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. 2023 Nov 1;8(45):42311–42318. doi: 10.1021/acsomega.3c04513

Quantum Chemical Insight into 1,2-Shift Rearrangement in Bromination of Allylaryls

David Hardy 1, Stephen R Isbel 1, Alejandro Bugarin 1,*, Durgesh V Wagle 1,*
PMCID: PMC10652718  PMID: 38024757

Abstract

graphic file with name ao3c04513_0007.jpg

In this work, we have provided mechanistic insight into the addition of bromine to an allylic double bond of allylaryl derivatives using experimental and DFT-based electronic structure methods. The experimental yields indicate the influence of the functional group on the aryl ring on the ratio of 1,2-dibromo and 1,3-dibromo adducts formed in the reaction. The optimized geometry and the electron density maps of the allylaryls and their cationic intermediates from DFT simulations revealed that electron-rich aryl rings promoted formation of cationic spiro[2.5] intermediate II, whereas electron-poor aryl rings resulted in formation of bromonium intermediate I. It was observed that electron-rich allylaryls promoted the 1,2-shift of the aryl ring that resulted in bond formation between the carbon atom (C1) on the aryl ring and the central carbon atom (C3) in the allylic double bond and formed spiro[2.5] intermediate II, a trend which was confirmed by harmonic oscillator model of aromaticity index. Also, Wiberg bond order analysis is in good agreement with the experimental work. Thermochemical analysis indicates that smaller C1···C3 distance resulted in favorable values for the difference in free energy change (ΔΔG). The favorable ΔΔG values are a result of higher electron density on the aryl ring, making it more nucleophilic toward C3 carbon and promoting 1,2-shift that led to formation of the spiro[2.5] intermediate. Thus, the underlying mechanism indicates that the electron-rich allylaryls promote the formation of 1,3-dibromo compounds through formation and stabilization of the spiro[2.5] intermediate II.

Introduction

Polymers and plastic have become an inseparable aspect of our everyday life, and polystyrene plays a central role in modernization of our society. Ever since its discovery in 1839, styrene in the form of polystyrene has found its way into everyday products as a versatile and inexpensive plastic material.1 Styrene being a highly tailorable monomer can be transformed into polystyrene with unique properties such as being able to extrude in a glassy solid or in the form of lightweight foam.2 Owing to the flexibility in the functional group chemistry on styrene monomers, and method involving copolymers, polystyrene with exceptional chemical and physical properties can be designed for specific applications, for instance, disposable packing in consumer products or heat-resistant polymer for industrial applications.3,4 One such example of heat-resistant styrene is the α-alkyl styrene which can also be functionalized and modified for further derivatization.5−7 Unfortunately, α-alkyl styrenes are difficult to produce due to a relative shortage of efficient synthetic methodologies. In most cases, aryl ketones are converted to terminal alkenes using Wittig reagents,8,9 but this method is limited only to synthesis of α-alkyl styrenes with simple alkyl groups.10−12 Some methods of α-alkyl styrene synthesis involving carbon-supported rhodium nanoparticle-assisted catalysis provide avenues for regioselective addition of branched or linear aldehydes.13 However, other existing methods require pre-existing α-methyl or other reactive groups in place at the α position. For example, new α-alkyl styrenes are synthesized from α-methylstyrenes by a regioselective elimination reaction via formation of tertiary alkyl radicals in a copper-mediated oxidation reaction.14 Duan et al. synthesized α-alkyl styrenes via enantioselective hydrogenation of β,γ-unsaturated phosphonates using Rh catalysts and chiral ferrocene-based monophosphoramidite ligands.15 Bunrit et al. demonstrate that α-alkyl styrenes can be synthesized in route to the synthesis of compounds having pyrrole substitution at β-position in benzyl or aryl groups.16 Gupton and co-workers synthesized α-alkyl styrenes by reaction of enolates with 2-aryl-3-(N,N-dimethylamino)-propene.17 Highly regio- and stereoselective methods to synthesize styrene derivatives have been illustrated in detail in our recently reported work on addition reactions to terminal alkenes.18,19

