Theoretical Investigation on Rh(III)- And Pd(II)- Catalyzed Regioselective Oxidative Annulation of 2-Arylimidazo[1,2-A]Pyridine with Cinnamalde-Hyde for Synthesis of N-Heterocycle

Introduction

As an interesting part with privileged chemical moiety, imidazo[1,2-a]pyridines have been found in several marketed drugs. The necopidem and saripidem were used for treatment of anxiety and insomnia [1]. The therapeutic effect of minodronic acid was evaluated for osteoporosis [2]. Olprinone was a newly developed phosphodiesterase III inhibitor and GSK812397 was CXCR4 receptor antagonist [3,4]. Hence, the bicyclic system imidazo-[1,2-a]pyridine with bridgehead nitrogen was an important biologically active moiety towards synthetic drug molecule in medicinal chemistry [5]. In addition, with extended π-system, this framework has shown electronic and optical properties [6,7]. The imidazo[1,2-a]pyridine has been targeted for synthetic chemists in decades due to its significance in material chemistry. Especially the C3-functionalized imidazo[1,2-a]pyridine was more easily attacked by electrophile or radical with electron-rich character including C3-alkylation, C3-carbonylation, C3-arylation, C3-selenation, C3-N-Substitution, and C3-halogenation [8]. Recently, transition-metal-catalyzed regioselective functionalization and transition-metal-free C-H functionalization have attracted considerable attention [9,10]. Therefore, it is important to construct such molecular skeleton efficiently and greenly.

As versatile organic electronic material, arene and heteroarene have received considerable attention with extended conjugated π-system [11]. These hybrid scaffolds especially 2-arylimidazo[1,2-a]pyridine were key components of pharmaceuticals [12]. The annulation with appropriate coupling partner catalyzed by transition-metal could lead to several heteropolycyclic aromatic systems. The direct dehydrogenative annulation of imidazo[1,2-a]pyridines with diarylalkynes catalyzed by Pd(OAc)₂ was developed to synthesize π-conjugated polyaromatic heterocycles [13]. Rh(III)-catalyzed annulative C-H functionalization of arenes with sulfoxonium ylides was realized affording structurally diverse fused hetero- and carbocycles [14]. The naphtho[1′,2′:4,5]imidazo[1,2-a]-pyridine was synthesized from cascade reaction of 2-arylimidazo[1,2-a]pyridines with α-diazo carbonyl compounds via Rh(III)-catalyzed regioselective C(sp2)-H alkylation followed by intramolecular annulation [15]. The bridged imidazopyridine was yielded by Rh(III)-catalyzed bicyclization with cyclic enone [16]. A selenium-coordinated Pd(II) trans-dichloride could catalyze site-selective annulation of 2-arylimidazo[1,2-a]pyridines leading to 2,3,4-triarylphenyl-1,7b-diaza-cyclopenta[cd]indene [17]. The naphtho[1′,2′:4,5]imidazo[1,2-a]pyridine was produced via oxidative C-H/C-H annulation of imidazopyridine with vinylene carbonate catalyzed by Rh(III) [18]. The Rh(III)-catalyzed [4 + 2] oxidative cycloaddition was reported to furnish maleimide fused benzocarbazoles [19]. Similarly, a diverse range of benzo[e]pyrido[1',2':1,2]imidazo[4,5-g]isoindole was achieved through Ru(II)-catalyzed C-H metalation followed by maleimide insertion and intramolecular cyclization [20].

As powerful platform of molecular synthesis, many advances are developed in electro catalytic, photo induced and asymmetric C-H activation [21]. Therefore the progress of transition-metal-catalyzed C-H activation in heterocycle has been particularly noticeable in recent years, such as the access to isogranulatimide alkaloid via Rh(III)-catalyzed dehydrogenative annulation/spirocyclization and switchable regioselective hydroalkylation of 2-arylindole with maleimide [22,23]. After Hanchate reported the synthesis of furanone-fused 1,2-benzothiazine via Rh(III)-catalyzed sulfoximine-directed C-H activation [24], a new breakthrough was Meena’s construction of fused N-heterocycle via regioselective oxidative annulation of 2-arylimidazo[1,2-a]pyridine with cinnamaldehyde [25]. Although two different isomeric annulated products were provided, there is no report about detailed mechanistic study explaining the obvious advantage of regioselective oxidative annulation. What’s the function of [RhCp*Cl₂]₂ in the generation of 5-arylnaphtho-[1′,2′:4,5]imidazo[1,2-a]pyridine-6-carbaldehyde?

How 1,7-diarylimidazo[5,1,2-cd]indolizine-6-carbaldehyde was afforded with Pd(OAc)₂ as catalyst? Why the regioselectivity was dependent on different transition-metal, wherein the regulation of changes in valence states and the effects of solvent? To solve these mechanic problems in experiment, an in-depth theoretical study was necessary for this strategy applied versatile 2-arylimidazo[1,2-a]pyridine. The Density Functional Theory (DFT) method was employed focusing on the promotion during the transformation from Rh(III) to Rh(I) and from Pd(II) to Pd(0).

Computational Details

The geometry optimizations were performed at the B3LYP/BSI level with the Gaussian 09 package [26,27]. The mixed basis set of LanL2DZ for Rh, Pd and 6-31G(d) for non-metal atoms [28-32] was denoted as BSI. Different singlet and multiplet states were clarified with B3LYP and ROB3LYP approaches including Becke's three-parameter hybrid functional combined with Lee-Yang-Parr correction for correlation [33-39]. The nature of each structure was verified by performing harmonic vibrational frequency calculations. Intrinsic Reaction Coordinate (IRC) calculations were examined to confirm the right connections among key transition-states and corresponding reactants and products. Harmonic frequency calculations were carried out at the B3LYP/BSI level to gain Zero-Point Vibrational Energy (ZPVE) and thermodynamic corrections at 393 K, 413 K and 1 atm for each structure in N,N-dimethylacetamide (DMA) and N,N-dimethylformamide (DMF). The solvation-corrected free energies were obtained at the B3LYP/6-311++G(d,p) (LanL2DZ for Rh, Pd) level by using Integral Equation Formalism Polarizable Continuum Model (IEFPCM) in Truhlar’s “density” solvation model [40-42] on the B3LYP/BSI-optimized geometries.

As an efficient method obtaining bond and lone pair of a molecule from modern ab initio wave functions, NBO procedure was performed with Natural bond orbital (NBO3.1) to characterize electronic properties and bonding orbital interactions [43-44]. The representation of electron localization function (ELF) attractors were obtained through Natural Population Analysis (NPA) based on the Molecular Electron Density Theory (MEDT) [45]. The wave function analysis was provided using Multiwfn_3.7_dev package [46] including research on Frontier Molecular Orbital (FMO), ELF and Mayer Bond Order (MBO).

Results and Discussion

Based on previous research [21-25], the mechanism was explored for regioselective oxidative annulation of 2-arylimidazo[1,2-a]pyridine 1 with cinnamaldehyde 2 catalyzed by and leading to different isomeric N-heterocycle 3 (path A) and 4 (path B) (Scheme 1). Illustrated by red arrow of Scheme 2, the monomeric cationic rhodium complex Cp*RhCl2 was taken as model catalyst of Rh(III) to coordinate with N atom of 1 forming intermediate A. After the removal of HCl, a rhodacycle B was generated via o-C-H bond activation of C1-phenyl ring. The chelation of it with 2 afforded C followed by oxidative migratory insertion into Rh-C1 bond. The elimination of another HCl promoted rollover along C5-C6 axis producing seven-membered rhodacycle D which underwent reduction giving E and Cp*Rh species. Finally, oxidation of E and Rh(I) furnished six-membered annulated product 3 and recovered Rh(III).

In the case catalyzed by PdL2(OAc)2 as Pd(II) (blue arrow), the electrophilic palladation at imidazolyl C4 of 1 deliver-ing HOAc takes place initially to generate intermediate I, from which the insertion of 2 afforded the carbopalladation II. Then the alkenylated III was produced via β-hydrogen elimination with the help of OAc and Pd(0)L2. Subsequently, IV was obtained with palladation C7 which furnished a six-membered palladacycle V by concerted metalation deprotonation. The reductive elimination from V yielded five-membered annulated product 4 and the regeneration of Pd(II) upon oxida-tion of Pd(0). The optimized structures of TSs in Scheme 2 were listed by Figure 1. The activation energy was shown in Table 1 for all steps. Supplementary Table S1, Table S2 provided the relative energies of all stationary points. According to experiment, the Gibbs free energies in DMA and DMF solution phase are discussed here.

Scheme 1: Regioselective oxidative annulation of 2-arylimidazo[1,2-a] pyridine 1 with cinnamaldehyde 2 catalyzed by Rh(III) and Pd(II) leading to different isomeric N-heterocycle 3 and 4.

Scheme 2: Proposed reaction mechanism of regioselective oxidative annulation of 1 with 2 leading to 3 preferred by Rh(III) and 4 favored by Pd(II). TS is named according to the two intermediates it connects.

Rh(III)-catalyzed Annulation Via Path A

Initially, a complex A was located through the coordination of Cp*RhCl2 with 1 at N atom (black dash line of Figure 2a). With the reactive intermediate in hand, dehydrogenation proceeds via ts-Ai1 as step 1 with a mediate activation energy of 26.0 kcal mol^-1 relative to the starting point A. The formation of i1 realized the o-C-H bond activation at C1-phenyl ring endoergic by 15.8 kcal mol^-1. The transition vector of ts-Ai1 corresponds to the moving of H1 from C1 to Cl1 and closing of C1 to Rh slightly later (1.32, 1.67, 2.19 Å) (Figure S1a). This indicated the activation of phenyl C1 was driven by one coordinating Cl atom of catalyst and the Rh···C1 bonding was further promoted by Rh(III). After the removal of HCl, a five-membered rhodacycle B was generated involving a similar relative energy with i1. Thankfully the following combination of 2 and B brought about the 7.7 kcal mol^-1 energy decrease of i2 as the starting point of step 2, which occurs via ts-i2C with activation energy of 35.9 kcal mol^-1 endoergic by 1.6 kcal mol^-1 furnishing seven-membered complex C with Rh-C2, C2-C3 and C1-C3 single bonds. The transition vector includes the elongation of Rh-C1, C2-C3 and concerted approach of Rh···C2, C1···C3 (2.24, 1.46, 2.15 and 1.98 Å), suggesting oxidative migratory insertion of C2-C3 double bond into Rh-C1 (Figure S1b). Kinetically, this chelation process is determined to be rate-limiting of path A leading to product 3.

Figure 1: Proposed reaction mechanism of regioselective oxidative annulation of 1 with 2 leading to 3 preferred by Rh(III) and 4 favored by Pd(II). TS is named according to the two intermediates it connects.

Table 1: The activation energy (in kcal mol-1) of all reactions in gas and solvent.

Figure 2: Relative Gibbs free energy profile catalysed by Rh(III) and Pd(II) in solvent phase starting from complex (a) A, A-pd, i2, i2-pd, i4 (b) in1, in1-rh, IV, V.

