Key Role of PdIV Intermediates in Promoting PdII-Catalyzed

Dec 14, 2017 - Palladium-catalyzed dehydrogenative homocoupling of two arenes provides a powerful and straightforward method for the synthesis of biar...
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Key Role of PdIV Intermediates in Promoting PdII-Catalyzed Dehydrogenative Homocoupling of Two Arenes: A DFT Study Lei Zhang†,‡ and De-Cai Fang*,† †

College of Chemistry, Beijing Normal University, Beijing 100875, People’s Republic of China School of Science, Tianjin Chengjian University, Tianjin 300384, People’s Republic of China

‡

S Supporting Information *

ABSTRACT: Palladium-catalyzed dehydrogenative homocoupling of two arenes provides a powerful and straightforward method for the synthesis of biaryls. In contrast to the Heck reaction for efficient cross-coupling of arene with alkene, dehydrogenative homocoupling of two arenes is not readily accessible through traditional PdII/0/II catalytic cycles, which limits its application to the construction of desired C−C bonds. Herein, we performed DFT studies to explore the detailed mechanisms of the PdII-catalyzed homocoupling of benzophenones in the presence of the strong oxidant K2S2O8. Calculation results demonstrated that the favorable reaction pathway is a PdII/IV/II catalytic cycle, including four sequential processes: C−H activation at the PdII center, oxidation of PdII to PdIV, C−H activation at the PdIV center, and reductive elimination. It was found that C−H activation at the PdIV center is the rate-determining process, with a free energy barrier of 26.0 kcal mol−1. The oxidant K2S2O8 plays an important role in converting PdII to PdIV and facilitating the second C−H activation step. In contrast, the alternative PdII/0/II pathway has been characterized as an inaccessible reaction channel from our calculations, because the second C−H activation is hindered by a free energy barrier of 38.9 kcal mol−1. In addition, the electronic effect of the spectator ligand on C−H activation has been investigated in terms of molecular orbital theory, which disclosed the origin of the critical role of PdIV intermediates in promoting the biaryl synthesis.

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INTRODUCTION Palladium-catalyzed dehydrogenative coupling of two C−H bonds represents a powerful and straightforward method to construct desired C−C bonds, which occupies an important position in modern organometallic chemistry due to its green chemistry advantage.1 A dehydrogenative Heck reaction2 furnishes arylalkenes by directly reacting arenes with alkenes, which has been believed to proceed via a catalytic cycle consisting of three sequential steps: arene C−H activation, alkene migratory insertion, and β-H elimination. It is noteworthy that dehydrogenation of alkene is accomplished through β-H elimination rather than C−H activation. In contrast to the Heck reaction, direct homocoupling of two arenes has been proven to be more challenging, and hence it has been paid more attention in recent years.3 Since aromatic rings are commonly less prone to undergo migratory insertion reactions than olefinic double bonds,4 dehydrogenation of both arenes should be realized via a C−H activation mechanism. In most cases, dehydrogenative homocouplings of two arenes have been inefficient for common-oxidation-state palladium-catalyzed transformations (e.g., Pd0 and PdII). However, the mediation of PdIV intermediates, resulting from oxidation of PdII complexes with strong oxidants in catalytic cycles, could substantially improve the reaction efficiency and afford the biaryl products in good yields.3a−c Additionally, high-oxidationstate palladium (e.g., PdIV) catalysis has become one of the © XXXX American Chemical Society

currently investigated research topics in modern organometallic chemistry.5 As early as 2006, Sanford and co-workers reported an efficient dehydrogenative homocoupling of 2-arylpyridines to synthesize the corresponding biaryls at room temperature.6 The use of oxone as an oxidant for converting PdII to PdIV during the reaction is a crucial contribution to high experimental yields. Subsequent to this, dehydrogenative homocouplings of various aromatics have been reported by different research groups.3a−g In fact, most of these reactions are facilitated by a strong coordination group on the reactant; however, the scope of weak-coordination-promoted arene−arene homocoupling has still been rather limited until now.7 In 2015, Zhang and Rao reported an unprecedented PdIIcatalyzed dehydrogenative homocoupling of arenes promoted by weak coordination, in which benzophenone as a reactant, under the catalysis of Pd(OAc)2+HOTf, could afford the corresponding 2,2′-difunctionalized biaryl in good yield at 70 °C (see Scheme 1).8 Comparison experiments showed that the strong oxidant K2S2O8 is a major requisite for the production of the desired biaryls, indicating the occurrence of Pd IV intermediates as a result of oxidation of PdII with K2S2O8. 1,1,1,3,3,3-Hexafluoropropan-2-ol (HFIP) as a solvent might Received: October 19, 2017

