Mechanism and Origins of Stereoinduction in an Asymmetric Friedel

Article Cite This: J. Org. Chem. 2018, 83, 4628−4640

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Mechanism and Origins of Stereoinduction in an Asymmetric Friedel−Crafts Alkylation Reaction of Chalcone Catalyzed by Chiral N,N′‑Dioxide−Sc(III) Complex Yini Zuo, Na Yang, Xunkun Huang, Changwei Hu, and Zhishan Su* Key Laboratory of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu, Sichuan 610064, P. R. China S Supporting Information *

ABSTRACT: The mechanism and selectivity of the asymmetric Friedel−Crafts (F−C) alkylation reaction between indole and chalcone catalyzed by chiral N,N′dioxide−Sc(III) complexes were investigated at the M06/6-311+G(d,p)//M06/ [LANL2DZ,6-31G(d)](SMD,CH2Cl2) level. The reaction occurred via a threestep mechanism: (i) the C3−Cβ bond formation by interacting the most mucleophilic C3 center of indole with the most electrophilic Cβ center of chalcone; (ii) the abstraction of the proton at the C3 atom of indole by counterion OTf−; (iii) proton transfer from HOTf to the Cα atom of chalcone, generating the F−C alkylation product. The reaction preferred to occur along the favorable reface attack pathway, producing the dominant R-product. The turnover frequency (TOF) of catalysis was predicted to be 1.59 × 10−7 s−1, with a rate constant of K(T) = 1.58 × 10−7 exp(−29057/RT) dm6·mol−2·s−1 over the temperature range of 248−368 K. Activation strain model (ASM) and energy decomposition analysis (EDA), as well as noncovalent interaction (NCI) analysis, for the stereocontrolling transition state revealed that the substituent attached to the N atom of the amide subunits as well as the amino acid backbone of ligand played important roles in chiral inductivity. The benzyl group with structural flexibility tended to form strong π−π stacking with substrate as well as the terminal phenyl group of chalcone, stabilizing re-face attack transition state.

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INTRODUCTION The Friedel−Crafts (F−C) alkylation reaction is one of the most powerful tools for carbon−carbon bond formation,1,2 which has been widely used to generate important building blocks for organic transformations.3−7 Since the first case of catalytic asymmetric F−C alkylation reaction was reported in the mid1980s,8 it has received much attention. Some organocatalysts (such as chiral amines,9,10 thiourea,11 phosphoric acid,12 ureas,13,14 cinchona alkaloids,15 or bissulfonamide16), Lewis acidic transition-metal complexes,3,4,17,18 as well as supramolecular metal-complexes/DNA catalysts6,19 have been proved to be efficient for catalytic asymmetric F−C alkylation reactions. In these successful cases, the reports involving chalcone derivatives as electrophiles were very limited, owing to their low reactivity and the difficulty in controlling the enantiofacial differentiation.20,21 The generally accepted mechanism of F−C alkylation reaction involves two continuous steps,22 i.e., C−C bond formation between the most electrophilic center and the most nucleophilic center of two reactants, followed by a proton transfer step. Some experimental and theoretical investigations have been performed to explore the mechanism as well as the selectivity of asymmetric F−C alkylation reactions.23−28 Herrera et al. studied the F−C alkylation reaction between indole and nitroalkene catalyzed by a © 2018 American Chemical Society

chiral amino indanol-derived thiourea at the PCM(CH2Cl2)/ M06-2X/6-311G(d,p) theoretically level. The −OH group of the catalyst was assumed to activate the nitroalkene as well as indole substrates by hydrogen bonding and orientated the preferential attack of the indole over the nitroalkene.23 In chiral phosphoric acid-catalyzed asymmetric F−C reactions, the good reactivity of 4,7-dihydroindoles substrate was attributed to its high HOMO energy and suitable trajectory to attack the nitroolefin in the transition state.29 A nine-membered transition state formed by hydrogen bonding between the N−H group of indole with the phosphoryl O atom of catalyst was proposed to explain the controlling step of the enantioselecivity for excellent ee.30 When ketimines generated in situ acted as electrophiles for F−C reaction of 2-methoxyfuran mediated by BINOL-derived phosphoric acid, the excellent enantiochemical outcomes arose from the suitable hydrogen-bonding network as well as the steric repulsion between the phenanthryl substituent of phosphoric acid and the methoxy group of 2-methoxyfuran.31 Electron localization function (ELF) bonding analysis by Domingo et al. indicated that C−C bond formation between indoles and the electrophilically activated nitroethylene occurred via C-to-C Received: February 9, 2018 Published: March 30, 2018 4628

DOI: 10.1021/acs.joc.8b00387 J. Org. Chem. 2018, 83, 4628−4640

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The Journal of Organic Chemistry coupling of two pseudoradical centers located at the most reactive centers of indoles and nitroethylene, producing a zwitterionic intermediate.22 Transition-metal complexes containing zirconium,32 aluminum,33 copper,34,35 nickel,36 zinc,3,17,37 and platinum38,39 or palladium40 have been successfully applied in asymmetric F−C reactions. In these Lewis acid-catalyzed transformations, coordination of the bidentate organic substrates (such as Nsulfonyl aldimine35 and nitroalkene37) to the metal center in chelating fashion enhanced stereochemical outcomes. A 1,3metal binding model of N-sulfonyl aldimine or nitroalkene substrates to a metal center was assumed to be the key point for enantiocontrol in M(II)−bisoxazoline complexes (M = Cu,35 Zn,37 and Ni36) catalyzing asymmetric F−C reactions. In Trost’s asymmetric F−C reactions catalyzed by dinuclear zinc complexes, the deprotonated indole and ethyl glyoxylate imine coordinated to the Zn center simultaneously, to form the key reactive species.3 Carmona and co-workers studied the rhodiumcatalyzed F−C reaction at the B3LYP-D3/def2-SVP level. The zwitterionic intermediate was generated by nucleophilic attack of the N-methyl-2-methylindole carbon on the trans-β-nitrostyrene. The participation of water molecules decreased the energy barrier of the 1,3-prototropic shift for final adducts.17 In addition, the π−π stacking between the phenyl group of the ligands (4R,5S)DiPh-BOX or Bis(sulfonamide)-diamine and substrates was supposed to stabilize the key species in Cu(II)-complex-catalyzed F−C alkylation of indoles, contributing to high ee.41,42 Recently, the chiral N,N′-dioxide−Sc(III) catalyst developed by Feng’s group has shown excellent performance on asymmetric F−C alkylation reactions.4,21 The β-heteroaryl-substituted dihydrochalcones were obtained with high yield (99%) and excellent stereoselectivity (85−92% ee) in the presence of Sc(III)-complexes.21 A transition state model was proposed, in which the chalcone and counterion OTf− coordinated to the scandium center simultaneously. The incoming indole preferred to attack the re-face rather than si-face of chalcone because of the shielding effect of the nearby anthracenyl ring in the ligand for the R-configured product. Interestingly, the aforementioned complex could also catalyze the asymmetric F−C reaction of ohydroxybenzyl alcohols with C3-substitutend N-protected indoles, providing diarylindol-2-ylmethanes in up to 99% yield and 99% ee. With the aid of LiBr, the OTf− anion might capture the proton to cleave the O−H bond of the phenyl hydroxyl group of alcohol, generating the key intermediate.4 Although the experimental results provided valuable information for beginning the mechanistic analysis of the asymmetric F−C reaction catalyzed by N,N′-dioxide−Sc(III) catalyst, the characteristic of the chiral environment and the major factors contributing to the chiral discrimination process were still unclear. Furthermore, the theoretical studies of the Lewis acid catalyzed asymmetric F−C reaction were very limited.17,23 Herein, the reaction mechanism and enantioselectivity of the asymmetric F−C alkylation reaction between chalcones and indole were investigated by using the DFT method. The key structural units in the chiral ligand affecting activation barriers as well as enantioselectivity were explored in detail. These results are expected to suggest a model to explain the stereochemical outcome, providing useful information for the rational design and synthesis of new chiral N,N′-dioxide−Sc(III) catalyst complex catalysts.

