Effects of PAr3 Ligands on Direct Arylation of

Oct 8, 2014 - ABSTRACT: The palladium-catalyzed direct arylation of hetero- arenes with aryl halides has attracted considerable attention as a...
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Effects of PAr3 Ligands on Direct Arylation of Heteroarenes with Isolated [Pd(2,6-Me2C6H3)(μ‑O2CMe)(PAr3)]4 Complexes Masayuki Wakioka,† Yuki Nakamura,† Yoshihiro Hihara,† Fumiyuki Ozawa,*,†,‡ and Shigeyoshi Sakaki§ †

International Research Center for Elements Science (IRCELS), Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan ‡ JST ACT-C, Uji, Kyoto 611-0011, Japan § Fukui Institute for Fundamental Chemistry, Kyoto University, Sakyo-ku, Kyoto 610-8103, Japan S Supporting Information *

ABSTRACT: The palladium-catalyzed direct arylation of heteroarenes with aryl halides has attracted considerable attention as a simple cross-coupling process that does not need organometallic reagents. It is generally accepted that this catalysis proceeds via an arylpalladium carboxylate intermediate, which produces direct arylation products via the sequence of three elementary processes: (a) substrate coordination, (b) C−H bond cleavage, and (c) C−C reductive elimination. This paper describes kinetic investigations into the effects of four kinds of PAr3 ligands on direct arylation using the isolated complexes [Pd(2,6-Me2C6H3)(μO2CMe)(PAr3)]4 (1: Ar = Ph (a), 4-MeOC6H4 (b), 4-FC6H4 (c), 4-F3CC6H4 (d)). While 1a−d have a tetrameric structure in the solid state, they are in rapid equilibrium with the monomeric species [Pd(2,6-Me2C6H3)(O2CMe-κ2O)(PAr3)] in solution. Complexes 1a−d react with 2-methylthiophene (3) and benzothiazole (4) in THF at 65 °C to give the corresponding direct arylation products in high yields. The reactivity order of 1a−d is reversed according to the heteroarene substrates; the reaction with 3 is accelerated by electron-deficient PAr3 (1b < 1a < 1c < 1d), whereas that with 4 is facilitated by electron-donating PAr3 (1d < 1c < 1a < 1b). The reasons for the opposite ligand effects are examined by DFT calculations using the model compounds [PdPh(O2CMe-κ2O)(PAr3)]. Unlike the general assumption, the C−H bond cleavage process is relatively insensitive to electronic properties of PAr3. Instead, the reaction of 3 invokes the C−C reductive elimination process as the rate-determining step, and the activation energy is significantly reduced by electron-deficient PAr3. On the other hand, although the ratedetermining step for 4 is assigned to the C−H bond cleavage process, the transition state is little affected by PAr3 ligands. In this case, electron-donating PAr3 destabilizes the precursor complex for C−H bond cleavage, thereby reducing the activation barrier for the rate-determining step.

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in high yields.6 The 2,6-dimethylphenyl complex 1a given in Scheme 1 is particularly reactive, serving as an excellent model of catalytic intermediates, where half of 1a is converted to the direct arylation product (Ar1Ar2), Pd-black, and acetic acid,

INTRODUCTION The palladium-catalyzed dehydrohalogenative coupling of heteroarenes with aryl halides (so-called direct arylation) has emerged as a simple cross-coupling process that does not need prepreparation of organometallic reagents.1 It is recognized that direct arylation is advantageous over conventional crosscoupling reactions in terms of fewer reaction steps and higher functional group tolerance. This catalysis involves C−H bond cleavage of heteroarenes, instead of transmetalation, to give diarylpalladium intermediates, which afford cross-coupling products via reductive elimination. Recent theoretical studies have revealed that the C−H bond cleavage proceeds via a concerted process involving an aryl carboxylate intermediate of the formula [Pd(Ar)(O2CR-κ2O)(L)] (A).2,3 While this mechanism is widely accepted, isolated models of A that sufficiently reactive toward heteroarenes have been scarcely documented.4,5 Recently, we have found that the isolated arylpalladium acetate complexes [Pd(Ar1)(μ-O2CMe)(PPh3)]n (Ar1 = Ph, 2MeC6H4, 2,6-Me2C6H3) successfully react with a series of heteroarenes (Ar2H) to give direct arylation products (Ar1Ar2) © XXXX American Chemical Society

Scheme 1. Direct Arylation of Heteroarenes (Ar2H) with Arylpalladium Acetate Complexes (1a−d)

Received: September 6, 2014

A

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whereas the other half is converted to the bis-PPh3 complex 2a. The reactions proceed cleanly under mild conditions, and we could elucidate mechanistic details of the reactions with 2methylthiophene (3) and benzothiazole (4), using kinetic experiments and DFT calculations. Substrates 3 and 4 follow essentially the same reaction pathway as illustrated in Scheme 2. Complex 1a has a

