NHC Effects on Reduction Dynamics in Iron-Catalyzed Organic Transformations*.

The high abundance, low toxicity and rich redox chemistry of iron has resulted in a surge of iron-catalyzed organic transformations over the last two decades. Within this area, N-heterocyclic carbene (NHC) ligands have been widely utilized to achieve high yields across reactions including cross-coupling and C-H alkylation, amongst others. Central to the development of iron-NHC catalytic methods is the understanding of iron speciation and the propensity of these species to undergo reduction events, as low-valent iron species can be advantageous or undesirable from one system to the next. This study highlights the importance of the identity of the NHC on iron speciation upon reaction with EtMgBr, where reactions with SIMes and IMes NHCs were shown to undergo ß-hydride elimination more readily than those with SIPr and IPr NHCs. This insight is vital to developing new iron-NHC catalyzed transformations as understanding how to control this reduction by simply changing the NHC is central to improving the reactivity in iron-NHC catalysis.

Synthesis and Characterization of a Sterically Encumbered Homoleptic Tetraalkyliron(III) Ferrate Complex.

Homoleptic iron-alkyl complexes have been implicated as key intermediates in iron-catalyzed cross-coupling with simple iron salts. Tetraalkyliron(III) ferrate species have been shown to be accessible with either methyl or benzyl ligands, where the former complex is S = 3/2 and distorted square planar while the latter is a S = 5/2 distorted tetrahedral species. In the current study, a new tetraalkyliron(III) complex is synthesized containing modified methylene substituents that incorporate large trimethylsilyl (TMS) groups to further probe steric and electronic ligand effects in tetraalkyliron(III) complexes by increasing the electron-donating ability of the ligand while retaining steric bulk. Detailed structural and DFT studies provide insight into electronic structure and bonding of the four-coordinate trimethylsilylmethyl iron(III) complex compared to the previously reported analogs containing methyl and benzyl ligands.

The Effect of ß-Hydrogen Atoms on Iron Speciation in Cross-Couplings with Simple Iron Salts and Alkyl Grignard Reagents.

The effects of ß-hydrogen-containing alkyl Grignard reagents in simple ferric salt cross-couplings have been elucidated. The reaction of FeCl3 with EtMgBr in THF leads to the formation of the cluster species [Fe8 Et12 ]2- , a rare example of a structurally characterized metal complex with bridging ethyl ligands. Analogous reactions in the presence of NMP, a key additive for effective cross-coupling with simple ferric salts and ß-hydrogen-containing alkyl nucleophiles, result in the formation of [FeEt3 ]- . Reactivity studies demonstrate the effectiveness of [FeEt3 ]- in rapidly and selectively forming the cross-coupled product upon reaction with electrophiles. The identification of iron-ate species with EtMgBr analogous to those previously observed with MeMgBr is a critical insight, indicating that analogous iron species can be operative in catalysis for these two classes of alkyl nucleophiles.

Mechanistic study of styrene aziridination by iron(iv) nitrides.

A combined experimental and computational investigation was undertaken to investigate the mechanism of aziridination of styrene by the tris(carbene)borate iron(iv) nitride complex, PhB( t BuIm)3Fe[triple bond, length as m-dash]N. While mechanistic investigations suggest that aziridination occurs via a reversible, stepwise pathway, it was not possible to confirm the mechanism using only experimental techniques. Density functional theory calculations support a stepwise radical addition mechanism, but suggest that a low-lying triplet (S = 1) state provides the lowest energy path for C-N bond formation (24.6 kcal mol-1) and not the singlet ground (S = 0) state. A second spin flip may take place in order to facilitate ring closure and the formation of the quintet (S = 2) aziridino product. A Hammett analysis shows that electron-withdrawing groups increase the rate of reaction σ p (ρ = 1.2 ± 0.2). This finding is supported by the computational results, which show that the rate-determining step drops from 24.6 kcal mol-1 to 18.3 kcal mol-1 when (p-NO2C6H4)CH[double bond, length as m-dash]CH2 is used and slightly increases to 25.5 kcal mol-1 using (p-NMe2C6H4)CH[double bond, length as m-dash]CH2 as the substrate.

