Unveiling the Mechanism and Stereochemical Pathways for BF 3 - mediated [3+2] Cycloaddition of N-boranonitrone with Alkenes: A DFT Study

Unveiling the Mechanism and Stereochemical Pathways for BF 3 - mediated [3+2] Cycloaddition of N-boranonitrone with Alkenes: A DFT Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Unveiling the Mechanism and Stereochemical Pathways for BF 3 - mediated [3+2] Cycloaddition of N-boranonitrone with Alkenes: A DFT Study Ravi Bariya, Ankit Patel, Sangita Sharma This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7581670/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract In this work, we present a density functional theory (DFT) investigation of the BF 3 -mediated [3 + 2] cycloaddition (32CA) of N-boranonitrone ( 6a) with three representative alkenes (styrene 7a , n-hexene 7b , and ethyl methacrylate 7c ). Calculations were carried out using hybrid meta-GGA M06-2X functional using standard 6–31 + G(d,p) basis set in both gas phase and dichloroethane solution using the PCM model. The reaction proceeds through a concerted one-step mechanism with two stereoisomeric pathways (endo/cis and exo/trans). Activation energy analyses reveal that the exo approach consistently provides lower barriers (by 1.4–3.4 kcal·mol⁻¹) than the endo pathway, in agreement with the experimentally observed predominance of trans cycloadducts. Bond orders and distances indicate asynchronous bond formation, with small differences between C–O and C–C bond development depending on the substrate, while ELF analysis confirms electron localization patterns characteristic of this process. Global reactivity descriptors show that N-boranonitrone acts as the electrophile, whereas the alkenes act as the nucleophiles. Noncovalent interaction (NCI) analysis highlights stabilizing attractive interactions in the exo transition states that further rationalize the stereochemical preference. [3 + 2] cycloaddition DFT ELF analysis stereoselectivity noncovalent interactions Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction [3 + 2] Cycloaddition (32CA) reactions are versatile synthetic methods for the preparation of five membered heterocycles (e.g. isoxazolidine ring system) [ 1 – 5 ]. Many experimental studies have shown the use of nitrone tautomers of oxime as dienophiles in the 32CA reaction for the synthesis of biologically active nitrogen containing compounds [ 6 , 7 ]. Despite this versatile reactivity, many oxime derivatives are not useful dienophiles in 32CA because of thermodynamically unfavorable tautomerization from oxime 1 to nitrone 2 (see Scheme 1 ) [ 8 ]. The use of oxime as dienophile in the 32CA reaction requires relatively high temperature and long reaction time [ 9 ]. The use of transition metal catalysts e.g. palladium (II)[ 10 ] salts has also been reported to promote the 32CA reaction of oxime with alkene (see Scheme 2 ). Unfortunately, palladium (II) salts are applicable only to a limited range of activated olefins such as N-methyl or N-phenylmaleimide. To overcome these limitations, a diverted synthetic route is needed. Tamura and coworkers[ 11 ] experimentally studied a highly efficient BF 3 -mediated cycloaddition of O-tert-butyldimethyl-silyloximes (O-TBS) 6 with alkene 7 to provide N-nonsubstituted isoxazolidines. Treatment of O-tert-butyldimethylsilyloximes (O-TBS) 6 with alkene 7 in the presence of BF 3 8 at 60°C temperature smoothly produced the mixture of stereoisomers of corresponding isoxazolidines via N-boranonitrone 6a as active intermediates (See Scheme 3 ). This procedure effectively generates the nitrone intermediate (N-boranonitrone 6a) by utilizing the strong N–B[ 12 – 14 ] and Si–F affinities. In the recent years, the reactivity of various newly synthesized nitrones has been studied theoretically, particularly via 32CA reactions. Nacereddine and coworkers[ 15 ] conducted a theoretical study on stereoselective BF 3 catalyzed 32CA reaction between nitrone isomers of methyl glyoxylate oxime 10 and cyclopentene 11 (see Scheme 4 ). In this study, the authors reveal that the reaction proceeds via two stereoisomeric pathways: the endo and exo approaches. The difference in energies for the transition states shows that the major isomer is the exo cycloadduct. Umar and coworkers[ 16 ] performed theoretical calculations to examine the stereoselectivity of the reactions of nitrone derived from adamantine with the alkene (e.g. maleimides) for the synthesis of a compound that contains both isoxazolidine and adamantane units. The authors revealed that the stereochemistry of the reaction is kinetically controlled and that the substituents on the dipolarophile decrease the activation energy of the diastereomeric isomers. Therefore, the substituents affect the activation energy and the stability of the reaction products of nitrone with maleimide. In this work, we present an M06-2X/6–31 + G(d,p) computational investigation of the 32CA reaction of an active intermediate, N-boranonitrone 6a (generated in situ by the reaction of O-TBS 6 with BF 3 8 ) with electron rich alkenes. For this purpose, the 32CA reaction between N-boranonitrone 6a and alkenes ( 7a : styrene; 7b : n-Hexene; and 7c : ethyl methacrylate) which was experimentally studied by Tamura and coworkers [ 11 ], is analyzed. Computational methods DFT calculations were carried out using the M06-2X, hybrid meta-GGA density functional[ 17 ] together with the standard 6–31 + G(d,p) basis set [ 18 , 19 ]. The stationary points were characterized by frequency calculations to verify that the transition states (TSs) had only one imaginary frequency. The intrinsic reaction coordinate (IRC)[ 20 , 21 ] has been further performed to check the energy profiles connecting each TS to the two associated minima for the proposed 32CA reaction. The electronic structures of stationary points were analyzed by the natural bond orbital (NBO)[ 22 ] method. The solvent effects of dichloroethane (DCE) were considered at the same level of theory by performing geometry optimization calculations of the gas-phase structures using a self-consistent reaction field (SCRF)[ 23 ] based on the polarizable continuum model (PCM)[ 24 ] of Tomasi's group. All calculations were carried out with the Gaussian 16 suite of programs [ 25 ]. ELF[ 26 , 27 ] topological analyses were performed with the Multiwfn Version 3.8 package [ 28 ]. The global electrophilicity index, ω , was calculated by the following expression [ 29 ], ω = (µ 2 /2η) , in terms of the electronic chemical potential µ and the chemical hardness η . Both properties can be expressed in terms of the energies of the frontier molecular orbitals HOMO ( ε H ) and LUMO ( ε L ), as µ ≈ ( ε H + ε L )/2 and η ≈ ( ε L - ε H ) respectively [ 30 ]. The nucleophilicity index, N [ 31 ], was calculated by the following expression, N = ε H( Nu ) -ε H( TCE) , where tetracyanoethylene (TCE) is chosen as reference. Results and Discussion The primary aim of this work is to provide a theoretical explanation for the mechanism and stereoselectivity observed in the reaction between N-boranonitrone 6a and alkenes 7a-c , as depicted Scheme 3 . To achieve this, we employed several computational approaches, including the evaluation of activation energies, frontier molecular orbital (FMO) analysis, and the use of electrophilic ( Pk⁺ ) and nucleophilic ( Pk⁻ ) Parr functions derived from spin electron-density variations. It should be emphasized that this reaction is governed by kinetic control, meaning the outcome is largely determined by the relative activation barriers of the competing pathways. 32CA Reaction of N-boranonitrone 6a with Alkenes 7a-c The 32CA reaction between N-boranonitrone 6a and alkenes 7a-c can take place along two stereoisomeric pathways namely the endo and exo approaches (see Scheme 5 ). Analysis of the stationary points involved in these two stereoisomeric pathways indicate that this 32CA reaction takes place along a one-step mechanism. Consequently, two stereoisomeric transition states (TSs) and their corresponding [3 + 2] cycloadducts (CAs) associated with the exo and endo approaches were located and characterized. Endo approach yields the cis cycloadduct CAn-cis via transition state TSn-cis while the exo approach yields trans cycloadduct CAn-trans by transition state TSn-trans. All the energetic parameters for the 32CA reaction between N-boranonitrone 6a and alkenes 7a–c are shown in Table 1 . Table 1 Energetic parameters for [3 + 2] cycloaddition reactions between N-boranonitrone 6a and alkenes 7a–c at the M06-2X/6–31 + G(d,p) computational study. Points ∆E [a] (gas−phase) ∆E [b] (DCE) ∆G [c] ∆H [d] ∆S [e] 1 TS 1 -cis 20.8 20.0 34.2 22.1 -40.5 TS 1 -trans 17.4 16.9 31.1 18.7 -41.6 CA 1 -cis -26.4 -22.1 -10.1 -22.1 -40.3 CA 1 -trans -27.7 -24.0 -12.9 -23.7 -36.2 2 TS 2 -cis 18.5 19.3 33.1 19.3 -46.3 TS 2 -trans 16.4 16.9 31.2 17.2 -46.8 CA 2 -cis -31.1 -27.5 -14.5 -27.5 -43.5 CA 2 -trans -29.9 -27.2 -14.2 -26.3 -40.5 3 TS 3 -cis 16.8 17.0 32.4 17.6 -49.8 TS 3 -trans 15.2 16.8 31.0 16.1 -50.1 CA 3 -cis -23.9 -21.5 -9.2 -20.8 -39.1 CA 3 -trans -27.6 -23.8 -12.4 -24.4 -40.3 All the properties are relative to reactants. [a] electronic energies in the gas phase. [b] electronic energies in (CH 2 Cl) 2 [c] Gibbs free energy change [d] enthalpy change [e] entropy change. All energies are in kcal·mol − 1 , and the entropies are in cal·mol⁻¹·K⁻¹. The relative gas phase activation energies associated with this 32CA reaction between N-boranonitrone 6a and styrene 7a are: 20.8 (TS 1 -cis) and 17.4 (TS 1 -trans) kcal mol − 1 . The relative gas phase activation energy for the TSs associated with the trans isomer (TS 1 -trans) is 3.4 kcal mol − 1 lower than that for the TS associated with the cis approach (TS 1 -cis), which clearly indicates that this 32CA reaction yields the trans cycloadduct as the major isomer. The formation of cycloadducts is exothermic by -26.4 (CA 1 -cis) and − 27.7 (CA 1 -trans) kcal mol − 1 . The relative enthalpies, entropies and Gibbs free energies of the TSs and cycloadducts involved in the 32CA reaction between N-boranonitrone 6a and styrene 7a are summarized in Table 1 . Analysis of the activation enthalpies associated with the 32CA reaction of N-boranonitrone 6a and styrene 7a indicates that the more favorable approach is the exo mode which yields the trans isomer. The relative enthalpy change for the TS 1 -trans is 3.4 kcal mol − 1 lower than that for TS 1 -cis. The addition of the entropic contribution associated with this bimolecular process to the enthalpies increases the Gibbs activation free energy of this reactive path to 31.1 kcal mol − 1 , which remains more favorable than the endo approach mode (∆∆G = 3.1 kcal mol − 1 ). Consequently, the