To highlight the idea of feasibility for changes in electron density and not molecular orbital interactions are responsible of the reactivity of organic molecules, quantum chemical tool Multiwfn was applied to analyze of electron density such as topological analysis of ELF, MBO results of bonding atoms and contribution of atomic orbital to HOMO of typical TSs (Table 2,3). ELF isosurface was presented by Figure 3 with green color denoting the electron localization. The marked small green part means good electron delocalization between two bonding atoms. The progress of bonding changes were fo-cused on along reaction coordinate based on a new reactivity theory named MEDT. On ELF isosurface of ts-Ai1, besides obvious connection of Rh-C1, the electron is mainly localized on H1 and Cl1 in agreement with the d electron of Rh (23.49%), bonding orbital of C1-H1 (6.77%, 3.34%) and p electron of Cl1 (7.07%) contributed to HOMO (Figure 4). This is beneficial for the abstraction of H1 by Cl1 and Rh-C1 bonding just as the results of MBO values for H1···Cl1 and Rh···C1 (0.46, 0.55). The correctness of ts-i2C is also verified by ELF analysis and HOMO composition. There is direct Rh-C2 linkage (25.56%, 3.23%) and bonding electron between C1 and C3 (5.61%, 8.86%), which is confirmed by MBO values of Rh···C2 and C1···C3 (0.59, 0.51).

Table 2: Mayer Bond Order (MBO) of typical transition states.

Table 3: Contribution (%) of Natural Atomic Orbital (NAO) to Highest Occupied Molecular Orbital (HOMO) of typical transition states.

Figure 3: Representation of ELF graph (isosurface value=0.84), attractors and valence basin population for typical TSs.

Figure 4: Highest Occupied Molecular Orbital (HOMO) of typical TSs. Different colors are used to identify the phase of the wave functions.

The next cleavage of another coordinated Cl atom in forms of HCl occurs in step 3 to get ready for the coordination of Rh transfer from N to C4 of step 4. Via ts-Ci3, the activation energy is 25.5 kcal mol^-1 with respect to C exothermic by -1.7 kcal mol^-1 leading to i3, from which the rupture of HCl gives i4 as the new starting point of following ring rotation. With previous preparation the rollover along C5-C6 axis is fairly easy via ts-i4D with a smaller barrier of 17.1 kcal mol^-1 tremendously exothermic by -32.5 kcal mol^-1 delivering stable complex D with seven-membered rhodacycle. Besides the breaking of Cl2 from Rh (2.8 Å), the transition vector of ts-Ci3 corresponds to the shift of H2 from C4 to Cl2 (1.97, 1.58 Å). The transition vector of ts-i4D indicates a loose structure with closing of Rh to C5 and transient no longer boned of Rh···C2 (2.54, 2.17 Å). The above two steps are both readily accessible with low activation energy from kinetics and quite favorable from thermodynamics with huge heat release.

From D the last step 5 takes place via ts-Di5 with small barrier of 23.2 kcal mol-¹ continuously exothermic by -50.9 kcal mol-¹. When this reduction elimination was completed, i5 would be generated binding complex E and Cp*Rh as precursors of one annulated product 3 and recovered catalyst Rh(III) with the participation of oxidants. From the transi-tion vector of ts-Di5, C2 and C4 is linking to form new six-membered ring along with the stretching of Rh-C2, Rh-C4 bond to squeeze Rh (2.03, 2.40, 2.11 Å) (Figure. S1c). The rationality of ts-Di5 can be approved by ELF isovalue of MEDT analy-sis. Although Rh-C2, Rh-C4 single bond still exists, there is remarkable green color denoting electron distribution between C2 and C4 (3.29%, 9.14%). The upcoming formation of C2-C4 bond is in accordance with MBO values for Rh···C2, Rh···C4, C2···C4 (0.77, 0.74, 0.25).

Pd(II)-Catalyzed Annulation Via Path B

When the reaction was catalyzed by Pd(II), the process delivering another major isomeric annulated product 4 was lo-cated as path B (black dash line of Figure 2b). The initial electrophilic palladation forms C4-Pd bond for complex I, which is reactive with a relative energy higher by 15.0 kcal mol-¹ than isolated species of 1 and catalyst after the departure of HOAc. The introduction of 2 stabilizes intermediate in1 as the starting point, from which the insertion of olefin double bond takes place via ts-in1II in step 1 with a barrier of 34.8 kcal mol-¹ generating carbopalladation complex II endoergic by 1.4 kcal mol-¹. The transition vector corresponds to the stretching of C4-Pd to breaking, extension of C2-C3 double bond to single one and the simultaneous bonding of C2···Pd, C3···C4 (2.12, 1.42, 2.28 and 2.26 Å) (Figure S1d). Next step 2 proceeds via ts-IIin2 with a slightly lower barrier of 32.5 kcal mol-1 relative to II exothermic by -5.4 kcal mol-¹ affording stable intermediate in2. Thus, step 1 is determined to be rate-limiting of path B, which is also the insertion process of 2. Two aspects of atomic motions can be seen from the transition vector. One is H3 transferring from C3 to O1 (1.60, 1.10 Å) denoting β-hydrogen elimination assisted by OAc. The other is C2-Pd fracture and C2-C3 contracted to double one (2.32, 1.47 Å). The alkenylated III is produced after the catalyst leaving in forms of HOAc and and Pd(0)L2.

The complex IV with C7-Pd bond is formed through a second electrophilic palladation based on the reintroduction of PdL2(OAc)2 and the removal of one HOAc just like the generation of I. The step 3 occurs via ts-IVin3 from IV with acti-vation energy of 23.0 kcal mol^-1 furnishing intermediate in3 exothermic by -1.5 kcal mol-¹. The transition vector demon-strates a concerted metalation deprotonation in collaborative asynchronous mode including the earlier H shifting C2···H4···O2 and later linkage of C2-Pd (1.43, 1.21, 2.33Å) (Figure S1f). Evidently, H4 can be easily taken away from C2 driven by OAc of catalyst. This assembles HOAc on one hand to leave freely and makes C2 more negative enhancing its nucleophilicity to Pd on the other. Hence in3 is characterized with stable six-membered palladacycle and C2-C3 double bond, from which complex V is given after the departure of HOAc. The reductive elimination takes place in step 4 via ts-Vin4 with lower barrier of 10.2 kcal mol-¹ more dramatically exothermic by -26.3 kcal mol-¹ delivering in4. Involving ring closure via C2···C7 approaching and departure of C2···Pd, C7···Pd (2.05, 2.09, 2.07 Å), the transition vector presents a process squeezing Pd(0)L2 and liberating five-membered product 4.

On ELF isosurface of ts-in1II, both the linkage between C2 and Pd and green color between C3 and C4 are obvious denoting bonding interaction. This echoes MBO values of Pd···C2 and C3···C4 (0.47, 0.29). Meanwhile Pd is leaving C4 together with the elongation of C2···C3 (0.72, 1.18). Here HOMO is composed by d electron of Pd, p lone pair of C4 (5.55%, 5.61%) and anti-bonding orbital on C2-C3 (1.02%, 10.71%), which indicates the coordination on Pd changing from C4 to C2. For ts-IIin2, C2 and Pd is still bonded with MBO value of 0.54. H3 is already leaving from C3 to O1 shown by the green color on ELF isosurface among them as well as MBO values for C3···H3 and H3···O1 (0.31, 0.52). The mismatch of d orbital on Pd (25.78%) and anti-bonding π electron on C2-C3 (14.58%, 6.01%) predicts the cleavage of C2-Pd. The electron on p lone pair orbital of O1 (3.79%) is conducive for H3 to approach. When it comes to ts-IVin3, HOMO is mainly located on bonding orbital of C2-Pd (26.32%, 6.33%) beneficial for the linkage. A small part on H4 and O2 points the following bonding between them (1.51%, 1.33%). The correctness is verified by green bond on C2-Pd and color by ELF analysis. MBO values for Pd···C2 and H4···O2 (1.06, 0.28) is also according to this outcome.

Regio-Divergence and Solvent Effect

To explore the relation of catalysts with regio-divergence puzzled in experiment, the annulation via Pd(II)-catalyzed path A and Rh(III)-catalyzed path B are also investigated (red dash line of Figure 2) in contrast with dominant paths (black dash line).

On one hand for the former, the H1 capture was realized with the assistance of OAc and phenyl C1 was coordinated to Pd(II) via ts-Ai1-pd (1.42, 1.19, 2.21 Å) (Figure 1) with a barrier of 37.8 kcal mol-¹ relative to its starting point A-pd, which turns to be rate-limiting as step 1. The olefin insertion into Pd-C1 in step 2 is via ts-i2C-pd with a barrier of 31.5 kcal mol-1 with respect to i2-pd. Compared with the case of Rh(III), although the barrier is slightly reduced owing to one OAc ligand not bonded to Pd alleviating space congestion, path A is more preferred by Rh(III) considering the lower barrier of chela-tion in rate-limiting step 2 (35.9 kcal mol-¹) yielding dominant 3 as regioselectivity. On the other for the latter, the barriers of step 1 via ts-in1II-rh and step 2 via ts-IIin2-rh (40.8, 41.3 kcal mol-¹) are both higher distinctly than the case with Pd(II) involving rate-limiting step 1 (34.8 kcal mol-¹). Furthermore from thermodynamics, compared with stable interme-diate in2 exothermic by -5.4 kcal mol-1, the production of in2-rh is required to be endoergic by 28.6 kcal mol-¹. Hence the regioselectivity of 4 via path B dominated by Pd(II) is more apparently. Finally, the region-divergence of isomeric 3 and 4 are both kinetically controlled by catalyst presenting with six- and five-membered annulated cycles.

The impact of DMA and DMF solution is studied in view of the solvent effect on reaction estimated by our approach [28-32]. Obviously, the absolute energies of all stationary points in solution are lower than those in gas phase (Table S1). In general, DMA exerted bigger influence than DMF on annulation via both path A and B with relative energies de-creased by -21~-45 kcal mol-¹ vs -20~-35 kcal mol-¹. This range was -25~-45 kcal mol-1 vs -21~-27 kcal mol-¹ in DMA for path A catalyzed by Rh(III) and Pd(II). For most steps, the activation energies are reduced in solution phase compared with in gas (Table S2). With reduction values -3~-5 kcal mol-1, the solvent effect of DMA is also more visible than DMF. Accordingly, the DMA and DMF solution both produce favorable influence on this regioselective oxidative annulation of 2-arylimidazo[1,2-a]pyridine with cinnamaldehyde catalyzed by Rh(III) and Pd(II) leading to different isomeric N-heterocycles.

Conclusions

Our DFT calculations provide the first theoretical investigation on regio-divergent oxidative annulation of 2-arylimidazo[1,2-a]pyridine with cinnamaldehyde. For reaction catalyzed by Rh(III), the coordination at N exists for initial complex followed by C-H activation of phenyl and chelation. The seven-membered rhodacycle generated by rollover undergoes elimination reduction gives six-membered N-heterocycle preferred as major product. For Pd(II) cata-lyzed case, the palladation at imidazolyl C takes place at first followed by alkenylated insertion and metalation deproto-nation furnishing six-membered palladacycle, the reductive elimination of which yields favored isomer with five-membered N-heterocycle. The olefin insertion is rate-limiting step for both Rh(III) and Pd(II).

