Mechanistic Investigation of Aromatic C(sp2)âH and Alkyl C(sp3)âH

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Mechanistic Investigation of Aromatic C(sp)-H and Alkyl C(sp)-H Bond Insertion by Gold Carbenes 3

Yuan Liu, Zhunzhun Yu, Zhoujie Luo, John Zenghui Zhang, Lu Liu, and Fei Xia J. Phys. Chem. A, Just Accepted Manuscript • DOI: 10.1021/acs.jpca.6b00636 • Publication Date (Web): 01 Mar 2016 Downloaded from http://pubs.acs.org on March 8, 2016

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The Journal of Physical Chemistry

Mechanistic Investigation of Aromatic C(sp2)-H and Alkyl C(sp3)-H Bond Insertion by Gold Carbenes Yuan Liu,†‡ Zhunzhun Yu,‡ Zhoujie Luo,‡ John Zenghui Zhang,†,§ Lu Liu*,‡ Fei Xia*,‡,§ †

Department of Physics and State Key Laboratory of Precision Spectroscopy, East China Normal University, Shanghai 200062, China ‡

School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China

§

NYU-ECNU Center for Computational Chemistry at New York University Shanghai, East China Normal University, Shanghai 200062, China

Abstract It was recently reported that the gold-carbenes have a unprecedented catalysis towards the functionalization of C(sp2)-H bonds of aromatic compounds. However, the associated mechanisms of C(sp2)-H bonds inserted by gold-carbenes have not been comprehensively understood. We carried out a detailed mechanistic investigation of gold-carbene insertion into the C(sp2)-H bond of anisole by means of theoretical calculations and control experiments. It significantly reveals that the aromatic C(sp2)-H bond activation starts with the electrophilic addition of aromatic carbon toward the carbene carbon and subsequently followed the [1,3]-proton shift to form an enol intermediate. The rearrangement of enol proceeds through the mechanisms of proton transfer assisted by water molecules or enol intermediates, which are supported by our control experiments. It was also found that the C(sp3)-H insertions of alkanes by gold-carbenes proceed through a concerted process via a three-centered transition state. The further comparison of different mechanisms provides a clear theoretical scheme to account for the difference in aromatic C(sp2)-H and alkyl C(sp3)-H bond activation, which is instructive for the further experimental functionalization of C-H bonds by gold-carbenes.

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1. INTRODUCTION The highly selective functionalization of carbon-hydrogen bonds1-5 attracts a great deal of interest of organic chemists since they constitute the fundamental frameworks of organic compounds. However, the functionalization of hydrocarbons is still challenging due to the inert property of C-H bonds. Metal carbenes that were generated from the transition-metal-catalyzed decomposition of diazo compounds have broad applications in organic synthesis, including the functionalization of C-H bond,6-8 O-H bond9-11 and N-H bond et al.12-14 Due to the high efficiency and selectivity of metallocarbenes, the latest developments and utilization of various metal carbenes for functionalizing C-H bonds has been reviewed in a few recent articles,15-18 including the copper, silver and rhodium carbenes. Yet, compared to other noble metals, gold-carbenes show very unique reactivity and selectivity in C-H functionalization. Recently, we19 and Shi’s group20 developed an unprecedented C(sp2)-H bond functionalization of electron-rich aromatic rings with α-phenyl-α-diazoacetate by the gold-complexes. This gold-carbene induced reaction shows a high selectivity and efficiency toward the C(sp2)-H functionalization of phenyl. Pérez and coworkers21-25 also conducted a comprehensively experimental investigation of gold-catalyzed reactions of diazoacetates with alkanes and aromatic compounds. They found that the gold catalysts equipped with N-hetercyclic carbene ligands could efficiently catalyze the C-H bond insertion reactions under mild conditions. These recent new discoveries in experiments reveal the different reactivity of gold-carbenes in the functionalization of C-H bonds compared to that with the commonly used metals such as Rh and Ag. Less theoretical studies on the mechanism of C-H bond insertion by gold-carbenes were performed so far. The most previous theoretical works mainly focused on the C-H bond insertion reactions by other metallocarbenes, such as rhodium, copper and silver carbenes.26-32 Pérez etc.27,28 reported a detailed computational study of alkyl C-H bond insertions with ethyl diazoacetate by copper and silver carbenes. They