formation of the trans cycloadduct (CA 1 -trans) is clearly favored over the cis (CA 1 -cis), which is in good agreement with the experimental results. Similar results are also observed for the 32CA reaction of N-boranonitrone 6a and n-hexene 7b . The relative gas phase activation energies associated with the 32CA reaction between N-boranonitrone 6a with n-hexene 7b are: 18.5 (TS 2 -cis) and 16.4 (TS 2 -trans) kcal mol − 1 . The relative gas phase activation energy for TSs associated with the trans isomer (TS 2 -trans) is 2.1 kcal mol − 1 lower than that for the TS associated with the cis approach (TS 2 -cis), which clearly indicates that this 32CA reaction yields the trans cycloadduct as major isomer. The formation of cycloadducts is exothermic by -31.1 (CA 2 -cis) and − 29.9 (CA 2 -trans) kcal mol − 1 . The Relative enthalpies, entropies and Gibbs free energies of the TSs and cycloadducts involved in the 32CA reaction between N-boranonitrone 6a and n-hexene 7b are summarized in Table 1 . The Relative enthalpy change for TS 2 -trans is 2.1 kcal mol − 1 lower than TS 2 -cis indicating trans isomer is favored over cis isomer (TS 2 -trans = 17.2 and TS 2 -cis = 19.3). Analysis of the Gibbs free energies also revealed a similar trend. The Gibbs activation free energy of this reactive path is 31.2 kcal mol − 1 , which is more favorable than the endo approach mode (∆∆G = 1.9 kcal mol − 1 ). Consequently, the formation of the trans cycloadduct (CA 2 -trans) is clearly favoured over the cis cycloadducts (CA 2 -cis). We also performed calculation on the 32CA reaction of N-boranonitrone 6a with another alkene, ethyl methacrylate 7c . Analysis of the computational results revealed lower energies for the trans isomer, which clearly indicates the formation of the trans isomer over the cis in this 32CA reaction. The relative gas phase activation energies associated with the 32CA reaction between N-boranonitrone 6a and ethyl methacrylate 7c are: 16.8 (TS 3 -cis) and 15.2 (TS 3 -trans) kcal mol − 1 . The relative gas phase activation energy for TS associated with the trans isomer (TS 3 -trans) is 1.6 kcal mol − 1 lower than that for the TS associated with the cis approach (TS 3 -cis), which clearly indicates that this 32CA reaction yields the trans cycloadduct as the major isomer. The formation of cycloadducts is exothermic by -23.9 (CA 3 -cis) and − 27.6 (CA 3 -trans) kcal mol − 1 . Table 1 clearly shows that the relative enthalpy change for TS 3 -trans is 1.5 kcal mol − 1 lower than TS 3 -cis indicating trans isomer is favored over the cis isomer (TS 3 -trans = 16.1 and TS 3 -cis = 17.6). The Gibbs activation free energy of this reactive path is 31.0 kcal mol − 1 , which remains more favorable than the endo approach mode (∆∆G = 1.4 kcal mol − 1 ). Consequently, the formation of the trans cycloadduct (CA 3 -trans) is clearly favored over the formation of the cis cycloadduct (CA 3 -cis), which is in good agreement with the experimental results. NBO Analysis of the 32CA Reaction of N-boranonitrone 6a with alkenes 7a-c The geometries of the transition states (TSs) involved in the [3 + 2] cycloaddition (32CA) of N-boranonitrone 6a with alkenes 7a–c are shown in Fig. 1 . For the 32CA between N-boranonitrone 6a and styrene 7a , the forming C3–C5 and O1–C4 bond lengths at the TSs leading to CA 1 are 2.108 and 2.031 Å at TS 1 -cis, and 2.119 and 2.034 Å at TS 1 -trans, respectively. The extent of bond formation at the TSs can be evaluated by bond order (BO).[ 32 ] The BO values for the forming C3–C5 and O1–C4 bonds are 0.41 and 0.37 at TS 1 -cis, and 0.40 and 0.36 at TS 1 -trans, respectively. These results indicate that both bonds are only partially formed and that the process is asynchronous but nearly concerted. Interestingly, the bond distances suggest O–C formation is slightly more advanced, whereas the BO values show a small opposite bias toward C–C formation. Given the small magnitude of these differences, we conclude that both metrics consistently point to an asynchronous transition state with no strong preference for either bond. Analysis of charge transfer (CT) further characterizes the electronic nature of these cycloadditions: charge flows from styrene 7a to N-boranonitrone 6a by 0.07 e at both TS 1 -cis and TS 1 -trans. The small CT values account for the very low polar character of this 32CA between N-boranonitrone 6a and styrene 7a . For the 32CA reaction between N-boranonitrone 6a and n-hexene 7b , the forming C3–C5 and O1–C4 bond lengths at the TSs leading to CA 2 are 2.177 and 2.007 Å at TS 2 -cis, and 2.210 and 1.981 Å at TS 2 -trans, respectively. The corresponding bond order (BO) values are 0.37 and 0.38 at TS 2 -cis, and 0.38 and 0.34 at TS 2 -trans. These results show that both bonds are only partially formed and that the reaction proceeds through asynchronous transition states. While the bond distances suggest earlier formation of the O–C bond, the BO values show a small and inconsistent bias between the two bonds. Overall, the process can be described as nearly concerted with slight asynchronicity. Charge transfer (CT) analysis indicates electron flow from n-hexene 7b to N-boranonitrone 6a of 0.09 e at both TS 2 -cis and TS 2 -trans, confirming the very low polar character of this cycloaddition. For the 32CA reaction between N-boranonitrone 6a and ethyl methacrylate 7c , the forming C3–C5 and O1–C4 bond lengths at the TSs leading to CA 3 are 2.047 and 2.059 Å at TS 3 -cis, and 2.043 and 2.065 Å at TS 3 -trans, respectively. The BO values for these bonds are 0.44 and 0.35 at TS 3 -cis, and 0.45 and 0.33 at TS 3 -trans. Both the bond distances and BOs clearly indicate asynchronous bond formation in which C–C bond formation is more advanced than O–C. Thus, these TSs also correspond to nearly concerted but asynchronous processes. CT analysis shows electron transfer from ethyl methacrylate 7c to N-boranonitrone 6a of 0.03 e (TS 3 -cis) and 0.02 e (TS 3 -trans), confirming the very low polar character of this cycloaddition. ELF topological analysis of the reactants In 1990, Becke and Edgecombe developed the electron localization function (ELF) [ 32 ] which was later perfected by Silvi and Savin [ 33 ] in 1994. This ELF approach offers a very unique perspective on the distribution of electrons in a molecule by their localization rather than total electron density. Herein, the electronic structures of the four reagents, namely N-boranonitrone 6a and alkenes 7a-c , in the ground state are examined by the electron localization function topological analysis as depicted in Fig. 2 and the values of basin populations are shown in Table 2 . Two monosynaptic basins, V(O1) and V’(O1) have been discovered for N-boranonitrone 6a , which together integrate 5.59e, indicating the non-bonding electron density on the O1 oxygen atom. Moreover, the disynaptic basins, V(O1, N2) and V(N2,C3), integrate 1.71 e and 2.45 e, respectively, revealing the polar single bond connecting N2 and O1 and the double bond involving N2 and C3 in the molecular structure. In addition, two small monosynaptic basins V(C3) and V’(C3) which together integrate 0.72e on C3 shows the splitting of π lobes on the carbon side of the N = C bond. Table 2 ELF valence basin populations for reagents, N-boranonitrone 6a and alkenes ( 7a , 7b , and 7c ) in electrons e. calculated by M06-2x/6–31 + G(d,p). 6a 7a 7b 7c V(O1) 2.76 V’(O1) 2.83 V(O1,N2) 1.71 V(C3) 0.36 V’(C3) 0.36 V(N2,C3) 2.44 V(C4,C5) 1.73 1.74 1.74 V’(C4,C5) 1.73 1.73 1.74 In addition, the ELF analysis of styrene 7a revealed the presence of two disynaptic basins V(C4, C5) and V’ (C4, C5) with a population of 1.73e for each shows the presence of one double bond between C4 and C5. For n-hexene 7b , two disynaptic basins V(C4, C5) and V’(C4, C5) with a population of 1.74e and 1.73e respectively, shows the presence of one double bond between C4 and C5. For ethyl methacrylate 7c , two disynaptic basins V(C4, C5) and V’(C4, C5) with population of 1.74e for each one shows the presence of one double bond between C4 and C5 . DFT-based reactivity indices analysis of the reactants at the ground state Table 3 M06-2X/6–31 + G(d,p) electronic chemical potential ( µ , in eV), chemical hardness ( η , in eV), global electrophilicity ( ω , in eV), and global nucleophilicity (N, in eV), of reactants N-boranonitrone 6a and alkenes ( 7a , 7b , and 7c ) in the gas phase. µ ƞ ω N 6a -5.40 7.14 2.04 1.84 7a -4.01 7.25 1.11 3.18 7b -3.85 9.30 0.80 2.30 7c -4.61 8.61 1.23 1.90 Many theoretical studies[ 34 , 35 ] devoted to Diels–Alder and cycloaddition reactions have shown that the analysis of the reactivity indices defined within the conceptual DFT[ 36 , 37 ] are powerful tools to understand the reactivity in polar cycloadditions. The DFT reactivity indices, namely electronic chemical potential µ , chemical hardness ƞ , global electrophilicity ω , and global nucleophilicity, N, for N-boranonitrone 6a and alkenes ( 7a , 7b , and 7c ) are given in Table 3 . The electronic chemical potential µ of N-boranonitrone 6a is -5.40 eV, which is lower than that of alkenes ( 7a : -4.01, 7b : -3.85, 7c : -4.61) indicating that during a polar 32CA reaction, the CT takes place from alkene toward N-boranonitrone 6a , which is in good agreement with the CT observed at the TSs. N-boranonitrone 6a has a high electrophilicity ω index, 2.04 eV, being classified as strong electrophile within the electrophilicity scale.[ 38 ] On the other hand, it has low nucleophilicity N index, 1.84 eV being classified as marginal nucleophile.