Computational Studies of Versatile Heterogeneous Palladium

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Computational Studies of Versatile Heterogeneous PalladiumCatalyzed Suzuki, Heck, and Sonogashira Coupling Reactions Pitchaimani Veerakumar,*,†,§ Pounraj Thanasekaran,*,‡ Kuang-Lieh Lu,‡ King-Chuen Lin,†,§ and Seenivasan Rajagopal*,∥ †

Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 10617, Taiwan Institute of Chemistry, Academia Sinica, Taipei 11529, Taiwan § Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan ∥ School of Chemistry, Madurai Kamaraj University, Madurai 625021, India ‡

ABSTRACT: This perspective focuses on the mechanistic insights and complexity, which are difficult to acquire from pure experimental techniques, of the computational studies of Pd-catalyzed Suzuki, Heck, and Sonogashira carbon−carbon bond-forming reactions. These reactions consist of three fundamental steps including oxidative addition (OA), transmetalation (TM), and reductive elimination (RE) for the generation of carbon−carbon bonds from the bond-forming reactions of aryl halides (R1X) and organometallic species (R2M). Computational studies of these coupling reactions allow us to understand specific reaction pathways in the analysis of OA (resolving the linkage between coordination number and selectivity in Suzuki reaction), TM (the function of the base in the Suzuki reaction and various mechanistic options in the Sonogashira reaction), and RE (way of efficient β-hydride elimination in the Heck reaction). In addition, the reaction pathways and complexities in the full catalytic cycle of each reaction along with the future perspective are also discussed. KEYWORDS: C−C cross-coupling, Density functional theory, Heterogeneous, Mechanism, Palladium, Suzuki reaction, Heck reaction, Sonogashira reaction

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INTRODUCTION Palladium-based catalysts remain the most useful transition metal catalysts and are pivotal tools for the synthesis of organic molecules carrying carbon−carbon bonds. This is because of selectivity of the reaction, tunability of the catalyst, and the choice of ligand toward reactivity and selectivity. Further, these reactions proceed with a high TON (turnover number) and TOF (turnover frequency) using a small amount of Pd (ppb to ppm) species under green reaction conditions.1−4 These reactions find applications frequently on the synthesis of organic molecules with biological and pharmaceutical importance. Among the main bond-forming reactions by Pd catalysts, the Suzuki, Heck, and Sonogashira reactions, which occur between a nucleophile (organometallic reagents, alkenes, or alkynes) and an electrophile (aryl or alkyl halides), highlight some of the most practical and important applications of palladium nanoparticles (PdNPs) in the chemical industries. In palladium-catalyzed Suzuki, Heck, and Sonogashira carbon−carbon bond-forming reactions, competing pathways appear to be involved in many steps containing similar energy barriers, thus making their mechanism difficult.5 For example, since most of the intermediates are short-lived species that are difficult to be detected, developing a coherent mechanism for these reactions using experimental techniques is a challenging task. © 2017 American Chemical Society

It is known that various chemical reactions are facilitated by heterogeneous catalysts through changes in the surface charge of the catalyst. Recent interest is in the application of density functional theory (DFT) as a better approach to understand the mechanism of these reactions.6 However, to date, only limited efforts have been made to use computational techniques based on DFT to screen improved catalysts in heterogeneous systems. The nature of the active Pd catalysts in solid supports for the carbon−carbon bond-forming reaction is a subject of considerable debate. There are two extremes where either the reaction is catalyzed by heterogeneous Pd catalysis (Pd/support, Pd clusters, Pd surface) or the leaching of active Pd species occurs from the supporting solid and catalyzes the reaction homogeneously. Determining whether a bond-forming reaction proceeds exclusively homogeneously or heterogeneously is a very difficult task. It is likely that both homogeneous and heterogeneous catalyses may occur at the same time or consecutively (Scheme 1). If the catalysis occurs at the same time, it would be extremely difficult to characterize.7 Usually, the mechanism of Pd catalyzed Received: March 27, 2017 Revised: July 28, 2017 Published: August 24, 2017 8475

DOI: 10.1021/acssuschemeng.7b00922 ACS Sustainable Chem. Eng. 2017, 5, 8475−8490

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ACS Sustainable Chemistry & Engineering

Hybrid B3LYP,11 M06,12 and BP8613 functionals are applied for these reactions. Among them, B3LYP shows promise and is thus extensively used to understand the mechanism of these catalyzed reactions. Oxidative Addition. In coupling reactions, the first step is OA, which is determined to be the rate-determining step. When the coupling reaction occurs between electron-rich Pd(0)Ln(n = 1−4) and an electrophile organic halide R−X, not only bond breaking takes place in between the aryl and the halide groups in R−X but also the generation of two bonds in Pd(0)Ln, where the oxidation state of Pd species is increased from 0 to +2 (Scheme 3).

Scheme 1. General Mechanism for Heterogeneous and Homogeneous Bond-Forming Reactions Catalyzed by Pd Species

Scheme 3. General Scheme for Oxidative Addition Reaction

carbon−carbon bond-forming reactions is similar to the mechanism proposed for homogeneous catalysis. However, a clear picture on the mechanism of heterogeneous catalysis is yet to emerge. We report herein on recent developments in computational studies of Pd-catalyzed carbon−carbon bondforming reactions, which could provide readers with some guidance for designing Pd nanocatalysts with desirable catalytic activities. Most of the empirical and computational studies on the mechanism of carbon−carbon bond-forming reactions catalyzed by Pd species have involved the use of homogeneous catalysts.8−10 General Pd-Mediated Suzuki, Heck, and Sonogashira Catalytic Cycles for Carbon−Carbon Bond-Forming Reactions. Pd-mediated Suzuki carbon−carbon bond-forming reactions usually involve the reaction of aryl halides (or triflate), R1−X, with a boronic acid, R2−B(OH)2, in the presence of a base and take place through three steps, viz., OA, TM, and RE, in the catalytic cycle. Other Pd-mediated Heck and Sonogashira carbon−carbon bond-forming reactions have various steps that are in common with the Suzuki bond-forming reaction. Both Suzuki and Heck reactions begin with the oxidative addition of an aryl halide to a Pd(0) in the catalytic cycle to produce a more soluble σ-aryl Pd(II) complex. The addition of a base intends to replace the halide of the σ-aryl Pd(II) in a ligand substitution reaction. The resulting σ-aryl Pd(II) complex reacts with an aryl boronate in the Suzuki reaction, while an alkene or alkyne is preferred in the Heck or Sonogashira reaction, respectively. Reductive elimination then produces a unique product for each reaction and regenerates Pd(0) catalytically active species to begin the catalytic cycle again (Scheme 2). In the past decades, computational chemists have primarily focused on solving chemically related problems in the catalytic cycles for carbon−carbon bond-forming reactions catalyzed by Pd species.

Although the reaction appears to be reversible, the use of strong electron-donating ligands may lead the equilibrium to be shifted to the oxidative addition (OA) product. For this step, two mechanisms, i.e., concerted mechanism and an SN2 mechanism, are proposed (Scheme 4). Scheme 4. Concerted and SN2 Mechanisms for OA Reaction

The concerted mechanism involves the formation of a threecentered transition state (TS), in which R1−X binds first to the Pd center, and then, the cleavage of the R1−X bond and the generation of new Pd−R1 and Pd−X bonds take place simultaneously. This mechanism induces the retention of configuration at a stereogenic center in the case of chiral a R1−X molecule. In contrast, the SN2 mechanism is an associative bimolecular reaction, involving two pathways. In this reaction, the R1 of R1−X is encountered by Pd(0)Ln and X− is released, resulting in the formation of a [Pd−R]+ intermediate. Finally, both charged species combine to yield the coupling product. This second mechanism results in the inversion of configuration of a stereogenic center. The first computational studies by Low and Goddard proposed three models (three-coordinate (one ligand removed from metal center), four-coordinate, and five-coordinate (one ligand added to metal center) models) in OA reactions that involved the use of Pd dialkylbis(phosphino ligands).14 They reported that the RE barrier follows the following order: three-coordinate complex > four-coordinate complex > fivecoordinate complex. Although the OA process has been investigated in some depth, the more reactivity of a Pd species carrying bulky and electron-rich ligands is not clearly realized. This might be due to the more rapid OA reaction of monoligated [PdL] species compared to the bis-ligated compound, [PdL2]. When relatively inert aryl chlorides are used as substrates, the carbon−carbon bond-forming reactions become more facile in the presence of bulky and electron-rich phosphine ligands. A detailed DFT study on the Ph-X (X = Cl, Br, I) OA to a [Pd(PMe3)2] complex reveals that aryl halides, ArCl and ArBr,