The promotion of catalyst is reflected in the deprotonation assisted by ligand OAc or Cl and coordination of metal. Based on the comparison between possible paths, regio-divergence of isomeric product is kinetically controlled by cata-lyst presenting as six- and five-membered annulated cycles. The positive solvation effect is suggested by decreased abso-lute and activation energies in DMA and DMF solution compared with in gas. These results are supported by Multiwfn analysis on ELF isosurface, FMO composition of specific TSs, and MBO value of vital bonding, breaking.

Electronic Supplementary Material

Supplementary data available: [Computation information and cartesian coordinates of stationary points; Calculated rela-tive energies for the ZPE-corrected Gibbs free energies (ΔG_gas), and Gibbs free energies (ΔG_sol) for all species in solution phase at 393, 413 K.]

Acknowledgements

This work was supported by National Natural Science Foundation of China (21973056, 21972079) and Natural Science Foundation of Shandong Province (ZR2019MB050) and Key Laboratory of Agricultural Film Application of Ministry of Agriculture and Rural Affairs, P.R. China.

Conflicts of Interest

The authors declare no conflicts of interest.

References

• Sanger DJ (1995) Behavioural effects of novel benzodiazepine (ω) receptor agonists and partial agonists: increases in punished responding and antagonism of the pentylenetetrazole cue. Behav Pharmacol 6(2): 116-126.
• Kitamura N, Shiraiwa, H, Inomata H, Nozaki T, Ikumi N, et al. (2018) Efficacy and safety of minodronic acid hydrate in patients with steroid-induced osteopo-rosis. Int J Rheum Dis 21: 813-820.
• Mizushige K, Ueda T, Yukiiri K, Suzuki H (2002) Olprinone: A phosphodiesterase III inhibitor with positive inotropic and vasodilator effects. Cardiovasc Drug Rev 20(3): 163-174.
• Jenkinson S, Thomson M, McCoy D, Edelstein M, Danehower S, et al. (2010) Blockade of X4-tropic HIV-1 Cellular entry by GSK812397, a potent noncompetitive CXCR4 receptor antagonist. Antimicrob. Agents Chemother 54: 817-824.
• Goel R, Luxami V, Paul K (2016) Imidazo[1,2-a] pyridines: Promising drug candidate for antitumor therapy. Curr Top Med Chem 16(30): 3590-3616.
• Kielesiński L, Tasior M, Gryko DT (2015) Polycyclic imidazo[1,2-a] pyridine analogs - synthesis via oxidative intra-molecular C-H amination and optical properties. Org Chem Front 2: 21-28.
• Firmansyah D, Banasiewicz M, Deperasińska I, Makarewicz A, Kozankiewicz B, et al. (2014) Vertically π-expanded imidazo[1,2-a] pyridine: The missing link of the puzzle. Chem Asian J 9(9): 2483-2493.
• Tashrifi Z, Mohammadi Khanaposhtani M, Larijani B, Mahdavi M (2020) C3-Functionalization of imid-azo[1,2-a] pyridines. Eur J Org Chem 2020: 269-284.
• Konwar D, Bora U (2021) Recent developments in transition-metal-catalyzed regioselective functionalization of imid-azo[1,2-a] pyridine. Chemistry Select 6: 2716-2744.
• Shi L, Li T, Mei GJ (2022) Recent advances in transition-metal-free C-H functionalization of imid-azo[1,2-a]-pyridines. Green Synth Catal 3: 227-242.
• Wang C, Dong H, Hu W, Liu Y, Zhu D (2012) Semiconducting π-Conjugated Systems in Field-Effect Transistors: A Material Odyssey of Organic Electronics. Chem Rev 112(4): 2208-2267.
• Samanta S, Mondal S, Ghosh D, Hajra A (2019) Rhodium-Catalyzed Directed C-H Amidation of Imidazoheterocy-cles with Dioxazolones. Org Lett 21(12): 4905-4909.
• Ghosh M, Naskar A, Mishra S, Hajra A (2015) Palladium-catalyzed dehydrogenative annulation of imid-azo[1,2-a] pyridines with diary-lalkynes. Tetrahedron Lett 56: 4101-4104.
• Zheng G, Tian M, Xu Y, Chen X, Li X (2018) Rhodium (III)-catalyzed annulative coupling between arenes and sul-foxonium ylides via C-H activation. Org Chem Front 5: 998-1002.
• Li B, Shen N, Zhang X, Fan X (2019) Synthesis of fused imidazo[1,2-a] pyridines derivatives through cascade C (sp 2) -H functionalizations. Org Biomol Chem 17: 9140-9150.
• Reddy KN, Chary DY, Sridhar B, Reddy BVS (2019) Rh (III)-catalyzed tandem bicyclization of 2-arylimidazo[1,2-a] pyridines with cyclic enones for the construction of bridged scaffolds. Org Lett 21: 8548-8552.
• Meena N, Sharma S, Bhatt R, Shinde VN, Sunda AP, et al. (2020) A seleni-um-coordinated palladium (II) trans-dichloride molecular rotor as a catalyst for site-selective annulation of 2-arylimidazo[1,2-a] pyridines. Chem Commun 56: 10223-10226.
• Ghosh K, Nishii Y, Miura M (2020) Oxidative C-H/C-H annulation of imidazopyridines and indazoles through rhodium-catalyzed vinylene transfer. Org Lett 22: 3547-3550.
• Li B, Guo C, Shen N, Zhang X, Fan X (2020) Synthesis of maleimide fused benzocarbazoles and imid-azo[1,2-a] pyridines via rhodium (III)-catalyzed [4 + 2] oxidative cycloaddition. Org Chem Front 7: 3698-3704.
• Yogananda Chary D, Nagarjuna Reddy K, Sridhar B, Subba Reddy BV (2021) Ru (II) catalyzed dehydrogenative annulation of 2-arylimidazo[1,2-a] pyridines with maleimides. Tetrahedron Lett 66: 152830.
• Rogge T, Kaplaneris N, Chatani N, Kim J, Chang S, et al. (2021) C-H activation. Nat Rev Methods Primers 1: 43.
• Shinde VN, Rangan K, Kumar D, Kumar A (2021) Rhodium (III)-catalyzed dehydrogenative annulation and spirocyclization of 2-arylindoles and 2-(1H-pyrazol-1-yl)-1H-indoles with maleimides: A facile access to isogranulatimide alkaloid analogues. J Org Chem 86(3): 2328-2338.
• Nipate DS, Shinde VN, Rangan K, Kumar A (2021) Switchable regioselective hydroalkylation of 2-arylindoles with maleimides. Org Biomol Chem 19: 4910-4921.
• Hanchate V, Kumar A, Prabhu KR (2019) Synthesis of Furanone-Fused 1,2-Benzothiazine by Rh (III)-Catalyzed C-H Activation: Regioselective Oxidative Annulation Leading to in Situ Lactonization in One Pot. J Org Chem 84(17): 11335-11342.
• Meena N, Shinde VN, Swami PN, Rangan K, Kumar A, et al. (2023) Catalyst-Controlled Regiodivergent Oxidative An-nulation of 2-Arylimidazo[1,2-a] pyridines with Cinnamaldehyde Derivatives for Construction of Fused N-Heterocyclic Frameworks. J Org Chem 88(18): 12902-12913.
• Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, et al. (2010) Gaussian 09 (Revision B.01), Gaussian, Inc. Wallingford CT.
• Hay PJ, Wadt WR (1985) Ab initio effective core potentials for molecular calculations-potentials for the transi-tion-metal atoms Sc to Hg J Chem Phys 82, 270-283.
• Lv H, Han F, Wang N, Lu N, Song Z, et al. (2022) Ionic Liquid Catalyzed C-C Bond Formation for the Synthesis of Polysubstituted Olefins. Eur J Org Chem e202201222.
• Zhuang H, Lu N, Ji N, Han F, Miao C (2021) Bu4NHSO4‐Catalyzed Direct N‐Allylation of Pyrazole and its Deriva-tives with Allylic Alcohols in Water: A Metal‐free, Recyclable and Sustainable System. Advan Synthe Catal 363: 5461-5472.
• Lu N, Lan X, Miao C, Qian P (2020) Theoretical investigation on transformation of Cr (II) to Cr (V) complexes bearing tetra-NHC and group transfer reactivity. Int J Quantum Chem 120: e26340.
• Lu N, Liang H, Qian P, Lan X, Miao C (2020) Theoretical investigation on the mechanism and enantioselectivity of organocatalytic asymmetric Povarov reactions of anilines and aldehydes. Int J Quantum Chem 120: e26574.
• Lu N, Wang Y (2023) Alloy and Media Effects on the Ethanol Partial Oxidation Catalyzed by Bimetallic Pt6M (M= Co, Ni, Cu, Zn, Ru, Rh, Pd, Sn, Re, Ir, and Pt). Comput Theoret Chem 1228: 114252.
• Becke AD (1996) Density-functional thermochemistry. IV. A new dynamical correlation functional and implications for exact-exchange mixing. J Chem Phys 104: 1040-1046.
• Lee CT, Yang WT, Parr RG (1998) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B Condens Matter 37(2): 785-789.
• Catellani M, Mealli C, Motti E, Paoli P, Perez Carren˜o, et al. (2002) Palladium-Arene Interactions in Cat-alytic Intermediates: An Experimental and Theoretical Investigation of the Soft Rearrangement between η1 and η2 Co-ordination Modes. J AM CHEM SOC 124(16): 4336-4346.
• Zicovich Wilson CM, Pascale F, Roetti C, Saunders VR, Dovesi R, et al. (2004) Calculation of the Vibration Frequencies of α-Quartz: The Effect of Hamiltonian and Basis Set. J Comput Chem 25(15): 1873-1881.
• Nielsen RJ, Goddard WA (2006) Mechanism of the Aerobic Oxidation of Alcohols by Palladium Complexes of N-Heterocyclic Carbenes. J AM CHEM SOC 128(30): 9651-9660.
• Zandler ME, D’Souza F (2006) The remarkable ability of B3LYP/3-21G(*) calculations to describe geometry, spectral and electrochemical properties of molecular and supramolecular porphyrin-fullerene conjugates. 9(7-8): 960-981.
• Marenich AV, Cramer CJ, Truhlar DG (2009) Universal Solvation Model Based on Solute Electron Density and on a Continuum Model of the Solvent Defined by the Bulk Dielectric Constant and Atomic Surface Tensions. J Phys Chem B 113(18): 6378-6396.
• Tapia O (1992) Solvent effect theories: Quantum and classical formalisms and their applications in chemistry and biochemistry. J Math Chem 10: 139-181.
• Tomasi J, Persico M (1994) Molecular Interactions in Solution: An Overview of Methods Based on Continuous Distributions of the Solvent. Chem Rev 94: 2027-2094.
• Tomasi J, Mennucci B, Cammi R (2005) Quantum Mechanical Continuum Solvation Models. Chem Rev 105(8): 2999-3093.
• Reed AE, Weinstock RB, Weinhold F (1985) Natural population analysis. J Chem Phys 83: 735-746.
• Reed AE, Curtiss LA, Weinhold F (1988) Intermolecular interactions from a natural bond orbital donor-acceptor viewpoint. Chem Rev 88: 899-926.
• Domingo LR, Ríos Gutiérrez M, Pérez P (2016) A new model for CeC bond formation processes derived from the Molecular Electron Density Theory in the study of the mechanism of [3+2] cycloaddition reactions of carbenoid nitrile ylides with electron-deficient ethylenes. Tetrahedron 72(12): 1524-1532.
• Lu T, Chen F (2012) Multiwfn: A multifunctional wavefunction analyzer. J Comput Chem 33(5): 580-592.

