Factors Controlling the Reactivity of Heteroarenes in Direct Arylation

Article pubs.acs.org/Organometallics

Factors Controlling the Reactivity of Heteroarenes in Direct Arylation with Arylpalladium Acetate 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 emerged as a viable alternative to conventional cross-coupling reactions. This paper reports a detailed mechanistic study on factors controlling the reactivity of heteroarenes in direct arylation with well-defined models of the presumed intermediate [PdAr(O2CMe-κ2O)L] (1). Although recent theoretical studies have provided a reasonable description of the mechanism of C−H bond cleavage by 1, its model compounds so far tested have been evidently less reactive than that expected. We found that [PdPh(O2CMe-κ2O)(PPh3)] (1a) and [Pd(2,6-Me2C6H3)(O2CMe-κ2O)(PPh3)] (1c), generated in situ from isolated [PdPh(μ-O2CMe)(PPh3)]2 (4a) and [Pd(2,6-Me2C6H3)(μ-O2CMe)(PPh3)]4 (4c), respectively, react with a variety of heteroarenes in almost quantitative yields. The reactivity order of heteroarenes was evaluated by competitive reactions, showing that benzothiazole (8) is significantly less reactive than 2-methylthiophene (6), despite the acidity of 8 (pKa = 27) being much higher than that of 6 (pKa = 42). This reason was examined by kinetic experiments using 1c as well as DFT calculations using the model compound [PdPh(O2CMe-κ2O)(PH3)] (1d). Both heteroarenes reacted with 1 via a sequence of three elementary processes (i.e., substrate coordination, C−H bond cleavage, and C−C reductive elimination), but their energy profiles were significantly different from each other. The reaction of 6 obeyed simple second-order kinetics, and the deuterium-labeling experiments and DFT calculations indicated the occurrence of rate-determining reductive elimination. On the other hand, the reaction of 8 displayed saturation kinetics due to the occurrence of relatively stable coordination of 8 prior to C−H bond cleavage. This coordination stability enhances the activation barrier for C−H bond cleavage, thereby causing the modest reactivity of 8. Thus, although the previous mechanistic studies on direct arylation have been focused largely on the C−H bond cleavage process, not only the C−H bond cleavage but also the substrate coordination and C−C reductive elimination must be considered.

■

INTRODUCTION The palladium-catalyzed dehydrohalogenative coupling of heteroarenes with aryl halides (so-called direct arylation), which does not need prepreparation of organometallic reagents, has emerged as a viable alternative to conventional crosscoupling reactions.1 Although this catalysis should be widely applicable, its utilization for constructing functional molecules has been poorly developed until very recently.2 In 2010, we documented the first successful example of direct arylation polymerization, in which 2-bromo-3-hexylthiophene is converted to highly regioregular poly(3-hexylthiophene) with high molecular weight in quantitative yield.3,4 Thereafter, several research groups have succeeded in the synthesis of alternating copolymers of heteroarenes via direct arylation.5−9 The resulting products are π-conjugated polymers that have found wide application in optoelectronic devices such as photovoltaic cells and field-effect transistors.10 It has been pointed out that rational design of polymers with donor−acceptor combinations © 2013 American Chemical Society

of constitution units is of particular importance for gaining high device performance.10c Although such polymers have often been prepared by Migita−Stille type cross-coupling polymerization, this method uses highly toxic organotin reagents.11 The direct arylation polymerization most likely serves as a safe alternative to this method.5 To develop such a catalytic polymerization process that enables precise control of constitution units, it is crucial to gain a deep understanding of the factors governing the reactivity of each heteroarene. Scheme 1 outlines a generally accepted catalytic cycle for direct arylation, which is basically similar to that for crosscoupling reactions. A distinct difference between the two catalytic cycles exists in the conversion of arylpalladium complex 1 into diarylpalladium complex 3 (steps b and c). This process has been examined in detail by DFT calculations, Received: June 30, 2013 Published: July 12, 2013 4423

dx.doi.org/10.1021/om400636r | Organometallics 2013, 32, 4423−4430

Organometallics

Article

Scheme 1. Plausible Catalytic Cycle for Direct Arylation of Heteroarenes (Ar′H) with Aryl Halides (ArX)

Scheme 3. Reactivity Ratios of Heteroarenes in Direct Arylation with 4a in 1,4-Dioxane at 90 °C

