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.     

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.     

Boosting Low‐Valent Aluminum(I) Reactivity with a Potassium Reagent

The reagent RK [R=CH(SiMe₃)₂ or N(SiMe₃)₂] was expected to react with the low‐valent (^DIPPBDI)Al (^DIPPBDI=HC[C(Me)N(DIPP)]₂, DIPP=2,6‐iPr‐phenyl) to give [(^DIPPBDI)AlR]^?K⁺. However, deprotonation of the Me group in the ligand backbone was observed and [H₂C=C(N‐DIPP)?C(H)=C(Me)?N?DIPP]Al^?K⁺ ( 1 ) crystallized as a bright‐yellow product (73 %). Like most anionic Al^I complexes, 1 forms a dimer in which formally negatively charged Al centers are bridged by K⁺ ions, showing strong K⁺???DIPP interactions. The rather short Al–K bonds [3.499(1)–3.588(1) Å] indicate tight bonding of the dimer. According to DOSY NMR analysis, 1 is dimeric in C₆H₆ and monomeric in THF, but slowly reacts with both solvents. In reaction with C₆H₆, two C?H bond activations are observed and a product with a para‐phenylene moiety was exclusively isolated. DFT calculations confirm that the Al center in 1 is more reactive than that in (^DIPPBDI)Al. Calculations show that both Al^I and K⁺ work in concert and determines the reactivity of 1 .     

Formation and High Reactivity of the anti‐Dioxo Form of High‐Spin μ‐Oxodioxodiiron(IV) as the Active Species That Cleaves Strong C−H Bonds

Recently, it was shown that μ‐oxo‐μ‐peroxodiiron(III) is converted to high‐spin μ‐oxodioxodiiron(IV) through O?O bond scission. Herein, the formation and high reactivity of the anti‐dioxo form of high‐spin μ‐oxodioxodiiron(IV) as the active oxidant are demonstrated on the basis of resonance Raman and electronic‐absorption spectral changes, detailed kinetic studies, DFT calculations, activation parameters, kinetic isotope effects (KIE), and catalytic oxidation of alkanes. Decay of μ‐oxodioxodiiron(IV) was greatly accelerated on addition of substrate. The reactivity order of substrates is toluene<ethylbenzene≈cumene<trans‐β‐methylstyrene. The rate constants increased proportionally to the substrate concentration at low substrate concentration. At high substrate concentration, however, the rate constants converge to the same value regardless of the kind of substrate. This is explained by a two‐step mechanism in which anti‐μ‐oxodioxodiiron(IV) is formed by syn‐to‐anti transformation of the syn‐dioxo form and reacts with substrates as the oxidant. The anti‐dioxo form is 620 times more reactive in the C?H bond cleavage of ethylbenzene than the most reactive diiron system reported so far. The KIE for the reaction with toluene/[D₈]toluene is 95 at ?30 °C, which the largest in diiron systems reported so far. The present diiron complex efficiently catalyzes the oxidation of various alkanes with H₂O₂.     

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.     

Pathways of the Extremely Reactive Iron(IV)-oxido complexes with Tetradentate Bispidine Ligands

The nonheme iron(IV)-oxido complex trans-N3-[(L¹)Fe^IV=O(Cl)]⁺, where L¹ is a derivative of the tetradentate bispidine 2,4-di(pyridine-2-yl)-3,7-diazabicyclo[3.3.1]nonane-1-one, is known to have an S=1 electronic ground state and to be an extremely reactive oxidant for oxygen atom transfer (OAT) and hydrogen atom abstraction (HAA) processes. Here we show that, in spite of this ferryl oxidant having the “wrong” spin ground state, it is the most reactive nonheme iron model system known so far and of a similar order of reactivity as nonheme iron enzymes (C−H abstraction of cyclohexane, −90 °C (propionitrile), t_1/2=3.5 sec). Discussed are spectroscopic and kinetic data, supported by a DFT-based theoretical analysis, which indicate that substrate oxidation is significantly faster than self-decay processes due to an intramolecular demethylation pathway and formation of an oxido-bridged diiron(III) intermediate. It is also shown that the iron(III)-chlorido-hydroxido/cyclohexyl radical intermediate, resulting from C−H abstraction, selectively produces chlorocyclohexane in a rebound process. However, the life-time of the intermediate is so long that other reaction channels (known as cage escape) become important, and much of the C−H abstraction therefore is unproductive. In bulk reactions at ambient temperature and at longer time scales, there is formation of significant amounts of oxidation product – selectively of chlorocyclohexane – and it is shown that this originates from oxidation of the oxido-bridged diiron(III) resting state.     