Supplementary Information

Theoretical Investigation on Rh(III)- And Pd(II)-Catalyzed Regioselective Oxidative Annulation of 2-Arylimidazo[1,2-A]Pyridine with Cinnamaldehyde for Synthesis of N-Heterocycle

Nan Lu*, Chengxia Miao and Xiaozheng Lan

College of Chemistry and Material Science, Shandong Agricultural University, China.

Table of Contents Pages

Computation information and geometries of stationary points; 2-22

Additional tables and figures 23-26

Software: GAUSSIAN09

Level of Theory: B3LYP

Basis Set: 6-31G(d)

Geometry [Cartesian coordinates]:

Optimized Cartesian coordinates for ts-Ai1

---------------------------------------------------------------------

Center Atomic Atomic Coordinates (Angstroms)

Number Number Type X Y Z

---------------------------------------------------------------------

1 6 0 1.385763 1.745614 -0.858810

2 6 0 0.456002 2.630505 -1.441679

3 6 0 0.868122 3.881518 -1.836412

4 6 0 2.220402 4.283223 -1.660849

5 6 0 3.124372 3.423456 -1.104109

6 6 0 3.423767 1.139439 -0.140578

7 6 0 2.516737 0.119658 0.057350

8 1 0 -0.563025 2.296009 -1.565629

9 1 0 0.159540 4.569351 -2.285215

10 1 0 2.550230 5.269301 -1.965819

11 1 0 4.169195 3.656576 -0.940972

12 1 0 4.472271 1.225910 0.092464

13 6 0 2.643592 -1.208640 0.625819

14 6 0 1.409004 -1.816572 0.998489

15 6 0 3.863113 -1.863268 0.805500

16 6 0 1.467077 -3.133141 1.506510

17 1 0 0.839324 -1.002406 1.873392

18 6 0 3.877736 -3.154027 1.330466

19 1 0 4.793287 -1.385974 0.509574

20 6 0 2.679915 -3.791761 1.677439

21 1 0 0.552301 -3.626788 1.818302

22 1 0 4.824194 -3.669980 1.464449

23 1 0 2.701852 -4.798030 2.086122

24 7 0 1.267991 0.503155 -0.382643

25 7 0 2.715352 2.170778 -0.715924

26 6 0 -2.175389 -0.384481 0.496443

27 6 0 -2.302415 -0.328809 -0.951646

28 6 0 -2.112776 -1.634867 -1.465108

29 6 0 -1.849720 -2.528607 -0.346874

30 6 0 -1.985011 -1.759345 0.864858

31 6 0 -2.420247 0.743254 1.451788

32 1 0 -3.457845 0.721021 1.811630

33 1 0 -1.747909 0.675029 2.310827

34 1 0 -2.255369 1.713907 0.977341

35 6 0 -2.003252 -2.283206 2.266280

36 1 0 -3.025310 -2.219133 2.661847

37 1 0 -1.703037 -3.332045 2.310928

38 1 0 -1.352137 -1.697817 2.923217

39 6 0 -1.709944 -4.015625 -0.475525

40 1 0 -2.686057 -4.482534 -0.661836

41 1 0 -1.044261 -4.267206 -1.304838

42 1 0 -1.296379 -4.461586 0.430988

43 6 0 -2.208773 -2.064369 -2.894218

44 1 0 -2.330837 -1.211474 -3.565000

45 1 0 -1.304696 -2.602749 -3.193298

46 1 0 -3.071422 -2.729322 -3.028023

47 6 0 -2.720259 0.865453 -1.757568

48 1 0 -2.156883 0.947102 -2.690770

49 1 0 -3.782138 0.785500 -2.023351

50 1 0 -2.603880 1.793918 -1.194560

51 45 0 -0.186440 -1.108610 -0.329745

52 17 0 1.118469 -2.113336 -2.151921

53 17 0 0.589268 -0.042525 3.225081

---------------------------------------------------------------------

Optimized Cartesian coordinates for ts-i2C

---------------------------------------------------------------------

Center Atomic Atomic Coordinates (Angstroms)

Number Number Type X Y Z

---------------------------------------------------------------------

1 6 0 3.616071 -2.693174 2.804684

2 6 0 4.207175 -3.145880 1.606172

3 6 0 5.556435 -3.415635 1.603489

4 6 0 6.344340 -3.238941 2.773804

5 6 0 5.773611 -2.764467 3.920486

6 6 0 3.634481 -1.969694 4.933733

7 6 0 2.366119 -1.882284 4.402158

8 1 0 3.599919 -3.166593 0.694433

9 1 0 6.028982 -3.742635 0.683141

10 1 0 7.406861 -3.454593 2.766801

11 1 0 6.308322 -2.573678 4.842592

12 1 0 4.038236 -1.689387 5.893001

13 6 0 1.114757 -1.393111 4.959304

14 6 0 0.073158 -1.111928 4.038257

15 6 0 0.900533 -1.257336 6.337658

16 6 0 -1.174099 -0.718146 4.556248

17 6 0 -0.343196 -0.856975 6.821571

18 1 0 1.700995 -1.495512 7.033176

19 6 0 -1.388820 -0.597739 5.928169

20 1 0 -1.981420 -0.473942 3.869489

21 1 0 -0.500098 -0.752010 7.891010

22 1 0 -2.361136 -0.288110 6.301024

23 7 0 2.352904 -2.341002 3.104281

24 7 0 4.425983 -2.488130 3.930182

25 6 0 -0.700521 -4.100211 0.945721

26 6 0 0.404108 -4.710909 1.604512

27 6 0 0.082808 -4.842011 3.035387

28 6 0 -1.185578 -4.268162 3.243694

29 6 0 -1.650623 -3.723246 1.971064

30 6 0 -0.830858 -3.944524 -0.535961

31 1 0 -1.130224 -4.907165 -0.973110

32 1 0 -1.575402 -3.197224 -0.807581

33 1 0 0.124251 -3.636639 -0.978510

34 6 0 -3.032022 -3.189970 1.725575

35 1 0 -3.732186 -4.022900 1.576288

36 1 0 -3.398301 -2.605511 2.574040

37 1 0 -3.068864 -2.564337 0.832354

38 6 0 -1.962698 -4.234041 4.523898

39 1 0 -2.727992 -5.020966 4.521359

40 1 0 -1.321685 -4.396512 5.393045

41 1 0 -2.474525 -3.278693 4.660850

42 6 0 0.939830 -5.552862 4.038710

43 1 0 0.824957 -6.640409 3.943935

44 1 0 1.998391 -5.324568 3.889130

45 1 0 0.678111 -5.279046 5.063607

46 6 0 1.582921 -5.311330 0.908086

47 1 0 2.421221 -5.471360 1.589722

48 1 0 1.301466 -6.289347 0.493454

49 1 0 1.914612 -4.667555 0.084188

50 45 0 0.249774 -2.628493 2.401064

51 17 0 2.473213 -2.384789 -1.078819

52 6 0 0.228968 -0.849589 1.179663

53 6 0 0.451185 -0.069404 2.391797

54 1 0 1.020176 -1.031931 0.447939

55 1 0 -0.395947 0.566609 2.637760

56 6 0 1.738831 0.654998 2.610046

57 6 0 2.853048 0.465024 1.774841

58 6 0 1.801763 1.637570 3.613808

59 6 0 4.000249 1.239600 1.954968

60 1 0 2.828210 -0.268771 0.973139

61 6 0 2.947893 2.407402 3.790152

62 1 0 0.941228 1.794915 4.259681

63 6 0 4.054566 2.206897 2.959866

64 1 0 4.849420 1.088882 1.294978

65 1 0 2.976280 3.166829 4.566431

66 1 0 4.949151 2.809690 3.089943

67 6 0 -1.130828 -0.684713 0.629943

68 8 0 -1.501185 -0.921522 -0.506147

69 1 0 -1.869220 -0.287727 1.373894

---------------------------------------------------------------------

Optimized Cartesian coordinates for ts-Ai1-pd

---------------------------------------------------------------------

Center Atomic Atomic Coordinates (Angstroms)

