Heterolytic Bond Research Articles

Metal-Carbon Bond Heterolysis Energy Scale for Model Palladium Catalysts.

Thermodynamic studies of transition-metal intermediates are crucial for understanding of metal-catalyzed transformations. Herein, a series of arylpalladium cyanomethanides were synthesized and characterized. Their palladium-carbon bond heterolysis energies (ΔGhet(Pd-C)) were determined in DMSO for the first time by equilibrium methods. ΔGhet(Pd-C) values of 7.9-19.1 kcal/mol, located between the ΔGhet(Pd-O) and ΔGhet(Pd-N) scales previously established, are much smaller than the corresponding ΔGhet(C-H)s of phenylacetonitrile (30.0 kcal/mol). Linear free energy relationship (LEFR) analysis reveals insights into the structure-property relationship and the factor dictating the thermodynamics of metalation. These ΔGhet(Pd-X)s in combination with ΔGhet(X-H)s are successfully used to diagnose the reaction feasibility and selectivity of X-H bond activation.

A Selective Iron(I) Hydrogenation Catalyst.

Iron is the most abundant transition metal of the Earth's crust, and the understanding of its function in key technologies, such as catalysis, is highly important. We report here on an iron(I) hydrogenation catalyst. Our catalyst activates hydrogen via heterolytic bond cleavage, forms a monohydride, and hydrogenates polar double bonds via a bimetallic pathway (potassium-assisted hydride transfer). The mechanism observed seems to exclude oxidative addition and reductive elimination pathways, permitting the tolerance of numerous hydrogenation-sensitive functional groups, as demonstrated for the hydrogenation of C═O bonds.

Facile heterolytic bond splitting of molecular chlorine upon reactions with Lewis bases: Comparison with ICl and I2

AbstractFormation of molecular complexes and subsequent heterolytic halogen‐halogen bond splitting upon reactions of molecular Cl2 with nitrogen‐containing Lewis bases (LB) are computationally studied at M06‐2X/def2‐TZVPD and for selected compounds at CCSD(T)/aug‐cc‐pvtz//CCSD/aug‐cc‐pvtz levels of theory. Obtained results are compared with data for ICl and I2 molecules. Reaction pathways indicate, that in case of Cl2∙LB complexes the activation energies for the heterolytic Cl‐Cl bond splitting are lower than the activation energies of the homolytic splitting of Cl2 molecule into chlorine radicals. The heterolytic halogen splitting of molecular complexes of X2∙Py with formation of [XPy2]+… contact ion pairs in the gas phase is slightly endothermic in case of Cl2 and I2, but slightly exothermic in the case of ICl. Formation of {[ClPy2]+…}2 dimers makes the overall process exothermic. Taking into account that polar solvents favor ionic species, generation of donor‐stabilized Cl+ in the presence of the Lewis bases is expected to be favorable. Thus, in polar solvents the oxidation pathway via donor‐stabilized Cl+ species is viable alternative to the homolytic Cl‐Cl bond breaking.

Density functional theory study of substituent effects on gas-phase heterolytic Fe-N bond energies of m-G-C6H4NHFe(CO)2(η5-C5H5) and m-G-C6H4N(COMe)Fe(CO)2(η5-C5H5)

