Chemical Society Reviews Challenges in Modelling Homogeneous Catalysis: New Answers from Ab Initio Molecular Dynamics to the Controversy over the Wacker Process Journal: Chemical Society Reviews Manuscript ID: CS-TRV-12-2013-060469.R1 Article Type: Tutorial Review Date Submitted by the Author: 24-Feb-2014 Complete List of Authors: Lledos, A; Universitat Autonoma de Barcelona, Ujaque, Gregori; Universitat Autonoma de Barcelona, Stirling, Andras; Chemical Research Center of the Hungarian Academy of Sciences, Theoretical Chemistry Department Nair, Nisanth; Indian Institute of Technology Kanpur, Department of Chemistry Page 1 of 16Journal Name Chemical Society Reviews Dynamic Article Links ► Cite this: DOI: 10.1039/c0xx00000x www.rsc.org/xxxxxx ARTICLE TYPE Challenges in Modelling Homogeneous Catalysis: New Answers from Ab Initio Molecular Dynamics to the Controversy over the Wacker Process András Stirling,* a Nisanth N. Nair,*b Agustí Lledós*c and Gregori Ujaque*c Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX 5 DOI: 10.1039/b000000x We present here a review on the mechanistic studies of the Wacker process stressing the long controversy about the key reaction steps. We give an overview of the previous experimental and theoretical works on the topic. Then we describe the importance of the most recent Ab Initio Molecular Dynamics (AIMD) calculations in modelling organometallic reactivity in water. As a prototypical example of homogeneous 10 catalytic reactions, the Wacker process poses serious challenges to modelling. The adequate description of the multiple role of the water solvent is very difficult by using static quantum chemical approaches including cluster and continuum solvent models. In contrast, such reaction systems are suitable for AIMD, and by combining with rare event sampling techniques, the method provides reaction mechanisms and the corresponding free energy profiles. The review also highlights how AIMD has helped to obtain 15 novel understanding of the mechanism and kinetics of the Wacker process. reactions for the addition of several nucleophiles to alkenes. Introduction Importantly, the formation of new C–O, C–N and C–C bonds, including intra- and intermolecular reactions has been extensively The Wacker process is an outstanding example of homogeneous 4 1,2,3 45 investigated. The application of this process in synthesis, catalytic reaction applied in industry. The process was however, required development of appropriate conditions, such as 20 discovered in the late 1950s by Schmid et al. at Wacker Chemie those worked out by Tsuji. 5 A common issue in designing an for producing acetaldehyde from ethene and oxygen (Scheme 1). economic catalytic cycle for these olefin oxidations is the It allowed the use of ethene, instead of the more expensive and efficient regeneration of the active Pd(II) catalyst. In this sense, energy-rich acetylene as feedstock for aliphatic organic 50 recent progress is achieved moving toward using molecular chemistry. Moreover, this reaction was the starting point for the 6 oxygen as oxidant in synthetic reactions. 25 development of catalytic palladium chemistry. The rate expression for the Wacker process was established + + 2+ by Henry’s group in a seminal work, exhibiting a first order in 1/2 O2 + 2H 2Cu Pd C2H4 + H2O 2– ethene and the catalyst (taking [PdCl 4] as the resting state) and (2) (1) + – 7 55 inhibition by [H ] and [Cl ] to the second order (eq. 4). 2+ 0 + H2O 2Cu Pd CH3CHO + 2H Additional kinetic studies by the same group also established a – Scheme 1 General scheme of the Wacker process. Numbers correspond to new rate equation at high [Cl ] with no proton inhibition term (eq. 8 chemical equations. 5). 2- The stoichiometric oxidation of ethene by Pd(II) salts was ‾ ƬPdCl 4 ưʞC2H4ʟ Low [Cl ] (4) 30 known for a long time, but the crucial discovery of the Wacker ⇒ ͪ Ɣ ͟ 2 ʞ ƍʟ - process was that the catalyst could be regenerated (oxidized) by H3O ʢCl ʣ 60 molecular oxygen in the presence of the cocatalyst CuCl 2 (eq. 1- 3). 2- ‾ ƬPdCl 4 ưʞC2H4ʟ High [Cl ] ⇒ ͪ Ɣ ͟ (5) - 35 Pd + 2 CuCl 2 → PdCl 2 + 2 CuCl (1) ʢCl ʣ 2 CuCl + 2 HCl + ½ O 2 → 2 CuCl 2 + H 2O (2) PdCl 2 / CuCl 2 Since its discovery a lot of experimental and theoretical studies H C=CH + ½ O → CH CHO (3) 2 2 2 3 have been carried out in order to elucidate the reaction 65 mechanism for this process. The reaction goes through the net 40 The publication of the Wacker process focused the research addition of a Pd and a hydroxide group across the C=C bond, of many groups on the chemistry of Pd(II) thus developing new This journal is © The Royal Society of Chemistry [year] [journal] , [year], [vol] , 00–00 | 1 Chemical Society Reviews Page 2 of 16 named “hydroxypalladation”. How this process takes place is measures the isotope effect. The obtained kinetic ratio (D shift / crucial and motivated the controversy on the mechanism over H shift) of 1.70 was taken as a support for the previous 10 decades. 