[ 39 ] On the other hand, alkenes ( 7a , 7b , 7c ) present a low electrophilicity indices, ω = 7a :1.11 eV, 7b :0.80 eV and 7c :1.23 eV, being classified as moderate electrophiles, but have high nucleophilicity N indices, N = 7a :3.18 eV, 7b :2.30 eV and 7c :1.90 eV, being classified as strong nucleophiles. Therefore, N-boranonitrone 6a will participate as an electrophile and alkenes 7a , 7b , and 7c will react as nucleophiles during 32CA reactions. Recently, Domingo and coworkers[ 40 ] introduced electrophilic, P k + , and nucleophilic, P k - , Parr functions. These functions are formulated on the basis of the atomic spin density distribution in the radical anion and radical cation of the neutral molecules. The electrophilic and nucleophilic Parr functions are obtained through the single-point energy computation of the Mulliken atomic spin density of the radical anion and the radical cation, respectively. The electrophilic P k + Parr functions of N-boranonitrone 6a and nucleophilic Parr functions P k - of alkenes 7a , 7b , and 7c were analyzed. They are presented in Fig. 3 . This figure reveals that the terminal O1 oxygen at N-boranonitrone 6a is the most electrophilic center of this molecule with P k + =0.348 whereas the C3 carbon is less electrophilic than the O1 atom (P k + =-0.169). On the other hand, the nucleophilic parr function, P k - for the C5 atom is 0.503 for 7a , 0.617 for 7b and 0.589 for 7c and the same for the C4 atom is -0.034 for 7a 0.351 for 7b and 0.331 for 7c . Analysis of this nucleophilic parr function P k - of alkenes ( 7a-c ) revealed that the C5 carbon of alkenes is more nucleophilic than the C4 carbon. Electron localization function study of the transition state involved in the 32CA reaction between N-boranonitrone 6a and alkenes 7a-c To describe the main path of the reaction mechanism, ELF analysis at the transition state involved in this 32CA reaction was performed. This analysis can reveal the regions of electron localization on the molecular surface and then specify the nature of the bonds between atoms. Figure 4 displays two planes (N2-C3-C5 and N2–O1-C4) of the 2D surface map for the formed TS 1 − 3 -trans involved in this 32CA reaction between N-boranonitrone 6a and alkenes 7a-c . The ELF plane was generated by selecting three successive atoms, and the map shows a significant variation in the electron localization density with a characteristic color code around the 3-atom plane [ 41 ]. As shown in Fig. 4 (1a,2a and 3a), the ELF maps revealed a symmetric distribution of electron density between the two carbon nuclei C3 and C5. The localization of the electron density along the internuclear axis reflects the incipient character of bond formation. Figure 4 (1b,2b and 3b) clearly shows that the O1–C4 interaction has a stronger tendency toward electron localization compared to the C3–C5. Owing to the high electronegativity and availability of low-lying empty orbitals, oxygen tends to polarize and attract electron density from C4 atom (note that nucleophilicity indices, N of alkenes 7a-c are higher than that of N-boranonitrone 6a. NCI analysis As proven in the previous section, the 32CA reaction between N-boranonitrone 6a and alkenes 7a-c yields the CA 1 − 3 -trans, resulting from the exo approach mode. Many previous theoretical studies confirmed that the selectivity approach is generally governed by covalent and noncovalent interactions.[ 42 , 43 ] To better understand the origin of the stereoselectivity in the studied 32CA reactions, noncovalent interaction (NCI) analysis was performed on the optimized transition states. The reduced density gradient (RDG) plots for the cis and trans conformations of TSs are shown in Fig. 5 . These plots provide a direct visualization of weak interactions by correlating the reduced density gradient with the sign(λ)ρ parameter. Negative values of sign(λ)ρ correspond to stabilizing attractive interactions (blue regions), whereas positive values represent repulsive or steric effects (red regions). Regions close to zero are generally associated with van der Waals interactions (green regions). A comparison between the cis and trans pathways revealed a clear difference in their interaction profiles. For the cis-configured transition states TS 1 − 3 –cis, the plots show scattered interaction points with limited clustering in the attractive region. Although some blue and green domains are observed, these are relatively weaker and not well-defined, suggesting that stabilization through noncovalent forces is modest. In contrast, the trans-configured transition states TS 1 − 3 –trans, exhibit stronger and more concentrated blue and green regions in the negative sign(λ)ρ domain. This indicates the presence of significant attractive interactions, which play a major role in stabilizing these geometries. The circled regions in the scatter plots highlight these zones of noncovalent stabilization. Furthermore, the trans pathways consistently display fewer points in the destabilizing (red) region, confirming a reduced steric penalty relative to the cis counterparts. These observations suggest that the enhanced stability of the trans transition states arises from a combination of stronger attractive noncovalent interactions and reduced steric repulsion. The overall effect is a lowering of the activation barrier, which explains why the trans products are predicted to dominate as the major outcome of the reaction. Conclusion The molecular mechanism and stereoselectivity of the BF 3 -mediated [3 + 2] cycloaddition (32CA) reaction between N-boranonitrone 6a and alkenes 7a–c has been studied theoretically using DFT at the M06-2X/6–31 + G(d,p) level. Several important conclusions can be drawn on the basis of our computational results. Our study revealed that the 32CA between N-boranonitrone 6a and alkenes 7a–c is stereoselective, with exo pathway being the most favorable. This pathway leads both kinetically and thermodynamically to the formation of the cycloadduct CA 1-3 -trans, which matches very well with the experimental outcomes. The low values of CT found at the corresponding TSs indicate the low polar character of this 32CA reaction. Study of the bond order (BO) of transition states (TSs) reveals that the 32CA reaction occurs through an asynchronous mechanism between N-boranonitrone 6a and alkenes 7a–c . Analysis of the DFT reactivity indices at the ground state of the reagents involved in this 32CA reaction indicates that alkenes 7a–c are nucleophiles and N-boranonitrone 6a is an electrophile. RDG-NCI analysis was used to determine van der Waals interactions and steric repulsive interactions which supports formation of trans isomer as major isomer. The inclusion of Solvent effects shows slight change in activation energy but decrease in exothermic character for this cycloaddition reaction. Declarations Ethical Approval Not applicable (This study does not involve human participants or animal experiments). Declaration of Competing Interest The authors declare no competing interests. Funding This manuscript did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Author Contribution Ravi Bariya: Writing-original draft, Visualization, Validation, Methodology, Formal analysis, Data curation. Ankit Patel: Methodology, Formal analysis. Sangita Sharma: Writing- review & editing, Supervision, Software, Resources, Investigation, Formal analysis, Conceptualization. Acknowledgement R.B. is grateful to Department of Chemistry, HNGU, Patan. for computational Facilities. Data Availability No datasets were generated or analysed during the current study. References Gothelf KV, Jørgensen KA (1998) Asymmetric 1,3-Dipolar Cycloaddition Reactions. 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Supplementary Files image1.png Scheme 1 oxime 1 nitrone 2 tautomerization. image2.png Scheme 2 Pd (II) catalyzed 32CA reaction. image3.png Scheme 3 Summary of experimental results for the 32CA reaction between O-TBS 6and alkenes 7a-c [11]. image4.png Scheme 4 BF 3 -catalysed 32 CA reaction between nitrone 10 and cyclopentene 11 studied by Nacereddine and co-workers [15]. image5.png Scheme 5Possible stereoselective pathways for the 32CA reaction between N-boranonitrone 6a and alkenes 7a-c. ElectronicSupplementaryMaterial.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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13:29:45","extension":"png","order_by":22,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":29598,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage8.png","url":"https://assets-eu.researchsquare.com/files/rs-7581670/v1/35ed6a25b2314cd5d19de754.png"},{"id":91870855,"identity":"4f5a505b-1e4e-4db8-a227-70cd4d966a2b","added_by":"auto","created_at":"2025-09-22 13:54:07","extension":"png","order_by":23,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":75612,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage9.png","url":"https://assets-eu.researchsquare.com/files/rs-7581670/v1/4e3d1c6e7731bb961d4d44a3.png"},{"id":91867878,"identity":"d388f952-8f4b-40a8-8298-36a9f8214d67","added_by":"auto","created_at":"2025-09-22 13:29:45","extension":"xml","order_by":24,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":135101,"visible":true,"origin":"","legend":"","description":"","filename":"71eeeeb4dfef4e3082b4a736f97213401structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7581670/v1/c1f15ca1caf6cdf7c2079a42.xml"},{"id":91867879,"identity":"b1e2d918-83ad-4750-ae5d-1addd2cd7269","added_by":"auto","created_at":"2025-09-22 13:29:45","extension":"html","order_by":25,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":147088,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7581670/v1/b10223bf8ad23602761a1bce.html"},{"id":91867844,"identity":"a674e45b-5330-4c25-b89e-61d917122e7c","added_by":"auto","created_at":"2025-09-22 13:29:45","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":137397,"visible":true,"origin":"","legend":"\u003cp\u003eM06-2X/6-31+G(d,p) optimized structures of the TSs of the 32CA reaction of N-boranonitrone \u003cstrong\u003e6a\u003c/strong\u003e with alkenes \u003cstrong\u003e7a-c\u003c/strong\u003e.\u003c/p\u003e","description":"","filename":"image6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7581670/v1/5a35334fe3fd45edfa83cb41.jpeg"},{"id":91869983,"identity":"762822e4-c7f9-4e6f-9f16-635bbc3630c4","added_by":"auto","created_at":"2025-09-22 13:45:45","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":125093,"visible":true,"origin":"","legend":"\u003cp\u003eELF basin attractor positions, together with the most representative valence basin populations.\u003c/p\u003e","description":"","filename":"image7.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7581670/v1/ba28e40243b887b0f59d28a4.jpeg"},{"id":91867855,"identity":"0e54e454-4a03-49b7-ae03-330f788ce313","added_by":"auto","created_at":"2025-09-22 13:29:45","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":730030,"visible":true,"origin":"","legend":"\u003cp\u003eThree-dimensional (3D) representations of the M06-2X/6-31+G(d,p) Mulliken atomic spin densities of radical anion (6a•\u003csup\u003e-\u003c/sup\u003e), radical cations (\u003cstrong\u003e7a\u003c/strong\u003e\u003csup\u003e•+\u003c/sup\u003e, \u003cstrong\u003e7b\u003c/strong\u003e\u003csup\u003e•+\u003c/sup\u003e, and \u003cstrong\u003e7c\u003c/strong\u003e\u003csup\u003e•+\u003c/sup\u003e), together with the electrophilic \u003cem\u003eP\u003c/em\u003e\u003csub\u003e\u003cem\u003ek\u003c/em\u003e\u003c/sub\u003e\u003csup\u003e\u003cem\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/em\u003e\u003c/sup\u003e\u003csup\u003e \u003c/sup\u003eParr functions of N-boranonitrone (\u003cstrong\u003e6a\u003c/strong\u003e), and the nucleophilic \u003cem\u003eP\u003c/em\u003e\u003csub\u003e\u003cem\u003ek\u003c/em\u003e\u003c/sub\u003e\u003csup\u003e\u003cem\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/em\u003e\u003c/sup\u003e Parr functions of alkenes \u003cstrong\u003e7a\u003c/strong\u003e, \u003cstrong\u003e7b\u003c/strong\u003e, and \u003cstrong\u003e7c\u003c/strong\u003e.