An Introduction to Fluorous Technology
Light Fluorous Compounds and Solid Phase Separations
Benefits
Fluorous technology offers a novel approach to solution phase chemistry and delivers significant benefits when applied to high-throughput synthesis and purification. The use of light fluorous compounds (permanent or temporarily tagged) in conjunction with fluorous sorbents yields the following benefits:
- Broad applicability to solution phase chemistry with no special reaction conditions or solvents required.
- Quick SPE separations after each serial or parallel synthetic step with purities often comparable to HPLC quality.
- Faster parallel generation and separation of compounds via fluorous HPLC.
How does it work?
Fluorous compounds (Fig. 1) contain a perfluoroalkyl group and virtually any molecule can have a fluorous analog. The perfluoroalkyl chain remains chemically inert during the reaction, while imparting unique properties to the reagents and sorbents during separation. These properties are due to a highly selective partitioning between the reagent fluorous groups and the sorbent fluorous groups.[1]
During separation, the chromatographic properties of the perfluoroalkyl group dominate the molecule's other functional groups. This critical property makes the organic domains of the fluorous molecules become chromatographically irrelevant to the fluorous sorbent. Hence the immense benefit of fluorous technology: diverse chemical structures containing the same fluorous group can be purified by simply using a single chromatographic method.
Basic Techniques
Fluorous Solid Phase Extraction (F-SPE) quickly separates fluorous compounds from non-fluorous compounds in three easy steps (Fig. 2). First, the reaction mixture is loaded onto the column. Second, the non-fluorous compounds are eluted with a fluorophobic solvent in one fraction. Third, the fluorous compounds are eluted with a fluorophilic solvent. Watch the movie, see FluoroFlash® SPE in action!
Basic Applications
Fluorous Substrates and Reagents
Fluorous substrates are used to deliver a product that contains a fluorous tag. SPE over FluoroFlash® silica gel [Fluorous SPE - Learn More] can then be used to recover the individual, highly pure fluorous product from non-fluorous reagents. In the reverse approach, fluorous reagents can be used such that the byproducts are fluorous while the desired product is non-fluorous (for example in fluorous Mitsunobu reactions).[2] Again, simple separation by F-SPE yields a high purity product.
Scavenging
When excess reagents are used to drive a reaction to completion, fluorous solution phase scavengers provide an effective means of capturing and removing reagents from the product. The scavenger and scavenged reagent are simply separated from the product by SPE over FluoroFlash® silica gel. In cases where product mixtures are complicated and a number of different side products are likely, the selective capture of the desired product may be preferred. Compared to analogous solid phase scavenging reactions, the fluorous reactions are faster, cleaner, and do not require large excesses of scavenging reagents. [Scavenging - Learn More]
Parallel Synthesis
In parallel synthesis where multiple reaction wells (96 for example) need to be purified concurrently, F-SPE offers another advantage. This technology dramatically simplifies the purification steps in parallel because all fluorous containing products can be separated from non-fluorous starting materials by using a single chromatographic method. In applications where gram quantities are required, fluorous chemistry greatly enhances the efficiency of Parallel Flash Chromatography. [Parallel Synthesis - Learn More]
Advanced Techniques
A unique and highly beneficial property of fluorous partitioning interactions is the ability of HPLC-grade fluorous sorbents to chromatographically resolve compounds containing different length fluorous chains from one another. Each fluorous tagged compound travels through the FluoroFlash® HPLC column at a different speed. This powerful tool is the basis for Fluorous Mixture Synthesis.
Advanced Applications
Mixture Synthesis
In Fluorous Mixture Synthesis (FMS), substrates are tagged with fluorous protecting groups of variable fluorine content. [FMS - Learn More] The substrates then undergo reaction as a single mixture. Upon completion of the reaction, the separation is performed on a semi-preparative or preparative FluoroFlash® HPLC column containing high-performance, microparticulate fluorous sorbents. The tagged compounds are easily identifiable as baseline resolved peaks.
Fluorous Technology Primer
To learn more about the basics of fluorous technology, please refer to our technology primer. This collection of articles will introduce you to the various features of fluorous compounds. Go to Primer Now.
Selected References
• Curran, D.P. Fluorous reverse phase silica gel. A new tool for preparative separations in synthetic organic and organofluorine chemistry Synlett 2001, 1488-1496.• Dandapani, S.; Curran, D. P. Fluorous Mitsunobu reagents and reactions. Tetrahedron 2002, 58, 3855-3864.