Substrate-Dependent Two-State Reactivity in Iron-Catalyzed Alkene [2+2] Cycloaddition Reactions

Iron-catalyzed alkene [2+2] cycloaddition reactions represent a promising stepwise pathway to effect the kinetically hindered concerted [2+2] cycloaddition. However, the fundamental reactivity paradigm of these reactions remains unclear. Based on high level combined CASPT2/DFT modelings, herein we reveal an unprecedented substrate-dependent two-state reactivity scenario for the key CC coupling in this iron catalysis, in which the representative substrates of mono-olefins only and mono-olefin plus 1,3-diene exhibit different reactivity paradigms. The role of the redox-active ligand is found to generate a ferric oxidation state for the metallacyclic intermediate of CC coupling, thereby rendering a thermodynamically more accessible Fe^III/Fe^I reductive elimination process compared with the otherwise Fe^II/Fe⁰ one. The enhancement of the spin state transition efficiency between the singlet and triplet states is predicted as an alternative way to increase the CC coupling reactivity in the cross [2+2] cycloaddition reactions between mono-olefins and dienes. This work highlights the ab initio multi-reference method in describing very complicated open-shell iron catalysis

What Factors Control the Reactivity of Cobalt–Imido Complexes in C–H Bond Activation via Hydrogen Abstraction?

Metal–imido complexes are critical intermediates in transition metal-catalyzed C–H amination reactions. Discerning the factors that control their reactivity, however, remains largely open for exploration, particularly for the territory of cobalt–imido’s. Herein we describe a systematic computational exploration of this new frontier via the C–H activation mechanisms of typical well-defined cobalt–imido complexes, whose formal oxidation states cover an extremely wide range from Co­(II) to Co­(V). Hydrogen atom abstraction (HAA) is found to be the rate-limiting step in all these systems, with the open-shell electronic states of radical character consistently bearing kinetic advantage over the closed-shell ones. Surprisingly, there is no correlation found between the cobalt oxidation state and the HAA reactivity. To render a more accessible HAA channel, the dichotomous EER/anti-EER electron-shift scenarios for the open-shell electronic structure are dependent on the cobalt oxidation states [Co­(III), different from others], implying a paradigm shift from an EER to an anti-EER scenario in the periodic table from Fe to Co. In contrast to the kinetic factor that determines the HAA reactivity, the reaction outcomes of C–H activation (amination or cyclometalation product) in cobalt–imido complexes are found to be controlled by the thermodynamic stabilities of the products. Our results for the cobalt–imido complexes imply that, in addition to HAA chemistry of metal–oxo’s, the HAA promoted by metal–imido species could also be subject to the radical-facilitated reactivity. From this work, it is predictable that the stabilization of the less reactive closed-shell singlet state relative to other more reactive open-shell states is generally not beneficial to the HAA reactivity of cobalt–imido species

Assessment of DFT Methods for Computing Activation Energies of Mo/W-Mediated Reactions

Using high level ab initio coupled cluster calculations as reference, the performances of 15 commonly used density functionals (DFs) on activation energy calculations for typical Mo/W-mediated reactions have been systematically assessed for the first time in this work. The selected representative Mo/W-mediated reactions cover a wide range from enzymatic reactions to organometallic reactions, which include Mo-catalyzed aldehyde oxidation (aldehyde oxidoreductase), Mo-catalyzed dimethyl sulfoxide (DMSO) reduction (DMSO reductase), W-catalyzed acetylene hydration (acetylene hydratase), Mo/W-mediated olefin metathesis, Mo/W-mediated olefin epoxidation, W-mediated alkyne metathesis, and W-mediated C–H bond activation. Covering both Mo- and W-mediated reactions, four DFs of B2GP-PLYP, M06, B2-PLYP, and B3LYP are uniformly recommended with and without DFT empirical dispersion correction. Among these four DFs, B3LYP is notably improved in performance by DFT empirical dispersion correction. In addition to the absolute value of calculation error, if the trend of DFT results is also a consideration, B2GP-PLYP, B2-PLYP, and M06 keep better performance than other functionals tested and constitute our final recommendation of DFs for both Mo- and W-mediated reactions

Comparative Assessment of DFT Performances in Ru- and Rh-Promoted σ‑Bond Activations