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found that the C(sp3)-H bonds of alkanes were directly activated and cleaved by interacting with metallocarbenes through a three-center transition state. Differing from the results proposed by Pérez et al., Bonge et al.26 reported a stepwise mechanism

for

the

C-H

insertion

reaction

of

1,4-cyclohexandiene

with

bromodiazoacetate, which indicates that the different substrates might follow the distinct reaction mechanisms. Very recently, we reported a combined theoretical and experimental study33 on the mechanism of gold-catalyzed C-H functionalization of phenols with diazo compounds, which could account for the unique reactivity of gold-carbenes.19 We proposed a new mechanism for the selective functionalization of C-H bond and O-H bond of phenols and the mechanism was strongly supported by our control experiments.33 It was the first example in which the mechanism of gold-mediated functionalization of aromatic C(sp2)-H bond was investigated. In our further unpublished experiments, we found that the generated gold-carbenes have high reactivity toward the aromatic C(sp2)-H bonds of phenol and anisole, but they almost have no reactivity toward the aromatic C(sp2)-H bonds of toluene and benzene. These results intrigues us to perform a further theoretical study on the mechanisms of C(sp2)-H bond insertion of a series of arenes. Several mechanistic questions associated with the reactive behavior of gold-carbenes are required to be solved, including the insertion mechanisms of aromatic C(sp2)-H bonds and the alkyl C(sp3)-H bonds. To answer these questions, we performed a systematically density functional theory (DFT) calculations as well as theoretical analyses on the reaction mechanisms of the aromatic C(sp2)-H and alkyl C(sp3)-H bond insertions by gold-carbenes. In the study of aromatic C(sp2)-H bond insertion, we conducted the reactions of diazoacetates with a series of arenes including anisole, toluene and benzene catalyzed by (PhO)3PAuSbF6 and took the anisole as a model system for a detailed DFT calculation. Since we have demonstrated in our previous study33 that it was facile to generate gold-carbenes from the mixture of diazoacetate and (PhO)3PAuSbF6, it is reasonable to take gold-carbenes as the precursors of C-H insertion reactions. In the calculated free energy profiles, the



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gold-carbenes (PhO)3PAu=C(Ph)CO2Me and substrates were regarded as reactants and their sum of energies was calibrated as reference in our calculations. On the other hand, we studied the mechanisms of gold-carbene insertion into a series of alkanes and compared them with that of C(sp2)-H bonds, which provided a clear theoretical explanation for identifying the insertion of aromatic C(sp2)-H bonds and alkyl C(sp3)-H bonds by gold-carbenes. 2. COMPUTATIONAL METHODS All the DFT calculations throughout this work were carried out using the Gaussian 09 software package.34 The geometric structures of intermediates and transition states were optimized and located with using the M06 functional.35,36 The M06 functional was demonstrated to give accurate descriptions for intramolecular interactions in organometallic systems, especially for the noncovalent interactions of aromatic groups. The Lanl2dz basis set37,38 combined with the effective core potential was used to describe the heavy elements Au and P, and the 6-31G* basis set39 was utilized to describe the nonmetallic elements C, N, O and H, as the same as the computational level used before.33 The frequency analyses were further performed on the gaseous structures to verify that the intermediates are stable and transition states have only one imaginary frequency. The solvent effect of CH2Cl2 on the reactions was evaluated using the integral equation formalism model (IEFPCM)40 with a dielectric constant ε = 8.93, based on the structures obtained in gas phase. All the calculated energies of intermediates and transition states discussed in the text refer to the standard Gibbs free energies ∆Gsol at the temperature 298 Kelvin in the units of kcal/mol, including the solvation corrections evaluated from the IEFPCM40 model. The natural bond orbital (NBO) analyses41 were performed at the same computational level and the data were further used in the analyses of reaction mechanisms. The 3D images of molecular orbitals of reactants were plotted using the package GaussView.42 More details about the


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structures of intermediates and transition states are provided in the Supporting Information.

