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C–H Arylation of Phenanthrene with Trimethylphenylsilane by Pd/o...

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C-H Arylation of Phenanthrene with Trimethylphenylsilane by Pd/o-Chloranil Catalysis: Computational Studies on the Mechanism, Regioselectivity, and Role of o-Chloranil Mari Shibata, Hideto Ito, and Kenichiro Itami J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b11260 • Publication Date (Web): 11 Jan 2018 Downloaded from http://pubs.acs.org on January 11, 2018

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Journal of the American Chemical Society

C–H Arylation of Phenanthrene with Trimethylphenylsilane by Pd/ o -Chloranil Catalysis: Computational Studies on the Mechanism, Regioselectivity, and Role of o -Chloranil Mari Shibata†, Hideto Ito*,†,‡ and Kenichiro Itami*,†,‡,# †

Graduate School of Science, Nagoya University, Chikusa, Nagoya 464-8602, Japan



JST-ERATO, Itami Molecular Nanocarbon Project, Nagoya University, Chikusa, Nagoya 464-8602, Japan

#

Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Chikusa, Nagoya 464-8602, Japan

ABSTRACT: The transition metal-catalyzed C–H arylation of aromatic hydrocarbons represents a useful and ideal method for the production of biaryls and multi-arylated aromatic compounds. We have previously reported the palladium-catalyzed direct C–H arylation of polycyclic aromatic hydrocarbons, such as phenanthrene, pyrene, and corannulene with various organosilicon, -borane, and -germanium compounds. In these reactions, o-chloranil proved to be an essential and unique promoter (stoichiometrically as an oxidant) and arylation occurred exclusively at the K-region. Herein, we report our mechanistic investigation of Pd/o-chloranil catalysis in C–H arylation of phenanthrene with trimethylphenylsilane by computational calculations. The results revealed that C–H arylation occurs through a sequence of transmetalation, carbometalation, and trans-β-hydrogen elimination steps. In addition, the triple role of o-chloranil as a ligand, oxidant, and base is also elucidated.

(a)

1. INTRODUCTION Transition-metal-catalyzed aromatic C–H arylation reactions represent an ideal and efficient synthesis method for the production of biaryl and oligoaryl compounds in terms of atom and step economies.1 Various reactions, arylation reagents, catalysts, and reaction conditions have been developed and in particular, palladium-catalyzed aromatic C–H arylation reactions have been extensively investigated.2,3,4 Among the many reported examples, C–H arylation has been easily achieved using directing groups on aromatic rings3 or employing reactive heteroaromatics such as azoles, thiophenes, indoles, and thiazoles.4 On the other hand, C–H arylation of unfunctionalized aromatic hydrocarbons is challenging and limited to some examples. For example, Fagnou has pioneered the C–H arylation of unfunctionalized aromatics through a concerted metalation-deprotonation (CMD) mechanism.5 Subsequently, Sanford,6a,b Oi and Inoue,6c,d and Glorius6e also reported the Pd-catalyzed C–H arylation of unfunctionalized benzene, naphthalene, and their derivatives. However, C–H arylation of polycyclic aromatic hydrocarbons (PAHs, aromatic hydrocarbons having more than two fused aromatic rings including nanographenes) is still in its infancy, displaying low reactivity and poor regioselectivity. To the best of our knowledge, successful examples of direct C–H arylation of unfunctionalized PAHs are limited to reports by our group,7 Oi and Inoue,6c,d and Glorius.6e

Cl +

B O

K-region

3

cat. Pd(OAc)2 o-chloranil

O

ClCH2CH2Cl 80 ºC, 12 h

O

0.67 eq.

o-chloranil

cat. Pd(OAc)2 o-chloranil

+

Me3Si

ClCH2CH2Cl 80 ºC, 16 h

2.0 eq.

(c)

Cl Cl

64% yield

(b)

Cl

32% yield tBu

tBu

+

cat. Pd(CH3CN)4(SbF6)2 o-chloranil

Me Si Me

tBu

ClCH2CH2Cl 80 ºC, 2 h tBu 87% yield

3.0 eq.

(d) This work: computational mechanistic studies on Pd-catalyzed C–H arylation of phenathrene Pd cat. o-chloranil +

Me3Si

Elucidation of i) Reaction mechanism ii) K-region selectivity iii) Role of o-chloranil

Previously, we have reported palladium-catalyzed C–H arylation of PAHs such as phenanthrenes and pyrenes using arylboroxines as arylating reagents and o-chloranil as oxidant (Scheme 1a).7a Interestingly, C–H arylation exclusively occurs at the K-region, the convex armchair edge of a PAH, to afford arylation products in good yield. Moreover o-chloranil proved to be the only effective oxidant in this reaction; p-chloranil, dichlorodicyanobenzoquinone (DDQ), benzoquinone, and other conventional oxidants did not

Scheme 1. Pd-catalyzed C–H arylation of PAHs with arylsilanes and arylboroxines

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effectively promote the reaction. Recently, we have further applied Pd/o-chloranil catalytic systems to the direct arylation of fluoranthene with aryltrimethylsilanes (Scheme 1b),7b,c penta- or decaarylation of corannulene for the synthesis of warped nanographenes,7d,e annulative π-extension (APEX)8a reaction of PAHs with dibenzosiloles (Scheme 1c),8b,c,d and APEX of heteroaromatics and alkynes with dibenzosiloles and dibenzogermoles.8e,f Although these reactions are highly important in the step-economical synthesis and late-stage functionalization of nanographenes and π-extended heteroaromatics, details on the reaction mechanism, catalytically active species, and origin of regioselectivity are yet to be uncovered. Motivated by this unique, powerful, yet mysterious Pd/ochloranil catalytic system, we undertook computational studies on the reaction mechanism. To limit the calculation cost, we chose the Pd-catalyzed C–H arylation of phenanthrene (1) with trimethylphenylsilane (2) and o-chloranil as the model reaction (Scheme 1d). By exhaustive calculations on possible reaction mechanisms, intermediates, and transition states by density functional theory/spin-component-scaled Møller–Plesset perturbation theory (DFT/SCS-MP2) methods, we have elucidated a reasonable reaction mechanism, the origin of K-region selectivity, and the triple role of o-chloranil as ligand, base, and oxidant.

Entry

Pd cat.

Ag salt

Yield of 3a

1 2

Pd(OAc)2 PdCl2

none none

54% 52%

3

Pd(OTf)2

none

56%

4

Pd(PPh3)4

none

3%

5

Pd2(dba)3·CHCl3

6

Pd(OAc)2

AgOTf

73%

7

PdCl2

AgOTf

62%

8

PdCl2

AgBF4

83%

9

Pd(MeCN)4(BF4)2

none

82% (72%)b

5%

In previous reports, only o-chloranil was used to promote C–H arylation and APEX reactions.7,8 To check the same oxidant specificity, we investigated the effect of the oxidant in the presence of Pd(MeCN)4(BF4)2 catalyst (Scheme 2). The use of p-chloranil, which displays a similar oxidation ability to that of o-chloranil, proved unsuccessful, indicating the importance of the obenzoquinone skeleton in this reaction. Moreover, although DDQ is a stronger oxidant than o-chloranil, it did not promote the reaction. Interestingly, reaction with another o-benzoquinone-type weak oxidant, 3,5-di-tert-butyl-o-benzoquinone (DTBQ), slightly proceeded to afford the product in 5% yield. Thus, we established that both an o-benzoquinone skeleton and a high oxidation ability are important factors in the current C–H arylation. While an inorganic oxidant such as Cu2Cl26c,d also exhibited little activity toward C–H arylation, K2S2O8 and the absence of oxidant were inactive. The observed reaction trends for both the oxidant specificity of o-chloranil and the advantage of a cationic palladium catalyst are similar to previously reported reactions.7,8 Hence, we concluded that the present Pd-catalyzed C–H arylation of 1 by 2 is suitable as a model reaction for a series of C–H arylation reactions of PAHs by a Pd/o-chloranil catalytic system. Scheme 2. Effect of oxidants in the Pd-catalyzed K region-selective C–H arylation of 1 with 2 5 mol% Pd(MeCN)4(BF4)2 1.5 equiv. oxidant