The nature and strength of metal–ligand bonds in organotransition-metal complexes are crucial to the understanding of organometallic reactions and catalysis. Quantum chemical calculations at different levels of theory have been used to investigate heterolytic Fe-N bond energies of meta-substituted anilinyldicarbonyl(η5-cyclopentadienyl)iron [m-G-C6H4NH(η5-C5H5)Fe(CO)2, abbreviated as m-G-C6H4NHFp (1), where G=NO2, CN, COMe, CO2Me, CF3, Br, Cl, F, H, Me, MeO and NMe2] and meta-substituted α-acetylanilinyldicarbonyl(η5-cyclopentadienyl)iron [m-G-C6H4N(COMe)(η5-C5H5)Fe(CO)2, abbreviated as m-G-C6H4N(COMe)Fp (2)] complexes. The results show that BP86 and TPSSTPSS can provide the best price/performance ratio and more accurate predictions in the study of ΔHhet(Fe-N)′s. ΔΔHhet(Fe-N)′s (1 and 2) conform to the captodative principle. There are excellent linear free energy relations among ΔΔHhet(Fe-N)′s and the experimental and computational substituent effects on acidities of m-G-C6H4NH2, the differences of acidic dissociation constants (ΔpKas) of NH bonds for m-G-C6H4NH2 for series 1 or the substituent σm constants. The former correlations imply that the govering factors for these bond scissions are similar; the latter ones suggest that polar effects of meta-substituents show the dominant role to the magnitudes of ΔHhet(Fe-N)′s. And these correlations are in accordance with Hammett linear free energy relationships. The Fe-N bonds in series 1 are stronger than those in series 2. Therefore m-G-C6H4N(COMe)- are more stable than m-G-C6H4NH-. The absolute magnitudes of AEs, AEα-COMes and AEα-COMe,para-Gs are far larger than MEs, MEα-COMes and MEα-COMe,para-Gs. The influences of MEs, MEα-COMes and MEα-COMe,para-Gs are subtle. A better understanding of organometallic bond energies can suggest whether proposed new catalytic systems may work well.

Unimolecular net heterolysis of symmetric and homopolar σ-bonds

The unimolecular heterolysis of covalent σ-bonds is integral to many chemical transformations, including SN1-, E1- and 1,2-migration reactions. To a first approximation, the unequal redistribution of electron density during bond heterolysis is governed by the difference in polarity of the two departing bonding partners1–3. This means that if a σ-bond consists of two identical groups (that is, symmetric σ-bonds), its unimolecular fission from the S0, S1, or T1 states only occurs homolytically after thermal or photochemical activation1–7. To force symmetric σ-bonds into heterolytic manifolds, co-activation by bimolecular noncovalent interactions is necessary4. These tactics are only applicable to σ-bond constituents susceptible to such polarizing effects, and often suffer from inefficient chemoselectivity in polyfunctional molecules. Here we report the net heterolysis of symmetric and homopolar σ-bonds (that is, those with similar electronegativity and equal leaving group ability3) by means of stimulated doublet–doublet electron transfer (SDET). As exemplified by Se–Se and C–Se σ-bonds, symmetric and homopolar bonds initially undergo thermal homolysis, followed by photochemically SDET, eventually leading to net heterolysis. Two key factors make this process feasible and synthetically valuable: (1) photoexcitation probably occurs in only one of the incipient radical pair members, thus leading to coincidental symmetry breaking8 and consequently net heterolysis even of symmetric σ-bonds. (2) If non-identical radicals are formed, each radical may be excited at different wavelengths, thus rendering the net heterolysis highly chemospecific and orthogonal to conventional heterolyses. This feature is demonstrated in a series of atypical SN1 reactions, in which selenides show SDET-induced nucleofugalities3 rivalling those of more electronegative halides or diazoniums.

A DFT study on the heterolytic bond cleavage of hydrazones under cathodic conditions in acetonitrile.

Hydrazones have been studied for a myriad of chemical and physiochemical properties, such as sensors, chelators and numerous biological activities. Experimental data indicates that hydrazones are unstable under cathodic potentials irrespective of the solvent. The single electron reduction of hydrazones to produce radical anions result in unstable species that cleaves at the N-N bond in a heterolytic manner. The literature has proposed a mechanism favouring the radical on the imine moiety, however in this study DFT calculations suggest the radical on the amine product is more likely upon bond cleavage. This has implications on electrochemical mechanisms, and the active molecule in biological studies viz the method of delivery to target areas. Density functional theory calculations were carried out using the GAMESS software package. The structures were optimized in the gas phase (B3LYP/6-31G(d,p)) as indicated by the absence of imaginary frequencies in the Hessian, and in CH3CN (B3LYP/6-31G(d,p)/SMD) with the Pople polarization functions. As a comparison, selected pathways were fully optimized using PBE0/6-31G(d,p) and PBE0/6-31G(d,p)/SMD for gas phase and CH3CN, respectively with the Pople polarization functions. The values were not significantly different (< 5% difference). As such only the B3LYP is evaluation is discussed.

