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How Does it Work?

In parallel synthesis where multiple reaction wells need to be purified concurrently, fluorous technology offers a distinct advantage. During separation, the organic domains of the fluorous molecules become chromatographically irrelevant to the fluorous sorbent.

For example, shown in Figure 1, for the non-fluorous version, each of the R groups dictates the separation method needed. In contrast, on the fluorous side of the diagram, a FluoroFlash® F-BOC-ON reagent has been employed. As a result, all three species can be separated in parallel by using the same method.

Basic Techniques

Solid Phase Extraction

The powerful separation characteristics of fluorous silica gel are illustrated by using fluorous and organic dyes as shown in Figure 2. [Watch the SPE-Movie] The organic (Solvent Blue®) and fluorous (F-Orange®) aminoanthraquinone dyes have similar polarities and cannot readily be separated with normal phase or reverse phase silica. However, their separation with FluoroFlash® silica gel is trivial.

Set 1 of test tubes (far left) show FluoroFlash® columns immediately after loading a mixture of the two dyes. Sets 2 and 3 of tubes result after elution with 80% methanol/water; the separation is immediate and the Solvent Blue® dye (organic fraction) elutes into the first test tube while the F-Orange® dye (fluorous fraction) remains adsorbed on the column.

The adsorbed fluorous dye is not eluted even with extensive flushing with 80% methanol/water; however, it elutes immediately after washing with about 1 ml of THF as shown in set 4 of test tubes. Careful fractionation and analysis are not required; there is one organic fraction and one fluorous fraction.

Because the separation is so easy, loading levels can be very high (2-5 times or more higher than normal chromatographic loadings). In addition, this procedure is general and can be used for many given protecting group and sorbent combinations. [Flash Chromatography - Learn More]

Basic Application

F-BOC Protection

Figure 3 shows a typical F-BOC protection. F-BOC-ON is used in protecting amino groups in peptide synthesis or multi-step organic synthesis. Protection of the amino group with F-BOC-ON and deprotection are achieved with traditional reaction conditions as with non-fluorous BOC-ON. The F-BOC group can easily be separated from organic reagents, reactants, or products by performing a quick F-SPE (Fluorous Solid Phase Extraction).

The utility of F-BOC-ON has been demonstrated in typical amide coupling reactions in a parallel synthesis of a library of 16 amides using F-BOC as a fluorous tag. In this application, fluorous parallel synthesis and separation delivered the ability to purify products after each reaction step as well as reduced the over-all amount of separation steps.

Advanced Techniques

Automated SPE and Parallel Flash Chromatography

Newly introduced by FTI are 24, 48, 96-well F-SPE plates (with 3g, 1g, 0.5g FluoroFlash® silica in gel each well, respectively) for parallel purification and high throughput purification of fluorous reaction mixtures.  These separations use either vacuum or positive pressure and procedures have been developed using commercially available manifolds.  Other fluorous solid phase extraction options include gravity-driven plate-to-plate F-SPE using larger particle size FluoroFlash® silica and automated serial F-SPE using a RapidTrace® workstation.  All of these options are used in conjunction with our fluorous reagents, tags, and scavengers to provide fast and effective purifications to increase your productivity.

Selected References and Notes

1. Results vary based on chemistry performed.
2. Curran, D.P. Fluorous reverse phase silica gel. A new tool for preparative separations in synthetic organic and organofluorine chemistry Synlett 2001, 1488-1496. [PDF Article]
3. Luo, Z.; Williams, J.; Read, R. W.; Curran, D. P. Fluorous Boc (F-Boc) Carbamates: New Amine Protecting Groups for Use in Fluorous Synthesis J. Org. Chem. 2001, 4261. [PDF Article]
4. Zhang, W.; Curran, D. P. “Synthetic applications of fluorous solid-phase extraction (F-SPE)” Tetrahedron Report No. 777, Tetrahedron 2006, 62, 11837–11865.
5. Zhang, W. “Fluorous Tagging Strategy for Solution-Phase Synthesis of Small Molecules, Peptides and Oligosaccharides” Curr. Opin. Drug Discov. Develop. 2004, 7, 784-797.