+

ClCH2CH2Cl 80 °C, 12 h

Me3Si 1 0.20 mmol

Table 1. Effect of palladium and silver salts in the K region-selective C–H arylation of 1 with 2

2 2.0 equiv. Cl O

oxidant

Cl

o-chloranil

p-chloranil

GC yield 82% 2% (72% isolated yield)

ClCH2CH2Cl 80 °C, 12 h

O O

Cl O Cl

tBu

Cl O Cl

Cl O Cl

+

3

Cl Cl

O

5 mol% Pd cat. 10 mol% Ag salt 1.5 equiv. o-chloranil

2 2.0 equiv.

none

Determined by GC analysis. bIsolated yield. c2.5 mo% catalyst loading.

We first conducted the C–H arylation of 1 (1.0 equiv.) with 2 (2.0 equiv.) in the presence of Pd(OAc)2 (5 mol%) and o-chloranil (1.5 equiv.) in 1,2-dichloroethane at 80 °C for 12 h. These conditions are similar to those of previously reported C–H arylation reactions with arylboroxines and aryltrimethylsilanes (Table 1, entry 1).8a,b,c As expected, C–H arylation occurred smoothly to afford 9-phenylphenanthrene (3) in 54% GC yield with perfect K-region selectivity. Other palladium salts such as PdCl2 and Pd(OTf)2 also exhibited the same catalytic activities in terms of yield (entries 2 and 3). On the other hand, Pd(0) catalysts such as Pd(PPh)4 and Pd2(dba)3·CHCl3 did not show catalytic activity (entries 4 and 5). The combination of Pd(OAc)2 and PdCl2 with 10 mol% AgOTf increased the yields of 3 (entries 6 and 7, respectively), while the use of PdCl2 with AgBF4 provided the best yield (83% GC yield, entry 8). These results suggest a cationic Pd species as the active species in this reaction. Indeed, the commercially available cationic Pd catalyst [Pd(MeCN)4(BF4)2] presented high catalytic activity and an excellent yield (82% GC yield and 72% isolated yield, entry 9) comparable to yield 3.

1 0.20 mmol

c

a

2. EXPERIMENTAL DETAILS

Me3Si

Page 2 of 14

tBu

CN O CN DDQ 3%

DTBQ K2S2O8 5%

trace

Cu2Cl2 none 7%

1%

DDQ: 2,3-dichloro-5,6-dicyanobenzoquinone. DTBQ: 3,5-di-tertbutyl-o-benzoquinone.

3

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Journal of the American Chemical Society

3. WORKING HYPOTHESIS Since C–H arylation is effectively catalyzed by cationic Pd(II) with o-chloranil but not with p-chloranil, we envisioned that a highly electron-deficient cationic Pd(II)/o-chloranil complex would be suitable as an active species in this reaction (Figure 1a). The reactivities of each region on 1 (Figure 1b) help explain the perfect K-region selectivity observed in the reaction: (i) the C2and C3-positions are the sterically least congested regions, and reactive toward aromatic electrophilic substitution (SEAr) reactions, such as Friedel–Crafts reactions and halogenation;9 (ii) the C4position is the most hindered region due to steric repulsion between “bay-region” hydrogen atoms, the most acidic hydrogen atoms in the molecule;10 and (iii) the C1- and C9 (C10)-positions are also sterically hindered but this region (K-region) is the most olefinic and least aromatic region because an isolated olefin is drawable even in the Clar structure and the HOMO and LUMO are located in this region.11 In addition, preliminary control experiments in the absence of 1 resulted in the formation of a significant amount of biphenyl product, the outcome of the transmetalation of Pd with 2.26 While we also considered possible other catalytic cyclic involving Pd(0) and Pd(IV), any positive experimental and computational results were not obtained at all (see SI for details).30

4. COMPUTATIONAL DETAILS To elucidate the reaction mechanism, including the origin of Kregion selectivity and the role of o-chloranil, we carried out computational studies by using the DFT13 and SCS-MP214 in the Gaussian 0915 package (see SI for the summary of basis sets). All geometry optimizations of the minima and transition states were conducted using B3PW9116/double-zeta basis sets in the gas phase at 353 K: 6-31G(d,p) for all the H atoms involved in the reactions, 6-31G for other H atoms , 6-31+G(d) for all B, C, N, O, F, and Si atoms involved in the reactions, 6-31G(d) for other C and Cl atoms, and LANL2DZ17 with effective core potential (ECP) for Pd atoms. Frequency analyses were carried out at the same level to evaluate the zero-point vibrational energy and thermal corrections at 353 K. The nature of the stationary points was determined in each case according to the appropriate number of negative eigenvalues of the Hessian matrix. Intrinsic reaction coordinate (IRC)18 calculations were also carried out for each transition state to ensure the connection of appropriate reactants and products. Single point energies for all DFT-optimized structures were determined using the SCS-MP2 function/triple-zeta basis sets in ClCH2CH2Cl with the integral equation formalism for the polarizable continuum model (IEF-PCM)19: 6-311G(d,p) for all H atoms, 6-311+G(d,p) for all B, C, N, O, F, and Si atoms involved in the reactions, 6-311G(d) for other C and Cl atoms not involved in the reactions, and the Stuttgart-Dresden (SDD)20 basis set with ECP for Pd atoms. Computed structures are illustrated using CYLview visualization software.21

Therefore, we proposed that the reaction is initiated by transmetalation of Pd(II) with 2 to form a cationic phenylpalladium species (Figure 1c). Taking the olefinic nature of the K-region into account, carbometalation of the Ph–Pd species across the K-region most likely occurs next and the subsequent deprotonation and demetalation processes would afford arylation product 3 (pathway A). The C–H metalation/reductive elimination route is also considered as another possible pathway (pathway B), while it is difficult to rationalize the origin of K-region selectivity and the driving force of C–H metalation via both electronic and steric factors.12 (a)

(b) Cl

X

O

Cl

O

Cl

sterically least congested H • Friedel-Crafts reaction 2 H 3 • halogenation

PdII

Y

4

Cl

• most acidic proton • sterically most hindered proton

Pathway A carbometalation

[PdII]

2

transmetalation

[PdII] Ph

5.1. Brief considerations on the catalytic cycle. We first performed preliminary calculations of the key intermediates and transition states in pathways A and B (Figure 2) to reveal the expected transition state (TS), with an activation free energy of 14.3 kcal/mol, in the carbometalation step (pathway A). For C–H metalation pathway B, we assumed several possible mechanisms including C–H activation via a CMD mechanism (pathway B1) and an SEAr mechanism (pathway B2). We excluded the mechanism involving C–H oxidative addition to the electron deficient cationic Pd(II) complex under oxidative reaction conditions. C–H metalation by a CMD mechanism generally requires a carboxylate or carbonate ion on the Pd center to facilitate deprotonation/metalation through a kinetically and thermodynamically stable six-membered ring transition state.22 While such species are not present in the reaction, we explored the possibility of CMD via o-chloranil, BF4–, and MeCN species. Only the reaction with o-chloranil afforded a CMD-like transition state, while the other species did not produce a transition state. As expected, the activation energy of CMD by o-chloranil is very high (ΔG‡ = 50.7 kcal/mol) due to the presence of an unfavorable seven-membered ring transition state (see the Supporting Information for details). Pathway B2 represents C–H metalation via an SEAr mechanism that often occurs on electron deficient and high-valent transition metal centers.23 Electrophilic addition of the electron-deficient phenyl-Pd/o-chloranil complex to the K-region of 1 may occur to provide an alkyl-phenyl-palladium intermediate (pathway B2). However, calculations did not afford any stationary

• sterically hindered proton H 1

H

H

10

K-region

9

• sterically hindered proton • most olefinic region

possible active species

(c)

5. RESULTS AND DISCUSSION

deprotonation & [PdII]demetalation Ph

1

3 Pathway B

reductive elimination

C–H metalation

[PdII] Ph

Figure 1. Working hypotheses and possible reaction pathways for C–H arylation of phenanthrene (1) with trimethylphenylsilane (2) catalyzed by the Pd/o-chloranil system. (a) Possible active catalytic species. (b) Steric and electronic natures of each region and the hydrogen atoms on 1. (c) Possible reaction pathways to form phenylphenanthrene (3) initiated by the formation of the phenylpalladium species via transmetalation.