40 hydroxypalladation step as rate-determining step. This assertion The first part of the review briefly summarizes the controvery was later supported by means of analyzing the correlation 5 over the Wacker mechanism arising from experimental between relative rates of oxidation to ionization potentials, mechanistic studies. The second and most extended part HOMOs and LUMOs. 11 summarizes some of the most important challenges theoreticians face when studying the Wacker process. The review of the computational studies, from the early molecular orbital analysis 10 to the most recent AIMD simulations, also shows the debate. Mechanistic studies from experiment Two mechanisms have been postulated for the explanation of the 45 Scheme 3 Comparative isotope effect for the oxidation of 1,2- rate law (Scheme 2): a) anti nucleophilic attack by a water dideuterioethene. molecule from the bulk prior to the rate determining step of the 15 process, b) syn nucleophilic attack by a coordinated hydroxide The stereochemical studies on the Wacker mechanism carried group located cis to the alkene as rate determining step. They are out by Stille and co-workers supported an anti addition (in high also described by cis or trans terms, or by inner- or outer-sphere [Cl –]). These authors showed that uncoordinated nucleophile mechanisms in the literature. This nucleophilic addition is 50 attacks at the most substituted carbon atom of the double bond; intimately linked to the proton inhibition observed in the rate law this was the exclusive reaction observed for the olefins studied 12 20 and has been at the core of the mechanistic debate. (cyclic, linear, etc). Additional stereochemical studies by other groups also supported the anti addition for the Wacker process. 13,14 15,16 55 Bäckvall, Akermark and co-workers used dideuterio- ethene (cis and trans species) with an excess of LiCl (which forms 2-chloroethanol along with acetaldehyde) to carry out their mechanistic studies. The stereochemistry of hydroxypalladation for the reaction pathway leading to 2-chloroethanol 60 unequivocally showed that the process takes place through an anti mechanism. They proposed that the trans hydroxypalladation is an equilibrium process prior the rate determining step; the subsequent reaction step corresponding to the loss of chloride is the rate determining step (Scheme 4). Such mechanistic proposal 65 obeys the rate law. This contribution was crucial for supporting the anti pathway, and nowadays there is a general consensus that anti pathway is the operative one (at least for high [Cl –], see below). Scheme 2. The two postulated reaction pathways for the Wacker process. The mechanistic analyses in the laboratory have been mainly done by means of deuterium-labeling experiments and 25 stereochemical studies. The oxidation of C 2H4 carried out in D 2O gives CH 3CHO as 9 the only product, whereas the process using C 2D4 in H 2O 70 Scheme 4 generates CD CDO.7 These results indicate that hydrogen Main steps of the reaction mechanism proposed by Bäckvall 3 and cowokers. 16 transfers between carbon atoms take place intramolecularly (there 30 is no exchange with protons from the solvent). The measured Some authors, however, suggested that these stereochemical kinetic isotope effect was found to be small (k H/k D =1.07), studies supporting the anti pathway might not be relevant to the consistent with the fact that the hydrogen transfer process is not mechanism of the Wacker process because the reaction – involved in the rate determining step. A comparative isotope 75 conditions are not those of the common Wacker process (low [Cl effect was evaluated for the oxidation of 1,2-dideuterioethene ]). 3,17 The main argument is that the nature of the nucleophilic 10 35 (C 2H2D2); the hydroxypalladate intermediate [L nPd(CHD– attack, whether it is an equilibrium process or not, must be crucial CHDOH)] evolves to give two different products: CHD2CHO (D to differentiating between the two pathways. shift) and CH 2DCDO (H shift), see Scheme 3. The product ratio Kinetic experiments on the oxidation of ethene by 2 | Journal Name , [year], [vol] , 00–00 This journal is © The Royal Society of Chemistry [year] Page 3 of 16 Chemical Society Reviews – [PdCl 3(pyridine) ] in aqueous solution (in the presence and Note that one factor that is usually not considered in most absence of CuCl 2) showed that the rate law was the same at low mechanistic analyses is related to the role of CuCl2. The validity – [Cl ] as for the regular catalyst used in the Wacker process; the 45 of this assumption has been called into question by Hosokawa reaction, however, was significantly slower. 18 The product and co-workers 23 (proving the activity of a Pd-Cu heterometallic 5 distribution observed was consistent with a mechanism involving as a catalyst for the process) and by Sigman and co-workers on a – – 24 an anti addition at high [Cl ] and a syn addition at low [Cl ].