Lowest Energy Transition State Research Articles

Mechanism and Origin of Stereoselectivity of N-Heterocyclic Carbene (NHC)-Catalyzed Transformation Reaction of Benzaldehyde with o-QDM as Key Intermediate: A DFT Study.

N-heterocyclic carbene (NHC)-bound ortho-quinodimethane, served as a nucleophile, has occupied an important position for constructing various all-carbon or heterocyclic compounds and attracted increasing attention for the functionalization of benzylic carbon of aromatic aldehydes, whereas the mechanistic studies on the generation and transformations of dienolate intermediate are rare. In the present study, the mechanism of activation/transformation of aldehyde catalyzed by NHC was theoretically studied using the density functional theory (DFT) method. Based on the calculations, the nucleophilic addition process is the stereoselectivity-determining step with RS-configured product being generated preferentially. Furthermore, non-covalent index (NCI) and atoms-in-molecules (AIM) analyses have been performed to disclose the origin of stereoselectivity, by which the larger number and stronger weak interactions are the key for stabilizing the low-energy transition state and thus leading to the stereoselectivity inducing.

From loose to tight: unveiling bond stretch isomerism in π-complexes of Li, Na and K.

The study investigates the phenomenon of bond stretch isomerism (BSI) in complexes formed between alkali metals (Li, Na, K) and various non-aromatic, aromatic hydrocarbons, as well as heteroaromatic systems. The research employs density functional theory (DFT) calculations to optimize complex geometries and analyze their electronic structures using molecular electrostatic potential (MESP), charge, and spin density analyses. The results reveal that these complexes can exist in two distinct configurations: 'loose' long-bond isomers (lbi) that retain the original hydrocarbon geometry and 'tight' short-bond isomers (sbi) that undergo geometrical distortion upon complexation, with sbi generally being more stable. The interconversion between lbi and sbi occurs through a transition state. The study highlights the crucial role of electron transfer in BSI, with sbi involving valence electron transfer from the metal to the hydrocarbon, leading to zwitterionic radical complexes. In contrast, lbi exhibit a slight electron density transfer from the hydrocarbon to the metal. The presence of low-energy transition states between lbi and sbi suggests a dynamic shuttling mechanism for alkali metals, particularly Li, on hydrocarbon surfaces. The study identifies Li complexes as potential candidates for anode materials in batteries due to their stability and electron transfer properties, offering valuable insights into the design of advanced materials for energy storage applications.

Theoretical study of an N-heterocyclic carbene-catalyzed annulation reaction between an enal and a β-silyl enone: Mechanism and origin of stereoselectivity

In this study, the mechanism and origin of the stereoselectivity of an N-heterocyclic carbene (NHC)-catalyzed transformation reaction between an enal and a β-silyl enone are systematically investigated using density functional theory (DFT) at the M06-2X level. Multiple pathways are proposed and studied to identify the most energetically favorable mechanism for the reaction. The calculation results show that the most energetically favorable pathway comprises the following processes: nucleophilic addition of NHC to the Si-face of the enal to form a zwitterionic intermediate, two sequential CsHCO3-assisted intramolecular proton shifts to produce an enolate intermediate, Michael-type addition of the enolate intermediate to the β-silyl enone, ring closure to construct a six-membered ring intermediate, and the dissociation of NHC to release the final product. The reaction between the enolate intermediate and the β-silyl enone is identified as the stereoselectivity-determining step, preferentially generating an RS-configured product. Subsequent atoms-in-molecules (AIM) and noncovalent interaction (NCI) analyses verify that the main factor for inducing stereoselectivity is the higher number of noncovalent intermolecular interactions in the low-energy transition state.

Amide isomerization pathways: Electronic and structural background of protonation- and deprotonation-mediated cis-trans interconversions.

