Catalytic Cycle and Intermediates

For a chemical reaction to be experimentally observed, the thermodynamic and the kinetic changes should not be too unfavorable. The thermodynamic change is measured in terms of the change in Gibbs free energy, or simply free energy (AG), while the kinetic requirement is measured by free energy of activation (AG ). 

The relationship between AG and AG is normally presented in a diagram, where free energies of the reactants, products, transition state, and intermediates are plotted against the extent of reaction, or more precisely the reaction coordinate. This is shown in Fig. 2.9. Even a simple homogeneous catalytic reaction such as alkene hydrogenation involves many intermediates and transition states. The free energy diagram thus resembles (c) rather than (a) or (b). 

Finally, the relationship between equilibrium constant and free energy change in the standard state on the one hand, and rate constant and energy of 

Consider a hypothetical metal complex ML +1 (M = metal, L = ligand, n + 1 = number of ligands) that acts as a catalyst for the hydrogenation of an alkene. Also consider the following sequence of reactions  

If all these reactions excepting the first are added, we get the net stoichiometric reaction alkene +H2 — alkane. The metal complex ML reacts with dihydrogen in the first step, undergoes a series of reactions in the following steps, and is regenerated in the final step. As shown in Fig. 2.10, all these reactions are conveniently presented as a catalytic cycle. 

The relationship between the equilibrium constant ( 0 aiid free energy change in the standard state (AGO is given by Equation 3.1.1. On the other hand, the relationship between the rate constant (k) and the free energy of activation (AGO is given by Equation 3.1.2. For calculating the AG of a given reaction, AH and AS of the same reaction are calculated first. 

Let us consider the basic reactions involved in hydrogenation of an alkene, using Wilkinson s complex (see Section 2.2.2) as the catalyst. The detailed mechanism involves additional reactions, but here we discuss only the more important ones. 

58 undergoes ligand dissociation to give 3.1, a three-coordinate 14-electron complex. Oxidative addition of to 3.1 gives 3.2. In the next step, coordination of RCH=CH2 to 3.2 produces 3.3, an alkene complex with hydride ligands. This is then followed by the insertion of RCH=CH2 into one of the Rh-H bonds. Notice that for insertion to take place, the alkene and the hydride must be cis to each other. 

The complex 3.4 formed in this step is usually the anti-Markovnikov product. In the final step, reductive elimination of RCH CHj from 3.4 regenerates 3.1 and gives the hydrogenated product. 

It is important to note that 3.1, by its reaction with the alkene, can also form a complex of structure 3.5. The reason for not showing this in the catalytic cycle will be discussed in Section 5.1, where we explain the mechanism of catalytic hydrogenation in more detail. 

In the early studies of nonenantioselective hydrogenation it has been found that b/s-monophosphine Ir complexes give stable trans-solvate dihydrides 1 upon removal of the coordinated diene from a precatalyst. These solvate dihydrides were found to be capable of exchanging one or two of their solvent molecules for olefins yielding dihydride olefin complexes 2 or 3, respectively which were characterized at -80°C, Equation 1.1.354,355 

Binuclear iridium hydrides like 8 often form as off-loop species that can result in decreasing of the catalytic activity. Formation of trinuclear complexes completely deactivating the catalyst has been also observed. Nevertheless, the dimeric hydrides formed reversibly before the elimination of the proton are catalytically active, since they can recover mononuclear dihydrides via reversible dissociation.  

The same research group recently characterized key intermediates in the Ir-catalyzed asymmetric hydrogenation of simple olefins. When a 

At -20°C 15a and 15b demonstrated rapid exchange with each other and the free alkene 14-[Ds], thus indicating fast equilibration between isomers via alkene dissociation/association. This evidently means that other less stable isomers may be kinetically accessible. 

The most important feature of the Ir-catalyzed asymmetric hydrogenation is the impossibility of a chelate binding for the vast majority of the substrates. Besides, the most effective catalysts in this field have Ci-symmetry. 

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In an industrial hydroformylation reaction with a rhodium catalyst in the presence of excess phosphine and high pressures of CO, what would probably be the minimum number of catalytic cycles and intermediates ... 

Scheme 10.9 Possible catalytic cycles and intermediates traversed of pincer-catalyzed Heck reactions, exemplarily evaluated with 10.

During the catalytic cycle, surface intermediates include both the starting compounds and the surface metal atoms. This working site is a kind of supramolecule that has organometallic character, and, one hopes, the rules of the organometallic chemistry can be valid for this supramolecule. The synthesis of molecular models of these supramolecules makes it possible to study the elementary steps of the heterogeneous catalysis at a molecular level. Besides similarities there are, of course, also differences between the reactivity of a molecular species in solution and an immobilized species. For example, bimo-lecular pathways on surfaces are usually prohibited. 