Combined Effects of Backbone and N-Substituents on Structure, Bonding, and Reactivity of Alkylated Iron(II)-NHCs.

Iron and N-heterocyclic carbenes (NHCs) have proven to be a successful pair in catalysis, with reactivity and selectivity being highly dependent on the nature of the NHC ligand backbone saturation and N-substituents. Four (NHC)Fe(1,3-dioxan-2-ylethyl)2 complexes have been isolated and spectroscopically characterized to correlate their reactivity to steric effects of the NHC from both the backbone saturation and N-substituents. Only in the extreme case of SIPr where NHC backbone and N-substituent steric effects are the largest is there a major structural perturbation observed crystallographically. The addition of only two hydrogen atoms is sufficient for a drastic change in product selectivity in the coupling of 1-iodo-3-phenylpropane with (2-(1,3-dioxan-2-yl)ethyl)magnesium bromide due to resulting structural perturbations to the precatalyst. Mössbauer spectroscopy and magnetic circular dichroism enabled the correlation of covalency and steric bulk in the SIPr case to its poor selectivity in alkyl-alkyl cross-coupling with iron. Density functional theory calculations provided insight into the electronic structure and molecular orbital effects of ligation changes to the iron center. Finally, charge donation analysis and Mayer bond order calculations further confirmed the stronger Fe-ligand bonding in the SIPr complex. Overall, these studies highlight the importance of considering both N-substituent and backbone steric contributions to structure, bonding, and reactivity in iron-NHCs.

Multinuclear iron-phenyl species in reactions of simple iron salts with PhMgBr: identification of Fe4(µ-Ph)6(THF)4 as a key reactive species for cross-coupling catalysis.

The first direct syntheses, structural characterizations, and reactivity studies of iron-phenyl species formed upon reaction of Fe(acac)3 and PhMgBr in THF are presented. Reaction of Fe(acac)3 with 4 equiv. PhMgBr in THF leads to the formation of [FePh2(µ-Ph)]2 2- at -80 °C, which can be stabilized through the addition of N-methylpyrrolidone. Alternatively, at -30 °C this reaction leads to the formation of the tetranuclear iron-phenyl cluster, Fe4(µ-Ph)6(THF)4. Further synthetic studies demonstrate that analogous tetranuclear iron clusters can be formed with both 4-F-PhMgBr and p-tolylMgBr, illustrating the generality of this structural motif for reactions of simple ferric salts and aryl Grignard reagents in THF. Additional studies isolate and define key iron species involved in the synthetic pathway leading to the formation of the tetranuclear iron-aryl species. While reaction studies demonstrate that [FePh2(µ-Ph)]2 2- is unreactive towards electrophile, Fe4(µ-Ph)6(THF)4 is found to rapidly react with bromocyclohexane to selectively form phenylcyclohexane. Based on this reactivity, a new catalytic reaction protocol has been developed that enables efficient cross-couplings using Fe4(µ-Ph)6(THF)4, circumventing the current need for additives such as TMEDA or supporting ligands to achieve effective cross-coupling of PhMgBr and a secondary alkyl halide.

The N-Methylpyrrolidone (NMP) Effect in Iron-Catalyzed Cross-Coupling with Simple Ferric Salts and MeMgBr.

The use of N-methylpyrrolidone (NMP) as a co-solvent in ferric salt catalyzed cross-coupling reactions is crucial for achieving the highly selective, preparative scale formation of cross-coupled product in reactions utilizing alkyl Grignard reagents. Despite the critical importance of NMP, the molecular level effect of NMP on in situ formed and reactive iron species that enables effective catalysis remains undefined. Herein, we report the isolation and characterization of a novel trimethyliron(II) ferrate species, [Mg(NMP)6 ][FeMe3 ]2 (1), which forms as the major iron species in situ in reactions of Fe(acac)3 and MeMgBr under catalytically relevant conditions where NMP is employed as a co-solvent. Importantly, combined GC analysis and 57 Fe Mössbauer spectroscopic studies identified 1 as a highly reactive iron species for the selective formation generating cross-coupled product. These studies demonstrate that NMP does not directly interact with iron as a ligand in catalysis but, alternatively, interacts with the magnesium cations to preferentially stabilize the formation of 1 over [Fe8 Me12 ]- cluster generation, which occurs in the absence of NMP.