The cis-trans isomerization of amide bonds leads to wide range of structural and functional changes in proteins and can easily be the rate-limiting step in folding. The trans isomer is thermodynamically more stable than the cis, nevertheless the cis form can play a role in biopolymers' function. The molecular system of N-methylacetamide · 2H2O is complex enough to reveal energetics of the cis-trans isomerization at coupled cluster single-double and coupled cluster single-double and perturbative triple [CCSD(T)] levels of theory. The cis-trans isomerization cannot be oversimplified by a rotation along ω, since this rotation is coupled with the N-atom pyramidal inversion, requesting the introduction of a second dihedral angle "α." Full f(ω,α) potential energy surfaces of the different amide protonation states, critical points and isomerization reaction paths were determined, and the barriers of the neutral, O-protonated and N-deprotonated amides were found too high to allow cis-trans interconversion at room temperature: ∼85, ∼140, and ∼110 kJ mol-1, respectively. For the N-protonated amide bond, the cis form (ω = 0°) is a maximum rather than a minimum, and each ω state is accessible for less than ∼10 kJ mol-1. Here we outline a cis-trans isomerization pathway with a previously undescribed low energy transition state, which suggests that the proton is transferred from the more favorable O- to the N-protonation site with the aid of nearby water molecules, allowing the trans → cis transition to occur at an energy cost of ≤11.6 kJ mol-1. Our results help to explain why isomerase enzymes operate via protonated amide bonds and how N-protonation of the peptide bond occurs via O-protonation.

Mixed-Valence Tetrametallic Iridium Chains.

Neutral [X-{Ir2 }-{Ir2 }-X] (X=Cl, Br, SCN, I) and dicationic [L-{Ir2 }-{Ir2 }-L]2+ (L=MeCN, Me2 CO) tetrametallic iridium chains made by connecting two dinuclear {Ir2 } units ({Ir2 }=[Ir2 (μ-OPy)2 (CO)4 ], OPy=2-pyridonate) by an iridium-iridium bond are described. The complexes exhibit fractional averaged oxidation states of +1.5 and electronic delocalization along the metallic chain. While the axial ligands do not significantly affect the metal-metal bond lengths, the metallic chain has a significant impact on the iridium-L/X bond distances. The complexes show free rotation around the unsupported iridium-iridium bond in solution, with a low-energy transition state for the chloride chain. The absorption spectra of these complexes show characteristic bands at 438-504 nm, which can be fine-tuned by varying the terminal capping ligands.

Sulfonyl Diazaborine 'Click' Chemistry Enables Rapid and Efficient Bioorthogonal Labeling.

Finding an ideal bioorthogonal reaction that responds to a wide range of biological queries and applications is of great interest in biomedical applications. Rapid diazaborine (DAB) formation in water by the reactions of ortho-carbonyl phenylboronic acid with α-nucleophiles is an attractive conjugation module. Nevertheless, these conjugation reactions demand to satisfy stringent criteria for bioorthogonal applications. Here we show that widely used sulfonyl hydrazide (SHz) offers a stable DAB conjugate by combining with ortho-carbonyl phenylboronic acid at physiological pH, competent for an optimal biorthogonal reaction. Remarkably, the reaction conversion is quantitative and rapid (k2 >103 M-1 s-1 ) at low micromolar concentrations, and it preserves comparable efficacy in a complex biological milieu. DFT calculations support that SHz facilitates DAB formation via the most stable hydrazone intermediate and the lowest energy transition state compared to other biocompatible α-nucleophiles. This conjugation is extremely efficient on living cell surfaces, enabling compelling pretargeted imaging and peptide delivery. We anticipate this work will permit addressing a wide range of cell biology queries and drug discovery platforms exploiting commercially available sulfonyl hydrazide fluorophores and derivatives.