Recently, we reported the synthesis of α-alkyl styrene using transition metal-free one-pot reaction conducted under mild conditions.20−22 Interestingly, this reaction resulted in a mixture of two distinct styrene derivatives, a and b (Scheme 1). Based on the experimental observations in our previously reported work and the bromine-mediated rearrangement reaction studies done by Dubois and Costa, it was proposed that allylaryl undergoes an alkene bromination to form bromonium intermediate I, which later on undergoes an intramolecular rearrangement, a 1,2-shift by the electron-rich aryl moiety to form the spiro[2.5] intermediate II.23,24 The spiro[2.5] intermediate II can be ring-opened by a nucleophilic attack by a Br– anion on the three-membered ring to produce either a 2,3-dibromo derivative (a) or a 1,3-dibromo derivative (b). Furthermore, the 2,3-dibromo derivative (a) can also be formed by nucleophilic attack by a Br– anion on intermediate I. In this work, we have provided a detailed mechanistic insight into bromination of an allylic double bond in allylaryl derivatives using quantum chemical simulations based on density functional theory (DFT).

Scheme 1. Proposed Mechanism for Formation of α-Alkyl Styrene from Allylaryl.

Scheme 1

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Experimental Methods

General Information

All reactions were carried out under air in oven-dried glassware with magnetic stirring at room temperature. All commercially obtained reagents were used as received. Solvents were dried and degassed from a JC Meyer company solvent purification system. Purification of reaction products was carried out by flash column chromatography using silica gel 60 (230–400 mesh). TLC visualization was accompanied with UV light. Concentration in vacuo refers to the removal of volatile solvent using a rotary evaporator attached to a dry diaphragm pump (10–15 mmHg) followed by pumping to a constant weight with an oil pump (<300 mTorr). 1H NMR spectra were recorded at 400 MHz, and they are reported relative to CDCl3 (δ = 7.26). 1H NMR coupling constants (J) are reported in hertz (Hz), and multiplicities are indicated as follows: s (singlet), d (doublet), t (triplet), and m (multiplet). Proton-decoupled 13C NMR spectra were recorded at 100 MHz and reported relative to those of CDCl3 (δ = 77). IR experiments were recorded with neat samples on a Jasco FT/IR-4700 fitted with a diamond ATR sample plate. GCMS data were recorded on a Shimadzu GC-2010 plus System (GCMS-QP2010 SE).

Reagents and Materials

The following starting materials were used as received from MilliporeSigma (St. Louis, MO): estragole (98%, cat. no. A29208), 4-allyltoluene (97%, cat. no. 706728), 1-allyl-4-fluorobenzene (97%, cat. no. 706787), allylbenzene (98%, cat. no. A29402), 1-allyl-4-(trifluoromethyl)benzene (95%, cat. no. 706779), and allylpentafluorobenzene (97%, cat. no. A34759). Hexanes (>98.5%, cat. no. H29220) and ethyl acetate (>99.5%, cat. no. E14520) were used as received from Fisher Scientific (Hanover Park, IL). Chloroform-d (99.8%, cat. no. DLM-7) was used as received from Cambridge Isotope Laboratory (Tewksbury, MA).

General Method for the Preparation of Dibromo Compounds (2–7)

Allylbenzene (0.25 mmol, 1.0 equiv) and CDCl3 (1.0 mL) were added to a 10 mL round-bottomed flask, equipped with a stir bar, at room temperature under air. The mixture was cooled down to 0 °C (ice bath), followed by dropwise addition of Br2 (0.33 mmol, 17 μL, 1.3 equiv). The reaction was stirred at 0 °C for 10 min. Then, the mixture was concentrated in vacuo. Purification by flash chromatography (SiO2, EtOAc/hexanes mixtures) provided pure dibromo products.

Computational Methods

The simulations were performed using Gaussian 16 software package, and molecular visualization was done using GaussView.25 In this work, we used DFT-based M06-2X/6-31++G(d,p) theory and a basis set for prediction of geometry, electron density, and thermochemistry. This combination of theory and basis set has been effectively used in our earlier work to predict molecular geometry and thermochemical properties for ionic and molecular species.26−28 Furthermore, M06 suite of density functionals has been successfully applied to the main group thermochemistry, noncovalent interactions, and excited states.29 A scaling factor of 0.986 was used for the correction of vibrational frequencies calculated using the M06-2X/6-31++G(d,p) level of theory.29 All simulations were carried out with no symmetry restrictions in the singlet ground state. The absence of imaginary frequency in the optimized structures indicates that they were a minima. The charge density was determined using charges from electrostatic potential maps using a grid-based method (CHELPG).30 Dispersion corrections were accounted using the method developed by Grimme.31 The harmonic oscillator model of aromaticity (HOMA) index and Wiberg bond order analysis were carried out using Multiwfn―a multifunctional wave function analyzer software package.32−34 Change in the free energy (G) of formation of intermediates of bromination was determined using the following equation:

graphic file with name ao3c04513_m001.jpg 1

The difference in the change of free energy (ΔΔG) of formation of intermediate I and spiro[2.5] intermediate II for various allylaryl derivatives was obtained using eq 2 in which the allylaryl derivative with R = H was assigned a value of zero and ΔΔG for other derivatives was calculated relative to the allylaryl derivative R = H. The allylaryl derivative R = −H was used as a baseline as it is the allylaryl derivative with an aryl ring having no substitutions other than the allylic group.