3. RESULTS AND DISCUSSION 3.1 C(sp2)-H BOND INSERTION of ANISOLE REACTION REGIOSELECTIVITY The optimized structure of the gold-carbene (PhO)3PAu=C(Ph)CO2Me and anisole are shown in Figure 1 and related geometric parameters are provided in Table 1. The metal ligand (PhO)3PAu in the metallocarbene adopts a compact pattern with the almost C3 symmetry. The calculated distance of the Au-C1 bond is 2.04 Å and the metal atom Au bonds to the sp2-hybrid C1 atom through a hybridization of its 5d and 6s orbitals according to the NBO analysis. It is apparent that the carboxyl plane defined with respect to the C1-C2-O1 atoms is almost vertical to the plane defined with respect to the Au-C1-C2 atoms, with the calculated dihedral of Au-C1-C2-O1 being -98.1°. It is reasonable to envision that the anisole could interact with the carbene carbon from two sides, namely, the side of carbonyl group and the side of methoxy group. At each side, the anisole could adopt two distinct conformations, with the aromatic ring upward or downward. In addition, the para-site insertion product of anisole was obtained in our experiments. Based on the experimental information and theoretical reasoning, four reasonable structures of transition states representing the addition with the Cp atom at the para site of anisole, TS-oxy-down, TS-oxy-up, TS-methoxy-down and TS-methoxy-up were obtained in Figure 2. The notations oxy and methoxy mean attacking the carbene carbon from the carbonyl group side and the methoxy group side respectively, with down and up denoting the directions of aromatic rings in anisole. Among the four transition states, the structure TS-oxy-down has the lowest free energy barrier 15.0 kcal/mol, indicating that TS-oxy-down is the most favorable transition state in energetics. Additionally, the frequency analysis on TS-oxy-down unambiguously shows that the vibrational mode



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of imaginary frequency corresponds to the stretching motion between the C1 carbon in the gold-carbene and the Cp carbon in anisole. Despite the addition at the para site of anisole, we also evaluated the possible addition reactions at the ortho and meta sites in anisole, with the corresponding transition states TS-1o and TS-1m shown in Figure 3. The free energy barriers of TS-1o and TS-1m are higher than that of TS-1p by 4.7 kcal/mol and 8.1 kcal/mol, respectively. Thus, both ortho and meta sites are less favored than the para site in the step of electrophilic addition. REACTION PATHWAYS AND ENERGY PROFILES The overall pathways involving the crucial intermediates and transition states for the reaction of gold-carbene and anisole are displayed in Figure 3. As discussed aforementioned, the addition at the para site of anisole via TS-1p is the most favorable pathway, which is in line with our experimental observation that only the para-site product was obtained. The electrophilic addition at the para-carbon of anisole leads to a stable intermediate Int-2p, also according with the assumption proposed by Doyle et al.43 The next step is how the hydrogen transfers from the aromatic C-H bond to the carbene moiety. According to the direct [1,2]-H transfer mechanism assumed by Hu et al.,44 we located the transition state TS-3* and found that it has a barrier of 24.9 kcal/mol, which implies this pathway is less favorable in energetics. Besides, an alternative pathway is that the metal complex migrates to the oxygen atom of carbonyl group of carbene.45 It is unexpected that a direct migration of gold-complex gives rise to a cyclopropanation product Int-4*, which is not a reasonable intermediate connecting to the final product. Previously, Wood46-48 and Xie et al.49 suggested that the enol might be probably one of the active intermediates in the rhodium-catalyzed O-H insertion reaction. In this case, it is interesting to find that the aromatic hydrogen in Int-2p readily transfers to the carbonyl oxygen atom through a five-member ring structure TS-3, with a small barrier 6.8 kcal/mol. The


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formed enolate Int-4 is quite stable in energetics with being exothermic by 6.9 kcal/mol relative to reactants. The intermediate Int-4 might properly transform to products through two possible reaction pathways, namely, the dissociation of gold-complex into the solution or the intramolecular [1,3]-migration of gold-complex to the phenyl group. Both two processes are calculatedly endothermic by 8.5 and 4.7 kcal/mol, which lead to the intermediates Int-5* and Int-5, respectively. The structure of enol moiety in the gold-associated complex Int-5 is very similar to the free structure of enol form Int-5*. In both structures, we notice that the hydroxylic hydrogens stay far away from the carbene C1 atoms. For the rearrangement of intermediates to the final insertion products, the key issue is how the hydroxylic hydrogens transfer to the C1 atoms and form the C(sp3)-H bonds in products. We firstly explored the possibility of the direct [1,3]-H transfer in Int-5* via the transition state structure TS-6-0w*, as shown in Figure 4(a). Surprisingly, the calculated barrier of direct [1,3]-H transfer is highly up to 41.5 kcal/mol relative to Int-5* such that the direct [1,3]-H transfer could be ruled out from the mechanisms. The study of a trace amount of water in catalyzing proton transfer50 indicates that the water molecules in solution might participate in the remote hydrogen transfer, instead of the direct intramolecular migration. In this case, it is most likely that the process of hydrogen transfer in Int-5* and Int-5 was facilitated by the water molecules.

