α- and β-Eliminations in Transition Metal Complexes: Strategies to Cleave Unstrained C−C and C−F Bonds

Oxidative addition is the standard process for single-bond activation in transition metal catalysis and it is known to operate for many types of bonds, but challenging σ-bonds e. g. C(sp³)−F and C(sp³)−C(sp³) bonds are the exceptions in this respect. This short review aims at demonstrating how both α- and β-eliminations may be better options for activation of unstrained C−F and C−C single bonds. Selected examples of such eliminations are presented with a mechanistic focus indicating how unstrained and unactivated C−C and C−F bonds can be broken by employing α- and β-eliminations in transition metal hydrocarbyl ligands. Our examples show that the reaction barrier in β-eliminations is controlled by the s-character of the participating bonds where a higher s-character gives a better overlap in the multi-center transition state thereby increasing the reactivity; still β-aryl eliminations can compete with the classical β-hydrogen eliminations in certain cases.     

Transition Metal-Free Aromatic C−H,C−N,C−S and C−O Borylation

Aromatic organoboron compounds are highly valuable building blocks in organic chemistry. They were mainly synthesized through aromatic C−H and C−Het borylation, in which transition metal-catalysis dominate. In the past decade, with increasing attention to sustainable chemistry, numerous transition metal-free C−H and C−Het borylation transformations have been developed and emerged as efficient methods towards the synthesis of aromatic organoboron compounds. This account mainly focuses on recent advances in transition metal-free aromatic C−H, C−N, C−S, and C−O borylation transformations and provides insights to where further developments are required.     

Insertion Chemistry of Lutetacyclopropene toward Unsaturated C−O/C−N Bonds

Although the reaction chemistry of transition metallacyclopropenes has been well-established in the last decades, the reactivity of rare-earth metallacyclopropenes remains elusive. Herein, we report the reaction of lutetacyclopropene 1 toward a series of unsaturated molecules. The reaction of 1 with one equiv. of PhCOMe, Ar¹CHO (Ar¹=2,6-Me₂C₆H₃), W(CO)₆, and PhCH=NPh provided oxalutetacyclopentenes, metallacyclic lutetoxycarbene, and azalutetacyclopentene via 1,2-insertion of C=O, C≡O, or C=N bonds into Lu−C_sp2 bond, respectively. However, the reaction between 1 and Ar²N=C=NAr² (Ar²=4-MeC₆H₄) gave an acyclic lutetium complex with a diamidinate ligand by the coupling of one molecule of 1 with two carbodiimides, irrespective of the amount of carbodiimide employed. More interestingly, when 1 was treated with two equiv. of Ar¹CHO, the reductive coupling of two C=O bonds was discovered to give a lutetium pinacolate complex along with the release of tolan. Remarkably, the reactivity of 1 is significantly different from that of scandacyclopropenes; these metallacycles derived from 1 all represent the first cases in rare-earth organometallic chemistry.     

Activation of N−O σ Bonds with Transition Metals: A Versatile Platform for Organic Synthesis and C−N Bonds Formation**

N−O σ bonds containing compounds are versatile substrates for organic synthesis under transition metal catalysis. Their ability to react through both polar (oxidative addition, formation of metallanitrene, nucleophilic substitution) and radical pathways (single electron transfer, homolytic bond scission) have triggered the development of various synthetic methodologies, particularly toward synthesizing nitrogen-containing compounds. In this review, we discuss the different modes of activation of N−O bonds in the presence of transition metal catalysts, emphasizing the experimental and computational mechanistic proofs in the literature to help to design new synthetic pathways toward the synthesis of C−N bonds.     