Scheme 2. Similarities in Catalytic Cycle between Suzuki and Heck Reactions

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ranging from 26.0 (R = Me) to 19.4 kcal mol−1 (R = t-Bu) and followed the order of R = Me > Et > PPh3 > i-Pr > t-Bu. It was suggested that the choice of phosphine ligands can significantly affect the energetics of the OA process. It is noteworthy that P(t-Bu)3 had a unique ability in the bond-forming of aryl chlorides, which was attributed to an energy barrier difference. The Pd coordination number and nature of ligands in a solvent or the gas phase determine the fate of the addition reaction. For example, Senn and Ziegler used DFT calculations to investigate the OA of Ph-X (X = Cl, Br, or I) to [Pd(PP)] (PP = 1,2-bis(dimethylphosphino)ethane or (P)-2,2′-bis(dimethylphosphino)-1,10-biphenyl) in THF solution.22 In this study, the authors were not able to locate concerted TS in a solution state but in a gas phase. The halide dissociation and its recombination with phenyl complex were strongly exothermic and barrier free, leading a facile process in solution. However, Schoenebeck and co-workers successfully located the transition states using a DFT approach for the addition reaction of C−Cl and C−OTf to Pd(PtBu3), Pd(PtBu3)(MeCN), and Pd(PtBu3)F− in MeCN.23 Legault et al. theoretically studied the OA of polyhalogenated heterocyclic compounds to Pd(PH3)2 and showed that both C−X bond strength and the frontier molecular orbital (MO) interactions controlled regioselectivities. The frontier interaction is related to the TS structure in which the interaction occurs between PdL2 and η2-Ar−X. For example, in the case of 2,5-dibromo-7-methoxybenzofuran, C(2)−Br is first activated since it is a stronger bond than that of C(5)−Br. As the C(2) is linked nearby hetero-oxygen atom, its π* orbital gets lower energy, leading to generate d−π* backbonding.24 It was also found that anionic Pd species such as Pd(PR3)2Cl− and [Pd(PMe3)2]OAc− promoted the addition process even in the presence of anionic additives.25,26 A different mechanism for the addition of organic iodides to [Pd(PMe3)2OAc]− using BP86/LANL2DZ theory was proposed (Scheme 6). Goossen and

assist the OA reaction through promoting the monoligand pathway when the bulky and hemilabile ligands are used (Scheme 5).15 Scheme 5. Reaction Mechanism for Aryl Halide Addition to [Pd(PMe3)2]

But, when the OA involves electron-withdrawing groups (EWGs) containing ArI, less sterically hindered ligands are proposed. The choice of the bulky ligand might be less important for ArI derivatives compared with other halogen derivatives owing to their weak C−I bond and viable process with a few energy barriers in both pathways. These results clearly explained the use of electron-rich and sterically hindered ligands in bondforming reactions of ArBr, ArCl, and ArI using Pd catalysts.15 Jutand et al. reported that the mechanism of the addition of an aryl halide to a PdL2 complex was influenced by the nature of the ligand (L) size.16 In another computational study, Norrby et al. reported that, with PdL2 complexes, the OA of Ar-X occurred more qucikly due to low energy barriers involved compared with PdL complexes.17 Phosphine ligands performed a significant contribution on the reactivity and selectivity in the Suzuki bond-forming reaction of dibromo sulfoxide mediated by a Pd catalyst.18 The less hindered phosphine PPh3 ligand was linked with a bisphosphine catalyst, which favored an SN2 pathway through bromoaryl group activation, while the bulky P(1-naphthyl)3phosphine complex was associated with the monophosphine catalyst, which promoted a concerted pathway through bromoaryl moiety activation. DFT and DFT/MM calculation studies showed that the coordination number of the catalyst played a key role for the reaction selectivity. Bisphosphine catalysts preferred sp3 carbon coupling where the substrate occupied only one site around a Pd center. In the case of monophosphine catalysts, they favored coupling at the sp2 carbon, in which the substrate occupied more portions around a Pd center. The OA of mono- and bis-ligated forms of [Pd(L)] and [Pd(L)2] catalysts was postulated and computed. As monoligated catalysts possessed a lower energy barrier to the progress of the reaction, the ligand dissociation energy from the Pd complex was responsible for the prevalence of one or the other in the cycle.19,20 The mechanistic study of the addition of PhX to [Pd(PR3)2] and PdPR3(R = Me, Et, i-Pr, t-Bu, Ph) was carried out using DFT studies.21 These calculations showed that a 12-electron monophosphine species PdPR3 catalyst was more active compared with bisphosphine Pd(PR3)2. Interestingly, the computed free-energy barriers did not show any differences in the addition reaction of PhCl to the [Pd(PR3)] catalyst ( benzyl> Ph > vinyl. In fact, C(sp3)−X bonds are less reactive compared to C(sp2)−X bonds this step,31 the π* orbitals of aryl halides give a better reactivity, and (iv) the length of the alkyl chain and the larger bite angles of the ligands are the critical parameters for the addition barriers of aryl halides to Pd-phosphine complexes. Hong et al.32 computationally examined OA processes related to the mechanism of the Suzuki bond-forming reaction of PhCl and phenyl boronicacid with diimine, diphosphine, and diamine ligands. More accurate energies of the optimized structures were calculated and were resembled with the metal coordination geometries in these reactions. However, the use of an IM ligand was found to be more favorable than that of other ligands, including P′ or AM′ (Table 2). Especially, the introduction of trifluoromethyl functional groups on an IM ligand lowered the activation energies of this process. Upon chelating diphosphine P into a Pd metal center, the energy was greatly affected by chelate ring size, while the methylene unit on the backbone of a P ligand increased the activation energy. For diimine ligands, ring size had no significant effect on the activation energies (Table 2). Therefore, the activation energies increased along the order of IM (diamine) < AM (diamine) < P (diphosphine) for the OA process of these reactions. cis−trans Isomerization. On the basis of concerted mechanism, OA generally results in the generation of a square planar cis-Pd(II)L2(R1)(X) complex. Experimentally, transPd(II)L2(R1)(X) isomers are obtained from the reaction of organohalides with Pd(0) complexes. It is commonly believed that a fast isomerization occurs leading to the formation of a cis-isomer (eq 1) cis‐Pd(II)L 2(R1)X → trans‐Pd(II)L 2(R1)(X)

Table 2. Computed Relative Energies of Various Ligands with Respect to Reactants energy (kcal mol−1) ∧

entry

ligand (L L)

transition statea

product

1 2 3 4b 5 6 7 8 9 10 11 12

P PM IMc P′d AM′e IM′ IM−Me IM-F IM−Me′ IM−F′ IM−Cy IM−Ph

14.1 (241i) 11.9 (165i) 9.1 (184i) 17.6 (246i) 11.9 (132i) 10.2 (162i) 10.1 (172i) 9.0 (217i) 9.7 (173i) 8.6 (205i) 10.5 (161i) 10.5 (191i)

−13.3 −26.3 −22.6 −12.1 −29.8 −28.3 −23.6 −12.5 −24.8 −17.9 −24.5 −19.7

a

Imaginary frequencies in parentheses. b Phenyl chloride is η -coordinated to Pd via C2 and C3 atoms. cDiimine. dDiphosphine. e Diamine. 2

Three major potential mechanisms have been identified including (i) a ligand-assisted process, (ii) direct ligand rearrangement, and (iii) dissociative mechanism for the cis−trans isomerization (Scheme 7). Computational results showed that the ligand-assisted process is kinetically favored,33 and the calculated barrier is 20 kcal mol−1.33,34 The ligand dissociation from a cis-Pd(II) complex, pathway (iii), also involves a barrier >20 kcal mol−1.35 Many factors including solvent, ligand, and temperature can have a significant influence on the isomerization mechanism and its rate. Transmetalation. In the carbon−carbon bond-forming reactions involving the TM step, the organic group R 2 attached with electropositive moiety “m” is transferred to the

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ACS Sustainable Chemistry & Engineering Scheme 7. Possible Mechanisms for cis−trans Isomerization

proceeds through the low energy barrier pathway A or B. The results observed by Braga et al. were also valid when the PH3 or vinyl ligands were replaced with PPh3 or phenyl groups, respectively.41 Hence, the authors suggested that both pathways may be operative and competitive.42−45 In 2008, Cid and co-workers reported the mechanistic studies of the reaction of 2(4)-bromopyridines with phenylboronic acid. 1 H and 31P NMR spectral techniques were used to monitor the reaction at various stages. Bromopyridine first reacted with Pd(PPh3)4 to give the trans-(Ph3P)2Pd(II)(Ar)(Br). As experimental studies gave little information, DFT studies were performed to identify the structure of intermediates of this reaction. Scheme 10 displays the energy profile showing that a TM step is involved for this system.46 Scheme 10. B3LYP Energy Profile for TM Reaction Between Ph−B(OH)3− and trans-[PdBr{C5H3N(4-C6H5)C2}(PH3)2]a

Scheme 8. Transmetalation Reaction of Electronegative Organic Group with Pd Catalyst

Pd(LnR1)X catalyst without any change in the oxidation state of Pd (Scheme 8). The mechanism for the TM step has been less studied because of the difficulty involved in the isolation and characterization of reaction intermediates, when the reaction is carried out experimentally. Among the different mechanistic studies attempted so far, Suzuki bond-forming reactions are probably the most studied.36−38 Issues like role of the base, R−X, and boronic acid, R−B(OH)2 on the TM step in the Suzuki−Miyaura reaction have been addressed and several proposals emerged.39 Two important roles were proposed for these species (Scheme 9).

a

All computed structures are labeled as I or TS.

