Caught in the Act of Substitution: Interadsorbate Effects on an Atomically Precise Fe/Co/Se Nanocluster.

Directing groups guide substitution patterns in organic synthetic schemes, but little is known about pathways to control reactivity patterns, such as regioselectivity, in complex inorganic systems such as bioinorganic cofactors or extended surfaces. Interadsorbate effects are known to encode surface reactivity patterns in inorganic materials, modulating the location and binding strength of ligands. However, owing to limited experimental resolution into complex inorganic structures, there is little opportunity to resolve these effects on the atomic scale. Here, we utilize an atomically precise Fe/Co/Se nanocluster platform, [Fe3(L)2Co6Se8L'6]+ ([1(L)2]+; L = CN t Bu, THF; L' = Ph2PN(-)Tol), in which allosteric interadsorbate effects give rise to pronounced site-differentiation. Using a combination of spectroscopic techniques and single-crystal X-ray diffractometry, we discover that coordination of THF at the ligand-free Fe site in [1(CN t Bu)2]+ sets off a domino effect wherein allosteric through-cluster interactions promote the regioselective dissociation of CN t Bu at a neighboring Fe site. Computational analysis reveals that this active site correlation is a result of delocalized Fe···Se···Co···Se covalent interactions that intertwine edge sites on the same cluster face. This study provides an unprecedented atom-scale glimpse into how interfacial metal-support interactions mediate a collective and regiospecific path for substrate exchange across multiple active sites.

Mechanistic investigations of the Fe(ii) mediated synthesis of squaraines.

The scission and homologation of CO is a fundamental process in the Fischer-Tropsch reaction. However, given the heterogeneous nature of the catalyst and forcing reaction conditions, it is difficult to determine the intermediates of this reaction. Here we report detailed mechanistic insight into the scission/homologation of CO by two-coordinate iron terphenyl complexes. Mechanistic investigations, conducted using in situ monitoring and reaction sampling techniques (IR, NMR, EPR and Mössbauer spectroscopy) and structural characterisation of isolable species, identify a number of proposed intermediates. Crystallographic and IR spectroscopic data reveal a series of migratory insertion reactions from 1Mes to 4Mes. Further studies past the formation of 4Mes suggest that ketene complexes are formed en route to squaraine 2Mes and iron carboxylate 3Mes, with a number of ketene containing structures being isolated, in addition to the formation of unbound, protonated ketene (8). The synthetic and mechanistic studies are supported by DFT calculations.

Ni(2,2':6',2''-terpyridine)2: a high-spin octahedral formal Ni(0) complex.

We have synthesised and characterised the complex Ni(tpy)2 (tpy = 2,2':6',2''-terpyridine). This formally Ni(0) complex is paramagnetic both in the solid state and in solution (S = 2). The crystal structure shows an octahedral geometry, with molecules arranged in independent dimers involving π-stacking between pairs of complexes. Magnetic measurementes and DFT calculations suggest the existence of temperature-dependent intermolecular antiferromagnetic coupling in the solid state.

Iron-catalyzed stereoselective C-H alkylation for simultaneous construction of C-N axial and C-central chirality.

The assembly of chiral molecules with multiple stereogenic elements is challenging, and, despite of indisputable advances, largely limited to toxic, cost-intensive and precious metal catalysts. In sharp contrast, we herein disclose a versatile C-H alkylation using a non-toxic, low-cost iron catalyst for the synthesis of substituted indoles with two chiral elements. The key for achieving excellent diastereo- and enantioselectivity was substitution on a chiral N-heterocyclic carbene ligand providing steric hindrance and extra represented by noncovalent interaction for the concomitant generation of C-N axial chirality and C-stereogenic center. Experimental and computational mechanistic studies have unraveled the origin of the catalytic efficacy and stereoselectivity.

Divergent Fe-Mediated C-H Activation Paths Driven by Alkali Cations.

The association of the ferrous complex FeIICl2(dmpe)2 (1) with alkali bases M(hmds) (M = Li, Na, K) proves to be an efficient platform for the activation of Ar-H bonds. Two mechanisms can be observed, leading to either Ar-FeII species by deprotonative ferration or hydrido species Ar-FeII-H by oxidative addition of transient Fe0(dmpe)2 generated by reduction of 1. Importantly, the nature of the alkali cation in M(hmds) has a strong influence on the preferred path. Starting from the same iron precursor, diverse catalytic applications can be explored by a simple modulation of the MI cation. Possible strategies enabling cross-coupling using arenes as pro-nucleophiles, reductive dehydrocoupling, or deuteration of B-H bonds are discussed.

Mechanistic manifold in a hemoprotein-catalyzed cyclopropanation reaction with diazoketone.

