Transition-state selective catalysis

Figure C2.12.10. Different manifestations of shape-selectivity in zeolite catalysis. Reactant selectivity (top), product selectivity (middle) and transition state selectivity (bottom).

Catalytic Properties. In zeoHtes, catalysis takes place preferentially within the intracrystaUine voids. Catalytic reactions are affected by aperture size and type of channel system, through which reactants and products must diffuse. Modification techniques include ion exchange, variation of Si/A1 ratio, hydrothermal dealumination or stabilization, which produces Lewis acidity, introduction of acidic groups such as bridging Si(OH)Al, which impart Briimsted acidity, and introducing dispersed metal phases such as noble metals. In addition, the zeoHte framework stmcture determines shape-selective effects. Several types have been demonstrated including reactant selectivity, product selectivity, and restricted transition-state selectivity (28). Nonshape-selective surface activity is observed on very small crystals, and it may be desirable to poison these sites selectively, eg, with bulky heterocycHc compounds unable to penetrate the channel apertures, or by surface sdation. 

Xiang, S.B., Short, S.A., Wolfenden, R. and Carter, C.W. (1995) Transition-state selectivity for a single hydroxyl group during catalysis by cytidine deaminase. Biochemistry, 34, 4516-4523. 

Restricted transition state selectivity Figure 1 Mechanisms of shape-selective catalysis. 

Supported non-framework elements, as well as substituted or doped framework atoms, have been important for zeolite catalyst regeneration. By incorporating metal atoms into a microporous crystalline framework, a local transition state selectivity can be built into the active site of a catalytic process that is not readily attainable in homogeneous catalysis. The use of zeolites for carrying out catalysis with supported transition metal atoms as active sites is just beginning. The local environment of transition metal elements as a function of reaction parameters is being defined by in situ Mossbauer spectroscopy, electron spin echo measurements, EXAFS, and other novel spectroscopic techniques. This research is described in the second part of this text. 

H. van Bekkum et al. (72) studied a number of catalysts in the Fischer synthesis starting from l-phenyl-2-butanone 40 (with R, = Ph, R2 = CH3) and phenylhydrazine. The isomeric products are the bulky 2-ethyl-3-phenylindole 45 (with R, = Ph, R2 = CH3) and the linear 2-benzyl-3-methylindole 46 (with R, = Ph, R2 = CH3). Catalysis of the inolization of 40 by soluble as well as solid (e.g. Amberlyst 15) catalysts typically yielded a mixture of the two isomers in a bulky/linear ratio of about 75/25. Zeolite BEA reverses this bulky/linear ratio giving 75% of the linear isomer 46, a result interpreted in terms of restricted transition-state selectivity. Although in zeolite BEA the intraporous formation of 45 is largely suppressed, it is in fact probably not completely inhibited. 

We also mentioned stereospecificity of metal-catalyzed reactions inside zeolite cavities. In acid catalysis by zeolites it is well known that shape selectivity can be imposed by (1) selective admission of reactants fitting into zeolite pores, (2) selective release of products able to diffuse through zeolite channels, while larger molecules are retained, and (3) transition state selectivity, favoring, e.g., a monomolecular transition state over a bimolecular state in a narrow cavity. New tools that have conceptually been added to this arsenal include the collimation of molecules diffusing through well-defined pores, which then hit an active site preferentially via one particular atom or group. 

Heterogeneous catalysts which are active for the catalysis of the MPVO reactions include amorphous metal oxides and zeolites. Their activity is related to their surface basicity or Lewis acidity. Zeolites are only recently being developed as catalysts in the MPVO reactions. Their potential is related to the possibility of shape-selectivity as illustrated by an example showing absolute stereoselectivity as a result of restricted transition-state selectivity. In case of alkali or alkaline earth exchanged zeolites with a high aluminium content (X-type) the catalytic activity is most likely related to basic properties. For zeolite BEA (Si/Al=12), however, the dynamic character of those aluminium atoms which are only partially connected to the framework appear to play a role in the catalytic activity. Similarly, the Lewis acid character of the titanium atoms in aluminium free [Ti]-BEA explains its activity in the MPVO reactions. 

