The catalytic hydrogenolysis of compounds derived from guaiacol on the Cu (111) surface: mechanisms from DFT studies.

Pyrolysis oils have inferior properties compared to liquid hydrocarbon fuels, owing to the presence of oxygenated compounds such as guaiacol, C6H4(OH)(OCH3). The catalytic hydro-deoxygenation (HDO) of phenolic compounds derived from guaiacol, i.e. catechol, phenol and anisole were investigated over the Cu (111) surface to unravel the elementary steps involved in the process of bio-oil upgrade. The phenolic compounds adsorb through their π systems to the surface, where steric effects of the methoxy group reduce the stability of anisole on the surface. To produce benzene, hydroxyl removal from catechol and phenol occurs in a stepwise fashion, where dehydroxylation of catechol is more challenging than phenol. Thermodynamically, catechol is the preferred oxygenated product, but it is the most challenging to transform to benzene, requiring an energy barrier of 1.8 eV to be overcome, which is similar to the HDO of anisole with an activation energy of 1.7 eV but more difficult than the HDO of phenol with an activation energy of 1.2 eV. The rate limiting steps in the HDO reactions are catechol dehydroxylation, anisole demethoxylation and phenol dehydroxylation. Our results show that ortho substituents impede C-O bond cleavage, as seen for catechol, whereas in the absence of an ortho substituent -OH cleavage is easier than -OCH3 cleavage to form benzene.

Ab initio investigation of O2 adsorption on Ca-doped LaMnO3 cathodes in solid oxide fuel cells.

We present a Hubbard-corrected density functional theory (DFT+U) study of the adsorption and reduction reactions of oxygen on the pure and 25% Ca-doped LaMnO3 (LCM25) {100} and {110} surfaces. The effect of oxygen vacancies on the adsorption characteristics and energetics has also been investigated. Our results show that the O2 adsorption/reduction process occurs through the formation of superoxide and peroxide intermediates, with the Mn sites found to be generally more active than the La sites. The LCM25{110} surface is found to be more efficient for O2 reduction than the LCM25{100} surface due to its stronger adsorption of O2, with the superoxide and peroxide intermediates shown to be energetically more favorable at the Mn sites than at the Ca sites. Moreover, oxygen vacancy defect sites on both the {100} and {110} surfaces are shown to be more efficient for O2 reduction, as reflected in the higher adsorption energies calculated on the defective surfaces compared to the perfect surfaces. We show from Löwdin population analysis that the O2 adsorption on the pure and 25% Ca-doped LaMnO3 surfaces is characterized by charge transfer from the interacting surface species into the adsorbed oxygen πg orbital, which results in weakening of the O-O bonds and its subsequent reduction. The elongated O-O bonds were confirmed via vibrational frequency analysis.

Water-soluble SNS cationic palladium(II) complexes and their Suzuki-Miyaura cross-coupling reactions in aqueous medium.

Unlike their SCS analogues, SNS pincer complexes are poorly studied for their use in coupling reactions. Accordingly, a series of water soluble cationic Pd(II) SNS pincer complexes have been successfully synthesised and investigated in detail for their catalytic activity in Suzuki-Miyaura coupling reactions. By using only 0.5 mol % loading of the complexes, the coupling of inactivated aryl bromides and activated aryl chlorides with various boronic acids in water was achieved in excellent yields and the catalysts were found to be reusable for three cycles without a significant loss of activity. The investigation of the mechanism of the reaction revealed that a Pd(II) to Pd(IV) route is the more likely pathway which was further supported by computational studies.

CO2 activation and dissociation on the low miller index surfaces of pure and Ni-coated iron metal: a DFT study.