The B3LYP energy profiles (in kcal mol−1) for the TM reaction between Ph−B(OH)3− and trans-[PdBr{C6H5}(PH3)2] or trans-[PdBr{C6H5}(PH3)2] in the gas phase and toluene, respectively, can also be found in Table 1. After realizing the role of the base in this reaction, the next issue was to find out the number of phosphine ligands involved, one or two, in the mechanism of the reaction. The effect of vinyl bromide with bisphosphine- and monophosphine-ligated Pd complexes in the presence of H2C = CHB(OH)2 within the full cycle of the Suzuki bond-forming reaction was computationally analyzed by Braga and co-workers.40,41 In addition, an alternative mechanism was also considered, depending on whether the isomer around the Pd center was cis or trans isomer. The authors began by mapping the Suzuki reaction, then diverged into investigating whether or not the Suzuki reaction proceeded via a monophosphine reaction pathway (Scheme 11) or biphosphine reaction pathway (Scheme 12). The Pd−P dissociation energy for the reaction was originally calculated using two phosphine ligands. Its energy barrier would then be compared to that for the reaction where one phosphine ligand was used. However, monophosphine species are very solvent dependent. Large entropy differences would cause difficulties in accurately modeling ligand dissociation energies. They found that both biphosphine and monophosphine reaction pathways could be involved in the TM step but were not able to distinguish which pathway was preferred. An interesting result from Schemes 11 and 12 is that the energy

Scheme 9. Role of Base in TM Process of Suzuki Reaction

Pathway A involves the binding of the base with the boronic acid to form organoboronate, but in pathway B, the base substitutes the leaving group X in the coordination sphere of the catalyst. Braga et al.40 postulated a direct mechanism in the absence of a base (pathway 0) apart from pathways A and B for a model reaction. In the absence of a base, pathway 0 requires a greater energy barrier (44 kcal mol−1) compared to the energy barrier (21 kcal mol−1) involved in the presence of OH− (pathways A and B). These results show the importance of adding the base in accordance with the experimental results. Therefore, the final conclusion is that the catalytic cycle likely 8479


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barriers never exceeded 25 kcal mol−1, indicating that the reaction involves low heat and could proceed at room temperature. The authors extended their work to the study of the participation of aryls in the same overall mechanism.41 The role of monophosphine complexes in the Suzuki reaction mechanism was also explained.47,48 The efficiency and selectivity of the Suzuki reaction were improved by dialkyl and biaryl phosphine ligands.49,50 Baillie et al.51 experimentally investigated the effect of introducing P(biphenyl)nPh3‑n type ligands, and among the biphenylphosphine ligands, P(biphenyl)Ph2 gave the highest conversions and turn overs. On the basis of a theoretical study on the use of P- and N-containing ligands with Pd catalysts in the Suzuki reaction, Hong et al.32 proposed two reaction pathways for this TM step (Scheme 13). Since the first step of the dissociative pathway (Route 1) was highly endothermic, Route 2 leading to the formation of a stable biaryl Pd complex as a reaction intermediate was favored. The activation energy for the TM process was lower in the presence of EWG but higher in the presence of EDG. Thus, the diimine ligands appear to act as excellent coordinating ligands for the Pd-catalyzed Suzuki reaction. The reaction rate was observed to be slow in the absence of a base. In order to realize the steric and electronic effects on the Suzuki−Miyaura reaction, a computational study has been carried out using a phosphine ligand (PMe3) and its analogues. In the TM step, a tetracoordinated Pd complex is transformed to a four-membered TS due to the chelation of the boronate, resulting in the formation of a Pd complex as shown in Scheme 14.

Scheme 11. Mechanistic Details for Monophosphine Pd Catalysts Derived from Theoretical Analysis Carried Out by Maseras et al.19

Scheme 12. Mechanistic Details for Bisphosphine Pd Catalysts Derived from Theoretical Analysis Carried Out by Maseras et al.19

Scheme 14. Effect of Phosphine Ligands in TM Reaction Pathway Analyzed by Harvey et al.52

The conclusion reached from the computational studies is that both steric and electronic effects were important, and their energy barriers were in the following order: P(CF3)3 < PPh3 < PMe3 < P(t-Bu3). Furthermore, π-acceptor phosphine ligands lowered the energy barrier for this step. It was rationalized by Scheme 13. Two Probable Pathways (Dissociative Pathway (Route 1) and Associative Pathway (Route 2)) for TM Process

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ACS Sustainable Chemistry & Engineering these facts that phosphine ligands had an ability to stabilize the electron density at the Pd center due to the nucleophilic attack of the boronate phenyl group on Pd.53 Reductive Elimination. A reductive elimination (RE) process is required in order for a full catalytic cycle to be completed in addition to the OA and TM steps, but it is less studied in depth computationally because this step continues very easily.54 A concerted mechanism was the most probable mechanism for this step. This last step features a cyclic TS, which accompanies the carbon−carbon bond-forming reaction, and the concomitant reformation of the PdL2 catalyst through a cyclic TS can be explained as shown in Scheme 15.

Scheme 16. Simplified Reaction Mechanisms for RE Step from PdR2L2

Scheme 15. Generally Accepted Mechanism for RE Step

For example, the use of PCy3 resulted in an increased reactivity through the monoligated reaction pathway, whereas the PMe3 ligand decreased the reactivity with respect to RE by stabilizing the four-coordinated complexes. Alternatively, the PPh3 ligand showed a good reactivity for both mechanisms, and therefore, it is treated as a more universal choice. The study of the effect of ancillary ligand L (L = acetonitrile, ethylene, maleic anhydride (ma)) on the C−C coupling reaction of [PdMe2(PMe3)L) showed that the reaction barrier at the DFT-B3LYP level increased in the order of maleic anhydride < “empty” < ethylene < PMe3 ≈ MeCN, confirming that the barrier decreased with the nature of π-accepting L.62 The bond-forming reaction was easier for the four-coordinated species with “ma” than that of the three-coordinated complex (ΔG# = 13.2 kcal mol−1 for L = empty and 8.6 kcal mol−1 for L = ma), owing to its better π-acceptor ability. The four coordinated complex with “ma” had an easier coupling compared to the three-coordinated complex. It, thus, appears that the reaction will be accelerated with strong π-accepting additives ability. The authors concluded this result with the features of RE in cis-[Pd(η1-allyl)2(PMe3)(L)],63 where Csp2−C′sp2 elimination is favored. Hong et al. used IM, P′, and AM′ ligands for the Suzuki−Miyaura bond-forming reaction of Ph−Cl with phenyl boronic acid.32 It is interesting to note the reverse order of the energy barrier calculated for the RE reaction (AM > IM > P) compared to the OA step. The values of activation energies collected in Table 3 clearly established the trend. Furthermore, the energy barrier for the RE reaction was in the following order: electron-withdrawing group on the diamine ligand < unsubstituted ligand < ligand carrying electron-donating group. Full Catalytic Cycle. All the DFT studies performed so far were carried out only for homogeneous-catalyzed reactions and not heterogeneous-catalyzed reactions, but a very few of them were attempted to study the full catalytic cycle.32,64−71 Suzuki−Miyaura Bond-Forming Reactions. The use of model systems is a common tool in computational chemistry to provide insights into their respective real systems, often yielding a very good results. Braga et al. characterized the different stages in the full catalytic cycle of a Suzuki−Miyaura model reaction of vinyl bromide with vinyl boronic acid by a Pd diphosphine catalyst through calculations of the corresponding intermediates and transition states.33 On the basis of these calculations, different alternative mechanisms were

Bulky and bidentate ligands with a big bite angles and Pd at a higher oxidation state facilitate the reaction which is usually irreversible. Apart from these facts, the solvent and additive used, temperature, and ligand features give significant effects on this step.55 In the RE reaction, the reaction rate is accelerated by the sterically bulky phosphine ligands as a repulsive interaction arises between L and the R groups in the parent R2PdL2 complex that influences the two groups in a close manner, thus facilitating this RE step. The three-coordinated complex generated by the leaving of a phosphine atom from the parent R2PdL2 accounts for the improved reactivity.56,57 The RE rate is enhanced by phosphine ligands carrying electron-donating groups. Pd(II) complexes with more electrophilic character than Pd(0) complexes become highly stable with electrondonating phosphine ligands. Hence, these ligands maintain a R2PdL2 complex to become more stable, thus enhancing their barrier for this step. Contrary to this, diphosphine ligands with a wide bite angles stabilize TS, resulting in the accelerated rate of the reaction.58 Ananikov et al.59−61 theoretically demonstrated the effects of different X ligands and alkyl groups on the RE of [Pd(CHCH 2 ) 2 X n ] (X = Cl, Br, I, NH 3 , PH 3 ) and cis-[Pd(R1)(R2)(PH3)2] complexes (R1 or R2= Me, vinyl, Ph, ethynyl), respectively. The rate of C−C bond formation increased in the order of Cl < Br < NH3 < I < PH3, and the energy barrier for the carbon−carbon bond formation from the symmetrical R2Pd(PH3)2 complex enhanced in the order of R = vinyl < Ph < ethynyl < Me. Furthermore, the exothermic values and energy barriers for asymmetrical R1−R2 coupling in R1R2Pd(PH3)2 were close to the averages of their corresponding values for symmetrical R1−R1 and R2−R2 coupling in R12Pd(PH3)2 and R22Pd(PH3)2, respectively. In the ONIOM approach, Me−Me bond formation from [PdR2Ln] (L = PPh3, PCy3, PMe3, and PH3; n = 1, 2) complexes was studied. The calculations showed that the parent complex energy is influenced by a steric effect, but the TS energy is affected by electronic effects. The RE barriers followed in the order of PPh3< PH3< PCy3< PMe3, and therefore, different reaction pathways may be involved upon changing the different types of L ligands, as shown in Scheme 16. 8481


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The reaction barriers for the insertion of olefin into the Pd(II)−(CHCH 2 ) bond in [Pd(PH 3 )(I)(CHCH 2 )(RHCCH2)] and cationic [Pd(H2PCH2PH2)(CHCH2) (RHCCH2)]+ complexes depended mostly on the regiochemistry of the system.72 For different substituents R under cationic and neutral conditions, the order of selectivity followed in the order of Cationic: COOMe < CN < CF3 < Ph < H < Me < CH2OH ∼ CH2NMe2 < 2-pyrolidone ∼ CH2SiMe3 < OAc < OMe < F and Neutral: COOMe < CN < CH2NMe2 < CF3 < Ph < CH2OH < Me ∼ OAc < CH2SiMe3 ∼ H< 2-pyrolidone ≪ OMe < F. The position of the R group either left or right of H decided the nature of the migratory reaction. Groups to the left of H directed to the β-carbon atom, while those to the right tended to direct the R group to the α-carbon atom. Scheme 1873 was proposed as the pathways based on these experimental results.