Number Number Type X Y Z

---------------------------------------------------------------------

1 6 0 -1.400705 3.408822 -3.412884

2 6 0 -0.249201 3.715590 -4.174320

3 6 0 0.019430 5.022394 -4.505636

4 6 0 -0.855205 6.064920 -4.086737

5 6 0 -1.970564 5.777015 -3.350113

6 6 0 -3.268930 3.906778 -2.302664

7 6 0 -3.023041 2.537572 -2.285386

8 1 0 0.392666 2.896384 -4.477706

9 1 0 0.900244 5.267273 -5.089984

10 1 0 -0.648905 7.096956 -4.345943

11 1 0 -2.676799 6.520257 -3.000076

12 1 0 -4.066866 4.508418 -1.898372

13 6 0 -3.843625 1.490002 -1.655328

14 6 0 -3.570000 0.117156 -1.891160

15 6 0 -4.927859 1.855456 -0.840072

16 6 0 -4.423204 -0.835302 -1.300383

17 1 0 -3.327054 -0.163770 -3.264975

18 6 0 -5.740835 0.887862 -0.255332

19 1 0 -5.135641 2.904306 -0.645610

20 6 0 -5.496462 -0.468080 -0.489401

21 1 0 -4.241440 -1.891458 -1.486559

22 1 0 -6.570085 1.192852 0.377553

23 1 0 -6.136534 -1.225183 -0.044141

24 7 0 -1.872561 2.248375 -2.973974

25 7 0 -2.239070 4.471517 -3.017721

26 46 0 -1.441609 -0.512417 -1.898022

27 6 0 -2.162550 -0.831710 -4.753500

28 8 0 -3.312353 -0.381161 -4.439826

29 8 0 -1.220202 -1.024751 -3.935299

30 6 0 -1.924142 -1.139274 -6.213508

31 1 0 -1.861537 -0.195924 -6.765423

32 1 0 -0.997970 -1.698626 -6.345068

33 1 0 -2.770261 -1.700616 -6.616428

34 15 0 0.749898 -1.300196 -1.672032

35 15 0 -0.592984 -5.811807 1.275781

36 6 0 1.822489 -0.672543 -3.034827

37 1 0 2.811119 -1.142784 -3.014802

38 1 0 1.330226 -0.880918 -3.986526

39 1 0 1.936170 0.410242 -2.933753

40 6 0 1.695631 -0.880304 -0.153218

41 1 0 1.230211 -1.388094 0.692035

42 1 0 2.737772 -1.200854 -0.252560

43 1 0 1.660323 0.198726 0.014940

44 6 0 0.866067 -3.126684 -1.810561

45 1 0 0.405375 -3.440399 -2.750756

46 1 0 1.908448 -3.461516 -1.787630

47 1 0 0.316107 -3.573678 -0.979892

48 6 0 -2.385329 -5.344203 1.079010

49 1 0 -2.965447 -5.512802 1.994354

50 1 0 -2.426434 -4.282065 0.821211

51 1 0 -2.835755 -5.921433 0.265369

52 6 0 -0.777524 -7.490349 2.074400

53 1 0 -1.453380 -7.470894 2.937445

54 1 0 -1.164730 -8.206206 1.342363

55 1 0 0.202136 -7.850483 2.404432

56 6 0 -0.187091 -4.779730 2.772731

57 1 0 -0.861052 -4.979658 3.614436

58 1 0 0.842240 -4.968832 3.093527

59 1 0 -0.281427 -3.729738 2.480745

60 6 0 -1.482187 -0.937365 0.980138

61 8 0 -1.567929 -0.007160 0.079733

62 8 0 -1.125987 -2.108809 0.788438

63 6 0 -1.884532 -0.450309 2.369232

64 1 0 -1.472747 0.542340 2.567078

65 1 0 -2.975593 -0.365449 2.407410

66 1 0 -1.554615 -1.158460 3.130816

---------------------------------------------------------------------

Optimized Cartesian coordinates for ts-i2C-pd

---------------------------------------------------------------------

Center Atomic Atomic Coordinates (Angstroms)

Number Number Type X Y Z

---------------------------------------------------------------------

1 6 0 0.393439 1.868566 -0.886176

2 6 0 1.492790 1.795415 -1.772821

3 6 0 2.197304 2.937653 -2.071093

4 6 0 1.824145 4.185416 -1.494851

5 6 0 0.754849 4.263318 -0.646720

6 6 0 -1.052925 2.918735 0.446151

7 6 0 -1.323384 1.558134 0.379840

8 1 0 1.740641 0.829412 -2.199937

9 1 0 3.043738 2.894805 -2.748677

10 1 0 2.381206 5.087350 -1.721137

11 1 0 0.417284 5.178532 -0.175618

12 1 0 -1.492326 3.720734 1.016670

13 6 0 -2.369543 0.827323 1.108787

14 6 0 -2.337101 -0.579655 1.268570

15 6 0 -3.414936 1.541753 1.720405

16 6 0 -3.320173 -1.210420 2.041386

17 6 0 -4.388321 0.901883 2.483964

18 1 0 -3.467927 2.619313 1.592261

19 6 0 -4.337010 -0.482344 2.659685

20 1 0 -3.285722 -2.289334 2.174048

21 1 0 -5.185344 1.483393 2.938609

22 1 0 -5.083453 -0.990412 3.264152

23 7 0 -0.430921 0.927085 -0.444054

24 7 0 0.044658 3.125067 -0.353859

25 6 0 -0.797376 -2.248214 -0.731704

26 6 0 -2.154502 -1.849835 -0.533273

27 1 0 -0.173186 -1.700802 -1.430573

28 1 0 -2.768114 -2.601458 -0.041968

29 6 0 -2.930617 -1.009069 -1.472497

30 6 0 -2.339113 -0.337318 -2.556016

31 6 0 -4.330291 -0.963639 -1.334867

32 6 0 -3.129578 0.361714 -3.467144

33 1 0 -1.264526 -0.359293 -2.684729

34 6 0 -5.116976 -0.267360 -2.246853

35 1 0 -4.796522 -1.468485 -0.493480

36 6 0 -4.517155 0.401214 -3.317512

37 1 0 -2.657633 0.875886 -4.299517

38 1 0 -6.195838 -0.245397 -2.123710

39 1 0 -5.128117 0.945618 -4.032003

40 6 0 -0.495681 -3.674136 -0.595018

41 8 0 0.463128 -4.243065 -1.111625

42 1 0 -1.221227 -4.252676 0.019079

43 46 0 -0.388600 -1.481089 1.263943

44 15 0 1.316224 -2.114056 -4.289582

45 15 0 1.822540 -2.326925 1.474290

46 6 0 -0.169061 -3.165121 -4.691013

47 1 0 0.025868 -3.866615 -5.510363

48 1 0 -0.441435 -3.734826 -3.798144

49 1 0 -1.017557 -2.529353 -4.961248

50 6 0 1.806795 -1.574446 -6.007368

51 1 0 2.768005 -1.052535 -5.967122

52 1 0 1.893736 -2.417013 -6.703255

53 1 0 1.064106 -0.872123 -6.398556

54 6 0 2.565954 -3.463893 -3.998855

55 1 0 2.278415 -4.008201 -3.094854

56 1 0 2.622070 -4.168667 -4.836581

57 1 0 3.557048 -3.027826 -3.839583

58 6 0 2.795619 -1.580484 2.843476

59 1 0 3.817892 -1.972244 2.841759

60 1 0 2.794747 -0.495344 2.729523

61 1 0 2.311064 -1.822147 3.792096

62 6 0 2.001516 -4.136060 1.796618

63 1 0 3.055407 -4.400300 1.933084

64 1 0 1.449472 -4.392461 2.704980

65 1 0 1.596220 -4.703076 0.956142

66 6 0 2.864973 -2.042753 -0.016124

67 1 0 3.882175 -2.420751 0.130114

68 1 0 2.404853 -2.552763 -0.865326

69 1 0 2.902007 -0.969846 -0.220816

70 6 0 0.260434 0.346033 3.474566

71 8 0 -0.297026 -0.809334 3.271523

72 8 0 0.891725 1.007072 2.642601

73 6 0 0.060368 0.870052 4.898638

74 1 0 0.753202 1.689311 5.099196

75 1 0 -0.965982 1.238900 5.001614

76 1 0 0.193361 0.071286 5.633202

---------------------------------------------------------------------

Optimized Cartesian coordinates for ts-Ci3

---------------------------------------------------------------------

Center Atomic Atomic Coordinates (Angstroms)

Number Number Type X Y Z

---------------------------------------------------------------------

1 6 0 -5.289867 -3.036204 3.706420

2 6 0 -6.544617 -2.516711 4.108240

3 6 0 -6.837946 -2.466363 5.449253

4 6 0 -5.908832 -2.935287 6.424592

5 6 0 -4.698235 -3.418361 6.023925

6 6 0 -3.167139 -3.865841 4.147924

7 6 0 -3.418688 -3.719315 2.753449

8 1 0 -7.221174 -2.133691 3.358748

9 1 0 -7.785227 -2.048217 5.775428

10 1 0 -6.148783 -2.897472 7.480502

11 1 0 -3.915089 -3.776490 6.679717

12 1 0 -3.813514 -5.110206 2.758196

13 6 0 -2.284832 -3.621884 1.769478

14 6 0 -2.322215 -3.310577 0.388018

15 6 0 -1.017370 -3.846251 2.364637

16 6 0 -1.083970 -3.183205 -0.284695

17 6 0 0.173334 -3.746586 1.667905

18 1 0 -1.010747 -4.084764 3.421291

19 6 0 0.144188 -3.391254 0.318361

20 1 0 -1.106022 -2.929779 -1.341337

21 1 0 1.115117 -3.925362 2.178732

22 1 0 1.060281 -3.280577 -0.254599

23 7 0 -4.730640 -3.183433 2.502999

24 7 0 -4.386602 -3.461978 4.685345

25 6 0 -7.843377 -4.838486 0.427063

26 6 0 -7.906723 -3.390929 0.332825

27 6 0 -7.818454 -3.061693 -1.142503

28 6 0 -7.483953 -4.195380 -1.808054

29 6 0 -7.365889 -5.298029 -0.809602

30 6 0 -8.303523 -5.671836 1.596710

31 1 0 -7.832673 -6.656884 1.607532

32 1 0 -8.089813 -5.194584 2.558367

33 1 0 -9.391530 -5.815725 1.544015

34 6 0 -7.062370 -6.712820 -1.185852

35 1 0 -7.897356 -7.132830 -1.764694

36 1 0 -6.170916 -6.772665 -1.816057

37 1 0 -6.903296 -7.345519 -0.310746

38 6 0 -7.270174 -4.404000 -3.275419

39 1 0 -7.972509 -5.144069 -3.680890

40 1 0 -7.412295 -3.476278 -3.835029

41 1 0 -6.260097 -4.770961 -3.488458

42 6 0 -8.091996 -1.693655 -1.681527

43 1 0 -7.475019 -0.949623 -1.167132

44 1 0 -7.897387 -1.634299 -2.755447

45 1 0 -9.140620 -1.408097 -1.521235

46 6 0 -8.693270 -2.494667 1.245367

47 1 0 -8.206936 -1.518811 1.339244

48 1 0 -9.696521 -2.319809 0.831164

49 1 0 -8.824481 -2.932413 2.237342

50 45 0 -5.871136 -4.113080 0.996729

51 17 0 -4.665054 -6.326593 2.217944

52 6 0 -4.922563 -2.712312 -0.187085

53 6 0 -3.497440 -3.128048 -0.603481

54 1 0 -5.537470 -2.652755 -1.086434

55 1 0 -3.184704 -2.248525 -1.190577

56 6 0 -3.501898 -4.272194 -1.626164

57 6 0 -3.551138 -3.971125 -2.994525

58 6 0 -3.408355 -5.617350 -1.244056

59 6 0 -3.514867 -4.981058 -3.959095

60 1 0 -3.605653 -2.931511 -3.310967

61 6 0 -3.376016 -6.629631 -2.205475

62 1 0 -3.343654 -5.878554 -0.193219

63 6 0 -3.428121 -6.317688 -3.566462

64 1 0 -3.541628 -4.721004 -5.013812

65 1 0 -3.294948 -7.665149 -1.886450

66 1 0 -3.388037 -7.106621 -4.312150

67 6 0 -4.948532 -1.388304 0.525824

68 8 0 -5.888900 -0.609772 0.531916

69 1 0 -4.006031 -1.114875 1.043444

---------------------------------------------------------------------

Optimized Cartesian coordinates for ts-i4D

---------------------------------------------------------------------

Center Atomic Atomic Coordinates (Angstroms)

