Fluorous Synthesis and Combinatorial Chemistry

Nagashima, T. and Zhang, W. 2004. Fluorous parallel synthesis of an A-aUcylated dihydropte-ridinone library. Journal of Combinatorial Chemistry, 6 942-49. 

In the last few years fluorous combinatorial chemistry has been extended and augmented by other fluorous techniques developed by analogy with established methods in solid-phase-supported synthesis. Use of fluorous condensation reagents for the Mitsunobu reaction [23] enables easy removal of all condensation reagents except the coupled starting materials after the reaction [24] (Scheme 3.23). A fluorous variant of the Swern [25] and Corey-Kim oxidations [26] enables handling of stoichiometric quantities of malodorous dimethyl sulfide to be avoided [27] (Scheme 3.24). 

Many of these new techniques are especially suited to the preparation of combinatorial libraries by solution phase parallel synthesis. This chapter provides a brief introduction to the concepts of strategy level purification, and then introduces fluorous chemistry with representative examples of reactions, reagents and techniques. 

FMS is an elegant application of fluorous chemistry. Its solution-phase reaction kinetics, the split-mix technique, and separative fluorous tags expedite synthesis by increasing the speed, efficacy, and purity (Scheme 7.3). It is especially suitable for the combinatorial synthesis of a large number of compounds in larger quantities than existing mixture synthesis techniques. The synthesis usually begins with... 

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