We have used spin polarized density functional theory calculations to perform extensive mechanistic studies of CO2 dissociation into CO and O on the clean Fe(100), (110) and (111) surfaces and on the same surfaces coated by a monolayer of nickel. CO2 chemisorbs on all three bare facets and binds more strongly to the stepped (111) surface than on the open flat (100) and close-packed (110) surfaces, with adsorption energies of -88.7 kJ mol-1, -70.8 kJ mol-1 and -116.8 kJ mol-1 on the (100), (110) and (111) facets, respectively. Compared to the bare Fe surfaces, we found weaker binding of the CO2 molecules on the Ni-deposited surfaces, where the adsorption energies are calculated at +47.2 kJ mol-1, -29.5 kJ mol-1 and -65.0 kJ mol-1 on the Ni-deposited (100), (110) and (111) facets respectively. We have also investigated the thermodynamics and activation energies for CO2 dissociation into CO and O on the bare and Ni-deposited surfaces. Generally, we found that the dissociative adsorption states are thermodynamically preferred over molecular adsorption, with the dissociation most favoured thermodynamically on the close-packed (110) facet. The trends in activation energy barriers were observed to follow that of the trends in surface work functions; consequently, the increased surface work functions observed on the Ni-deposited surfaces resulted in increased dissociation barriers and vice versa. These results suggest that measures to lower the surface work function will kinetically promote the dissociation of CO2 into CO and O, although the instability of the activated CO2 on the Ni-covered surfaces will probably result in CO2 desorption from the nickel-doped iron surfaces, as is also seen on the Fe(110) surface.

A DFT+U investigation of hydrogen adsorption on the LaFeO3(010) surface.

The ABO3 perovskite lanthanum ferrite (LaFeO3) is a technologically important electrode material for nickel-metal hydride batteries, energy storage and catalysis. However, the electrochemical hydrogen adsorption mechanism on LaFeO3 surfaces remains under debate. In the present study, we have employed spin-polarized density functional theory calculations, with the Hubbard U correction (DFT+U), to unravel the adsorption mechanism of H2 on the LaFeO3(010) surface. We show from our calculated adsorption energies that the preferred site for H2 adsorption is the Fe-O bridge site, with an adsorption energy of -1.18 eV (including the zero point energy), which resulted in the formation of FeOH and FeH surface species. H2 adsorption at the surface oxygen resulted in the formation of a water molecule, which leaves the surface to create an oxygen vacancy. The H2 molecule is found to interact weakly with the Fe and La sites, where it is only physisorbed. The electronic structures of the surface-adsorption systems are discussed via projected density of state and Löwdin population analyses. The implications of the calculated adsorption strengths and structures are discussed in terms of the improved design of nickel-metal hydride (Ni-MH) battery prototypes based on LaFeO3.

A density functional theory study of arsenic immobilization by the Al(III)-modified zeolite clinoptilolite.

We present density functional theory calculations of the adsorption of arsenic acid (AsO(OH)3) and arsenous acid (As(OH)3) on the Al(III)-modified natural zeolite clinoptilolite under anhydrous and hydrated conditions. From our calculated adsorption energies, we show that adsorption of both arsenic species is favorable (associative and exothermic) under anhydrous conditions. When the zeolite is hydrated, adsorption is less favourable, with the water molecules causing dissociation of the arsenic complexes, although exothermic adsorption is still observed for some sites. The strength of interaction of the arsenic complexes is shown to depend sensitively on the Si/Al ratio in the Al(III)-modified clinoptilolite, which decreases as the Si/Al ratio increases. The calculated large adsorption energies indicate the potential of Al(iii)-modified clinoptilolite for arsenic immobilization.

Chem4Energy: a consortium of the Royal Society Africa Capacity-Building Initiative.

The Africa Capacity-Building Initiative is a Royal Society programme funded by the former UK Department for International Development to develop collaborative research between scientists in sub-Saharan Africa and the UK. Initially, four institutions were involved in the Chem4Energy consortium: Cardiff University in the UK and three African partners, the Kwame Nkrumah University of Science and Technology, Ghana, the University of Namibia and the University of Botswana, soon also including the Botswana International University of Science and Technology. The Chem4Energy research programme focused on 'New materials for a sustainable energy future: linking computation with experiment', aiming to deploy the synergy between state-of-the-art computational and experimental techniques to design and optimize new catalysts and semiconductor materials for renewable energy applications, based on materials that are abundant and readily available in African countries. The Chem4Energy consortium has achieved ambitious research goals, graduated seven PhD students and delivered a high-quality cross-disciplinary training programme in materials science and simulation techniques relevant to renewable energy applications. Since 2021, the extended consortium, including North-West University and the Centre for High-Performance Computing in South Africa, has remained active through an annual Chem4Energy conference series, with the sixth meeting taking place in Namibia in April 2025.

