Intermolecular combinatorial chemistry

B.xiv.c. Intermolecular Heck Reactions on Polymeric Support. Combinatorial chemistry has initiated a reappraisal and consequent renaissance in synthesis of compounds attached to polymeric supports. Therefore, it comes as no surprise that Pd-catalyzed reactions are among the most widely explored reactions for the generation of combinatorial libraries on solid phase. The first example of the intermolecular Heck reaction on solid phase was reported in 1994. In this article, 4-vinylbenzoic acid was attached to Wang resin and coupled with aryl halides/triflates under catalysis with Pd(OAc)2 (Scheme 45). Similar... 

The ability to produce 1,3-dipoles, through the rhodium-catalyzed decomposition of diazo carbonyl compounds, provides unique opportunities for the accomplishment of a variety of cycloaddition reactions, in both an intra- and intermolecular sense. These transformations are often highly regio- and diastereoselective, making them extremely powerful tools for synthetic chemistry. This is exemplified in the number of applications of this chemistry to the construction of heterocyclic and natural-product ring systems. Future developments are likely to focus on the enantioselective and combinatorial variants of these reactions. 

The next era of supramolecular chemistry will undoubtedly be one of adaptability and evolution. As the complexity and the sophistication of these systems increases the need for viable alternatives to covalent synthesis is essential. One such is offered by the exploitation of weak intermolecular forces for the construction of arrays and aggregates with defined composition, shape and functionahty. Hydrogen bonding provides and ideal motif for such systems, and together with the well-established reactivity patterns and shape adaptability of porphyrins, the way is clear to the development of new systems with increasing chemical diversity and controlled dynamics. It is clear that the most rapid advances will be made through the use of dynamic combinatorial libraries, which allows for the chemical evolution of mixtures and amplification of specific components, with built-in error checking and control. 

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