Number Number Type X Y Z

---------------------------------------------------------------------

1 6 0 -0.683842 3.380178 1.466044

2 6 0 -0.355634 4.681452 1.917672

3 6 0 -0.501011 5.747319 1.061784

4 6 0 -0.982791 5.539526 -0.265190

5 6 0 -1.309608 4.283991 -0.693415

6 6 0 -1.459123 1.873967 -0.138138

7 6 0 -1.122044 1.297222 1.096763

8 1 0 -0.014795 4.812838 2.939754

9 1 0 -0.259559 6.752179 1.393754

10 1 0 -1.099072 6.376608 -0.944605

11 1 0 -1.685384 4.045657 -1.680520

12 6 0 -1.266743 -0.121035 1.508013

13 6 0 -0.692227 -1.234017 0.816854

14 6 0 -2.079705 -0.384806 2.649188

15 6 0 -1.027401 -2.538302 1.255833

16 6 0 -2.380920 -1.669340 3.053951

17 1 0 -2.493983 0.471178 3.171586

18 6 0 -1.860893 -2.763696 2.336148

19 1 0 -0.618962 -3.382471 0.706087

20 1 0 -3.033044 -1.834760 3.906974

21 1 0 -2.110636 -3.779633 2.629294

22 7 0 -0.659456 2.203882 2.086961

23 7 0 -1.168529 3.204731 0.147156

24 6 0 1.633045 1.069438 4.163869

25 6 0 1.527332 -0.327029 4.173577

26 6 0 2.445263 -0.866978 3.158775

27 6 0 3.212251 0.226120 2.627232

28 6 0 2.599276 1.433105 3.119849

29 6 0 0.870256 2.051561 4.996368

30 1 0 0.434877 1.573933 5.877296

31 1 0 1.524519 2.859477 5.340496

32 1 0 0.060080 2.485869 4.400771

33 6 0 3.052367 2.827316 2.820367

34 1 0 2.203944 3.513256 2.761116

35 1 0 3.724646 3.187943 3.610848

36 1 0 3.590357 2.872206 1.871257

37 6 0 4.499500 0.149616 1.869131

38 1 0 4.694332 -0.861914 1.506586

39 1 0 4.524494 0.815852 1.003595

40 1 0 5.320368 0.427761 2.542636

41 6 0 2.720970 -2.327841 2.968842

42 1 0 3.381767 -2.700393 3.763125

43 1 0 1.797593 -2.911756 3.006446

44 1 0 3.207558 -2.523797 2.010934

45 6 0 0.653460 -1.175555 5.042076

46 1 0 0.039209 -1.857947 4.445930

47 1 0 1.265016 -1.787289 5.717166

48 1 0 -0.021688 -0.569819 5.648807

49 45 0 1.082212 0.365666 1.970016

50 6 0 1.210532 0.099259 -0.180000

51 6 0 0.319324 -1.140228 -0.338660

52 1 0 0.805694 1.015800 -0.602370

53 1 0 0.987847 -1.994047 -0.161315

54 6 0 -0.263750 -1.385322 -1.733577

55 6 0 -1.230167 -0.543614 -2.305541

56 6 0 0.183457 -2.496807 -2.463897

57 6 0 -1.730800 -0.823455 -3.578223

58 1 0 -1.563180 0.338864 -1.753576

59 6 0 -0.320045 -2.772841 -3.736104

60 1 0 0.936886 -3.154650 -2.034220

61 6 0 -1.283952 -1.934536 -4.297152

62 1 0 -2.478219 -0.163533 -4.011438

63 1 0 0.040227 -3.639154 -4.284599

64 1 0 -1.680782 -2.144208 -5.286984

65 6 0 2.615189 -0.090479 -0.556341

66 8 0 3.381615 0.791470 -0.921365

67 1 0 2.989188 -1.140642 -0.458185

---------------------------------------------------------------------

Optimized Cartesian coordinates for ts-Di5

---------------------------------------------------------------------

Center Atomic Atomic Coordinates (Angstroms)

Number Number Type X Y Z

---------------------------------------------------------------------

1 6 0 4.601376 -0.436689 5.026859

2 6 0 5.519803 -0.527377 6.095174

3 6 0 5.122021 -1.082037 7.289782

4 6 0 3.787821 -1.551852 7.451381

5 6 0 2.890093 -1.452383 6.424041

6 6 0 2.566564 -0.670472 4.049449

7 6 0 3.543021 -0.138565 3.188571

8 1 0 6.524835 -0.154847 5.932812

9 1 0 5.822681 -1.163883 8.114320

10 1 0 3.466258 -1.991119 8.388898

11 1 0 1.858358 -1.775238 6.482897

12 6 0 3.371230 0.116877 1.753999

13 6 0 2.561644 -0.713066 0.951896

14 6 0 4.065152 1.188169 1.160585

15 6 0 2.426995 -0.403966 -0.409782

16 6 0 3.927966 1.471874 -0.193502

17 1 0 4.713236 1.787703 1.791690

18 6 0 3.092100 0.677418 -0.983328

19 1 0 1.807665 -1.044619 -1.032993

20 1 0 4.465986 2.307718 -0.631633

21 1 0 2.969132 0.890293 -2.041409

22 7 0 4.754604 0.040820 3.794791

23 7 0 3.284581 -0.907582 5.225376

24 6 0 -1.599770 0.341065 4.571021

25 6 0 -0.712436 1.142748 5.436079

26 6 0 0.173056 1.839865 4.608018

27 6 0 -0.132540 1.468758 3.218206

28 6 0 -1.317335 0.645876 3.215235

29 6 0 -2.727681 -0.527316 5.047440

30 1 0 -3.663952 0.043606 5.107701

31 1 0 -2.887497 -1.366461 4.365059

32 1 0 -2.530507 -0.935350 6.042694

33 6 0 -2.045101 0.095070 2.024387

34 1 0 -3.098492 0.399920 2.028472

35 1 0 -1.603036 0.450912 1.090565

36 1 0 -2.011815 -1.002421 2.017434

37 6 0 0.482514 2.121961 2.018169

38 1 0 0.426779 1.487140 1.131548

39 1 0 -0.044965 3.059631 1.793568

40 1 0 1.533744 2.364457 2.180865

41 6 0 1.250452 2.803471 5.005796

42 1 0 0.982876 3.830767 4.726240

43 1 0 1.426049 2.789994 6.084118

44 1 0 2.197767 2.566848 4.511458

45 6 0 -0.819112 1.212596 6.930451

46 1 0 0.087193 1.622689 7.382244

47 1 0 -1.659301 1.852736 7.232259

48 1 0 -0.995328 0.227017 7.371472

49 45 0 0.467728 -0.467471 4.152223

50 6 0 1.690274 -2.151271 2.957767

51 6 0 1.853349 -1.975050 1.446928

52 1 0 2.447769 -2.771824 3.432210

53 1 0 0.829463 -1.925307 1.058431

54 6 0 2.468930 -3.265505 0.891919

55 6 0 1.640545 -4.381598 0.698917

56 6 0 3.839978 -3.385643 0.629520

57 6 0 2.171281 -5.587132 0.239227

58 1 0 0.581583 -4.297171 0.928447

59 6 0 4.369649 -4.593554 0.171944

60 1 0 4.492813 -2.529733 0.772156

61 6 0 3.537697 -5.696719 -0.027825

62 1 0 1.516225 -6.440998 0.089063

63 1 0 5.434187 -4.670091 -0.031930

64 1 0 3.951104 -6.634561 -0.388229

65 6 0 0.320117 -2.418745 3.419273

66 8 0 -0.642124 -2.914522 2.816018

67 1 0 0.285737 -2.360556 4.613407

---------------------------------------------------------------------

Optimized Cartesian coordinates for ts-in1II

---------------------------------------------------------------------

Center Atomic Atomic Coordinates (Angstroms)

Number Number Type X Y Z

---------------------------------------------------------------------

1 6 0 2.924288 -0.227545 1.706101

2 6 0 3.852733 -1.012310 2.422520

3 6 0 3.620323 -2.360656 2.575361

4 6 0 2.452141 -2.950263 2.022187

5 6 0 1.546048 -2.180126 1.341097

6 6 0 1.011265 0.140631 0.532998

7 6 0 1.791035 1.318560 0.717771

8 1 0 4.727399 -0.521140 2.832920

9 1 0 4.324657 -2.977232 3.124361

10 1 0 2.259097 -4.010660 2.138803

11 1 0 0.617950 -2.543978 0.917161

12 6 0 1.572747 2.672417 0.179020

13 6 0 2.578445 3.644400 0.360915

14 6 0 0.279499 4.311117 -1.064658

15 6 0 2.431064 4.924887 -0.162868

16 1 0 3.468260 3.371155 0.916608

17 6 0 1.281222 5.264826 -0.882942

18 1 0 -0.623508 4.557951 -1.615605

19 1 0 3.216269 5.660761 -0.011540

20 1 0 1.168843 6.264478 -1.293717

21 7 0 2.929657 1.075290 1.429162

22 7 0 1.776831 -0.837822 1.185566

23 6 0 1.212554 -0.268368 -1.685767

24 6 0 0.018419 -0.979964 -1.979014

25 1 0 1.173383 0.801373 -1.879398

26 1 0 0.070244 -2.062922 -2.048265

27 46 0 -0.952951 -0.490732 0.028054

28 6 0 -3.312269 1.865964 -0.650235

29 8 0 -2.211817 1.521355 -1.182227

30 8 0 -3.838088 1.346937 0.370218

31 6 0 -4.043459 3.041567 -1.317255

32 1 0 -4.045084 2.921382 -2.404573

33 1 0 -5.066902 3.132560 -0.947357

34 1 0 -3.507581 3.972247 -1.095779

35 15 0 -2.875441 -1.914369 -0.530173

36 15 0 -1.565075 0.211381 2.224346

37 6 0 -3.823275 -2.733903 0.833209

38 1 0 -4.507538 -3.476877 0.411333

39 1 0 -3.144336 -3.235254 1.528697

40 1 0 -4.407153 -1.993087 1.379406

41 6 0 -4.227337 -1.199501 -1.548625

42 1 0 -3.804332 -0.806754 -2.474656

43 1 0 -4.968640 -1.970856 -1.782964

44 1 0 -4.680401 -0.384886 -0.980831

45 6 0 -2.366437 -3.395538 -1.520680

46 1 0 -1.578542 -3.951718 -1.003589

47 1 0 -3.222483 -4.059981 -1.678213

48 1 0 -2.000756 -3.050930 -2.490265

49 6 0 -0.411325 -0.340934 3.565268

50 1 0 -0.779907 0.007551 4.535537

51 1 0 -0.335650 -1.430955 3.585386

52 1 0 0.584842 0.073485 3.401234

53 6 0 -1.515885 2.041532 2.398163

54 1 0 -1.585338 2.307741 3.458353

55 1 0 -0.593561 2.445608 1.980308

56 1 0 -2.373787 2.439111 1.854876

57 6 0 -3.197221 -0.188388 2.980743

58 1 0 -3.292327 0.362886 3.922164

59 1 0 -3.970697 0.137988 2.284825

60 1 0 -3.279234 -1.255986 3.191710

61 6 0 2.562856 -0.840590 -1.698860

62 6 0 3.668515 0.034133 -1.702694

63 6 0 2.804410 -2.227463 -1.756803

64 6 0 4.967615 -0.459867 -1.772585

65 1 0 3.498308 1.104990 -1.652764

66 6 0 4.105508 -2.718220 -1.820122

67 1 0 1.973063 -2.923744 -1.770736

68 6 0 5.190517 -1.837755 -1.828720

69 1 0 5.805975 0.229967 -1.781853

70 1 0 4.274362 -3.789861 -1.870025

71 1 0 6.204138 -2.224000 -1.884074

72 6 0 -0.932507 -0.360969 -2.925943

73 8 0 -1.693754 -1.020087 -3.625275

74 1 0 -0.910956 0.739058 -2.983800

75 6 0 0.415174 3.025146 -0.537980

76 1 0 -0.403130 2.323508 -0.677182

---------------------------------------------------------------------

Optimized Cartesian coordinates for ts-IIin2

---------------------------------------------------------------------

Center Atomic Atomic Coordinates (Angstroms)