Quantum Mechanical Elucidation on [3+2] cycloaddition reaction of aryl nitrile oxide with cyclopentenones.

The [3 + 2] cycloaddition (32CA) reaction of benzonitrile oxide (BNO) with 4-substituted 4-hydroxy-2-cyclopentenone has been investigated using molecular electron density theory (MEDT) at the Density Functional Theory (DFT) B3LYP/6-31G (d), M06/6-311G (d,p) and M06-2X/6-311++G (d,p) levels. The present theoretical computations indicate that the reaction of BNO with 4-substituted 4-hydroxy-2-cyclopentenones is via [3 + 2] cycloaddition, where the three atom component (TAC) chemo-selectively adds across the alkene functionality in the 2-cyclopentenones (Path A). Analysis of the electrophilic PA+ and nucleophilic PA- Parr functions at the different reaction sites in the alkene counterpart indicates that the aryl nitrile oxides add across the atomic centers with the highest Mulliken atomic spin densities. The results reported in this study are in good agreement with previous experimental work. The GEDT calculations unravel the low polar character of the [3 + 2] cycloaddition reactions. This reaction occurs with poor enantioselectivity, but a high degree of stereo-, peri-, diastereo, and regioselectivity is seen for the reaction of the BNO with 4-hydroxy-4-methyl-2-cyclopentenones. The regioselectivity of the reactions is the same in all the solvents investigated.

Exploring the peri- and stereo- selectivities of the cycloaddition reaction of 2-(2- dimethylaminovinyl)-1-benzopyran-4-one with N-phenylmaleimide (NPM) and dimethylacetylenedicarboxylate (DMAD) - A DFT study.

The [4 + 2] cycloaddition reactions of 2-styrylchromones have been predominantly described as one of the efficient methods for the synthesis of xanthones-a prominent class of tricyclic molecules that occur widely in nature. These xanthones are well known for their pharmacological activities especially their role as anti-cancer agents in the medicinal world. In this study, the mechanistic insight into the unusual (peri- and stereo-) selectivities of the reaction of 2-(2-dimethylaminovinyl)-1-benzopyran-4-one (A1) with N-phenylmaleimide (NPM) and dimethylacetylenedicarboxylate (DMAD) has been studied using density functional theory (DFT) at the M06-2X/6-311G (d, p) level of theory. The reaction of A1 and NPM in dimethylformamide (DMF) is periselective towards the initial formation of a [4 + 2] cycloadduct and stereoselectively in an exo fashion with an activation energy of 6.8kcalmol-1 and a rate constant of 6.43×107s-1 which occurs about 878 million times faster than the closest competing pathway for the initial [2 + 2] cycloaddition fashion with an activation energy of 19.0kcalmol-1 and a rate constant of 7.32×10-2s-1. For the substituent effect on the reaction, the reaction selectivity is still maintained where the exo intermediate remains the most kinetically favored cycloadduct. However, the magnitude of the barriers increases slightly with a margin of about 0.1-4.8kcalmol for the electron-donating groups (EDGs) in the order; strong EDGs (OH < NH2 < OCH3) < weak EDGs (

A quantum mechanistic insight into the chemo- and regio-selective [3 + 2]-cycloaddition reaction of aryl hetaryl thioketones with diazoalkanes and nitrile oxide derivatives.