are reactivity ratios evaluated by competitive reactions of 6 and each heteroarene (each 0.4 mmol) with 4a (0.01 mmol) in 1,4dioxane (0.5 mL) at 90 °C. It is seen that benzothiazole (8) is clearly less reactive than 2-methylthiophene (6), though 8 (pKa = 27) is much more acidic than 6 (pKa = 42).19 It is also seen that, despite their structural similarity, 5-methyl-2,2′-bithiophene (10) is more reactive than 2-methylthiophene (6). To clarify the reasons for the difference in reactivity of these heteroarenes, the reaction mechanisms of 6 and 8 were investigated in detail by kinetic experiments and DFT calculations. Kinetic Study on Direct Arylation of 2-Methylthiophene (6). In a previous study,18 we carried out kinetic examination of the conversion of 4a and 6 into 7a, but this system involved a side reaction giving biphenyl. In this study, we investigated a more selective system using 2,6-dimethylphenyl complex 4c in place of phenyl complex 4a. Complex 4c has a marked tendency to dissociate into 1c as the reactive species in solution and thereby cleanly reacts with 6 to afford the direct arylation product 7c and bis-PPh3 complex 5c in quantitative yields. Complex 4c (9.1 mM) was treated with an excess amount of 6 (0.182−1.09 M) at 65 °C in THF in the presence of iPr2EtN.20 When the reaction was followed by 31P{1H} NMR spectroscopy, a broad singlet at δ 31.0, which is assignable to an equilibrium mixture of 4c and 1c, gradually decreased to be replaced by a sharp singlet of 5c at δ 20.9. The reaction obeyed pseudo-first-order kinetics over 3−4 half-lives (see Figure S1 in the Supporting Information). The observed rate constants (kobsd) exhibited a good linear correlation with the concentrations of 6: d[5c]/dt = kobsd[PdAr] = k2[6][PdAr] (k2 = [3.42(8)] × 10−4 s−1 M−1) (Figure 1a).21 These kinetic observations are consistent with the reaction mechanism presented in Scheme 4, which is basically identical with that previously proposed for 4a.18 Complex 4c is in equilibrium with 1c in solution. Coordination of 6 to 1c, followed by C−H bond cleavage on 2c{6}, forms the diaryl intermediate 3c{6}, which reductively eliminates the direct

and a concerted metalation−deprotonation (CMD) pathway involving the arylpalladium carboxylate intermediate [PdAr(O2CR-κ2O)L] (1) has been postulated.12−14 Although a reasonable theoretical description has been provided for the C−H bond cleavage process in step c, isolated models of 1 tested so far have been much less reactive than that expected from catalytic reactions.15,16 Therefore, an alternative pathway with the aid of a cyclometalated complex has been proposed.17 On the other hand, recently we have found that aryl acetate complexes of the formula [PdAr(μ-O2CMe)(PPh3)]n (4a−c) smoothly react with 2-methylthiophene (6) to afford 5-aryl-2methylthiophenes (7a−c) in high yields, where half of 4a−c is converted to 7a−c and Pd black and the other half is converted to bis-PPh3 complexes 5a−c (Scheme 2).18 It has been Scheme 2. Direct Arylation of 2-Methylthiophene (6) with Arylpalladium Acetate Complexes (4)

confirmed that, while 4a−c adopt a dimeric or tetrameric structure in the solid state, they are in rapid equilibrium with the monomeric species [PdAr(O2CMe-κ2O)(PPh3)] (1a−c) in solution, and the monomeric species react with 6 to afford direct arylation products 7a−c. Having highly selective models of catalytic intermediate 1 in hand, in this study we attempted a detailed description of the mechanism of direct arylation using kinetic techniques and DFT calculations, focusing particularly on the factors controlling the reactivity of heteroarenes. So far, most of the mechanistic studies on direct arylation have been focused on the C−H bond cleavage process.12,13 On the other hand, this study has clearly indicated that direct arylation is a multistep process, and its reaction rate is controlled not only by C−H bond cleavage but also by substrate coordination and C−C reductive elimination.

■

RESULTS AND DISCUSSION Relative Reactivity of Heteroarenes. Complex 4a was sufficiently reactive to compare the reactivity of the series of heteroarenes given in Scheme 3. The numbers in parentheses

Figure 1. Plots of pseudo-first-order rate constants (kobsd) against the concentrations of (a) 6 and (b) 8 for the reactions with 4c in THF at 65 °C. 4424


Organometallics

Article

Scheme 4. Proposed Mechanism of Direct Arylation of 6 with 4c

Figure 2. ORTEP drawing of 2c{8} with 50% probability ellipsoids. Hydrogen atoms and a solvent molecule (THF) are omitted for clarity. Selective bond distances (Å) and angles (deg): Pd−C1 = 2.004(3), Pd−O1 = 2.139(2), Pd−N = 2.115(2), Pd−P = 2.2555(8); C1−Pd− N = 89.03(11), O1−Pd−N = 88.79(8), C1−Pd−P = 91.29(9), O1− Pd−P = 91.26(6), C1−Pd−O1 = 174.14(10), N−Pd−P = 176.03(7).

arylation product 7c, along with the formation of [Pd(PPh3)] and acetic acid. The highly coordinatively unsaturated Pd(0) species thus generated rapidly decomposes to release free PPh3, which combines with a [Pd(2,6-Me2C6H3)(μ-O2CMe)(PPh3)] unit in 4c to form 5c. Kinetic Study on Direct Arylation of Benzothiazole (8). The reaction of 4c (9.1 mM) with 8 (0.182−1.45 M) in THF in the presence of i-Pr2EtN20 at 65 °C was followed by 31 1 P{ H} NMR spectroscopy. Upon addition of 8 to the system, a broad signal at δ 31.0 arising from an equilibrium mixture of 1c and 4c instantly disappeared and a sharp singlet at δ 28.5 appeared. As direct arylation proceeded, this signal gradually decreased, to be replaced by the signal of bis-PPh3 complex 5c at δ 20.9. After the signal at δ 28.5 disappeared, the reaction solution was examined by HPLC, showing the formation of 2(2,6-dimethylphenyl)benzothiazole (9c) in quantitative yield (Scheme 5).

