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Fluorous Technologies, Inc. (FTI) provides the scavengers, reagents, and sorbents to meet your chemistry needs.  Go directly to our product catalog pages by clicking on the product categories above or, read on and learn more about this exciting application of fluorous chemistry.  To download a PDF version of our catalog, please click here.

Fluorous covalent scavengers bear familiar nucleophilic, electrophilic, and other scavenging functional groups, modified to include a perfluoroalkyl chain [1].  These chains, or fluorous tags, allow for the rapid separation of the scavenged products from target products by Fluorous Solid Phase Extraction (F-SPE) [2].   The product chart shows examples of FluoroFlash® covalent scavengers along with some of the functional groups they can be used to target.

Benefits

Fluorous scavenging technique unites the attractive features of solution phase chemistry with the convenient workup of F-SPE. Fluorous scavengers have distinct advantages over more conventional polymer and ionic scavengers.  When used in combination with FluoroFlash® products, including other reagents and sorbents, fluorous scavengers provide the following benefits:

• Rapid quenching of reactions in the solution phase without a large excess of scavenging reagents.
• Easy removal of scavenged products and unreacted scavenging reagents, yielding final compounds of high purity.
• Scalable reactions and purification strategies.
• Multiple applications in solution and solid phase synthesis.
• Access to a full range of solution phase scavenging chemistries.
• Chemically inert and thermally stable products

In a side-by-side comparison, researchers at FTI have shown that FluoroFlash® scavenger 1 outperforms a solid phase scavenger 2 in reacting with an active halide (Figure 1) [3].  Results shown in Figure 2 demonstrate that when 1.5 equiv of F-Thiol 1 was used (green line), greater than 95% conversion was achieved in less than 40 minutes.  The reactions with silica gel-supported thiol 2 (red line) had much lower conversion; 50% of the halide was still unreacted even after 80 minutes.  By doubling the amount of Si-thiol 2 to 3.0 equiv, the reaction was significantly improved to give 95% conversion after 60 minutes (blue line).  Furthermore, fluorous scavenging reactions are not limited to electrophilic and nucleophilic chemistries, making a full range of scavenging chemistries accessible.

Methods of Use

Basic Method

ln a typical process, an excess of one reagent starting materials is used to rapidly drive a solution phase reaction to completion (Figure 2). The final mixture is composed of the desired product and one or more byproducts (either excess reagents and/or spent reagents). The soluble fluorous scavenger is then introduced and scavenges the byproducts to form fluorous-tagged compounds. Rapid F-SPE of the reaction mixture retains the scavenged byproducts and any unreacted scavenger while allowing the target product to quickly pass through.

Fluorous compounds used in these reactions are referred to as "light fluorous" scavengers because they are usually have one or two perfluoroalkly chains.   Light fluorous scavengers used in conjunction with this method can be applied in many discovery applications.

Variations of Basic Method

Fluorous Chemistry in Solid Phase Synthesis of Peptides and Oligomers

Fluorous scavenging reagents are also convenient caps of unreacted functional groups in solid phase synthesis.  After cleaving products from the solid phase, the truncated fluorous products are readily separated from the target products by F-SPE or chromatography.  By taking advantage of the unique properties of fluorous compounds, peptide oligomers of 7-22 amino acids produced using traditional solid phase methods are quickly and reliably purified. [4]  An analogous strategy incorporates the use of fluorous scavenging technology in the synthesis of oligosaccharides.  In this case, however, the fluorous portion is a "captag" which is used to render the undesired material fluorous, while the desired oligomeric species is non-fluorous. [5]

Fluorous Target Product Capture

Post-reaction fluorous tagging is not limited to removal of undesired products. When a number of different side products are present, FluoroFlash® scavengers can selectively capture the desired product from either a solution or a solid phase synthesis using the same basic process described above [6].

Microwave Assisted Synthesis

Microwave assisted fluorous synthesis techniques provide a useful method to speed up fluorous scavenging reactions [7].

Heavy Fluorous Scavenging

Using "heavy fluorous" scavengers (those containing >60% fluorine by molecular weight) and liquid/liquid separation and extraction methods three processes are described for the scavenging of particular classes of compounds [4, 8, 15].