Enhanced Electron Transfer Reactivity of a Nonheme Iron(IV)–Imido Complex as Compared to the Iron(IV)‐Oxo Analogue

Reactions of N,N‐dimethylaniline (DMA) with nonheme iron(IV)‐oxo and iron(IV)‐tosylimido complexes occur via different mechanisms, such as an N‐demethylation of DMA by a nonheme iron(IV)‐oxo complex or an electron transfer dimerization of DMA by a nonheme iron(IV)‐tosylimido complex. The change in the reaction mechanism results from the greatly enhanced electron transfer reactivity of the iron(IV)‐tosylimido complex, such as the much more positive one‐electron reduction potential and the smaller reorganization energy during electron transfer, as compared to the electron transfer properties of the corresponding iron(IV)‐oxo complex.     

Shedding Light on the Diverse Reactivity of NacNacAl with N‐Heterocycles

The aluminum(I) compound NacNacAl (NacNac=[ArNC(Me)CHC(Me)NAr]^?, Ar=2,6‐iPr₂C₆H₃, 1 ) shows diverse and substrate‐controlled reactivity in reactions with N‐heterocycles. 4‐Dimethylaminopyridine (DMAP), a basic substrate in which the 4‐position is blocked, induces rearrangement of NacNacAl by shifting a hydrogen atom from the methyl group of the NacNac backbone to the aluminum center. In contrast, C?H activation of the methyl group of 4‐picoline takes place to produce a species with a reactive terminal methylene. Reaction of 1 with 3,5‐lutidine results in the first example of an uncatalyzed, room‐temperature cleavage of an sp² C?H bond (in the 4‐position) by an Al^I species. Another reactivity mode was observed for quinoline, which undergoes 2,2′‐coupling. Finally, the reaction of 1 with phthalazine produces the product of N?N bond cleavage.     

Reactivity of Oxygen Radical Anions Bound to Scandia Nanoparticles in the Gas Phase: CH Bond Activation

The activation of C?H bonds in alkanes is currently a hot research topic in chemistry. The atomic oxygen radical anion (O^?.) is an important species in C?H activation. The mechanistic details of C?H activation by O^?. radicals can be well understood by studying the reactions between O^?. containing transition metal oxide clusters and alkanes. Here the reactivity of scandium oxide cluster anions toward n‐butane was studied by using a high‐resolution time‐of‐flight mass spectrometer coupled with a fast flow reactor. Hydrogen atom abstraction (HAA) from n‐butane by (Sc₂O₃)_NO^? (N=1–18) clusters was observed. The reactivity of (Sc₂O₃)_NO^? (N=1–18) clusters is significantly sizedependent and the highest reactivity was observed for N=4 (Sc₈O₁₃^?) and 12 (Sc₂₄O₃₇^?). Larger (Sc₂O₃)_NO^? clusters generally have higher reactivity than the smaller ones. Density functional theory calculations were performed to interpret the reactivity of (Sc₂O₃)_NO^? (N=1–5) clusters, which were found to contain the O^?. radicals as the active sites. The local charge environment around the O^?. radicals was demonstrated to control the experimentally observed size‐dependent reactivity. This work is among the first to report HAA reactivity of cluster anions with dimensions up to nanosize toward alkane molecules. The anionic O^?. containing scandium oxide clusters are found to be more reactive than the corresponding cationic ones in the C?H bond activation.     

Pentamethylcyclopentadienylrhodium(III) and -iridium(III) Complexes Showing P,O Coordination: Unprecedented Insertion of tcne and tcnq into a C−H Bond

Strongly electron withdrawing cyanoolefins tetracyanoethylene (tcne) and 7,7,8,8-tetracyano-p-quinodimethane (tcnq) react with [(η⁵-C₅Me₅)MCl(MDMPP-P,O)] (M=Rh, Ir; MDMPP-P,O=PPh₂(2-O-6-MeO-C₆H₃), a P,O chelating phosphane) by insertion into the C−H bond adjacent to the M−O σ bond. The crystal structure of the iridium complex formed upon insertion of tcne is shown.     

A Rhodium–Pentane Sigma‐Alkane Complex: Characterization in the Solid State by Experimental and Computational Techniques

The pentane σ‐complex [Rh{Cy₂P(CH₂CH₂)PCy₂}(η²:η²‐C₅H₁₂)][BAr^F₄] is synthesized by a solid/gas single‐crystal to single‐crystal transformation by addition of H₂ to a precursor 1,3‐pentadiene complex. Characterization by low temperature single‐crystal X‐ray diffraction (150 K) and SSNMR spectroscopy (158 K) reveals coordination through two Rh???H?C interactions in the 2,4‐positions of the linear alkane. Periodic DFT calculations and molecular dynamics on the structure in the solid state provide insight into the experimentally observed Rh???H?C interaction, the extended environment in the crystal lattice and a temperature‐dependent pentane rearrangement implicated by the SSNMR data.     

