein we report that the C?H bond activation of hydrocarbons by a synthetic mononuclear nonheme high‐spin (S=2) iron(IV)–oxo complex occurs through an oxygen non‐rebound mechanism, as previously demonstrated in the C?H bond activation by nonheme intermediate (S=1) iron(IV)–oxo complexes. We also report that C?H bond activation is preferred over C=C epoxidation in the oxidation of cyclohexene by the nonheme high‐spin (HS) and intermediate‐spin (IS) iron(IV)–oxo complexes, whereas the C=C double bond epoxidation becomes a preferred pathway in the oxidation of deuterated cyclohexene by the nonheme HS and IS iron(IV)–oxo complexes. In the epoxidation of styrene derivatives, the HS and IS iron(IV) oxo complexes are found to have similar electrophilic characters.     

Catalytic C−H Trifluoromethoxylation of Arenes and Heteroarenes

The intermolecular C?H trifluoromethoxylation of arenes remains a long‐standing and unsolved problem in organic synthesis. Herein, we report the first catalytic protocol employing a novel trifluoromethoxylating reagent and redox‐active catalysts for the direct (hetero)aryl C?H trifluoromethoxylation. Our approach is operationally simple, proceeds at room temperature, uses easy‐to‐handle reagents, requires only 0.03 mol % of redox‐active catalysts, does not need specialized reaction apparatus, and tolerates a wide variety of functional groups and complex structures such as sugars and natural product derivatives. Importantly, both ground‐state and photoexcited redox‐active catalysts are effective. Detailed computational and experimental studies suggest a unique reaction pathway where photoexcitation of the trifluoromethoxylating reagent releases the OCF₃ radical that is trapped by (hetero)arenes. The resulting cyclohexadienyl radicals are oxidized by redox‐active catalysts and deprotonated to form the desired products of trifluoromethoxylation.     

Neutral Tridentate PNP Ligands and Their Hybrid Analogues: Versatile Non‐Innocent Scaffolds for Homogeneous Catalysis

Ligands in coordination chemistry and homogeneous catalysis are traditionally “static” spectators that do not actively participate in the catalytic cycle. However, such classic systems do not provide additional “handles” that could facilitate or trigger alternative productive reaction pathways. Recent advances in the use of novel nitrogen‐centered pincer systems have unveiled interesting opportunities for cooperative catalysis. The chemistry of pyridine‐derived, neutral ligands is discussed, with a specific focus on their non‐innocent behavior and potential as facilitators for metal‐mediated organic transformations. This overview should provide inspiration and an incentive to incorporate non‐innocent ligands and their metal complexes within old and new homogeneously catalyzed reactions.     

Biologically Inspired C−H and C=C Oxidations with Hydrogen Peroxide Catalyzed by Iron Coordination Complexes

The development of catalysts for the selective oxidation of readily available hydrocarbons or organic precursors into oxygenated products is a long‐standing goal in organic synthesis. In the last decade, some iron coordination complexes have shown the potential to fit this role. These catalysts can mimic the O?O activation mode of far more sophisticated iron oxygenase enzymes, generating powerful yet selective oxidants. In this review, we report state‐of‐the‐art C?H and C=C oxidations catalyzed by non‐heme iron complexes and H₂O₂ as the oxidant. Finally, we briefly describe some novel oxidative reactivity and the perspectives of this chemistry.     

Fe‐Catalyzed Cross‐Coupling Reaction of Vinylic Ethers with Aryl Grignard Reagents

Iron‐catalyzed cross‐coupling reaction of vinylic ethers with aryl Grignard reagents is described. The reaction proceeded at room temperature with catalytic amounts of an iron salt without the aid of costly ligands and additives. In this catalytic system, vinylic C?O bonds were preferentially cleaved over aromatic C?O bonds of aryl ethers or aryl sulfonates.     

C−H Bond Activation/Arylation Catalyzed by Arene–Ruthenium–Aniline Complexes in Water

Water‐soluble arene–ruthenium complexes coordinated with readily available aniline‐based ligands were successfully employed as highly active catalysts in the C?H bond activation and arylation of 2‐phenylpyridine with aryl halides in water. A variety of (hetero)aryl halides were also used for the ortho‐C?H bond arylation of 2‐phenylpyridine to afford the corresponding ortho‐ monoarylated products as major products in moderate to good yields. Our investigations, including time‐scaled NMR spectroscopy and mass spectrometry studies, evidenced that the coordinating aniline‐based ligands, having varying electronic and steric properties, had a significant influence on the catalytic activity of the resulting arene–ruthenium–aniline‐based complexes. Moreover, mass spectrometry identification of the cycloruthenated species, {(η⁶‐arene)Ru(κ²‐C,N‐phenylpyridine)}⁺, and several ligand‐coordinated cycloruthenated species, such as [(η⁶‐arene)Ru(4‐methylaniline)(κ²‐C,N‐phenylpyridine)]⁺, found during the reaction of 2‐phenylpyridine with the arene–ruthenium–aniline complexes further authenticated the crucial roles of these species in the observed highly active and tuned catalyst. At last, the structures of a few of the active catalysts were also confirmed by single‐crystal X‐ray diffraction studies.     