basis set with an effective core potential for scandium ion and the 6-31G(d) basis set for other atoms. The solvation effect was considered in optimization, using the SMD45 solvation model. Frequency calculations were carried out at the same level of theory as those for the structural optimization to characterize the nature of the stationary points on the potential energy surface. The intrinsic reaction coordinate (IRC) calculations were used to confirm the connectivity between each transition state (TS) and two associated minima of the proposed mechanism.46 Natural bond orbital (NBO)47,48 and reactivity indices analyses (electrophilicity index ω and nucleophilicity index N)49,50 of the reactants were performed to obtain further insight into the electronic properties of stationary points at the M06/6-311+G(d,p)(SMD,CH2Cl2) level. The corresponding local reactive indices (ωk and Nk) of reactants or molecular complexes were calculated using the following equations: ωk = ωPk+, Nk = NPk‑, where the electrophilic Parr functions Pk+ and nucleophilic Parr functions Pk− were obtained from ASD at the radical anion and the radical cation of the corresponding reagents. Unless specified, the Gibbs free energies corrected by both solvation and zero-point vibrational effects at the M06/6-311+G(d,p)(SMD,CH2Cl2) level at 308 K21 were used in the discussions. To explore the origin of selectivity of the reaction, we employed activation strain model analysis (ASM)51,52 (or distortion/strain model calculation53) to decompose the bonding energy or activation barrier into the distortion energy (ΔEstrain) and interaction energy (ΔEint) at the B3LYP/6311+G(d,p) level by using the Gaussion 09 program. Furthermore, the interaction (ΔEint) between reacting species was further decomposed into an electrostatic interaction (ΔVelstat), the Pauli repulsion (ΔEPauli) as well as orbital interaction (ΔEoi) (i.e., ΔEint = ΔEPauli + ΔVelstat + ΔEoi) based on the conceptual framework provided by the Kohn−Sham molecular orbital (KS-MO) model.54 Energy decomposition analysis55 (EDA) as well as the extended transition state-natural orbitals for chemical valence analysis (ETS-NOCV)56,57 were performed by single-point calculations using the Amsterdam density functional (ADF) program55,58,59 at the M06/TZP level.

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RESULTS AND DISCUSSION Activation of Chalcone Substrate. X-ray structural analysis60 and our previous calculations61 indicate that chiral N,N′-dioxide ligand interacts with Sc3+ metal center, forming a tetracoodinate-Sc(III) complex (CAT) with “pocketlike” chiral environment.61−63 The chalcone substrate and counteranion OTf− from metal salt Sc(OTf)3 could interact with the central metal Sc3+ ion of tetradentate-Sc(III) catalyst simultaneously, forming a hexacoordinate chiral N,N′-dioxide−Sc(III) complex (L-COM)59b. Considering that there exist two possible conformations (s-cis and s-trans) for free chalcone substrate, scis-chalcone and s-trans-chalcone as well as that their corresponding Sc(III) complexes were optimized first. As shown in Table S1 of the Supporting Information (SI), s-cischalcone is more stable than s-trans-chalcone by 2.1 kcal mol−1. In addition, the relative energy of hexacoordinate-Sc(III) complex with s-cis-chalcone (s-cis-L1-COM) is also slightly lower than that of s-trans-chalcone−Sc(III) complex (s-trans-L1-COM) by 0.6 kcal mol−1. Thus, unless otherwise specified, s-cis-chalcone was used in the following discussions. The geometry and electronic properties of L1-COM formed by the interaction of chalcone with [L1-Sc(OTf)]2+ are analyzed as a representative (Figure 1). The calculations indicate that the coordination processes are exothermic by 35.3 kcal mol−1.

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COMPUTATIONAL DETAILS All structures were fully optimized using the Gaussian 09 software program,43 employing the M0644 functional, with the LANL2DZ 4629


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also leads to electron density flowing from chalcone substrate to [L1-Sc(OTf)]2+ moiety and redistribution in the complex. To quantify the electron-transfer process, we visualized the deformation density (Δρ), and the corresponding orbital interaction energies by ETS-NOCV analysis are shown in Figure S1 (SI). Δρ(2) represents the σ-donation from the O atom of chalcone to the unoccupied dx2‑y2 orbital of the Sc(III) center, with an orbital interaction energy ΔEorb(2) of −18.7 kcal mol−1. For Δρ(3), the electronic density depletion in the CO π orbital of chalcone indicates the weakening of the CO bond. Accordingly, the electrophilicity (ω) of chalcone in L1-COM is enhanced, with a larger global electrophilic index (3.75 eV vs 2.35 eV in free chalcone) and local electrophilic index at the Cβ atom (ωk = 1.75 eV vs 0.63 eV in free chalcone). We also performed a conformation search and located another possible complex, L1-COM-1, in which the phenyl group of chalcone attached to the CO bond is placed on the same side with the coordinated OTf− anion (Figure S2, SI). Although L1COM-1 exhibits a similar global electrophilic index as L1-COM, the local electrophilic index of the Cβ atom in L1-COM-1 is lower than that in L1-COM (1.25 eV vs 1.75 eV). Moreover, the corresponding WBI of the CαCβ double bond in L1-COM-1 is larger than that of L1-COM (1.653 vs 1.630). These results indicate that the CαCβ double bond in L1-COM-1 is less activated, compared to L1-COM. Thus, we just focus on the reaction pathways using L1-COM as the starting complex. Mechanism of the Catalytic Reaction. The reaction mechanism and catalytic cycle for the F−C alkylation reaction of indole (R1) with chalcone (R2) is further investigated at the same theoretical level (Scheme 1). The calculations indicate that the reaction occurs along a stepwise mechanism, namely, C3−Cβ bond formation followed by H-transfer from indole to the activated chalcone (Scheme 2). Considering the orientation of indole to metal-activated chalcone, four possible pathways (si-a, si-b, re-a, and re-b) are studied (Scheme 3), in which two re-face approach pathways (re-a and re-b) and two si-face approach pathways (si-a and si-b) produce the R-product and S-product,

Figure 1. Optimized geometry of hexacoordinate-Sc(III) complex (L1COM). The bond lengths are in Å.