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points for both ground and transition states in SEAr but converged to a Pd/phenanthrene π-complex 8 K (see Schemes 3 and 5). With these preliminary results in hand, we next focused our investigation on the most plausible pathway (pathway A).

afforded the relatively stable complex 5 (ΔG = –3.05 kcal/mol, Figure 4). While this process is enthalpically unfavorable, the release of two coordinating MeCN molecules and weak anion-π interactions24 between the BF4– anion and o-chloranil promote the formation of electron-deficient complex 5 (Scheme 3). We next discovered that the formation of silylarenium-palladium intermediate 6 is not a high-energy process (ΔΔG = 2.09 kcal/mol) and does not include a transition state. The complexation of 6 with another intermolecular o-chloranil moiety was also possible. This afforded the more stable complex (by 6.44 kcal/mol) 6-Chl whose additional o-chloranil moiety is also weakly bound to the BF4– ion through anion-π interactions. Subsequently, nucleophilic substitution via the oxygen atom of the outer o-chloranil species onto a silicon atom forms cationic phenyl-palladium(II)/ochloranil complex 7, o-chloranil/Me3SiBF4 complex 13 through a TS6Chl-7 transition state. Notably, the O, Si, and Cipso atoms are located on almost the same line in TS6Chl-7 (∠O–Si–Cipso = 171°), clearly indicating that this substitution process is an SN2-like reaction. The whole process, from 5 to 7, involves SEAr-type transmetalation between dicationic Pd and 2 in the presence of ochloranil. Alternatively, the BF4– ion could be participating in SEAr transmetalation instead of o-chloranil, however, we could not produce any appropriate structures to support this. In the general Hiyama-type silicon-based cross-coupling reaction, transmetalation of arylsilane requires electron-deficient OH, OMe, Cl, and F substituents on the silicon center to activate the silicon atom.25 In addition, transmetalation of inactive aryltrimethylsilanes require intermolecular “activators” such as an F– ion to enable transmetalation through a silicate intermediate.25 To the best of our knowledge, few examples of intermolecular transmetalation of aryltrimethylsilanes without a F– ion source have been reported to and date. These include [Pd(OAc)2/o-chloranil Pd(MeCN)4(BF4)2/o-chloranil],7b,26 (PdCl2),6b (PdCl2/CuCl2),6d and [Au(OTs)PPh3/PhI(OAc)2].27 We considered that the electron-deficient nature of the dicationic palladium/o-chloranil complex and the outer o-chloranil stabilized by anion π-interaction enable the effective transmetalation of inactive 2.

Pathway A BF4– H



Cl Cl

+

O

PdII

Cl

O

H

Cl

TS in carbopalladation ∆G‡ = 14.3 kcal/mol Pathaway B1

Pathway B2 ‡ F PdII

H

O

F

Cl

Cl Cl

+

B F

Cl

O

BF4–

F

O II H Pd O

Cl Cl

Cl Cl

TS in CMD ∆G‡ = 50.7 kcal/mol

Page 4 of 14

intermediate in SEAr not located

Figure 2. Working hypothesis and possible reaction pathways in the C– H arylation of phenanthrene (1) with trimethylphenylsilane (2) catalyzed by the Pd/o-chloranil system.

5.2. Overview of the catalytic cycle in pathway A. Figures 3 and 4 depict the overview of possible catalytic cycles and the energy profile for each intermediate and transition state in pathway A comprising (i) transmetalation, (ii) carbometalation, (iii) trans-β-hydrogen elimination and reoxidation, and (iv) ligand exchange. Firstly, the reaction is initiated by the transmetalation of Pd(MeCN)4(BF4)2 with 2 in the presence of o-chloranil to form monocationic phenyl-palladium(II)/o-chloranil complex 7. Next, K-region selective carbopalladation of complex 7 with 1 affords insertion adduct 9 K . The next step represents trans-β-hydrogen elimination along with reductive demetalation and reoxidation of Pd(0) by o-chloranil coordination to provide arylation product 3 with palladium(II) catecholate complex 10b. Subsequently, ligand exchange regenerates Pd(MeCN)4(BF4)2 with O-trimethylsilyl3,4,5,6-tetrachlorocatechol (12) as a co-product. Notably, the formation of 12 is experimentally supported by the observation of a mass peak (m/z calcd for C9H10O2Cl4Si [M]+: 318) in the GC-MS spectrum of the crude mixture. As a whole, our reaction seems to prefer the pseudo redox-neutral Pd(II) processs to Pd(II)/Pd(IV) cycle predicted by Sanford6a,b and Oi6c,d. 5.3. Transmetalation of PhSiMe 3 with Pd(MeCN 4 ) 4 (BF 4 ) 2 . During the initiation of the reaction, ligand substitution of MeCN with Me3SiPh (2) was slightly unfavorable (ΔG = 1.62 kcal/mol) for the formation of Pd-πcomplex 4. An alternative pathway regarding to the formation of Pd(MeCN4)2(o-chloranil)(BF4)2 complex through the ligand exchange on Pd(MeCN4)4(BF4)2 with o-chloranil resulted in the more unfavorable route (ΔG = 5.57 kcal/mol). However, subsequent coordination of o-chloranil toward the complex 4

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Journal of the American Chemical Society Cl

Cl

HO

O

Cl

Me3SiO

MeCN

Cl Cl

12

O

NCMe

2+

PdII

MeCN

Cl

2+

2 BF4–

Cl Cl

NCMe

Me3Si–BF4 [H+] BF4– 2 MeCN

i) transmetalation

3 MeCN

iv) ligand exchange Cl O

MeCN

O

+

Cl

PdII

PdII

MeCN

Cl

BF4–

MeCN

Cl

O+

BF4– Me3Si

Cl

O

Pathway A

Cl

11

Cl Cl

7

1

ii) carbometalation [Me3Si–BF4]

Cl O

MeCN

Cl

PdII

MeCN

iii) β-H elimination & reoxidation

Cl H

MeCN O

+

MeCN Cl

O

PdII

Cl

10b Cl

H

+ [H+] + BF4–

BF4–

Cl

O Cl

9K

3

Figure 3. Proposed catalytic cycle of pathway A in the Pd-catalyzed C– H arylation of phenanthrene (1) with trimethylphenylsilane (2) and ochloranil.