The sequence is exactly opposite to that of conventional acid catalysis The reactants that are best able to form carbenium ions in solution are the least reactive with zeolite catalysis. The restricted transition state selectivity suppresses cracking of the more highly branched hydrocarbons in the cavities [T25]. 

In the previous section, we explained the steric and energetic consequences of the zeo-hte micropore shape for the activation energy of an elementary zeohte-catalyzed reaction step. In this section we discuss transition-state selectivity whereby differences in selectivity are ascribed to a more or less optimum match of the reaction transition state with the micropore cavity. We will demonstrate that the difference in the selectivity for the reaction is determined by the probabihty that a preferred pre-transition state orientation can form rather than by differences in the activation barrier for the reaction step in which protonation occurs. This result is analogous to the finding that the preferred reaction channel for enantioselective homogeneous catalysts proceeds through the adsorption complex with the most favorable free energy (see Section 2.4.4). Similarly, we will discuss the importance of the pre-transition-state complex in enzyme catalysis in Chapter 7. 

The regioselectivity benefits from the increased polarisation of the alkene moiety, reflected in the increased difference in the orbital coefficients on carbon 1 and 2. The increase in endo-exo selectivity is a result of an increased secondary orbital interaction that can be attributed to the increased orbital coefficient on the carbonyl carbon ". Also increased dipolar interactions, as a result of an increased polarisation, will contribute. Interestingly, Yamamoto has demonstrated that by usirg a very bulky catalyst the endo-pathway can be blocked and an excess of exo product can be obtained The increased di as tereo facial selectivity has been attributed to a more compact transition state for the catalysed reaction as a result of more efficient primary and secondary orbital interactions as well as conformational changes in the complexed dienophile" . Calculations show that, with the polarisation of the dienophile, the extent of asynchronicity in the activated complex increases . Some authors even report a zwitteriorric character of the activated complex of the Lewis-acid catalysed reaction " . Currently, Lewis-acid catalysis of Diels-Alder reactions is everyday practice in synthetic organic chemistry. 

A structural anomaly in subtilisin has functional consequences Transition-state stabilization in subtilisin is dissected by protein engineering Catalysis occurs without a catalytic triad Substrate molecules provide catalytic groups in substrate-assisted catalysis Conclusion Selected readings... 

Zeolites have led to a new phenomenon in heterogeneous catalysis, shape selectivity. It has two aspects (a) formation of an otherwise possible product is blocked because it cannot fit into the pores, and (b) formation of the product is blocked not by (a) but because the transition state in the bimolecular process leading to it cannot fit into the pores. For example, (a) is involved in zeolite catalyzed reactions which favor a para-disubstituted benzene over the ortho and meso. The low rate of deactivation observed in some reactions of hydrocarbons on some zeoUtes has been ascribed to (b) inhibition of bimolecular steps forming coke. 

The most interesting developments involve catalysis of simple aldol reactions. The key to reactive immunisation is the use of a hapten that is chemically reactive, rather than a passive template. This means that (i) relevant chemistry is going on during the course of antibody induction, which thus happens in the presence of intermediates involved in the reaction, and so may be modified to favor the formation of antibodies which bind these intermediates (and perhaps transition states leading to them). Furthermore (ii) it becomes possible to select for antibodies that react with, rather than just bind, to the hapten. The system used for the development of aldolase antibodies is outlined in Scheme 2... 

The reason for the high selectivity of zeohte catalysts is the fact that the catalytic reaction typically takes place inside the pore systems of the zeohtes. The selectivity in zeohte catalysis is therefore closely associated to the unique pore properties of zeohtes. Their micropores have a defined pore diameter, which is different from all other porous materials showing generally a more or less broad pore size distribution. Therefore, minute differences in the sizes of molecules are sufficient to exclude one molecule and allow access of another one that is just a little smaller to the pore system. The high selectivity of zeolite catalysts can be explained by three major effects [14] reactant selectivity, product selectivity, and selectivity owing to restricted size of a transition state (see Figure 4.11). 

One of the systems was found to be very efficient catalyzing enantioface-selective hydrogen transfer reactions to aromatic and in particular to aliphatic ketones with up to 95% ee. Regarding the latter reaction these are unprecedented ee values. The reaction mechanism of these transformations is best described as a metal-ligand bifunctional catalysis passing through a pericyclic-like transition state. 

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