Fluoride-Mediated Aryne 1,2-Difunctionalization Involving C═S Bond Heterolysis.

We have successfully synthesized a series of bidentate ligands by utilizing 2-(trimethylsilyl)phenyl trifluorosulfonate as a precursor for the benzyl group. This method proceeded by inserting a polythiourea into the C═S π-bond, intramolecular ring proton migration, and ring opening. Salient features of this strategy are mild reaction conditions, a novel product structure, excellent stereochemistry, and a good functional group tolerance. Furthermore, a series of density functional theory calculations were performed to gain insights into the transfer mechanism.

Distinguishing homolytic vs heterolytic bond dissociation of phenylsulfonium cations with localized active space methods

Modeling chemical reactions with quantum chemical methods is challenging when the electronic structure varies significantly throughout the reaction and when electronic excited states are involved. Multireference methods, such as complete active space self-consistent field (CASSCF), can handle these multiconfigurational situations. However, even if the size of the needed active space is affordable, in many cases, the active space does not change consistently from reactant to product, causing discontinuities in the potential energy surface. The localized active space SCF (LASSCF) is a cheaper alternative to CASSCF for strongly correlated systems with weakly correlated fragments. The method is used for the first time to study a chemical reaction, namely the bond dissociation of a mono-, di-, and triphenylsulfonium cation. LASSCF calculations generate smooth potential energy scans more easily than the corresponding, more computationally expensive CASSCF calculations while predicting similar bond dissociation energies. Our calculations suggest a homolytic bond cleavage for di- and triphenylsulfonium and a heterolytic pathway for monophenylsulfonium.

A case study of depolymerization in silicates: Melting of quartz and zircon crystallization at high pressure

The experimental study of depolymerization reaction SiO2 + ZrO2 → ZrSiO4 reveals that melting of quartz and crystallization of zircon in the presence of water increases at high pressure. The melting rate of quartz is identified as the rate-determining step of the reaction. In highly polymerized silicates, Si-O-Si bond angles are subject to alteration under the influence of pressure. This phenomenon is particularly noticeable within the three-dimensional lattice structure of quartz, where each corner of the tetrahedra is shared. Theoretical analysis of the Si-O-Si bond angle bending demonstrates a change in oxygen hybridization from sp to sp2, favoring larger Si-O distances. The sp2 hybridization in bridging oxygen promotes acid attack by hydrogen ions of water, resulting in SiO bond heterolysis in quartz. The depolymerization from tectosilicates to nesosilicates leads to an increase in oxygen “size” and polarizability, as well of closer packing of oxygen atoms. This change in behavior and packing of oxygens is further illustrated by the high-pressure-driven transition from tridymite to stishovite. Additionally, the impact of network-modifying elements on the structure of polymerized silicates is investigated; particularly those acting as electron donors, which lengthen Si-O distances in quartz. The findings are discussed in relation to key topics in Earth Sciences, including the crystal chemical basis of the Bowen's reaction series, the “metallization” in rocky planets and the structural controls of hydrous and dry melting in silicates.

Silicon Nitride Surface Enabled Propane Dehydrogenation Catalyzed by Supported Organozirconium.

Mesoporous silicon nitride (Si3N4) is a nontraditional support for the chemisorption of organometallic complexes with the potential for enhancing catalytic activity through features such as the increased Lewis basicity of nitrogen for heterolytic bond activation, increased ligand donor strength, and metal-ligand orbital overlap. Here, tetrabenzyl zirconium (ZrBn4) was chemisorbed on Si3N4, and the resulting supported organometallic species was characterized by Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS), Dynamic Nuclear Polarization-enhanced Solid State Nuclear Magnetic Resonance (DNP-SSNMR), and X-ray Absorption Spectroscopy (XAS). Based on the hypothesis that the nitride might enable facile heterolytic C-H bond activation along the Zr-N bond, this material was found to be a highly active (1.53 molpropene molZr-1 h-1 at 450 °C) and selective (99% to propylene) catalyst for propane dehydrogenation. In contrast, the homologous silica supported complex exhibited negligible activity under these conditions.