In this quantum mechanistic study, density functional theory computations at the B3LYP hybrid level of theory, in addition to triple zeta basis set 6-311G (d, p), were utilized to investigate the chemoselectivities and regioselectivities of the [3 + 2] cycloaddition reaction of phenyl (2-thienyl) thioketone (B1) derivatives with nitrile oxide (B2) and diazopropane derivatives (B3). From the computations obtained, the reactions of nitrile oxide and diazopropane derivatives with phenyl (2-thienyl) thioketone proceed through an asynchronous one-step mechanism. The initial [3 + 2] cycloaddition reaction of B1 and B3 is followed by a nitrogen extrusion which is also highly asynchronous. Despite the steric and electronic effects of the substituent on the energetics, the reaction center is selectively observed at the thiocarbonyl site of B1. A study of the Parr functions at the different reaction sites in B1 indicates the addition of B2 and B3 via the atomic centers with the largest Mulliken atomic spin densities. These results show that the thiocarbonyl site is the most reactive center compared to the other ethylene groups on B1, irrespective of the three atom components used. The global electron density transfer results are in agreement with the selectivity and activation barriers observed in the reaction. Our results agree well with experimental observations.

A DFT Mechanistic Study on Base-Catalyzed Cleavage of the ß-O-4 Ether Linkage in Lignin: Implications for Selective Lignin Depolymerization.

The detailed mechanism of the base-catalyzed C-C and C-O bond cleavage of a model compound representing the ß-O-4 linkage in lignin is elucidated using DFT calculations at the M06/6-31G* level of theory. Two types of this linkage have been studied, a C2 type which contains no γ-carbinol group and a C3 type which contains a γ-carbinol. Cleavage of the C2 substrate is seen to proceed via a 6-membered transition structure involving the cation of the base, the hydroxide ion and the α-carbon adjacent to the ether bond. The reaction with KOH has the lowest activation barrier of 6.1 kcal mol-1 with a calculated rate constant of 2.1 × 108 s-1. Cleavage of the C3 substrate is found to proceed via two pathways: an enol-formation pathway and an epoxide-formation pathway. The first path is the thermodynamically favored pathway which is similar to the pathway for the C2 substrate and is the preferred pathway for the isolation of an enol-containing monomer. The second path is the kinetically favored pathway, which proceeds via an 8-membered transition state involving a hydrogen hopping event, and is the preferred pathway for the isolation of an epoxide-containing monomer. The KOH-catalyzed reaction also has the lowest activation barrier of 10.1 kcal mol-1 along the first path and 3.9 kcal mol-1 along the second path, with calculated rate constants of 2.4 × 105s-1 and 8.6 × 109s-1 respectively. Overall, the results provide clarity on the mechanism for the base-catalyzed depolymerization of lignin to phenolic monomers. The results also suggest both NaOH and KOH to be the preferred catalysts for the cleavage of the ß-O-4 linkage in lignin.

A DFT mechanistic study on oxidative dehydrogenative Diels-Alder reaction of alkylbenzenes.

Cross-dehydrogenative Diels-Alder cycloaddition reaction between readily-available alkyl benzenes and electron-deficient dienophiles is an attractive synthetic route to access carbocyclic compounds which have high utility in the chemical and pharmaceutical industries. This work reports a study at the M06-2X/6-311G(d) and M06-2X/6-311++G(d,p) levels of theory on the reaction of alkyl benzenes with electron-deficient dienophiles in the presence of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as an oxidant and hydroquinone as an activator, so as to understand the chemoselectivity of the reaction (addition across the alkene functionality versus the ketone functionality), the role of the activator, the effects of substituents and the effect of solvent on the reaction. The results show the addition of the alkene bonds of methylstyrene across the alkene functionality of the electron-deficient dienophiles has generally low barriers compared to the addition across the carbonyl functionality of the electron-deficient dienophile. Powerful electron-withdrawing group (cyano) on the electron-deficient dienophile decrease the energy barrier for the cycloaddition and decrease the stability of the product whiles weak electron-withdrawing (bromine and chlorine) and electron-donating groups increase the energy barrier for the cycloaddition and decrease the stability of the product. The hydroquinone as an activator decreases the activation barrier for the Diels-Alder cycloaddition reaction.

Exploring the chemo-, regio-, and stereoselectivities of the (3 + 2) cycloaddition reaction of 5,5-dimethyl-3-methylene-2-pyrrolidinone with C,N-diarylnitrones and nitrile oxide derivatives: a DFT study.