Niobium Bis- and Mono(Pentafulvene) Complexes: E−H Bond Cleavage and Insertion Reactions (E=C,N, O)

Bis(η⁵:η¹-(di-para-tolyl)pentafulvene)niobium chloride ( 1 ) reacts with methyl lithium via salt metathesis to the methylated bis(pentafulvene)niobium complex 2 , and with lithium 2,6-diisopropylanilide addition and subsequent N−H bond activation to the imido mono(pentafulvene)niobium complex 3 . Avoiding the competing protonation of the chloride, bis(pentafulvene)niobium complex 2 reacts with primary aromatic and aliphatic amines to form terminal niobocene imido complexes, and with water to form the analog terminal oxo complex. Secondary methyl amines undergo a simultaneous N−H and C−H activation to form niobaaziridines under mild conditions. In contrast to other reported examples, 3 can be employed to investigate the uncontested reactivity of mono(pentafulvene)niobium complexes. Reaction with 4-tert-butylphenol selectively yields a niobocene phenolate complex. Unprecedented for mono(pentafulvene)niobium complexes, treating 3 with multiple-bond-containing substrates (nitriles, isocyanates) smoothly results the insertion into the Nb-C_exo σ-bond, forming the corresponding alkylidene amido and imidato complexes.     

C−H Bond Activation by Iridium(III) and Iridium(IV) Oxo Complexes

Oxidation of an iridium(III) oxo precursor enabled the structural, spectroscopic, and quantum-chemical characterization of the first well-defined iridium(IV) oxo complex. Side-by-side examination of the proton-coupled electron transfer thermochemistry revealed similar driving forces for the isostructural oxo complexes in two redox states due to compensating contributions from H⁺ and e⁻ transfer. However, C−H activation of dihydroanthracene revealed significant hydrogen tunneling for the distinctly more basic iridium(III) oxo complex. Our findings complement the growing body of data that relate tunneling to ground state properties as predictors for the selectivity of C−H bond activation.     

Activation of Aromatic C−F Bonds by a N-Heterocyclic Olefin (NHO)

A N-heterocyclic olefin (NHO), a terminal alkene selectively activates aromatic C−F bonds without the need of any additional catalyst. As a result, a straightforward methodology was developed for the formation of different fluoroaryl-substituted alkenes in which the central carbon–carbon double bond is in a twisted geometry.     

Forging C−S Bonds on the Azetidine Ring by Continuous Flow Photochemical Addition of Thiols and Disulfides to Azetines

A strategy for anti-Markovnikov hydroalkyl/aryl thiolation and disulfidation of 2-azetines under continuous flow conditions has been developed. Thiyl radicals are generated from thiols or disulfides and subsequently propagate into the azetine unsaturation to forge the C−S bond and shape a secondary radical intermediate. This carbon-centered radical chain transfers to another thiol via hydrogen atom transfer (HAT) or another disulfide to regenerate the key thiyl radical intermediates. The use of flow technology ensures efficient irradiation of the reaction mixture leading to extremely fast, robust, and scalable protocols. Furthermore, ethyl acetate was adopted as an environmentally responsible solvent.     

M≡E and M=E Complexes of Iron and Cobalt that Emphasize Three-fold Symmetry (E = O, N, NR)

Mid-to-late transition metal complexes that feature terminal, multiply bonded ligands such as oxos, imides, and nitrides have been invoked as intermediates in several catalytic transformations of synthetic and biological significance. Until about ten years ago, isolable examples of such species were virtually unknown. Over the past decade or so, numerous chemically well-defined examples of such species have been discovered. In this context, the presentreview summarizes the development of 4- and 5-coordinate Fe(E) and Co(E) species under local three-fold symmetry.     