Scheme 3. Synthetic Routes to 1a−d

Scheme 2. Direct Arylation Pathway of Heteroarenes (Ar2H) with 1a

OH precursors with p-substituted PAr3 ligands could not be isolated, the μ-OH complexes were once converted to μ-I complexes, and then to the desired complexes by anionic ligand exchange with silver acetate. Complexes 1b−d were isolated as crystalline solids and identified by IR and NMR spectroscopy and elemental analysis. The structure of 1c was also examined by X-ray diffraction analysis. Figure 1a shows the crystal structure of 1c, which is a tetramer of [Pd(2,6-Me2C6H4)(μ-O2CMe){P(C6H4F)3}] units.

tetrameric structure in the solid state, but forms an equilibrium mixture with the monomeric complex [Pd(2,6-Me2C6H4)(O2CMe-κ2O)(PPh3)] (5a) in solution. Coordination of 5a with Ar2H, followed by C−H bond cleavage on 6a, forms the diaryl complex 7a, which reductively eliminates Ar1Ar2. The 12e species [Pd(PPh3)] thus generated decomposes to release free PPh3, which combines with 1a to form 2a. While 3 and 4 follow the same reaction pathway, their kinetic profiles are significantly different from each other. The reaction of 3 obeys simple second-order kinetics and exhibits no deuterium kinetic isotope effect (kH/kD = 1.0), due to the occurrence of rate-determining reductive elimination from 7a. On the other hand, the reaction of 4 displays a saturation kinetics behavior with respect to the concentration of 4, due to the formation of the relatively stable intermediate 6a{4} through the nitrogen coordination (see Scheme 2). In this case, the subsequent C−H bond cleavage becomes a high-energy process, serving as the rate-determining step (kH/kD = 4.2). In this study, we examined the ligand effects of p-substituted PPh3 derivatives (PAr3) on direct arylation of 3 and 4, using isolated complexes 1a−d in Scheme 1. Information about the ligand effects on individual elementary processes in catalytic cycles is of particular importance for the development of highly active catalysts.7,8 We found that the direct arylation reactions of 3 and 4 exhibit the reverse dependence on electronic properties of PAr3. The reaction of 3 is accelerated by electrondeficient ligands, whereas that of 4 is facilitated by electrondonating ligands. The reasons for the opposite ligand effects are investigated by DFT calculations.

Figure 1. (a) Molecular structure of 1c·6THF with 50% probability ellipsoids. Hydrogen atoms and crystal solvents (THF) are omitted for clarity. Selected bond distances (Å) and angles (deg): Pd1−C5 2.001(3), Pd1−P1 2.2271(9), Pd1−O1 2.109(2), Pd1−O3 2.136(2), Pd2−O2 2.135(2), O1−C1 1.263(4), C1−O2 1.268(4), C1−C2 1.496(5), C5−Pd1−O3 176.38(12), O1−Pd1−P1 168.43(7), C1− O1−Pd1 129.5(2), C1−O2−Pd2 123.0(2), O1−C1−O2 122.0(3), O1−C1−C2 120.5(3), O2−C1−C2 117.4(3). (b) Molecular structure of [Pd(2-MeC6H4)(μ-O2CMe)(PPh3)]2.6a

We reported a similar structure for 1a.6a The four Pd atoms are linked with μ-O2CMe ligands in a syn,anti-configuration. This geometry is quite different from the anti,anti-configuration found in dimeric analogues such as [PdPh(μ-O2CMe)(PPh3)]29 and [Pd(2-MeC6H4)(μ-O2CMe)(PPh3)]2.6a As seen from the crystal structure of [Pd(2-MeC6H4)(μ-O2CMe)(PPh3)]2 in Figure 1b, the dimeric complex has a folded structure of two square-planar units bridged by μ-O2CMe ligands in an anti,anti-configuration. The 2-MeC6H4 ligand on one of the Pd centers is located close to the PPh3 ligand on the other Pd center, and they undergo steric repulsion from each other. It is likely that 1a and 1c having bulky 2,6-Me2C6H3 ligands are difficult to form this dimeric structure, and instead

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RESULTS AND DISCUSSION Synthesis and Structures of Arylpalladium Acetate Complexes. The synthetic routes to 1a−d are given in Scheme 3. The PPh3 complex 1a6a was prepared from [Pd(2,6Me2C6H4)(μ-OH)(PPh3)]2, referring to the synthetic procedures for related compounds.9 On the other hand, since the μB

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of 2-methylthiophene (3) is facilitated by electron-deficient PAr3 (1b < 1a < 1c < 1d). On the contrary, electron-donating PAr3 accelerates the reaction of benzothiazole (4) (1d < 1c < 1a < 1b). In both cases, the observed rate constants showed a Hammett correlation with the σp values of p-substituents on PAr3 ligands: ρ = +0.76 (r = 0.92) for 3; ρ = −0.56 (r = 0.94) for 4 (Figure 2).