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SiMe3 BF4 2+ PdII

L

SiMe3 BF4–



L L

L

2+ PdII

SiMe3

O

+ PdII

O

5

Cl

O

Cl BF4–

Cl

Si

O

+ PdII

O BF4–

L

BF4–

BF4–

4

BF4

Cl O



MeCN

6

Page 6 of 14

Cl

H + PdII

O

L

BF4–

O BF4–

O

O

7

8K

6-Chl

+

PdII

O

+ PdII

O

H

O O

1.62 (1.35)

0.00 Pd(L)4(BF4)2 (L = MeCN) phenanthrene (1) PhSiMe3 (2) 2 o-chloranil

–20.0

4

–20.7 (3.61)

Cl

Cl

O

O

Cl

Cl

Cl

O

Cl

Si

–32.1 (–11.5)

BF4–

MeCN

O O

∆G‡ = 14.3

8K

O

O Cl

Cl

TS9-10K –30.2 (–8.66)

∆G‡ = 12.5

–35.0 (–15.7)

kcal/mol

H

Cl

–22.6 (–11.6) TS9-10K

TS8-9K

7

Cl

O + PdII

353.15 K in ClCH2CH2Cl ΔG / kcal/mol (ΔH / kcal/mol)



kcal/mol

10b

–49.0 (–58.8)

–39.0 (–26.7)

9K

O

Pd(L)4(BF4)2

3 + 12 o-chloranil

11

BF4–

TS6Chl-7 i) transmetalation

–60.0

iii) β-H elimination & reoxidation

ii) carbometalation



O

PdII

TS8-9K

–17.8 (2.60)

∆G‡ = 5.42

Cl O

BF4– +

O

H

kcal/mol

O

–50.0



Cl

6-Chl

Cl Cl

11

O

+

Cl

O+

BF4– Me3Si

PdII

TS6Chl-7

–5.78 (7.54)

6

5

–30.0

–40.0

–0.356 (4.67)

0.656 (16.3)

–1.43 (14.2)

Cl Cl

BF4–

0.00 (0.00)

–10.0

O

L

10b

H

O

L PdII

L

9K

kcal/mol 10.0

Cl

PdII

BF4–

BF4–

Cl

O

L

iv) ligand exchange

Figure 4. Møller–Plesset perturbation theory (MP2) free energy profile for the pathway in 1,2-dichloroethane at 80 °C. Enthalpies are listed in parentheses. Free phenanthrene, Me3SiBF4, MeCN, o-chloranil, 13, 14 and other side-products are omitted in each intermediate and transition states for clarity.

Scheme 3. o -Chloranil-assisted transmetalation of trimethylphenylsilane (2) with Pd. Cl

BF4

Si + PdII

5

O BF4–

Cl

O

Cl

Cl

O +

PdII

Cl

MeCN

6 ΔG = 6.44 kcal/mol (ΔH = 8.80 kcal/mol)

Cl BF4– O O

Cl

Cl Cl

Si

Cl

Cl

Cl O

Cl

Cl

O

MeCN

ΔG = 4.35 kcal/mol (ΔH = 6.64 kcal/mol)



O

transmetalation

Si Cl Cl

BF4–

BF4

PdII

MeCN

6-Chl

BF4–

5.42 kcal/mol (–2.87 kcal/mol)

+



O O

TS6Chl-7

0.00 kcal/mol (0.00 kcal/mol)

BF4–

Cl

O +

Cl Cl



Cl

O

Cl O

Cl

PdII

Cl Cl

MeCN

Cl Cl

Cl Cl

O

BF4– +O Me3Si

Cl

O

7

Cl Cl

–15.0 kcal/mol (3.92 kcal/mol)

Cl

13

5

7

6 6-Chl

TS6Chl-7

relatively low. Subsequently, the reaction produced a more stable insertion product 9 K (ΔG = 2.91 kcal/mol). Notably, the weak interaction (π-coordination) between the Cipso–Cortho bond and the Pd center thermodynamically stabilizes compound 9 K .

5.4. Carbometallation of cationic phenyl-palladium/ o chloranil complex with 1. We next investigated the K-region selective carbometalation of complex 7 with 1 (Scheme 4). The coordination of 1 to 7 at the K-region to form π-complex 8 K is an exothermic reaction. The calculated Gibbs free energy (ΔG‡ =14.3 kcal/mol) for the four-membered-ring transition state TS8-9 K was

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Journal of the American Chemical Society

Scheme 4. K -region selective π-coordination of phenanthrene and carbopalladation.

K-region BF4– +

Cl O

1

Cl

+

PdII

MeCN

O

7

ΔG = 11.4 kcal/mol (ΔH = 15.1 kcal/mol)

O

H

Cl

O

K-region selective π-coordination

BF4

Cl Cl



O

+

H

BF4–

H

Cl

BF4–

TS8-9K

8K

8K

Cl

O Cl

9K

–2.91 kcal/mol (4.15 kcal/mol)

14.3 kcal/mol (14.1 kcal/mol)

0.00 kcal/mol (0.00 kcal/mol)

Cl

O

+

PdII

Cl

O

H

carbopalladation

Cl

Cl PdII

PdII

–MeCN

Cl Cl



Cl

Cl

9K

TS8-9K

Scheme 5. Trans -β-hydrogen elimination, reductive demetalation, and simultaneous reoxidation.

‡ Cl

O

PdII +

o-chloranil Cl

0.00 kcal/mol (0.00 kcal/mol)

O

H O

Cl Cl

BF4

Cl

TS9-10K

O

MeCN

Cl

reoxidation

Cl

Cl



BF4–

MeCN

+

Cl

O

Cl

O

3 +

O

Cl

MeCN

O

Cl

H

Cl

PdII Cl Cl

10a

10b

not located

4.82 kcal/mol (7.00 kcal/mol)

Cl

12.5 kcal/mol (4.03 kcal/mol)

O

MeCN

Pd0

Cl

Cl

Cl

2 MeCN

Cl

O

9K

β-H elimination & demetalation

L

14

9K

TS9-10K

5.5. K -region selectivity in carbopalladation. We also compared the activation energies of carbopalladation at other positions on the phenanthrene molecule to reveal the origin of Kregion selectivity in the current C–H arylation (Figure 5). The results demonstrated that in the phenanthrene molecule, metal coordination could also occur at the C1–C2, C2–C3, and C3–C4 positions and that complexation with a Ph-Pd/o-chloranil complex (7) affords four possible unstable coordination modes, namely, 8 C 1 -C 2 , 8 C 2 -C 3 , 8 C 2 ’-C 3 ’ and 8 C 3 -C 4 . Relative free energies, based on the most stable mode 8 K , were calculated as 9.03, 4.83, 4.91, and 9.95 kcal/mol for 8 C 1 -C 2 , 8 C 2 -C 3 , 8 C 2 ’-C 3 ’ , and 8 C 3 -C 4 , respectively.

10b

The greater stability of the coordination at the K-region was attributed to the double-bond character of this region. As illustrated by the most stable Clar structure of 1, the six-membered rings at both ends indicate higher aromaticity, while the central ring exhibits weaker aromatic character. Therefore, the K-region possesses double-bond character and thus, the HOMO and LUMO are slightly localized on the K-region; this enhances the effective πcoordination and back donation from Pd. π-Complex 8 next undergoes carbometalation with the neighboring C–C bonds to form adducts 9 1 P h -P d 2 , 9 2 P h -3 P d , 9 3 P h -2 P d , and 9 4 P h -3 P d through four transition states, namely, TS8-9 1 P h -P d 2 , TS8-9 2 P h -3 P d , TS8-9 3 P h -

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Figure 5. Comparison of the energy profiles in the carbometalation step at each region of the phenanthrene molecule.