graphic file with name ao3c04513_m002.jpg 2

where Y = −OMe, −Me, −F, −CF3, and pentafluoro derivative of allylaryl.

Results and Discussion

The experimental evidence strongly pointed toward the influence of the functional group on the aryl ring in allylaryl derivatives on the outcome of the bromination reaction, as indicated by the ratio of 2,3-dibromo (a) and 1,3-dibromo (b) formed in the reaction, see Table 1. It was observed that the presence of the strong electron-withdrawing group (EWG) such as −CF3 on the aryl ring or the lack of electron density of the aryl ring (pentafluoro derivative) exclusively results in formation of a in the reaction. On the other hand, because of the presence of a strong electron-donating group (EDG) on the aromatic ring such as −OMe, a is formed as a minor product and b is the major product. This ratio of a and b gradually favored formation of a over b as the functional group gradually switched from a strong EDG to a moderate EDG/EWG to a strong EWG, see Table 1.

Table 1. Comparative Study Depicting Reaction Yields and Ratio of 2,3-Dibromo (a) and 1,3-Dibromo (b) Formed after the Addition of Bromine to Allylaryls (EDG vs EWG).

graphic file with name ao3c04513_0005.jpg

graphic file with name ao3c04513_0006.jpg

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a

Reaction conditions: allylaryl 1a–f (0.25 mmol, 1 equiv), bromine (0.33 mmol, 53 mg, 17 μL, 1.3 equiv), in 1.0 mL of CDCl3 at 0 °C for 10 min.

b

Crude 1H NMR yield of reaction using mesitylene as the internal standard.

c

Isolated yield using silica gel flash chromatography.

d

Ratio determined by 1H NMR spectroscopy.

According to the proposed mechanism in Scheme 1, the 1,3-dibromo adduct is produced when the spiro[2.5] intermediate II is formed during the reaction. The experimental ratios of a and b are a function of the amount of spiro[2.5] intermediate II formed during the reaction. Therefore, in order to understand the underlying factors that influence the formation of intermediate I and spiro[2.5] intermediate II, we investigated the influence of the functional group on the electronic environment of the aryl ring in allylaryl derivatives using the DFT-based method M06-2X/6-31++G(d, p) theory and basis set. The geometrical optimization of bromonium intermediate I (Figure 1, center) of allylaryl derivatives was used as a starting point for this investigation as it is the first intermediate formed during addition of bromine to alkenes. It was observed that the optimized geometry of the starting structure of intermediate I either had rearranged to resemble more like spiro [2.5] intermediate II or resemble more like intermediate I. The optimized structures showed that the extent of rearrangement was dependent on the functional group present on the aryl ring. This extent was measured in terms of the distance between carbon atoms C1 and C3 (C1···C3) as shown in Figure 1. The C1···C3 is crucial for the formation of the three-membered ring in the spiro[2.5] intermediate II. The influence of the nature of the R-group on the distance between C1 and C3 can be clearly observed in Figure 1. For instance, in the presence of strong EDG like −OMe, there is a bond formation between C1 and C3 atoms with a bond length of 1.602 Å (Figure 1a), leading to formation of the spiro [2.5] intermediate II. However, this bond distance gradually increases (weakens) as the nature of the functional group gradually shifts from EDG to EWG with longest C1···C3 distance of 2.384 Å in the case of pentafluoro derivative. The interatomic distance between C1···C3 in allylaryl derivatives increases in the following order: −OMe < −Me < −F < −H < −CF3 < pentafluoro, see Figure 1 and Table 2. Alternatively, the C3···Br distance had an inverse relationship to C1···C3, with shortest C3···Br distance of 2.066 Å in the pentafluoro derivative, which indicates the preference to form bromonium intermediate I, whereas derivatives that form spiro[2.5] intermediate II had a significantly longer C3···Br distance, see Table 2. Thus, the optimized structures clearly indicate the formation of the spiro[2.5] intermediate II in allylaryl derivatives R = −OMe, −Me, −F, and −H, which results in the formation of the 1,3-dibromo compound b, whereas the −CF3 and pentafluoro derivatives resembled bromonium intermediate I that leads to the formation of the 2,3-dibromo compound a in the reaction. These observations from the optimized structures of intermediates I and II are in good agreement with experimentally observed trends indicating gradual change in the ratio of formation of a:b such as (1:4), (2:1), (8.5:1), (11.5:1), (1:0), and (1:0) for allylaryl derivatives with R = −OMe, −Me, −F, −H, −CF3, and pentafluoro derivatives, respectively (Table 1).