constitute the tetramers. As seen from Figure 1a, the squareplanar units connected by μ-O2CMe ligands in a syn,anticonfiguration are successfully arranged for avoiding the steric repulsion from each other. Table 1 lists the IR data of 1a−d in a solid (KBr) and a solution (CH2Cl2). The solid samples show the νCO2asym and Table 1. IR Data for 1a−d in KBr and CH2Cl2 (cm−1) solution (CH2Cl2)a complex 1b 1a 1c 1d

solid (KBr)a 1551, 1547, 1547, 1544,

1412 1412 1413 1416

bridging (1) 1552, 1551, 1552, 1550,

1412 1413 1415 1417

ratiob

bidentate (5) 1519, 1516, 1511, 1507,

1:5

1449 1450 1450 1451

50:50 57:43 68:32 84:16

Wavenumbers of νCO2asym and νCO2sym absorptions in KBr and CH2Cl2 ([Pd] = 20 mM). bAbsorbance ratios of the νCO2asym bands of bridging (1) and bidentate (5) complexes. a

νCO2sym bands at almost the same wavenumbers each other. Moreover, the wavenumbers for νCO2asym bands (1544−1551 cm−1) are clearly lower than that for the μ-O2CMe ligand in an anti,anti-configuration (1578−1580 cm−1).6a Thus, we concluded that 1b and 1d are tetramers in the solid state, similarly to 1a and 1c. On the other hand, 1a−d dissolved in CH2Cl2 exhibit two sets of νCO2 bands, respectively. In the previous study, we analyzed the solution IR spectrum of 1a in detail using DFT calculations and assigned the absorptions at 1551 and 1413 cm−1 to the bridging acetate ligand in 1a, and those at 1516 and 1450 cm−1 to the bidentate acetate ligand in [Pd(2-MeC6H4)(O2CMe-κ2O)(PPh3)] (5a). We also confirmed that 1a and 5a are in rapid equilibrium in an NMR time scale at room temperature.10 It is seen from Table 1 that 1b−d exhibit the νCO2 bands at almost the same wavenumbers as 1a, showing the occurrence of a dissociation equilibrium between 1 and 5 as well. With consideration of the absorbance ratios of νCO2asym bands, the equilibrium tends to shift to the side of 5 in the order 1d < 1c < 1a < 1b. This order is in accord with the increasing electrondonating ability of PAr3 ligands. Comparison of Reactivities of Arylpalladium Acetate Complexes toward Direct Arylation of 3 and 4. Complexes 1a−d were subjected to the reactions with 3 and 4 in THF at 65 °C in the presence of i-Pr2EtN,11 and the reaction progress was followed by 31P{1H} NMR spectroscopy. The reactions obeyed pseudo-first-order kinetics over 3−4 halflives. Table 2 lists the observed rate constants.12 The reaction

Figure 2. Plots of the log (kY/kH) values against the Hammett parameters σp (Y) for direct arylation of 3 (blue) and 4 (green) with 1a−d having p-substituted PAr3 ligands (Ar = 4-YC6H4). The data are taken from Table 2.

Next, we examined the effects of PAr3 ligands on direct arylation of 2-methylthiophene (3) by DFT calculations. Although the tetramers 1a−d are dissociated to the monomeric species 5a−d prior to the reaction with 3, the dissociation equilibrium indicated from the absorbance ratios in Table 1 (1d < 1c < 1a < 1b) is clearly the opposite of the reactivity order found in Table 2 (1b < 1a < 1c < 1d). Thus, we compared free energy changes associated with direct arylation using the model compounds [PdPh(O2CMe-κ2O)(PAr3)] (5′) having the four kinds of PAr3 ligands. All geometries were optimized with the B3LYP functional. The energy changes were evaluated with the M06-2X functional and triple-ζ-quality basis sets, where solvent effects were included using the polarizable continuum model (PCM) for THF. Table 3 summarizes the results. It is noted that the energy variations in the transition states of C−H bond cleavage (TSCH) are small. This is probably because this process involves a relatively early transition state. Actually, the Pd−C(thenyl) distance of TSCH (2.16−2.18 Å) was significantly longer than that of the diaryl intermediate 7′{3} (2.05 Å). On the other hand, the C−C reductive elimination via TSRE is clearly facilitated by electron-deficient ligands, as experimentally demonstrated recently.13 In this case, the C−C reductive elimination is assigned to the rate-determining step, because TSRE is higher in energy than TSCH.12 Moreover, the energy difference between TS RE and the reactants (3 + 5′) corresponds to the Gibbs activation energy (ΔG°⧧) for the whole process, because no intermediate is more stable than the reactants. The decreasing order of the ΔG°⧧ values is consistent with the increasing order of the observed rate constants (kobsd) in Table 2 (1b < 1a < 1c < 1d). Similarly, the effects of PAr3 ligands were examined for benzothiazole (4) by DFT calculations. The results are given in Table 4. The ligand effects on the transition states of C−H