Investigating Ligand Sphere Perturbations on MnIII-Alkylperoxo Complexes.

Manganese catalysts that activate hydrogen peroxide carry out several different hydrocarbon oxidation reactions with high stereoselectivity. The commonly proposed mechanism for these reactions involves a key manganese(III)-hydroperoxo intermediate, which decays via O-O bond heterolysis to generate a Mn(V)-oxo species that institutes substrate oxidation. Due to the scarcity of characterized MnIII-hydroperoxo complexes, MnIII-alkylperoxo complexes are employed to understand factors that affect the mechanism of the O-O cleavage. Herein, we report a series of novel complexes, including two room-temperature-stable MnIII-alkylperoxo species, supported by a new amide-containing pentadentate ligand (6Medpaq5NO2). We use a combination of spectroscopic methods and density functional theory computations to probe the effects of the electronic changes in the ligand sphere trans to the hydroxo and alkylperoxo units to thermal stability and reactivity. The structural characterizations for both MnII(OTf)(6Medpaq5NO2) and [MnIII(OH)(6Medpaq5NO2)](OTf) were obtained via single-crystal X-ray crystallography. A perturbation to the ligand sphere allowed for a marked increase in reactivity towards an organic substrate, a modest change in the distribution of the O-O cleavage products from homolytic and heterolytic pathways, and little change in thermal stability.

[Fe(NCMe)6](BF4)2 is a bifunctional catalyst for styrene aziridination by nitrene transfer and heterocycle expansion by subsequent dipolar insertion

The solvated iron(II) salt [Fe(NCMe)6](BF4)2 (Me = methyl) is shown to be a bifunctional catalyst with respect to aziridination of styrene. The salt serves as an active catalyst for nitrene transfer from PhINTs to styrene to form 2-phenyl-N-tosylaziridine (Ph = phenyl; Ts = tosyl, –S{O}2–p-C6H4Me). The iron(II) salt also acts as a Lewis acid in non-coordinating CH2Cl2 solution, to catalyze heterolytic CN bond cleavage of the aziridine and insertion of dipolarophiles. The 1,3-zwitterionic intermediate is presumably supported by interaction of the metal dication with the anion, and by resonance stabilization of the carbocation. Nucleophilic dipolarophiles then insert to give a five-membered heterocyclic ring. The result is a two-step cycloaddition, formally [2 + 1 + 2], that is typically regiospecific, but not stereospecific. This reaction mechanism was confirmed by conducting a series of one-step, [3 + 2] additions of unsaturated molecules into pre-formed 2-phenyl-N-tosylaziridine, also catalyzed by [Fe(NCMe)6](BF4)2. Relevant substrates include styrenes, carbonyl compounds and alkynes. These yield five-membered heterocylic rings, including pyrrolidines, oxazolidines and dihydropyrroles, respectively. The reaction scope appears limited only by the barrier to formation of the dipolar intermediate, and by the nucleophilicity of the captured dipolarophile. The bifunctionality of an inexpensive, earth-abundant and non-toxic catalyst suggests a general strategy for one-pot construction of heterocyclic rings, as demonstrated specifically for pyrrolidine ring formation.

Light in a Heartbeat: Bond Scission by a Single Photon above 800 nm.

Photocages enable scientists to take full control over the activity of molecules using light as a biocompatible stimulus. Their emerging applications in photoactivated therapies call for efficient uncaging in the near-infrared (NIR) window, which represents a fundamental challenge. Here, we report synthetically accessible cyanine photocages that liberate alcohol, phenol, amine, and thiol payloads upon irradiation with NIR light up to 820 nm in aqueous media. The photocages display a unique chameleon-like behavior and operate via two distinct uncaging mechanisms: photooxidation and heterolytic bond cleavage. The latter process constitutes the first example of a direct bond scission by a single photon ever observed in cyanine dyes or at wavelengths exceeding 800 nm. Modulation of the beating rates of human cardiomyocytes that we achieved by light-actuated release of adrenergic agonist etilefrine at submicromolar concentrations and low NIR light doses (∼12 J cm-2) highlights the potential of these photocages in biology and medicine.