Activation of Protic,Hydridic and Apolar E−H Bonds by a Boryl-Substituted GeII Cation

The synthesis of a boryl-substituted germanium(II) cation, [Ge{B(NDippCH)₂}(IPrMe)]⁺, (Dipp=2,6-diisopropylphenyl) featuring a supporting N-heterocyclic carbene (NHC) donor, has been explored through chloride abstraction from the corresponding (boryl)(NHC)GeCl precursor. Crystallographic studies in the solid state and UV/Vis spectra in fluorobenzene solution show that this species dimerizes under such conditions to give [(IPrMe){(HCNDipp)₂B}Ge=Ge{B(NDippCH)₂}(IPrMe)]²⁺ (IPrMe = 1,3-diisopropyl-4,5-dimethylimidazolin-2-ylidene), which can be viewed as an imidazolium-functionalized digermene. The dimer is cleaved in the presence of donor solvents such as [D₈]thf or [D₅]pyridine, to give monomeric adducts of the type [Ge{B(NDippCH)₂}(IPrMe)(L)]⁺. In the case of the thf adduct, the additional donor is shown to be sufficiently labile that it can act as a convenient in situ source of the monomeric complex [Ge{B(NDippCH)₂}(IPrMe)]⁺ for oxidative bond-activation chemistry. Thus, [Ge{B(NDippCH)₂}(IPrMe)(thf)]⁺ reacts with silanes and dihydrogen, leading to the formation of Ge^IV products, whereas the cleavage of the N−H bond in ammonia ultimately yields products containing C−H and B−N bonds. The facile reactivity observed in E−H bond activation is in line with the very small calculated HOMO–LUMO gap (132 kJ mol⁻¹).     

Carbene–Transition Metal Complexes Formed by Double C?H Bond Activation

The activation of a single sp³ C? H bond of alkanes and their derivatives by electron‐rich transition metal complexes has been a topic of interest since the landmark work by Bergman and Graham in 1982. Ten years later, it was shown that compounds of 5d elements, such as osmium and iridium, even enable a double α‐C? H bond activation of alkane or cycloalkane derivatives containing an OR or NR₂ functional group, thus opening up a new route to obtain Fischer‐type transition metal carbene complexes. Subsequent work focused in particular on the conversion of methyl alkyl and methyl aryl ethers into bound oxocarbenes and also of dimethyl amines to bound aminocarbenes. In the context of this work, it was recently shown that square‐planar oxocarbene–iridium(I) complexes prepared in this way exhibit an unusual mode of reactivity: They react with CO₂, CS₂, COS, PhNCO, and PhNCS by an atom‐ or group‐transfer metathesis, which has no precedent. Organic azides RN₃ and N₂O behave similarly. Recent results confirm that this novel type of metathesis can be made catalytic, thus offering a novel possibility for C? H bond functionalization.     

Vacancy-Rich Ni(OH)2 Drives the Electrooxidation of Amino C−N Bonds to Nitrile C≡N Bonds

Electrochemical synthesis based on electrons as reagents provides a broad prospect for commodity chemical manufacturing. A direct one-step route for the electrooxidation of amino C−N bonds to nitrile C≡N bonds offers an alternative pathway for nitrile production. However, this route has not been fully explored with respect to either the chemical bond reforming process or the performance optimization. Proposed here is a model of vacancy-rich Ni(OH)₂ atomic layers for studying the performance relationship with respect to structure. Theoretical calculations show the vacancy-induced local electropositive sites chemisorb the N atom with a lone pair of electrons and then attack the corresponding N(sp³)−H, thus accelerating amino C−N bond activation for dehydrogenation directly into the C≡N bond. Vacancy-rich nanosheets exhibit up to 96.5 % propionitrile selectivity at a moderate potential of 1.38 V. These findings can lead to a new pathway for facilitating catalytic reactions in the chemicals industry.     