Figure 1.

Figure 1

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Extent of formation of intermediate II from geometrical optimization of bromonium cation intermediate I for various allylaryl derivatives: (a) −OMe, (b) −Me, (c) −F, (d) −H, (e) −CF3, and (f) pentafluoro. The simulations were performed with the M06-2X/6-31++G(d,p) theory and basis set.

Table 2. Values of the Harmonic Oscillator Model of Aromaticity (HOMA) Index for the Allylaryls, Carbocationic Intermediates, and the Difference in HOMA Index between Allylaryls and Cationic Intermediates.

harmonic oscillator model of aromaticity (HOMA)
derivatives allylaryls (A) cationic intermediates (C) difference (A–C)
pentafluoro 0.9989 0.9949 0.0040
–CF3 0.9865 0.9023 0.0842
–F 0.9881 0.8217 0.1664
–H 0.9857 0.8743 0.1114
–Me3 0.9816 0.7995 0.1821
–OMe 0.9819 0.6136 0.3683
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Figures 1 and 2 indicates that this order of electron density is inversely correlated with the distance between C1 and C3 carbon atoms. The higher is the electron density on the aryl ring, the smaller the distance between C1 and C3, which is key to the formation of the spiro[2.5] intermediate II. For instance, the C1···C3 distance in allylaryl derivatives (−OMe) with highest electron density in the aryl ring is 1.602 Å, while the C1···C3 distance in the pentafluoro derivative with lowest electron density in the phenyl ring

Figure 2.

Figure 2

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Electron density map of allylaryl derivatives obtained from electrostatic potential using the CHELPG method at the M06-2X/6-31++G(d,p) theory and basis set. The allylaryl derivatives are as follows: (a) −OMe, (b) −Me, (c) −H, (d) −F, (e) −CF3, and (f) pentafluoro.

In order to understand the underlying factors responsible for the formation of the spiro [2.5] intermediate II, we investigated the electronic environment of starting allylaryl derivatives (1) in Scheme 1. The analysis of the electronic environment was performed by estimation of atomic charges using CHarges from Electrostatic Potentials using a Grid-based (CHELPG) method developed by Breneman and Wiberg.30 In Figure 2, the electron density maps indicate a gradual decrease in the electron density on the phenyl ring of the allylaryl derivatives in the following order: −OMe > −Me > −H > −F > −CF3 > pentafluoro. A comparison between is 2.384 Å.

In order to further investigate the influence of functional groups on the 1,2-shift rearrangement reaction, we estimated the HOMA index for allylaryls and cationic intermediates. The HOMA index is a widely used molecular descriptor that is based on the geometrical aromaticity of the compounds. This index assigns a value to the molecules indicating their aromatic character, with benzene as a standard with a HOMA value of 1 indicating that it is perfectly aromatic, whereas a compound with a HOMA value of 0 indicates that it is not aromatic.35 The HOMA values of allylaryls ranged between 0.9816 for −Me and 0.9989 for pentafluoro derivative, indicating that all allylaryl derivatives are significantly aromatic (Table 2). Interestingly, cationic intermediates exhibited significant loss of aromatic character in derivatives containing EDG as indicated by lower values for HOMA index. The loss of aromatic character was the most dramatic in the case of cation intermediates with strong EDG such as R= −OMe, indicating significant involvement of the aromatic ring and resulting in formation of the spiro[2.5] intermediate II. On the contrary, the cationic intermediate with an electron-deficient aryl ring such as the pentafluoro derivative exhibited little to no loss of aromatic character compared to its starting allylaryl, indicating no involvement of the aryl ring and promotion of formation of cationic intermediate I.