Scheme 6. Proposed Mechanism of Direct Arylation of 8 with 4c

Scheme 5. Direct Arylation of Benzothiazole (8) with 4c and 1c undergoes coordination of 8 to form 2c{8}. In this case, the equilibrium for the resulting mixture lies far to the side of 2c{8}, and this situation is consistent with the saturation kinetics observed in Figure 1b. Then, 2c{8} undergoes C−H bond cleavage to form the diaryl intermediate 3c{8}, and finally, the direct arylation product 9c is reductively eliminated from 3c{8}, along with the formation of [Pd(PPh3)] and acetic acid. The subsequent process is the same as that for 6. Deuterium Kinetic Isotope Effects. Deuterium kinetic isotope effects on direct arylation of 6 (or 8) with 4a (or 4c) were examined by two experimental methods. One is based on competitive experiments using a common reference compound (method A), and the other is based on the rate constants evaluated by individual kinetic runs for deuterated and nondeuterated substrates, respectively (method B). Table 1 summarizes the results. 5-Deuterio-2-methylthiophene (6-d) exhibited no notable kinetic isotope effects, irrespective of the starting complexes and reaction conditions (entries 1−3). On the other hand, 2-deuteriobenzothiazole (8-d) provided kH/kD values ranging from 3.3 to 5.5 (entries 4−6). This difference in kinetic isotope effects suggests that C−H bond cleavage serves as the rate-determining step for 8 but not for 6. DFT Calculations on Direct Arylation of 2-Methylthiophene (6). The reaction mechanisms and kinetic observations describe above were examined by DFT calculations using the model compound [PdPh(O2CMe-κ2O)(PH3)] (1d) bearing PH3 instead of PPh3, and the energy diagrams in Figures 3 and 4 emerged. All geometries were optimized with the B3LYP functional. The energy changes were evaluated with the M06-2X functional and triple-ζ-quality basis sets. The

The reaction obeyed pseudo-first-order kinetics over 3−4 half-lives (see Figure S2 in the Supporting Information). Unlike the reaction of 6, the reaction rate was saturated at high concentrations of 8 (Figure 1b). This phenomenon indicates the occurrence of coordination of 8 in a stable form prior to direct arylation. In fact, treatment of 4c with 8 in THF resulted in the selective formation of [Pd(2,6-Me2C6H3)(O2CMe)(8)(PPh3)] (2c{8}), which was isolated in 77% yield. Figure 2 shows the X-ray structure of 2c{8}. While two molecules of 2c{8} were associated with each other by hydrogen bonding in the crystal (see Figure S3 in the Supporting Information), one of the molecules is shown in Figure 2 for clarity. The complex adopts a typical square-planar configuration; the sum of the four bond angles around palladium is 360.3°. Benzothiazole is linked to palladium via the nitrogen atom (dPd−N = 2.115(2) Å) at the cis position of the acetate ligand. This geometry is suitable for subsequent C−H bond cleavage via the CMD pathway. Thus, the mechanism for direct arylation of 8 with 4c may be depicted as shown in Scheme 6. An equilibrium mixture of 4c 4425


Organometallics

Article

As can be seen from Figure 3, the coordination of 6 is much easier than for the others. On the other hand, the transition state for reductive elimination (TSRE) is clearly located higher in energy (4.0 kcal/mol) than that for C−H bond cleavage (TSCH). Hence, the reductive elimination can be assigned to the rate-determining step, and this situation is consistent with the deuterium-labeling experiments showing no kinetic isotope effects (entries 1−3 in Table 1). 5-Methyl-2,2′-bithiophene (10) followed almost the same reaction course, involving the rate-determining reductive elimination (see Table S2 in the Supporting Information). TSRE for 10 was located slightly lower in energy (0.6 kcal/mol) than that for 6. This tendency is in accord with the experimental reactivity order in Scheme 3 (10 > 6), though the calculated energy difference is small. DFT Calculations on Direct Arylation of Benzothiazole (8). Direct arylation of 8 with 1d to give 9a was similarly examined by DFT calculations. As is shown in Figure 4, benzothiazole (8) is coordinated to 1d via the nitrogen atom (dPd−N = 2.17 Å) without a notable activation barrier, giving 2d{8}, in which the C−H group at the 2-position of 8 is linked to the acetate ligand by a hydrogen bond (dO···H = 2.02 Å). Complex 2d{8} then undergoes C−H bond cleavage via TSCH to give 3d{8}. The benzothiazol-2-yl ligand is oriented parallel to the coordination plane owing to the occurrence of a hydrogen bond between the nitrogen atom and the acetic acid ligand (dO···H···N = 2.61 Å). On the other hand, for reductive elimination to take place, the benzothiazol-2-yl ligand is must be oriented perpendicular to the coordination plane so as to interact with the phenyl ligand. Thus, the benzothiazol-2-yl ligand rotates around the Pd−C bond via TSRot, and the resulting 3d′{8} undergoes reductive elimination via TSRE to afford a Pd(0) complex coordinated with 9a and acetic acid. The three transition states TSCH, TSRot, and TSRE are located at 23.8, 12.6, and 21.4 kcal/mol, respectively, against the substrates (1d + 8). Thus, unlike the reaction of 6, the ratedetermining step is assigned to the C−H bond cleavage process. TSCH for 8-d is located at 24.7 kcal/mol and is 0.9 kcal/mol higher than that for 8. The energy difference

