Catalytic cascade

Up to the late 1990s, combined multi-step chemo-chemo conversions were restricted to a few catalytic examples. Apparently, there has been little effort or interest in developing a toolkit of chemocatalytic reactions that are mutually compatible with respect to reaction conditions. Consequently, chemocatalysts have not yet reached the same level of mutual compatibility as biocatalysts. Some recent examples prove, however, the potential power of chemo-chemo catalytic cascades. 

Table 13.2 Benefits of the one-pot bio-chemo catalytic cascade as compared with the traditional step-wise stoichiometric organic synthesis of 4-deoxyglucose [27, 28].

Issue Step-wise chemistry Catalytic cascade... 

Multi-catalytic cascades continuous and in situ separation... 

Strictly speaking a catalytic cascade process is one in which all of the catalysts (enzymes or chemocatalysts) are present in the reaction mixture from the outset. A one-pot process, on the other hand, is one in which several reactions are conducted sequentially in the same reaction vessel, without the isolation of intermediates. However, not all of the reactants or catalysts are necessarily present from the outset. Hence, a cascade process is by definition a one-pot process, but the converse is not necessarily true. Clearly a cascade process is a more elegant solution, but a one-pot process that is not, according to the strict definihon, a cascade reaction may have equal practical uhlity. In this chapter we shall be primarily concerned with enzymatic cascade processes, but the occasional chemocatalytic step may be included where relevant and sometimes a sequential one-pot procedure may slip through the net. 

Abstract Ruthenium holds a prominent position among the efficient transition metals involved in catalytic processes. Molecular ruthenium catalysts are able to perform unique transformations based on a variety of reaction mechanisms. They arise from easy to make complexes with versatile catalytic properties, and are ideal precursors for the performance of successive chemical transformations and catalytic reactions. This review provides examples of catalytic cascade reactions and sequential transformations initiated by ruthenium precursors present from the outset of the reaction and involving a common mechanism, such as in alkene metathesis, or in which the compound formed during the first step is used as a substrate for the second ruthenium-catalyzed reaction. Multimetallic sequential catalytic transformations promoted by ruthenium complexes first, and then by another metal precursor will also be illustrated. 

This catalytic cascade was first realized using propanal, nitrostyrene and cinnamaldehyde in the presence of catalytic amounts of (9TMS-protected diphenylprolinol ((.S )-71,20 mol%), which is capable of catalyzing each step of this triple cascade. In the first step, the catalyst (S)-71 activates component A by enamine formation, which then selectively adds to the nitroalkene B in a Michael-type reaction (Hayashi et al. 2005). The following hydrolysis liberates the catalyst, which is now able to form the iminium ion of the a, 3-unsaturated aldehyde C to accomplish in the second step the conjugate addition of the nitroalkane (Prieto et al. 2005). In the subsequent third step, a further enamine reactivity of the proposed intermediate leads to an intramolecular aldol condensation. Hydrolysis returns the catalyst for further cycles and releases the desired tetrasubstituted cyclohexene carbaldehyde 72 (Fig. 8) (Enders and Hiittl 2006). 

The ultimate in integration is to combine several catalytic steps into a one-pot, multi-step catalytic cascade process [138]. This is truly emulating Nature where metabolic pathways conducted in living cells involve an elegant orchestration of a series of biocatalytic steps into an exquisite multicatalyst cascade, without the need for separation of intermediates. 

An example of a one-pot, three-step catalytic cascade is shown in Fig. 1.51 [139]. In the first step galactose oxidase catalyses the selective oxidation of the primary alcohol group of galactose to the corresponding aldehyde. This is fol-... 

The ultimate in sustainable catalytic processes is the integration of chemocat-alytic and/or biocatalytic steps into catalytic cascade processes that emulate the metabolic pathways of the cell factory. It is an esthetically pleasing thought that, in the future, fuels, chemicals and polymers could be obtained from carbon dioxide and water as the basic raw materials via biomass, using sunlight as the external source of energy and water and supercritical carbon dioxide as solvents. The important difference between this bio-based scenario and the current oil-based one is the time required for renewal of the feedstocks. 

Table 9.1 Advantages and limitations of catalytic cascade processes.

As noted above, recovery and recycling of chemo- and biocatalysts is important from both an economic and an environmental viewpoint. Moreover, compart-mentalization (immobilization) of the different catalysts is a conditio sine qua non for the successful development of catalytic cascade processes. As discussed in Chapter 7, various approaches can be used to achieve the immobilization of a homogeneous catalyst, whereby the most well-known is heterogenization as a solid catalyst as in the above example. 

Multienzyme systems have been used in carbon paste electrodes, providing bio-catalytic cascades that result in an analytical amperometric signal. For example, acetylcholine esterase (AChE) and choline oxidase (ChOx) have been co-immobilized in carbon pastes, either with monomeric TTF [145] or flexible ferrocene-containing polymers [146] as electron mediators. The primary reaction includes the hydrolysis of acetylcholine biocatalyzed by AChE, then the choline produced is oxidized by the electrically contacted ChOx giving an analytical amperometric signal corresponding to the acetylcholine concentration. 

Phosphates have been detected through several catalytic cascades using the inhibition of alkaline phosphatase and coupling glucose oxidase [405] or... 

FIGURE 3.2 Catalytic cascades for oxidizing alkenes using 0s04 as one of the oxygen transfer catalysts and the environmentally benign H202 oxidant. 

Simons C, Hanefeld U, Arends IWCE, et al. Towards catalytic cascade reactions asymmetric synthesis nsing combined chemo-enzymatic catalysts. Topics in Catalysis... 

Novelization of the alkaloids is easy using the methods known in synthetic production, such as catalytic asymmetric reactions and inductions. Organo-catalytic cascade, asymmetric photocycloaddition, cyclization, and asymmetric decarboxylative allylation are used in total synthesis, as well as catalytic asymmetric induction reactions and condensation of alkaloid molecules (two or more). Novelization of alkaloids by total synthesis is generally used by the pharmacological industry around the globe. 

The next two sections of this review chapter will introduce the reader to the world of lactic acid. The acid is both a key platform chemical of the biorefinery concept, from which other interesting molecules may be formed (Sect. 2), and a monomer for commercial bioplastic polylactic acid (PLA) (Sect. 3). In the platform approach, the assessment from Chap. 1 in this volume [23] proves its value, as it is an equally useful tool to seek out the most desired routes for transforming a biomass-derived platform molecule as it is to select the most relevant carbohydrate-based chemicals from a chemist s point of view. In what follows, the desired catalytic cascade from cellulose to lactic acid will be described (Sect. 4) as well as the specific catalytic data reported for different feedstock (Sects. 5 and 6). Section 7 will introduce the reader to recent synthesis routes for other useful AHA compounds such as furyl and vinyl glycolic acid, as well as others shown in Fig. 1. Before concluding this chapter, Sect. 8 will provide a note on the stereochemistry of the chemically produced AHAs. 

Catalytic cascade cross-coupHng reactions involving metal carbene migratory insertion 13ACC2586. 

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