Table 2. Pseudo-First-Order Rate Constants (sec−1) for Direct Arylation of 3 and 4 with 1a−da 3 complex

σp (Y)

1b 1a 1c 1d

−0.27 (MeO) 0.00 (H) 0.06 (F) 0.54 (CF3)

b

4

10 kobsd

10 kobsd

kH/kDc

0.98(2) 2.41(2) 2.90(9) 4.5(1)

1.43(1) 1.05(1) 0.685(4) 0.499(7)

4.4 4.2 4.3 2.8

4

4

All reactions were run in THF at 65.0 °C in the presence of i-Pr2EtN (0.182 M). Initial concentrations: [1]0 = 9.1 mM, [3 or 4]0 = 0.73 M. b Hammett parameters for para-substituents (Y) of PAr3 ligands. c Kinetic isotope effects for 2-deuteriobenzothiazole (4-d). a

C

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Table 3. Gibbs Energy Changes (ΔG°, kcal/mol) in Direct Arylation of 2-Methylthiophene (3) with [PdPh(O2CMeκ2O)(PAr3)] (5′) Evaluated by DFT Calculations (M06-2X)a

a

The PCM method was employed to incorporate solvation effect of THF.

Table 4. Gibbs Energy Changes (ΔG°, kcal/mol) in Direct Arylation of Benzothiazole (4) with [PdPh(O2CMe-κ2O)(PAr3)] (5′) Evaluated by DFT Calculations (M06-2X)a

a

The PCM method was employed to incorporate solvation effect of THF.

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CONCLUSION We have succeeded in systematic investigations into the effects of PAr3 ligands on direct arylation, using the well-defined models of catalytic intermediates (5 and 5′). The direct arylation of 2-methylthiophene (3) is accelerated by electrondeficient ligands, which facilitate most remarkably the C−C reductive elimination from the diaryl intermediate 7′{3}. On the contrary, the direct arylation of benzothiazole (4) is accelerated by electron-donating ligands, because the precursor complex 6′{4} for the C−H bond cleavage is destabilized by electrondonating ligands, and thereby the activation barrier for the C− H bond cleavage process is reduced. It is worth noting that the energy variations in the transition states of C−H bond cleavage are relatively small in both cases. Thus far, the mechanistic discussions on direct arylation have been focused on the C−H bond cleavage process.2,15 However, it is reasonable that the C−H bond cleavage is not always a high energy process, and the rate of direct arylation is often controlled by multiple factors associated with other elementary processes, including substrate coordination and C−C reductive elimination.

bond cleavage (TSCH) and C−C reductive elimination (TSRE) are insignificant;14 in contrast, the stability of 6′{4} and 7′{4} changes to a considerable extent. In this case, the stabilization of 6′{4} should be crucial for the reaction rate, because this intermediate is located lower in energy than the reactants (5′ + 4). The Gibbs activation energy (ΔG°⧧) for the C−H bond cleavage process is defined as the energy difference between 6′{4} and TSCH; i.e., ΔG°⧧ (kcal/mol) = 27.84 (P(4MeOC6H4)3), 28.16 (PPh3), 29.64 (P(4-FC6H4)3), and 29.90 (P(4-CF3C6H4)3). Since the ΔG°⧧ values are much larger than those for the C−C reductive elimination, the C−H bond cleavage is assigned to the rate-determining step. This computational observation is consistent with the relatively large deuterium kinetic isotope effects (kH/kD = 2.8−4.4) in Table 2. The increasing order of the ΔG°⧧ values is in good agreement with the decreasing reactivity order of 1a−d (1b > 1a > 1c > 1d). It should be noted that this increasing order of the activation energy is mainly due to the increasing order of the stabilization energy of benzothiazole coordination. In other words, the strong coordinate bond of benzothiazole leads to the formation of stable 6′{4}, and thereby the C−H bond cleavage serves as the rate-determining step. In the reaction of 2methylthiophene (3), the coordinate bond is not very strong, and hence the C−C reductive elimination becomes ratedetermining.