\u003c/p\u003e","description":"","filename":"image8.png","url":"https://assets-eu.researchsquare.com/files/rs-7581670/v1/352324cecb721cb322344e07.png"},{"id":91867851,"identity":"e23b5e68-27a2-4953-a986-32e9bc396a7f","added_by":"auto","created_at":"2025-09-22 13:29:45","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":561486,"visible":true,"origin":"","legend":"\u003cp\u003eELF map of 3-atoms plane for TS\u003csub\u003e1-3\u003c/sub\u003e-trans, N2-C3-C5 (1a,2a,3a) plane and N2–O1-C4 (1b,2b,3b).\u003c/p\u003e","description":"","filename":"image9.png","url":"https://assets-eu.researchsquare.com/files/rs-7581670/v1/7d7556b66977fb43feee6424.png"},{"id":91868327,"identity":"13e3ff9f-94b6-4660-b8df-9423c51943cf","added_by":"auto","created_at":"2025-09-22 13:37:45","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":337615,"visible":true,"origin":"","legend":"\u003cp\u003eRDG scatter plots of transition states involved in this 32CA reaction between N-boranonitrone \u003cstrong\u003e6a\u003c/strong\u003e and alkenes \u003cstrong\u003e7a–c\u003c/strong\u003e.\u003c/p\u003e","description":"","filename":"image10.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7581670/v1/a65955022775ab657e8e8ff5.jpeg"},{"id":92332898,"identity":"7eb1732e-c5d2-4b0b-a729-287558d560b0","added_by":"auto","created_at":"2025-09-28 01:46:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2751670,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7581670/v1/c23a661f-2667-4449-9bb8-d0f5c045c603.pdf"},{"id":91867842,"identity":"730147eb-f9ec-4d46-82f7-06125fa1d639","added_by":"auto","created_at":"2025-09-22 13:29:45","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":12940,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScheme 1 \u003c/strong\u003eoxime \u003cstrong\u003e1\u003c/strong\u003e nitrone \u003cstrong\u003e2\u003c/strong\u003e tautomerization.\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-7581670/v1/e7efc8fd0f5dca70d62b752f.png"},{"id":91867843,"identity":"28283447-aaec-4d62-8efc-2f5d3a7f4eb6","added_by":"auto","created_at":"2025-09-22 13:29:45","extension":"png","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":30396,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScheme 2 \u003c/strong\u003ePd (II) catalyzed 32CA reaction.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-7581670/v1/c0d9cb97eb9d26723a077778.png"},{"id":91867847,"identity":"4852af15-b960-4787-93d4-f489ae483194","added_by":"auto","created_at":"2025-09-22 13:29:45","extension":"png","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":116443,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScheme 3 \u003c/strong\u003eSummary of experimental results for the 32CA reaction between O-TBS \u003cstrong\u003e6\u003c/strong\u003eand alkenes \u003cstrong\u003e7a-c\u003c/strong\u003e [11].\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-7581670/v1/55363a7901371e71624c1f90.png"},{"id":91868325,"identity":"20d9174a-be1c-4694-bd78-f35e77158a85","added_by":"auto","created_at":"2025-09-22 13:37:45","extension":"png","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":41308,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScheme 4\u003c/strong\u003e BF\u003csub\u003e3\u003c/sub\u003e-catalysed 32 CA reaction between nitrone \u003cstrong\u003e10\u003c/strong\u003e and cyclopentene \u003cstrong\u003e11\u003c/strong\u003e studied by Nacereddine and co-workers [15].\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-7581670/v1/b6dfeca02f59b9a9f20239d9.png"},{"id":91867852,"identity":"bd4804f2-f96d-4330-9d11-29e6f9f442fa","added_by":"auto","created_at":"2025-09-22 13:29:45","extension":"png","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":47014,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScheme 5\u003c/strong\u003ePossible stereoselective pathways for the 32CA reaction between N-boranonitrone \u003cstrong\u003e6a\u003c/strong\u003e and alkenes \u003cstrong\u003e7a-c\u003c/strong\u003e.\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-7581670/v1/d5f30d350eff7cda87da5e7f.png"},{"id":91868328,"identity":"d0d7a9ca-0d1b-414d-bab9-55f2f480391e","added_by":"auto","created_at":"2025-09-22 13:37:45","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":35922,"visible":true,"origin":"","legend":"","description":"","filename":"ElectronicSupplementaryMaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-7581670/v1/ef530e800864fd83f6038bae.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Unveiling the Mechanism and Stereochemical Pathways for BF 3 - mediated [3+2] Cycloaddition of N-boranonitrone with Alkenes: A DFT Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003e[3\u0026thinsp;+\u0026thinsp;2] Cycloaddition (32CA) reactions are versatile synthetic methods for the preparation of five membered heterocycles (e.g. isoxazolidine ring system) [\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Many experimental studies have shown the use of nitrone tautomers of oxime as dienophiles in the 32CA reaction for the synthesis of biologically active nitrogen containing compounds [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Despite this versatile reactivity, many oxime derivatives are not useful dienophiles in 32CA because of thermodynamically unfavorable tautomerization from oxime \u003cb\u003e1\u003c/b\u003e to nitrone \u003cb\u003e2\u003c/b\u003e (see Scheme \u003cspan refid=\"Sch1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The use of oxime as dienophile in the 32CA reaction requires relatively high temperature and long reaction time [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe use of transition metal catalysts e.g. palladium (II)[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] salts has also been reported to promote the 32CA reaction of oxime with alkene (see Scheme \u003cspan refid=\"Sch2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Unfortunately, palladium (II) salts are applicable only to a limited range of activated olefins such as N-methyl or N-phenylmaleimide. To overcome these limitations, a diverted synthetic route is needed.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eTamura and coworkers[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] experimentally studied a highly efficient BF\u003csub\u003e3\u003c/sub\u003e-mediated cycloaddition of O-tert-butyldimethyl-silyloximes (O-TBS) \u003cb\u003e6\u003c/b\u003e with alkene \u003cb\u003e7\u003c/b\u003e to provide N-nonsubstituted isoxazolidines. Treatment of O-tert-butyldimethylsilyloximes (O-TBS) \u003cb\u003e6\u003c/b\u003e with alkene \u003cb\u003e7\u003c/b\u003e in the presence of BF\u003csub\u003e3\u003c/sub\u003e \u003cb\u003e8\u003c/b\u003e at 60\u0026deg;C temperature smoothly produced the mixture of stereoisomers of corresponding isoxazolidines via N-boranonitrone \u003cb\u003e6a\u003c/b\u003e as active intermediates (See Scheme \u003cspan refid=\"Sch3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). This procedure effectively generates the nitrone intermediate (N-boranonitrone \u003cb\u003e6a)\u003c/b\u003e by utilizing the strong N\u0026ndash;B[\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] and Si\u0026ndash;F affinities.\u003c/p\u003e\u003cp\u003eIn the recent years, the reactivity of various newly synthesized nitrones has been studied theoretically, particularly via 32CA reactions. Nacereddine and coworkers[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] conducted a theoretical study on stereoselective BF\u003csub\u003e3\u003c/sub\u003e catalyzed 32CA reaction between nitrone isomers of methyl glyoxylate oxime \u003cb\u003e10\u003c/b\u003e and cyclopentene \u003cb\u003e11\u003c/b\u003e (see Scheme \u003cspan refid=\"Sch4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). In this study, the authors reveal that the reaction proceeds via two stereoisomeric pathways: the endo and exo approaches. The difference in energies for the transition states shows that the major isomer is the exo cycloadduct.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eUmar and coworkers[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] performed theoretical calculations to examine the stereoselectivity of the reactions of nitrone derived from adamantine with the alkene (e.g. maleimides) for the synthesis of a compound that contains both isoxazolidine and adamantane units. The authors revealed that the stereochemistry of the reaction is kinetically controlled and that the substituents on the dipolarophile decrease the activation energy of the diastereomeric isomers. Therefore, the substituents affect the activation energy and the stability of the reaction products of nitrone with maleimide.\u003c/p\u003e\u003cp\u003eIn this work, we present an M06-2X/6\u0026ndash;31\u0026thinsp;+\u0026thinsp;G(d,p) computational investigation of the 32CA reaction of an active intermediate, N-boranonitrone \u003cb\u003e6a\u003c/b\u003e (generated in situ by the reaction of O-TBS \u003cb\u003e6\u003c/b\u003e with BF\u003csub\u003e3\u003c/sub\u003e \u003cb\u003e8\u003c/b\u003e) with electron rich alkenes. For this purpose, the 32CA reaction between N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and alkenes (\u003cb\u003e7a\u003c/b\u003e: styrene; \u003cb\u003e7b\u003c/b\u003e: n-Hexene; and \u003cb\u003e7c\u003c/b\u003e: ethyl methacrylate) which was experimentally studied by Tamura and coworkers [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], is analyzed.