Reagents, Linkers, and Scavengers

Several fluorous counterparts of common reagents have been reported and many of these are also commercially available. Of some interest is the development of fluorous Mitsunobu reagents. A first generation fluorous DEAD reagent was found to have poor reactivity when difficult Mitsunobu reactions were encountered it has since been replaced with two enhanced, second-generation reagents, (1) and (2), for use in parallel or sequential fluorous chromatography and rapid F-SPE isolation, respectively. 

An interesting apphcation of the unique possibilities inherent in fluorous chemistry is the phase-vanishing reactions reported by Ryu and co-workers.This strategy encompasses no fluorous reagents as such but uses a fluorous phase as a physical barrier for passive transport between an organic phase (hexane) and a reagent (BBrj) in brominations of alkenes. The completion of the reaction is easily monitored by the disappearance of the reagent. 

An important reagent in fluorous chemistry is the fluorous version of the Marshall resin, dubbed FluoMar (4). This separation tag is reported to dissolve readily in dichloromethane, tetrahydrofuran, and ethyl acetate and can, as many other fluorous reagents, be monitored by traditional chromatographic and spectroscopic methods. The usefulness of (4) was demonstrated in a multistep parallel synthesis of a 3 X 3 array of diamides, where the final products were efficiently purified by F-SPE and cleaved from the FluoMar tag. Tentative results indicated that the homogeneous kinetics of the soluble (4) resulted in reactions that proceeded approximately three times faster than polymer-support bound reactions using standard Marshall resin. 

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