Cascade catalysis

SCHEME 2.91 Ir(III) salts and Af-triflylphosphoramide-cocatalyzed asymmetric reduction of quinaldines. 

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Ley and Baxendale have shown that it is possible to complete a total synthesis by using a number of flow devices in series, which contained immobihzed reagents (14). Use of a number of CCSs in series would allow cascade catalysis in which the catalytic systems have been separated (Figure 4.2). This is quite attractive in view of the fact that often each catalyst needs highly specific operating conditions, such as temperature and pH. 

Figure 4.2 Cascade catalysis using centrifugal contact separators in series. Experimental section...

Cascade catalysis without Intermediate products recovery... 

Decreasing the number of reaction steps via a one-pot reaction associating two or more catalytic steps. This can be achieved by multistep reactions carried out by cascade catalysis without intermediate product recovery, thus decreasing the operating time and reducing considerably the amount of waste produced. 

Cascade catalysis without recovery of intermediate products may require more than two steps, involving enzymatic, homogeneous, and heterogeneous catalysis. Several examples of this approach have been given [72, 73] one of the most representative consists of a four-step conversion of glucoside into aminodeoxysugar without intermediate product recovery. 

Cascade Catalysis and Multi-step Conversions in Concert... 

Full exploitation of cascade catalysis and multi-step conversions in concert will require the development of novel, mutually compatible, organic and biosynthetic methods and procedures. Eventually, a full integration of organic synthesis and biosynthesis can be envisaged. 

Apart from new catalytic methods, cascade conversions require new process technologies, such as in situ product recovery, reactor design, and compartmental-ization. In the long term, part of the present-day stoichiometric chemistry as well as bio- and chemocatalytic conversions in multi-step syntheses will gradually be replaced by cascade catalysis in concert, and full fermentations by cell factory design, or combinations thereof (Fig. 13.17). 

Cascade Catalysis Merging Iminium and Enamine Activations... 

Perhaps the most important point in these studies was the discovery that two discrete amine catalysts could be employed to enforce cycle-specific selectivities (Scheme 3.18) [20]. Conceptually, this achievement demonstrates that these cascade-catalysis pathways can be readily modulated to afford a required... 

In conclusion, the potential of soluble, nanosized metallodendrimers as catalysts in homogeneous reactions is well-consolidated. Future applications of these species are foreseen in high-tech nanotechnology applications in the fields of nano- and microreactors, cascade catalysis, and catalytic biomonitoring and biosensing. In this respect, the recent use of noncovalent strategies for the construction of multicomponent catalytic assemblies, and the use of biomacromolecules within dendritic structures is intriguing [60-62,92,93]. 

Huang Y, Walji AM, Larsen CH, MacMillan DWC (2005) Enantioselective organo-cascade catalysis. J Am Chem Soc 127 15051-15053... 

The need for novel catalytic processes is clear and, as discussed in Chapter 9, combining catalytic steps into cascade processes, thus obviating the need for isolation of intermediate products, results in a further optimization of both the economics and the environmental footprint of the process. In vivo this amounts to metabolic pathway engineering [20] of the host microorganism (see Chapter 8) and in vitro it constitutes a combination of chemo- and/or biocatalytic steps in series and is referred to as cascade catalysis (see Chapter 9). Metabolic engineering involves, by necessity, renewable raw materials and is a vital component of the future development of renewable feedstocks for fuels and chemicals. 

Achievements made wifhin fhe field of reaction engineering will increase fhe applicability of biocatalysts even more. For example, the use of microreactors is still in its infancy. Cascade catalysis and multi step conversions [81], a common domain of biocatalysis, will boost the application of biocatalysis for the transformation of highly reactive compounds or intermediates. Moreover, this might diminish operating time and costs as well as consumption of auxiliary chemicals and use of energy. For example, Bacher et al. published fhe six-step synthesis of labelled riboflavin using eight different enzymes in one reaction vessel [82]. 

A one-pot reaction with cascade catalysis is not only particularly relevant in the case of fine chemistry but also for the new area of bioresource use. Several interesting examples have been discussed recently by Gallezot [344]. 

Kiehoom, T. (2007) Integration of hiocatalysis with chemocatalysis cascade catalysis and multi-step conversions in... 

Dusseller, M., Van Wouwe, R, De Smet, S., De Clercq, R, Verbelen, L., Van Pu5Tvelde, R, et al. Toward functional polyester building blocks from renewable glycolaldehyde with Sn cascade catalysis. ACS CataL 2013,3,1786-800. 

This radical mechanism can be exploited for cascade catalysis if the rate of radical cychzation (or other rearrangement reactions) for R " is significantly faster than the rate of R attack on nickel. Cardenas and coworkers [53] have proved this concept... 

Dusselier M, Van Wouwe P, De Smet S, De Clercq R, Verbelen L, Van Puyvelde P, Du Prez PE, Sels BF (2013) Toward functional polyester building blocks liom rtaiewable glycolaldehyde with Sn cascade catalysis. ACS Catal 3 1786-1800... 

Walji AM, MacMillan DWC (2(X)7) Strategies to Bypass the Taxol Problem. Enantioselective Cascade Catalysis, a New Approach for the Efficient Construction of Molecular Complexity. Synlett 1477... 

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