Table 1. Deuterium Kinetic Isotope Effects on Direct Arylation of Heteroarenes with Arylpalladium Acetate Complexes entry

complex

1 2 3 4 5 6

4a 4c 4c 4a 4c 4c

substrate 6, 6, 6, 8, 8, 8,

6-d 6-d 6-d 8-d 8-d 8-d

methoda

kH/kD

A A B A A B

1.0 1.0 1.00(2) 3.3 5.5 4.2(1)

a

Method A: the kH/kD values were estimated from reactivity ratios of deuterated and nondeuterated substrates to 2-ethylthiophene as a common reference compound. Competitive reactions were conducted in 1,4-dioxane at 90 °C (entries 1 and 4) or in THF at 65 °C (entries 2 and 5), using 4a (18.2 mM) or 4c (9.1 mM) and a substrate (0.727 M). Method B: the kH and kD values were evaluated by individual kinetic runs for 4c (9.1 mM) and a substrate (0.727 M) in THF in the presence of i-Pr2EtN (0.182 M) at 65 °C.

solvent effect (1,4-dioxane) was included in PCM calculations: see the Supporting Information for details of the computation. Figure 3 shows the schematic geometry changes and Gibbs energy changes in the direct arylation of 6 with 1d to give 7a, where the values for 6-d are given in parentheses. The whole reaction consists of three elementary processes. First, substrate 6 is coordinated with 1d via precursor complex P (ΔG = 3.8 kcal/mol) and transition state TSCO (ΔG = 5.8 kcal/mol). The thiophene unit in 6 is initially associated with the bidentate acetate ligand in 1d by two sets of hydrogen bonds (dO···H = 2.58 and 2.66 Å in P) and then coordinated to palladium with keeping one of the hydrogen bonds being kept (dO···H = 2.30 Å in TSCO). The hydrogen bonding is further strengthened in the resulting complex 2d{6} (dO···H = 2.18 Å), as if to compensate for loose coordination of the thiophene unit (dPd···C = 2.43 and 2.54 Å). Complex 2d{6} then undergoes C−H bond cleavage via TSCH, and finally, C−C reductive elimination from 3d{6} via TSRE forms a Pd(0) complex coordinated with direct arylation product 7a, together with acetic acid.

Figure 3. Free energy change (ΔG, kcal/mol) in direct arylation of 2-methylthiophene (6) with [PdPh(O2CMe-κ2O)(PH3)] (1d). The values for 6d are given in parentheses. 4426


Organometallics

Article

Figure 4. Free energy change (ΔG, kcal/mol) in direct arylation of benzothiazole (8) with [PdPh(O2CMe-κ2O)(PH3)] (1d). The values for 8-d are given in parentheses.

as a high-energy species on the reaction coordinate,13b,15b and in this situation, it is difficult to conclude that the reactivity is governed by the C−H bond cleavage process. Actually, the present study has clearly demonstrated that direct arylation is a multistep process, and the energy profile varies significantly with substrates. Therefore, it is concluded that the reactivity of heteroarenes is controlled by multiple factors in elementary processes, including substrate coordination, C−H bond cleavage, and C−C reductive elimination. Kinetic studies with well-defined models of key intermediates in conjunction with theoretical support provide a deep insight into the mechanisms of reactivity control.

corresponds to kH/kD = 4.6, and this value is in agreement with the experimental data (kH/kD = 3.3−5.5; entries 4−6 in Table 1). The transition state of the rate-determining step for 8 (TSCH, 23.8 kcal/mol) is apparently lower in energy than that for 6 (TSRE, 25.2 kcal/mol). However, because the thermodynamic stability of precursor complex 2d{8}, which is caused by coordination of 8 to palladium via the nitrogen atom, leads to an additional activation barrier for 8 (23.8 + 5.0 = 28.8 kcal/ mol), the reactivity of 8 becomes lower than that of 6, in accordance with the experimental observation in Scheme 3.

■

■

CONCLUSION We have described detailed mechanistic investigations into the factors controlling the reactivity of heteroarenes (6 and 8) in direct arylation with well-defined models of the presumed intermediate [PdAr(O2CMe-κ2O)L] (1). The experimental data have been reproduced consistently by theoretical treatments. Both substrates react with 1 via three elementary processes (i.e., coordination, C−H bond cleavage, and reductive elimination) but display significantly different kinetic aspects from each other. The reaction of 6 obeys simple second-order kinetics. The deuterium-labeling experiments and DFT calculations have revealed the occurrence of rate-determining reductive elimination. On the other hand, substrate 8 displays saturation kinetics because of its relatively stable coordination through the nitrogen atom. This coordination stability enhances the activation barrier for the subsequent C−H bond cleavage process and thus results in the modest reactivity of 8. So far, mechanistic studies on palladium-catalyzed direct arylation have been focused largely on the C−H bond cleavage process, and there has been a tendency for the difference in reactivity of heteroarenes to be discussed only with theoretical values of activation energy for this process.13 However, the resulting diarylpalladium complex 3 has often been illustrated