Additionally, we performed Wiberg bond order (BO) analysis to investigate the strength of the C1···C3 interaction in the cationic intermediates. Table 3 depicts the C1···C3 interaction bond distance and the corresponding bond order. It can be clearly observed that the shorter the distance between the C1 and C3 carbon atoms, the higher is the bond order. The cationic derivative with the −OMe group exhibited a BO of 0.8, giving the C1···C3 interaction a single bond-like character, whereas the pentafluoro derivative exhibited a BO of 0.12, an indication of a very weak C1···C3 interaction. In other words, EDGs on the aryl ring enhanced the electron density and resulted in shorter distance between the C1···C3 carbon atoms, thus promoting 1,2-shift and the formation of the spiro[2.5] intermediate II; whereas, the derivatives containing EWGs lack electron density and thus favor conservation of bromonium intermediate I. This highlights the influence of EDGs and EWGs on the extent of formation of intermediates I and II.

Table 3. Table Comparing the C1···C3 Interaction Distance and the Wiberg Bond Order Values.

derivatives C1···C3 distance (Å) C3···Br distance (Å) Wiberg bond order
pentafluoro 2.384 2.066 0.12
–CF3 1.700 2.739 0.65
–F 1.647 2.765 0.73
–H 1.670 2.754 0.69
–Me 1.640 2.772 0.74
–OMe 1.602 2.791 0.80
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Although it is clear that the electron density on the phenyl ring of the allylaryl derivative plays a significant role in the outcome of the bromination reaction, there are exceptions. For instance, in monofluoro derivative of allylaryl, despite a lower electron density in the phenyl ring compared to the unsubstituted derivative (Figure 2c,d), the former has a slightly shorter C1···C3 distance of 1.647 Å compared to the latter with a C1···C3 distance of 1.670 Å (Figure 1c,d). This indicates that there is a greater chance of formation of spiro [2.5] intermediate II in monofluorinated derivative compared to unsubstituted derivative. This was confirmed from the experimental data in Table 1, which indicate the formation of higher amounts of b in the monofluorinated derivative compared to the unsubstituted derivative. Upon further investigation, the electrostatic potential (ESP) charge analysis indicated a charge of −0.255 on the fluorine atom in the monofluorinated derivative of allylaryl, suggesting that fluorine is pulling the electron density due to the inductive effect. On the other hand, the Wiberg BO value of 1.21 for the C–F bond in the monofluorinated derivative indicated a partial double bond character; this BO increases to 1.32 in the spiro[2.5] intermediate II, which is suggestive of the resonance effect in action. Interestingly, the ESP charge on the F atom in the spiro[2.5] intermediate II is reduced to −0.18, which is an indication that fluorine loses the overall electron density during the rearrangement reaction. Furthermore, there is a bigger difference in the HOMA index value of the allyaryl and the spiro[2.5] intermediate in the case of the monofluorinated derivative compared to the unsubstituted derivative; see Table 2. This is indicative of higher involvement of the benzene ring in the 1,2-shift rearrangement in the monofluorinated derivative compared to the unsubstituted allylaryl derivative. Overall, the analysis indicates that the resonance effect dominates over the inductive effect in the monofluorinated derivative, thus leading to the formation of a tighter spiro[2.5] intermediate II compared to the unsubstituted derivative.

The thermochemical analysis of a system provides critical insight into the feasibility of a process by gauging the stability of the intermediates and the products with respect to starting materials involved in the chemical process. It also helps us in understanding the relative stability of various reaction intermediates that are involved in the systems under consideration and provides mechanistic insight. The free energy of formation of reaction intermediates I and II from 1 was calculated using eq 1, which revealed that it is a thermodynamically favorable process (Table 4). Further, we calculated the difference in the free energy change (ΔΔG) of intermediates of various allylaryl derivatives using eq 2. During this calculation, we used the allylaryl derivative R = H as a baseline (ΔΔG = 0) with respect to which ΔΔG for other allylaryl derivatives containing EDGs and EWGs was calculated. It was noted that the ΔΔG values for allylaryl derivatives with EDGs such as R= −OMe and −Me were lower than that of the allylaryl derivative R= −H by 12.48 and 5.45 kcal/mol, respectively. However, in the case of allylaryl derivatives with EWGs such as R= −F, −CF3, and pentafluoro, the ΔΔG values were higher than that of R= −H by 1.26, 9.92, and 14.47 kcal/mol, respectively (Table 4). This trend of ΔΔG of allylaryl derivatives is inversely related to the C1···C3 distance in the optimized structures of the cationic intermediates. In Figure 3, it can be clearly observed that the allylaryl cationic intermediates with shorter C1···C3 distance have low ΔΔG values, whereas the longer distance between C1···C3 leads to higher values in ΔΔG. From this correlation, the shorter C1···C3 distance results in a better interaction of the C3 atom with the aryl ring and enhanced charge distribution that leads to stabilization of the spiro[2.5] intermediate II and lower ΔΔG values, whereas the longer C1···C3 distance reduced the interaction of C3 carbon atom with the aryl ring and leads to formation of a structure that resembles intermediate I, which has higher ΔΔG values. Interestingly, from the plot, it can also be observed that for the pentafluoro derivative, the ΔΔG value does not rise proportionally with the increase in the C1···C3 distance of 2.384 Å. This is an indication that for the reaction intermediates of bromination of allylaryl derivatives containing EWGs that are stronger than −CF3, the ΔΔG value attains a plateau. This is because the C1···C3 distance reached the limit of maximum distance between carbon atoms in a three-atom system with bond angles between C1–C2–C3 getting close to a tetrahedral angle of 104.74 degrees.