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activation transformations at the PdII center, reductive elimination of PdII → Pd0, and oxidation of Pd0 → PdII by K2S2O8. However, this PdII/0/II pathway has been confirmed to be a kinetically inaccessible reaction channel from our calculations. The indispensable role of the occurrence of PdIV intermediates in activating catalytic cycles is the main focus of this study. In addition, the low efficiency of the traditional PdII/0/II mechanism for the dehydrogenative homocoupling of arenes will be investigated from the viewpoint of ligand field effect. The PdII/IV/II Mechanism. The First C−H Activation at the PdII Center. In the past decade, substantial attention has been paid to the structural determinations of palladium acetate both in the solid state and in solution,15 due to the fact that palladium acetate has been the most widely used palladium catalyst in modern organometallic chemistry. X-ray determinations demonstrated that high-purity palladium acetate in the solid state actually exists as the trimeric form Pd3(OAc)6, whereas a series of spectroscopy experiments revealed that the monomer Pd(OAc)2, dimer Pd2(OAc)4, and trimer Pd3(OAc)6 all coexist in solution and their relative contents should depend on the solvent, concentration, and temperature.15 Indeed, dilute solution, polar solvent, and high temperature could favor the dominance of monomer and dimer, and the presence of external coordinating ligands could facilitate the disaggregation of polymerized palladium acetate species into the corresponding monomeric species. Our calculation results confirm that catalytic palladium acetate in the presence of stoichiometric HOTf and benzophenone (reactant, R) could generate monomeric Pd(OTf)2 and Pd(OTf)2·R spontaneously, regardless of the resting state of the catalyst. It is shown that all of the metathetical reactions in Scheme 3 occur with negative free energy changes of −4.2, −11.0, and −1.8 kcal mol−1, respectively, which means that both monomeric and polymerized palladium acetates could be converted to monomeric Pd(OTf)2 and Pd(OTf)2·R spontaneously. Therefore, only the monomeric form of the catalyst will be used to discuss the reaction mechanism afterward. A similar treatment of the disaggregation of polymerized palladium acetate catalysts has previously been carried out by Wang and co-workers in their computational study.16

Scheme 1. Palladium-Catalyzed Dehydrogenative Homocoupling of Benzophenone in the Presence of Strong Oxidant K2S2O8, Characterized in This Study Using DFT Calculations

increase the optimal product yield to 90%; however, other solvents, such as dichloroethane (DCE), could also afford the desired product in moderate yields (ca. 50%). Up to now, no convincing evidence has been available in the literature to confirm whether the PdIV intermediate appears in catalytic cycles and plays a critical role in promoting the reaction efficiency for this kind of reaction. In light of our previous computational studies on the characterization of PdII-catalyzed C−H activation,9−14 we conduct herein a series of density functional theory (DFT) calculations to locate the most plausible reaction mechanism for the dehydrogenative homocoupling of benzophenone shown in Scheme 1. In addition, the occurrence and explicit role of PdIV intermediates will be explored in this article. It is our belief that such a systematic molecular modeling can shed more light on the understanding of high-oxidation-state palladium-mediated coupling reactions.