EXPERIMENTAL SECTION

General Considerations. All manipulations were carried out under a nitrogen atmosphere using standard Schlenk techniques. Nitrogen was dried by passing through P2O5 (Merck, SICAPENT). NMR spectra were recorded on a Bruker Avance 400 spectrometer (1H NMR, 400.13 MHz; 13C NMR, 100.62 MHz; 31P NMR, 161.97 MHz). Chemical shifts are reported in δ (ppm), referenced to 1H (residual) and 13C signals of deuterated solvents as internal standards or to the 31P signal of 85% H3PO4 (δ 0.0) as an external standard. Elemental analysis was performed by ICR Analytical Laboratory, Kyoto University. Analytical HPLC was carried out on a JASCO HPLC assembly consisting of a PU-2080 Plus pump, a Model RI-1530 refractive index detector, and an Intersil ODS-P column (2/1 v/v CH3CN/H2O). Mass spectra were measured on a Shimadzu GC-MS QP2010 spectrometer (EI, 70 eV). GLC analysis was performed on a Shimadzu GC-2025 instrument equipped with a FID detector and a CBP-1 capillary column (25 m × 0.25 mm). Pentane (Kanto, dehydrated) was used as received. THF and 1,4dioxane were dried over Na/Ph2CO, distilled, and stored over activated MS4A. CD2Cl2 was dried over CaH2, distilled, and stored over activated MS4A. 2-Methylthiophene (6), benzothiazole (8), pentafluorobenzene, and 2-ethylthiophene were distilled after passing through a short pad of activated alumina. [PdPh(μ-O2CMe)(PPh3)]2 (4a),22 [Pd(2,6-Me2C6H3)(μ-O2CMe)(PPh3)]2 (4c),18 5-methyl-2,2′bithiophene (10),23 2-phenylthiazole,24 [Pd(η5-C5H5)(η3-C3H5)],25 5deuterio-2-methylthiophene (6-d),26 and 2-deuteriobenzothiazole (84427


Organometallics

Article

d)27 were prepared according to the literature procedures. All other chemicals were obtained from commercial suppliers and used without further purification. Relative Reactivity of Heteroarenes. Reactivity ratios of heteroarenes were estimated by competitive reactions. A typical procedure is as follows. Complex 4a (10.1 mg, 0.010 mmol) and C6Me6 (4.1 mg, 0.025 mmol; an internal standard for HPLC analysis) were placed in an NMR sample tube equipped with a Teflon screw cock (J. Young). 1,4-Dioxane (0.50 mL), 2-methylthiophene (6; 39 μL, 0.40 mmol), and benzothiazole (8; 44 μL, 0.40 mmol) were added at room temperature. The mixture was degassed three times by freeze−pump−thaw cycles and then heated for 35 min to 90 °C in an oil bath. 31P{1H} NMR analysis of the resulting solution at room temperature revealed a 55% conversion of the starting complex, and HPLC analysis showed the formation of 5-phenyl-2-methylthiophene (7a) and 2-phenylbenzothiazole in 38 and 15% yields, respectively. Thus, the reactivity ratio of 8 to 6 was estimated to be 0.39 (15/38). Kinetic Study. A typical procedure is as follows. Complex 4c (8.5 mg, 0.0040 mmol) and C6Me6 (3.2 mg, 0.020 mmol; an internal standard for HPLC analysis) were placed in an NMR sample tube equipped with a Teflon screw cock (J. Young). THF (0.30 mL), iPr2EtN (10 mg, 0.080 mmol), and 2-methylthiophene (6; 31 μL, 0.32 mmol) were added, and the total volume of the 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 to 40 °C to dissolve 4c. 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 (4c + 1c), 20.9 (5c), and −13.9 (PPh2(C6H4-2OMe)). After the signal at δ 31.0 disappeared, the amount of direct arylation product was analyzed by HPLC. The solution was concentrated to dryness, dissolved in CD2Cl2 (0.5 mL), and examined by 1H and 31P{1H} NMR spectroscopy, showing the formation of 5c in quantitative yield. The reaction of 4c with 8 was similarly examined using marker signals at δ 28.5 (2c{8}), 20.9 (5c), and −13.9 (PPh2(C6H4-2-OMe)). The first-order plots are shown in Figures S1 and S2 in the Supporting Information. The observed rate constants are given in Table S1 in the Supporting Information. Deuterium Kinetic Isotope Effects. Method A. A typical procedure is as follows. Complex 4c (8.5 mg, 0.0040 mmol) and C6Me6 (3.2 mg, 0.020 mmol; an internal standard for HPLC analysis) were placed in an NMR sample tube equipped with a Teflon screw cock (J. Young). THF (0.30 mL), i-Pr2EtN (10 mg, 0.080 mmol), 2methylthiophene (6; 31 μL, 0.32 mmol), and 2-ethylthiophene (36 μL, 0.32 mmol; reference compound) were added, and the total volume of the solution was adjusted to 0.44 mL by adding a small amount of THF at room temperature. The mixture was degassed three times by freeze−pump−thaw cycles and heated for 1 h to 65 °C in an oil bath. GLC analysis of the resulting solution revealed the formation of a 38/41 ratio of 5-phenyl-2-methylthiophene (7a) and 5-phenyl-2ethylthiophene. Similarly, a competitive reaction of 5-deuterio-2methylthiophene (6-d) and 2-ethylthiophene was conducted, and a 41/46 ratio of 5-phenyl-2-methylthiophene (7a) and 5-phenyl-2ethylthiophene were obtained. On the basis of these product ratios, the reactivity ratio of 6 to 6-d (kH/kD) was estimated as 1.0. Method B. The pseudo-first-order rate constants for 6 and 6-d (or 8 and 8-d; kH and kD, respectively) were evaluated by individual kinetic runs for 4c (9.1 mM) with substrates (0.727 M) in THF in the presence of i-Pr2EtN (0.182 M) at 65 °C. The observed rate constants are reported in Table S1 (entries 3, 4, 8, and 9). Isolation of [Pd(2,6-Me2C6H3)(O2CMe)(8)(PPh3)] (2c{8}). To a suspension of 4c (42.6 mg, 0.0400 mmol) in THF (2.0 mL) was added benzothiazole (8; 433 mg, 1.60 mmol). The mixture was stirred at 45 °C to dissolve 4c. The solution was concentrated (ca. 0.3 mL), and pentane (4.0 mL) was added to precipitate a white solid, which was collected by filtration, washed with pentane (2 × 0.5 mL), and dried under vacuum (41.3 mg, 77%). 1H NMR (CD2Cl2, −80 °C): δ 1.11