Atmospheric breakdown chemistry of the new “green” solvent 2,2,5,5-tetramethyloxolane via gas-phase reactions with OH and Cl radicals

Abstract. The atmospheric chemistry of 2,2,5,5-tetramethyloxolane (TMO), a promising “green” solvent replacement for toluene, was investigated in laboratory-based experiments and computational calculations. Results from both absolute and relative rate studies demonstrated that the reaction OH + TMO (Reaction R1) proceeds with a rate coefficient k1(296 K) = (3.1±0.4) ×10-12 cm3 molecule−1 s−1, a factor of 3 smaller than predicted by recent structure–activity relationships. Quantum chemical calculations (CBS-QB3 and G4) demonstrated that the reaction pathway via the lowest-energy transition state was characterised by a hydrogen-bonded pre-reaction complex, leading to thermodynamically less favoured products. Steric hindrance from the four methyl substituents in TMO prevents formation of such H-bonded complexes on the pathways to thermodynamically favoured products, a likely explanation for the anomalous slow rate of Reaction (R1). Further evidence for a complex mechanism was provided by k1(294–502 K), characterised by a local minimum at around T=340 K. An estimated atmospheric lifetime of τ1≈3 d was calculated for TMO, approximately 50 % longer than toluene, indicating that any air pollution impacts from TMO emission would be less localised. An estimated photochemical ozone creation potential (POCPE) of 18 was calculated for TMO in north-western Europe conditions, less than half the equivalent value for toluene. Relative rate experiments were used to determine a rate coefficient of k2(296 K) = (1.2±0.1) ×10-10 cm3 molecule−1 s−1 for Cl + TMO (Reaction R2); together with Reaction (R1), which is slow, this may indicate an additional contribution to TMO removal in regions impacted by high levels of atmospheric chlorine. All results from this work indicate that TMO is a less problematic volatile organic compound (VOC) than toluene.

A Combined DFT, Energy Decomposition, and Data Analysis Approach to Investigate the Relationship Between Noncovalent Interactions and Selectivity in a Flexible DABCOnium/Chiral Anion Catalyst System.

Developing strategies to study reactivity and selectivity in flexible catalyst systems has become an important topic of research. Herein, we report a combined experimental and computational study aimed at understanding the mechanistic role of an achiral DABCOnium cofactor in a regio- and enantiodivergent bromocyclization reaction. It was found that electron-deficient aryl substituents enable rigidified transition states via an anion-π interaction with the catalyst, which drives the selectivity of the reaction. In contrast, electron-rich aryl groups on the DABCOnium result in significantly more flexible transition states, where interactions between the catalyst and substrate are more important. An analysis of not only the lowest-energy transition state structures but also an ensemble of low-energy transition state conformers via energy decomposition analysis and machine learning was crucial to revealing the dominant noncovalent interactions responsible for observed changes in selectivity in this flexible system.

Molecular Electrochemical Reductive Splitting of Dinitrogen with a Molybdenum Complex**

AbstractNitrogen reduction under mild conditions (roomTand atmosphericP), using a non‐fossil source of hydrogen remains a challenge. Molecular metal complexes, notably Mo based, have recently been shown to be active for such nitrogen fixation. We report electrochemical N2splitting with a MoIIItriphosphino complex [(PPP)MoI3], at room temperature and a moderately negative potential. A MoIVnitride species was generated, which is confirmed by electrochemistry and NMR studies. The reaction goes through two successive one electron reductions of the starting Mo species, coordination of a N2molecule, and further splitting to a MoIVnitride complex. Preliminary DFT studies support the formation of a bridging MoIN2MoIdinitrogen dimer evolving to the Mo nitride via a low energy transition state. This example joins a short list of molecular complexes for N2electrochemical reductive cleavage. It opens a door to electrochemical proton‐coupled electron transfer (PCET) conversion studies of N2to NH3.

Theoretical investigation on cobalt-catalyzed hydroacylation reaction: Mechanism and origin of stereoselectivity

In the present study, the mechanism of a cobalt-catalyzed hydroacylation reaction between aldehydes and 1,6-enynes and the origin of its stereoselectivity have been systematically investigated using the DFT calculational method. Two possible reaction mechanisms have been investigated: one that starts with oxidative addition of the aldehyde (aldehyde-first) or one that starts with oxidative cyclization of the 1,6-enyne (enyne-first). The computational results show that the aldehyde-first mechanism is energetically more favorable than is the enyne-first mechanism. The aldehyde-first mechanism contains several steps: oxidative addition, acyl migratory insertion, alkene insertion, and reductive elimination. Based on the calculations, the alkene insertion is the stereoselectivity-determining step, generating the S-configured product preferentially. The key to inducing the observed stereoselectivity is the lesser distortion of the structure of the lower-energy transition state that leads to the S-configured product.