Figure 4(b) and 4(c) show the located structures of TS-6-1w* and

TS-6-2w* in which one and two water molecules serve as the proton shuttle, respectively. A further comparison to the TS-6-3w* in Figure 4(d) indicates that the two-water assisted mechanism is the most reasonable ones due to a lower barrier of 14.7 kcal/mol. The reason can be explained from the fact that TS-6-2w* stays in a relaxed structure that could enjoy the proton transfer, whereas the TS-6-0w*, TS-6-1w* and TS-6-3w* bear the intramolecular strain generated from the severe distortion from the planar structures. We calculated the two-water assisted transition state structures TS-6-2w and TS-6-2w* for the gold-associated pathway and free



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pathway respectively and found that the barrier of hydrogen transfer via TS-6-2w* is 14.7 kcal/mol, lower than that via TS-6-2w by 0.9 kcal/mol. In the previous study by Xie et al.,49 it was proposed that the enol intermediate such as Int-5* could also participate in the C-H bond insertion. We have calculated the transition state TS-6-2w** with the energy of 15.9 kcal/mol, with its corresponding structure in Figure 4(f). The relative energy of TS-6-2w** is even lower than that of TS-6-2w* by 0.4 kcal/mol, which means that the enol Int-5* could serve as the proton shuttle in the process of hydrogen transfer. The overall barrier from Int-4 to TS-6-2w sums to 20.3 kcal/mol, which could be regarded as the rate-determining step, while the free pathway has a high barrier of 22.8 kcal/mol. The final C-H insertion product Pro-8 is exothermic by 23.6 kcal/mol and quite stable in energetics. CONTROL EXPERIMENTS The pivotal process in the pathways of Figure 3 is the hydrogen transfer. In order to verify the water-assisted mechanism proposed by us, the control experiments were carried out on the reaction of anisole 1 and α-phenyl-α-diazoacetate 2 in our lab (Scheme 1). Eq. 1 shows that when the gold-carbenes insert into the C-D bond of deuterated anisole, about 61% deuterated products 8 are obtained. The direct deuterium transfer from deuterated anisol to product 8 is showed impossible in our calculations. So, it indicates that the deuterated enol may play an important role in the

Scheme 1. Control experiments. ACS Paragon Plus Environment

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hydrogen transfer process. The other 39% hydrogenated products 8 means that the hydrogens in the newly formed C-H bonds come from other sources (the trace amount of water in solvent) rather than the para sites of anisoles. Eq. 2 shows that, when 1 equivalent of D2O was added to the anisole reaction system, Pro-8 was deuterated with the percentage of 50%. It further demonstrates that at least 50% products accept the deuteriums from D2O, which indicate the water molecules indeed play a significant role in the insertion reaction. Eq.3 excludes the possibility of a direct exchange of H and D between the D2O and Pro-8. It is emphasized that the experimental results of Eq.1 and Eq.2 are remarkably different from that of phenol reported in the previous study. For phenol, 100% deuterated Pro-8 was obtained by the experiments based on Eq.2,33 which excludes the possibility of enol-mediated mechanism. REACTIVITY OF SUBSTRATES The current calculated pathways and control experiments provide a reasonable explanation for the functionalization of C-H bonds of anisole by the gold-carbenes. To enrich the knowledge of mechanisms of gold-carbene insertion into distinct substrates, we also explored the reactivity of gold-carbene toward different substrates, including the phenol, toluene and benzene compounds. Due to the high structural similarity of these substrates, we thus assumed that these substrates follow the similar reaction pathways of anisole. Since the electrophilic additions of the para-carbons of substrates with carbenes leading were crucial steps for the C-H bond functionalization as indicated beore,33 our current DFT calculations mainly focus on the steps of electrophilic addition with different substrates. The calculated free energy profiles and structures for different substrates are shown in Figure 5. The calculated results in Figure 5 indicate that the barriers of TS-Anisole and TS-Phenol are relatively low, with 15.0 and 15.7 kcal/mol respectively, while the barriers of TS-Toluene and TS-Benzene are 20.1 and 22.4 kcal/mol. Moreover, the possible addition products Int-Toluene and Int-Benzene are quite unstable, being exothermic by 13.1 and 15.7 kcal/mol. The calculated results are in good agreement with our experimental