Arrested α-hydride migration activates a phosphido ligand for C-H insertion.

Bulky tris(carbene)borate ligands provide access to high spin iron(ii) phosphido complexes. The complex PhB(MesIm)3FeP(H)Ph is thermally unstable, and [PPh] group insertion into a C-H bond of the supporting ligand is observed. An arrested α-hydride migration mechanism suggests increased nucleophilicity of the phosphorus atom facilitates [PPh] group transfer reactivity.

Styrene Aziridination by Iron(IV) Nitrides.

Thermolysis of the iron(IV) nitride complex [PhB(tBuIm)3Fe≡N] with styrene leads to formation of the high-spin iron(II) aziridino complex [PhB(tBuIm)3Fe-N(CH2CHPh)]. Similar aziridination occurs with both electron-rich and electron-poor styrenes, while bulky styrenes hinder the reaction. The aziridino complex [PhB(tBuIm)3Fe-N(CH2CHPh)] acts as a nitride synthon, reacting with electron-poor styrenes to generate their corresponding aziridino complexes, that is, aziridine cross-metathesis. Reaction of [PhB(tBuIm)3Fe-N(CH2CHPh)] with Me3SiCl releases the N-functionalized aziridine Me3SiN(CH2CHPh) while simultaneously generating [PhB(tBuIm)3FeCl]. This closes a synthetic cycle for styrene azirdination by a nitride complex. While the less hindered iron(IV) nitride complex [PhB(MesIm)3Fe≡N] reacts with styrenes below room temperature, only bulky styrenes lead to tractable aziridino products.

Reaction of an iron(IV) nitrido complex with cyclohexadienes: cycloaddition and hydrogen-atom abstraction.

The iron(IV) nitrido complex PhB(MesIm)3Fe≡N reacts with 1,3-cyclohexadiene to yield the iron(II) pyrrolide complex PhB(MesIm)3Fe(η(5)-C4H4N) in high yield. The mechanism of product formation is proposed to involve sequential [4 + 1] cycloaddition and retro Diels-Alder reactions. Surprisingly, reaction with 1,4-cyclohexadiene yields the same iron-containing product, albeit in substantially lower yield. The proposed reaction mechanism, supported by electronic structure calculations, involves hydrogen-atom abstraction from 1,4-cyclohexadiene to provide the cyclohexadienyl radical. This radical is an intermediate in substrate isomerization to 1,3-cyclohexadiene, leading to formation of the pyrrolide product.

Ligand modification transforms a catalase mimic into a water oxidation catalyst.

The catalytic reactivity of the high-spin Mn(II) pyridinophane complexes [(Py2NR2)Mn(H2O)2](2+) (R=H, Me, tBu) toward O2 formation is reported. With small macrocycle N-substituents (R=H, Me), the complexes catalytically disproportionate H2O2 in aqueous solution; with a bulky substituent (R=tBu), this catalytic reaction is shut down, but the complex becomes active for aqueous electrocatalytic H2O oxidation. Control experiments are in support of a homogeneous molecular catalyst and preliminary mechanistic studies suggest that the catalyst is mononuclear. This ligand-controlled switch in catalytic reactivity has implications for the design of new manganese-based water oxidation catalysts.

Tris(carbene)borate ligands featuring imidazole-2-ylidene, benzimidazol-2-ylidene, and 1,3,4-triazol-2-ylidene donors. Evaluation of donor properties in four-coordinate {NiNO}10 complexes.

The synthesis and characterization of new tris(carbene)borate ligand precursors containing substituted benzimidazol-2-ylidene and 1,3,4-triazol-2-ylidene donor groups, as well as a new tris(imidazol-2-ylidene)borate ligand precursor are reported. The relative donor strengths of the tris(carbene)borate ligands have been evaluated by the position of ν(NO) in four-coordinate {NiNO}(10) complexes, and follow the order: imidazol-2-ylidene > benzimidazol-2-ylidene > 1,3,4-triazol-2-ylidene. There is a large variation in ν(NO), suggesting these ligands to have a wide range of donor strengths while maintaining a consistent ligand topology. All ligands are stronger donors than Tp* and Cp*.