In this work, the performances of 19 density functional theory (DFT) methods are calibrated comparatively on Ru- and Rh-promoted σ-bond (C–H, O–H, and H–H) activations. DFT calibration reference is generated from explicitly correlated coupled cluster CCSD­(T)-F12 calculations, and the 4s4p core–valence correlation effect of the two 4d platinum group transition metals is also included. Generally, the errors of DFT methods for calculating energetics of Ru-/Rh-mediated reactions appear to correlate more with the magnitude of energetics itself than other factors such as metal identity. For activation energy calculations, the best performing functionals for both Ru and Rh systems are MN12SX < CAM-B3LYP < M06-L < MN12L < M06 < ωB97X < B3LYP < LC-ωPBE (in the order of increasing mean unsigned deviations, MUDs, of less than 2 kcal/mol). For reaction energy calculations, best functionals with MUDs less than 2 kcal/mol are PBE0 < CAM-B3LYP ≈ N12SX. The effect of the DFT empirical dispersion correction on the performance of the DFT methods is beneficial for most density functionals tested in this work, reducing their MUDs to different extents. After including empirical dispersion correction, ωB97XD, B3LYP-D3, and CAM-B3LYP-D3 (PBE0-D3, B3LYP-D3, and ωB97XD) are the three best performing DFs for activation energy (reaction energy) calculations, from which B3LYP-D3 and ωB97XD can notably be recommended uniformly for both the reaction energy and reaction barrier calculations. The good performance of B3LYP-D3 in quantitative description of the energetic trends further adds value to B3LYP-D3 and singles this functional out as a reasonable choice in the Ru/Rh-promoted σ-bond activation processes

Calculated Mechanism of Cyanobacterial Aldehyde-Deformylating Oxygenase: Asymmetric Aldehyde Activation by a Symmetric Diiron Cofactor

Cyanobacterial aldehyde-deformylating oxygenase (cADO) is a nonheme diiron enzyme that catalyzes the conversion of aldehyde to alk­(a/e)­ne, an important transformation in biofuel research. In this work, we report a highly desired computational study for probing the mechanism of cADO. By combining our QM/MM results with the available ⁵⁷Fe Mössbauer spectroscopic data, the gained detailed structural information suggests construction of asymmetry from the symmetric diiron cofactor in an aldehyde substrate and O₂ activation. His₁₆₀, one of the two iron-coordinate histidine residues in cADO, plays a pivotal role in this asymmetric aldehyde activation process by unprecedented reversible dissociation from the diiron cofactor, a behavior unknown in any other nonheme dinuclear or mononuclear enzymes. The revealed intrinsically asymmetric interactions of the substrate/O₂ with the symmetric cofactor in cADO are inspirational for exploring diiron subsite resolution in other nonheme diiron enzymes

An Iron(II) Ylide Complex as a Masked Open-Shell Iron Alkylidene Species in Its Alkylidene-Transfer Reactions with Alkenes

Transition-metal alkylidenes are important reactive organometallic intermediates, and our current knowledge on them has been mainly restricted to those with closed-shell electronic configurations. In this study, we present an exploration on open-shell iron alkylidenes with a weak-field tripodal amido-phosphine-amido ligand. We found that a high-spin (amido-phosphine-amido)­iron­(II) complex can react with (<i>p</i>-tolyl)₂CN₂ to afford a high-spin (amido-ylide-amido)­iron­(II) complex, <b>2</b>, which could transfer its alkylidene moiety to a variety of alkenes, either the electron-rich or electron-deficient ones, to form cyclopropane derivatives. The reaction of <b>2</b> with <i>cis</i>-β-deuterio-styrene gave deuterated cyclopropane derivatives with partial loss of the stereochemical integrity with respect to the <i>cis</i>-styrene. Kinetic study on the cyclopropanation reaction of <b>2</b> with 4-fluoro-styrene disclosed the activation parameters of Δ<i>H</i>^⧧ = 23 ± 1 kcal/mol and Δ<i>S</i>^⧧ = −20 ± 3 cal/mol/K, which are comparable to those of the cyclopropanation reactions involving transition-metal alkylidenes. However, the cyclopropanation of <i>para</i>-substituted styrenes by <b>2</b> shows a nonlinear Hammett plot of log­(<i>k</i>_X/<i>k</i>_H) vs σ_p. By introduction of a radical parameter, a linear plot of log­(<i>k</i>_X/<i>k</i>_H) vs 0.59σ_p + 0.55σ_c^• was obtained, which suggests the “nucleophilic” radical nature of the transition state of the cyclopropanation step. In corroboration with the experimental observations, density functional theory calculation on the reaction of <b>2</b> with styrene suggests the involvement of an open-shell (amido-phosphine-amido)­iron alkylidene intermediate that is higher in energy than its (amido-ylide-amido)­iron­(II) precursor and an “outer-sphere” radical-type mechanism for the cyclopropanation step. The negative charge distribution on the alkylidene carbon atoms of the open-shell states (<i>S</i> = 2 and 1) explains the high activity of the cyclopropanation reaction toward electron-deficient alkenes. The study demonstrates the unique activity of open-shell iron alkylidene species beyond its closed-shell analogues, thus pointing out their potential synthetic usage in catalysis