The (3 + 2) cycloaddition (32CA) reaction is an efficient method for the synthesis of many biologically active heterocyclic compounds, but there are several regio- and stereochemical issues that must be fully understood to exploit the full utility of its synthetic power. We herein explored the chemo-, regio-, and stereoselectivities of the 32CA reaction of 5,5-dimethyl-3-methylene-2-pyrrolidinone (B1) to C,N-diarylnitrones (B2), and nitrile oxide derivatives (B3) with DFT at the M06/6-311G(d,p) level of theory. The reactions occur via an asynchronous one-step mechanism, with the chemoselective addition of the C,N-diarylnitrones, and nitrile oxide derivatives across the olefinic bond of 5,5-dimethyl-3-methylene-2-pyrrolidinone being the most preferred kinetically and thermodynamically. The regio- and stereoselectivities of the reactions are affected by the electronic and steric nature of substituents on B2 but they are not affected by the electronic and steric nature of substituents on B3. The C,N-nitrones and the nitrile oxide derivatives add across the atomic centers with the largest atomic spin densities on 5,5-dimethyl-3-methylene-2-pyrrolidinone as seen through the local electrophilic ([Formula: see text]) and nucleophilic ([Formula: see text]) Parr functions of the various reaction centers. Results from the global electron density transfer (GEDT) reveal the low polar nature of the reactions.

A DFT study of the double (3 + 2) cycloaddition of nitrile oxides and allenoates for the formation of spirobiisoxazolines.

The molecular mechanism of the double (3 + 2) cycloaddition (32CA) reaction between nitrile oxides and allenoates has been studied using density functional theory at the M06-2X/6-311G (d,p) level of theory. In the first 32CA, the nitrile oxide adds chemo- and regio-selectively to the C-C double bond of the allenoate closest to the carboxylate group followed by a subsequent regioselective addition to the olefinic bond of the isoxazoline intermediate. The rate constant for the preferred pathway (formation of 4-methylene-2-isoxazoline intermediate) in the reaction of ethyl substituted allenoate and mesitonitrile oxide is 5.3 × 102 s-1 in THF which is about 13 times faster than the closest competing step (formation of its regioisomer 5-methylene-2-isoxazoline intermediate) which has a rate constant of 4.4 × 101 s-1. Strong electron-donating groups (EDGs) and electron-withdrawing groups (EWGs) decrease activation barriers and hence increase the reaction rate. Also, the dimerization of nitrile oxide to form furaxon is found to be kinetically unfavored.

Does the reaction of nitrone derivatives with allenoates proceed by an initial (3 + 2) cycloaddition or O-Nucleophilic addition? A quantum chemical investigation.

The question of whether the reaction between nitrone derivatives and allenoates proceeds with initial (3 + 2) cycloaddition (32CA) or the oxygen-nucleophilic (O-nucleophilic) addition has been theoretically investigated using density functional theory (DFT) at the M06-2X/6-311G(d,p) level of theory. In all of the reactions considered, the initial 32CA route is kinetically and thermodynamically preferred over the initial O-nucleophilic addition. Increasing the steric bulk of the substituents on the reactants bridges the kinetic and thermodynamic gap between the initial 32CA and O-nucleophilic addition but the 32CA is still energetically preferred, showing that with increasing steric bulk, the O-nucleophilic addition may become competitive with the 32CA route. Within the 32CA reactions, analysis of electrophilic (Pk+) and nucleophilic (Pk-) Parr functions at the various reaction centers in the allenoate indicates that the three-atom-components (TACs) chemo-selectively add across the olefinic bond bearing the ester functionality (COOMe) with the largest Mulliken spin density coefficients and this observation agrees with the energetic trends and experimental outcomes. The global electron density transfer (GEDT) analysis reveals a high polar character associated with the 32CA reaction of methylbuta-2,3-dienoate with N-methyl-C-phenylnitrone while that of the 32CA reaction of methylpenta-2,3-dienoate with N-cyclohexenylnitrone has a low polar character.