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RESULTS AND DISCUSSION Reaction mechanisms of PdII-catalyzed homocoupling of benzophenone in the presence of the oxidant K2S2O8 will be characterized in the present study, in which two competing reaction pathways (see Scheme 2) will be discussed and compared both kinetically and thermodynamically. One reaction pathway is the plausible PdII/IV/II mechanism involving four sequential processes: namely, C−H activation at the PdII center, oxidation of PdII → PdIV by K2S2O8, C−H activation at the PdIV center, and reductive elimination to form the biaryl product and regenerate PdII. The other reaction pathway could yield the same homocoupling product on the basis of a catalytic cycle consisting of four sequential processes as well: two C−H

Scheme 2. Comparison of Two Reaction Pathways for the Dehydrogenative Homocoupling of Two Arenes: PdII/IV/II Catalytic Cycle (Left) and PdII/0/II Catalytic Cycle (Right)

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PdII to form PdIV; however, the detailed mechanism of such a process has not been characterized computationally in the literature until now. Our molecular modeling led to the location of the five-membered-ring transition state TS-5, in which the cleavage of the peroxide O3−O4 bond is accompanied by the formation of both Pd−O2 and Pd−O4 bonds. This oxidation process can be formally considered as a 1,4-addition mechanism, since O2 and O4 are separated by two atomic centers, S and O3. Attempts to locate a 1,2-addition mechanism corresponding to the simultaneous formation of Pd−O3 and Pd−O4 bonds failed, presumably because of the weaker coordination ability of peroxide oxygen (O3) in comparison to that of sulfonyl oxygen (O2). Then TS-5 leads to the intermediate INT-5, completing the change of oxidation state from Pd II to PdIV , concomitant with the increase in coordination number from 4 to 6. Afterward, an intramolecular ligand substitution mediated by a κ1-SO4K moiety can replace the Pd−O5 coordination bond and convert itself to a κ2-SO4K structure in INT-6. The calculated free energy data suggest that the combination of INT-3 with K2S2O8 is thermodynamically favored by 4.7 kcal mol−1 to form the more stable complex intermediate INT-4, and then a relatively stable PdIV species INT-5 is formed via TS-5, with the rate-determining free energy barrier being 24.1 kcal mol−1. Such a barrier height is surmountable at the experimental temperature of 70 °C, corresponding to a half-life of ca. 3.6 min from transition state theory. The last step, INT-5 → INT-6, involves a free energy barrier of only 0.9 kcal mol−1 and releases a free energy of 4.9 kcal mol−1, indicative of a very facile reaction step. Importantly, the overall oxidation reaction from INT-3 to INT-6 is a spontaneous process with the free energy change being −12.0 kcal mol−1, demonstrating the strong oxidizing ability of K2S2O8. The Second C−H Activation at the PdIV Center. INT-6 can react with a second benzophenone via a PdIV-mediated C−H activation pathway. In the first step, the carbonyl oxygen of benzophenone replaces an O arm of the κ2-SO4K ligand, leading to the different hexacoordinate PdIV-intermediate INT7. Then a Pd···π interaction replaces the TfO···HOTf ligand via the transition state TS-8, which generates the ion-pair complex intermediate INT-8 bearing a cationic PdIV coordination unit and an outer-shell TfO···HOTf anion. The hydrogen atom on the target carbon center can be abstracted by a sulfonyl oxygen of the adjacent κ1 -SO4 K ligand, affording the doubly palladacyclic PdIV ion-pair complex INT-9. The free energy variations of these elementary processes deserve more attention, because they involve the ratedetermining activation barrier of the entire catalytic cycle. Two ligand substitution steps (INT-6 → INT-7 and INT-7→ INT-8) have to overcome free energy barriers of 13.5 and 8.0 kcal mol−1, but they also need to absorb free energies of 10.6 and 1.1 kcal mol−1, respectively. Proton-transfer transition state TS-9 is characterized as the highest-lying stationary point, and therefore, the rate-determining free energy barrier of the PdIVmediated C−H activation should be equal to the free energy difference between TS-9 and INT-6, which is calculated to be 26.0 kcal mol−1, corresponding to a half-life of ca. 84 min at the experimental temperature of 70 °C. The generated intermediate INT-9 is the most stable PdIV intermediate on the potential energy hypersurfaces. In comparison with the first PdII-mediated C−H activation process (activation free energy barrier of 20.8 kcal mol−1), the second PdIV-mediated C−H

Scheme 3. Generation Pathways of Monomeric Pd(OTf)2 and Pd(OTf)2·R from Preliminary Palladium Acetate Catalysts, along with the Calculated Free Energy Changes (kcal mol−1) Determined at the B3LYP-IDSCRF/DGDZVP Level of Theorya

a

R stands for the reactant of benzophenone.