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EXPERIMENTAL SECTION

General Considerations. All manipulations were carried out under a nitrogen atmosphere using standard Schlenk techniques. Nitrogen gas was dried by passing through P2O5. NMR spectra were recorded on a 400 spectrometer (1H NMR 400.13 MHz, 13C NMR 100.62 MHz, 19F NMR 376.46 MHz, and 31P NMR 161.97 MHz). Chemical shifts are reported in δ (ppm), referenced to 1H (residual) D

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and 13C signals of deuterated solvents as internal standards or to the 19 F signal of C6F6 (δ −163.0) and the 31P signal of 85% H3PO4 (δ 0.0) as external standards. Elemental analysis was performed by ICR Analytical Laboratory, Kyoto University. IR spectra were recorded on an FT/IR spectrometer in a KBr pellet or a NaCl cell (path length = 1 mm). Analytical HPLC was performed with a refractive index detector and an ODS column (CH3CN/H2O = 2/1 v/v). CH2Cl2, Et2O, and pentane (dehydrated) were used as received. THF was dried over Na/Ph2CO, distilled, and stored over activated MS4A. CD2Cl2 was dried over CaH2, distilled, and stored over activated MS4A. 2-Methylthiophene (3), benzothiazole (4), and iPr2EtN were passed through a short column of activated alumina and distilled. [Pd(2,6-Me2C6H3)(μ-O2CMe)(PPh3)]4 (1a),6a 2-(2,6dimethylphenyl)-5-ethylthiophene, 6b 2-(2,6-dimethylphenyl)benzothiazole,16 and 2-deuteriobenzothiazole (4-d)17 were prepared according to the literature. The other chemicals were obtained from commercial suppliers and used without purification. Synthesis of [Pd(2,6-Me2C6H3)(μ-O2CMe)(PAr3)]4 (1b−d). Synthesis of [Pd(2,6-Me2C6H3)(μ-I)(PAr3)]2. These complexes were prepared according to the synthetic procedure for [PdPh(μI)(PPh3)]2,9 and isolated in 84% (Ar = 4-MeOC6H4), 56% (4FC6H4), and 60% (4-CF3C6H4) yields, respectively. [Ar = 4-MeOC6H4]: 1H NMR (CD2Cl2): δ 2.47 (s, 3.6H), 2.48 (s, 8.4H), 3.78 (s, 12.6H), 3.80 (s, 5.4H), 6.43 (d, J = 6.7 Hz, 1.2H), 6.45 (d, J = 7.3 Hz, 2.8H), 6.56 (t, J = 6.7 Hz, 0.6H), 6.58 (t, J = 7.3 Hz, 1.4H), 6.70−6.80 (m, 12H), 7.18−7.40 (m, 12H). 31P{1H} NMR (CD2Cl2): 22.8 (s, 0.6P), 23.4 (s, 1.4P). Anal. Calcd for C58H60I2O6P2Pd2: C, 50.42; H, 4.38. Found: C, 50.16; H, 4.37. [Ar = 4-FC6H4]: NMR analysis was infeasible due to low solubility. Anal. Calcd for C52H42F6I2P2Pd2: C, 47.70; H, 3.23. Found: C, 47.61; H, 3.21. [Ar = 4-CF3C6H4]: 1H NMR: δ 2.45 (s, 8.4H), 2.46 (s, 3.6H), 6.44 (d, J = 7.0 Hz, 1.2H), 6.46 (d, J = 7.2 Hz, 2.8H), 6.58 (t, J = 7.0 Hz, 0.6H), 6.60 (t, JHH = 7.2 Hz, 1.4H), 7.50−7.60 (m, 24H). 31P{1H} NMR (CD2Cl2): 24.1 (s, 0.6P), 25.8 (s, 1.4P). 19F NMR (CD2Cl2): −63.6 (s). Anal. Calcd for C58H42F18I2P2Pd2: C, 43.28; H, 2.63. Found: C, 43.41; H, 2.54. Synthesis of 1b−d. A typical procedure is reported for 1b. To a suspension of [Pd(2,6-Me2C6H3)(μ-I){P(4-MeOC6H4)3}]2 (345 mg, 0.50 mmol) in THF (15 mL) was added AgO2CMe (83.5 mg, 0.50 mmol) at 0 °C. The mixture was stirred at this temperature for 5 h and evaporated under reduced pressure. The residue was extracted three times with a mixed solvent of THF (1 mL) and pentane (5 mL), and the combined extract was filtered through a Celite pad. The filtrate was concentrated to dryness under reduced pressure. The residue was washed with Et2O (4 × 5 mL) and dried under vacuum, affording 1b as a white solid (272 mg, 87%). Complexes 1c and 1d were similarly prepared. For the extraction of 1d, a mixed solvent of Et2O (1 mL) and pentane (5 mL) was used instead of THF and pentane. [1b]: 1H NMR (CD2Cl2): δ 1.87 (br, 12H), 2.47 (s, 24H), 3.78 (s, 36H), 6.47 (d, J = 7.0 Hz, 8H), 6.67 (t, J = 7.0 Hz, 4H), 6.77 (d, J = 7.9 Hz, 24H), 7.20−7.33 (m, 24H). 31P{1H} NMR (CD2Cl2): 26.9 (br). Anal. Calcd for C124H132O20P4Pd4: C, 59.77; H, 5.34. Found: C, 59.94; H, 5.62. [1c]: 70% yield. 1H NMR (CD2Cl2): δ 1.92 (br, 12H), 2.43 (br, 24H), 6.48 (d, J = 7.0 Hz, 8H), 6.70 (t, J = 7.0 Hz, 4H), 6.92−7.12 (m, 24H), 7.30−7.45 (br, 24H). 31P{1H} NMR (CD2Cl2): 29.4 (br). 19F NMR (CD2Cl2): −108.8 (br). Anal. Calcd for C112H96F12O8P4Pd4: C, 57.30; H, 4.12. Found: C, 57.25; H, 4.15. [1d]: 65% yield. 1H NMR (CD2Cl2): δ 1.90 (br, 12H), 2.44 (br, 24H), 6.45 (d, J = 7.0 Hz, 8H), 6.68 (t, J = 7.0 Hz, 4H), 7.55 (br, 48H). 31P{1H} NMR (CD2Cl2): 31.4 (br). 19F NMR (CD2Cl2): −63.8 (br). Anal. Calcd for C124H96F36O8P4Pd4: C, 50.57; H, 3.28. Found: C, 50.26; H, 3.23. Kinetic Study. A typical procedure is as follows. Complex 1a (8.5 mg, 4.0 μmol) and C6Me6 (3.2 mg, 20 μmol; an internal standard for HPLC analysis) were placed in an NMR sample tube equipped with a Teflon screw cock (J. Young). THF (0.40 mL), i-Pr2EtN (10 mg, 80 μmol), and 2-methylthiophene (3; 31 μL, 0.32 mmol) were added, and the total volume of solution was adjusted to 0.44 mL by adding