Investigating the site-, regio-, and stereo-selectivities of the reactions between organic azide and 7-heteronorbornadiene: a DFT mechanistic study.

The site-, regio-, and stereo-selectivities of the title reactions have been studied using density functional theory (DFT) at the M06/6-311G(d,p) level of theory. The effects of substituents on both the three-atom component (TAC) and norbornadiene derivatives have been investigated with a focus on the site-selectivity. The reaction of benzylazide with (1S,4R)-2-tosyl-7-oxabicyclo[2.2.1]hepta-2,5-diene and (1R,4S)-2-bromo-3-tosyl-7-oxabicyclo[2.2.1]hepta-2,5-diene proceeds via addition across the substituted olefinic bond of the two norbornadiene derivatives. Substituents on the TAC do not affect the selectivity of the reaction while substituents on the norbornadiene significantly affect the selectivity of the reaction. Benzylazide preferentially adds across the substituted olefinic bond of the norbornadiene derivative when strong electron-withdrawing group (EWGs) and electron-releasing group (ERGs) substituents are on the norbornadiene while weak ERGs and EWGs on the norbornadiene significantly decreases the site-selectivity such that addition across either double is no longer favored over the other. The formation of exo-cycloadducts is generally favored over the endo-cycloadducts. The reaction of benzylazide and norbornadiene derivatives is a highly irreversible exergonic reaction. The direction of electron density flux is dependent on the nature of the substituent on the reactants. Global reactivity indices and Parr function calculations are in good agreement with the activation barriers and the selectivity of the reactions.

Permanganyl chloride-mediated oxidation of tetramethylethylene: A density functional theory study.

The mechanisms of the oxidation of tetramethylethylene (TME) by permanganyl chloride (MnO3Cl) have been explored on the singlet and triplet potential energy surfaces at the B3LYP LANL2DZ/6-31G (d) level of theory. The results show that the pathway leading to the formation of the five-membered dioxylate through concerted [3 + 2] addition is favored kinetically and thermodynamically over the three other possible pathways, namely the [2 + 2] addition via the transient metallaoxetane intermediate, epoxidation, and hydrogen transfer pathways. The epoxide precursor that on hydrolysis would yield the epoxide product will most likely arise from a stepwise path through the intermediacy of an organometallic intermediate. This pathway affords the product that is more stable (thermodynamically favorable). However, kinetically, both the stepwise and the concerted [2 + 1] addition pathways leading to the epoxide precursors are very competitive (activation barrier difference of <0.7 kcal/mol).

(3 + 2) cycloaddition reaction of 7-isopropylidenebenzonorbornadiene and diazomethane derivatives: A theoretical study.

The ability to synthesize targeted molecules hinges on detailed mechanistic insight of the reaction. The 1,3-dipolar cycloaddition reaction between diazomethane derivatives and 7-isopropylidenebenzonorbornadiene have been extensively studied using density functional theory (DFT) at the M06-2X/6-311G(d,p) level of theory in order to delineate the peri-, regio-, and stereo-selectivities of the reaction. The diazomethane is shown to periselectively add across the endocyclic olefinic bond of the 7-isopropylidenebenzonorbornadiene and stereoselectively in the exo fashion, yielding the exo-cycloadduct as the major product, with a rate constant of 3.83 × 104 s-1. The endo approach of this periselective path is the closest competing pathway with a rate constant of 8.78 × 101 s-1. Neither electron-donating groups (R = methyl, ethyl, amine, cyclopropyl) nor electron-withdrawing groups (R = cyano, nitro, carbonyl) on the diazomethane alters the peri- and stereo-selectivity of the reaction. However, the substituents do have an effect on whether the addition follow normal or inverse electron demand mechanisms. EDGs favor a normal electron demand mechanism while EWGs favor an inverse electron demand 1,3-dipolar cycloaddition reaction. While EDGs-substituted diazomethane derivatives behave as nucleophiles in reactions with 7-isopropylidenebenzonorbornadiene, EWGs-substituted diazomethane derivatives behave as electrophiles. The 1,3-dipole adds across the dipolarophile via a concerted asynchronous mechanism, but a stepwise diradical mechanism has been ruled out. The selectivities observed in the title reaction are kinetically controlled. Analysis of the nucleophilic Parr function (PK-) at the different reaction sites in the dipolarophile indicates that the diazomethane adds across the atomic centers with highest NBO and Mulliken atomic spin densities.