Table 3. Computed Relative Energies of Various Ligands with Respect to Reactants energy (kcal mol−1) no. 1 2 3 4 5 6 7 8 9 10 11 12 a c

∧

ligand (L L) b

P AMc IMd P′ AM′ IM′ IM−Me IM−F IM−Me′ IM−F′ IM−Cy IM−Ph

transition statea

products

9.0 (309i) 15.7 (330i) 13.2 (329i) 10.1 (313i) 17.7 (332i) 16.6 (327i) 13.6 (323i) 8.5 (315i) 14.4 (325i) 10.9 (314i) 13.7 (322i) 10.4 (316i)

−26.5 −9.4 −14.6 −27.9 −6.6 −9.0 −12.3 −24.0 −12.3 −20.2 −11.3 −15.8

Imaginary frequencies are given in parentheses. Diamine. dDiimine.

b

Diphosphine.

Scheme 18. Reaction Pathways Proposed for Migratory Insertion Step

Scheme 17. Free Energy Profile of Entire Catalytic Cycle for Reaction of H2CCHBr and H2C=B(OH)2 in Presence of OH− using [Pd(PH3)2] Catalyst According to Becke3LYP DFT Functional

DFT studies on the reaction of PhBr with CH2CH2 demonstrated that a Pd monophosphine species, Pd(PH3), Pd(PMe3), or Pd(PPh3), provides a favorable pathway compared to that involving Pd bisphosphine species.74,75 Oxidative addition is the rate-determining step in the full catalytic cycle in contrary to an earlier study where alkene coordination/migratory insertion was proposed as the rate-controlling step.76,77 When diaminocarbene ligands were employed in the Heck coupling reaction of PhBr with H2CCH2,78 the cationic pathway could be favored. A viable alternative reaction pathway (Scheme 19) is generated when a dipalladium species is involved in the reaction.79

proposed, and Scheme 17 shows the energy profile for the full catalytic cycle of the model reaction calculated from the Becke3LYP DFT functional. Through an exothermic reaction, cis-CH2CHPdBr(PH3)2 was formed due to the oxidative addition of vinyl halide to a linear Pd0(PH3)2 complex, and this reaction was proposed as the rate-determining step of the catalytic cycle. The alternative paths, either the dissociation or association of the phosphine external ligand, were difficult to compute because of the high barriers involved. According to Scheme 17, the energy difference between the reference point and TSOA, i.e., ΔG#, was the energy barrier for the rate-controlling step. Heck Bond-Forming Reactions. In the Heck reactions (eq 2), R1 from an aryl halide can attach to the α- or β-carbon of the alkene, and the migratory insertion step determined the regioselectivity.

Scheme 19. Alternative Heck Reaction Pathway Using Dipalladium Pd2(PMe3)2

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Therefore, the energetically less favored β-hydride elimination can be avoided in this reaction.85 In an attempt to understand the full Heck catalytic cycle, computational studies were carried out on a model system using PhBr and styrene as the reagents and HCO3− and [(NHC)PdCl]− (NHC = N-heterocyclic carbene) as a base and a catalyst, respectively.86 Plausible catalytic cycles involving anionic Pd intermediates in analogous cross-coupling reactions have been proposed based on theoretical findings47,48 as well as from the previous experimental results.87,88 Scheme 23 describes the computed full catalytic cycle profile (OA, migratory insertion, β-hydride elimination, and RE as the main steps) of this model reaction. In the text, the prefixes I and TS stand for intermediates and transition states, respectively. The energetic difference between the products and reactants is −50.3 kcal mol−1, indicating an exoergic process. The overall catalytic reaction profile goes downhill smoothly. In the first step, when the coupling between bromobenzene and [(NHC)PdCl]− species occurs, the first intermediate I1 is produced (−10.4 kcal mol−1 in relation to the separated reactants), which corresponds to the coordination of the benzene ring to the Pd complex via an η2-coordination mode. The OA continues the process to yield the intermediate I2 (exoergic, −43.5 kcal mol−1) via TS1 (higher by 4.7 kcal mol−1 with respect to I1), indicating that OA is the rate-determining step. The inclusion of the solvent effect elevates this value to 9.1 kcal mol−1 above the separate reactants. Since the bulky charged TS is largely altered by the nature of the polar solvent, the solvent has significant influence over the OA step in the overall profile. After the completion of the OA process, the styrene should replace Br− from the coordination sphere of the Pd metal center in intermediate I2. However, the authors were not able to locate TS for the direct Br− substitution by styrene. For styrene to coordinate to the metal center, it is necessary to have a vacant coordination site. Since Pd−Cl and Pd−NHC bonds are stronger than that of the Pd−Br bond, the dissociation of the Pd−Br bond was assumed. To estimate the value of an existing dissociation barrier of the Pd−Br bond, several constrained optimizations, including a Linear Least Motion (LLM) pathway were performed.89 It was assumed that the dissociation of bromine may bear a very small barrier. After Br− leaves the metal center, the styrene is inserted into the vacant site of the Pd metal center to create two intermediates, I3a and I3b. Intermediate I4a lying lower in energy than I4b is the major product of the insertion process. The energetics of the mechanism shows that the β-hydride syn elimination step proceeds

Scheme 2080 shows the steps involved when the reaction continued through the generation of Pd0(PPh3)2(OAc)−. Scheme 20. Acetate Ion-Ligated Pd(0) Complex

The production of anionic tricoordinated Pd(0) complexes gained support from the theoretical work of Shaik81 and Goossen.26,82 Generation of protons was likely to destabilize Pd0(PPh3)2(OAc)−, but the added amine (NEt3) captured the protons, thus making the anionic Pd0(PPh3)2(OAc)− more stable (Scheme 21). Scheme 21. Capture of Proton from Anionic Pd0(PPh3)2(OAc)−by NEt3

Scheme 22 shows the possibility of an ionic mechanism for the reaction of a cationic complex ArPdS(L)+ in the absence of a base at low temperature, which involved β-hydride elimination. The characterization of the cationic complex, σ-ArCH2CH(R)−Pd(THF)(dppf)+ (Ar = Ph, R = CO2Me; dppf = 1,1′-bis(diphenyl phosphino) ferrocene), in the absence of a base was achieved by 1H and 31P NMR spectroscopy.83 During β-hydride elimination, a linear alkene (E)-ArCHCHR and HPd(THF)(dppf)+ were formed. Another cationic complex, σ-PhCH2CH(R)−Pd(DMF)(dppp)+(R = Ph), obtained by the reaction of PhPd(dppp)+BF4− with styrene in DMF at −20 °C, was also characterized.84 Upon β-hydride elimination, (E)-stilbene and HPd(DMF)(dppp)+ were formed. DFT calculations indicated that a Pd0 complex was directly formed from the cationic σ-alkyl−Pd(II) adduct through the deprotonation of the agostic hydrogen in the presence of a base (Scheme 22).

Scheme 22. Formation of Linear and Branched Alkenes from (a, a′) Experimental Work and (b) DFT Calculations through Ionic Pathways

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ACS Sustainable Chemistry & Engineering Scheme 23. M06L/6-31+G(d) Integrated Relative Energy Profile for a Model Mizoroki−Heck Reactiona

a

Only stationary points with the lowest energy in the explored PES (potential energy surface).

through TS3a, and therefore, the major product is the trans Heck adduct. After releasing the product, Pd-hydride intermediate 17 is formed. In the RE step, the Pd metal center undergoes reduction with the active species [(NHC)PdCl]− being regenerated. RE occurs with no barriers, and the relative energy of the transition state TS4 is −48.0 kcal mol−1, in connection to the separate reactants. The relative electronic energy becomes −35.8 kcal mol−1 with similar structures when solvent effects are included. The protonated base, H2CO3, is still coordinated with Pd in I9, which is 50.3 kcal mol−1 below the energy state of reactants. Finally, after departing H2CO3 from the metal center, the catalyst [(NHC)PdCl]− species is regenerated (12). Sonogashira Bond-Forming Reaction. The Sonogashira reaction is a widely used method for producing aryl alkynes or conjugated enynes by the coupling of aryl halides (or triflates) with terminal acetylenes in the presence of a base (Scheme 24).