THF at room temperature. The mixture was degassed three-times by freeze−pump−thaw cycles and heated at 40 °C to dissolve 1a. A sealed capillary containing a solution of PPh2(C6H4-2-OMe) (40 mM) in toluene-d8 was loaded into the NMR sample tube as an internal standard. The system was degassed three times by freeze−pump−thaw cycles again and placed in an NMR sample probe controlled to 65.0 ± 0.1 °C. The reaction progress was monitored at intervals by 31P{1H} NMR spectroscopy using marker signals at δ 31.0 (5a + 1a), 20.9 (2a), and −13.9 (PPh2(C6H4-2-OMe)). After the signal at δ 31.0 disappeared, the amount of direct arylation product was analyzed by HPLC, showing quantitative formation of 5-phenyl-2-methylthiophene. The reactions of 1b−d with 3 and 1a−d with 4 were similarly examined using the following marker signals: [1a + 4] δ 28.5 (6a{4}), 20.9 (2a). [1b + 3] δ 27.8 (5b + 1b), 17.5 (2b). [1b + 4] δ 28.7 (6b{4}), 17.5 (2b). [1c + 3] δ 28.8 (5c + 1c), 18.9 (2c). [1c + 4] δ 26.3 (6c{4}), 18.9 (2c). [1d + 3] δ 31.6 (5d + 1d), 21.3 (2d). [1d + 4] δ 31.5 (6d{4}), 21.3 (2d). X-ray Structural Analysis of 1c. Single crystals of 1c suitable for X-ray diffraction study were grown by slow diffusion of pentane into a THF solution at −20 °C. The intensity data were collected on a Rigaku Saturn CCD diffractometer with graphite monochromated Mo Kα radiation (λ = 0.71070 Å) at 173 K. The data were corrected for Lorentz and polarization effects and for absorption (numerical). The structures were solved by direct methods (SHELXS-97)18 and refined by least-squares calculations on F2 for all reflections (SHELXL-97)19 using Yadokari-XG 2009 software.20 Non-hydrogen atoms, except for the carbon and oxygen atoms of crystal THF, were refined anisotropically. Hydrogen atoms were placed at calculated positions using AFIX instructions. The crystal data and the summary of data collection and refinement are summarized in Table S1 (Supporting Information). DFT Calculations. All calculations were carried out with the Gaussian 09 program package.21 Geometry optimization was performed by the DFT method without any symmetry constraints, where the B3LYP functional was used.22 The Pd atom was described with the LANL2DZ basis set including a double-ζ basis set and effective core potentials (ECPs) proposed by Hay and Wadt.23 The 631G(d) basis sets were applied to other atoms.24 The Cartesian coordinates of optimized structures are reported in Table S2 (Supporting Information). Each equilibrium geometry exhibited no imaginary frequency, and each transition state exhibited one imaginary frequency (see Figure S1, Supporting Information). IRC calculations25 were carried out to confirm that the transition state connects the reactant and product. Energy change was evaluated by the DFT method with the M06-2X functional26 using the above-optimized geometries. For these calculations, the Pd atom was described with a triple-ζ basis set and ECPs proposed by the Stuttgart−Dresden−Bonn group.27 Two f-polarization functions were also added for Pd (ζf = 0.621 and 2.203).28 The 6-311G(d) basis sets were employed for other atoms, where one set of anion function was added to the O atom of the acetate ligand.29 The solvent effect (THF) was taken into consideration using the polarized continuum model (PCM) at 298.15 K.30 The Gibbs free energy in solution was employed for discussion, where the translational entropy was evaluated with the method developed by Whitesides et al.31