Hemoproteins have recently emerged as promising biocatalysts for new-to-nature carbene transfer reactions. However, mechanistic understanding of the interplay between productive and unproductive pathways in these processes is limited. Using spectroscopic, structural, and computational methods, we investigate the mechanism of a myoglobin-catalyzed cyclopropanation reaction with diazoketones. These studies shed light on the nature and kinetics of key catalytic steps in this reaction, including the formation of an early heme-bound diazo complex intermediate, the rate-determining nature of carbene formation, and the cyclopropanation mechanism. Our analyses further reveal the existence of a complex mechanistic manifold for this reaction that includes a competing pathway resulting in the formation of an N-bound carbene adduct of the heme cofactor, which was isolated and characterized by X-ray crystallography, UV-Vis, and Mössbauer spectroscopy. This species can regenerate the active biocatalyst, constituting a non-productive, yet non-destructive detour from the main catalytic cycle. These findings offer a valuable framework for both mechanistic analysis and design of hemoprotein-catalyzed carbene transfer reactions.

Palladium and Iron Cocatalyzed Aerobic Alkene Aminoboration.

Aminoboration of simple alkenes with nitrogen nucleophiles remains an unsolved problem in synthetic chemistry; this transformation can be catalyzed by palladium via aminopalladation followed by transmetalation with a diboron reagent. However, this catalytic process faces inherent challenges with instability of the alkylpalladium(II) intermediate toward ß-hydride elimination. Herein, we report a palladium/iron cocatalyzed aminoboration, which enables this transformation. We demonstrate these conditions on a variety of alkenes and norbornenes with an array of common nitrogen nucleophiles. In the developed strategy, the iron cocatalyst is crucial to achieving the desired reactivity by serving as a halophilic Lewis acid to release the transmetalation-active cationic alkylpalladium intermediate. Furthermore, it serves as a redox shuttle in the regeneration of the Pd(II) catalyst by reactivation of nanoparticulate palladium.

Mechanistic Studies of Iron-PyBOX-Catalyzed Olefin Amino-Oxygenation with Functionalized Hydroxylamines.

Iron-catalyzed amino-oxygenation of olefins often uses discrete ligands to increase reactivity and broaden substrate scope. This work is focused on examining ligand effects on reactivity and in situ iron speciation in a system which utilizes a bisoxazoline ligand. Freeze-trapped 57Fe Mössbauer and EPR spectroscopies as well as SC-XRD experiments were utilized to isolate and identify the species formed during the catalytic reaction of amino-oxygenation of olefins with functionalized hydroxylamines, as well as in the precatalytic mixture of iron salt and ligand. Experiments revealed significant influence of ligand and solvent on the speciation in the precatalytic mixture which led to the formation of different species which had significant influence on the reactivity. In situ experiments showed no evidence for the formation of an Fe(IV)-nitrene intermediate, and the isolation of a reactive intermediate was unsuccessful, suggesting that the use of the PyBOX ligand led to the formation of more reactive intermediates than observed in the previously studied system, preventing direct detection of intermediate species. However, isolation of the seven coordinate Fe(III) species with three carboxylate units of the hydroxylamine and spin-trap EPR experiments suggest formation of a species with unpaired electron density on the hydroxylamine nitrogen, which is in accordance with formation of a potential iron iminyl radical species, as recently proposed in literature. An observed increase in yield when substrates devoid of C-H bonds as well as isolation of a ring-closed dead-end species with substrates containing these bonds suggests the identity of the functionalized hydroxylamine can dictate the reactivity observed in these reactions.

Insight into Radical Initiation, Solvent Effects, and Biphenyl Production in Iron-Bisphosphine Cross-Couplings.

Iron-bisphosphines have attracted broad interest as highly effective and versatile catalytic systems for two- and three-component cross-coupling strategies. While recent mechanistic studies have defined the role of organoiron(II)-bisphosphine species as key intermediates for selective cross-coupled product formation in these systems, mechanistic features that are essential for catalytic performance remain undefined. Specifically, key questions include the following: what is the generality of iron(II) intermediates for radical initiation in cross-couplings? What factors control reactivity toward homocoupled biaryl side-products in these systems? Finally, what are the solvent effects in these reactions that enable high catalytic performance? Herein, we address these key questions by examining the mechanism of enantioselective coupling between α-chloro- and α-bromoalkanoates and aryl Grignard reagents catalyzed by chiral bisphosphine-iron complexes. By employing freeze-trapped 57Fe Mössbauer and EPR studies combined with inorganic synthesis, X-ray crystallography, reactivity studies, and quantum mechanical calculations, we define the key in situ iron speciation as well as their catalytic roles. In contrast to iron-SciOPP aryl-alkyl couplings, where monophenylated species were found to be the predominant reactive intermediate or prior proposals of reduced iron species to initiate catalysis, the enantioselective system utilizes an iron(II)-(R,R)-BenzP* bisphenylated intermediate to initiate the catalytic cycle. A profound consequence of this radical initiation process is that halogen abstraction and subsequent reductive elimination result in considerable amounts of biphenyl side products, limiting the efficiency of this method. Overall, this study offers key insights into the broader role of iron(II)-bisphosphine species for radical initiation, factors contributing to biphenyl side product generation, and protocol effects (solvent, Grignard reagent addition rate) that are critical to minimizing biphenyl generation to obtain more selective cross-coupling methods.