The complete catalytic mechanism of the PdII/IV/II pathway is schematically depicted in Figure 1, which is complemented with free energy variations (red values in kcal mol−1) determined at the B3LYP-IDSCRF/DGDZVP level of theory. The first elementary step is benzophenone bonding with the catalyst Pd(OTf)2 through a ligand exchange for replacement of an O arm of κ2-OTf with the carbonyl oxygen of benzophenone, involving the pentacoordinate transition state TS-1 to form the intermediate structure INT-1. This step connects Pd(OTf)2 and Pd(OTf)2·R, as shown in Scheme 3. Then a Pd···π interaction replaces a second Pd−O coordination bond intramolecularly via the ligand exchange transition state TS-2, which leads to species INT-2, the real precursor of C−H activation. The proton-transfer transition state TS-3 could afford the five-membered palladacycle INT-3, through which the direct dehydrogenation of the first benzophenone is accomplished and the first C−H activation process is finished. Free energy results reflect the ease of dehydrogenation of benzophenone catalyzed by Pd(OTf) 2, since the ratedetermining step of INT-2 → TS-3 → INT-3 involves a free energy barrier of 20.8 kcal mol−1 that should be readily accessible at the reaction temperature of 70 °C. In addition, INT-3 is strongly stabilized by 16.6 kcal mol−1 relative to Pd(OTf)2 + benzophenone, demonstrating the spontaneity and speediness of the first C−H activation step mediated by the PdII catalyst. It should be pointed out that relaxation of TS-3 along the forward direction as determined by IRC calculations does not lead to INT-3 but leads to the similar intermediate INT-3′ without the hydrogen bond between HOTf and OTf. However, INT-3′ is 9.5 kcal mol−1 less stable in free energy than INT-3, and their interconversion only involves a free energy barrier of 0.6 kcal mol−1. This intermediate is omitted in Figure 1 for the sake of simplicity. Oxidation of PdII to PdIV by the Strong Oxidant K2S2O8. The formed intermediate INT-3 is a stable PdII species, which could be oxidized to a PdIV intermediate by the strong oxidant K2S2O8. First, the combination of INT-3 with K2S2O8 is realized via the ligand substitution step INT-3 → TS-4 → INT4, which cleaves the Pd−O1 coordination bond and forms the Pd−O2 coordination bond simultaneously. The oxidant K2S2O8 exhibits a strong oxidizing ability due to the existence of a peroxide O−O bond in its molecular structure, in that cleavage of this O−O bond can transfer two SO4 moieties onto C

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Figure 1. Depiction of the entire PdII/IV/II catalytic cycle for the dehydrogenative homocoupling of two benzophenones, along with relative free energy values (kcal mol−1) determined at the B3LYP-IDSCRF/DGDZVP level of theory.

activation process should be more difficult, but it is still accessible under the experimental conditions reported. Reductive Elimination and Separation of Product. The C− C reductive elimination between two phenyl groups that come from two benzophenones can be realized via the three-centered transition state TS-10, which subsequently leads to the formation of intermediate INT-10. This reductive elimination step recovers the oxidation state of Pd from +4 to +2 and

concurrently decreases the coordination number from 6 to 4. It should be mentioned herein that reductive elimination from PdII and PdIV has been systematically studied by Ananikov and co-workers.17 Although the homocoupling product moiety has already formed, two additional ligand substitution steps are still necessary to liberate it from INT-10. The removal of the homocoupling product can be facilitated by the attack of the outer-shell TfOH···OTf anion, involving two transition states D

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Figure 2. Entire free energy (in kcal mol−1) profiles of the PdII/IV/II catalytic cycle, determined at the B3LYP-IDSCRF/DGDZVP level of theory.

