Solid-supported Reagents and Catalysts

Supported reagents and catalysts are reactive species that are associated with a support material. They transform a substrate into a new chemical product, with the excess or spent reagent being easily removed by filtration (Fig. 2.1). The prod- 

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A significant limitation of flow reactors is that solids, either as suspensions of starting materials or precipitated products, easily block the channels, although solid-supported reagents and catalysts can be used by immobilisation onto the walls or as packing. 

Some of the most widely used solid-supported reagents and catalysts are summarised in the following tables ... 

Figure 2. Selected examples of solid-supported reagents and catalysts.

SCHEME 6.24. Illustration of the use of multiple solid-supported reagents and catalysts for the synthesis of the API Gleevac (Novartis, Basel, Switzerland). 

In the 1970s and 1980s, however, it was believed that the key to wider use of solid-phase supported reagents and catalysts is their adoption in industry for fine chemical and pharmaceutical manufacturing on a large scale. In fact, this restricted view hampered their wide use [7]. The dramatic developments in the need for compound library preparation in pharmaceutical and agrochemical industries have finally removed functionalized supports from their academic corner and helped reinvent them for industrial purposes and applications. 

The advantages of heterogeneous solid phase in combinatorial chemistry, especially in terms of purification procedures, can be obtained also by solution-phase chemistry, using solid support assistance. The resin performs a specific function during the library synthesis and then is simply removed by filtration, leaving the pure library components in solution. A well-known adapted technique uses solid supported reagents or catalysts during a combinatorial synthesis, where the solid phase is filtered off and discarded after the reaction in which it was involved. A new application is represented by solid-phase purification, where one or more solid supports are added to trap the excess of... 

Merrifield peptide synthesis is the most highly developed method of synthesis with solid supports. Every step of the synthesis is carried out in the same polymer. Polymer-supported species also have been used as reagents and catalysts for single step synthetic transformations. Useful single step syntheses should be much easier to achieve than multi-step syntheses in polymer supports because they do not require >99% yield to be valuable. This book emphasizes one step processes in the synthesis of low molecular weight organic compounds carried out with polymer-supported reagents and catalysts. 

Scheme 74 Continuous flow protocol employed for the synthesis of the natural product grossamide (260) using a series of solid-supported reagents, catalysts and scavengers.

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