Table 4. Calculated Change in Free Energy (ΔG) of Formation of Carbocation Intermediate for Various Allylaryl Derivatives and the Relative Difference in the Free Energy Change (ΔΔG) of Formation of Carbocation Intermediate among Allylaryl Derivatives.

allylaryl derivative ΔG (kcal/mol) carbocation intermediate ΔΔG (kcal/mol) between carbocation intermediate
pentafluoro –105.27 14.47
–CF3 –109.82 9.92
–F –118.48 1.26
–H –119.74 0
–Me –125.19 –5.45
–OMe –132.22 –12.48
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Figure 3.

Figure 3

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Plot depicting the correlation between the interatomic distance between carbon atoms C1 and C3 and ΔΔG of various allylaryl derivatives.

In summary, the optimized geometries of the cationic intermediates indicate that the allylaryl derivatives containing EDGs formed a spiro[2.5] intermediate II as indicated by the bond formation between the carbon atom C1 on the aryl ring and the carbon atom C3 of the allylic double bond. The C1···C3 interaction distance was shortest in allylaryl compounds with strong EDG such as −OMe. A gradual shift in the nature of the functional group from EDG to EWG resulted in elongation/weakening of C1···C3 interaction with no interaction in the case of the aryl ring with strong EWG. This trend was in agreement with experimentally observed results indicating the formation of the 1,3-dibromo product in reaction with allylaryl derivatives containing EDG and their gradual decrease in the case of allylaryls containing EWG. The electron density mapping of the allylaryls indicates inverse relationship between the electron density on the aryl ring and the interaction distance between the C1 and C3 carbon atoms, clearly indicating that electron-rich aryl ring promotes formation of spiro[2.5] intermediate II. The HOMA index indicated that the phenyl rings with EDG participated in the 1,2-shift and promoted the formation of spiro[2.5] intermediate II. The Wiberg BO analysis agreed with the trend for C1 and C3 interaction distance with higher BO values for shorter C1···C3 distance. The thermochemical analysis of the cationic intermediates indicated that the allylaryl derivatives with EDG exhibited lower ΔΔG values compared to the derivatives with EWG. The lower ΔΔG values in the allylaryl derivative containing EDG arise from the involvement of the aryl moiety in stabilization of the cationic intermediate and formation of spiro[2.5] intermediate II, which is absent in the case of derivatives containing EWG. Therefore, experimental observations coupled with computational insight on geometry analysis, electron density mapping, and thermochemical analysis indicate that the aryl ring in the electron-rich allylaryl systems undergoes a 1,2-shift to produce spiro[2.5] intermediates, which then form 1,3-dibromo compounds.

Acknowledgments

The authors would like to acknowledge the College of Arts and Science and the high-performance computing facility at Florida Gulf Coast University and Seidler Fellowship for partially supporting this work.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.3c04513.

  • Dibromide Compounds, Experimental Data, Cartesian coordinates (PDF)

Author Contributions

A.B. and D.V.W. conceived, designed the work, and analyzed the data. D.H. performed the simulations, and S.R.I. conducted the experimental part. The manuscript was written by A.B. and D.V.W. All authors have given approval to the final version of the manuscript.

This original research article was supported by the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH) under award number 1R15GM141726-01.

The authors declare no competing financial interest.

Supplementary Material

ao3c04513_si_001.pdf (1.1MB, pdf)

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