Number Number Type X Y Z

---------------------------------------------------------------------

1 6 0 -2.790051 1.212953 2.827663

2 6 0 -3.686339 2.142166 3.407129

3 6 0 -4.598047 2.791504 2.610265

4 6 0 -4.642727 2.526959 1.211298

5 6 0 -3.780153 1.627574 0.647787

6 6 0 -1.882981 0.040721 1.118413

7 6 0 -1.287431 -0.252923 2.351812

8 1 0 -3.620700 2.311626 4.475868

9 1 0 -5.291376 3.505755 3.042693

10 1 0 -5.364717 3.028373 0.576859

11 1 0 -3.772416 1.367260 -0.402178

12 6 0 -0.218962 -1.217680 2.681506

13 6 0 0.693891 -0.901773 3.703491

14 6 0 0.847058 -3.396008 2.470636

15 6 0 1.675183 -1.812268 4.091543

16 1 0 0.602451 0.058668 4.199475

17 6 0 1.757907 -3.064608 3.475315

18 1 0 0.887683 -4.375512 2.001659

19 1 0 2.368341 -1.550515 4.886710

20 1 0 2.514569 -3.779858 3.785622

21 7 0 -1.835705 0.475312 3.378423

22 7 0 -2.866294 0.980359 1.444694

23 6 0 -1.607779 -0.268038 -0.319207

24 6 0 -0.937988 0.862149 -0.978193

25 1 0 -0.397791 -1.284923 -0.562728

26 1 0 -1.094791 1.830883 -0.513762

27 46 0 1.355862 0.612307 -0.701932

28 6 0 0.891635 -2.639490 -1.604734

29 8 0 0.623440 -1.546478 -0.858077

30 8 0 2.007785 -2.833167 -2.047343

31 6 0 -0.269938 -3.579173 -1.835978

32 1 0 -1.060050 -3.076365 -2.401544

33 1 0 0.084812 -4.449388 -2.387544

34 1 0 -0.711853 -3.893674 -0.886420

35 15 0 1.630170 2.928031 -0.713067

36 15 0 3.711460 -0.189918 -0.456603

37 6 0 2.659478 3.651623 0.641010

38 1 0 2.747356 4.736518 0.521934

39 1 0 2.187087 3.436533 1.603277

40 1 0 3.657850 3.213326 0.644903

41 6 0 2.469800 3.476366 -2.260614

42 1 0 1.839395 3.175352 -3.101799

43 1 0 2.607633 4.562530 -2.279198

44 1 0 3.442564 2.987435 -2.355986

45 6 0 0.155459 4.036032 -0.674728

46 1 0 -0.388353 3.911473 0.265752

47 1 0 0.473371 5.079897 -0.764859

48 1 0 -0.495986 3.773502 -1.511460

49 6 0 5.044779 0.854957 0.302937

50 1 0 5.995953 0.312301 0.326023

51 1 0 5.187014 1.771982 -0.275954

52 1 0 4.772993 1.126552 1.326684

53 6 0 3.892617 -1.754801 0.505894

54 1 0 4.944125 -2.055821 0.570467

55 1 0 3.486651 -1.627011 1.512130

56 1 0 3.323410 -2.533184 -0.004343

57 6 0 4.472966 -0.629820 -2.082604

58 1 0 5.486375 -1.025445 -1.954345

59 1 0 3.840542 -1.387360 -2.549793

60 1 0 4.512098 0.252258 -2.727945

61 6 0 -2.647912 -1.109894 -0.989268

62 6 0 -3.052515 -0.968889 -2.336620

63 6 0 -3.289773 -2.132061 -0.247159

64 6 0 -3.994426 -1.824368 -2.911588

65 1 0 -2.659043 -0.163676 -2.945518

66 6 0 -4.236597 -2.975354 -0.819641

67 1 0 -3.042735 -2.248548 0.803743

68 6 0 -4.590042 -2.841451 -2.165500

69 1 0 -4.276279 -1.675585 -3.950974

70 1 0 -4.702484 -3.743923 -0.208115

71 1 0 -5.325707 -3.501446 -2.615073

72 6 0 -0.666950 0.961001 -2.419304

73 8 0 -0.638664 2.014423 -3.064716

74 1 0 -0.463823 0.002119 -2.936897

75 6 0 -0.131906 -2.482218 2.079002

76 1 0 -0.860349 -2.764747 1.327077

---------------------------------------------------------------------

Optimized Cartesian coordinates for ts-in1II-rh

---------------------------------------------------------------------

Center Atomic Atomic Coordinates (Angstroms)

Number Number Type X Y Z

---------------------------------------------------------------------

1 6 0 -1.986981 0.362521 1.322556

2 6 0 -3.203632 0.864526 1.823901

3 6 0 -4.159902 1.321193 0.944052

4 6 0 -3.905863 1.279252 -0.450106

5 6 0 -2.711825 0.797172 -0.923934

6 6 0 -0.469765 -0.202119 -0.292439

7 6 0 -0.021181 -0.476171 1.042679

8 1 0 -3.344456 0.872996 2.898487

9 1 0 -5.102482 1.713919 1.310924

10 1 0 -4.646856 1.627864 -1.160612

11 1 0 -2.456102 0.761860 -1.970594

12 6 0 1.254109 -1.022314 1.568071

13 6 0 1.876785 -0.322352 2.617301

14 6 0 2.953872 -2.745939 1.779332

15 6 0 3.033832 -0.812435 3.218503

16 1 0 1.433013 0.606306 2.961425

17 6 0 3.576996 -2.029721 2.800977

18 1 0 3.363281 -3.696881 1.451141

19 1 0 3.505253 -0.249480 4.019412

20 1 0 4.475096 -2.418843 3.272576

21 7 0 -0.935113 -0.126566 1.983477

22 7 0 -1.753753 0.350991 -0.053879

23 6 0 -0.951255 -1.943471 -1.617623

24 6 0 -0.896682 -1.273766 -2.881558

25 1 0 -0.041826 -2.470679 -1.343994

26 1 0 -1.807130 -0.803207 -3.247522

27 6 0 -2.176396 -2.439291 -0.977121

28 6 0 -2.081756 -3.145245 0.240857

29 6 0 -3.445383 -2.294770 -1.570516

30 6 0 -3.213512 -3.680547 0.843569

31 1 0 -1.111397 -3.261161 0.713791

32 6 0 -4.578686 -2.834686 -0.964244

33 1 0 -3.540204 -1.796989 -2.528965

34 6 0 -4.468055 -3.523651 0.243878

35 1 0 -3.120614 -4.221108 1.780554

36 1 0 -5.547892 -2.723971 -1.441543

37 1 0 -5.352141 -3.944809 0.713671

38 6 0 -0.076904 -1.792022 -3.991329

39 8 0 -0.316912 -1.517195 -5.163887

40 1 0 0.763155 -2.449209 -3.715698

41 6 0 1.805507 -2.245564 1.165337

42 1 0 1.344088 -2.813681 0.368879

43 6 0 0.704856 2.517855 -1.649674

44 6 0 2.000164 1.988664 -1.918815

45 6 0 2.030884 1.571342 -3.325836

46 6 0 0.757823 1.808885 -3.885843

47 6 0 -0.099243 2.342148 -2.838022

48 6 0 0.269186 3.189328 -0.381439

49 1 0 0.486860 4.264124 -0.427331

50 1 0 -0.803503 3.076553 -0.209679

51 1 0 0.791441 2.781314 0.486546

52 6 0 -1.442695 2.959991 -3.096635

53 1 0 -1.316206 3.941488 -3.573350

54 1 0 -2.046626 2.351455 -3.776486

55 1 0 -2.011497 3.115653 -2.178207

56 6 0 0.343605 1.589644 -5.310204

57 1 0 1.207125 1.632918 -5.978386

58 1 0 -0.130575 0.610060 -5.453093

59 1 0 -0.362766 2.362676 -5.629072

60 6 0 3.250572 1.067791 -4.031823

61 1 0 3.991663 1.871756 -4.127928

62 1 0 3.706058 0.245497 -3.473509

63 1 0 3.011377 0.700805 -5.031821

64 6 0 3.190553 1.990104 -1.009633

65 1 0 3.738316 1.048206 -1.092028

66 1 0 3.872789 2.810279 -1.270425

67 1 0 2.898333 2.115016 0.035252

68 45 0 0.535026 0.298274 -2.085258

69 17 0 2.320700 -1.396490 -1.843843

---------------------------------------------------------------------

Optimized Cartesian coordinates for ts-IIin2-rh

---------------------------------------------------------------------

Center Atomic Atomic Coordinates (Angstroms)