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ASSOCIATED CONTENT

* Supporting Information S

Crystallographic and computational details, and crystallographic data (CIF). This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] (F.O.). Notes

The authors declare no competing financial interest. E

dx.doi.org/10.1021/om500922n | Organometallics XXXX, XXX, XXX−XXX

Organometallics

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Article

(14) The Pd−C distance of TSCH (2.26−2.24 Å) was much longer than that of 7′{4} (2.05−2.04 Å). (15) Previous theoretical studies have revealed the occurrence of rate-determining C−C reductive elimination in direct arylation: (a) Ishikawa, A.; Nakao, Y.; Sato, H.; Sakaki, S. Dalton Trans. 2010, 39, 3279. (b) Guihaumé, J.; Clot, E.; Eisenstein, O.; Perutz, R. N. Dalton Trans. 2010, 39, 10510. (16) Yamamoto, T.; Muto, K.; Komiyama, M.; Canivet, J.; Yamaguchi, J.; Itami, K. Chem.Eur. J. 2011, 17, 10113. (17) Join, B.; Yamamoto, T.; Itami, K. Angew. Chem., Int. Ed. 2009, 48, 3644. (18) Sheldrick, G. M. SHELXS-97; University of Gö ttingen: Germany, 1997. (19) Sheldrick, G. M. SHELXL-97; University of Gö ttingen: Germany, 1997. (20) Kabuto, C.; Akine, S.; Kwon, E. J. Cryst. Soc. Jpn. 2009, 51, 218. (21) 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 B.01; Gaussian, Inc.: Wallingford, CT, 2010. (22) (a) Becke, A. D. Phys. Rev. A 1988, 38, 3098. (b) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785. (c) Becke, A. D. J. Chem. Phys. 1993, 98, 5648. (23) Wadt, W. R.; Hay, P. J. J. Chem. Phys. 1985, 82, 299. (24) Francl, M. M.; Pietro, W. J.; Hehre, W. J.; Binkley, J. S.; Gordon, M. S.; DeFrees, D. J.; Pople, J. A. J. Chem. Phys. 1982, 77, 3654. (25) (a) Gonzalez, C.; Schlegel, H. B. J. Chem. Phys. 1989, 90, 2154. (b) Gonzalez, C.; Schlegel, H. B. J. Phys. Chem. 1990, 94, 5523. (26) Zhao, Y.; Truhlar, D. G. Theor. Chem. Acc. 2008, 120, 215. (27) Kuechle, W.; Dolg, M.; Stoll, H.; Preuss, H. J. Chem. Phys. 1994, 100, 7535. (28) Martin, J. M. L.; Sundermann, A. J. Chem. Phys. 2001, 114, 3408. (29) (a) Krishnan, R.; Binkley, J. S.; Seeger, R.; Pople, J. A. J. Chem. Phys. 1980, 72, 650. (b) McLean, A. D.; Chandler, G. S. J. Chem. Phys. 1980, 72, 5639. (30) (a) Miertus, S.; Scrocco, E.; Tomasi, J. Chem. Phys. 1981, 55, 117. (b) Tomasi, J.; Persico, M. Chem. Rev. 1994, 94, 2027. (c) Tomasi, J.; Cammi, R. J. Comput. Chem. 1995, 16, 1449. (31) Mammen, M.; Shakhnovich, E. I.; Deutch, J. M.; Whitesides, G. M. J. Org. Chem. 1998, 63, 3821.

ACKNOWLEDGMENTS This work was supported by KAKENHI (23350042, 24750088) from the Japan Society for the Promotion of Science and the ACT-C program of Japan Science and Technology Agency.