of solvent by adding one or two HFIP molecules to some intermediates and transition states. For the PdII → PdIV oxidation process, two HFIP molecules are added to both INT-4 and TS-5 through hydrogen bonds with two SO4 groups, which results in the reduction of the rate-determining free energy barrier by ca. 2.9 kcal mol−1. For the second C−H activation process, an HFIP molecule is added to both INT-6 and TS-9 through a hydrogen bond with the proton-accepting SO4 group, and consequently the rate-determining free energy barrier is decreased by merely 0.5 kcal mol−1. In fact, incorporating one or two HFIP molecules could neither evidently alter the molecular geometries of these intermediates and transition states nor change the general conclusions in this study. The solvent-incorporating molecular geometries of some intermediates and transition states are available in the Supporting Information. Overview of the Entire Free Energy Profile. Figure 2 provides the whole free energy profile of the reaction, from which the relationship among different processes can be clearly observed. The rate-determining free energy barriers for C−H activation at the PdII center, oxidation of PdII → PdIV, C−H activation at the PdIV center, and reductive elimination are estimated to be 20.8, 24.1, 26.0, and 14.1 kcal mol−1, respectively, indicating that the overall rate-limiting process is the second C−H activation at the PdIV center. However, the free energy barrier of oxidation is only 1.9 kcal mol−1 lower than that of the second C−H activation, from which one might not preclude the influence of the oxidation process on the reaction rate and efficiency. Remarkably, the relative free energy dramatically decreases after successive PdII → PdIV → PdII conversions, since INT-10 is 46.7 kcal mol−1 more stable than INT-3 (both of them are PdII). The PdII/0/II Mechanism. Dehydrogenative homocoupling of arenes to synthesize biaryls must proceed via two dehydrogenation steps from two arenes. The plausible PdII/IV/II mechanism includes two C−H activation processes mediated respectively by PdII and PdIV complex intermediates. Alter-

TS-11 and TS-12 on the potential energy hypersurfaces, which can eventually yield the PdII complex INT-12 and a free homocoupling product. The free energy barrier of reductive elimination is computed to be 14.1 kcal mol−1 , from which a very stable Pd II intermediate (INT-10) would be formed with a free energy release of up to 33.6 kcal mol−1. These results indicate that the PdIV → PdII conversion through reductive elimination is definitely more favorable both kinetically and thermodynamically than the corresponding PdII → PdIV conversion through oxidation discussed before, though the latter is accessible and spontaneous as well. The homocoupling product can easily be removed from the central palladium, according to our calculated free energy data. Regeneration of the Catalyst. Although the formation of the homocoupling product has been accomplished, the regeneration of the original catalyst Pd(OTf)2 from the intermediate INT-12 to close the catalytic cycles is a multistep process. The reaction step INT-12 → TS-13 → INT-13 can change κ1-SO4K to the corresponding κ2-SO4K, and then the last two reaction steps enable the regeneration of Pd(OTf)2, with release of two KHSO4 molecules or their dimeric form (KHSO4)2 as the side product. Free energy calculations show that regeneration of the catalyst involves three free energy barriers, namely, 6.5, 4.4, and 17.9 kcal mol−1, respectively, all of which are easily overcome under the experimental conditions. Indeed, the overall transformation of INT-12 → Pd(OTf)2 + (KHSO4)2 is moderately free energy endothermic (i.e., ΔG = 5.7 kcal mol−1), which might prevent regeneration of the catalyst from thermodynamics. However, KHSO4 can be effectively solvated by HFIP solvent molecules to promote its release, since the overall transformation of INT-12 + 2HFIP → Pd(OTf)2 + (KHSO4)2·(HFIP)2 becomes near free energy neutral (i.e., ΔG = 0.3 kcal mol−1) in the presence of explicit HFIP molecules. This might be a part of the solvent contribution observed experimentally. In addition, we have examined the explicit roles E

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Figure 3. Key stationary points of the PdII/0/II catalytic cycle for the dehydrogenative homocoupling of two benzophenones, along with relative free energy values (kcal mol−1) determined at the B3LYP-IDSCRF/DGDZVP level of theory.