Methandiide as a Non‐Innocent Ligand in Carbene Complexes: From the Electronic Structure to Bond Activation Reactions and Cooperative Catalysis

The synthesis of a ruthenium carbene complex based on a sulfonyl‐substituted methandiide and its application in bond activation reactions and cooperative catalysis is reported. In the complex, the metal–carbon interaction can be tuned between a Ru?C single bond with additional electrostatic interactions and a Ru?C double bond, thus allowing the control of the stability and reactivity of the complex. Hence, activation of polar and non‐polar bonds (O?H, H?H) as well as dehydrogenation reactions become possible. In these reactions the carbene acts as a non‐innocent ligand supporting the bond activation as nucleophilic center in the 1,2‐addition across the metal–carbon double bond. This metal–ligand cooperativity can be applied in the catalytic transfer hydrogenation for the reduction of ketones. This concept opens new ways for the application of carbene complexes in catalysis.     

α‐MsO/TsO/Cl Ketones as Oxidized Alkyne Equivalents: Redox‐Neutral Rhodium(III)‐Catalyzed CH Activation for the Synthesis of N‐Heterocycles

α‐Halo and pseudohalo ketones are used for the first time as C(sp³)‐based electrophiles in transition‐metal‐catalyzed C? H activation and as oxidized alkyne equivalents in Rh^III‐catalyzed redox‐neutral annulations to generate diverse N‐heterocycles. This transformation is efficient and scalable. Due to the mild reaction conditions, a variety of functional groups could be tolerated.     

Metal‐Induced Thiophene Ring Opening and CC Bond Formation To Produce Unique Hexa‐1,3,5‐trienediyl‐Coupled Non‐Innocent Ligand Chelates

Ring opening of thiophenes containing an azo function in 2‐position and subsequent dimerization through C?C coupling were observed on reaction with [Ru(acac)₂(CH₃CN)₂] (acac=acetylacetonate) to produce two 1,3,5‐hexatriene‐linked redox‐active azothiocarbonyl chelate systems. Interaction of the non‐innocent chelate ligands and of the metals at a nanoscale distance of 1.45 nm via the conjugated hexatriene bridge was studied by magnetic and electron spectroscopic measurements in conjunction with DFT calculations, revealing four‐center magnetic interactions of this unique setting and weak intervalence coupling after reduction.     

Ligand‐Enabled Nickel‐Catalyzed Redox‐Relay Migratory Hydroarylation of Alkenes with Arylborons

A redox‐relay migratory hydroarylation of isomeric mixtures of olefins with arylboronic acids catalyzed by nickel complexes bearing diamine ligands is described. A range of structurally diverse 1,1‐diarylalkanes, including those containing a 1,1‐diarylated quaternary carbon, were obtained in excellent yields and with high regioselectivity. Preliminary experimental evidence supports the proposed non‐dissociated chainwalking of aryl‐nickel(II)‐hydride species along the alkyl chain of alkenes before selective reductive elimination at a benzylic position. A catalyst loading as low as 0.5 mol % proved to be sufficient in large‐scale synthesis while retaining high reactivity, highlighting the practical value of this transformation.     

Directed meta‐Selective Bromination of Arenes with Ruthenium Catalysts

A Ru‐catalyzed direct C? H activation/meta‐bromination of arenes bearing pyridyl, pyrimidyl, and pyrazolyl directing groups has been developed. A series of bromo aryl pyridines and pyrimidines have been synthesized, and further coupling reactions have also been demonstrated for a number of representative functionalized arenes. Preliminary mechanistic studies have revealed that this reaction may proceed through radical‐mediated bromination when NBS is utilized as the bromine source. This type of transformation has opened up a new direction for the radical non‐ipso functionalization of metal with regard to future C? H activation development that would allow the remote functionalization of aromatic systems.     

Catalytic C−H Borylation Using Iron Complexes Bearing 4,5,6,7‐Tetrahydroisoindol‐2‐ide‐Based PNP‐Type Pincer Ligand

Catalytic C?H borylation has been reported using newly designed iron complexes bearing a 4,5,6,7‐tetrahydroisoindol‐2‐ide‐based PNP pincer ligand. The reaction tolerated various five‐membered heteroarenes, such as pyrrole derivatives, as well as six‐membered aromatic compounds, such as toluene. Successful examples of the iron‐catalyzed sp³ C?H borylation of anisole derivatives were also presented.     

Iron and Manganese Catalysts for the Selective Functionalization of Arene C(sp2)−H Bonds by Carbene Insertion

The first examples of the direct functionalization of non‐activated aryl sp² C?H bonds with ethyl diazoacetate (N₂CHCO₂Et) catalyzed by Mn‐ or Fe‐based complexes in a completely selective manner are reported, with no formation of the frequently observed cycloheptatriene derivatives through competing Buchner reaction. The best catalysts are Fe^II or Mn^II complexes bearing the tetradentate pytacn ligand (pytacn= 1‐(2‐pyridylmethyl)‐4,7‐dimethyl‐1,4,7‐triazacyclononane). When using alkylbenzenes, the alkylic C(sp³)?H bonds of the substituents remained unmodified, thus the reaction being also selective toward functionalization of sp² C?H bonds.