Scheme 1. Asymmetric F−C Alkylation Reactions between Indole (R1) and Chalcone (R2) Catalyzed by Chiral N,N′Dioxide−Sc(III) Complexes

Compared to free chalcone (R2), the CαCβ double bond in L1COM is lengthened by 0.015 Å. Moreover, the corresponding Wiberg bond index (WBI) is decreased from 1.743 to 1.630. These results indicate that CαCβ double bond of chalcone in L1-COM is significantly weakened. The formation of L1-COM

Scheme 2. Reaction Mechanism of F−C Alkylation Reactions between Indole (R1) and Chalcone (R2) Catalyzed by Chiral L− Sc(III) catalyst via Intramolecular H-Transfer and OTf-Assisted H-Transfer Processes, Respectively (L = chiral N,N′-dioxide ligand)

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The Journal of Organic Chemistry Scheme 3. Four Possible Reaction Pathways Corresponding to the Formation of Products with S- and R-Configuration, Respectively

Figure 2. Energy profile associated with a intramolecular H-transfer mechanism in the F−C alkylation reaction between indole (R1) and chalcone (R2) catalyzed by chiral L1−Sc(III) catalyst. Relative Gibbs free energies are shown in parentheses (kcal mol−1).

are decreased by 8.6−19.8 kcal mol−1, suggesting that the counterion OTf− could accelerate the reaction process. For the OTf-L1-re-b pathway, the relative Gibbs free energies of the two H-transfer transition states (OTf-L1-re-b-TS2 and OTf-L1-re-bTS3) are predicted to be 26.6 and 19.7 kcal mol−1, respectively, which are significantly lower than those along the other three pathways (OTf-L1-re-a, OTf-L1-si-a, and OTf-L1-si-b). As a result, the product with the R-configuration is produced predominantly.21 As shown in Figure 4, the distances between H and OTf− are 1.301 Å for transition state OTf-L1-re-b-TS2 and 1.063 Å for transition state OTf-L1-re-b-TS3, respectively. The negative Laplacian of electronic densities ∇2ρ at (3, −1) bonding critical points (a, Figure 4) by AIM analysis indicate the covalent interaction between OTf− and H atom in OTf-L1-re-b-TS2 and OTf-L1-re-b-TS3. These results suggest that OTf− takes part in proton transfer, acting as a proton shuttle in the reaction. Thus, counterion OTf− is crucial for the F−C reaction between indole and chalcone, which takes part in proton transfer and decreases the reaction barrier. The roles of proton transfer agent and the OTf-assisted H-transfer process were also addressed by Ujaque

respectively. As shown in Figure 2, the C3−Cβ bond formation step is predicted to be the chirality-controlling step, with energy barriers of 19.8−22.4 kcal mol−1. The relative energies of L1-re-aTS1 and L1-re-b-TS1 along re-face attack pathways in chiralcontrolling step are lower than those of L1-si-a-TS1 and L1-si-bTS1 along si-face pathways by 1.0−2.6 kcal mol−1. From the viewpoint of energy, the energy barriers for the intramolecular H transfer step are as high as 40.0−49.6 kcal mol−1, indicating that it is difficult for reaction to occur via an intramolecular H transfer step. Role of Counterion OTf−. The presence of an anion (counterion) in the proton transfer step has been found to be important in several reaction processes.64,65 On the basis of experimental assumptions,4 a possible H-transfer mechanism assisted by counteranion was studied, in which basic OTf− anion generated from metal salt precursor (Sc(OTf)3) abstracts a H atom from indole substrate and transfers the proton to the C atom at the α position of chalcone via an intermolecular H transfer process along OTf-L1-re-a to OTf-L1-si-b pathways (Figure S3, SI). As shown in Figures 3 and S4 (SI), the energy barriers for the OTf-assisted intermolecular H-transfer process 4631


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Figure 3. Comparison of energy profiles associated with intramolecular H-transfer (red line) and OTf-assisted H-transfer (blue line) along si-a (a) and reb pathways (b) for the catalytic F−C alkylation reaction between indole (R1) and chalcone (R2) mediated by L1−Sc(III) complex. Relative Gibbs free energies are shown in parentheses (kcal mol−1).

Figure 4. Laplacian (∇2ρ) and electronic density (ρ, in parentheses) of selected bond critical points (BCP) for transition states were obtained by AIM analysis.

and co-workers in gold(I)-catalyzed addition of phenols to olefins.64 Origin of Stereoselectivity. The optimized geometries of the four competing transition states (L1-si-a-TS1, L1-si-b-TS1, L1-re-a-TS1, and L1-re-b-TS1) in the C−C bond formation step are shown in Figure 5. For transition states L1-re-TS1-a and OTfL1-re-b along the re-face pathway, the terminal Ph group of

chalcone is placed away from the bulky chiral backbone of ligand, avoiding the unfavorable steric repulsion. As a result, the relative energies of L1-re-a-TS1 and L1-re-b-TS1 are slightly lower than those of L1-si-a-TS1 and L1-si-b-TS1 by 1.0−2.6 kcal mol−1. Compared to transition state L1-re-b-TS1, the repulsion between the aromatic ring of indole and the OTf− anion increases the instability of L1-re-a-TS1, leading to slightly higher relative 4632


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Figure 5. Optimized geometries of four competing transition states in the C3−Cβ bond formation step (chiral-controlling step) and their relative Gibbs free energies (kcal mol−1) in the F−C alkylation reaction between indole (R1) and chalcone (R2) catalyzed by chiral L1−Sc(III)complex.

Table 1. Results of Activation Strain Analysis (ASM) for Competing Transition States for Catalytic F−C Alkylation Reaction between Indole (R1) and Chalcone (R2) Catalyzed by L-Sc(III) Catalysts (L = chiral N,N′-dioxide liagnd) (energies in kcal mol−1)a ΔE⧧strain

a b

TSs

ΔE

⧧

ΔE⧧int

indole (R1)

chalcone (R2)

[L-Sc(OTf)]2+

sum

G(L) (%)

L1-si-a-TS1 L1-re-b-TS1 L2-si-b-TS1 L2-re-a-TS1 L3-si-b-TS1 L3-re-a-TS1

14.9 11.8 12.6 15.9 17.2 23.5

−6.9 −12.7 −12.6 −8.7 −8.9 −6.7

6.9 7.1 6.9 6.5 6.2 6.7

15.5 16.4 17.6 17.2 16.2 17.7

0.3 1.0 0.7 0.9 3.7 5.7

21.8 24.5 25.2 24.6 17.2 30.2

67.1 67.9 61.7 62.6 65.4 66.1

ΔΔG⧧

eeb (%)

2.2

94.4

0.9

62.3

−4.0

99.7

G(L) is the percentage of metal center coordination sphere shielded by the chiral N,N′-dioxide ligands (L1−L3), obtained by Solid-G program.66. Theoretical enantioselectivity excess (ee) obtained by the Curtin−Hammett principle.67

energy (19.8 vs 21.0 kcal mol−1). In contrast to L1-re-b-TS1, the terminal phenyl group in chalcone becomes closer to the sixmembered aliphatic ring in ligand when indole approaches to chalcone from the si-face via transition state L1-si-a-TS1. Accordingly, more significant structural deformation of the chiral pocket is observed, accompanying the slightly larger variance in the G-parameter66 (from 70.2% to 67.1%). As shown in Figures 3 and S4 (SI), the energy barrier corresponding to the re-face attack along the OTf-L1-re-b pathway is the lowest among the four pathways either in the chiral-controlling step (C−C bond formation step) or in the intermolecular H transfer step, producing the predominant R-product observed in experiment (Figure 3b). The corresponding low-energy competing pathway

for enantioselectivity is predicted to be OTf-L1-si-a, with an energy barrier of 22.0 kcal mol−1 in the chiral-controlling step via transition state L1-si-a-TS1 (Figure 3a). The difference of energy barriers (ΔΔG) along two competing pathways (L1-si-a-TS1 and L1-re-b-TS1) is 2.2 kcal mol−1. According to the Curtin− Hammett principle,67 the predicted enantioselectivity is 94% ee (Table 1), which is close to the experimental result (87% ee). As expected, similar selectivity results (93% ee) are also obtained when L4−Sc(III) catalyst with 9-anthracenylmethyl groups at the amino moiety is used for the F−C alkylation reaction between indole (R1) and chalcone (R2) Figure S5, SI). These results are in good agreement with experimental observations. 4633


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The Journal of Organic Chemistry To gain insight into the origin of the stereoselectivity of reaction and explore the key factor contributing to the favorable re-face attack pathway, activation−strain model (ASM) analysis is adopted to study the evolution of energy components in formation of L1-si-a-TS1 and L1-re-b-TS1 in the chiralitycontrolling step. As shown in Figure 6a, two competing pathways

Figure 7. Energy decomposition analysis (EDA) of the catalytic F−C reaction between indole (R1) and chalcone (R2) along the reaction coordinate projected onto the C3···Cβ distance in two competing pathways (L1-si-a and L1-re-b). (a) Evolution of Pauli repulsion (ΔEpauli) along the reaction coordinate; (b) Evolution of electrostatic interaction (ΔV⧧elstat) and orbital energy (ΔEoi) along the reaction coordinate.