Although INT-3 has difficulty in reacting with a second benzophenone, the following reductive elimination process has also been considered in our calculations for completeness (see Figure 3B). Since INT-5a has two cis phenyl ligands, it should stand for the real precursor of the reductive elimination step. It can be observed that the reductive elimination step INT-5a → TS-6a → INT-6a involves a free energy barrier of 23.0 kcal mol−1 and a free energy change of −13.5 kcal mol−1, but the extreme instability of INT-5a makes this process unlikely to be accessible. For example, TS-6a and INT-6a are 51.1 and 14.6 kcal mol−1 in free energy above INT-3, being unfavorable both kinetically and thermodynamically. From all of these results, one can state that the PdII/0/II catalytic cycle is inaccessible for the desired homocoupling of arenes, mainly due to the hindrance of the second C−H activation process. The free energy profiles of the PdII/0/II pathways are provided in Figure 4. Ligand Field Effect on C−H Activation. C−H activation of benzophenone with Pd(OTf)2 involves a free energy barrier of 20.8 kcal mol−1 and releases a free energy of 16.6 kcal mol−1 afterward, meaning that the first C−H activation mediated by PdII is a favorable transformation under the experimental conditions. However, the formed intermediate INT-3 activating the target C−H bond of the second benzophenone has to pass over rather a high free energy barrier of 38.9 kcal mol−1; in other words, catalytic Pd(OTf)2 has great difficulty in undergoing two C−H activation transformations in succession

natively, two C−H activation processes might both take place at the PdII center, which means that INT-3 might activate the target C−H bond of the second benzophenone prior to being oxidized to PdIV species with the oxidant K2S2O8. Such a mechanistic pattern matches the right catalytic cycle (PdII/0/II) depicted in Scheme 2, in which K2S2O8 serves as the terminal oxidant for converting Pd0 to PdII in the regeneration of the catalyst. This PdII/0/II catalytic mechanism has also been explored in our calculations for comparative purposes. Figure 3 shows the located possible stationary points for the PdII/0/II mechanism, with the computed relative free energies being provided beside each structure. The C−H activation of INT-3 with benzophenone might proceed via one of two reaction channels, associated with the relative positions (cis or trans) of two formed phenyl ligands. The red reaction channel could afford the doubly palladacyclic intermediate INT-5a containing two cis phenyl ligands, whereas the blue reaction channel would furnish the corresponding trans isomer INT-5b. Likewise, the proton-transfer transition states TS-5a and TS-5b display the same kind of geometric isomerism. However, TS-5a and TS-5b lie at 38.9 and 46.1 kcal mol−1 in free energy above INT-3, respectively, which indicate insurmountable activation free energy barriers at a moderate experimental temperature. Moreover, the formed palladacycles INT-5a and INT-5b are strongly destabilized by 28.1 and 40.8 kcal mol−1 with respect to INT-3, negating any possibility for two sequential C−H activation reactions happening at the PdII center. F

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Figure 4. Free energy (kcal mol−1) profiles of PdII/0/II pathways, determined at the B3LYP-IDSCRF/DGDZVP level of theory.

due to the kinetic hindrance of the second C−H activation. Hence, the PdII/0/II catalytic cycle is inoperative and the PdII/IV/II catalytic cycle should be recommended for such a case, for which oxidation of INT-3, by using K2S2O8 with a PdIV intermediate (INT-6), could facilitate the second C−H activation that has an accessible free energy barrier of 26.0 kcal mol−1 from our calculations. Therefore, changing PdII to PdIV could effectively enhance the chemical reactivity of the second C−H activation. In addition, a reactivity order is obtained as follows on the basis of the calculated free energy barriers: the first C−H activation at PdII > the second C−H activation at PdIV > the second C−H activation at PdII. It is very important to explore why the second C−H activation has difficulty taking place at the PdII center but becomes accessible at the PdIV center, which requires a careful comparison of the proton-transfer transition state of TS-3 (see Figure 1) with those of TS-5a and TS-5b (see Figure 3). The main structural difference between TS-3 and TS-5a (or TS-5b), from a ligand field perspective, lies in the nature of the spectator ligand. In addition to the developing phenyl ligand that is deprotonated in progress, both TS-5a and TS-5b have a spectator phenyl ligand formed from the first C−H activation step; in contrast, all of the spectator ligands in TS-3 are oxygencentered ligands. In terms of the electronic effect, phenyl is a strongly σ donating ligand while most of the oxygen-center ligands have relatively weaker σ-donating ability, which might cause distinct spectator ligand effects on the C−H activation in progress. In order to elucidate the spectator ligand effect on the relative ease of different C−H activation transformations or, more specifically, on the relative stabilities of TS-3, TS-5a, and TS-5b, some model reaction systems have been designed as shown in Figure 5. In our calculations, INT-3 and INT-3g are modeled as two PdII catalysts, which only differ in the replacement of a phenyl ligand with a carboxyl group, to react with benzophenone via C−H activation. The results clearly show that C−H activation of INT-3 with benzophenone involves much higher free energy barriers in comparison to that of INT-3g with benzophenone, regardless of the position of the C−H activation site. In other words, the existence of a spectator phenyl ligand would retard the C−H activation process with respect to that of a spectator carboxyl ligand. The

