Applications split-pool synthesis

The isorniinchnone cyclization/isocyanate cycloreversion process for substituted furan synthesis has been well studied, as exemplified by the conversion of 104 to 106 (Scheme 19.19). In a solid-phase adaptation of this transformation, two groups independently utilized this reaction to estabhsh a traceless self-cleaving method for the synthesis of substituted furans [176, 177]. Further investigation of the thermal requirements of this cycloreversion led to its application in the split-pool synthesis of a small library of amides [178]. 

When performing a synthetic combinatorial chemistry experiment, several basically different strategies may be followed to create a library of compounds. The most commonly used are mixelsplU (or split and pool) synthesis [1] masking strategies [15, 16] and parallel synthesis. In this chapter, the attention is focussed on the application of parallel synthesis to catalysis in the liquid phase. 

Klein, J., Zech, T., Newsam, J. M., Schunk, S. A., Application of a novel split pool principle for the fully combinatorial synthesis of functional inorganic materials, Appl. Catal. A 2003, 254, 121-131. 

The extension of the application of combinatorial chemistry from lead discovery to lead optimization has resulted in a gradual shift from split-pool protocol-based libraries generating mixtures of compounds to the parallel synthesis of discrete analogs (see Fig. 5). The emphasis in the latter case is not on the size of the libraries but rather on the yield, purity,... 

The principal differences between those two methods are reflected in their applications. The random spht-and-pool method is suited for the synthesis of smaller quantities of large sizable libraries (i.e., million compounds), whereas the directed split-and-pool technique is suited for the synthesis of larger quantities of smaller compound collections (i.e., several hundred to several thousand compounds). In this chapter, a simple technique for directed spht-and-pool technique is described. 

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