Number Number Type X Y Z

---------------------------------------------------------------------

1 6 0 -3.368367 -0.861706 -1.617434

2 6 0 -4.347369 -1.726344 -2.161343

3 6 0 -4.594682 -2.935285 -1.559758

4 6 0 -3.874980 -3.303941 -0.388332

5 6 0 -2.918072 -2.478294 0.132297

6 6 0 -1.744048 -0.251003 -0.174838

7 6 0 -2.039187 0.761722 -1.107669

8 1 0 -4.885526 -1.388203 -3.039303

9 1 0 -5.346564 -3.605841 -1.962461

10 1 0 -4.081556 -4.240851 0.116144

11 1 0 -2.361558 -2.706462 1.029669

12 6 0 -1.486574 2.122249 -1.265028

13 6 0 -1.728132 2.804608 -2.474372

14 6 0 -0.255618 4.072871 -0.480881

15 6 0 -1.228293 4.085899 -2.686211

16 1 0 -2.314385 2.306459 -3.238056

17 6 0 -0.479425 4.725163 -1.693060

18 1 0 0.302770 4.564170 0.310788

19 1 0 -1.424460 4.589255 -3.629108

20 1 0 -0.089012 5.725504 -1.858174

21 7 0 -3.006537 0.356130 -1.989839

22 7 0 -2.636858 -1.281471 -0.491383

23 6 0 -0.793721 -0.379837 0.969127

24 6 0 -0.086885 -1.633167 1.060517

25 1 0 1.359591 1.336829 0.677888

26 1 0 -0.248648 -2.333877 0.246885

27 6 0 -1.179014 0.399528 2.205408

28 6 0 -0.345536 0.551892 3.331026

29 6 0 -2.472827 0.953489 2.291096

30 6 0 -0.785047 1.209302 4.478319

31 1 0 0.672373 0.191347 3.306557

32 6 0 -2.913513 1.610359 3.439208

33 1 0 -3.148077 0.865215 1.447992

34 6 0 -2.073133 1.741353 4.543739

35 1 0 -0.107676 1.312173 5.321256

36 1 0 -3.919452 2.019659 3.464360

37 1 0 -2.412508 2.255324 5.438291

38 6 0 0.439061 -2.347623 2.231342

39 8 0 0.819391 -3.513866 2.152031

40 1 0 0.492166 -1.817571 3.196410

41 6 0 -0.758396 2.787855 -0.264642

42 1 0 -0.610639 2.324257 0.700392

43 6 0 2.967845 0.338915 -1.387979

44 6 0 3.537671 -0.807900 -0.655534

45 6 0 2.734474 -1.937097 -0.885580

46 6 0 1.582907 -1.473746 -1.661534

47 6 0 1.817134 -0.097352 -2.073424

48 6 0 3.630539 1.678514 -1.501700

49 1 0 2.936912 2.436345 -1.872586

50 1 0 4.010987 2.018528 -0.535162

51 1 0 4.480150 1.630132 -2.195669

52 6 0 1.031739 0.645174 -3.108773

53 1 0 1.431220 0.431128 -4.110007

54 1 0 -0.019746 0.351995 -3.107035

55 1 0 1.071083 1.724947 -2.956506

56 6 0 0.554693 -2.379431 -2.271652

57 1 0 0.892382 -2.702622 -3.265429

58 1 0 0.400407 -3.280023 -1.672842

59 1 0 -0.406935 -1.877609 -2.401045

60 6 0 2.956625 -3.346884 -0.422903

61 1 0 2.984249 -4.033514 -1.278204

62 1 0 3.909470 -3.441491 0.103004

63 1 0 2.171283 -3.690192 0.260844

64 6 0 4.805868 -0.735668 0.138866

65 1 0 4.968389 -1.642994 0.723953

66 1 0 5.670016 -0.599736 -0.524221

67 1 0 4.786976 0.112569 0.829608

68 45 0 1.403786 -0.335692 0.219269

69 17 0 2.300009 1.652818 1.816894

---------------------------------------------------------------------

Optimized Cartesian coordinates for ts-IVin3

---------------------------------------------------------------------

Center Atomic Atomic Coordinates (Angstroms)

Number Number Type X Y Z

---------------------------------------------------------------------

1 6 0 2.463415 -2.150365 -1.230532

2 6 0 2.117538 -2.841107 -2.408045

3 6 0 0.959283 -2.493505 -3.058170

4 6 0 0.151895 -1.438541 -2.557600

5 6 0 0.480625 -0.726397 -1.419857

6 6 0 2.225548 -0.638758 0.416651

7 6 0 3.365439 -1.451332 0.590782

8 1 0 2.775712 -3.632507 -2.746334

9 1 0 0.652530 -3.020742 -3.956984

10 1 0 -0.777943 -1.204894 -3.061546

11 6 0 4.314446 -1.515819 1.719673

12 6 0 5.665390 -1.801596 1.462034

13 6 0 4.808256 -1.511388 4.098363

14 6 0 6.577528 -1.921599 2.508026

15 1 0 5.982437 -1.935161 0.433019

16 6 0 6.153231 -1.772588 3.830869

17 1 0 4.465636 -1.414391 5.124775

18 1 0 7.620587 -2.136139 2.291626

19 1 0 6.863770 -1.869477 4.647119

20 7 0 3.505467 -2.342863 -0.424562

21 7 0 1.628007 -1.115240 -0.759348

22 6 0 1.687661 0.461824 1.196331

23 6 0 0.326362 0.668706 1.324537

24 1 0 -0.402987 -0.548488 1.509455

25 46 0 -0.886053 0.584777 -0.666861

26 6 0 -1.714239 -2.060051 0.967955

27 8 0 -0.849516 -1.626345 1.818751

28 8 0 -2.126244 -1.423245 -0.028944

29 6 0 -2.237259 -3.459984 1.235835

30 1 0 -2.550342 -3.549995 2.279556

31 1 0 -3.066988 -3.693460 0.567378

32 1 0 -1.428215 -4.180004 1.075210

33 15 0 -2.948086 1.669643 0.118191

34 15 0 -0.505343 1.921847 -2.559964

35 6 0 -3.064867 3.428405 0.674795

36 1 0 -4.104477 3.685238 0.903085

37 1 0 -2.461935 3.528580 1.580640

38 1 0 -2.690394 4.113390 -0.088254

39 6 0 -4.243093 1.550712 -1.198850

40 1 0 -4.305096 0.510880 -1.530529

41 1 0 -5.221472 1.866708 -0.822416

42 1 0 -3.980964 2.172506 -2.059407

43 6 0 -3.740048 0.774035 1.517104

44 1 0 -3.048259 0.792489 2.361257

45 1 0 -4.681414 1.261137 1.792002

46 1 0 -3.925854 -0.255874 1.211609

47 6 0 -1.008046 3.694963 -2.404488

48 1 0 -0.655168 4.270814 -3.266288

49 1 0 -2.095643 3.781015 -2.348143

50 1 0 -0.577900 4.117339 -1.493107

51 6 0 1.291082 2.091722 -2.944990

52 1 0 1.452638 2.780956 -3.780329

53 1 0 1.811464 2.465181 -2.059222

54 1 0 1.700689 1.111081 -3.194778

55 6 0 -1.223848 1.477662 -4.207411

56 1 0 -0.943897 2.213640 -4.968677

57 1 0 -0.856118 0.496189 -4.512426

58 1 0 -2.313510 1.431012 -4.134324

59 6 0 2.688036 1.352475 1.858829

60 6 0 2.514629 1.807046 3.178117

61 6 0 3.812549 1.804563 1.143441

62 6 0 3.425288 2.690816 3.756795

63 1 0 1.675485 1.441734 3.761314

64 6 0 4.715006 2.696503 1.717723

65 1 0 3.970486 1.452153 0.128978

66 6 0 4.526336 3.142323 3.028446

67 1 0 3.277006 3.019034 4.781639

68 1 0 5.570655 3.040744 1.143422

69 1 0 5.236401 3.829605 3.479536

70 6 0 -0.138948 1.891272 1.979410

71 8 0 -1.116673 1.994046 2.724108

72 1 0 0.431242 2.814936 1.724082

73 6 0 3.894402 -1.387752 3.052594

74 1 0 2.845361 -1.216495 3.268843

---------------------------------------------------------------------

Optimized Cartesian coordinates for ts-Vin4

---------------------------------------------------------------------

Center Atomic Atomic Coordinates (Angstroms)

Number Number Type X Y Z

---------------------------------------------------------------------

1 6 0 0.578107 -2.806538 0.473005

2 6 0 -0.450754 -3.697350 0.792405

3 6 0 -1.732589 -3.167508 0.963159

4 6 0 -2.025393 -1.808033 0.735975

5 6 0 -1.035736 -0.926881 0.271964

6 6 0 1.370230 -0.710907 0.284156

7 6 0 2.423032 -1.679831 0.314402

8 1 0 -0.225367 -4.742040 0.968793

9 1 0 -2.540511 -3.831291 1.259640

10 1 0 -3.042992 -1.449739 0.844491

11 6 0 3.873065 -1.474836 0.190512

12 6 0 4.754471 -2.482738 0.619954

13 6 0 5.784505 -0.157330 -0.527781

14 6 0 6.130940 -2.323095 0.484394

15 1 0 4.336344 -3.384533 1.053640

16 6 0 6.652197 -1.159036 -0.087403

17 1 0 6.180868 0.745966 -0.982766

18 1 0 6.800139 -3.108465 0.824837

19 1 0 7.726450 -1.036092 -0.193406

20 7 0 1.923514 -2.932946 0.438048

21 7 0 0.224114 -1.484993 0.262983

22 6 0 1.060436 0.631139 0.662732

23 6 0 -0.308129 0.966322 0.602868

24 46 0 -1.474116 0.561526 -1.093554

25 15 0 -2.460040 -0.880876 -2.797217

26 15 0 -1.966302 2.826451 -1.892129

27 6 0 -1.442848 -2.408256 -3.049216

28 1 0 -1.912023 -3.093092 -3.763957

29 1 0 -0.452297 -2.128925 -3.418639

30 1 0 -1.313941 -2.919370 -2.092032

31 6 0 -4.115670 -1.605358 -2.385670

32 1 0 -4.865460 -0.810093 -2.343411

33 1 0 -4.426992 -2.352591 -3.123402

34 1 0 -4.062712 -2.076307 -1.401217

35 6 0 -2.738136 -0.358064 -4.557133

36 1 0 -1.809622 0.041229 -4.974235

37 1 0 -3.072801 -1.197218 -5.176498

38 1 0 -3.496798 0.428575 -4.596944

39 6 0 -3.673883 3.318502 -1.377538

40 1 0 -3.911980 4.344715 -1.677713

41 1 0 -4.404746 2.636853 -1.822187

42 1 0 -3.728842 3.223821 -0.290736

43 6 0 -0.968114 4.241605 -1.236232

44 1 0 -1.364210 5.202613 -1.581794

45 1 0 -0.992661 4.214987 -0.145449

46 1 0 0.068906 4.146598 -1.570929

47 6 0 -1.972614 3.246193 -3.701367

48 1 0 -2.261546 4.288836 -3.873317

49 1 0 -0.974541 3.082673 -4.118502

50 1 0 -2.671231 2.596511 -4.233553

51 6 0 2.065148 1.528830 1.287445

52 6 0 2.941690 1.062600 2.284755

53 6 0 2.140024 2.882453 0.914940

54 6 0 3.857525 1.922171 2.886470

55 1 0 2.889247 0.024817 2.596205

56 6 0 3.061235 3.741435 1.514605

57 1 0 1.476573 3.251053 0.140198

58 6 0 3.923346 3.264269 2.502595

59 1 0 4.519225 1.544277 3.660581

60 1 0 3.105350 4.782893 1.208257

61 1 0 4.640449 3.931803 2.971818

62 6 0 -0.889466 1.926485 1.531101

63 8 0 -2.039992 2.363442 1.481312

64 1 0 -0.225883 2.246886 2.361735

65 6 0 4.406309 -0.313579 -0.393361

66 1 0 3.737138 0.461914 -0.750604

---------------------------------------------------------------------

Table S1: Calculated relative energies (all in kcal mol-1, relative to isolated species) for the ZPE-corrected Gibbs free energies (ΔG_gas), Gibbs free energies for all species in solution phase (ΔG_sol) at 393 K, 413 K by B3LYP/6-311++G(d,p)//B3LYP/6-31G(d) method and difference between absolute energy.

Table S2: The activation energy (local barrier) (in kcal mol-1) of all reactions in the gas, solution phase calculated with B3LYP/ 6-311++G(d,p)//B3LYP/6-31G(d) method and difference between the two.

Figure S1: Evolution of bond lengths along the IRC for (a) ts-Ai1 (b) ts-i2C (c) ts-Di5 (d) ts-in1II (e) ts-IIin2 (f) ts-IVin3 at the B3LYP/6-311++G(d,p) level