Table 2. Results of Energy Decomposition Analysis (EDA) for Two Competing Transition States in the ChiralityControlling Step (C−C bond formation step) in the Asymmetric F−C Alkylation Reaction between Indole (R1) and Chalcone (R2) Mediated by Chiral N,N′-dioxide−Sc(III) Catalysts (energies in kcal mol−1)

Figure 6. Activation−strain analysis (ASM) of the catalytic F−C reaction between indole (R1) and chalcone (R2) along the reaction coordinate projected onto the C3···Cβ distance in two competing pathways (L1-si-a and L1-re-b). (a) Evolution of ΔE, ΔEint, and ΔEstrain along the reaction coordinate. (b) Evolution of the three components of ΔEstrain along the reaction coordinate.

presented a similar tendency in the strain energy curve, although the deformation energy of catalyst moiety {[L1-Sc(OTf)]2+} along the favorable re-face pathway is more destabilizing than that along the si-face pathway (Figure 6b). The main difference of energy barrier along two competing pathways arises from the interaction energy term (ΔEint). Moreover, ΔEint corresponding to the re-face attack along the OTf-L1-re-b pathway is more stabilizing at any given point along the reaction coordinate than along the si-face attack one, which is responsible for the lower reaction barrier of the favorable re-face attack pathway. Then, the interaction energies (ΔEint) of reacting fragments along two competing pathways are decomposed into the electrostatic interaction (ΔVelstat), Pauli repulsion (ΔEPauli), and orbital interaction (ΔEoi). As shown in Figure 7 and Table 2, EDA

TSs

ΔE≠int

ΔE⧧Pauli

ΔV⧧elstat

ΔE⧧oi

L1-si-a-TS1 L1-re-b-TS1 L2-si-b-TS1 L2-re-a-TS1 L3-si-b-TS1 L3-re-a-TS1

−85.4 −89.5 −92.3 −87.7 −90.2 −92.8

149.7 161.4 160.4 160.4 150.1 165.3

−116.0 −127.3 −125.1 −125.3 −119.8 −129.9

−119.1 −123.8 −127.5 −122.8 −120.4 −128.2

analysis suggests that the orbital energy ΔE⧧oi and electrostatic energy ΔV⧧elstat for L1-si-a-TS1 are −119.1 and −116.0 kcal mol−1, respectively, which are less stabilizing than those of L1-reb-TS1 (−123.8 and −127.3 kcal mol−1). In the formation of transition state L1-re-b-TS1, the orbital energy term ΔEoi of chalcone fragment and Sc-based fragment is less stabilizing than that of ΔVelstat by 3.5−17.0 kcal mol−1 (Figure 7b). Although the Pauli repulsion ΔE⧧Pauli in L1-re-b-TS1 is slightly more 4634


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The Journal of Organic Chemistry destabilizing than that of L1-si-a-TS1 by 11.7 kcal mol−1, the stronger attractive terms, especially the electrostatic energy term (ΔV⧧elstat), overwhelm the unfavorable Pauli repulsion ΔE⧧Pauli. As a result, the interaction energy (ΔE⧧int) in L1-re-b-TS1 is stronger than that of L1-si-a-TS1 by 4.1 kcal mol−1. As shown in Figure 5, structural analysis of transition state L1-re-b-TS1 suggests that the planar indole substrate is parallel to the left benzyl group of ligand, with the distance of 3.349 Å. Noncovalent interaction (NCI) analysis indicates that there exists a strong π−π stacking effects for these three subparallel π-conjugated aromatic rings (Figure 8). This effect stabilizes the transition state L1-re-b-

Scheme 4. Asymmetric F−C Alkylation Reactions between Pyrole (R3) or N-Methylindole (R4) and Chalcone (R2) Catalyzed by Chiral L1−Sc(III) Catalyst

Similar to indole substrate, the π−π stacking effects between substrates (pyrrole and N-methylindole) and benzyl group of the chiral ligand are also observed in the favorable transition states L1-pyrrole-re-b-TS1 or L1-N-methyl-re-b-TS1 (Figure S9, SI). These results indicate that removing the phenyl ring from indole (R3, pyrrole) or introducting the N-methyl group to indole (R4, N-methylindole) do not break completely the π−π stacking between substrate and ligand in the re-face attack transition states (L1-pyrrole-re-b-TS1 for pyrrole and L1-N-methyl-re-b-TS1 for N-methylindole), although this stabilizing effect is weakened to some extent (the electrostatic interaction energy ΔV⧧elstat between reaction fragments for pyrrole and N-methylindole (−120.2 and −126.0 kcal mol−1) are lower than that of indole [−127.3 kcal mol−1; see Tables 2 and S2 (SI)]. Analysis of Turnover Frequency (TOF) and Rate Constant in the Catalytic Cycle. On the basis of the transition state theory and energetic span model,68 we evaluated the theoretical turnover frequency (TOF) of catalytic cycles via intramolecular and OTf-assisted H-transfer mechanism catalyzed by L1−Sc(III) catalyst. In eqs 1 and 2,69−71 the δE (the energetic span) is the energy difference between the summit and the trough of the catalytic cycle. GTDTS and GTDI are defined as the Gibbs free energies of the TOF-determining transition state (TDTS) and the TOF-determining intermediate (TDI), and ΔGr is the global free energy of the whole cycle.72

Figure 8. Stacking (π−π) interaction between indole, phenyl group of chalcone, and benzyl group of chiral N,N′-dioxide ligand (L1) in transition state L1-re-b-TS1, visualized by Multiwfn software (isovalue = 0.70).