\u003c/p\u003e"},{"header":"Computational methods","content":"\u003cp\u003eDFT calculations were carried out using the M06-2X, hybrid meta-GGA density functional[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] together with the standard 6\u0026ndash;31\u0026thinsp;+\u0026thinsp;G(d,p) basis set [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The stationary points were characterized by frequency calculations to verify that the transition states (TSs) had only one imaginary frequency. The intrinsic reaction coordinate (IRC)[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] has been further performed to check the energy profiles connecting each TS to the two associated minima for the proposed 32CA reaction. The electronic structures of stationary points were analyzed by the natural bond orbital (NBO)[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] method. The solvent effects of dichloroethane (DCE) were considered at the same level of theory by performing geometry optimization calculations of the gas-phase structures using a self-consistent reaction field (SCRF)[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] based on the polarizable continuum model (PCM)[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] of Tomasi's group. All calculations were carried out with the Gaussian 16 suite of programs [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. ELF[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] topological analyses were performed with the Multiwfn Version 3.8 package [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe global electrophilicity index, \u003cem\u003eω\u003c/em\u003e, was calculated by the following expression [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], \u003cem\u003eω = (\u0026micro;\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u003cem\u003e/2η)\u003c/em\u003e, in terms of the electronic chemical potential \u0026micro; and the chemical hardness \u003cem\u003eη\u003c/em\u003e. Both properties can be expressed in terms of the energies of the frontier molecular orbitals HOMO (\u003cem\u003eε\u003c/em\u003e\u003csub\u003e\u003cem\u003eH\u003c/em\u003e\u003c/sub\u003e) and LUMO (\u003cem\u003eε\u003c/em\u003e\u003csub\u003e\u003cem\u003eL\u003c/em\u003e\u003c/sub\u003e), as \u0026micro; \u0026asymp; (\u003cem\u003eε\u003c/em\u003e\u003csub\u003e\u003cem\u003eH\u003c/em\u003e\u003c/sub\u003e\u0026thinsp;\u003cem\u003e+\u0026thinsp;ε\u003c/em\u003e\u003csub\u003e\u003cem\u003eL\u003c/em\u003e\u003c/sub\u003e)/2 and \u003cem\u003eη\u003c/em\u003e \u0026asymp; (\u003cem\u003eε\u003c/em\u003e\u003csub\u003e\u003cem\u003eL\u003c/em\u003e\u003c/sub\u003e \u003cem\u003e- ε\u003c/em\u003e\u003csub\u003e\u003cem\u003eH\u003c/em\u003e\u003c/sub\u003e) respectively [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. The nucleophilicity index, N [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], was calculated by the following expression, N\u0026thinsp;=\u0026thinsp;\u003cem\u003eε\u003c/em\u003e\u003csub\u003e\u003cem\u003eH(\u003c/em\u003eNu\u003cem\u003e)\u003c/em\u003e\u003c/sub\u003e\u003cem\u003e-ε\u003c/em\u003e\u003csub\u003e\u003cem\u003eH(\u003c/em\u003eTCE)\u003c/sub\u003e, where tetracyanoethylene (TCE) is chosen as reference.\u003c/p\u003e"},{"header":"Results and Discussion","content":"\u003cp\u003eThe primary aim of this work is to provide a theoretical explanation for the mechanism and stereoselectivity observed in the reaction between N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and alkenes \u003cb\u003e7a-c\u003c/b\u003e, as depicted Scheme \u003cspan refid=\"Sch3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. To achieve this, we employed several computational approaches, including the evaluation of activation energies, frontier molecular orbital (FMO) analysis, and the use of electrophilic (\u003cem\u003ePk⁺\u003c/em\u003e) and nucleophilic (\u003cem\u003ePk⁻\u003c/em\u003e) Parr functions derived from spin electron-density variations. It should be emphasized that this reaction is governed by kinetic control, meaning the outcome is largely determined by the relative activation barriers of the competing pathways.\u003c/p\u003e\u003cp\u003e\u003cb\u003e32CA Reaction of N-boranonitrone 6a with Alkenes 7a-c\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe 32CA reaction between N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and alkenes \u003cb\u003e7a-c\u003c/b\u003e can take place along two stereoisomeric pathways namely the endo and exo approaches (see Scheme \u003cspan refid=\"Sch5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Analysis of the stationary points involved in these two stereoisomeric pathways indicate that this 32CA reaction takes place along a one-step mechanism. Consequently, two stereoisomeric transition states (TSs) and their corresponding [3\u0026thinsp;+\u0026thinsp;2] cycloadducts (CAs) associated with the exo and endo approaches were located and characterized. Endo approach yields the cis cycloadduct CAn-cis via transition state TSn-cis while the exo approach yields trans cycloadduct CAn-trans by transition state TSn-trans. All the energetic parameters for the 32CA reaction between N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and alkenes \u003cb\u003e7a\u0026ndash;c\u003c/b\u003e are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eEnergetic parameters for [3\u0026thinsp;+\u0026thinsp;2] cycloaddition reactions between N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and alkenes \u003cb\u003e7a\u0026ndash;c\u003c/b\u003e at the M06-2X/6\u0026ndash;31\u0026thinsp;+\u0026thinsp;G(d,p) computational study.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePoints\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e∆E\u003csup\u003e[a]\u003c/sup\u003e\u003csub\u003e(gas\u0026minus;phase)\u003c/sub\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e∆E\u003csup\u003e[b]\u003c/sup\u003e \u003csub\u003e(DCE)\u003c/sub\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e∆G\u003csup\u003e[c]\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e∆H\u003csup\u003e[d]\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e∆S\u003csup\u003e[e]\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTS\u003csub\u003e1\u003c/sub\u003e-cis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e20.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e20.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e34.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e22.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-40.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTS\u003csub\u003e1\u003c/sub\u003e-trans\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e17.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e16.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e31.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e18.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-41.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA\u003csub\u003e1\u003c/sub\u003e-cis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-26.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-22.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-10.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e-22.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-40.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA\u003csub\u003e1\u003c/sub\u003e-trans\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-27.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-24.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-12.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e-23.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-36.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTS\u003csub\u003e2\u003c/sub\u003e-cis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e18.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e19.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e33.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e19.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-46.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTS\u003csub\u003e2\u003c/sub\u003e-trans\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e16.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e31.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e17.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-46.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA\u003csub\u003e2\u003c/sub\u003e-cis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-31.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-27.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-14.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e-27.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-43.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA\u003csub\u003e2\u003c/sub\u003e-trans\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-29.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-27.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-14.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e-26.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-40.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTS\u003csub\u003e3\u003c/sub\u003e-cis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e17.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e32.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e17.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-49.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTS\u003csub\u003e3\u003c/sub\u003e-trans\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e15.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e16.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e31.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e16.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-50.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA\u003csub\u003e3\u003c/sub\u003e-cis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-23.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-21.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-9.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e-20.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-39.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA\u003csub\u003e3\u003c/sub\u003e-trans\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-27.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-23.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-12.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e-24.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-40.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eAll the properties are relative to reactants. [a] electronic energies in the gas phase. [b] electronic energies in (CH\u003csub\u003e2\u003c/sub\u003eCl)\u003csub\u003e2\u003c/sub\u003e [c] Gibbs free energy change [d] enthalpy change [e] entropy change. All energies are in kcal\u0026middot;mol\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e, and the entropies are in cal\u0026middot;mol⁻\u0026sup1;\u0026middot;K⁻\u0026sup1;.