π P d , and TS8-9 4 P h -3 P d , respectively. These activation energies (ΔG‡) are much higher (by 3.6–12 kcal/mol) than that of TS K and all the carbometalation reactions, except for K-region-phenylation, result in endothermic reactions from the most stable π-complex 8 K . These results can also be explained by taking the aromaticity of each region into account: among all the insertion products, 9 K exhibits the greatest aromatic stabilization because as well as the starting phenanthrene, two disjointed aromatic π-sextets are still drawable. On the other hand, the other products disrupt the aromaticity of the phenanthrene ring to increase their thermodynamic energy.

(a)

5.6. o -Chloranil-induced trans -β-hydrogen elimination and reoxidation of palladium. The next step was to consider trans-β-hydrogen elimination and demetalation. While in the general palladium-catalyzed Heck-type reactions, β-hydrogen elimination favors the cis-position against Pd, 9 K does not possess cis-β-hydrogens. We considered and estimated various possibilities of trans-β-hydrogen elimination by using intermolecular potential bases such as BF4–, MeCN, and o-chloranil. As a result, we found that o-chloranil can participate in trans-β-hydrogen elimination as a formal base. The activation energy for this transition state (TS910 K ) was calculated as 12.5 kcal/mol, which is slightly lower than that of the carbometalation step. In this step, Pd(II) tetrachlorocatecholate complex 10b is produced along with product 3 and protonated o-chloranil 14. A comparison of the bond lengths of the C1–C2 and C–O bonds of the coordinating ochloranil in each complex and reported palladium(II) catecholate complex28 revealed that o-chloranil acts as a neutral bidentatechelating quinone ligand in complexes 5 to TS9-10 K ’, whereas it clearly changes to an anionic catechol ligand after the formation of intermediate 10b (Figure 6). This clearly indicates that Pd is oxidized by the coordinating o-chloranil molecules. This process can also be rationalized by considering that Pd(0)/o-chloranil complex 10a initially forms through reductive demetalation via TS9-10 K and subsequently, simultaneous reoxidation of Pd(0) to Pd(II) occurs via the coordinating o-chloranil. Consequently, an apparent redox-neutral Pd(II)-catalytic process may prevent the aggregation of inactive Pd(0) and enables the unprecedented C–H arylation of 1.

(b)

1

1 2 2

8C1-C2

91Ph-2Pd

ΔG = 4.91kcal/mol (ΔH = 5.13 kcal/mol)

ΔG = 5.48 kcal/mol (ΔH = 4.65 kcal/mol)

2

3

3

2

8C2-C3

92Ph-3Pd

9.03 kcal/mol (11.1 kcal/mol)

17.9 kcal/mol (17.6 kcal/mol)

10a 1

2 3

Page 8 of 14

2

3

8C2’-C3’

93Ph-πPd

9.95 kcal/mol (10.8 kcal/mol)

7.31 kcal/mol (7.93 kcal/mol)

3 4 4

3

8C3-C4

94Ph-3Pd

4.83 kcal/mol (5.22 kcal/mol)

3.78 kcal/mol (2.43 kcal/mol)

(c) kcal/mol 30.0 2 3

TS8-93Ph-πPd 1

TS8-92Ph-3Pd

25.0 4

C4-phenylation C3-phenylation C2-phenylation C1-phenylation K-phenylation

10

20.0

(K-region)

TS8-91Ph-2Pd

92Ph-3Pd

9

Figure 6. Comparison of the o-chloranil bond lengths in each intermediate and transition state. Blue markers: bond lengths between C1 and C2 atoms. Red markers: averaged bond lengths of two C–O bonds. Ref = palladium(II) 3,4,5,6-tetrachlorobenzene-1,2bis(olate)/diimine complex reported in ref 28.

TS8-94Ph-3Pd 15.0

8C2’-C3’ 10.0

TS8-9K 14.3 (14.1)

93Ph-πPd

8C2-C3 5.00

8C3-C4 8C1-C2 8K

–0.00

–5.00

0.00 (0.00) ΔG / kcal/mol (ΔH / kcal/mol)

91Ph-2Pd Phenylation

ΔG‡ kcal/mol

K-region C1 C2

14.3 19.1 26.3

C3

26.3

C4

17.9

94Ph-3Pd

5.7. Ligand exchange and regeneration of Pd(MeCN) 4 (BF 4 ) 2 . The ligand exchange steps following the formation of complex 10b were energetically downhill reactions

9K –2.91 (–3.60)

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Journal of the American Chemical Society

(Scheme 6). Silylation by o-chloranil/Me3SiBF4 complex (13) takes place easily to form complex 11 (ΔG = –8.72 kcal/mol) and subsequent protonation by 14 regenerates Pd(MeCN)4(BF4)2 and provides silyl catechol ether 12 as a co-product through exothermic process (ΔG = –18.8 kcal/mol; ΔH = 50.1 kcal/mol).

MeCN ligands or DTBQ instead of the o-chloranil ligand in intermediates 5, 6, 6-Chl, 7, 8 K , 9 K , 10b, 11, 12, 13, 14 and transition states TS6Chl-7, TS8-9 K , and TS9-10 K , respectively. The results are summarized as blue lines (for 5´ to TS9-10 K ´) and red lines (for 5˝ to TS9-10 K ˝) in the energy profile in Figure 7. The coordination of o-chloranil lowers the energy at each stationary point. In particular, the activation energies of transmetalation (ΔG‡TM) and carbometalation (ΔG‡CM) are lower by 4.0 kcal/mol and 4.6 kcal/mol, respectively, than those without o-chloranil coordination. On the other hand, the activation barrier in β-H elimination (ΔG‡ -H) is higher by 1.1 kcal/mol than that without o-chloranil coordination.

Scheme 6. Ligand exchange and reoxidation of the palladium catalyst.

o-chloranil/Me3SiBF4 (13)

10b 0.00 kcal/mol (0.00 kcal/mol)

Cl O

MeCN

Cl

β

PdII

MeCN

–o-chloranil

O+

BF4– Me3Si

Cl

In the case of coordination by DTBQ, the each stationary intermediate and transitions state are also stabilized to some extent compared to the non-chloranil coordination pathway. Unexpected destabilizations at 6-Chl˝ and TS6Chl-7˝ are well rationalized by the loss of one anion-π interaction between BF4– and outer DTBQ (Figure 7, ball and stick models), while the complexes 6Chl and TS6Chl-7 are highly stabilized by three strong anion-π interactions between BF4– and inner and outer o-chloranil molecules (Scheme 3). For these reasons, DTBQ is not effective in the transmetalation (ΔG‡TM = 10.3 kcal/mol), whereas it has the enhancing ability toward the carbometalation step (ΔG‡CM = 14.1 kcal/mol) as in the case of o-chloranil. However, the activation energy in β-H elimination is dramatically increased to reach to 31.1 kcal/mol. We considered that the degree of reaction progress in βhydrogen elimination could be simply affected by the basicity of carbonyl oxygen atom on quinone and the elimination ability of Pd atom in complex 9 K ˝ and TS9-10 K ˝. From the above calculation results, we speculate the elimination ability of Pd atom mainly affect this step rather than the basicity of quinone because DTBQ is more electron-rich and basic than o-chloranil. Thus, the β-H elimination becomes a rate-determining step along with high activation energy when DTBQ is employed in the reaction.