Readily Accessible Bulky Iron Catalysts exhibiting Site Selectivity in the Oxidation of Steroidal Substrates

Bulky iron complexes are described that catalyze the site‐selective oxidation of alkyl C?H bonds with hydrogen peroxide under mild conditions. Steric bulk at the iron center is introduced by appending trialkylsilyl groups at the meta‐position of the pyridines in tetradentate aminopyridine ligands, and this effect translates into high product yields, an enhanced preferential oxidation of secondary over tertiary C?H bonds, and the ability to perform site‐selective oxidation of methylenic sites in terpenoid and steroidal substrates. Unprecedented site selective oxidation at C6 and C12 methylenic sites in steroidal substrates is shown to be governed by the chirality of the catalysts.     

Tandem CH Activation/Arylation Catalyzed by Low‐Valent Iron Complexes with Bisiminopyridine Ligands

Tandem C?H activation/arylation between unactivated arenes and aryl halides catalyzed by iron complexes that bear redox‐active non‐innocent bisiminopyridine ligands is reported. Similar reactions catalyzed by first‐row transition metals have been shown to involve substrate‐based aryl radicals, whereas our catalytic system likely involves ligand‐centered radicals. Preliminary mechanistic investigations based on spectroscopic and reactivity studies, in conjunction with DFT calculations, led us to propose that the reaction could proceed through an inner‐sphere C?H activation pathway, which is rarely observed in the case of iron complexes. This bielectronic noble‐metal‐like behavior could be sustained by the redox‐active non‐innocent bisiminopyridine ligands.     

Unprecedented Reaction Pathway of Sterically Crowded Calcium Complexes: Sequential C−N Bond Cleavage Reactions Induced by C−H Bond Activations

Five bis(quinolylmethyl)‐(1H ‐indolylmethyl)amine (BQIA) compounds, that is, {(quinol‐8‐yl‐CH₂)₂NCH₂(3‐Br‐1H ‐indol‐2‐yl)} ( L¹H ) and {[(8‐R³‐quinol‐2‐yl)CH₂]₂NCH(R²)[3‐R¹‐1H ‐indol‐2‐yl]} ( L^2–5H ) ( L²H : R¹=Br, R²=H, R³=H; L³H : R¹=Br, R²=H, R³=i Pr; L⁴H : R¹=H, R²=CH₃, R³=i Pr; L⁵H : R¹=H, R²=n Bu, R³=i Pr) were synthesized and used to prepare calcium complexes. The reactions of L^1–5H with silylamido calcium precursors (Ca[N(SiMe₂R)₂]₂(THF)₂, R=Me or H) at room temperature gave heteroleptic products ( L^{1, 2} )CaN(SiMe₃)₂ ( 1 , 2 ), ( L^{3, 4} )CaN(SiHMe₂)₂ ( 3 a , 4 a ) and homoleptic complexes ( L^{3, 5} )₂Ca ( D3 , D5 ). NMR and X‐ray analyses proved that these calcium complexes were stabilized through Ca⋅⋅⋅C−Si, Ca⋅⋅⋅H−Si or Ca⋅⋅⋅H−C agostic interactions. Unexpectedly, calcium complexes (( L^3–5 )CaN(SiMe₃)₂) bearing more sterically encumbered ligands of the same type were extremely unstable and underwent C−N bond cleavage processes as a consequence of intramolecular C−H bond activation, leading to the exclusive formation of (E )‐1,2‐bis(8‐isopropylquinol‐2‐yl)ethane.     

Spin-State Variations of Iron(III) Complexes with Tetracarbene Macrocycles

Starting from their six-coordinate iron(II) precursor complexes [L^8RFe(MeCN)]²⁺, a series of iron(III) complexes of the known macrocyclic tetracarbene ligand L^8H and its new octamethylated derivative L^8Me, both providing four imidazol-2-yliden donors, were synthesized. Several five- and six-coordinate iron(III) complexes with different axial ligands (Cl⁻, OTf⁻, MeCN) were structurally characterized by X-ray diffraction and analyzed in detail with respect to their spin state variations, using a bouquet of spectroscopic methods (NMR, UV/Vis, EPR, and ⁵⁷Fe Mößbauer). Depending on the axial ligands, either low-spin (S=1/2) or intermediate-spin (S=3/2) states were observed, whereas high-spin (S=5/2) states were inaccessible because of the extremely strong in-plane σ-donor character of the macrocyclic tetracarbene ligands. These findings are reminiscent of the spin state patterns of topologically related ferric porphyrin complexes. The ring conformations and dynamics of the macrocyclic tetracarbene ligands in their iron(II), iron(III) and μ-oxo diiron(III) complexes were also studied.