Bond Strength and Interaction Energies in Togni Reagents: Insights from Molecular Electrostatic Potential-Based Parameters.

Togni reagents and their analogs, classified as hypervalent iodine(III) complexes, serve as potent trifluoromethylation agents. The interplay of cis and trans factors plays a pivotal role in shaping their performance, affecting aspects such as bond strength, interaction energies, stability, and subsequent nucleophilic reactions. In this context, we propose the utilization of the molecular electrostatic potential (MESP) at the carbon atom (VC) of the I-CF3 moiety as a sensitive parameter to quantify the cis and trans influences in Togni-type reagents. Our study has shown that VC serves as a convenient probe for determining the heterolytic bond dissociation energy (BDE) and, consequently, assessing the reactivity of these reagents. Moreover, these parameters have been successfully applied to evaluate the strength of the σ-hole interactions with nucleophiles (Cl- and NMe3). Additionally, we provide insights into interactions of Togni reagents with Brønsted acids such as HCl and HSO3F, elucidating them in terms of MESP topological parameters. These findings yield valuable information about the electronic properties of hypervalent iodine reagents, particularly Togni-type reagents, offering the potential for optimizing structurally modified reagents with enhanced activity and stability.

Introducing AFS ([Al(SO3F)3]x) - a thermally stable, readily available, and catalytically active solid Lewis superacid.

Common Lewis superacids often suffer from low thermal stability or complicated synthetic protocols, requiring multi-step procedures and expensive starting materials. This prevents their large-scale application. Herein, the easy and comparably cheap synthesis of high-purity aluminium tris(fluorosulfate) ([Al(SO3F)3]x, AFS) is presented. All starting materials are commercially available and no work-up is required. The superacidity of this thermally stable, polymeric Lewis acid is demonstrated using both theoretical and experimental methods. Furthermore, its synthetic and catalytic applicability, e.g. in bond heterolysis reactions and C-F bond activations, is shown.

C-H bond activation at antimony(III): synthesis and reactivity of Sb(III)-oxyaryl species.

We report on the synthesis, structure and reactivity of [{NCNMe4}Sb(C6H2-tBu2-3,5-O-4)] (3), an organoantimony(III)-oxyaryl species obtained upon Csp2-H bond activation in a phenolate ligand and stabilised by the monoanionic pincer {NCNMe4}-. The mechanism leading to the formation of 3 is highly sensitive to steric considerations. It was probed experimentally and by DFT calculations, and a number of intermediates and related complexes were identified. All data agree with successive heterolytic bond cleaving and bond forming processes involving charged species, rather than a pathway involving free radicals as previously exemplified with congeneric bismuth species. The nucleophilic behaviour of the oxyaryl ligand in 3, a complex that features both zwitterionic and quinoidal attributes, was illustrated in derivatisation reactions. In particular, insertion of CS2 in the Sb-Coxyaryl bond generates [{NCNMe4}Sb(S2C-C6H2-tBu2-3,5-O-4)].

Unveiling distinct bonding patterns in noble gas hydrides via interference energy analysis.

Despite their apparent simplicity, the helium hydride ion (HeH+) and its analogues with heavier noble gas (Ng) atoms present intriguing challenges due to their unusual electronic structures and distinct ground-state heterolytic bond dissociation profiles. In this work, we employ modern valence bond calculations and the interference energy analysis to investigate the nature of the chemical bond in NgH+ (Ng = He, Ne, Ar). Our findings reveal that the energy well formation in their ground-state potential energy curves is driven by a reduction in kinetic energy caused by quantum interference, identical to cases of homolytic bond dissociation. However, clear differences in bonding situation emerge: in HeH+ and ArH+, electron charge transfer leads to Ng+-H covalent bonds, while in NeH+, a preferred Ne + H+ valence bond structure suggests the formation of a dative bond. This study highlights the distinct bonding mechanisms within the NgH+ series, showcasing the interplay between quantum interference and quasi-classical effects in molecules featuring noble gases.