Cl

11

–8.72 kcal/mol (–18.1 kcal/mol)

o-chloranil/HBF4 (14) 2 MeCN –o-chloranil

Cl

HO

2 BF4–

Cl

+

Me3SiO

Cl

MeCN MeCN

2+

PdII

NCMe NCMe

Cl

12

–18.8 kcal/mol (–50.1 kcal/mol)

5.8. Role of o -chloranil as ligand. As mentioned in section 5.5, o-chloranil works as an oxidant for the reoxidation of Pd(0) and an apparent base in trans-β-hydrogen elimination. Additionally, we investigated the ligand effect of o-chloranil in each reaction step. For comparison, we performed calculations for non-o-chloranilcoordinating complexes 5´, 6´, 6-Chl´, 7´, 8 K ´, 9 K ´, 10a´, TS6Chl-7´, TS8-9 K ´, and TS9-10 K ´, and DTBQ-coordinating complexes 5˝, 6-Chl˝, 7˝, 8 K ˝, 9 K ˝, 10b˝, 11˝, 12˝, 13˝, 14˝, TS6Chl-7˝, TS8-9 K ˝, and TS9-10 K ˝, which comprise two

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∆G kcal/mol 20.0

i) transmetalation with DTBQ coordination without o-chloranil coordination with o-chloranil coordination

10.0 ∆G‡trans 4

5′ (= 4)

0.00

–10.0

–20.0

iii) β-H elimination & reoxidation

ii) carbometalation

TS6Chl-7″ TS6Chl-7′ 6′

iv) ligand exchange t-Bu

NCMe

MeCN

PdII

MeCN

∆G‡trans

5

∆G‡trans

TS8-9K′

∆G‡CM

TS8-9K 8K′

7

9K″

∆G‡CM

–30.0

10a′

∆G‡β-H TS9-10K

9K’

∆G‡CM

8K″

10b″

TS9-10K′

TS8-9K″

7″ 353.15 K in ClCH2CH2Cl ΔG / kcal/mol (ΔH / kcal/mol)

10b

10b

11″

∆G‡β-H

8K –40.0

–50.0

with o-chloranil (kcal/mol)

ΔG‡TM ΔG‡CM ΔG‡β-H

without o-chloranil (kcal/mol)

5.42 14.3 12.5

with DTBQ (kcal/mol)

9.42 18.9 11.4

t-Bu HO

PdII

L

Cl

Si

+

MeCN

Cl Cl

Cl

TS9-10K′ BF4–

H

t-Bu

TS8-9K″

TS6Chl-7″

O

t-Bu

O t-Bu

O BF4–



+

PdII

O

PdII t-Bu

H O

t-Bu +

NCMe

NCMe

O

‡ H

O O BF4–

Cl





BF4–

PdII

NCMe

TS8-9K′

t-Bu

O

+

BF4

BF4–

t-Bu

Si



PdII

NCMe

PdII H

NCMe NCMe

TS6Chl-7′ O

BF4– +

H

BF4–

MeCN

Pd(L)4(BF4)2 3 + 12 o-chloranil

12″



Cl

+ PdII

11″

t-Bu

Me3SiO

BF4–



Cl O

t-Bu

O+ Me3Si

Cl

TS6Chl-7″

t-Bu

O

L

10.3 14.1 31.1

O

6-Chl″

Pd(L)4(BF4)2 3 + 12″ DTBQ

11

9K

activation energy

t-Bu

O

10b″

∆G‡β-H

6-Chl 7′

MeCN

NCMe

10a′

TS9-10K″

TS6Chl-7 6-Chl′

O

MeCN

Pd0

6-Chl″

6 5″

Pd(L)4(BF4)2 (L = MeCN) phenanthrene (1) PhSiMe3 (2) 2 o-chloranil (or 2 DTBQ)

Page 10 of 14

O

H

t-Bu

O

t-Bu t-Bu

TS9-10K″

Figure 7. Comparison of the energy profiles of the reaction with or without the coordination of o-chloranil and DTBQ. In the reaction without ochloranil coordination (blue line), two MeCN moieties are coordinated to a Pd center instead of o-chloranil. Free phenanthrene, MeCN, o-chloranil or DTBQ, 13, 14, 13˝, 14˝ and other side-products are omitted in each intermediate and transition states for clarity (see SI for all structures).

values also computationally support the above mentioned electron density-increasing process. A similar trend is also found in the carbometalation process from 8 K ´ to TS8-9 K ´, which is also an electron density-increasing process from a monocationic phenylPd(II) species to a monocationic alkyl-Pd(II) complex (qNBO = +0.455 e for 8 K ´ and +0.420 e for TS8-9 K ´).

To rationalize the observed stabilization/destabilization effects of the o-chloranil ligand on each transition states, we also conducted a natural bond order (NBO) analysis29 focusing on the natural charge on the Pd atoms in each intermediate and transition state. We defined the degree of stabilization by o-chloranil as the following equation; ΔΔG(X ´) = ΔG(X ´) – ΔG(X )

We consider the reasons why the NBO charge in complex TS89 K ´ is lower than those in complex 8 K ´ and 9 K ´ as follows. TS89 K ´ can be regarded as a pseudo 14-electron alkyl-aryl-Pd(II) complex because the Pd-C(phenanthrene) bond is almost connected (2.09 Å), judging from the comparison of before (2.30 Å) and after (2.05 Å) the reaction, while Ph-Pd bond (2.06 Å) seems to be still retained (Ph-Pd: 1.98 Å in 8 K ´, 2.24 Å in 9 K ´) (Table 3). Thus the electron-rich character on a Pd center in transition state TS8-9 K ´ possibly results in the unexpected decrease of NBO charge. This explanation also satisfy our discussion that the coordination of o-chloranil can effectively stabilize the more electron-rich Pd in complex TS8-9 K ´ rather than 8 K ´ by the coordination, which leads to the decrease of activation energy. Therefore, it is reasonable to assume that the stabilization effects on Pd by the electron-deficient o-chloranil ligand work more effectively in TS8-9 K than in 8 K (and also in

(1)

where X represents 5, 6, 6-Chl, 7, 8 K , 9 K , TS6Chl-7, TS7-8 K , TS8-9 K , and TS9-10 K , respectively. As expected, the NBO charges (qNBO) and ΔΔG(X ´) values are approximately correlated to each other (Table 2). The ΔΔG(X ´) value tends to increase when qNBO decreases, which implies that the less cationic Pd moieties are more stabilized by the coordination of o-chloranil. In the transmetalation process from 6-Chl´ to TS6Chl-7´ and 7´, the dicationic Pd(II) species change into monocationic phenylPd(II) complexes. This suggests an increase in the electron density on Pd. Indeed, the NBO (qNBO) on Pd is estimated at +0.700 e for 6-Chl´, +0.576 e for TS6Chl-7´, and +0.457 e for 7´. These

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Journal of the American Chemical Society

TS6Chl-7 rather than 6-Chl), thus resulting in lower activation energies.

region selective carbometalation of the phenyl-Pd species, trans-βhydrogen elimination and simultaneous reoxidation of Pd(0) to Pd(II), and finally, ligand exchange. The rate-determining step was estimated to be the carbometalation step with a relatively low activation barrier of 14.3 kcal/mol. Perfect K-region selectivity in C–H arylation is well rationalized by the observed favored πcoordination of the phenyl-Pd species to the K-region in 1 (energy >4.8 kcal/mol). In addition, the carbometalation activation energy at the K-region is also lower (>3.6 kcal/mol) than that of the other regions. These values are attributed to the lower aromatic/higher olefinic nature at the K-region, so that perfect K-region selectivity in the C–H arylation is achieved. We also investigated the effect of o-chloranil coordination by calculating the energies and NBO charges of each intermediate and transition state in the absence of the o-chloranil ligand or the presence of DTBQ. As a result, the coordination of o-chloranil was found to stabilize each complex, especially the transition states in the transmetalation and carbometalation steps. As a whole, we have uncovered the triple unique roles of o-chloranil, namely, as a ligand, oxidant, and base.