The molecular-level effect of alkoxide additives in iron-catalyzed Kumada cross-coupling with simple ferric salts.

The molecular-level role of alkoxide salts, used as alternative additive to N-methylpyrrolidone in iron-catalyzed alkyl-alkenyl/aryl cross-coupling reactions, is investigated. Detailed spectroscopic studies reveal that alkoxides promote the formation of homoleptic organoferrates such as [FeMe3]-, providing an alternative to toxic NMP to access these reactive intermediates.

Homoleptic Uranium-Bis(acyl)phosphide Complexes.

The first uranium bis(acyl)phosphide (BAP) complexes were synthesized from the reaction between sodium bis(mesitoyl)phosphide (Na(mesBAP)) or sodium bis(2,4,6-triisopropylbenzoyl)phosphide (Na(trippBAP)) and UI3(1,4-dioxane)1.5. Thermally stable, homoleptic BAP complexes were characterized by single-crystal X-ray diffraction and electron paramagnetic resonance (EPR) spectroscopy, when appropriate, for the elucidation of the electronic structure and bonding of these complexes. EPR spectroscopy revealed that the BAP ligands on the uranium center retain a significant amount of electron density. The EPR spectrum of the trivalent U(trippBAP)3 has a rhombic signal near g = 2 (g1 = 2.03; g2 = 2.01; and g3 = 1.98) that is consistent with the EPR-observed unpaired electron being located in a molecular orbital that appears ligand-derived. However, upon warming the complex to room temperature, no resonance was observed, indicating the presence of uranium character.

Anion-induced disproportionation of Th(III) complexes to form Th(II) and Th(IV) products.

A new synthesis of Th(II) complexes has been identified involving addition of simple MX salts (M = Li, Na, K; X = H, Cl, Me, N3) to Cp''3ThIII [Cp'' = [C5H3(SiMe3)2] in the presence of 18-crown-6 or 2.2.2-cryptand, forming [M(chelate)][Cp''3ThII] and Cp''3ThIVX. Cptet3ThIII (Cptet = C5Me4H) reacts with KH to form Cptet3ThIVH and the C-H bond activation product, [K(crypt)]{[Cptet2ThIVH[η1:η5-C5Me3H(CH2)]}.

Side-on coordination of diphosphorus to a mononuclear iron center.

The diagonal relationship in the periodic table between phosphorus and carbon has set an expectation that the triple-bonded diatomic diphosphorus molecule (P2) should more closely mimic the attributes of acetylene (HC≡CH) rather than its group 15 congener dinitrogen (N2). Although acetylene has well-documented coordination chemistry with mononuclear transition metals, coordination complexes that feature P2 bound to a single metal center have remained elusive. We report the isolation and x-ray crystallographic characterization of a mononuclear iron complex featuring P2 coordination in a side-on, η2-binding mode. An analogous η2-bound bis-timethylsilylacetylene iron complex is reported for comparison. Nuclear magnetic resonance, infrared, and Mössbauer spectroscopic analysis-in conjunction with density functional theory calculations-demonstrate that η2-P2 and η2-acetylene ligands exert a similar electronic demand on mononuclear iron centers but exhibit different reactivity profiles.

A TMEDA-Iron Adduct Reaction Manifold in Iron-Catalyzed C(sp2 )-C(sp3 ) Cross-Coupling Reactions.

Herein, we expand the current molecular-level understanding of one of the most important and effective additives in iron-catalyzed cross-coupling reactions, N,N,N',N'-tetramethylethylenediamine (TMEDA). Focusing on relevant phenyl and ethyl Grignard reagents and slow nucleophile addition protocols commonly used in effective catalytic systems, TMEDA-iron(II)-aryl intermediates are identified via in situ spectroscopy, X-ray crystallography, and detailed reaction studies to be a part of an iron(II)/(III)/(I) reaction cycle where radical recombination with FePhBr(TMEDA) (2Ph ) results in selective product formation in high yield. These results differ from prior studies with mesityl Grignard reagent, where poor product selectivity and low catalytic performance can be attributed to homoleptic iron-ate species. Overall, this study represents a critical advance in how amine additives such as TMEDA can modulate selectivity and reactivity of organoiron species in cross-coupling.

Creation of an unexpected plane of enhanced covalency in cerium(III) and berkelium(III) terpyridyl complexes.