Figure 5. Model reaction systems designed to show the spectator ligand effect on the C−H activation transition state, along with the calculated free energy barriers (in kcal mol−1) of proton transfer at the B3LYP-IDSCRF/DGDZVP level of theory. The dashed sphere in each transition state denotes the HOTf···TfO moiety, serving as a base for proton abstraction.

deactivating effect is more pronounced when the spectator phenyl ligand is trans to the C−H activation site, because TS5b is 22.1 kcal mol−1 higher in free energy barrier than TS-5bg, but TS-5a is 16.5 kcal mol−1 higher in free energy barrier than TS-5ag. These findings are consistent with the inertness of the second C−H activation happening at the PdII center discussed before. One may find another difference between TS-3 and TS-5a that the proton-accepting group is OTf in the former but becomes TfOH···OTf in the latter. In this regard, we can remove the hydrogen-bonded TfOH molecule from both TS5a and INT-4a to examine the change of the proton-transfer activation barrier. As a result, the free energy difference between TS-5a and INT-4a is reduced merely by 2.1 kcal/mol, which means that the effect caused by the proton-accepting group is less obvious than that caused by the spectator phenyl ligand. Next, we will explore from the perspective of chemical structure why the strongly σ donating ligand phenyl would hinder the C−H activation in progress. Since the effect caused by a trans phenyl is evidently larger than that caused by a cis phenyl, we believe that the electronic effect plays an important role in governing the relative stability of different transition states. In this regard, molecular orbital analyses may provide a deeper understanding. Figure 6 provides the key molecular orbitals that contribute most to the developing Pd−C6H5 coordination bond in the proton-transfer transition state. The two molecular orbitals share a common feature that the developing Pd−C6H5 G

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Figure 6. Key molecular orbital distributions in the proton-transfer transition state, showing the antibonding combination between two cis or trans Pd−C6H5 σ lobes.

coordination bond is in an antibonding combination with the σtype lobe of the spectator Pd−C6H5 bond, which might hinder Pd−C6H5 bond formation and thus retard the C−H activation. It is understandable that a trans phenyl ligand could exert a larger effect than a cis phenyl ligand, since an antibonding interaction from the back should be more significant than that from the front. Additionally, the antibonding combination of two cis Pd−C6H5 σ lobes suggests the component of fourelectron repulsion (overlap repulsion) between two localized orbitals, which makes TS-5a unlikely to be accessible. The spectator ligand effect of phenyl on C−H activation is obvious, because phenyl is a strongly σ donating ligand and hence the antibonding interaction coming from phenyl should be strong as well. This is also related to the concept of trans influence18 in coordination chemistry, which states that the strongly σ donating ligand tends to weaken the trans coordination bond (see bond lengths marked in Figure 5); in fact, it may also weaken the cis coordination bond but to a lesser degree. For the relatively weaker σ-donating ligand (e.g., oxygen-centered ligand), however, its effect on C−H activation should be less obvious.