Predicting bond dissociation energies of cyclic hypervalent halogen reagents using DFT calculations and graph attention network model.

Although hypervalent iodine(III) reagents have become staples in organic chemistry, the exploration of their isoelectronic counterparts, namely hypervalent bromine(III) and chlorine(III) reagents, has been relatively limited, partly due to challenges in synthesizing and stabilizing these compounds. In this study, we conduct a thorough examination of both homolytic and heterolytic bond dissociation energies (BDEs) critical for assessing the chemical stability and functional group transfer capability of cyclic hypervalent halogen compounds using density functional theory (DFT) analysis. A moderate linear correlation was observed between the homolytic BDEs across different halogen centers, while a strong linear correlation was noted among the heterolytic BDEs across these centers. Furthermore, we developed a predictive model for both homolytic and heterolytic BDEs of cyclic hypervalent halogen compounds using machine learning algorithms. The results of this study could aid in estimating the chemical stability and functional group transfer capabilities of hypervalent bromine(III) and chlorine(III) reagents, thereby facilitating their development.

A general copper-catalysed enantioconvergent C(sp3)-S cross-coupling via biomimetic radical homolytic substitution.

Although α-chiral C(sp3)-S bonds are of enormous importance in organic synthesis and related areas, the transition-metal-catalysed enantioselective C(sp3)-S bond construction still represents an underdeveloped domain probably due to the difficult heterolytic metal-sulfur bond cleavage and notorious catalyst-poisoning capability of sulfur nucleophiles. Here we demonstrate the use of chiral tridentate anionic ligands in combination with Cu(I) catalysts to enable a biomimetic enantioconvergent radical C(sp3)-S cross-coupling reaction of both racemic secondary and tertiary alkyl halides with highly transformable sulfur nucleophiles. This protocol not only exhibits a broad substrate scope with high enantioselectivity but also provides universal access to a range of useful α-chiral alkyl organosulfur compounds with different sulfur oxidation states, thus providing a complementary approach to known asymmetric C(sp3)-S bond formation methods. Mechanistic results support a biomimetic radical homolytic substitution pathway for the critical C(sp3)-S bond formation step.

Fragment-based models for dissociation of strong acids in water: Electrostatic embedding minimizes the dependence on the fragmentation schemes.

Fragmentation methods such as MIM (Molecules-in-Molecules) provide a route to accurately model large systems and have been successful in predicting their structures, energies, and spectroscopic properties. However, their use is often limited to systems at equilibrium due to the inherent complications in the choice of fragments in systems away from equilibrium. Furthermore, the presence of charges resulting from any heterolytic bond breaking may increase the fragmentation error. We have previously suggested EE-MIM (Electrostatically Embedded Molecules-In-Molecules) as a method to mitigate the errors resulting from the missing long-range interactions in molecular clusters in equilibrium. Here, we show that the same method can be applied to improve the performance of MIM to solve the longstanding problem of dependency of the fragmentation energy error on the choice of the fragmentation scheme. We chose four widely used acid dissociation reactions (HCl, HClO4, HNO3, and H2SO4) as test cases due to their importance in chemical processes and complex reaction potential energy surfaces. Electrostatic embedding improves the performance at both one and two-layer MIM as shown by lower EE-MIM1 and EE-MIM2 errors. The EE-MIM errors are also demonstrated to be less dependent on the choice of the fragmentation scheme by analyzing the variation in fragmentation energy at the points with more than one possible fragmentation scheme (points where the fragmentation scheme changes). EE-MIM2 with M06-2X as the low-level resulted in a variation of less than 1 kcal/mol for all the cases and 1 kJ/mol for all but three cases, rendering our method fragmentation scheme-independent for acid dissociation processes.