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REFERENCES

(1) Recent reviews on catalytic direct arylation: (a) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107, 174. (b) Satoh, T.; Miura, M. Chem. Lett. 2007, 36, 200. (c) Seregin, I. V.; Gevorgyan, V. Chem. Soc. Rev. 2007, 36, 1173. (d) Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew. Chem., Int. Ed. 2009, 48, 9792. (e) Bellina, F.; Rossi, R. Tetrahedron 2009, 65, 10269. (2) Recent reviews on the mechanisms of C−H bond cleavage: (a) Boutadla, Y.; Davies, D. L.; Macgregor, S. A.; PobladorBahamonde, A. I. Dalton Trans. 2009, 5820. (b) Balcells, D.; Clot, E.; Eisenstein, O. Chem. Rev. 2010, 110, 749. (c) Lapointe, D.; Fagnou, K. Chem. Lett. 2010, 39, 1118. (d) Ackermann, L. Chem. Rev. 2011, 111, 1315. (3) Several terms including “Concerted Metalation−Deprotonation (CMD)” and “Ambiphilic Metal Ligand Activation (AMDA)” have been introduced to describe the C−H bond cleavage process promoted by a palladium carboxylate species.2 (4) (a) Sun, H.-Y.; Gorelsky, S. I.; Stuart, D. R.; Campeau, L.-C.; Fagnou, K. J. Org. Chem. 2010, 75, 8180. (b) Tan, Y.; Hartwig, J. F. J. Am. Chem. Soc. 2011, 133, 3308. (5) For related studies using isolated arylpalladium complexes, see: (a) Sugie, A.; Kobayashi, K.; Suzaki, Y.; Osakada, K.; Mori, A. Chem. Lett. 2006, 35, 1100. (b) Mori, A.; Sugie, A.; Furukawa, H.; Suzaki, Y.; Osakada, K.; Akita, M. Chem. Lett. 2008, 37, 542. (c) Sugie, A.; Furukawa, H.; Suzaki, Y.; Osakada, K.; Akita, M.; Monguchi, D. Bull. Chem. Soc. Jpn. 2009, 82, 555. (d) Tan, Y.; Barrios-Landeros, F.; Hartwig, J. F. J. Am. Chem. Soc. 2012, 134, 3783. (e) Steinmetz, M.; Ueda, K.; Grimme, S.; Yamaguchi, J.; Kirchberg, S.; Itami, K.; Studer, A. Chem.Asian J. 2012, 7, 1256. (6) (a) Wakioka, M.; Nakamura, Y.; Wang, Q.; Ozawa, F. Organometallics 2012, 31, 4810. (b) Wakioka, M.; Nakamura, Y.; Hihara, Y.; Ozawa, F.; Sakaki, S. Organometallics 2013, 32, 4423. (7) (a) Hartwig, J. F. Organotransition Metal Chemistry: From Bonding to Catalysis; University Science Book: Sausalito, CA, 2010. (b) Crabtree, R. H. The Organometallic Chemistry of the Transition Metals, 5th ed.; John Wiley and Sons: Hoboken, NJ, 2009. (c) Yamamoto, A., Kurosawa, H., Eds. Fundamentals of Molecular Catalysis; Current Methods in Inorganic Chemistry; Elsevier Science: Amsterdam, The Netherlands, 2003; Vol. 3. (8) For ligand effects on catalytic direct arylation systems, see: (a) Campeau, L.-C.; Parisien, M.; Leblanc, M.; Fagnou, K. J. Am. Chem. Soc. 2004, 126, 9186. (b) Hitce, J.; Retailleau, P.; Baudoin, O. Chem.Eur. J. 2007, 13, 792. (c) Lafrance, M.; Lapointe, D.; Fagnou, K. Tetrahedron 2008, 64, 6015. (d) René, O.; Fagnou, K. Adv. Synth. Catal. 2010, 352, 2116. (e) Théveau, L.; Verrier, C.; Lassalas, P.; Martin, T.; Dupas, G.; Querolle, O.; Van Hijfte, L.; Marsais, F.; Hoarau, C. Chem.Eur. J. 2011, 17, 14450. (f) Théveau, L.; Querolle, O.; Dupas, G.; Hoarau, C. Tetrahedron 2013, 69, 4375. (9) Grushin, V. V.; Bensimon, C.; Alper, H. Organometallics 1995, 14, 3259. (10) The 31P{1H} NMR signal of 1a in CD2Cl2 is broaden due to the occurrence of rapid interconversion with 5a in an NMR time scale.6a Similarly, 1b−d display broad signals in the 31P{1H} NMR spectra. (11) i-Pr2EtN was added to avoid side reactions caused by free acetic acid generated in the system. It was confirmed that the reaction rate is little affected by i-Pr2EtN.6a (12) Similarly to 1a,6b complexes 1b−d did not show the primary kinetic isotope effect on the reaction with 3-d: kH/kD = 0.85 (1b), 0.89 (1c), 1.0 (1d). This result is consistent with the occurrence of ratedetermining reductive elimination. (13) Korenaga, T.; Abe, K.; Ko, A.; Maenishi, R.; Sakai, T. Organometallics 2010, 29, 4025 and references cited therein. F

dx.doi.org/10.1021/om500922n | Organometallics XXXX, XXX, XXX−XXX