Fluorous Combinatorial Chemistry

In 2004, Kumar and Montanari introduced a fluorous tagged trivalent iodonium compound that can be used as a tag for /-Boc based solid phase peptide synthesis by tagging free amines with a perfluoroheptyl (W-C7F15) group.It is an efficient fluorous tagging reagent that has the potential to help in the synthesis of both routine and difficult peptide and protein sequences. The 

Fluorous reverse phase silica gel (FRPSG) has been used in the purification of synthetic DNA fragments.In solid phase DNA synthesis, truncated sequences are often separated from the desired product after deprotection using HPLC or electrophoresis. In order to perform, parallel syntheses and separations of nucleotides the trityl-on purification procedure was developed, in which a lipophilic support material is used to separate the desired and undesired product, followed by deprotection. If the protecting group is labelled with a fluorous group, fiuorous-fiuorous interactions between the FRPSG and the protected nucleotide can be used to aid separation of the aqueous mixture. 

---

In the last few years fluorous combinatorial chemistry has been extended and augmented by other fluorous techniques developed by analogy with established methods in solid-phase-supported synthesis. Use of fluorous condensation reagents for the Mitsunobu reaction [23] enables easy removal of all condensation reagents except the coupled starting materials after the reaction [24] (Scheme 3.23). A fluorous variant of the Swern [25] and Corey-Kim oxidations [26] enables handling of stoichiometric quantities of malodorous dimethyl sulfide to be avoided [27] (Scheme 3.24). 

Chapters 1 and 2 have been reorganised and updated in line with recent developments. A new chapter on the Future of Purification has been added. It outlines developments in syntheses on solid supports, combinatorial chemistry as well as the use of ionic liquids for chemical reactions and reactions in fluorous media. These technologies are becoming increasingly useful and popular so much so that many future commercially available substances will most probably be prepared using these procedures. Consequently, a knowledge of their basic principles will be helpful in many purification methods of the future. 

Keywords m Fluorous BiphasicCatalysis m Fluorous Synthesis m Combinatorial Chemistry... 

Nagashima, T. and Zhang, W. 2004. Fluorous parallel synthesis of an A-aUcylated dihydropte-ridinone library. Journal of Combinatorial Chemistry, 6 942-49. 

Zhang, W. 2007. Fluorous-enhanced multicomponent reactions for making drug-like library scaffolds. Combinatorial Chemistry High Throughput Screening, 10 219-29. 

A different extractive work-up is based on fluorous biphasic systems. This concept was first introduced for fhe recovery of rhodium complexes from hydroformylation processes [13] and was soon extended to separation procedures in combinatorial chemistry [14]. It has been fhe subject of several reviews [15-21]. 

Fluorous chromatography is a simple means of separating different perfluoralkyl homologs of structurally similar compounds and a unique opportunity for combinatorial chemistry. 

Fluorous synthesis protocols for combinatorial chemistry have been developed for various reactions ... 

Adsorption on silica gel surfaces or silica gels coated with water or thin layers of ionic liquids has been used to immobilize transition metal complexes % ionic interactions and hydrogen bonding. Reversed-phase silica gels were used to retain catalysts by hydrophobic interactions. Support of catalysts on fluorous reversed-phase silica gel by the solvophobic nature of perfluoroalkyl chains is a new and promising approach with potential in catalysis and combinatorial chemistry. 

---