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observations that only the anisole and phenol possess high reactivity with gold-carbenes, whereas the toluene and benzene did not react with it at all. The difference of substrates in reactivity is mainly due to the effects of electronic structures of substrates. A further theoretical analysis on the electronic structures of substrates is presented in the section 3.3 3.2 INSERTION INTO C(sp3)-H BOND of ALKANES For the theoretical study of functionalization of C(sp3)-H bonds by gold-carbenes, we chose three representative alkanes, namely, methane, ethane and propane as model systems to explore the mechanisms of C(sp3)-H bonds inserted by gold-carbenes. Figure 6 shows the calculated pathways and free energy profiles for the insertion of gold-carbenes into the C-H bonds of alkanes. The optimized structure TS-1 is a representative of a three-member transition state for the insertion of C-H bond of methane, with a barrier of 35.1 kcal/mol. The vibrational mode of imaginary frequency in TS-1 shows that the C-H and C-C bond formation process is almost a concerted process. During this process, the bond orders of formed C1-C2 and C1-H1 bonds in Table 2 reduce to 0.54 and 0.50 respectively. The bond order of C2-H1 bond in methane decreases from 0.94 to 0.33, implying that the C-H bond of methane is drastically weakened. Meanwhile, the attacking of methane to the carbene carbon weakens the strength of C1-Au bond. The bond order of C1-Au decreases from a calculated value of 0.63 to 0.37, exhibiting a tendency for dissociation. Along the pathway, a gold-associated intermediate Int-1 is formed by releasing an energy of 25.1 kcal/mol. This formation of Int-1 is irreversible because of a high reverse activation barrier, and eventually yields the product Pro-1 by liberating the gold-complex. The whole reaction of the C-H bond insertion of methane is calculatedly exothermic by 21.1 kcal/mol. In addition, we calculated the reaction pathways of gold-carbene insertions into C-H bonds of ethane and propane, as shown by the blue and red pathways in Figure 6. The calculated crucial barriers decrease in turn from methane, ethane to propane, with the values of 35.1, 28.8 and 24.6 kcal/mol.


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This tendency is in line with the dissociation energies of (CH3)2HC-H < (CH3)H2C-H < H3C-H bonds. 3.3 ELECTRONIC STRUCTURE ANALYSIS In the C(sp2)-H and C(sp3)-H insertion reactions, what we most concern is the first step that is closely associated with the C-H bond activation. Doyle et al.43 proposed that the metal carbenes reacted with aromatic substrates through electrophilic addition. However, a systematically theoretical explanation about the nature of C(sp2)-H bond activation is still lacked until now. We herein make a detailed electronic structure analysis for the aromatic C(sp2)-H addition of anisole and gold-carbene. Figure 7 shows the contours of molecular orbitals of various structures, including the reactants, transition state TS-oxy-up and intermediate Int-oxy-up. Figure 7(a) and 7(b) present the highest occupied molecular orbital (HOMO) of anisole and the lowest unoccupied molecular orbital (LUMO) of (PhO)3PAu=C(Ph)CO2Me. It can be clearly seen in Figure 7(a) that the p orbitals of the para-carbon and meta-carbons constitute the conjugated π-orbital in HOMO. On the other hand, the vacant p orbital of carbenoid carbon constitutes the LUMO. Thus, a direct p-p orbital addition between the carbene carbon and anisole is feasible, through the direct HOMO-LUMO interaction between the anisole and carbene. The HOMO of TS-oxy-up in Figure 7(c) clearly shows that the p orbitals of two reactants overlap with other each to large extent to form the stable intermediate Int-oxy-up. The NBO analysis of Int-oxy-up in Figure 7(d) indicates that the newly formed C-C bond adopts the sp3-sp3 hybridization by mixing the s and p orbitals of carbons. Further, we analyzed the electronic structures of anisole, phenol, toluene and benzene to explain their different chemoselectivites toward the addition to gold-carbenes. In our experiments, both anisole and phenol could react with the gold-carbenes, but toluene and benzene could not. An empirical explanation for this difference relies on that the electron-donating groups such as CH3O- and OH- could