Scheme 25. (a) Mechanism of Sonogashira Reaction and (b) Copper-Free Sonogashira Bond-Forming Reaction

Scheme 24. Generally Accepted Reaction Pathway for Sonogashira Reaction by Pd-Catalyst Alhough a large amount of experimental data regarding the copper-co-catalyzed Sonogashira reaction has been published, computational studies are limited.90,91 Scheme 2692 shows the mechanism proposed for the transmetalation step which proceeds through either deprotonation or carbopalladation. Both mechanisms proceed through oxidative addition followed by ligand substitution to generate complex 3. However, despite difference in the subsequent steps, these two mechanisms lead to generate the same final product. In the deprotonation mechanism (Scheme 26), the Pd complex containing two organic groups in a cis configuration is formed through deprotonation of the alkyne and coordination of L. Finally, RE results in the formation of coupled product. In contrast, in the carbopalladation mechanism, the organic group R1 is added to complex 3 and then to the terminal R2≡H, followed by the coordination of L. Moreover, a subsequent base-mediated RE gives the coupled product. The deprotonation mechanism involves ligand exchange in the coordination sphere of the Pd center,66 and therefore, depending on the order of the ligand exchanges, both cationic and anionic mechanisms have been proposed for the deprotonation (Scheme 27).

The reaction mechanism consists of four steps, viz., OA, cis−trans isomerization, TM, and RE. In this protocol, copper (Cu) is employed as a co-catalyst, and the formation of a copper acetylide facilitates the transfer of an alkynyl moiety to the palladium catalyst. This, sometimes, greatly enhances the rate of the reaction but also can lead to homocoupling to yield adiyne. The mechanism of this reaction comprises two catalytic cycles: A and B (Scheme 25). Most computational studies have mainly concentrated on the pathways responsible for a copper-free Sonogashira reaction. The first step of this process, OA (see Scheme 25(B), I) is similar to that proposed for other bond-forming reactions. The next step, isomerization (Scheme 25(B), II) results in a product with a trans configuration. The third step (Scheme 25(B), III) leads to the formation of a cis-configured complex. The last step results in the formation of an acetylenic derivative, RCCR′ (Scheme 25 (B), IV), along with the reproduction of the Pd catalyst. 8484


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ACS Sustainable Chemistry & Engineering Scheme 26. Deprotonation (A) and Carbopalladation (B) Mechanisms

As far as the RE step is concerned, the carbopalladation pathway is preferred to the traditional mechanism.92 Though a number of reaction mechanisms are possible for the RE step depending on the presence of coordinating additives, it proceeds through a four-coordinated cis-PdR2L2 complex (R = Me, Ph, vinyl) as the most favored energetic patheway.62 From some theoretical studies, it was confirmed that steric and electronic effects of phosphine ligands have large impacts on the rate and mechanism of the reaction.61 A nice comparison is attempted for the Sonogashira crosscoupling reaction in the gas phase and in dichloromethane solution. In this reaction, Pd diphosphane and trimethylamine were used as the catalyst and base, respectively.69 In the gasphase reaction, through interaction with the phosphane ligands and reduction in the P−Pd−P angle, the halide ion reduced the steric interaction between the ligands and bromobenzene, thus lowering the transition state energy from 25.7 to 10.2 kcal mol−1. It was reversed in dichloromethane, but a halide ion alone is not responsible for this trend. Through an experiment carried out using a halide ion and the cation of the organic base, it was shown that both of these ions play important roles in the reaction.103,104 From the detailed experimental and theoretical study, a complete catalytic cycle in Sonogashira cross-coupling reactions is exothermic (eq 3).

Scheme 27. Cationic and Anionic Alternatives for Deprotonation Mechanism

Apart from the above examples, based on theoretical evaluations of the reaction mechanisms, an ionic mechanism was identified as the third reaction pathway. In this mechanism, the base serves as the substituent for the halide in the coordination sphere of the Pd species. This mechanism supports the experimental observation that alkynes carrying electron-withdrawing groups react faster. The conclusions regarding that oxidative addition (reaction of aryl halide with a Pd(0)catalyst) is the rate-limiting step and halide anion accelerates the reaction are supported from many experimental and theoretical studies.25,27,82,93−99 In the case of Sonogashira cross-coupling, the deprotonation step takes part in the reaction between a terminal acetylene and the oxidative addition product and results in the formation of PdL2Ar(CCAr′). Starting from the trans-PdL2ArX complex, this deprotonation step is generally thought to be the dominant reaction pathway.99,100 But, at the same time, their corresponding cis-isomer also proceeds a similar reaction, in which trans-PdL2ArX is not formed.96 The copper co-catalyst activates acetylenic compounds through the production of a copper acetylide derivative. Although reaction mechanisms have been proposed for the transmetalation step describing the role of copper acetylides, no theoretical evidence has appeared in the literature.101,102

PhBr + PhC = CH + Me3 → PhC = CPh + Me3N· HBr (3)

ΔGGP = −18.3 kcal mol−1, ΔG DCM = −28.0 kcal mol−1

Another computational study carried out by Sikk et al.70,71 on the copper-free Sonogashira bond-forming reaction between Ph−Br and phenylacetylene using tetrakis(triphenylphosphano)palladium and sec-butylamine as a catalyst and a base, respectively, showed that the complete catalytic cycle was exothermic (ΔH = −40.3 kcal mol−1, ΔG = −27.5 kcal mol−1) and was composed of four steps, as shown in Scheme 28.

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CONCLUSION AND FUTURE PERSPECTIVE The aim of this perspective is to provide readers with important developments achieved through computational studies on the mechanism of Pd-catalyzed organic transformations in the Suzuki, Heck, and Sonogashira reactions. Significant contributions through computational studies have been made in the past two decades based on the nature of ligands, metal catalysts, reactants used, and mechanistic details on Pd-catalyzed carbon−carbon bond-forming reactions. Since this reaction is a complicated and different kind of multistep catalytic process, the proposal of a suitable mechanism through identification of 8485


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ACS Sustainable Chemistry & Engineering Scheme 28. B3LYP/cc-pVDZ Integrated Relative Energy Profile for a Model Sonogashira Reaction

reaction intermediates by experimental techniques alone is difficult. Under these circumstances, computational chemistry is a powerful tool, facilitating to identify the mechanistic pathways and to fully clarify mechanisms in selected cases. In fact, it is possible to alter surfaces with enhanced catalytic properties based on computation studies. Density functional theory (DFT) studies predicted several competitive pathways with close energy barriers in many reactions. Indeed, both experimental and computational methods have been successfully applied to the OA and RE steps, and the mechanisms for these steps are now quite well understood. For example, computational studies have clarified the relationship between coordination number and selectivity in OA reactions, different issues including the role of the base in the TM step, and various mechanistic alternatives in the Sonogashira reaction. Computational chemistry should make additional contributions to get a more clear picture on the mechanism of the reaction. Most of the theoretical calclations have concentrated on the effect of the P group but little importance to chelating ligands containing S and O atoms. Thus, it is more important to understand the role of the ligands coordinated to Pd, as the ligand plays a key factor in stabilizing a supported Pd complex, and improving catalytic activity. In Heck reactions, several issues are still missing in the OA step. In the copper-free Sonogashira reaction, several reaction pathways appear to be operative, which might have competitive rates and could result in a change in the reaction conditions including solvent, ligands, substrates, bases, etc. These parameters might favor one reaction mechanism over the other. Thus, a detailed study is needed to access which mechanism is preferred for a particular reaction. To date, considerable efforts have been made to use computational techniques based on DFT to screen for improved homogeneous catalysts. As heterogeneous catalysts perform different reactions through modifying their surface charge, the mechanism for the solid-supported Pd-catalyzed reactions using DFTs should be performed to provide readers with additional guidance in assistance with designing solid supports and

nanocatalysts with desirable catalytic activities. It is strongly believed that computational study will further extend the scope of the carbon−carbon bond-forming reactions by solidsupported Pd catalysts to new reactant substrates, selectivity of the reactions, mechanistic elucidation, and help to design highly stable and efficient catalysts.

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AUTHOR INFORMATION

Corresponding Authors

*P. Veerakumar. E-mail: [email protected]. *P. Thanasekaran. E-mail: [email protected]. *S. Rajagopal. E-mail: [email protected]. ORCID

Pitchaimani Veerakumar: 0000-0002-6899-9856 Kuang-Lieh Lu: 0000-0002-5529-7126 King-Chuen Lin: 0000-0002-4933-7566 Notes

The authors declare no competing financial interest. Biographies

Dr. Pitchaimani Veerakumar obtained his M.Sc. (2004), M.Phil., (2007), and Ph.D. (2012) at the School of Chemistry Madurai Kamaraj University, Madurai, India. After his doctoral research (2008−2012), 8486


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include metallacycles, metal−organic materials, supramolecular chemistry, and green chemistry. In the past few years, his research effort has been devoted primarily to the design of very efficient synthetic self-assembly strategies and to the understanding of the simplicity-to-complexity processes that occur in supramolecular systems.

he joined as a Postdoctoral research fellow (2012−2016) the Institute of Atomic and Molecular Sciences, Academia Sinica (Prof. Shang-Bin Liu), Taiwan. Presently, he is jointly appointed as a Postdoctoral research fellow in the Department of Chemistry, National Taiwan University (Prof. King-Chuen Lin’s group), Taiwan. His research interests include the synthesis and characterization of mesoporous porous carbon/silica and their catalytic developments, preparation of high surface area porous carbons from biowastes for sustainable energy applications, and synthesis and modification of novel porous carbon materials for applications as electrocatalysts in supercapacitors and electrochemical sensors.

Prof. King-Chuen Lin is a Distinguished Professor of the Department of Chemistry at National Taiwan University and a Distinguished Research Fellow of National Science Council, Taiwan. He received his B.S. degree in Chemistry from National Taiwan University, Taiwan, his Ph.D. in Chemistry from Michigan State University, USA, and he pursued his postdoctoral career at Cornell University. His research interests include photodissociation and reaction dynamics in gas and condensed phases, atmospheric chemistry, and single molecule spectroscopy.