P-phosphino-NHPs but the reverse reaction of a P-chloro NHP with diphenyl-trimethylsilylphosphine and subsequent reaction with a chloroalkane can be combined to produce high yields of P-alkyl-diphenylphosphines [74], Since the chloro-NHP is recovered in the second step, the overall reaction can be performed by employing this species merely as catalyst (Scheme 13). NMR investigations confirm that the appropriate P-phosphino-NHPs are in fact key intermediates in the resulting catalytic cycle, and it has been pointed out that P-X bond polarization represents a crucial factor for the overall acceleration of the catalyzed P-C... 

The formation of metal-oxygen bonds has previously been found to occur for the stoichiometric hydrogenation of CO to methanol with metal hydrides of the early transition metals (20). Moreover, in ruthenium-phosphine catalyzed hydrogenation (with H2) of aldehydes and ketones, metal-oxygen bonded catalytic intermediates have been proposed for the catalytic cycle and in one case isolated (21,22). 

For an ea HRh(CO)(alkene)(diphosphine), in which the hydride is assumed, as in Figure 3, to be in axial position, alkene have two coordination sites available, four conformations for each site, two rotation sides, N ligand conformations, and therefore 16xN TS s. Computation of the full catalytic cycle, all intermediates and TS s, from the entry of the substrate to the departure and regeneration of the catalyst, complemented with IRC calculations to confirm the connection between TS s and intermediates is out of reach for current computational resources. However, suitable modeling strategies can reduce of the problem, and still provide useful insight. 

The above applications show that computational chemistry has provided the answers to a number of questions. Much work still needs to be done, however. Despite the severe approximations involved in using model systems, a first step has now been taken. From the structure of intermediates and TS s determined for model systems, we have described the main features of the catalytic cycle and laid the ground for the development of more elaborate models. Topics such as ee ea equilibrium and the infrared spectra of HRh(CO)2(diphosphine) have been satisfactorily interpreted. 

The intramolecular nucleophilic attack of a nitrogen atom on an allylpalladium complex was also used to construct a five and a six membered heterocycle in the same step. TV-substituted 2-iodobenzamides bearing an allene function in the appropriate distance from the iodine underwent cyclization through the carbopalladation of the allene moiety by the arylpalladium complex, formed in the first step of the catalytic cycle. The intermediate allylpalladium complex, part of a nine membered ring, cyclized readily to give the pyrroloisoquinolone derivative in excellent yield (4.23.). The nature of the added ligand and the solvent both had a marked influence on the efficiency of the transformation.26... 

A unique feature of the transition-metal-catalyzed allylic alkylation is its ability to convert starting materials of various symmetry types, such as racemic, meso- and achiral compounds, into optically pure material, Strategies to effect such transformations derive from recognition of the stereochemical courses in each step of the catalytic cycle and analysis of symmetry elements in the substrate or intermediate. Figure 8E.1 summarizes potential sources of enantio-discrimination in transition-metal-catalyzed allylic alkylation. 

Information about the catalytic cycle and catalytic intermediates is obtained by four methods kinetic studies, spectroscopic investigations, studies on model compounds, and theoretical calculations. Kinetic studies and the macroscopic rate law provide information about the transition state of the rate-determining step. Apart from the rate law, kinetic studies often include effects of isotope substitution and variation of the ligand structure on the rate constants. 

The basic catalytic cycles and the catalytic intermediates for the Monsanto process are shown in Fig. 4.1. A variety of rhodium salts may be added to the reaction mixture as precatalysts. In the presence of I and CO they are quickly converted to complex 4.1. The following points about the catalytic cycles deserve special attention. 

The catalytic cycle and the catalytic intermediates for the rhodium-plus-phosphine-based process are shown in Fig. 5.1. It is important to note that hydroformylation with rhodium can also be effected in the absence of phosphine. In such a situation CO acts as the main ligand (i.e., in Fig. 5.1, L = CO). The mechanistic implications of this is discussed later (Section 5.2.4). 

It is obvious that such equilibria would exist for all the other catalytic intermediates. The result of all this is coupled catalytic cycles and many simultaneous catalytic reactions. This is shown schematically in Fig. 5.5. The complicated rate expressions of hydroformylation reactions are due to the occurrence of many reactions at the same time. As indicated in Fig. 5.5, selectivity towards anti-Markovnikov product increases with more phosphinated intermediates, whereas more carbonylation shifts the selectivity towards Mar-kovnikov product. This is to be expected in view of the fact that a sterically crowded environment around the metal center favors anti-Markovnikov addition (see Section 5.2.2). 

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