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe relative gas phase activation energies associated with this 32CA reaction between N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and styrene \u003cb\u003e7a\u003c/b\u003e are: 20.8 (TS\u003csub\u003e1\u003c/sub\u003e-cis) and 17.4 (TS\u003csub\u003e1\u003c/sub\u003e-trans) kcal mol\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e. The relative gas phase activation energy for the TSs associated with the trans isomer (TS\u003csub\u003e1\u003c/sub\u003e-trans) is 3.4 kcal mol\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e lower than that for the TS associated with the cis approach (TS\u003csub\u003e1\u003c/sub\u003e-cis), which clearly indicates that this 32CA reaction yields the trans cycloadduct as the major isomer. The formation of cycloadducts is exothermic by -26.4 (CA\u003csub\u003e1\u003c/sub\u003e-cis) and \u0026minus;\u0026thinsp;27.7 (CA\u003csub\u003e1\u003c/sub\u003e-trans) kcal mol\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe relative enthalpies, entropies and Gibbs free energies of the TSs and cycloadducts involved in the 32CA reaction between N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and styrene \u003cb\u003e7a\u003c/b\u003e are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Analysis of the activation enthalpies associated with the 32CA reaction of N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and styrene \u003cb\u003e7a\u003c/b\u003e indicates that the more favorable approach is the exo mode which yields the trans isomer. The relative enthalpy change for the TS\u003csub\u003e1\u003c/sub\u003e-trans is 3.4 kcal mol\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e lower than that for TS\u003csub\u003e1\u003c/sub\u003e-cis. The addition of the entropic contribution associated with this bimolecular process to the enthalpies increases the Gibbs activation free energy of this reactive path to 31.1 kcal mol\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e, which remains more favorable than the endo approach mode (∆∆G\u0026thinsp;=\u0026thinsp;3.1 kcal mol\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e). Consequently, the formation of the trans cycloadduct (CA\u003csub\u003e1\u003c/sub\u003e-trans) is clearly favored over the cis (CA\u003csub\u003e1\u003c/sub\u003e-cis), which is in good agreement with the experimental results.\u003c/p\u003e\u003cp\u003eSimilar results are also observed for the 32CA reaction of N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and n-hexene \u003cb\u003e7b\u003c/b\u003e. The relative gas phase activation energies associated with the 32CA reaction between N-boranonitrone \u003cb\u003e6a\u003c/b\u003e with n-hexene \u003cb\u003e7b\u003c/b\u003e are: 18.5 (TS\u003csub\u003e2\u003c/sub\u003e-cis) and 16.4 (TS\u003csub\u003e2\u003c/sub\u003e-trans) kcal mol\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e. The relative gas phase activation energy for TSs associated with the trans isomer (TS\u003csub\u003e2\u003c/sub\u003e-trans) is 2.1 kcal mol\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e lower than that for the TS associated with the cis approach (TS\u003csub\u003e2\u003c/sub\u003e-cis), which clearly indicates that this 32CA reaction yields the trans cycloadduct as major isomer. The formation of cycloadducts is exothermic by -31.1 (CA\u003csub\u003e2\u003c/sub\u003e-cis) and \u0026minus;\u0026thinsp;29.9 (CA\u003csub\u003e2\u003c/sub\u003e-trans) kcal mol\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe Relative enthalpies, entropies and Gibbs free energies of the TSs and cycloadducts involved in the 32CA reaction between N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and n-hexene \u003cb\u003e7b\u003c/b\u003e are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The Relative enthalpy change for TS\u003csub\u003e2\u003c/sub\u003e-trans is 2.1 kcal mol\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e lower than TS\u003csub\u003e2\u003c/sub\u003e-cis indicating trans isomer is favored over cis isomer (TS\u003csub\u003e2\u003c/sub\u003e-trans\u0026thinsp;=\u0026thinsp;17.2 and TS\u003csub\u003e2\u003c/sub\u003e-cis\u0026thinsp;=\u0026thinsp;19.3). Analysis of the Gibbs free energies also revealed a similar trend. The Gibbs activation free energy of this reactive path is 31.2 kcal mol\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e, which is more favorable than the endo approach mode (∆∆G\u0026thinsp;=\u0026thinsp;1.9 kcal mol\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e). Consequently, the formation of the trans cycloadduct (CA\u003csub\u003e2\u003c/sub\u003e-trans) is clearly favoured over the cis cycloadducts (CA\u003csub\u003e2\u003c/sub\u003e-cis).\u003c/p\u003e\u003cp\u003eWe also performed calculation on the 32CA reaction of N-boranonitrone \u003cb\u003e6a\u003c/b\u003e with another alkene, ethyl methacrylate \u003cb\u003e7c\u003c/b\u003e. Analysis of the computational results revealed lower energies for the trans isomer, which clearly indicates the formation of the trans isomer over the cis in this 32CA reaction. The relative gas phase activation energies associated with the 32CA reaction between N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and ethyl methacrylate \u003cb\u003e7c\u003c/b\u003e are: 16.8 (TS\u003csub\u003e3\u003c/sub\u003e-cis) and 15.2 (TS\u003csub\u003e3\u003c/sub\u003e-trans) kcal mol\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e. The relative gas phase activation energy for TS associated with the trans isomer (TS\u003csub\u003e3\u003c/sub\u003e-trans) is 1.6 kcal mol\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e lower than that for the TS associated with the cis approach (TS\u003csub\u003e3\u003c/sub\u003e-cis), which clearly indicates that this 32CA reaction yields the trans cycloadduct as the major isomer. The formation of cycloadducts is exothermic by -23.9 (CA\u003csub\u003e3\u003c/sub\u003e-cis) and \u0026minus;\u0026thinsp;27.6 (CA\u003csub\u003e3\u003c/sub\u003e-trans) kcal mol\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e clearly shows that the relative enthalpy change for TS\u003csub\u003e3\u003c/sub\u003e-trans is 1.5 kcal mol\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e lower than TS\u003csub\u003e3\u003c/sub\u003e-cis indicating trans isomer is favored over the cis isomer (TS\u003csub\u003e3\u003c/sub\u003e-trans\u0026thinsp;=\u0026thinsp;16.1 and TS\u003csub\u003e3\u003c/sub\u003e-cis\u0026thinsp;=\u0026thinsp;17.6). The Gibbs activation free energy of this reactive path is 31.0 kcal mol\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e, which remains more favorable than the endo approach mode (∆∆G\u0026thinsp;=\u0026thinsp;1.4 kcal mol\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e). Consequently, the formation of the trans cycloadduct (CA\u003csub\u003e3\u003c/sub\u003e-trans) is clearly favored over the formation of the cis cycloadduct (CA\u003csub\u003e3\u003c/sub\u003e-cis), which is in good agreement with the experimental results.\u003c/p\u003e\n\u003ch3\u003eNBO Analysis of the 32CA Reaction of N-boranonitrone 6a with alkenes 7a-c\u003c/h3\u003e\n\u003cp\u003eThe geometries of the transition states (TSs) involved in the [3\u0026thinsp;+\u0026thinsp;2] cycloaddition (32CA) of N-boranonitrone \u003cb\u003e6a\u003c/b\u003e with alkenes \u003cb\u003e7a\u0026ndash;c\u003c/b\u003e are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. For the 32CA between N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and styrene \u003cb\u003e7a\u003c/b\u003e, the forming C3\u0026ndash;C5 and O1\u0026ndash;C4 bond lengths at the TSs leading to CA\u003csub\u003e1\u003c/sub\u003e are 2.108 and 2.031 \u0026Aring; at TS\u003csub\u003e1\u003c/sub\u003e-cis, and 2.119 and 2.034 \u0026Aring; at TS\u003csub\u003e1\u003c/sub\u003e-trans, respectively. The extent of bond formation at the TSs can be evaluated by bond order (BO).[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] The BO values for the forming C3\u0026ndash;C5 and O1\u0026ndash;C4 bonds are 0.41 and 0.37 at TS\u003csub\u003e1\u003c/sub\u003e-cis, and 0.40 and 0.36 at TS\u003csub\u003e1\u003c/sub\u003e-trans, respectively. These results indicate that both bonds are only partially formed and that the process is asynchronous but nearly concerted. Interestingly, the bond distances suggest O\u0026ndash;C formation is slightly more advanced, whereas the BO values show a small opposite bias toward C\u0026ndash;C formation. Given the small magnitude of these differences, we conclude that both metrics consistently point to an asynchronous transition state with no strong preference for either bond. Analysis of charge transfer (CT) further characterizes the electronic nature of these cycloadditions: charge flows from styrene \u003cb\u003e7a\u003c/b\u003e to N-boranonitrone \u003cb\u003e6a\u003c/b\u003e by 0.07 e at both TS\u003csub\u003e1\u003c/sub\u003e-cis and TS\u003csub\u003e1\u003c/sub\u003e-trans. The small CT values account for the very low polar character of this 32CA between N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and styrene \u003cb\u003e7a\u003c/b\u003e.\u003c/p\u003e\u003cp\u003eFor the 32CA reaction between N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and n-hexene \u003cb\u003e7b\u003c/b\u003e, the forming C3\u0026ndash;C5 and O1\u0026ndash;C4 bond lengths at the TSs leading to CA\u003csub\u003e2\u003c/sub\u003e are 2.177 and 2.007 \u0026Aring; at TS\u003csub\u003e2\u003c/sub\u003e-cis, and 2.210 and 1.981 \u0026Aring; at TS\u003csub\u003e2\u003c/sub\u003e-trans, respectively. The corresponding bond order (BO) values are 0.37 and 0.38 at TS\u003csub\u003e2\u003c/sub\u003e-cis, and 0.38 and 0.34 at TS\u003csub\u003e2\u003c/sub\u003e-trans. These results show that both bonds are only partially formed and that the reaction proceeds through asynchronous transition states. While the bond distances suggest earlier formation of the O\u0026ndash;C bond, the BO values show a small and inconsistent bias between the two bonds. Overall, the process can be described as nearly concerted with slight asynchronicity. Charge transfer (CT) analysis indicates electron flow from n-hexene \u003cb\u003e7b\u003c/b\u003e to N-boranonitrone \u003cb\u003e6a\u003c/b\u003e of 0.09 e at both TS\u003csub\u003e2\u003c/sub\u003e-cis and TS\u003csub\u003e2\u003c/sub\u003e-trans, confirming the very low polar character of this cycloaddition.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eFor the 32CA reaction between N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and ethyl methacrylate \u003cb\u003e7c\u003c/b\u003e, the forming C3\u0026ndash;C5 and O1\u0026ndash;C4 bond lengths at the TSs leading to CA\u003csub\u003e3\u003c/sub\u003e are 2.047 and 2.059 \u0026Aring; at TS\u003csub\u003e3\u003c/sub\u003e-cis, and 2.043 and 2.065 \u0026Aring; at TS\u003csub\u003e3\u003c/sub\u003e-trans, respectively. The BO values for these bonds are 0.44 and 0.35 at TS\u003csub\u003e3\u003c/sub\u003e-cis, and 0.45 and 0.33 at TS\u003csub\u003e3\u003c/sub\u003e-trans. Both the bond distances and BOs clearly indicate asynchronous bond formation in which C\u0026ndash;C bond formation is more advanced than O\u0026ndash;C. Thus, these TSs also correspond to nearly concerted but asynchronous processes. CT analysis shows electron transfer from ethyl methacrylate \u003cb\u003e7c\u003c/b\u003e to N-boranonitrone \u003cb\u003e6a\u003c/b\u003e of 0.03 e (TS\u003csub\u003e3\u003c/sub\u003e-cis) and 0.02 e (TS\u003csub\u003e3\u003c/sub\u003e-trans), confirming the very low polar character of this cycloaddition.