Dr. Pounraj Thanasekaran received his Ph.D. in 1998 under the supervision of Prof. S. Rajagopal from Madurai Kamaraj University, India. From 1999−2001, he received a Research Associateship from the Council of Scientific and Industrial Research, India. He worked as a Postdoctoral Fellow at the Institute of Chemistry, Academia Sinica, Taiwan, in Prof. Kuang-Lieh Lu’s group (2001−2006) then in Prof. David M. Stanbury’s group, Auburn University, Alabama, USA (2006− 2007). He served as a Lecturer in the School of Chemistry, Madurai Kamaraj University (2007−2008), before moving to Prof. Lan-Chang Liang’s laboratory, National Sun-Yat Sen University, Taiwan, as a Postdoctoral Fellow from 2008−2009. He worked again as a Postdoctoral Fellow with Prof. Kuang-Lieh Lu until 2014. Since 2014, he has been working as a Postdoctoral Fellow with Dr. Hsien-Ming Lee. His current research focuses on the development of upconversion nanoparticle-mediated NIR photoreleasing and biomedical imaging studies, cellular drug delivery systems using liposomes, and nanoparticles. His research interests also include synthesis, photophysical properties, and applications of supramolecular functional materials.

Prof. Seenivasan Rajagopal received his Ph.D. in 1984 from Madurai Kamaraj University under the tutelage of Prof. C. Srinivasan. In 1985, he was selected as an UNESCO fellow for postdoctoral research with Prof. Shigeo Tazuke at the Tokyo Institute of Technology, Tokyo, Japan. After over 40 years of teaching and research, at present, he is serving as an UGC-BSR Faculty Fellow, Department of Physical Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai. He has authored more than 100 papers with international repute. His current research is primarily focused on synthesis, characterization, and photophysical studies of some novel Ru, Os, and Re organometallic complexes. His research also targets the development of synthesis of novel metal nanocatalysts for organic transformations and luminescent materials for protein-binding studies and biosensors.

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ACKNOWLEDGMENTS The authors thank the Ministry of Science and Technology (MOST) and Academia Sinica, Taiwan, for financial supports. S.R. thanks the University Grants Commission-Basic Scientific Research (UGC-BSR), New Delhi, for financial support.

Prof. Kuang-Lieh Lu obtained his Ph.D. in 1989 from the National Taiwan University. He is currently a Research Fellow in the Institute of Chemistry at Academia Sinica and an Adjunct Professor at National Taiwan Normal University and National Central University. Current research interests 8487


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(22) Senn, H. M.; Ziegler, T. Oxidative addition of aryl halides to palladium(0) complexes: A density-functional study including solvation. Organometallics 2004, 23, 2980−2988. (23) Lyngvi, E.; Schoenebeck, F. Oxidative addition transition states of Pd(0) complexes in polar solvent-a DFT study involving implicit and explicit solvation. Tetrahedron 2013, 69, 5715−5718. (24) Legault, C. Y.; Garcia, Y.; Merlic, C. A.; Houk, K. N. Origin of regioselectivity in palladium-catalyzed cross-coupling reactions of polyhalogenated heterocycles. J. Am. Chem. Soc. 2007, 129, 12664− 12665. (25) Kozuch, S.; Amatore, C.; Jutand, A.; Shaik, S. What makes for a good catalytic cycle? A theoretical study of the role of an anionic palladium(0) complex in the cross-coupling of an aryl halide with an anionic nucleophile. Organometallics 2005, 24, 2319−2330. (26) Goossen, L. J.; Koley, D.; Hermann, H. L.; Thiel, W. Mechanistic pathways for oxidative addition of aryl halides to palladium(0) complexes: A DFT study. Organometallics 2005, 24, 2398−2410. (27) Goossen, L. J.; Koley, D.; Hermann, H.; Thiel, W. The mechanism of the oxidative addition of aryl halides to Pd-catalysts: A DFT investigation. Chem. Commun. 2004, 2141−2143. (28) Amatore, C.; Jutand, A. Anionic Pd(0) and Pd(II) intermediates in palladium-catalyzed Heck and cross-coupling reactions. Acc. Chem. Res. 2000, 33, 314−321. (29) Ahlquist, M.; Fristrup, P.; Tanner, D.; Norrby, P.-O. Theoretical evidence for low-ligated palladium(0): [Pd-L] as the active species in oxidative addition reactions. Organometallics 2006, 25, 2066−2073. (30) Ariafard, A.; Lin, Z. Understanding the relative easiness of oxidative addition of aryl and alkyl halides to palladium(0). Organometallics 2006, 25, 4030−4033. (31) Luh, T.-Y.; Leung, M.-K.; Wong, K.-T. Transition metal-catalyzed activation of aliphatic C−X bonds in carbon−carbon bond formation. Chem. Rev. 2000, 100, 3187−3204. (32) Huang, Y.-L.; Weng, C.-M.; Hong, F.-E. Density functional studies on palladium catalyzed Suzuki-Miyaura cross-coupling reactions assisted by N- or P-chelating ligands. Chem. - Eur. J. 2008, 14, 4426− 4434. (33) Braga, A. A. C.; Ujaque, G.; Maseras, F. A DFT study of the full catalytic cycle of the Suzuki−Miyaura cross-coupling on a model system. Organometallics 2006, 25, 3647−3658. (34) Alvarez, R.; Faza, O. N.; Lopez, C. S. D.; de Lera, A. R. Computational characterization of a complete Palladium-catalyzed cross-coupling process: The associative transmetalation in the Stille reaction. Org. Lett. 2006, 8, 35−38. (35) Nova, A.; Ujaque, G.; Maseras, F.; Lledos, A.; Espinet, P. A critical analysis of the cyclic and open alternatives of the transmetalation step in the Stille cross-coupling reaction. J. Am. Chem. Soc. 2006, 128, 14571− 14578. (36) Casado, A. L.; Espinet, P. On the configuration resulting from oxidative addition of RX to Pd(PPh3)4 and the mechanism of the cis-totrans isomerization of [PdRX(PPh3)2] complexes (R = aryl, X = halide). Organometallics 1998, 17, 954−959. (37) Miyaura, N.; Yamada, K.; Suzuki, A. New stereospecific crosscoupling by the palladium-catalyzed reaction of 1-alkenylboranes with 1alkenyl or 1-alkynyl halides. Tetrahedron Lett. 1979, 20, 3437−3440. (38) Miyaura, N.; Suzuki, A. Palladium-catalyzed cross-coupling reactions of organoboron compounds. Chem. Rev. 1995, 95, 2457− 2483. (39) Miyaura, N. Cross-coupling reaction of organoboron compounds via base-assisted transmetalation to palladium(II) complexes. J. Organomet. Chem. 2002, 653, 54−57. (40) Braga, A. A. C.; Morgon, N. H.; Ujaque, G.; Maseras, F. Computational characterization of the role of the base in the SuzukiMiyaura cross-coupling reaction. J. Am. Chem. Soc. 2005, 127, 9298− 9307. (41) Braga, A. A. C.; Morgon, N. H.; Ujaque, G.; Lledos, A.; Maseras, F. Computational study of the transmetalation process in the SuzukiMiyaura cross-coupling of aryls. J. Organomet. Chem. 2006, 691, 4459− 4466.

