In the medicinal chemistry arena, the use of solution phase parallel synthesis processes in the creation of analog arrays, based on high throughput screening hits, is a crucial step in the drug discovery process.  Here, Lindsley, Zhao and Leister use fluorous scavengers to overcome many of the limitations of resin-bound reagents (Tetrahedron Letters, (2002), 43, 4225-4228).

Lindsley and his groups initially examined a set of six inexpensive, functionalized fluorous-tethered reagents and allowed for general scavenging of the most common chemical moieties encountered in parallel synthesis libraries.  In general, the flurous-tethered reagents contained between 13 and 17 fluorine atoms.  Figure 1 represents the genral process used by Lindsley, et. al in their experiments.  The fluorous reagents are generic resin convention.  All six reagents used are liquids that can be used neat or stored and dispensed as stock solutions.

The key to the success of this new approach is the removal of the fluorous scavengers in a rapid and general manner with FluoroFlash® SPE columns.   Representative examples of reagents used in the general scavenging of electrophiles are shown in Figure 2.  These experiments gave final products of high yield (>98%) and purity.

Figure 3 shows examples fo reagents used in the general scavenging of nucleophiles, including amide and sulfonamide formation, alkoxide alkylation and epoxide openings, wherein fluorous reagents scavenge amines, anilines, alkoxides and epoxides.  In these experiments, once again, good chemical yields (>80%) and excellent purities (>95%) were obtained.

The Wipf group utilized fluorous vinyl ether to isolate a key intermediate from a reaction mixture in the synthesis of analogs of marine natural product curacin A.  Utilizing a "catch and release" strategy, the group identified, in short order, the most potent cuiracin A analogs identified to date (J. Am. Chem. Soc. (2000), 122, 9391-9395.