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enhance the reactivity of aromatic carbons. Theoretically, we plotted the reactive π orbitals of the substrates, as shown in Figure 7(e)-(h), and found that the oxygen atoms in anisole and phenol did play an important role in forming conjugation with their aromatic rings. A quantitative computation gives para-carbons the NBO charges of -0.270, -0.274, -0.247 and -0.238 respectively, corresponding to Figure 7(e)-(h), respectively. Obviously, the charges of toluene and benzene are less negative than anisole and phenol, because of the weak electron-donating effects in their aromatic rings. 4. CONCLUSION The mechanisms of the functionalization of the C(sp2)-H bond of anisole and C(sp3)-H bonds of alkanes by the gold-carbene (PhO)3PAu=C(Ph)CO2Me were systematically investigated using computational and experimental methods. Our study provides a clear theoretical scenario to account for the difference in the activation of aromatic C(sp2)-H and alkyl C(sp3)-H bonds by gold-carbenes, which is summarized as below. For the C(sp2)-H insertion, the whole reaction pathways and free energy profiles of anisole and gold-carbene were elaborately outlined based on the DFT calculations. The results indicate that the C(sp2)-H bond insertion of anisole initiated from the direct carbon-carbon electrophilic addition and an enol intermediate was then formed. Subsequently, we proposed that the enol intermediate rearranged to the final product through a remote hydrogen transfer, which might be participated by water molecules or enol intermediates. The proposed mechanism of hydrogen transfer was demonstrated by control experiments, which reveal a remarkable difference in the C-H bond insertion between the anisole and phenol. Through the electronic structure analyses, we explained the distinctive chemoselevitites of gold-carbenes towards different arenes.


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The mechanisms of C(sp3)-H bonds of alkanes inserted by gold-carbenes were also investigated using theoretical methods. The current DFT calculations support the viewpoint that the C(sp3)-H bond activation is a concerted process via a three-member transition state, which can serve as the theoretical prototype to account for the C-H bond insertion mechanisms of alkanes observed in experiments.22 In contrast, the functionalization of aromatic C(sp2)-H in anisole is actually a two-step process, which is composed of C-C bond addition and aromatic hydrogen transfer. Our theoretical study provides a clear theoretical explanation for the difference of mechanisms between the aromatic C(sp2)-H and alkyl C(sp3)-H bond insertions, which is instructive for facilitating the experimental functionalization of C-H bonds.

SUPPORTING INFORMATION Fig.S1-S40 list the structures and Cartesian coordinates of the intermediates and transition states in Figure 1-6. AUTHOR INFORMATION Corresponding author: Lu Liu Email: [email protected] +86-(0)21-54341205; Fei Xia Email: [email protected] +86-(0)21-20596009

Telephone: Telephone:

AUTHOR CONTRIBUTIONS Z. Yu, L. Liu performed experiments and Y. Liu, Z. Luo, J. Z. H. Zhang, F. Xia performed DFT calculations and theoretical analyses. ACKNOWLEDGEMENTS This work was supported by the National Natural Science Foundation of China (Grants No. 21572065, 21433004 and 21473056), Natural Science Foundation of Shanghai (14ZR1411800) and the Shanghai Pujiang Program (14PJ1403100). We acknowledge the support of the NYU-ECNU Center for Computational Chemistry at



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NYU Shanghai. We also thank the supercomputer center of ECNU for providing computer time.