(3H, s), 2.38 (6H, s), 6.30 (2H, d, J = 7.4 Hz), 6.49 (1H, t, J = 7.3 Hz), 7.10−50 (15H, m), 7.50 (1H, dd, J = 8.1, 7.6 Hz), 7.68 (1H, dd, J = 8.4, 7.5 Hz), 7.88 (1H, d, J = 8.1 Hz), 8.72 (1H, s), 8.82 (1H, d, J = 8.4 Hz). 31P{1H} NMR (CD2Cl2, −80 °C): δ 28.6 (s). 13C{1H} NMR (CD2Cl2, 20 °C): δ 24.6 (s), 25.8 (d, J = 4.4 Hz), 122.6 (s), 124.4 (s), 124.9 (s), 126.4 (s), 126.5 (s), 127.0 (s), 128.4 (br s) 128.7 (d, J = 11 Hz), 130.9 (d, J = 54 Hz), 131.2 (s), 133.8 (s), 134.8 (d, J = 12 Hz), 141.2 (s), 151.2 (br s), 153.0 (br s), 156.3 (br s). Anal. Calcd for C35H32NO2PPdS: C, 62.92; H, 4.83; N, 2.10. Found: C, 62.80; H, 4.81; N, 2.23. X-ray Structural Analysis of 2c{8}. Single crystals of 2c{8} suitable for X-ray diffraction study were grown by slow diffusion of pentane into THF solutions at −20 °C. The intensity data were collected on a RIGAKU Saturn70 CCD instrument with VariMax Mo Optic using Mo Kα radiation (λ = 0.71070 Å). The intensity data were collected at 103 K and corrected for Lorentz and polarization effects and for absorption (numerical). The structures were solved by direct methods (SHELXS-97)28 and refined by least-squares calculations on F2 for all reflections (SHELXL-97)29 using Yadokari-XG 2009 (software for crystal structure analyses).30 Non-hydrogen atoms, except for the carbon and oxygen atoms of THF of crystallization, were refined anisotropically. Hydrogen atoms were placed at calculated positions using AFIX instructions. The crystal data and a summary of data collection and refinement details are summarized in Table S3 (Supporting Information). DFT Calculations. All calculations were carried out with the Gaussian 09 program package.31 Geometry optimization was performed by the DFT method without any symmetry constraints, where the B3LYP functional was used.32 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.33 The 631G(d) basis set was applied to other atoms.34 The Cartesian coordinates of optimized structures are reported in Table S4 (Supporting Information). Each equilibrium geometry exhibited no imaginary frequency, and each transition state exhibited one imaginary frequency (see Figure S4 in the Supporting Information). IRC calculations35 were carried out to confirm that the transition state connects the reactant and product. Energy changes were evaluated by the DFT method with the M06-2X functional36 using the geometries optimized above. For these calculations, the Pd atom was described with a triple-ζ basis set and ECPs proposed by the Stuttgart− Dresden−Bonn group.37 Two f-polarization functions were also added for Pd (ζf = 0.621 and 2.203).38 The 6-311G(d) basis sets were employed for other atoms, where one set of anion functions was added to the O atom.39 Solvent effects (1,4-dioxane) were taken into consideration using the polarized continuum model (PCM) at 298.15 K.40 The Gibbs free energy in solution was employed for discussion, where the translational entropy was evaluated by the method developed by Whitesides et al.41

■

ASSOCIATED CONTENT

S Supporting Information *

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

■

AUTHOR INFORMATION

Corresponding Author

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

Notes. The authors declare no competing financial interest. The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS We are grateful to Dr. Y. Nakajima (AIST, Tsukuba, Japan) for X-ray crystallographic assistance. This work was supported by KAKENHI (23350042, 24750088, 22000009) from Japan 4428