TS1 well and contributes to strong electrostatic interaction of reacting fragments (ΔV⧧elstat = −127.3 kcal mol−1). The similar π−π stacking effect between conjugated 9-anthracenylmethyl group and indole substrate is also observed for transition states L4-re-b-TS1 in L4-Sc(III)-catalyzed F−C alkylation reaction between indole (R1) and chalcone (R2) (Figure S6) . Therefore, the combination of steric repulsion of chiral backbone with strong π−π stacking effect between chiral ligand and substrates enhances the difference of interaction energy of reacting fragments along two competing pathways, attributing to high enantioselectivity. The Friedel−Crafts alkylation reactions of chalcone with pyrrole (R3) or N-methylindole (R4), respectively, catalyzed by chiral L1−Sc(III) catalyst were further studied (Scheme 4). Four possible transition states in the chiral-controlling step (C−C bond formation step) were located at the same theoretical level. As shown Figures S7 and S8 (SI), the reaction barriers are 20.6− 24.0 kcal mol−1 for N-methylindole and 22.6−27.6 kcal mol−1 for pyrrole, respectively, indicating that the Friedel−Crafts reaction of chalcone with N-methylindole or pyrrole could also occur under the mild experimental conditions. Similar to indole (R1), the relative energies of transition states L1-pyrrole-re-b-TS1 or L1-N-methyl-re-b-TS1 in the re-face attack pathway are lower than those of L1-pyrrole-si-b-TS1 or L1-N-methyl-si-a-TS1 in the si-face attack pathway in the chiral-controlling step. These results indicate that the re-face attack pathway is more favorable than the si-face attack pathway either for N-methylindole or pyrrole substrates. These results are in good agreement with the experimental observations.21

TOF ≈

⎛ KBT ⎞ −δE / RT ⎜ ⎟e ⎝ h ⎠

δE = E(TDTS) − E(TDI)

(1)

if TDTS appears after TDI (2a)

δE = E(TDTS) − E(TDI) + ΔGr if TDTS appears before TDI

(2b)

where KB is Boltzmann’s constant, T is the absolute temperature, and h is Planck’s constant. As shown in Table 3, the intermediate L1-COM+R1 or L1COM+R1+OTf− is predicated to be TDI, and the H-transfer transition states are TDTS for the whole cycle of the F−C reaction between R1 and R2 catalyzed by L1−Sc(III) catalyst. As expected, the TOF of catalytic cycles involving OTf-assisted Htransfer pathways (OTf-L1-si-a to OTf-L1-re-b) are significantly higher than that of the intramolecular H-transfer pathways. Moreover, L1−Sc(III) exhibits better catalytic performance when the catalytic reaction occurs along path OTf-L1-re-b, with TOF being 1.59 × 10−7 s−1. 4635


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Table 3. Turnover Frequency (TOF) of the Catalytic Cycle for F−C Reaction Catalyzed by L1−Sc(III) Complex along Eight Pathwaysa path

TDI

L1-si-a L1-si-b L1-re-a L1-re-b OTf-L1-si-a OTf-L1-si-b OTf-L1-re-a OTf-L1-re-b a

L1-COM+R1

L1-COM+R1+OTf−

TDTS

TOF

L1-si-a-TS2 L1-si-b-TS2 L1-re-a-TS2 L1-re-b-TS2 OTf-L1-si-a-TS3 OTf-L1-si-b-TS2 OTf-L1-re-a-TS2 OTf-L1-re-b-TS2

3.21 × 10−23 s−1 8.40 × 10−17 s−1 2.03 × 10−20 s−1 1.72 × 10−20 s−1 4.42 × 10−9 s−1 1.01 × 10−10 s−1 1.03 × 10−8 s−1 1.59 × 10−7 s−1

product S-product R-product S-product R-product (major)

TDIs and TDTSs are TOF-determining intermediate and TOF-determining transition states, respectively.

Figure 9. Optimized geometries of four competing transition states in the C3−Cβ bond formation step (chiral-controlling step) and their relative Gibbs free energies (kcal mol−1) in the F−C alkylation reaction between indole (R1) and chalcone (R2) catalyzed by chiral L2−Sc(III) complex.

dm−3). ΔG⧧ is the activation Gibbs free energy barrier (kJ mol−1) between TDI and TDTS in the catalytic cycle, and ν⧧ is the imaginary frequency of TS, obtained at the M06/(6-31G(d),LanL2DZ) level. Then, the Winger’s tunneling effect corrected rate constants K(T) is calculated by the expression k(T) × κ(T). In the temperature range of 248−368 K, the rate constants K(T) for the OTf-L1-si-a pathway (si-a) and OTf-L1re-b pathway (re-b) can be fitted by the following expressions (in dm6·mol−2·s−1):

The rate constants K(T) along two low-energy competing pathways (OTf-L1-si-a and OTf-L1-re-b) were further evaluated according to conventional transition state theory (TST) and the following Winger’s formulations:73,74 K (T ) =

kB T hc

0

κ (T ) = 1 +

e−ΔG

⧧

/ kB T

1 hν ⧧ 24 kBT

Ksi ‐ a(T ) = 3.78 × 10−8 exp(44189/RT )

Where kB is Boltzmann’s constant, T is the absolute temperature, h is Planck’s constant, c0 is the standard concentration (1 mol

K re ‐ b(T ) = 1.58 × 10−7 exp(29057/RT ) 4636


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The Journal of Organic Chemistry Namely, the rate constants Ksi‑a are 2−3 orders of magnitude smaller than Kre‑b in the temperature range of 248−368 K, suggesting that the OTf-L1-re-b pathway is more favorable kinetically than the OTf-L1-si-a pathway. Effect of Ligand on Enantioselectivity. The influence of the substitute (R group in Scheme 1) of the amide moiety in ligand on the energy barrier and the enantioselectivity is further explored. When benzyl groups of ligand in L1 are replaced by phenyl groups (L2), an opening chiral pocket is constructed.75 NBO analysis indicates that the Wiberg bond index of the Cα Cβ bond in L2-COM is slightly larger than that in L1-COM (1.644 vs 1.630). As expected, the energy barriers of the C3−Cβ bond formation step for four pathways are higher than those of L1−Sc(III) catalyst (22.1−25.9 vs 19.8−22.0 kcal mol−1) (Figure 9). Different from L1, two low-energy competing transition states are L2-si-b-TS1 and L2-re-a-TS1, respectively, with the aromatic ring of indole being at the same side as the phenyl group of chalcone. Compared to L1−Sc(III) catalyst, the ΔΔG⧧ decreases from 2.2 kcal mol−1 to 0.9 kcal mol−1, with a theoretical enantioselectivity of 62% ee. Lacking the methylene linkage between the N atom of amide and phenyl group in ligand, it is difficult for the aromatic group to reach and overlap with the indole substrate well for π−π stacking along re-face attack pathways, although they still look parallel in geometry (the distance between the phenyl group of ligand and indole is about 3.627 Å). Consequently, the stabilizing effect along transition state L2-re-a-TS1 is significantly weakened, with comparable electrostatic energy (−125.1 vs −125.3 kcal mol−1) as well as orbital interaction energy (−127.5 vs −122.8 kcal mol−1) with L2-si-b-TS1 (Table 2). The inferior enantioselectivity for L2− Sc(III) catalyst was also obtained in experiment.21 When L3 with o-diisopropylphenyl groups is used to form the key reactive species (L3-COM), a contracted chiral pocket is observed with a G-parameter G(L3) of 68.0%. As shown in Figure 10, the o-isopropyl groups in left amide of ligand blocks the

Therefore, the R group attached to the N atom of amide subunits in ligand plays an important role for the asymmetric inductivity of chiral N,N′-dioxide−Sc(III) catalyst. The benzyl group with a suitable linker and structural flexibility in the L1 ligand makes the π−π stacking between indole, the phenyl group of the chalcone, and the benzyl group feasible. This favorable effect translates into more stabilizing interaction energy (ΔEint) of reacting fragments, facilitating the re-face pathway for Rproduct. When the benzyl group is replaced by a phenyl group, the stabilizing interaction along the re-face pathway disappears, leading to low ee. The additional bulky o-iPr in anline reverses the enantioselectivity of the F−C reaction by shielding the reacting site from the re-face and increases the deformation energy of the [L3−Sc(OTf)]2+ fragment. These results are in good agreement with experimental observations.