Conversely, the NBO charges on Pd become more cationic in the process from 9 K ´ (qNBO = +0.457 e) to TS9-10 K ´ (qNBO = +0.477 e). This indicates that the degree of stabilization by ochloranil is larger in the former complex. Indeed, complexes 9 K and TS9-10 K are stabilized by the coordination of o-chloranil by 11.4 and 10.3 kcal/mol, respectively, resulting in slightly increased activation energy for β-H elimination via the coordination of ochloranil. Accordingly, the coordination of o-chloranil to a Pd atom results in 3–12 kcal/mol of stabilization energy (ΔΔG(X ´)) in each intermediate and transition state (Table 2), which leads to a 4.6 kcal/mol reduction of activation energy in the rate-limiting carbometalation step (Figure 7). Table 2. NBO charges and degree of stabilization by o chloranil in each complex without o -chloranil coordination. Complex

qNBO

ΔΔG(X´) / kcal/mol

5´ (≡ 4) 6´

0.637

3.05

0.531

5.05

6-Chl´

0.700

6.30

TS6Chl-7´

0.576



0.457

4.73

8K ´

0.455

7.50

TS8-9K´

0.420

12.1

9K ´

0.457

11.4

TS9-10K´

0.477

10.3

We believe that the present findings will lead to the development of more reactive catalysts and ligands/oxidants, and the establishment of novel strategies for direct C–H arylation of unfunctionalized aromatics and efficient nanocarbon syntheses without the presence of directing groups and prefunctionalization.

10.3

ASSOCIATED CONTENT Supporting Information. The Supporting Information is available free of charge on the ACS Publications website. Experimental procedures and characterization data for all compounds; general procedures, and calculated results.

AUTHOR INFORMATION

Table 3. Comparison of bond lengths and NBO charges of 8 K ´, TS8-9 K ´ and 9 K ´.

Corresponding Author *E-mail: [email protected] (H.I.) *E-mail: [email protected] (K.I.) ORCID Hideto Ito: 0000-0002-4034-6247 Kenichiro Itami: 0000-0001-5227-7894

NBO charge on Pd Pd–Ph Pd–phenanthrene note

8K′

TS8-9K′

+0.455 e 1.98 Å 2.30 Å 14e aryl-Pd(II)

+0.420 e 2.06 Å 2.09 Å pseudo 14e alkylaryl-Pd(II)

9K′

ACKNOWLEDGMENT

+0.457 e 2.24 Å 2.05 Å 14e alkyl-Pd(II)

This work was supported by the ERATO program from JST (JPMJER1302 to K.I.), JSPS KAKENHI Grant Numbers JP26810057, JP16H00907, JP17K19155 (H.I.), the SUMITOMO Foundation (141495 to H.I.) and DAIKO Foundation (H.I.). The computations were performed using the Research Center for Computational Science, Okazaki, Japan. ITbM is supported by the World Premier International Research Center Initiative (WPI), Japan.

6. CONCLUSION We have investigated the reaction mechanism, K-region selectivity, and role of o-chloranil in the Pd-catalyzed C–H arylation of 1 with 2. Similar to the reactions reported in our previous study,7,8 in this reaction, a preference for cationic Pd catalysts, necessity of a stoichiometric amount of o-chloranil for the reaction to progress, and perfect K-region selectivity in C–H arylation were observed. DFT/SCS-MP2 calculations revealed that the reaction is most likely initiated by o-chloranil-assisted transmetalation of Pd(II) with 2 via SEAr. This is followed by K-

REFERENCES [1] Reviews on metal-catalyzed C–H arylations of aromatics: (a) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107, 174. (b) Kakiuchi, F.; Kochi, T. Synthesis 2008, 3013. (c) Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew. Chem., Int. Ed. 2009, 48, 9792. (d) Wencel-Delord, J.; Dröge, T.; Liu, F.; Glorius, F. Chem. Soc. Rev. 2011, 40, 4740. (e) Kuhl, N.; Hopkinson, M. N.; Wencel-Delord, J.;

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Glorius, F. Angew. Chem., Int. Ed. 2012, 51, 10236. (f) Yamaguchi, J.; Yamaguchi, A. D.; Itami, K. Angew. Chem., Int. Ed. 2012, 51, 8960. (g) Liu, C.; Yuan, J.; Gao, M.; Tang, S.; Li, W.; Shi, R.; Lei, A. Chem. Rev. 2015, 115, 12138. (h) Segawa, Y.; Maekawa, T.; Itami, K. Angew. Chem., Int. Ed. 2015 , 54, 66. [2] Reviews on palladium-catalyzed C–H arylation of aromatics: (a) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem., Int. Ed. 2009, 48, 5094. (b) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147. (c) Engle, K. M.; Mei, T.-S., Wasa, M.; Yu, J.-Q. Acc. Chem. Res. 2012, 45, 788. [3] Selected examples of Pd-catalyzed and directing group-assisted C–H arylation of aromatics: (a) Ackermann, L. Chem. Rev. 2011, 111, 1315. (b) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147. [4] Selected examples of Pd-catalyzed C–H arylation of reactive heteroaromatics: (a) Seregin, I. V.; Gevorgyan, V. Chem. Soc. Rev. 2007, 36, 1173. (b) Watanabe, T.; Oishi, S.; Fujii, N.; Ohno, H. J. Org. Chem. 2009, 74, 4720. (c) Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew. Chem., Int. Ed. 2009, 48, 9792. For other reviews, also see ref 1 and 2. [5] Representative examples of Pd-catalyzed C–H arylations via a concerted metalation-deprotonation mechanism: (a) Lafrance, M.; Rowley, C. N.; Woo, T. K.; Fagnou, K. J. Am. Chem. Soc. 2006, 128, 8754. (b) Lafrance, M.; Fagnou, K. J. Am. Chem. Soc. 2006, 128, 16496. (c) Gorelsky, S. I.; Lapointe, D.; Fagnou, K J. Am. Chem. Soc. 2008, 130, 10848. (d) Lapointe, D.; Fagnou, K. Chem. Lett. 2010, 39, 1118. [6] Pd-catalyzed C–H arylations of polycyclic aromatic hydrocarbons: (a) Hickman, A. J.; Sanford, M. S. ACS Catal. 2011, 1, 170. (b) Wagner, A. M.; Hickman, A. J.; Sanford, M. S. J. Am. Chem. Soc. 2013, 135, 15710. (c) Kawai, H.; Kobayashi, Y.; Oi, S.; Inoue, Y. Chem. Commun. 2008, 1464. (d) Funaki, K.; Kawai, H.; Sato, T.; Oi, S. Chem. Lett. 2011, 40, 1050. (e) Collins, K. D.; Honeker, R.; Vásquez-Céspedes, S.; Tang, D.-T. D.; Glorius, F. Chem. Sci. 2015, 6, 1816. [7] (a) Mochida, K.; Kawasumi, K.; Segawa, Y.; Itami, K. J. Am. Chem. Soc. 2011, 133, 10716. (b) Kawasumi, K.; Mochida, K.; Kajino, T.; Segawa, Y.; Itami, K. Org. Lett. 2012, 14, 418. (c) Kawasumi, K.; Mochida, K.; Segawa, Y.; Itami, K. Tetrahedron 2013, 69, 4371. (d) Kawasumi, K.; Zhang, Q.; Segawa, Y.; Scott, L. T.; Itami, K. Nat. Chem. 2013, 5, 739. (e) Zhang, Q.; Kawasumi, K.; Segawa, Y.; Itami, K.; Scott, L. T. J. Am. Chem. Soc. 2012, 134, 15664. [8] (a) Ito, H.; Ozaki, K.; Itami, K. Angew. Chem., Int. Ed. 2017, 56, 11144. (b) Ozaki, K.; Kawasumi, K.; Shibata, M.; Ito, H.; Itami, K. Nat. Commun. 2015, 6, 6251. (c) Yano, Y.; Ito, H.; Segawa, Y.; Itami, K. Synlett 2016, 27, 2081. (d) Kato, K.; Segawa, Y.; Itami, K. Can. J. Chem. 2017, 95, 329. (e) Ozaki, K.; Matsuoka, W.; Ito, H.; Itami K. Org. Lett. 2017, 19, 1930. (f) Ozaki, K.; Murai, K.; Matsuoka, W.; Kawasumi, K.; Ito, H.; Itami K. Angew. Chem., Int. Ed. 2017, 56, 1361. (g) Matsuoka, W.; Ito, H.; Itami K. Angew. Chem., Int. Ed. 2017, 56. 12224. [9] (a) Pozdnyakovich, Y. V. Russ. J. Org. Chem.. 1988, 24, 1076. (b) Pianka, M. J. Chem. Soc. C 1967, 2618. [10] (a) Kazeminejad, N.; Munzel, D.; Gamer, M. T.; Roesky, P. W. Chem. Commun. 2017, 53, 1060. (b) Ashe, A. J., III; Kampf, J. W.; Savla, P. M. Hetroatom Chem. 1994, 5, 113. (c) Grimme, S.; MückLichtenfeld, C.; Erker G.; Kehr, G.; Wang H.; Beckers, H.; Willner, H. Angew. Chem., Int. Ed. 2009, 48, 2592. [11] (a) Linstead, R. P.; Doering, W. E. J. Am. Chem. Soc. 1942, 64, 1991. (b) Plietker, B.; Niggemann, M.; Pollrich, A. Org. Biomole. Chem. 2004, 2, 1116. (c) Tandon, P. K.; Baboo, R.; Singh, A. K.; Gayatri Appl. Organometal. Chem. 2006 20, 20. (d) Tabatabaeian, K.; Zanjanchi, M. A.; Mahmoodi, N. O. RSC Adv. 2015, 5, 101013. [12] Related theoretical studies on palladium-catalyzed C–H activation/arylation of unactivated arenes: (a) Balcells, D.; Eisenstein, O. Chem. Rev. 2010, 110, 749. (b) Xing, Y.-M.; Zhang, L.; Fang, D.-C. Organometallics 2015, 34, 770. (c) Canty, A. J.; Ariafard, A.; Yates, B.