An Iron(II) Ylide Complex as a Masked Open-Shell Iron Alkylidene Species in Its Alkylidene-Transfer Reactions with Alkenes

Transition-metal alkylidenes are important reactive organometallic intermediates, and our current knowledge on them has been mainly restricted to those with closed-shell electronic configurations. In this study, we present an exploration on open-shell iron alkylidenes with a weak-field tripodal amido-phosphine-amido ligand. We found that a high-spin (amido-phosphine-amido)­iron­(II) complex can react with (<i>p</i>-tolyl)₂CN₂ to afford a high-spin (amido-ylide-amido)­iron­(II) complex, <b>2</b>, which could transfer its alkylidene moiety to a variety of alkenes, either the electron-rich or electron-deficient ones, to form cyclopropane derivatives. The reaction of <b>2</b> with <i>cis</i>-β-deuterio-styrene gave deuterated cyclopropane derivatives with partial loss of the stereochemical integrity with respect to the <i>cis</i>-styrene. Kinetic study on the cyclopropanation reaction of <b>2</b> with 4-fluoro-styrene disclosed the activation parameters of Δ<i>H</i>^⧧ = 23 ± 1 kcal/mol and Δ<i>S</i>^⧧ = −20 ± 3 cal/mol/K, which are comparable to those of the cyclopropanation reactions involving transition-metal alkylidenes. However, the cyclopropanation of <i>para</i>-substituted styrenes by <b>2</b> shows a nonlinear Hammett plot of log­(<i>k</i>_X/<i>k</i>_H) vs σ_p. By introduction of a radical parameter, a linear plot of log­(<i>k</i>_X/<i>k</i>_H) vs 0.59σ_p + 0.55σ_c^• was obtained, which suggests the “nucleophilic” radical nature of the transition state of the cyclopropanation step. In corroboration with the experimental observations, density functional theory calculation on the reaction of <b>2</b> with styrene suggests the involvement of an open-shell (amido-phosphine-amido)­iron alkylidene intermediate that is higher in energy than its (amido-ylide-amido)­iron­(II) precursor and an “outer-sphere” radical-type mechanism for the cyclopropanation step. The negative charge distribution on the alkylidene carbon atoms of the open-shell states (<i>S</i> = 2 and 1) explains the high activity of the cyclopropanation reaction toward electron-deficient alkenes. The study demonstrates the unique activity of open-shell iron alkylidene species beyond its closed-shell analogues, thus pointing out their potential synthetic usage in catalysis

Three-Coordinate Iron(IV) Bisimido Complexes with Aminocarbene Ligation: Synthesis, Structure, and Reactivity

High-valent iron imido species are implicated as reactive intermediates in many iron-catalyzed transformations. However, isolable complexes of this type are rare, and their reactivity is poorly understood. Herein, we report the synthesis, characterization, and reactivity studies on novel three-coordinate iron­(IV) bisimido complexes with amino­carbene ligation. Using our recently reported synthetic method for [LFe­(NDipp)₂] (L = IMes, <b>1</b>; Me₂-cAAC, <b>2</b>), four new iron­(IV) imido complexes, [(IPr)­Fe­(NDipp)₂] (<b>3</b>) and [(Me₂-cAAC)­Fe­(NR)₂] (R = Mes, <b>4</b>; Ad, <b>5</b>; CMe₂CH₂Ph, <b>6</b>), were prepared from the reactions of three-coordinate iron(0) compounds with organic azides. Characterization data acquired from ¹H and ¹³C NMR spectroscopy, ⁵⁷Fe Mössbauer spectroscopy, and X-ray diffraction studies suggest a low-spin singlet ground state for these iron­(IV) complexes and the multiple-bond character of their Fe–N bonds. A reactivity study taking the reactions of <b>1</b> as representative revealed an intra­molecular alkane dehydrogenation of <b>1</b> to produce the iron­(II) complex [(IMes)­Fe­(NHDipp)­(NHC₆H₃-2-Pr^<i>i</i>-6-CMeCH₂)] (<b>7</b>), a Si–H bond activation reaction of <b>1</b> with PhSiH₃ to produce the iron­(II) complex [(IMes)­Fe­(NHDipp)­(NDipp­SiPhH₂)] (<b>8</b>), and a [2+2]-addition reaction of <b>1</b> with PhNCNPh and <i>p</i>-Pr^<i>i</i>C₆H₄NCO to form the corresponding open-shell formal iron­(IV) mono­imido complexes [(IMes)­Fe­(NDipp)­(N­(Dipp)­C­(NPh)­(NPh))] (<b>9</b>) and [(IMes)­Fe­(NDipp)­(N­(Dipp)­C­(O)­N­(<i>p</i>-Pr^<i>i</i>C₆H₄))] (<b>10</b>), as well as [NDipp]-group-transfer reactions with CO and Bu^<i>t</i>NC. Density functional theory calculations suggested that the alkane chain dehydrogenation reaction starts with a hydrogen atom abstraction mechanism, whereas the Si–H activation reaction proceeds in a [2π+2σ]-addition manner. Both reactions have the pathways at the triplet potential energy surfaces being energetically preferred, and have formal iron­(IV) hydride and iron­(IV) silyl species as intermediates, respectively. The low-coordinate nature and low d-electron count (d⁴) of iron­(IV) imido complexes are thought to be the key features endowing their unique reactivity