■

CONCLUSION

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ASSOCIATED CONTENT

The mechanism and selectivity of the F−C alkylation reaction between indole (R1) and chalcone (R2) catalyzed by chiral N,N′dioxide−Sc(III) complexes are investigated theoretically, revealing the following results: (1) Chalcone substrate and counterion OTf− coordinate to the Sc(III) center of chiral N,N′-dioxide− Sc(III) complex to form a hexacoordinate reactive species, in which chalcone is significantly activated with a higher electrophilic reactivity index and weaker Wiberg bond index of the Cα Cβ double bond. (2) The catalytic asymmetric F−C alkylation reaction occurs via a three-step mechanism, i.e., the C3−Cβ bond formation between the most nucleophilic C3 center of indole and the most electrophilic Cβ center, followed by OTf-assisted intermoleculer H-transfer. The counter OTf− anion accelerates the reaction rate by taking part in the proton shift process. The TOF-determining transition state is characteristic of H-transfer for the catalytic cycle. The TOF of the most favorable pathway (OTf-L1-re-b) is predicted to be 1.59 × 10−7 s−1, with the rate constant of K(T) = 1.58 × 10−7 exp(−29057/RT) dm6·mol−2·s−1 over the temperature range 248−368 K. (3) The strong π−π stacking effect between indole, the phenyl group of chalcone, and the benzyl group of the amide moiety translates into a more stabilizing interaction, which favors the re-face pathway. Lacking a CH2 group between the N atom and phenyl group, the stabilizing interaction of the re-face pathway is significantly weakened, and even the additional bulky o-iPr in anline reverses the enantioselectivity by shielding the re-face reacting site.

* Supporting Information S

Figure 10. Optimized geometry of hexacoordinate-Sc(III) complex L3COM. The bond lengths are in Å.

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.8b00387. Comparison of relative energies (kcal mol−1) for chalcone with s-cis or s-trans conformations; deformation density Δρ associating with the coordination interaction in L1-COM; optimized geometry of the key intermediates and transitions states; energy profiles of OTf-assisted intermolecular H-transfer mechanism; visualization of π−π stacking interaction of L4-re-b-TS1, L1-pyrrole-re-b-TS1, and L1-N-methyl-re-b-TS1; results of energy decomposition analysis (EDA) for F−C reactions of chalcone with pyrrole or N-methylindole; the Cartesian coordinates, the 3D structures, and energies of all stationary points (PDF)

reacting site Cβ atom of chalcone. Accordingly, the indole is preferred to approach the chalcone substrate from the lesshindered si-face (not the re-face). This repulsion effect increases the deformation energy of reacting fragments, especially for the [L3−Sc(OTf)]2+ fragment in transition states L3-re-a-TS1 (ΔE⧧strain= 30.2 kcal mol−1). As a result, the relative energy of L3-si-b-TS1 is lower than that of L3-re-a-TS1 by 4.0 kcal mol−1 (Figure S10, SI), giving the predominant product with Sconfiguration. The inversed enantioselectivity results are also obtained in experiment.21 4637


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asymmetric C−C bond formation with new bifunctional organic catalysts based on cinchona alkaloids. J. Am. Chem. Soc. 2004, 126, 9906. (16) Zhuang, W.; Hazell, R. G.; Jorgensen, K. A. Enantioselective Friedel−Crafts type addition of indoles to nitro-olefins using a chiral hydrogen-bonding catalyst−synthesis of optically active tetrahydro-βcarbolines. Org. Biomol. Chem. 2005, 3, 2566. (17) Méndez, I.; Rodríguez, R.; Polo, V.; Passarelli, V.; Lahoz, F. J.; García-Orduña, P.; Carmona, D. Temperature Dual Enantioselective Control in a Rhodium-Catalyzed Michael-Type Friedel−Crafts Reaction: A Mechanistic Explanation. Chem. - Eur. J. 2016, 22, 11064. (18) Kang, Y. K.; Kwon, B. K.; Mang, J. Y.; Kim, D. Y. Chiral Pdcatalyzed enantioselective Friedel−Crafts reaction of indoles with γ, δunsaturated β-keto phosphonates. Tetrahedron Lett. 2011, 52, 3247. (19) Boersma, A. J.; Feringa, B. L.; Roelfes, G. Enantioselective Friedel−Crafts Reactions in Water Using a DNA-Based Catalyst. Angew. Chem. 2009, 121, 3396. (20) Hua, Y. Z.; Han, X. W.; Yang, X. C.; Song, X. X.; Wang, M. C.; Chang, J. B. Enantioselective Friedel−Crafts Alkylation of Pyrrole with Chalcones Catalyzed by a Dinuclear Zinc Catalyst. J. Org. Chem. 2014, 79, 11690. (21) Wang, W. T.; Liu, X. H.; Cao, W. D.; Wang, J.; Lin, L. L.; Feng, X. M. Highly Enantioselective Synthesis of β-Heteroaryl-Substituted Dihydrochalcones Through Friedel−Crafts Alkylation of Indoles and Pyrrole. Chem. - Eur. J. 2010, 16, 1664. (22) Domingo, L. R.; Pérez, P.; Sáez, J. A. Understanding C−C bond formation in polar reactions. An ELF analysis of the Friedel−Crafts reaction between indoles and nitroolefins. RSC Adv. 2013, 3, 7520. (23) Roca-López, D.; Marqués-López, E.; Alcaine, A.; Merino, P.; Herrera, R. P. A Friedel−Crafts alkylation mechanism using an aminoindanol-derived thiourea catalyst. Org. Biomol. Chem. 2014, 12, 4503. (24) Petrova, G. P.; Ke, Z. F.; Park, S.; Sugiyama, H.; Morokuma, K. The origin of enantioselectivity for intramolecular Friedel−Crafts reaction catalyzed by supramolecular Cu/DNA catalyst complex. Chem. Phys. Lett. 2014, 600, 87. (25) Zeroual, A.; Zoubir, M.; Hammal, R.; Benharref, A.; El Hajbi, A. Understanding the regioselectivity and reactivity of Friedel−Crafts benzoylation using Parr functions. Mor. J. Chem. 2015, 3, 356. (26) Zhang, L. L.; Zhou, Z. J.; Jiang, H. Y.; Liu, H. L.; Huang, X. R. Theoretical study of the imidazolidinone catalyzed 1, 4-addition of N, Ndimethyl-3-anisidine with α, β-unsaturated butyric aldehyde. Tetrahedron: Asymmetry 2013, 24, 1. (27) Bagi, A. H.; Khaledi, Y.; Ghari, H.; Arndt, S.; Hashmi, A. S. K.; Yates, B. F.; Ariafard, A. A Mechanistic Investigation of the Gold (III)Catalyzed Hydrofurylation of C−C Multiple Bonds. J. Am. Chem. Soc. 2016, 138, 14599. (28) Cao, X. J.; Wang, Y.; Mo, Y. W.; Wu, L.; Mo, W. M. Friedel−Crafts dealkylation reaction mediated by a stereoselective proton transfer in the fragmentation of protonated cyclic indolyl α-amino esters. Rapid Commun. Mass Spectrom. 2016, 30, 1454. (29) Zheng, C.; Sheng, Y. F.; Li, Y. X.; You, S. L. A theoretical investigation into chiral phosphoric acid-catalyzed asymmetric Friedel− Crafts reactions of nitroolefins and 4, 7-dihydroindoles: reactivity and enantioselectivity. Tetrahedron 2010, 66, 2875. (30) Itoh, J.; Fuchibe, K.; Akiyama, T. Chiral phosphoric acid catalyzed enantioselective Friedel−Crafts alkylation of indoles with nitroalkenes: Cooperative effect of 3 Å molecular sieves. Angew. Chem., Int. Ed. 2008, 47, 4016. (31) Kondoh, A.; Ota, Y.; Komuro, T.; Egawa, F.; Kanomata, K.; Terada, M. Chiral Brønsted acid-catalyzed enantioselective Friedel− Crafts reaction of 2-methoxyfuran with aliphatic ketimines generated in situ. Chem. Sci. 2016, 7, 1057. (32) Blay, G.; Fernández, I.; Pedro, J. R.; Vila, C. Highly enantioselective Friedel−Crafts alkylations of indoles with simple enones catalyzed by Zirconium (IV)−BINOL complexes. Org. Lett. 2007, 9, 2601. (33) Bandini, M.; Garelli, A.; Rovinetti, M.; Tommasi, S.; UmaniRonchi, A. Catalytic enantioselective addition of indoles to arylni-

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Changwei Hu: 0000-0002-4094-6605 Zhishan Su: 0000-0001-5168-3823 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the National Natural Science Foundation of China (Nos. 21290182 and 21572141), and the 111 project (B17030) for financial support.