\u003c/p\u003e\n\u003ch3\u003eELF topological analysis of the reactants\u003c/h3\u003e\n\u003cp\u003eIn 1990, Becke and Edgecombe developed the electron localization function (ELF) [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] which was later perfected by Silvi and Savin [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] in 1994. This ELF approach offers a very unique perspective on the distribution of electrons in a molecule by their localization rather than total electron density. Herein, the electronic structures of the four reagents, namely N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and alkenes \u003cb\u003e7a-c\u003c/b\u003e, in the ground state are examined by the electron localization function topological analysis as depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and the values of basin populations are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003eTwo monosynaptic basins, V(O1) and V\u0026rsquo;(O1) have been discovered for N-boranonitrone \u003cb\u003e6a\u003c/b\u003e, which together integrate 5.59e, indicating the non-bonding electron density on the O1 oxygen atom. Moreover, the disynaptic basins, V(O1, N2) and V(N2,C3), integrate 1.71 e and 2.45 e, respectively, revealing the polar single bond connecting N2 and O1 and the double bond involving N2 and C3 in the molecular structure. In addition, two small monosynaptic basins V(C3) and V\u0026rsquo;(C3) which together integrate 0.72e on C3 shows the splitting of π lobes on the carbon side of the N\u0026thinsp;=\u0026thinsp;C bond.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eELF valence basin populations for reagents, N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and alkenes (\u003cb\u003e7a\u003c/b\u003e,\u003cb\u003e7b\u003c/b\u003e, and \u003cb\u003e7c\u003c/b\u003e) in electrons e. calculated by M06-2x/6\u0026ndash;31\u0026thinsp;+\u0026thinsp;G(d,p).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6a\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7a\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7b\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7c\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eV(O1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eV\u0026rsquo;(O1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.83\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eV(O1,N2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eV(C3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eV\u0026rsquo;(C3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eV(N2,C3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eV(C4,C5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.74\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eV\u0026rsquo;(C4,C5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.74\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eIn addition, the ELF analysis of styrene \u003cb\u003e7a\u003c/b\u003e revealed the presence of two disynaptic basins V(C4, C5) and V\u0026rsquo; (C4, C5) with a population of 1.73e for each shows the presence of one double bond between C4 and C5. For n-hexene \u003cb\u003e7b\u003c/b\u003e, two disynaptic basins V(C4, C5) and V\u0026rsquo;(C4, C5) with a population of 1.74e and 1.73e respectively, shows the presence of one double bond between C4 and C5. For ethyl methacrylate \u003cb\u003e7c\u003c/b\u003e, two disynaptic basins V(C4, C5) and V\u0026rsquo;(C4, C5) with population of 1.74e for each one shows the presence of one double bond between C4 and C5\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e.\u003c/p\u003e\n\u003ch3\u003eDFT-based reactivity indices analysis of the reactants at the ground state\u003c/h3\u003e\n\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eM06-2X/6\u0026ndash;31\u0026thinsp;+\u0026thinsp;G(d,p) electronic chemical potential (\u003cem\u003e\u0026micro;\u003c/em\u003e, in eV), chemical hardness (\u003cem\u003eη\u003c/em\u003e, in eV), global electrophilicity (\u003cem\u003eω\u003c/em\u003e, in eV), and global nucleophilicity (N, in eV), of reactants N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and alkenes (\u003cb\u003e7a\u003c/b\u003e,\u003cb\u003e7b\u003c/b\u003e, and \u003cb\u003e7c\u003c/b\u003e) in the gas phase.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003e\u0026micro;\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eƞ\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eω\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eN\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-5.40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.84\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e7a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-4.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.18\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e7b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-3.85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.30\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e7c\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-4.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e8.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.90\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eMany theoretical studies[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] devoted to Diels\u0026ndash;Alder and cycloaddition reactions have shown that the analysis of the reactivity indices defined within the conceptual DFT[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] are powerful tools to understand the reactivity in polar cycloadditions. The DFT reactivity indices, namely electronic chemical potential \u003cem\u003e\u0026micro;\u003c/em\u003e, chemical hardness \u003cem\u003eƞ\u003c/em\u003e, global electrophilicity \u003cem\u003eω\u003c/em\u003e, and global nucleophilicity, N, for N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and alkenes (\u003cb\u003e7a\u003c/b\u003e,\u003cb\u003e7b\u003c/b\u003e, and \u003cb\u003e7c\u003c/b\u003e) are given in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. The electronic chemical potential \u003cem\u003e\u0026micro;\u003c/em\u003e of N-boranonitrone \u003cb\u003e6a\u003c/b\u003e is -5.40 eV, which is lower than that of alkenes (\u003cb\u003e7a\u003c/b\u003e: -4.01,\u003cb\u003e7b\u003c/b\u003e: -3.85,\u003cb\u003e7c\u003c/b\u003e: -4.61) indicating that during a polar 32CA reaction, the CT takes place from alkene toward N-boranonitrone \u003cb\u003e6a\u003c/b\u003e, which is in good agreement with the CT observed at the TSs. N-boranonitrone \u003cb\u003e6a\u003c/b\u003e has a high electrophilicity \u003cem\u003eω\u003c/em\u003e index, 2.04 eV, being classified as strong electrophile within the electrophilicity scale.[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e] On the other hand, it has low nucleophilicity N index, 1.84 eV being classified as marginal nucleophile.[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e] On the other hand, alkenes (\u003cb\u003e7a\u003c/b\u003e,\u003cb\u003e7b\u003c/b\u003e,\u003cb\u003e7c\u003c/b\u003e) present a low electrophilicity indices, \u003cem\u003eω\u003c/em\u003e\u0026thinsp;=\u0026thinsp;\u003cb\u003e7a\u003c/b\u003e:1.11 eV, \u003cb\u003e7b\u003c/b\u003e:0.80 eV and \u003cb\u003e7c\u003c/b\u003e:1.23 eV, being classified as moderate electrophiles, but have high nucleophilicity N indices, N\u0026thinsp;=\u0026thinsp;\u003cb\u003e7a\u003c/b\u003e:3.18 eV, \u003cb\u003e7b\u003c/b\u003e:2.30 eV and \u003cb\u003e7c\u003c/b\u003e:1.90 eV, being classified as strong nucleophiles. Therefore, N-boranonitrone \u003cb\u003e6a\u003c/b\u003e will participate as an electrophile and alkenes \u003cb\u003e7a\u003c/b\u003e, \u003cb\u003e7b\u003c/b\u003e, and \u003cb\u003e7c\u003c/b\u003e will react as nucleophiles during 32CA reactions.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eRecently, Domingo and coworkers[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e] introduced electrophilic, \u003cem\u003eP\u003c/em\u003e\u003csub\u003e\u003cem\u003ek\u003c/em\u003e\u003c/sub\u003e\u003csup\u003e\u003cb\u003e+\u003c/b\u003e\u003c/sup\u003e, and nucleophilic, \u003cem\u003eP\u003c/em\u003e\u003csub\u003e\u003cem\u003ek\u003c/em\u003e\u003c/sub\u003e\u003csup\u003e\u003cb\u003e-\u003c/b\u003e\u003c/sup\u003e, Parr functions. These functions are formulated on the basis of the atomic spin density distribution in the radical anion and radical cation of the neutral molecules. The electrophilic and nucleophilic Parr functions are obtained through the single-point energy computation of the Mulliken atomic spin density of the radical anion and the radical cation, respectively. The electrophilic \u003cem\u003eP\u003c/em\u003e\u003csub\u003e\u003cem\u003ek\u003c/em\u003e\u003c/sub\u003e\u003csup\u003e\u003cb\u003e+\u003c/b\u003e\u003c/sup\u003e Parr functions of N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and nucleophilic Parr functions \u003cem\u003eP\u003c/em\u003e\u003csub\u003e\u003cem\u003ek\u003c/em\u003e\u003c/sub\u003e\u003csup\u003e\u003cb\u003e-\u003c/b\u003e\u003c/sup\u003e of alkenes \u003cb\u003e7a\u003c/b\u003e, \u003cb\u003e7b\u003c/b\u003e, and \u003cb\u003e7c\u003c/b\u003e were analyzed. They are presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. This figure reveals that the terminal O1 oxygen at N-boranonitrone \u003cb\u003e6a\u003c/b\u003e is the most electrophilic center of this molecule with \u003cem\u003eP\u003c/em\u003e\u003csub\u003e\u003cem\u003ek\u003c/em\u003e\u003c/sub\u003e\u003csup\u003e\u003cem\u003e+\u003c/em\u003e\u003c/sup\u003e =0.348 whereas the C3 carbon is less electrophilic than the O1 atom (P\u003csub\u003ek\u003c/sub\u003e\u003csup\u003e+\u003c/sup\u003e=-0.169). On the other hand, the nucleophilic parr function, \u003cem\u003eP\u003c/em\u003e\u003csub\u003e\u003cem\u003ek\u003c/em\u003e\u003c/sub\u003e\u003csup\u003e\u003cb\u003e-\u003c/b\u003e\u003c/sup\u003e for the C5 atom is 0.503 for \u003cb\u003e7a\u003c/b\u003e, 0.617 for \u003cb\u003e7b\u003c/b\u003e and 0.589 for \u003cb\u003e7c\u003c/b\u003e and the same for the C4 atom is -0.034 for \u003cb\u003e7a\u003c/b\u003e 0.351 for \u003cb\u003e7b\u003c/b\u003e and 0.331 for \u003cb\u003e7c\u003c/b\u003e. Analysis of this nucleophilic parr function \u003cem\u003eP\u003c/em\u003e\u003csub\u003e\u003cem\u003ek\u003c/em\u003e\u003c/sub\u003e\u003csup\u003e\u003cb\u003e-\u003c/b\u003e\u003c/sup\u003e of alkenes (\u003cb\u003e7a-c\u003c/b\u003e) revealed that the C5 carbon of alkenes is more nucleophilic than the C4 carbon.