Specific Applications

Solution Phase Synthesis

The use of fluorous chemistries in solution phase synthesis processes has emerged as a unique and effective paradigm.  In the following examples fluorous scavengers are employed as quenching agents in the synthesis of various products, including parallel library synthesis applications [9-11].

Analog Library Synthesis for Lead Identification

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 fluorous scavengers are used to overcome many of the limitations of resin-bound reagents [12-13].

Scavenging Alkenes and Dienes

In addition to popular electrophile and nucleophile scavengers, fluorous scavengers for alkenes and dienes have also been introduced [14-15].

Selected References

1. Lindsley, Craig W.; Leister, William H. Fluorous Scavengers in Handbook of Fluorous Chemistry; Gladysz, J. A.; Curran, D. P.; Horvath, I. T. Eds. Wiley-VCH, 2004, pp236-246.
2. Zhang, W.; Curran, D. P. “Synthetic applications of fluorous solid-phase extraction (F-SPE)” Tetrahedron 2006, 62, 11837–11865. [PDF Article]
3. Chen, C. H.-T.; Zhang, W. “Fluorous Reagents and Scavengers versus Solid-Supported Reagents and Scavengers, A Reaction Rate and Kinetic Comparison” Mol. Diversity 2005, 9, 353-359. [PDF Article]
4. Wipf, P., et al. Synthesis and biological evaluation of a focused mixture library of analogues of the antimitotic marine natural product curacin A J. Am. Chem. Soc. 2000, 122, 9391-9395. [PDF Article]
5. Palmacci, E. R.; Hewitt, M. C.; Seeberger, P. H. 'Cap-Tag' - novel methods for the rapid purification of oligosaccharides prepared by automated solid-phase synthesis Angew. Chem. Int. Ed. 2001, 40, 4433. [PDF Article]
6. Laura A. McAllister, Rosemary A. McCormick, Karen M. James, Stephen Brand, Nigel Willetts, David J. Procter “A Fluorous, Pummerer Cyclative-Capture Strategy for the Synthesis of N-Heterocycles Chemistry - A European Journal 2007, 13, 1032-1046.
7. Zhang, W. “Microwave-Enhanced High-Speed Fluorous Synthesis” in Microwave Methods in Organic Synthesis; Topics Curr. Chem. Vol. 266, Larhed, M.; Olofsson, K. Eds.; Springer, 2006, pp145-166.
8. Linclau, Bruno; Sing, Ashvani K.; Curran, Dennis P. Organic-Fluorous Phase Switches: A Fluorous Amine Scavenger for Purification in Solution Phase Parallel Synthesis J. Org. Chem. 1999, 64, 2835-2842 [PDF Article]
9. Zhang, W.; Curran, D. P.; Chen, C. H. T. Use of fluorous silica gel to separate fluorous thiol quenching derivatives in solution-phase parallel synthesis Tetrahedron 2002, 58, 3871-3875.
10. Zhang, W; Hiu-Tung Chen, C; Nagashima, T. Fluorous electrophilic scavengers for solution-phase parallel synthesis Tetrahedron Letters 2003 , 44, 2065-2068.
11. Lu, Y.; Zhang, W. “Fluorous 2,4-Dichloro-1,3,5-triazine (F-DCT) for amine and thiol scavenging reactions” QSAR Comb. Sci. 2006, 25, 728-731.
12. Lindsley, C. W.; Zhao, Z.; Leister, W. H. Fluorous-tethered quenching reagents for solution phase parallel synthesis Tetrahedron Lett 2002, 43, 4225-4228.
13. Lindsley, C.W. ; Zhao, Z.;Leister, W.H.; Robinson, R.G.; Barnett, S.F.;  Defeo-Jones, D.; Jones, R.E.; Huber, H.E “Allosteric Akt (PKB) inhibitors: discovery and SAR of isozyme selective inhibitors” Bioorg. Med. Chem. Lett.  2005, 15, 761–764
14. Werner, S.; Curran, D. Fluorous Dienophiles are Powerful Diene Scavengers in Deils-Alder Reactions Organic Letters 2003 3293-3296, Vol.5 No. 18 [PDF Article]
15. Curran, Dennis P.; Hadida, Sabine; Kim, Sun-Young; Luo, Zhiyong Flurous Tin Hydrides: A New Family of Reagents for Use and Reuse in Radical Reactions J. Am. Chem. Soc. 1999 , 121, 6607-6615 [PDF Article]