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COMPUTATIONAL DETAILS

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ASSOCIATED CONTENT

All calculations were performed by using the B3LYP density functional method19 as implemented in the Gaussian 09 program.20 The standard double-ζ valence polarized all-electron DGDZVP basis set21 was applied for all elements to fully geometrical optimizations. The default self-consistent reaction field (SCRF) polarizable continuum model (PCM)22 was employed to mimic the implicit solvation effects (DCE solvent was employed), in which our IDSCRF radii23 were chosen as the atomic radii to define the molecular cavity, denoted as B3LYPIDSCRF in this article. All of the resultant stationary point structures were also characterized by vibrational calculations, from which zeropoint energies and Gibbs free energies were obtained, in addition to confirming whether all the structures resided at minima or first-order saddle points on the potential energy hypersurfaces. In addition, intrinsic reaction coordinate (IRC) computations with Hessian-based predictor−corrector integrator (HPC)24 were used to test some reaction steps to confirm the located transition states as residing on the correct reaction coordinates. The default translational entropy data obtained from the Gaussian 09 program is the ideal-gas-phase translational entropy based on the ideal-gas equation, which must exaggerate the entropy decrease for the bimolecular combination in solution and thus overestimate the free energy barrier of the bimolecular reaction in solution. Our solution translational entropy model can output solution entropy data by properly estimating the free volume that a solute molecule could move within the cavity. This entropy model was coded in our THERMO Program,25 which has been previously applied to different systems.26 We have also tested the performance of the B3LYP density functional method with respect to that of B3LYP-D3 (B3LYP with Grimme’s D3 correction27), and the obtained results suggested that the two methods gave close free energy barriers for unimolecular steps and processes (i.e., no change in the molecular number) while B3LYPD3 underestimated the free energy barrier of the PdIV-mediated C−H activation, a bimolecular process, by as much as 13.2 kcal mol−1 in comparison to B3LYP (see the Supporting Information for details). Considering the experimental temperature of 70 °C and reaction time of 6 h, B3LYP gave more reasonable free energy barriers in comparison to B3LYP-D3, since the latter method predicted that the reaction could proceed speedily even at room temperature. Therefore, the dispersion effect might not be so obvious for characterizing the present systems involving relatively tight ratedetermining transition structures. In fact, the present dispersion correction method has not considered the charge-distribution change of the atomic-interaction pairs for the different stationary points, which might not be correct for the transition states or even intermediates due to greater charge transfer between different fragments.

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CONCLUSIONS Density functional theory calculations have been carried out to characterize the detailed mechanisms of PdII-catalyzed dehydrogenative homocoupling of benzophenones, from which the following main conclusions have been drawn. (1) The most favorable reaction mechanism is a PdII/IV/II catalytic cycle, involving four sequential processes: C−H activation at the PdII center, oxidation of PdII → PdIV, C−H activation at the PdIV center, and reductive elimination, in which C−H activation at the PdIV center is the rate-determining step with a free energy barrier of 26.0 kcal mol−1. (2) The alternative PdII/0/II catalytic cycle is inaccessible for the desired biaryl homocoupling, since the second C−H activation process has great difficulty in taking place at the PdII center with a free energy barrier of 38.9 kcal mol−1. (3) Spectator ligand effects on C−H activation have been employed to better understand the distinct reactivity of different C−H activation transformations. The existence of a spectator phenyl ligand would destabilize the protontransfer transition state due to the antibonding combination between two Pd−C6H5 σ lobes, and it becomes more pronounced when the spectator phenyl ligand is trans to the developing phenyl ligand.

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.7b00778. H

DOI: 10.1021/acs.organomet.7b00778 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

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Vibrational frequencies, electronic energies, Gibbs free energies, and complementary mechanistic characterizations (PDF) Optimized Cartesian coordinates for all stationary points (XYZ)

AUTHOR INFORMATION

Corresponding Author

*E-mail for D.-C.F.: [email protected]. ORCID

De-Cai Fang: 0000-0003-3922-7221 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the National Nature Science Foundation of China (21773010). REFERENCES

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DOI: 10.1021/acs.organomet.7b00778 Organometallics XXXX, XXX, XXX−XXX