Organometallics

Article

K. Chem. Lett. 2010, 39, 1118. (d) Ackermann, L. Chem. Rev. 2011, 111, 1315. (e) Gorelsky, S. I. Coord. Chem. Rev. 2013, 257, 153. (13) (a) Lafrance, M.; Rowley, C. N.; Woo, T. K.; Fagnou, K. J. Am. Chem. Soc. 2006, 128, 8754. (b) Gorelsky, S. I.; Lapointe, D.; Fagnou, K. J. Am. Chem. Soc. 2008, 130, 10848. (c) Gorelsky, S. I.; Lapointe, D.; Fagnou, K. J. Org. Chem. 2012, 77, 658. (14) For related theoretical studies, see: (a) Biswas, B.; Sumitomo, M.; Sakaki, S. Organometallics 2000, 19, 3895. (b) Davies, D. L.; Donald, S. M. A.; Macgregor, S. A. J. Am. Chem. Soc. 2005, 127, 13754. (c) Ishikawa, A.; Nakao, Y.; Sato, H.; Sakaki, S. Dalton Trans. 2010, 39, 3279. (d) Guihaumé, J.; Clot, E.; Eisenstein, O.; Perutz, R. N. Dalton Trans. 2010, 39, 10510. (15) (a) Tan, Y.; Hartwig, J. F. J. Am. Chem. Soc. 2011, 133, 3308. (b) Sun, H.-Y.; Gorelsky, S. I.; Stuart, D. R.; Campeau, L.-C.; Fagnou, K. J. Org. Chem. 2010, 75, 8180. (16) For related studies on 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) Steinmetz, M.; Ueda, K.; Grimme, S.; Yamaguchi, J.; Kirchberg, S.; Itami, K.; Studer, A. Chem. Asian J. 2012, 7, 1256. (17) (a) Tan, Y.; Barrios-Landeros, F.; Hartwig, J. F. J. Am. Chem. Soc. 2012, 134, 3783. (b) Gorelsky, S. I. Organometallics 2012, 31, 4631. (18) Wakioka, M.; Nakamura, Y.; Wang, Q.; Ozawa, F. Organometallics 2012, 31, 4810. (19) Bordwell, F. G. Acc. Chem. Res. 1988, 21, 456. (20) The amine i-Pr2EtN (0.182 M) was added to avoid side reactions caused by free acetic acid generated in the system. It has been confirmed that the reaction rate is little affected by i-Pr2EtN.18 (21) The kinetic treatment was based on the reaction stoichiometry given in Scheme 2; i.e., the [PdAr] value corresponds to the amount of two of the four [Pd(2,6-Me2C6H3)(O2CMe)(PPh3)] units at time t. The consumption of a mixture of 1c and 4c was in good agreement with the amount of 5c formed in the reaction system, as confirmed by 31 1 P{ H} NMR spectroscopy. The quantitative formation of 7c was also confirmed for each run by HPLC analysis. (22) Grushin, V. V.; Bensimon, C.; Alper, H. Organometallics 1995, 14, 3259. (23) Xie, N.; Chen, Y. New J. Chem. 2006, 30, 1595. (24) Xu, M.-L.; Zhou, R.; Wang, G.-Y.; Yu, J.-Y. Inorg. Chim. Acta 2009, 362, 515. (25) Tatsuno, Y.; Yoshida, T.; Otsuka, S. Inorg. Synth. 1979, 19, 220. (26) Join, B.; Yamamoto, T.; Itami, K. Angew. Chem., Int. Ed. 2009, 48, 3644. (27) (a) Crowe, E.; Hossner, F.; Hughes, M. J. Tetrahedron 1995, 51, 8889. (b) Bayh, O.; Awad, H.; Mongin, F.; Hoarau, C.; Bischoff, L.; Trécourt, F.; Quéguiner, G.; Marsais, F.; Blanco, F.; Abarca, B.; Ballesteros, R. J. Org. Chem. 2005, 70, 5190. (28) Sheldrick, G. M. SHELXS-97; University of Gö ttingen, Germany, 1997. (29) Sheldrick, G. M. SHELXL-97; University of Gö ttingen, Germany, 1997. (30) Kabuto, C.; Akine, S.; Kwon, E. J. Cryst. Soc. Jpn. 2009, 51, 218. (31) 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.;

Society for the Promotion of Science, and by the ACT-C program of Japan Science and Technology Agency.