Controlling the properties of heavy element complexes, such as those containing berkelium, is challenging because relativistic effects, spin-orbit and ligand-field splitting, and complex metal-ligand bonding, all dictate the final electronic states of the molecules. While the first two of these are currently beyond experimental control, covalent M‒L interactions could theoretically be boosted through the employment of chelators with large polarizabilities that substantially shift the electron density in the molecules. This theory is tested by ligating BkIII with 4'-(4-nitrophenyl)-2,2':6',2"-terpyridine (terpy*), a ligand with a large dipole. The resultant complex, Bk(terpy*)(NO3)3(H2O)·THF, is benchmarked with its closest electrochemical analog, Ce(terpy*)(NO3)3(H2O)·THF. Here, we show that enhanced Bk‒N interactions with terpy* are observed as predicted. Unexpectedly, induced polarization by terpy* also creates a plane in the molecules wherein the M‒L bonds trans to terpy* are shorter than anticipated. Moreover, these molecules are highly anisotropic and rhombic EPR spectra for the CeIII complex are reported.

Intermediates and mechanism in iron-catalyzed C-H methylation with trimethylaluminum.

A mechanistic study is performed on the reaction method for iron-catalyzed C-H methylation with AlMe3 reagent, previously proposed to involve cyclometalated iron(III) intermediates and an iron(III)/(I) reaction cycle. Detailed spectroscopic studies (57Fe Mössbauer, EPR) during catalysis and in stoichiometric reactions identify iron(II) complexes, including cyclometalated iron(II) intermediates, as the major iron species formed in situ under catalytic reaction conditions. Reaction studies identify a cyclometalated iron(II)-methyl species as the key intermediate leading to C-H methylated product upon reaction with oxidant, consistent with a previously proposed iron(II)/iron(III)/iron(I) reaction manifold for C-H arylation.

General method for iron-catalyzed multicomponent radical cascades-cross-couplings.

Transition metal­catalyzed cross-coupling reactions are some of the most widely used methods in chemical synthesis. However, despite notable advantages of iron (Fe) as a potentially cheaper, more abundant, and less toxic transition metal catalyst, its practical application in multicomponent cross-couplings remains largely unsuccessful. We demonstrate 1,2-bis(dicyclohexylphosphino)ethane Fe­catalyzed coupling of α-boryl radicals (generated from selective radical addition to vinyl boronates) with Grignard reagents. Then, we extended the scope of these radical cascades by developing a general and broadly applicable Fe-catalyzed multicomponent annulation­cross-coupling protocol that engages a wide range of π-systems and permits the practical synthesis of cyclic fluorous compounds. Mechanistic studies are consistent with a bisarylated Fe(II) species being responsible for alkyl radical generation to initiate catalysis, while carbon-carbon bond formation proceeds between a monoarylated Fe(II) center and a transient alkyl radical.

Experimental and computational studies of the mechanism of iron-catalysed C-H activation/functionalisation with allyl electrophiles.

Synthetic methods that utilise iron to facilitate C-H bond activation to yield new C-C and C-heteroatom bonds continue to attract significant interest. However, the development of these systems is still hampered by a limited molecular-level understanding of the key iron intermediates and reaction pathways that enable selective product formation. While recent studies have established the mechanism for iron-catalysed C-H arylation from aryl-nucleophiles, the underlying mechanistic pathway of iron-catalysed C-H activation/functionalisation systems which utilise electrophiles to establish C-C and C-heteroatom bonds has not been determined. The present study focuses on an iron-catalysed C-H allylation system, which utilises allyl chlorides as electrophiles to establish a C-allyl bond. Freeze-trapped inorganic spectroscopic methods (57Fe Mössbauer, EPR, and MCD) are combined with correlated reaction studies and kinetic analyses to reveal a unique and rapid reaction pathway by which the allyl electrophile reacts with a C-H activated iron intermediate. Supporting computational analysis defines this novel reaction coordinate as an inner-sphere radical process which features a partial iron-bisphosphine dissociation. Highlighting the role of the bisphosphine in this reaction pathway, a complementary study performed on the reaction of allyl electrophile with an analogous C-H activated intermediate bearing a more rigid bisphosphine ligand exhibits stifled yield and selectivity towards allylated product. An additional spectroscopic analysis of an iron-catalysed C-H amination system, which incorporates N-chloromorpholine as the C-N bond-forming electrophile, reveals a rapid reaction of electrophile with an analogous C-H activated iron intermediate consistent with the inner-sphere radical process defined for the C-H allylation system, demonstrating the prevalence of this novel reaction coordinate in this sub-class of iron-catalysed C-H functionalisation systems. Overall, these results provide a critical mechanistic foundation for the rational design and development of improved systems that are efficient, selective, and useful across a broad range of C-H functionalisations.

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.