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REFERENCES

(1) Friedel, C. Sur une nouvelle méthode générale de synthèse d’hydrocarbures, d’acétones, etc. Hebd. C. R. Seances Acad. Sci. 1877, 84, 1392. (2) Friedel, C.; Crafts, J. M. Sur une methode genbrale nouvelle de synthese d’hydrocarbures, d’acbtones, etc. Compt. Rend. 1877, 84, 1450. (3) Wang, X. W.; Hua, Y. Z.; Wang, M. C. Synthesis of 3-Indolylglycine Derivatives via Dinuclear Zinc Catalytic Asymmetric Friedel−Crafts Alkylation Reaction. J. Org. Chem. 2016, 81, 9227. (4) Zheng, J. F.; Lin, L. L.; Dai, L.; Yuan, X.; Liu, X. H.; Feng, X. M. Chiral N, N′-Dioxide-Scandium (III) Complex-Catalyzed Asymmetric Friedel-Crafts Alkylation Reaction of ortho-Hydroxybenzyl Alcohols with C3-Substituted N-Protected Indoles. Chem. - Eur. J. 2016, 22, 18254. (5) Terrasson, V.; Marcia de Figueiredo, R.; Campagne, J. M. Organocatalyzed asymmetric Friedel−Crafts reactions. Eur. J. Org. Chem. 2010, 2010, 2635. (6) Park, S.; Ikehata, K.; Watabe, R.; Hidaka, Y.; Rajendran, A.; Sugiyama, H. Deciphering DNA-based asymmetric catalysis through intramolecular Friedel−Crafts alkylations. Chem. Commun. 2012, 48, 10398. (7) Marques-Lopez, E.; Diez-Martinez, A.; Merino, P.; Herrera, R. P. The role of the indole in important organocatalytic enantioselective Friedel-Crafts alkylation reactions. Curr. Org. Chem. 2009, 13, 1585. (8) Bigi, F.; Cadraghi, G.; Casnati, G.; Sartori, G.; Gasparri Fava, G. G.; Ferrari Belicchi, M. Asymmetric electrophilic substitution on phenols. Enantioselective ortho-hydroxyalkylation mediated by chiral alkoxyaluminum chlorides. J. Org. Chem. 1985, 50, 5018. (9) Łyżwa, D.; Dudziński, K.; Kwiatkowski, P. High-Pressure Accelerated Asymmetric Organocatalytic Friedel−Crafts Alkylation of Indoles with Enones: Application to Quaternary Stereogenic Centers Construction. Org. Lett. 2012, 14, 1540. (10) Bartoli, G.; Bosco, M.; Carlone, A.; Pesciaioli, F.; Sambri, L.; Melchiorre, P. Organocatalytic asymmetric Friedel-Crafts alkylation of indoles with simple α, β-unsaturated ketones. Org. Lett. 2007, 9, 1403. (11) Herrera, R. P.; Sgarzani, V.; Bernardi, L.; Ricci, A. Catalytic enantioselective Friedel−Crafts alkylation of indoles with nitroalkenes by using a simple thiourea organocatalyst. Angew. Chem., Int. Ed. 2005, 44, 6576. (12) Sheng, Y. F.; Li, G. Q.; Kang, Q.; Zhang, A. J.; You, S. L. Asymmetric Friedel−Crafts Reaction of 4, 7-Dihydroindoles with Nitroolefins by Chiral Brønsted Acids under Low Catalyst Loading. Chem. - Eur. J. 2009, 15, 3351. (13) Okino, T.; Hoashi, Y.; Takemoto, Y. Enantioselective Michael reaction of malonates to nitroolefins catalyzed by bifunctional organocatalysts. J. Am. Chem. Soc. 2003, 125, 12672. (14) Hoashi, Y.; Yabuta, T.; Takemoto, Y. Bifunctional thioureacatalyzed enantioselective double Michael reaction of γ, δ-unsaturated βketoester to nitroalkene: asymmetric synthesis of (−)-epibatidine. Tetrahedron Lett. 2004, 45, 9185. (15) Li, H. M.; Wang, Y.; Tang, L.; Deng, L. Highly enantioselective conjugate addition of malonate and β-ketoester to nitroalkenes: 4638


Article

The Journal of Organic Chemistry troalkenes: An effective route to enantiomerically enriched tryptamine precursors. Chirality 2005, 17, 522. (34) Arai, T.; Yamamoto, Y.; Awata, A.; Kamiya, K.; Ishibashi, M.; Arai, M. A. Catalytic Asymmetric Synthesis of Mixed 3, 3′-Bisindoles and Their Evaluation as Wnt Signaling Inhibitors. Angew. Chem., Int. Ed. 2013, 52, 2486. (35) Jia, Y. X.; Xie, J. H.; Duan, H. F.; Wang, L. X.; Zhou, Q. L. Asymmetric Friedel−Crafts addition of indoles to N-sulfonyl aldimines: a simple approach to optically active 3-indolyl-methanamine derivatives. Org. Lett. 2006, 8, 1621. (36) Gao, J. R.; Wu, H.; Xiang, B.; Yu, W. B.; Han, L.; Jia, Y. X. Highly enantioselective construction of trifluoromethylated all-carbon quaternary stereocenters via nickel-catalyzed Friedel−Crafts alkylation reaction. J. Am. Chem. Soc. 2013, 135, 2983. (37) Jia, Y. X.; Zhu, S. F.; Yang, Y.; Zhou, Q. L. Asymmetric Friedel− Crafts Alkylations of Indoles with Nitroalkenes Catalyzed by Zn (II)− Bisoxazoline Complexes. J. Org. Chem. 2006, 71, 75. (38) Hao, X. Q.; Xu, Y. X.; Yang, M. J.; Wang, L.; Niu, J. L.; Gong, J. F.; Song, M. P. A Cationic NCN Pincer Platinum (II) Aquo Complex with a Bis (imidazolinyl) phenyl Ligand: Studies toward its Synthesis and Asymmetric Friedel−Crafts Alkylation of Indoles with Nitroalkenes. Organometallics 2012, 31, 835. (39) Wu, L. Y.; Hao, X. Q.; Xu, Y. X.; Jia, M. Q.; Wang, Y. N.; Gong, J. F.; Song, M. P. Chiral NCN Pincer Pt(II) and Pd(II) Complexes with 1, 3-Bis(2′-imidazolinyl) benzene: Synthesis via Direct Metalation, Characterization, and Catalytic Activity in the Friedel−Crafts Alkylation Reaction. Organometallics 2009, 28, 3369. (40) Drabina, P.; Brož, B.; Padělková, Z.; Sedlák, M. Structure and catalytic activity of organopalladium(II) complexes based on 4, 5dihydro-1H-imidazol-5-one derivatives. J. Organomet. Chem. 2011, 696, 971. (41) Sui, Y.; Liu, L.; Zhao, J. L.; Wang, D.; Chen, Y. J. Catalytic and asymmetric Friedel−Crafts alkylation of indoles with nitroacrylates. Application to the synthesis of tryptophan analogues. Tetrahedron 2007, 63, 5173. (42) Wu, J.; Li, X. C.; Wu, F.; Wan, B. S. A New Type of Bis(sulfonamide)-Diamine Ligand for a Cu(OTf)2-Catalyzed Asymmetric Friedel−Crafts Alkylation Reaction of Indoles with Nitroalkenes. Org. Lett. 2011, 13, 4834. (43) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Keith, T.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, revision D.01; Gaussian, Inc.: Wallingford, CT, 2013. (44) Zhao, Y.; Truhlar, D. G. The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals. Theor. Chem. Acc. 2008, 120, 215. (45) Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. 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 2009, 113, 6378. (46) Gonzalez, C.; Schlegel, H. B. An improved algorithm for reaction path following. J. Chem. Phys. 1989, 90, 2154. (47) Reed, A. E.; Curtiss, L. A.; Weinhold, F. Intermolecular interactions from a natural bond orbital, donor-acceptor viewpoint. Chem. Rev. 1988, 88, 899.