Gallium “Shears” for C=N and C=O Bonds of Isocyanates

Digallane [L¹Ga−GaL¹] ( 1 , L¹=dpp-bian=1,2-[(2,6-iPr₂C₆H₃)NC]₂C₁₂H₆) reacts with RN=C=O (R=Ph or Tos) by [2+4] cycloaddition of the isocyanate C=N bonds across both of its C=C−N−Ga fragments to afford [L¹(O=C−NR)Ga−Ga(RN−C=O)L¹] (R=Ph, 3 ; R=Tos, 4 ). The reactions with both isocyanates result in new C−C and N−Ga single bonds. In the case of allyl isocyanate, the [2+4] cycloaddition across one C=C−N−Ga fragment of 1 is accompanied by insertion of a second allyl isocyanate molecule into the Ga−N bond of the same fragment to afford compound [L¹Ga−Ga(AllN− C=O)₂L¹] ( 5 ) (All=allyl). In the presence of Na metal, the related digallane [L²Ga−GaL²] ( 2 ; L²=dpp-dad=[(2,6-iPr₂C₆H₃)NC(CH₃)]₂) is converted into the gallium(I) carbene analogue [L²Ga:]⁻ ( 2 A ), which undergoes a variety of reactions with isocyanate substrates. These include the cycloaddition of ethyl isocyanate to 2 A affording [Na₂(THF)₅]{L²Ga[EtN−C(O)]₂GaL²} ( 6 ), cleavage of the N=C bond with release of 1 equiv. of CO to give [Na(THF)₂]₂[L²Ga(p-MeC₆H₄)(N−C(O))₂−N(p-MeC₆H₄)]₂ ( 7 ), cleavage of the C=O bond to yield the di-O-bridged digallium compound [Na(THF)₃]₂[L²Ga-(μ-O)₂-GaL²] ( 8 ), and generation of the further addition product [Na₂(THF)₅][L²Ga(CyNCO₂)]₂ ( 9 ). Complexes 3 – 9 have been characterized by NMR (¹H, ¹³C), IR spectroscopy, elemental analysis, and X-ray diffraction analysis. Their electronic structures have been examined by DFT calculations.     

Ruthenium Catalyzed Intramolecular C−X (X=C,N, O,S) Bond Formation via C−H Functionalization: An Overview

Ruthenium catalyzed C−H activation is well known for its high tolerance towards the functional group and broad applicability in organic synthesis and molecular sciences, with significant applications in pharmaceutical industries, material sciences, and polymer industry. In the last few decades, enormous progress has been observed with ruthenium-catalyzed C−H activation chemistry. Notably, the vast majority of the C−H functionalization known in the literature are intermolecular, although the intramolecular variant provides fascinating new structural facet starting from the simple molecular scaffolds. Intramolecular C−H functionalization is atom economical and step efficient, results in less formation of undesired products which is easy to purify. This has created a lot of interest in organic chemistry in developing new synthetic strategies for such functionalization. The focus of this review is to present the relatively unexplored intramolecular functionalization of C−H bonds into C−X (X=C, N, O, S) bonds utilizing versatile ruthenium catalysts, their scope, and brief mechanistic discussion.     

Electrochemical Enabled Cascade Phosphorylation of N−H/O−H/S−H Bonds with P−H Compounds: An Efficient Access to P(O)-X Bonds

An electrochemical three component cascade phosphorylation reaction of various heteroatoms-containing nucleophiles including carbazoles, indoles, phenols, alcohols, and thiols with Ph₂PH has been established. Electricity is used as the “traceless” oxidant and water and air are utilized as the “green” oxygen source. All kinds of structurally diverse organophosphorus compounds with P(O)-N/P(O)-O/P(O)-S bonds are assembled in moderate to excellent yields (three categories of phosphorylation products, 50 examples, up to 97 % yield). A tentative free radical course is put forward to rationalize the reaction procedure.     

Bis-[3]Ferrocenophanes with Central >E−E’< Bonds (E,E’=P,SiH): Preparation,Properties, and Thermal Activation

A series of bis-[3]ferrocenophanes of the general type Fe(C₅H₄E’)₂E−E(E'C₅H₄)₂Fe (E=P, SiH and E’=PtBu, NneoPentyl, NSi(CH₃)₃) with an isolobal molecular framework have been prepared and characterized by heteronuclear NMR spectroscopy and X-ray crystallography. The thermal dissociation behavior with respect to homolytic fission of the central bond generating phosphorus centered radicals was investigated using EPR spectroscopy and quantum chemical calculations.     