Front Cover: Mechanistic Insights into the Organocatalytic Kinetic Resolution of Oxazinones through Alcoholysis (Eur. J. Org. Chem. 3/2022)

The Front Cover represents a metaphor for the enantioselectivity produced by the organocatalyst in the studied reaction. Just like a traveler would never choose the dark and unsafe pathway and would always go through the light and easy road, the catalyst leads the reactants through the lowest energy transition state, producing the R enantiomer of the product over the S. Cover design by Inigo Iribarren. More information can be found in the Full Paper by C. Trujillo et al.

Unraveling the mechanism and substituent effects on the N-heterocyclic carbene-catalyzed transformation reaction of enals and imines

An intramolecular hydrogen bond-promoted activation of imines represents a new strategy in annulation reactions catalyzed by N-heterocyclic carbenes (NHCs). In this study, the mechanism and the origin of stereoselectivity in the NHC-catalyzed annulation of enals and imines are suggested and investigated theoretically. The computational results show that the reaction between a Breslow intermediate and an intramolecular hydrogen bond-activated imine is the rate- and stereoselectivity-determining step and results in the preferential generation of RS-configured products. The presence of intramolecular hydrogen bond is crucial for the reaction, because the formation of such bond significantly enhances the electrophilicity of the imine and thus facilitate the reaction. Non-covalent interaction (NCI) analysis shows that the CH•••π, CH•••O, π•••π, and lone pair (LP)•••π interactions contribute significantly to stabilizing the lower-energy transition state, thus inducing to the preferential formation of the RS-configured product.

Solid-State Structural Properties of Alloxazine Determined from Powder XRD Data in Conjunction with DFT-D Calculations and Solid-State NMR Spectroscopy: Unraveling the Tautomeric Identity and Pathways for Tautomeric Interconversion.

We report the solid-state structural properties of alloxazine, a tricyclic ring system found in many biologically important molecules, with structure determination carried out directly from powder X-ray diffraction (XRD) data. As the crystal structures containing the alloxazine and isoalloxazine tautomers both give a high-quality fit to the powder XRD data in Rietveld refinement, other techniques are required to establish the tautomeric form in the solid state. In particular, high-resolution solid-state 15N NMR data support the presence of the alloxazine tautomer, based on comparison between isotropic chemical shifts in the experimental 15N NMR spectrum and the corresponding values calculated for the crystal structures containing the alloxazine and isoalloxazine tautomers. Furthermore, periodic DFT-D calculations at the PBE0-MBD level indicate that the crystal structure containing the alloxazine tautomer has significantly lower energy. We also report computational investigations of the interconversion between the tautomeric forms in the crystal structure via proton transfer along two intermolecular N–H···N hydrogen bonds; DFT-D calculations at the PBE0-MBD level indicate that the tautomeric interconversion is associated with a lower energy transition state for a mechanism involving concerted (rather than sequential) proton transfer along the two hydrogen bonds. However, based on the relative energies of the crystal structures containing the alloxazine and isoalloxazine tautomers, it is estimated that under conditions of thermal equilibrium at ambient temperature, more than 99.9% of the molecules in the crystal structure will exist as the alloxazine tautomer.