■

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) (a) Schipper, D. J.; Fagnou, K. Chem. Mater. 2011, 23, 1594. (b) Liu, C.-Y.; Zhao, H.; Yu, H.-h. Org. Lett. 2011, 13, 4068. (c) Beydoun, K.; Boixel, J.; Guerchais, V.; Doucet, H. Catal. Sci. Technol. 2012, 2, 1242. (d) Zhang, J.; Kang, D.-Y.; Barlow, S.; Marder, S. R. J. Mater. Chem. 2012, 22, 21392. (e) Fillaud, L.; Trippé-Allard, G.; Lacroix, J. C. Org. Lett. 2013, 15, 1028. (f) Trippé-Allard, G.; Lacroix, J. C. Tetrahedron 2013, 69, 861. (g) Jiang, S.; Lu, X.; Zhou, G.; Wang, Z.-S. Chem. Commun. 2013, 49, 3899. (h) Liu, S.-Y.; Shi, M.-M.; Huang, J.-C.; Jin, Z.-N.; Hu, X.-L.; Pan, J.-Y.; Li, H.-Y.; Jen, A. K.-Y.; Chen, H.-Z. J. Mater. Chem. A 2013, 1, 2795. (3) (a) Wang, Q.; Takita, R.; Kikuzaki, Y.; Ozawa, F. J. Am. Chem. Soc. 2010, 132, 11420. (b) Wang, Q.; Wakioka, M.; Ozawa, F. Macromol. Rapid Commun. 2012, 33, 1203. (4) For related studies from other groups, see: (a) Sévignon, M.; Papillon, J.; Schulz, E.; Lemaire, M. Tetrahedron Lett. 1999, 40, 5873. (b) Hassan, J.; Schulz, E.; Gozzi, C.; Lemaire, M. J. Mol. Catal. A: Chem. 2003, 195, 125. (c) Rudenko, A. E.; Wiley, C. A.; Stone, S. M.; Tannaci, J. F.; Thompson, B. C. J. Polym. Sci., Part A: Polym. Chem. 2012, 50, 3691. (d) Tannaci, J. F.; Thompson, B. C. J. Polym. Sci. Part A: Polym. Chem. 2013, 51, 2660. (5) For reviews on direct arylation polymerization, see: (a) Facchetti, A.; Vaccaro, L.; Marrocchi, A. Angew. Chem., Int. Ed. 2012, 51, 3520. (b) Mercier, L. G.; Leclerc, M. Acc. Chem. Res. 2013, DOI: 10.1021/ ar3003305. (6) (a) Lu, W.; Kuwabara, J.; Kanbara, T. Macromolecules 2011, 44, 1252. (b) Fujinami, Y.; Kuwabara, J.; Lu, W.; Hayashi, H.; Kanbara, T. ACS Macro Lett. 2012, 1, 67. (c) Lu, W.; Kuwabara, J.; Iijima, T.; Higashimura, H.; Hayashi, H.; Kanbara, T. Macromolecules 2012, 45, 4128. (d) Lu, W.; Kuwabara, J.; Kanbara, T. Polym. Chem. 2012, 3, 3217. (e) Yamazaki, K.; Kuwabara, J.; Kanbara, T. Macromol. Rapid Commun. 2012, 34, 69. (f) Kuwabara, J.; Nohara, Y.; Choi, S. J.; Fujinami, Y.; Lu, W.; Yoshimura, K.; Oguma, J.; Suenobu, K.; Kanbara, T. Polym. Chem. 2013, 4, 947. (7) (a) Kowalski, S.; Allard, S.; Scherf, U. ACS Macro Lett. 2012, 1, 465. (b) Berrouard, P.; Najari, A.; Pron, A.; Gendron, D.; Morin, P.O.; Pouliot, J.-R.; Veilleux, J.; Leclerc, M. Angew. Chem., Int. Ed. 2012, 51, 2068. (c) Beaupre, S.; Pron, A.; Drouin, S. H.; Najari, A.; Mercier, L. G.; Robitaille, A.; Leclerc, M. Macromolecules 2012, 45, 6906. (d) Allard, N.; Najari, A.; Pouliot, J.-R.; Pron, A.; Grenier, F.; Leclerc, M. Polym. Chem. 2012, 3, 2875. (e) Berrouard, P.; Dufresne, S.; Pron, A.; Veilleux, J.; Leclerc, M. J. Org. Chem. 2012, 77, 8167. (f) Grenier, F.; Berrouard, P.; Pouliot, J.-R.; Tseng, H.-R.; Heeger, A. J.; Leclerc, M. Polym. Chem. 2013, 4, 1836. (8) (a) Kumar, A.; Kumar, A. Polym. Chem. 2010, 1, 286. (b) Chang, S.-W.; Waters, H.; Kettle, J.; Kuo, Z.-R.; Li, C.-H.; Yu, C.-Y.; Horie, M. Macromol. Rapid Commun. 2012, 33. (c) Zhao, H.; Liu, C.-Y.; Luo, S.C.; Zhu, B.; Wang, T.-H.; Hsu, H.-F.; Yu, H.-h. Macromolecules 2012, 45, 7783. (d) Abdo, N. I.; El-Shehawy, A. A.; El-Barbary, A. A.; Lee, J.S. Eur. J. Org. Chem. 2012, 5540. (9) Wakioka, M.; Kitano, Y.; Ozawa, F. Macromolecules 2013, 46, 370. (10) (a) Murphy, A. R.; Fréchet, J. M. J. Chem. Rev. 2007, 107, 1066. (b) Cheng, Y. J.; Yang, S. H.; Hsu, C. S. Chem. Rev. 2009, 109, 5868. (c) Zhou, H.; Yang, L.; You, W. Macromolecules 2012, 45, 607. (11) Carsten, B.; He, F.; Son, H. J.; Xu, T.; Yu, L. Chem. Rev. 2011, 111, 1493. (12) For reviews on the mechanism of C−H bond cleavage, see: (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, 4429


Organometallics

Article

Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö .; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, Revision A.1; Gaussian, Inc., Wallingford, CT, 2009. (32) (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. (33) Wadt, W. R.; Hay, P. J. J. Chem. Phys. 1985, 82, 299. (34) 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. (35) (a) Gonzalez, C.; Schlegel, H. B. J. Chem. Phys. 1989, 90, 2154. (b) Gonzalez, C.; Schlegel, H. B. J. Phys. Chem. 1990, 94, 5523. (36) Zhao, Y.; Truhlar, D. G. Theor. Chem. Acc. 2008, 120, 215. (37) Kuechle, W.; Dolg, M.; Stoll, H.; Preuss, H. J. Chem. Phys. 1994, 100, 7535. (38) Martin, J. M. L.; Sundermann, A. J. Chem. Phys. 2001, 114, 3408. (39) (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. (40) (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. (41) Mammen, M.; Shakhnovich, E. I.; Deutch, J. M.; Whitesides, G. M. J. Org. Chem. 1998, 63, 3821.

4430


Factors Controlling the Reactivity of Heteroarenes in Direct Arylation

Recommend Documents