Two-State Reactivity in Low-Valent Iron-Mediated C–H Activation and the Implications for Other First-Row Transition Metals

C–H bond activation/functionalization promoted by low-valent iron complexes has recently emerged as a promising approach for the utilization of earth-abundant first-row transition metals to carry out this difficult transformation. Herein we use extensive density functional theory and high-level ab initio coupled cluster calculations to shed light on the mechanism of these intriguing reactions. <i>Our key mechanistic discovery for C–H arylation reactions reveals a two-state reactivity (TSR) scenario in which the low-spin Fe­(II) singlet state, which is initially an excited state, crosses over the high-spin ground state and promotes C–H bond cleavage</i>. Subsequently, aryl transmetalation occurs, followed by oxidation of Fe­(II) to Fe­(III) in a single-electron transfer (SET) step in which dichloroalkane serves as an oxidant, thus promoting the final C–C coupling and finalizing the C–H functionalization. Regeneration of the Fe­(II) catalyst for the next round of C–H activation involves SET oxidation of the Fe­(I) species generated after the C–C bond coupling. <i>The ligand sphere of iron is found to play a crucial role in the TSR mechanism by stabilization of the reactive low-spin state that mediates the C–H activation</i>. This is the first time that the successful TSR concept conceived for high-valent iron chemistry is shown to successfully rationalize the reactivity for a reaction promoted by low-valent iron complexes. A comparative study involving other divalent middle and late first-row transition metals implicates iron as the optimum metal in this TSR mechanism for C–H activation. It is predicted that stabilization of low-spin Mn­(II) using an appropriate ligand sphere should produce another promising candidate for efficient C–H bond activation. This new TSR scenario therefore emerges as a new strategy for using low-valent first-row transition metals for C–H activation reactions

Factors That Control the Reactivity of Cobalt(III)–Nitrosyl Complexes in Nitric Oxide Transfer and Dioxygenation Reactions: A Combined Experimental and Theoretical Investigation

Metal–nitrosyl complexes are key intermediates involved in many biological and physiological processes of nitric oxide (NO) activation by metalloproteins. In this study, we report the reactivities of mononuclear cobalt­(III)–nitrosyl complexes bearing <i>N</i>-tetramethylated cyclam (TMC) ligands, [(14-TMC)­Co^III(NO)]²⁺ and [(12-TMC)­Co^III(NO)]²⁺, in NO-transfer and dioxygenation reactions. The Co­(III)–nitrosyl complex bearing 14-TMC ligand, [(14-TMC)­Co^III(NO)]²⁺, transfers the bound nitrosyl ligand to [(12-TMC)­Co^II]²⁺ via a dissociative pathway, {[(14-TMC)­Co^III(NO)]²⁺ → {(14-TMC)­Co···NO}²⁺}, thus affording [(12-TMC)­Co^III(NO)]²⁺ and [(14-TMC)­Co^II]²⁺ as products. The dissociation of NO from the [(14-TMC)­Co^III(NO)]²⁺ complex prior to NO-transfer is supported experimentally and theoretically. In contrast, the reverse reaction, which is the NO-transfer from [(12-TMC)­Co^III(NO)]²⁺ to [(14-TMC)­Co^II]²⁺, does not occur. In addition to the NO-transfer reaction, dioxygenation of [(14-TMC)­Co^III(NO)]²⁺ by O₂ produces [(14-TMC)­Co^II(NO₃)]⁺, which possesses an O,O-chelated nitrato ligand and where, based on an experiment using ¹⁸O-labeled O₂, two of the three O-atoms in the [(14-TMC)­Co^II(NO₃)]⁺ product derive from O₂. The dioxygenation reaction is proposed to occur via a dissociative pathway, as proposed in the NO-transfer reaction, and via the formation of a Co­(II)–peroxynitrite intermediate, based on the observation of phenol ring nitration. In contrast, [(12-TMC)­Co^III(NO)]²⁺ does not react with O₂. Thus, the present results demonstrate unambiguously that the NO-transfer/dioxygenation reactivity of the cobalt­(III)–nitrosyl complexes bearing TMC ligands is significantly influenced by the ring size of the TMC ligands and/or the spin state of the cobalt ion