REFERENCES

(1) Kohei, T.; Miyaura, N. Cross-Coupling Reactions; Springer, 2002; pp 1−9. (2) Miyaura, N.; Buchwald, S. L. Cross-Coupling Reactions: A Practical Guide; Springer, 2002; Vol. 219. (3) Melchor, M. G. A Theoretical Study of Pd-Catalyzed C−C CrossCoupling Reactions; Springer, 2013; pp 1−55. (4) Colacot, T. New Trends in Cross-Coupling: Theory and Applications; RSC Publishing, 2014, DOI:10.1039/9781782620259. (5) Xie, H.; Fan, T.; Lei, Q.; Fang, W. New progress in theoretical studies on palladium-catalyzed C−C bond-forming reaction mechanisms. Sci. China: Chem. 2016, 59, 1432−1447. (6) Dobrounig, P.; Trobe, M.; Breinbauer, R. Sequential and iterative Pd-catalyzed cross-coupling reactions in organic synthesis. Monatsh. Chem. 2017, 148, 3−35. (7) Narayanan, R.; Tabor, C.; El-Sayed, M. A. Can the observed changes in the Size or shape of a colloidal nanocatalyst reveal the nanocatalysis mechanism type: Homogeneous or heterogeneous? Top. Catal. 2008, 48, 60−74. (8) Sperger, T.; Sanhueza, I. A.; Kalvet, I.; Schoenebeck, F. Computational studies of synthetically relevant homogeneous organometallic catalysis involving Ni, Pd, Ir, and Rh: An overview of commonly employed DFT methods and mechanistic insights. Chem. Rev. 2015, 115, 9532−9586. (9) Sperger, T.; Fisher, H. C.; Schoenebeck, F. Computationally deciphering palladium-catalyzed reaction mechanisms. WIREs Comput. Mol. Sci. 2016, 6, 226−242. (10) Bonney, K. J.; Schoenebeck, F. Experiment and computation: Acombined approach to study the reactivity of palladium complexes in oxidation states 0 to IV. Chem. Soc. Rev. 2014, 43, 6609−6638. (11) Becke, A. D. Density-functional thermochemistry III. The role of exact exchange. J. Chem. Phys. 1993, 98, 5648−5652. (12) Zhao, Y.; Truhlar, D. G. The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: Two new functionals and systematic testing of four M06-class functionals and 12 other functionals. Theor. Chem. Acc. 2008, 120, 215−241. (13) Perdew, J. P.; Chevary, J. A.; Vosko, S. H.; Jackson, K. A.; Pederson, M. R.; Singh, D. J.; Fiolhais, C. Atoms, molecules, solids, and surfaces: Applications of the generalized gradient approximation for exchange and correlation. Phys. Rev. B: Condens. Matter Mater. Phys. 1992, 46, 6671−6687. (14) Low, J. J.; Goddard, W. A. Theoretical studies of oxidative addition and reductive elimination. 3. C-H and C-C reductive coupling frompalladium and platinum bis(phosphine) complexes. J. Am. Chem. Soc. 1986, 108, 6115−6128. (15) Lam, K. C.; Marder, T. B.; Lin, Z. DFT studies on the effect of the nature of the aryl halide Y−C6H4−X on the mechanism of its oxidative addition to Pd0L versus Pd0L2. Organometallics 2007, 26, 758−760. (16) Galardon, E.; Ramdeehul, S.; Brown, J. M.; Cowley, A.; Hii, K. K.; Jutand, A. Profound steric control of reactivity in arylhalide addition to bisphosphane palladium(0)complexes. Angew. Chem., Int. Ed. 2002, 41, 1760−1763. (17) Ahlquist, M.; Norrby, P.-O. Oxidative addition of aryl chlorides to monoligated palladium(0): A DFT-SCRF study. Organometallics 2007, 26, 550−553. (18) Barrios-Landeros, F.; Carrow, B. P.; Hartwig, J. F. Effect of ligand steric properties and halide identity on the mechanism for oxidative addition of haloarenes to trialkylphosphine Pd(0) complexes. J. Am. Chem. Soc. 2009, 131, 8141−8154. (19) Besora, M.; Gourlaouen, C.; Yates, B.; Maseras, F. Phosphine and solvent effects on oxidative addition of CH3Br to Pd(PR3) and Pd(PR3)2 complexes. Dalton Trans. 2011, 40, 11089−11094. (20) McMullin, C. L.; Jover, J.; Harvey, J. N.; Fey, N. Accurate modeling of Pd(0) + PhX oxidative addition kinetics. Dalton Trans. 2010, 39, 10833−10836. (21) Li, Z.; Fu, Y.; Guo, Q. X.; Liu, L. Theoretical study on monoligated Pd-catalyzed cross-coupling reactions of aryl chlorides and bromides. Organometallics 2008, 27, 4043−4049. 8488


Perspective

ACS Sustainable Chemistry & Engineering (42) Amatore, C.; Jutand, A.; Le Duc, G. Kinetic data for the transmetalation/reductive elimination in palladium-catalyzed SuzukiMiyaura reactions: Unexpected triple role of hydroxide ions used as base. Chem. - Eur. J. 2011, 17, 2492−2503. (43) Carrow, B. P.; Hartwig, J. F. Distinguishing between pathways for transmetalation in Suzuki-Miyaura reactions. J. Am. Chem. Soc. 2011, 133, 2116−2119. (44) Butters, M.; Harvey, J. N.; Jover, J.; Lennox, A. J. J.; Lloyd-Jones, G. C.; Murray, P. M. Aryltrifluoroborates in Suzuki-Miyaura coupling: The roles of endogenous arylboronic acid and fluoride. Angew. Chem., Int. Ed. 2010, 49, 5156−5160. (45) Lennox, A. J. J.; Lloyd-Jones, G. C. Transmetalation in the SuzukiMiyaura coupling: The fork in the trail. Angew. Chem., Int. Ed. 2013, 52, 7362−7370. (46) Sicre, C.; Braga, A. A. C.; Maseras, F.; Cid, M. M. Mechanistic insights into the transmetalation step of a Suzuki−Miyaura reaction of 2(4)-bromopyridines: Characterization of an intermediate. Tetrahedron 2008, 64, 7437−7443. (47) Goossen, L. J.; Koley, D.; Hermann, H. L.; Thiel, W. Palladium monophosphine intermediates in catalytic cross-coupling reactions: A DFT study. Organometallics 2006, 25, 54−67. (48) Goossen, L. J.; Koley, D.; Hermann, H. L.; Thiel, W. The palladium-catalyzed cross coupling reaction of carboxylic anhydrides with arylboronic acids: A DFT study. J. Am. Chem. Soc. 2005, 127, 11102−11114. (49) Martin, R.; Buchwald, S. L. Palladium-catalyzed Suzuki-Miyaura cross-coupling reactions employing dialkylbiaryl phosphine ligands. Acc. Chem. Res. 2008, 41, 1461−1473 and cited references therein.. (50) Barder, T. E.; Walker, S. D.; Martinelli, J. R.; Buchwald, S. L. Catalysts for Suzuki-Miyaura coupling processes: Scope and studies of the effect of the ligand structure. J. Am. Chem. Soc. 2005, 127, 4685− 4696. (51) Joshaghani, M.; Faramarzi, E.; Rafiee, E.; Daryanavard, M.; Xiao, J.; Baillie, C. Efficient Suzuki cross-coupling reactions using bulky phosphines. J. Mol. Catal. A: Chem. 2006, 259, 35−40. (52) Jover, J.; Fey, N.; Purdie, M.; Lloyd-Jones, G. C.; Harvey, J. N. A computational study of phosphine ligand effects in Suzuki-Miyaura coupling. J. Mol. Catal. A: Chem. 2010, 324, 39−47. (53) Kozuch, S.; Martin, J. M. L. What makes for a bad catalytic cycle? A theoretical study on the Suzuki-Miyaura reaction within the energetic span model. ACS Catal. 2011, 1, 246−253. (54) Ananikov, V. P.; Musaev, D. G.; Morokuma, K. Transition Metal Catalyzed CarbonCarbon Bond Formation: The Key of Homogeneous Catalysis. In Computational Modeling for Homogeneous and Enzymatic Catalysis A Knowledge-Base for Designing Efficient Catalysis; Ananikov, V. P.; Musaev, D. G.; Morokuma, K., Eds.; , Eds.; Wiley-VCH GmbH & Co KGaA: Weinheim, Germany, 2008; pp 131−148. (55) Hartwig, J. F. Electronic effects on reductive elimination to form carbon−carbon and carbon−heteroatom bonds from palladium(II) complexes. Inorg. Chem. 2007, 46, 1936−1947. (56) Brown, J. M.; Cooley, N. A. Carbon-carbon bond formation through organometallic elimination reactions. Chem. Rev. 1988, 88, 1031−1046. (57) Macgregor, S. A.; Neave, G. W.; Smith, C. Theoretical studies on C-heteroatom bond formation via reductive elimination from group 10 M(PH3)2(CH3)(X) species (X = CH3, NH2, OH, SH) and the determination of metal-X bond strengths using density functional theory. Faraday Discuss. 2003, 124, 111−127. (58) Zuidema, E.; van Leeuwen, P. W. N. M.; Bo, C. Reductive elimination of organic molecules from palladium-diphosphine complexes. Organometallics 2005, 24, 3703−3710. (59) Ananikov, V. P.; Musaev, D. G.; Morokuma, K. Vinyl-vinyl coupling on late transition metals through C−C reductive elimination mechanism. A computational study. J. Am. Chem. Soc. 2002, 124, 2839− 2852. (60) Ananikov, V. P.; Musaev, D. G.; Morokuma, K. Theoretical insight into the C−C coupling reactions of the vinyl, phenyl, ethynyl, and methyl complexes of palladium and platinum. Organometallics 2005, 24, 715−723.