UV-A light-assisted gas-phase formic acid decomposition on photo-thermo Ru/TiO2 catalyst

Although solar energy is considered as one of the ideal abundant sources of renewable energy to be integrated into the catalytic processing, photonic and thermal excitations were perceived till recently as independent strategies in overcoming Arrhenius-type activation energy barriers in catalytic reactions. However, this dual-mode excitation of catalysts is receiving a growing interest nowadays due to promising evidence of synergy effects. A Ru/TiO2 photo-thermo- catalyst was prepared according to a UV-A light photo-assisted synthesis method allowing a fine control of the Ru nanoparticle size distribution, and the influence of a combined photonic (UV-A) and thermal activation on its performances in the gas phase decomposition of formic acid into hydrogen was studied. The results showed that a dual photonic/thermal excitation in a one-pot operation allows to increase the formic acid conversion and consequently the production of hydrogen vs. the reaction in the dark, the enhancement being all the more pronounced as the irradiance is high. The combined excitation allowed to drive the reaction at lower temperatures upon irradiation while maintaining a similar conversion level. This low-temperature shift was all the more marked as the irradiance was high, and was accompanied by a strong increase in the selectivity to hydrogen. The change in both conversion and selectivity patterns suggested the implication of the light-excited electrons in the non-plasmonic Ru nanoparticles for conducting the reaction through an alternative low-energy transition state, with a lowering of the apparent energy activation, rather than a mechanism of localized-heat delivery.

Heteroleptic thiolate diamine nickel complexes: Noble-free-metal catalysts in electrocatalytic and light-driven hydrogen evolution reaction

Three mononuclear heteroleptic nickel complexes bearing the non-innocent o-aminobenzenethiolate (2-amnt) ligand and different diamine ligands, namely, [Ni(2-amnt)(o-phen)] (o-phen = o-phenylenediamine) (1), [Ni(2-amnt)(3,4-daba)] (3,4-daba = 3, 4-diamino benzoic acid) (2) and [Ni(2-amnt)(dmnt)] (dmnt = diaminomaleonitrile) (3), were synthesized and characterized. Complexes 1–3 are active homogeneous proton reduction electrocatalysts in dimethylformamide with trifluoroacetic acid as a proton source. All the three complexes are tested in light-driven hydrogen evolution reaction, indicating different catalytic efficiencies. Thus, although complex 3 indicates no catalytic action, both complexes 1 and 2 catalyze H2 evolution in water-dimethylformamide solutions using fluorescein (Fl) as a photosensitizer. Complex 2 acts as a homogeneous catalyst reached 834 turnovers (TON); whereas 1, despite being active in hydrogen evolution reaction (HER), decomposes to form nanomaterials. DFT calculations combined with electrochemical and spectroscopic data were employed to investigate the catalytic mechanism for H2 formation as well as to unravel the key factors that influence the relative catalytic efficiencies. The proposed catalytic pathway involves ligand-based reduction and protonation steps followed by the formation of a nickel-hydride intermediate that reacts with a solution proton to generate H2 via a very low energy transition state.

Theoretical Study of the Role of a Catalytic Water Molecule in the Hydrolysis of Thionyl Tetrafluoride (SOF4).

Sulfuryl fluoride (SO2F2) plays an important role in the operation of gas-insulated switchgear (GIS) equipment where it is widely used as the characteristic gas for discharge diagnostics. However, the formation mechanism of SO2F2 is currently unclear, and as a consequence, we have employed a range of ab initio methods to investigate the hydrolysis reaction of SOF4 that is known to afford SO2F2 in the gas phase. These results suggest that two H2O molecules are incorporated into a low energy transition state to afford an H-bond network that facilitates proton transfer during the hydrolysis of SOF4.

Computational Analysis of the Selective Formation of the C4α-C8' Bond in the Intermolecular Coupling of Catechin Derivatives.

Procyanidin B3 is a natural flavonoid composed of two catechins connected via a C4α-C8' bond. The couplings of catechin derivatives, promoted by Lewis acids, have been widely applied to the syntheses of procyanidin B3 and related flavonoids because the reactions construct the C4α-C8' bond in a highly stereo- and regioselective manner. However, the structural complexity of the catechin derivatives has complicated the exploration of a detailed mechanism for this selectivity. Here, we report the results of a computational study to provide plausible origins for the selective C4α-C8' bond formation of catechin derivatives 1 and 2 by using models 5 and 7. Although a systematic search did not provide SN2-like transition states, we successfully identified transition states TS-A, TS-B, and TS-C for the SN1-type C4α-C8', C4β-C8', and C4α-C6' bond formations, respectively, from a total of 233 transition states to justify the stereo- and regioselectivity of the experimental results. The analysis of these structures by NCIPLOT mapping and the distortion/interaction strain model suggests that the eclipsed interaction at the forming C-C bond between the electrophile and the nucleophile destabilizes TS-B, while the strain of the electrophile destabilizes TS-C. Consequently, the C4α-C8' bond is formed via the lowest energy transition state TS-A.