\u003c/p\u003e\u003cp\u003e\u003cb\u003eElectron localization function study of the transition state involved in the 32CA reaction between N-boranonitrone 6a and alkenes 7a-c\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTo describe the main path of the reaction mechanism, ELF analysis at the transition state involved in this 32CA reaction was performed. This analysis can reveal the regions of electron localization on the molecular surface and then specify the nature of the bonds between atoms. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e displays two planes (N2-C3-C5 and N2\u0026ndash;O1-C4) of the 2D surface map for the formed TS\u003csub\u003e1\u0026thinsp;\u0026minus;\u0026thinsp;3\u003c/sub\u003e-trans involved in this 32CA reaction between N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and alkenes \u003cb\u003e7a-c\u003c/b\u003e. The ELF plane was generated by selecting three successive atoms, and the map shows a significant variation in the electron localization density with a characteristic color code around the 3-atom plane [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e (1a,2a and 3a), the ELF maps revealed a symmetric distribution of electron density between the two carbon nuclei C3 and C5. The localization of the electron density along the internuclear axis reflects the incipient character of bond formation. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e (1b,2b and 3b) clearly shows that the O1\u0026ndash;C4 interaction has a stronger tendency toward electron localization compared to the C3\u0026ndash;C5. Owing to the high electronegativity and availability of low-lying empty orbitals, oxygen tends to polarize and attract electron density from C4 atom (note that nucleophilicity indices, N of alkenes \u003cb\u003e7a-c\u003c/b\u003e are higher than that of N-boranonitrone \u003cb\u003e6a.\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\n\u003ch3\u003eNCI analysis\u003c/h3\u003e\n\u003cp\u003eAs proven in the previous section, the 32CA reaction between N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and alkenes \u003cb\u003e7a-c\u003c/b\u003e yields the CA\u003csub\u003e1\u0026thinsp;\u0026minus;\u0026thinsp;3\u003c/sub\u003e-trans, resulting from the exo approach mode. Many previous theoretical studies confirmed that the selectivity approach is generally governed by covalent and noncovalent interactions.[\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e] To better understand the origin of the stereoselectivity in the studied 32CA reactions, noncovalent interaction (NCI) analysis was performed on the optimized transition states. The reduced density gradient (RDG) plots for the cis and trans conformations of TSs are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. These plots provide a direct visualization of weak interactions by correlating the reduced density gradient with the sign(λ)ρ parameter. Negative values of sign(λ)ρ correspond to stabilizing attractive interactions (blue regions), whereas positive values represent repulsive or steric effects (red regions). Regions close to zero are generally associated with van der Waals interactions (green regions).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eA comparison between the cis and trans pathways revealed a clear difference in their interaction profiles. For the cis-configured transition states TS\u003csub\u003e1\u0026thinsp;\u0026minus;\u0026thinsp;3\u003c/sub\u003e\u0026ndash;cis, the plots show scattered interaction points with limited clustering in the attractive region. Although some blue and green domains are observed, these are relatively weaker and not well-defined, suggesting that stabilization through noncovalent forces is modest. In contrast, the trans-configured transition states TS\u003csub\u003e1\u0026thinsp;\u0026minus;\u0026thinsp;3\u003c/sub\u003e\u0026ndash;trans, exhibit stronger and more concentrated blue and green regions in the negative sign(λ)ρ domain. This indicates the presence of significant attractive interactions, which play a major role in stabilizing these geometries. The circled regions in the scatter plots highlight these zones of noncovalent stabilization. Furthermore, the trans pathways consistently display fewer points in the destabilizing (red) region, confirming a reduced steric penalty relative to the cis counterparts.\u003c/p\u003e\u003cp\u003eThese observations suggest that the enhanced stability of the trans transition states arises from a combination of stronger attractive noncovalent interactions and reduced steric repulsion. The overall effect is a lowering of the activation barrier, which explains why the trans products are predicted to dominate as the major outcome of the reaction.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe molecular mechanism and stereoselectivity of the BF\u003csub\u003e3\u003c/sub\u003e-mediated [3\u0026thinsp;+\u0026thinsp;2] cycloaddition (32CA) reaction between N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and alkenes \u003cb\u003e7a\u0026ndash;c\u003c/b\u003e has been studied theoretically using DFT at the M06-2X/6\u0026ndash;31\u0026thinsp;+\u0026thinsp;G(d,p) level. Several important conclusions can be drawn on the basis of our computational results.\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eOur study revealed that the 32CA between N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and alkenes \u003cb\u003e7a\u0026ndash;c\u003c/b\u003e is stereoselective, with exo pathway being the most favorable. This pathway leads both kinetically and thermodynamically to the formation of the cycloadduct CA\u003csub\u003e1-3\u003c/sub\u003e-trans, which matches very well with the experimental outcomes.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThe low values of CT found at the corresponding TSs indicate the low polar character of this 32CA reaction. Study of the bond order (BO) of transition states (TSs) reveals that the 32CA reaction occurs through an asynchronous mechanism between N-boranonitrone \u003cb\u003e6a\u003c/b\u003e and alkenes \u003cb\u003e7a\u0026ndash;c\u003c/b\u003e.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eAnalysis of the DFT reactivity indices at the ground state of the reagents involved in this 32CA reaction indicates that alkenes \u003cb\u003e7a\u0026ndash;c\u003c/b\u003e are nucleophiles and N-boranonitrone \u003cb\u003e6a\u003c/b\u003e is an electrophile.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eRDG-NCI analysis was used to determine van der Waals interactions and steric repulsive interactions which supports formation of trans isomer as major isomer.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThe inclusion of Solvent effects shows slight change in activation energy but decrease in exothermic character for this cycloaddition reaction.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eEthical Approval\u003c/h2\u003e\u003cp\u003eNot applicable (This study does not involve human participants or animal experiments).\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eDeclaration of Competing Interest\u003c/strong\u003e\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis manuscript did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eRavi Bariya: Writing-original draft, Visualization, Validation, Methodology, Formal analysis, Data curation. Ankit Patel: Methodology, Formal analysis. Sangita Sharma: Writing- review \u0026amp; editing, Supervision, Software, Resources, Investigation, Formal analysis, Conceptualization.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eR.B. is grateful to Department of Chemistry, HNGU, Patan. for computational Facilities.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eNo datasets were generated or analysed during the current study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGothelf KV, J\u0026oslash;rgensen KA (1998) Asymmetric 1,3-Dipolar Cycloaddition Reactions. 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Struct Chem 35:1427\u0026ndash;1435. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/S11224-024-02292-7\u003c/span\u003e\u003cspan address=\"10.1007/S11224-024-02292-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Schemes","content":"\u003cp\u003eSchemes 1 to 5 are available in the Supplementary Files section\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"[3 + 2] cycloaddition, DFT, ELF analysis, stereoselectivity, noncovalent interactions","lastPublishedDoi":"10.21203/rs.3.rs-7581670/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7581670/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIn this work, we present a density functional theory (DFT) investigation of the BF\u003csub\u003e3\u003c/sub\u003e-mediated [3\u0026thinsp;+\u0026thinsp;2] cycloaddition (32CA) of N-boranonitrone (\u003cb\u003e6a)\u003c/b\u003e with three representative alkenes (styrene \u003cb\u003e7a\u003c/b\u003e, n-hexene \u003cb\u003e7b\u003c/b\u003e, and ethyl methacrylate \u003cb\u003e7c\u003c/b\u003e). Calculations were carried out using hybrid meta-GGA M06-2X functional using standard 6\u0026ndash;31\u0026thinsp;+\u0026thinsp;G(d,p) basis set in both gas phase and dichloroethane solution using the PCM model. The reaction proceeds through a concerted one-step mechanism with two stereoisomeric pathways (endo/cis and exo/trans). Activation energy analyses reveal that the exo approach consistently provides lower barriers (by 1.4\u0026ndash;3.4 kcal\u0026middot;mol⁻\u0026sup1;) than the endo pathway, in agreement with the experimentally observed predominance of trans cycloadducts. Bond orders and distances indicate asynchronous bond formation, with small differences between C\u0026ndash;O and C\u0026ndash;C bond development depending on the substrate, while ELF analysis confirms electron localization patterns characteristic of this process. Global reactivity descriptors show that N-boranonitrone acts as the electrophile, whereas the alkenes act as the nucleophiles. Noncovalent interaction (NCI) analysis highlights stabilizing attractive interactions in the exo transition states that further rationalize the stereochemical preference.\u003c/p\u003e","manuscriptTitle":"Unveiling the Mechanism and Stereochemical Pathways for BF 3 - mediated [3+2] Cycloaddition of N-boranonitrone with Alkenes: A DFT Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-22 13:29:40","doi":"10.21203/rs.3.rs-7581670/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bab722dd-50f6-40ad-81ac-9140856ee8f6","owner":[],"postedDate":"September 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-28T01:38:21+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-22 13:29:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7581670","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7581670","identity":"rs-7581670","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}