Computational study on the mechanism of the reaction of benzenesulfonyl azides with oxabicyclic alkenes.

The reaction of benzenesulfonyl azides with oxabicyclic alkenes to form aziridines could either proceed via initial [3 + 2] cycloaddition to form triazoline intermediates which then leads to aziridines, or via initial dinitrogen cleavage of the benzenesulfonyl azide to afford a nitrene intermediate followed by addition of this nitrene species across the olefinic C-C bond of the oxabicyclic alkene. Calculations at the DFT M06-2X/6-311G(d,p) level indicate that the initial [3 + 2] cycloaddition reaction of benzenesulfonyl azide and oxabicyclic alkene has barriers of 15.0 kcal/mol (endo) and 10.3 kcal/mol (exo) and rate constants of 5.23 × 103 s-1 (endo) and 3.86 × 106 s-1 (exo) whereas the pathway involving initial formation of nitrene species has a high activation barrier of 39.2 kcal/mol and rate constant of 8.92 × 10-12 s-1, indicating that the reaction will go through the former route to form an exo triazoline intermediate. The exo triazoline can either undergo a concerted C-C, N-N bond cleavage to form a ring-opened intermediate, a reaction that has a barrier of 23.4 kcal/mol, followed by dinitrogen extrusion and C-C, C-N bond regeneration with barriers of 29.1 and 23.5 kcal/mol respectively to form endo aziridines, or it can undergo direct nitrogen extrusion to form the exo product, a reaction with a barrier of 38.3 kcal/mol. Since the rate-determining step of the former route is 9.2 kcal/mol more favored than the latter, the former route rate is favored. The rate constants of the rate-determining steps are 1.30 × 10-5 s-1 (endo) and 3.16 × 10-11 s-1 (exo), indicating that endo aziridine would be formed as the major product and this is in conformity with the experimental observations of Chen et al. (J. Org. Chem. 18:11863-11872, 2019). The position of substituents on the benzene group of the benzenesulfonyl azide affects the endo/exo diastereoselectivity.Graphical abstract.

Investigating the regio-, stereo-, and enantio-selectivities of the 1,3-dipolar cycloaddition reaction of C-cyclopropyl-N-phenylnitrone derivatives and benzylidenecyclopropane derivatives: A DFT study.

The biomedical importance of spirocyclopropane isoxazolidine derivatives is widely known. The 1,3-dipolar cycloaddition (1,3-DC) of C-cyclopropyl-N-phenylnitrone derivative and benzylidenecyclopropane derivatives leading to the formation of 5- and 4-spirocyclopropane isoxazolidines derivatives have been studied using density functional theory (DFT) at M06-2X/6-311G (d,p) level of theory. An extensive exploration of the potential energy surface shows that the 1,3-dipole adds across the dipolarophile via an asynchronous concerted mechanism. While electron-donating groups (EDGs) on the benzylidenecyclopropane favor the formation of the 4-spirocyclopropane isomer, electron-withdrawing groups (EWGs) favor the reaction channels that furnish the 5-spirocyclopropane isoxazolidine isomer. Both EWDs and EDGs on the 1,3-dipole favor the formation of the 5-spirocyclopropane isoxazolidine isomer. Irrespective of the electronic nature of substituents on the C-cyclopropyl-N-phenylnitrone, the reaction channels that regioselectively lead to the formation of the 5-spirocyclopropane isoxazolidine isomer are favored. In all reactions considered, the channels that selectively lead to the formation of the cis-diastereoisomers proceed with lower activation barriers than the trans-diastereoisomers. In all cases, the observed selectivities in the title reaction are kinetically controlled.