Peroxocobalt(iii) species activates nitriles via a superoxocobalt(ii) diradical state.

The dioxygenation of nitriles by [CoIII(TBDAP)(O2)]+ (TBDAP = N,N-di-tert-butyl-2,11-diaza[3.3](2,6)-pyridinophane) is investigated using DFT-calculations. The mechanism proposed previously based on experimental observations, which invoked an outer-sphere cycloaddition, was found to be unreasonable. Instead, calculations suggest that an inner-sphere mechanism involving the cleavage of one of the Co-O bonds assisted by substrate uptake is much more likely. The reactively competent species is a triplet consisting of a Co(ii)-superoxo functionality, which can undergo O-C bond formation and O-O bond cleavage traversing low energy transition states. The role of the structurally rigid TBDAP ligand is to prevent the participation of the pyridyl ligand in the delocalization of the unpaired electron density.

A Mechanistic Study of the Stereochemical Outcomes of Rhodium‐Catalysed Styrene Aziridinations

AbstractThe stereoselective, rhodium‐catalysed aziridination of styrene derivatives with a chiral N‐mesyloxycarbamate was found to be highly substrate dependent. A density functional theory (DFT) study is herein reported to elucidate the stereochemical outcome of the aziridination process. Rhodium acetate was initially used as a model catalyst, followed by computational studies conducted with Rh2[(S)‐nttl]4. Both singlet and triplet rhodium nitrene species were identified as intermediates affording concomitant concerted and radical pathways. In the latter case, the radical intermediate appears to undergo a direct ring closure via a minimum energy crossing point (MECP) between the triplet and closed‐shell singlet surfaces. Exceptionally for the m‐Br‐styrene aziridination, an alternative radical pathway with a carbon‐carbon bond rotation was observed, accounting for the observed 74:26 mixture of diastereomers. The computational analysis also suggests little control of the metal nitrene conformation with Rh2(OAc)4 with the chiral N‐mesyloxycarbamate: two conformers were located affording two diastereomers of the aziridine and correlating our experimental results. On the other hand, only one conformer was found for the nitrene generated from the chiral N‐mesyloxycarbamate and Rh2[(S)‐nttl]4. The so‐called “all‐up” conformer of Rh2[(S)‐nttl]4 was not only the most stable metal nitrene species, but also afforded the lowest energy transition state. The calculated dr for p‐Br‐styrene aziridination agrees with the observed experimental result. The combination of experimental and computational results offers a detailed mechanistic picture, providing insights for further catalyst development to enhance reactivity and selectivity.magnified image

Directing isomerization reactions of cumulenes with electric fields

Electric fields have been proposed as having a distinct ability to catalyze chemical reactions through the stabilization of polar or ionic intermediate transition states. Although field-assisted catalysis is being researched, the ability to catalyze reactions in solution using electric fields remains elusive and the understanding of mechanisms of such catalysis is sparse. Here we show that an electric field can catalyze the cis-to-trans isomerization of [3]cumulene derivatives in solution, in a scanning tunneling microscope. We further show that the external electric field can alter the thermodynamics inhibiting the trans-to-cis reverse reaction, endowing the selectivity toward trans isomer. Using density functional theory-based calculations, we find that the applied electric field promotes a zwitterionic resonance form, which ensures a lower energy transition state for the isomerization reaction. The field also stabilizes the trans form, relative to the cis, dictating the cis/trans thermodynamics, driving the equilibrium product exclusively toward the trans.