Reference: (1) Sun, C. L.; Li, B. J.; Shi, Z. J. Direct C-H Transformation via Iron Catalysis. Chem. Rev. 2011, 111, 1293-1314. (2) Wencel-Delord, J.; Dröge, T.; Liu, F.; Glorius, F. Towards Mild Metal-Catalyzed C-H Bond Activation. Chem. Soc. Rev. 2011, 40, 4740-4761. (3) Chen, X.; Engle, K. M.; Wang, D. H.; Yu, J. Q. Palladium(Ⅱ)-Catalyzed C-H Activation/C-C Cross-Coupling Reactions: Versatility and Practically. Angew. Chem. Int. Ed. 2009, 48, 5094-5115. (4) Yeung, C. S.; Dong, V. M. Catalytic Dehydrogenative Cross-Coupling: Forming Carbon-Carbon Bonds by Oxidizing Two Carbon-Hydrogen Bonds. Chem. Rev. 2011, 111, 1215-1292. (5) Zheng, C.; You, S. L. Recent Development of Direct Asymmetric Functionalization of Inert C-H Bonds. RSC Adv. 2014, 4, 6173-6214. (6) Jia, S. K.; Xing, D.; Zhang, D.; Hu, W. H. Catalytic Asymmetric Functionalization

of

Aromatic

C-H

Bonds

by

Electrophilic

Trapping

of

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Tables: Table 1. The optimized structure of the gold carbene (PhO)3PAu=C(Ph)CO2Me and the NBO results for the Au-C1 bond. Bond Length(Å)

Angle(°)

Dihedral Angle(°)

Au-C1 Bond Composition

Au-P: 2.45

Au-C1-C2: 114.3

O1-C2-C1-C3: 79.1

C1: 2s(27%)2p(73%)

Au-C1: 2.04

C1-C2-O1: 119.7

Au-C1-C2-O1: -98.1

Au: 6s(85%)5d(13%)

C1-C2 :1.48

Au-C1-C2: 126.8

C2-O1: 1.21

P-Au-C1: 178.1

Table 2.

The calculated bond orders for the bonds in the transition states TS-1,

TS-2 and TS-3. TS-1

TS-2

TS-3

C1-Au

0.37

0.36

0.33

C1-H1

0.50

0.59

0.70

C1-C2

0.54

0.50

0.46

C2-H1

0.33

0.24

0.14


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Figures and Captions: Figure 1. Optimized structures of (a) the gold carbene (PhO)3PAu=C(Ph)CO2Me and (b) anisole, where the atomic numberings are shown and bond lengths are in the units of angstroms. Figure 2. Optimized structures of four transition states TS-oxy-down, TS-oxy-up, TS-methoxy-down and TS-methoxy-up. The distances are in the units of angstroms and the relative values of free energy barriers ∆∆G are in kcal/mol. Figure 3. Calculated free energy profiles ∆Gsol as well as the corresponding structures of intermediates and transtion states along different possible pathways of C-H insertion catalyzed by (PhO)3PAuSbF6. The most lowest energy pathway is shown in red and others are denoted in blue. All values of free energies are in the units of kcal/mol.

Figure 4. Optimized structures of six transition states (a) TS-6-0w*, (b) TS-6-1w*, (c) TS-6-2w*, (d) TS-6-3w*, (e) TS-6-2w and (f) TS-6-2w** for [1,3]-H shift. The structures in plots (b)-(c) are featured by hydrogen transfers assisted by water molecules, while the structure in the plot (f) involves the hydrogen transfer by the enol Int-5* and a water molecule. The values of free energy barriers ∆∆G are in kcal/mol. Figure 5. The calculated free energy profiles ∆Gsol and the corresponding structures of intermediates and transtion states of anisole/phenol/toluene/benzene for the para-site C-H insertions catalyzed by (PhO)3PAuSbF6. All values of free energies are in the units of kcal/mol.

Figure 6. The calculated free energy profiles ∆Gsol and the corresponding structures of intermediates and transtion states of H3C-H, (CH3)H2C-H and (CH3)2HC-H electrophilic addition catalyzed by (PhO)3PAuSbF6. All values of free energies are in the units of kcal/mol.

Figure 7. (a) The HOMO of anisol. (b) The LUMO of LAu=C(Ph)CO2Me. (c) The HOMO of TS-oxy-up. (d) The HOMO of Int-oxy-up. (e) The 23th occupied molecular orbital of anisol. (f) The 19th occupied molecular orbital of phenol. (g) The 21th occupied molecular orbital of toluene. (h) The 17th occupied molecular orbital of benzene.



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Figure 1.


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Figure 2.



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Figure 3.


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Figure 4.



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Figure 5.


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Figure 6.



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Figure 7.


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TOC：


Mechanistic Investigation of Aromatic C(sp2)âH and Alkyl C(sp3)âH

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