(48) Reed, A. E.; Weinstock, R. B.; Weinhold, F. Natural population analysis. J. Chem. Phys. 1985, 83, 735. (49) Parr, R. G.; Szentpaly, L. V.; Liu, X. B. Electrophilicity index. J. Am. Chem. Soc. 1999, 121, 1922. (50) Domingo, L. R.; Pérez, P.; Sáez, J. A. Understanding the local reactivity in polar organic reactions through electrophilic and nucleophilic Parr functions. RSC Adv. 2013, 3, 1486. (51) Wolters, L. P.; Bickelhaupt, F. M. The activation strain model and molecular orbital theory. WIREs Comput. Mol. Sci. 2015, 5, 324. (52) van Zeist, W. J.; Bickelhaupt, F. M. The activation strain model of chemical reactivity. Org. Biomol. Chem. 2010, 8, 3118. (53) Ess, D. H.; Houk, K. N. Distortion/interaction energy control of 1, 3-dipolar cycloaddition reactivity. J. Am. Chem. Soc. 2007, 129, 10646. (54) Lein, M.; Frenking, G. In Theory and Applications of Computational Chemistry: The First 40 Year; Elsevier: Amsterdam, 2011. (55) Hopffgarten, M. v.; Frenking, G. Energy decomposition analysis. WIREs Comput. Mol. Sci. 2012, 2, 43. (56) Mitoraj, M. P.; Parafiniuk, M.; Srebro, M.; Handzlik, M.; Buczek, A.; Michalak, A. Applications of the ETS-NOCV method in descriptions of chemical reactions. J. Mol. Model. 2011, 17, 2337. (57) Mitoraj, M. P.; Michalak, A.; Ziegler, T. A combined charge and energy decomposition scheme for bond analysis. J. Chem. Theory Comput. 2009, 5, 962. (58) Te Velde, G.; Bickelhaupt, F. M.; Baerends, E. J.; Fonseca Guerra, C.; van Gisbergen, S. J. A.; Snijders, J. G.; Ziegler, T. Chemistry with ADF. J. Comput. Chem. 2001, 22, 931. (59) Fonseca Guerra, C.; Snijders, J. G.; te Velde, G.; Baerends, E. Towards an order-N DFT method. Theor. Chem. Acc. 1998, 99, 391. (60) Liu, X. H.; Lin, L. L.; Feng, X. M. Chiral N, N′-dioxides: new ligands and organocatalysts for catalytic asymmetric reactions. Acc. Chem. Res. 2011, 44, 574. (61) Yang, N.; Su, Z. S.; Feng, X. M.; Hu, C. W. Theoretical Studies on the Asymmetric Baeyer−Villiger Oxidation Reaction of 4-Phenylcyclohexanone with m-Chloroperoxobenzoic Acid Catalyzed by Chiral Scandium(III)-N, N′-Dioxide Complexes. Chem. - Eur. J. 2015, 21, 7264. (62) Wang, J. M.; Zuo, Y. N.; Hu, C. W.; Su, Z. S. Theoretical and experimental studies on the structure−property relationship of chiral N, N′-dioxide−metal catalysts probed by the carbonyl−ene reaction of isatin. Catal. Sci. Technol. 2017, 7, 2183. (63) Su, Z. S.; He, W. Y.; Wang, J. M.; Zuo, Y. N.; Hu, C. W. Theoretical investigation on donor−acceptor interaction between a carbonyl compound and an N, N′-dioxide−Sc(iii) complex. RSC Adv. 2017, 7, 56054. (64) Kovács, G.; Lledós, A.; Ujaque, G. Reaction Mechanism of the Gold(I)-Catalyzed Addition of Phenols to Olefins: A Concerted Process Accelerated by Phenol and Water. Organometallics 2010, 29, 3252. (65) Clot, E. Ion-Pairing in Organometallic Chemistry: Structure and Influence on Proton Transfer from a Computational Perspective. Eur. J. Inorg. Chem. 2009, 2009, 2319. (66) Guzei, I. A.; Wendt, M. An improved method for the computation of ligand steric effects based on solid angles. Dalton Trans. 2006, 3991. (67) Schneebeli, S. T.; Hall, M. L.; Breslow, R.; Friesner, R. Quantitative DFT modeling of the enantiomeric excess for dioxiranecatalyzed epoxidations. J. Am. Chem. Soc. 2009, 131, 3965. (68) Amatore, C.; Jutand, A. Mechanistic and kinetic studies of palladium catalytic systems. J. Organomet. Chem. 1999, 576, 254. (69) Kozuch, S.; Shaik, S. A combined kinetic−quantum mechanical model for assessment of catalytic cycles: application to cross-coupling and Heck reactions. J. Am. Chem. Soc. 2006, 128, 3355. (70) Kozuch, S.; Shaik, S. Kinetic-Quantum Chemical Model for Catalytic Cycles: The Haber−Bosch Process and the Effect of Reagent Concentration. J. Phys. Chem. A 2008, 112, 6032. (71) Uhe, A.; Kozuch, S.; Shaik, S. Automatic analysis of computed catalytic cycles. J. Comput. Chem. 2011, 32, 978. (72) Qi, T.; Yang, H. Q.; Whitfield, D. M.; Yu, K.; Hu, C. W. Insights into the Mechanistic Role of Diphenylphosphine Selenide, Diphenylphosphine, and Primary Amines in the Formation of CdSe Monomers. J. Phys. Chem. A 2016, 120, 918. 4639


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The Journal of Organic Chemistry (73) Eyring, H. The activated complex in chemical reactions. J. Chem. Phys. 1935, 3, 107. (74) Wigner, E. Calculation of the Rate of Elementary Association Reactions. J. Chem. Phys. 1937, 5, 720. (75) Wang, J. M.; Su, Z. S.; Yang, N.; Hu, C. W. Mechanistic Study of the Asymmetric Carbonyl-Ene Reaction between Alkyl Enol Ethers and Isatin Catalyzed by the N,N′-Dioxide−Mg(OTf)2 Complex. J. Org. Chem. 2016, 81, 6444.

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