(61) Ananikov, V. P.; Musaev, D. G.; Morokuma, K. Critical effect of phosphane ligands on the mechanism of carbon-carbon bond formation involving palladium(II) complexes: a theoretical investigation of reductive elimination from square-planar and T-shape species. Eur. J. Inorg. Chem. 2007, 2007, 5390−5399. (62) Perez-Rodriguez, M.; Braga, A. A. C.; Garcia-Melchor, M.; PerezTemprano, M.; Casares, J. A.; Ujaque, G.; de Lera, A. R.; Alvarez, R.; Maseras, F.; Espinet, P. C−C reductive elimination in palladium complexes, and the role of coupling additives A DFT study supported by experiment. J. Am. Chem. Soc. 2009, 131, 3650−3655. (63) Perez-Rodríguez, M.; Braga, A. A. C.; de Lera, A.; Maseras, F.; Alvarez, R.; Espinet, P. A DFT study of the effect of the ligands in the reductive elimination from palladium bis(allyl) complexes. Organometallics 2010, 29, 4983−4991. (64) Xue, L.; Lin, Z. Theoretical aspects of palladium-catalysed carbon−carbon cross-coupling reactions. Chem. Soc. Rev. 2010, 39, 1692−1705. (65) García-Melchor, M.; Braga, A. A. C.; Lledós, A.; Ujaque, G.; Maseras, F. Computational perspective on Pd-Catalyzed C-C crosscoupling reaction mechanisms. Acc. Chem. Res. 2013, 46, 2626−2634. (66) García-Melchor, M.; Pacheco, M. C.; Nájera, C.; Lledós, A.; Ujaque, G. mechanistic exploration of the Pd-catalyzed copper-free Sonogashira reaction. ACS Catal. 2012, 2, 135−144. (67) Balcells, D.; Maseras, F.; Keay, B. A.; Ziegler, T. Polyene cyclization by a double intramolecular Heck reaction. A DFT study. Organometallics 2004, 23, 2784−2796. (68) Xie, H.; Fan, T.; Lei, Q.; Fang, W. New progress in theoretical studies on palladium-catalyzed C−C bond-forming reaction mechanisms. Sci. China: Chem. 2016, 59, 1432−1447. (69) Sikk, L.; Tammiku-Taul, J.; Burk, P.; Kotschy, A. Computational study of the Sonogashira cross-coupling reaction in the gas phase and in dichloromethane solution. J. Mol. Model. 2012, 18, 3025−3033. (70) Sikk, L.; Tammiku-Taul, J.; Burk, P. Computational study of copper-Free Sonogashira cross-coupling reaction. Organometallics 2011, 30, 5656−5664. (71) Sikk, L.; Tammiku-Taul, J.; Burk, P. Computational study of the copper-free Sonogashira cross-coupling reaction: shortcuts in the mechanism. Proc. Est. Acad. Sci. 2013, 62, 133−140. (72) Deeth, R. J.; Smith, A.; Brown, J. M. Electronic control of the regiochemistry in palladium−phosphine catalyzed intermolecular Heck reactions. J. Am. Chem. Soc. 2004, 126, 7144−7151. (73) Cabri, W.; Candiani, I. Recent developments and new perspectives in the Heck reaction. Acc. Chem. Res. 1995, 28, 2−7. (74) Surawatanawong, P.; Fan, Y.; Hall, M. B. Density functional study of the complete pathway for the Heck reaction with palladium diphosphines. J. Organomet. Chem. 2008, 693, 1552−1563. (75) Lee, M.-T.; Lee, H. M.; Hu, C.-H. A Theoretical study of the Heck reaction: N-Heterocyclic carbene versus phosphine ligands. Organometallics 2007, 26, 1317−1324. (76) van Strijdonck, G. P. F.; Boele, M. D. K.; Kamer, P. C. J.; de Vries, J. G.; van Leeuwen, P. W. N. M. Fast palladium catalyzed arylation of alkenes using bulky monodentate phosphorus ligands. Eur. J. Inorg. Chem. 1999, 1999, 1073−1076. (77) Knowles, J. P.; Whiting, A. The Heck−Mizoroki cross-coupling reaction: a mechanistic perspective. Org. Biomol. Chem. 2007, 5, 31−44. (78) Albert, K.; Gisdakis, P.; Rosch, N. On C−C coupling by carbenestabilized palladium catalysts: A density functional study of the Heck reaction. Organometallics 1998, 17, 1608−1616. (79) Surawatanawong, P.; Hall, M. B. Theoretical study of alternative pathways for the Heck reaction through dipalladium and “ligand-free” palladium intermediates. Organometallics 2008, 27, 6222−6232. (80) Amatore, C.; Carre, E.; Jutand, A.; M’Barki, M. A.; Meyer, G. Evidence for the ligation of palladium(0) complexes by acetate ions: Consequences on the mechanism of their oxidative addition with phenyl iodide and PhPd(OAc)(PPh3)2 as intermediate in the Heck reaction. Organometallics 1995, 14, 5605−5614. (81) Kozuch, S.; Shaik, S.; Jutand, A.; Amatore, C. Active anionic zerovalent palladium catalysts: characterization by density functional calculations. Chem. - Eur. J. 2004, 10, 3072−3080. 8489


Perspective

ACS Sustainable Chemistry & Engineering (82) Goossen, L. J.; Koley, D.; Hermann, H. L.; Thiel, W. The mechanism of the oxidative addition of aryl halides to Pd-catalysts: A DFT investigation. Chem. Commun. 2004, 2141−2143. (83) Brown, J. M.; Hii, K. K. Characterization of reactive intermediates in palladiumcatalyzed arylation of methyl acrylate (Heck reaction). Angew. Chem., Int. Ed. Engl. 1996, 35, 657−659. (84) Ludwig, M.; Stromberg, S.; Svensson, M.; Akermark, B. An exploratory study of regiocontrol in the Heck type reaction. Influence of solvent polarity and bisphosphine ligands. Organometallics 1999, 18, 970−975. (85) Deeth, R. J.; Smith, A.; Hii, K. K.; Brown, J. M. The Heck olefination reaction; A DFT study of the elimination pathway. Tetrahedron Lett. 1998, 39, 3229−3232. (86) Guest, D.; Menezes da Silva, V. H.; de Lima Batista, A. P.; Roe, S. M.; Braga, A. A. C.; Navarro, O. (N-heterocyclic carbene)-palladate complexes in anionic Mizoroki−Heck coupling cycles: A combined experimental and computational study. Organometallics 2015, 34, 2463−2470. (87) Amatore, C.; Jutand, A. Anionic Pd(0) and Pd(II) Intermediates in Palladium-Catalyzed Heck and cross-coupling reactions. Acc. Chem. Res. 2000, 33, 314−321. (88) Carrow, B. P.; Hartwig, J. F. A New Palladium precatalyst allows for the fast Suzuki−Miyaura coupling reactions of unstable polyfluorophenyl and 2-heteroaryl boronic acids. J. Am. Chem. Soc. 2010, 132, 79−81. (89) Bode, B.; Gordon, M. S. Macmolplt: A graphical user interface for GAMESS. J. Mol. Graphics Modell. 1998, 16, 133−138. (90) Chen, L.; Hong, S.; Hou, H. Theoretical study on the mechanism of Sonogashira coupling reaction. Chin. J. Struct. Chem. 2008, 27, 1404− 1411. (91) Fairlamb, I. J. S.; O’Brien, C. T.; Lin, Z.; Lam, K. C. Regioselectivity in the Sonogashira coupling of 4,6-dichloro-2-pyrone. Org. Biomol. Chem. 2006, 4, 1213−1216. (92) Ljungdahl, T.; Bennur, T.; Dallas, A.; Emtenas, H.; Martensson, J. Two competing mechanisms for the copper-free Sonogashira crosscoupling reaction. Organometallics 2008, 27, 2490−2498. (93) Amatore, C.; Pfluger, F. Mechanism of oxidative addition of palladium(0) with aromatic iodides in toluene, monitored at ultramicroelectrodes. Organometallics 1990, 9, 2276−2282. (94) Besora, M.; Gourlaouen, C.; Yates, B.; Maseras, F. Phosphine and solvent effects on oxidative addition of CH3Br to Pd(PR3) and Pd(PR3)2 complexes. Dalton Trans. 2011, 40, 11089−11094. (95) Sun, W.-J.; Chu, W.; Yu, L.-J.; Jiang, C.-F. Ligand size effect on PdLn oxidative addition with aryl bromide: A DFT study. Chin. J. Chem. Phys. 2010, 23, 175−179. (96) Mitchell, E. A.; Jessop, P. G.; Baird, M. C. A kinetics study of the oxidative addition of bromobenzene to Pd(PCy3)2 (Cy = cyclohexyl) in a nonpolar medium: the influence on rates of added PCy3 and bromide ion. Organometallics 2009, 28, 6732−6738. (97) Amatore, C.; Jutand, A.; Lemaitre, F.; Lucricard, J.; Kozuch, S.; Shaik, S. Formation of anionic palladium(0) complexes ligated by the trifluoroacetate ion and their reactivity in oxidative addition. J. Organomet. Chem. 2004, 689, 3728−3734. (98) Amatore, C.; Azzabi, M.; Jutand, A. Role and effects of halide ions on the rates and mechanisms of oxidative addition of iodobenzene to low-ligated zerovalent palladium complexes Pd0(PPh3)2. J. Am. Chem. Soc. 1991, 113, 8375−8384. (99) Soheili, A.; Albaneze-Walker, J.; Murry, J. A.; Dormer, P. G.; Hughes, D. L. Efficient and general protocol for the copper-free Sonogashira coupling of aryl bromides at room temperature. Org. Lett. 2003, 5, 4191−4194. (100) Amatore, C.; Jutand, A.; Suarez, A. Intimate mechanism of oxidative addition to zerovalent palladium complexes in the presence of halide ions and its relevance to the mechanism of palladium-catalyzed nucleophilic substitutions. J. Am. Chem. Soc. 1993, 115, 9531−9541. (101) Prokopcová, H.; Kappe, C. O. Desulfitative carbon−carbon cross-coupling of thioamide fragments with boronic acids. Adv. Synth. Catal. 2007, 349, 448−452.

(102) Prokopcová, H.; Kappe, C. O. Palladium(0)-catalyzed, copper (I)-mediated coupling of boronic acids with cyclic thioamides. Selective carbon-carbon bond formation for the functionalization of heterocycles. J. Org. Chem. 2007, 72, 4440−4448. (103) Senn, H. M.; Ziegler, T. Oxidative addition of aryl halides to palladium(0) complexes: A density-functional study including solvation. Organometallics 2004, 23, 2980−2988. (104) Barrios-Landeros, F.; Carrow, B. P.; Hartwig, J. F. Autocatalytic oxidative addition of PhBr to Pd(PtBu3)2 via Pd(PtBu3)2(H)(Br). J. Am. Chem. Soc. 2008, 130, 5842−5843.

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Computational Studies of Versatile Heterogeneous Palladium

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