Selective Activation of Ar–Cl and Ar–C Bonds with Iron(II) Complexes

The electrophilic iron–carbene chelate complexes 1 and 2 react with alkoxides RO⁻ to give the neutral chelate complex 3 and the carbene complex 4 , respectively. Depending on the nature of the chelating ortho substituent, selective activation of the Ar–Cl or Ar–C bond occurs; these processes are promoted by the chelation.     

N−X⋅⋅⋅O−N Halogen Bonds in Complexes of N-Haloimides and Pyridine-N-oxides: A Large Data Set Study

N−X⋅⋅⋅⁻O−N⁺ halogen-bonded systems formed by 27 pyridine N-oxides (PyNOs) as halogen-bond (XB) acceptors and two N-halosuccinimides, two N-halophthalimides, and two N-halosaccharins as XB donors are studied in silico, in solution, and in the solid state. This large set of data (132 DFT optimized structures, 75 crystal structures, and 168 ¹H NMR titrations) provides a unique view to structural and bonding properties. In the computational part, a simple electrostatic model (SiElMo) for predicting XB energies using only the properties of halogen donors and oxygen acceptors is developed. The SiElMo energies are in perfect accord with energies calculated from XB complexes optimized with two high-level DFT approaches. Data from in silico bond energies and single-crystal X-ray structures correlate; however, data from solution do not. The polydentate bonding characteristic of the PyNOs’ oxygen atom in solution, as revealed by solid-state structures, is attributed to the lack of correlation between DFT/solid-state and solution data. XB strength is only slightly affected by the PyNO oxygen properties [(atomic charge (Q), ionization energy (I_s,min) and local negative minima (V_s,min)], as the σ-hole (V_s,max) of the donor halogen is the key determinant leading to the sequence N-halosaccharin>N-halosuccinimide>N-halophthalimide on the XB strength.     

Unusual Nitrene Oxidation Product Formation by Metathesis Involving the Dioxygen O−O and Borylnitrene B−N Bonds

The reaction of dioxygen with nitrenes can have significant energy barriers, although both reactants are triplet diradicals and the formation of nitroso-O-oxides is spin-allowed. By means of matrix-isolation infrared spectroscopy in solid argon, nitrogen, and neon, and through high-level computational quantum chemistry, it is shown herein that a 3-nitreno-1,3,2-benzodioxaborole CatBN (Cat=catecholato) reacts with dioxygen under cryogenic conditions thermally at temperatures as low as 7 K to produce two distinct products, an anti-nitroso-O-oxide and a nitritoborane CatBONO. The computed barriers for the formation of nitroso-O-oxide isomers are very low. Whereas anti-nitroso-O-oxide is kinetically trapped, its bisected isomer has a very low barrier for metathesis, yielding the CatBO+NO radicals in a strongly exothermic reaction; these radicals can combine under matrix-isolation conditions to give nitritoborane CatBONO. The trapped isomer, anti-nitroso-O-oxide, can form the nitritoborane CatBONO only after photoexcitation, possibly involving isomerization to the bisected isomer of anti-nitroso-O-oxide.     

Direct Synthesis of Disubstituted 3-Isoquinolinone Derivatives through the Construction of C−N,C=O,and C(sp2)−C(sp3) Bonds under Transition-Metal-Free Conditions

The efficient three-component cascade coupling reaction of 3-haloisoquinolines, haloalkanes, and sp³-carbon nucleophiles (acetophenone or nitromethane) led to a series of structurally novel 1,2-disubstituted-3-isoquinolinones through the formation of C(sp³)−C(sp²), C−N, and C=O bonds. The NaOAc-promoted reaction described in this work is simple to operate, environment friendly, and highly selective.