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F.; Sanford, M. S. Organometallics 2015, 34, 1085. (d) Yang, Y.-F.; Cheng, G.-J.; Liu, P.; Leow, D.; Sun, T.-Y.; Chen, P.; Zhang, X.; Yu, J.Q.; Wu, Y.-D.; Houk, K. N. J. Am. Chem. Soc. 2014, 136, 344. (e) Bishajit, B.; Sugimoto, M.; Sakaki, S. Organometallics 2000, 19, 3895. (f) Dang, Y.; Qu, S.; Nelson, J. W.; Pham, H. D.; Wang, Z.-X.; Wang, X. J. Am. Chem. Soc. 2015, 137, 2006. [13] Hohenberg, P.; Kohn, W. Phys. Rev. 1964, 136, B864. [14] (a) Head-Gordon, M.; Pople, J. A.; Frisch, M. J. Chem. Phys. Lett. 1988, 153, 503. (b) Gerenkamp, M.; Grimme, S. Chem. Phys. Lett. 2004, 392, 229. [15] 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. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; 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, Ö.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, Revision E.01, Gaussian, Inc., Wallingford CT, 2009. [16] (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648. (b) Perdew, J. P.; Chevary, J. A.; Vosko, S. H.; Jackson, K. A.; Pederson, M. R.; Singh, D. J.; Fiolhais, C. Phys. Rev. B, 1992, 46, 6671. (c) Perdew, J. P.; Chevary, J. A. ; Vosko, S. H.; Jackson, K. A.; Pederson, M. R. ; Singh, D. J.; Fiolhais, C. Phys. Rev. B 1993, 48, 4978. [17] Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 270. [18] Gonzalez, C.; Schlegel, H. B. J. Chem. Phys. 1989, 90, 2154. [19] (a) Cances, E.; Mennunci, B.; Tomasi, J. J. Chem. Phys. 1997, 107, 3032. (b) Cossi, M.; Barone, V.; Cammi, R.; Tomasi, J. Chem. Phys. Lett. 1996, 255, 327. (c) Barone, V.; Cossi, M.; Tomasi, J. J. Comput. Chem. 1998, 19, 404. [20] Fuentealba, P.; Preuss, H.; Stoll, H.; Von Szentpály, L. Chem. Phys. Lett. 1982, 89, 418. [21] Prepared using CYLView: Legault, C. Y. CYLView, 1.0b; Université de Sherbrooke: Quebec, 2009; http://www.cylview.org. [22] (a) Davies, D. L.; Donald, S. M. ; Macgregor, S. A. J. Am. Chem. Soc. 2005, 127, 13754. (b) Lafrance, M.; Rowley, C. N.; Woo, T. K.; Fagnou, K. J. Am. Chem. Soc. 2006, 128, 8754. (c) Gorelsky, S. I.; Lapointe, D.; Fagnou, K. J. Am. Chem. Soc. 2008, 130, 10848. [23] (a) Azzena, U.; Melloni, G.; Pisano, L. J. Chem. Soc., Perkin Trans. 1 1995, 261. (b) Tunge, J. A.; Foresee, L. N. Organometallics 2005, 24, 6440. (c) Clark, G. R.; Johns, P. M.; Roper, W. R.; Söhnel, T.; Wright, L. J. Organometallics 2011, 30, 129. [24] Giese, M.; Albrecht, M.; Rissanen, K. Chem. Rev. 2015, 115, 8867. [25] (a) Hiyama, T. Organosilicon Compounds in Cross Coupling Reactions, in Metal-Catalyzed Cross-Coupling Reactions; Diederich, F.; Stang, P. J., Ed.; Wiley-VCH: Weinheim, 1998, pp. 421–453. (b) Hiyama,T.; Shirakawa, E. Top. Curr. Chem. 2002, 219, 61. (c) Y. Nakao, Y.; Hiyama, T. Chem. Soc. Rev. 2011, 40, 4893. (d) Komiyama, T.; Minami, Y.; Hiyama, T. ACS Catal. 2017, 7, 631. [26] Shibata, M; Ito, H.; Itami, K. Chem. Lett. 2017, 46, 1701. [27] (a) Ball, L. T.; Lloyd-Jones, G. C.; Russell, C. A. Science 2012, 337, 1644. (b) Ball, L. T.; Lloyd-Jones, G. C.; Russell, C. A. J. Am. Chem. Soc. 2014, 136, 254. (c) Corrie, T. J. ; Ball, L. T.; Russell, C. A.; LloydJones, G. C. J. Am. Chem. Soc. 2017, 139, 245. (d) Hata, K.; Ito, H.; Segawa, Y.; Itami, K. Beilstein J. Org. Chem. 2015, 11, 2737. [28] Brasse, M.; Cámpora, J.; Davies, M.; Teuma, E.; Palma, P.; Álvarez, E.; Sanz, E.; Reyes, M. L. Adv. Synth. Catal. 2007, 349, 2111.

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[29] Carpenter, J. E.; Weinhold, F. J. Mol. Struct. Theochem, 1988, 169, 41. [30] (a) Yamamoto, Y.; Ohno, T.; Itoh, K. Angew. Chem., Int. Ed. 2002, 41, 3662. (b) Yamamoto, Y.; Kuwabara, S.; Matsuo, S.; Ohno, T.; Nishiyama, H.; Itoh, K. Organometallics 2004, 23, 3898. See SI for

the detailed discussions on possible Pd(IV)-spirocycle by the reaction of Pd(0), o-chloranil and phenanthrene:

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