Fluorous reverse phase silica gel

Curran DP (2002) Fluorous Reverse Phase Silica Gel. A New Tool For Preparative Separations in Synthetic Organic and Organofluorine Chemistry. Syn-lett 1488-1496... 

Curran DP, Luo ZY (1999) Fluorous Synthesis with Fewer Fluorines (Light Flu-orous Synthesis) Separation of Tagged from Untagged Products by Solid-Phase Extraction with Fluorous Reverse-Phase Silica Gel. J Am Chem Soc 121 9069-9072... 

Curran, D. P. Hadida, S. He, M. Thermal Allylations of Aldehydes with a Fluorous Allylstannane. Separation of Organic and Fluorous Products by Solids Phase Extraction with Fluorous Reverse Phase Silica Gel, J. Org. Chem. 1997, 62, 6714. 

Fig. 7. Synthesis of a library containing 100 mappicine derivatives with fluorous tags (Rf) efficient separation on fluorous reversed-phase silica gel is possible on the basis of the fluorine content of the tag [44].

Fluorous reverse-phase silica gel (separation by solid phase extraction). The hydroxyl residues on silica gel are modified with perfluoroalkyl chains. This causes a fluorophilic effect between the fluorous reagent/ catalyst/product and allows facile separation independent of temperature. 

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. 

Curran, D. P. (2001) Fluorous reverse phase silica gel. A new tool for preparative separations in synthetic organic and organofluorine chemistry. Synlett, 1488-1496. 

Glatz, H., Blay, C., Engelhardt, H. and Bannwarth, W. (2004) New fluorous reversed phase silica gel for HPLC separations of perfluorinated compounds. Chromatographia, 59, 567-570. 

A tin hydride attached to fluorous ponytails is quite versatile in respect of easy separation of the desired products from organotin compounds. When an iodoalkene was treated with NaCNBHs in the presence of a catalytic amount of fluor-oalkyltin hydride, the desired tricyclic ketones were produced (Scheme 12.133) [240]. Application of the crude mixture to a small plug of fluorous reversed-phase silica gel enabled facile separation of the cyclic ketone obtained (fluorous solid-phase extraction, FSPE). In contrast, when tris(trimethylsilyl)silane (TTMSH) was employed as a hydride source chromatographic purification of the nonpolar and somewhat volatile products was impossible because of contamination by nonpolar silicon-containing byproducts. 

Eor the separation of perfluoro-tagged compounds from other molecules, fluorous silica gel (FSG also called fluorous reversed-phase silica gel, FRPSG) can be employed. Examples of how perfluoroalkyl chains have been attached to silica gel surfaces are shown in Fig. 5. 

To make effective use of fluorous biphasic systems, the fluorous phase may also be a stationary phase. Fluorous compounds or compounds carrying fluorous ponytails have high affinity for fluorous reversed-phase silica gel [Ic, 13] which has been modified by means of a fluorous silane [14]. This effect has been used to achieve convenient isolation and purification of a variety of compounds with high fluorine content, first by simple solid-phase extraction (SPE) [15] and later by chromatography with a mobile phase based on a fluorophilicity gradient [16]. 

A recent example of the parallel synthesis of different quinazoline-2,4-dione derivatives (46) demonstrates how to combine the advantages of fluorous synthesis with those of solid-phase chemistry without using expensive perfluorinated solvents [22] (Scheme 3.22). In the beginning, a fluorous benzyl alcohol (47) is adsorbed on fluorous reversed-phase silica gel (FRPSG). Then, in a sequence of splits and reactions, the linker group, which remains bound to the FRPSG by fluorophilic interactions, is converted into a library of differently substituted carboxamido-urethanes (48). These are cyclized and the liberated quinazoline-2,4-diones (46) are eluted from the support with the fluorophobic solvents water and CHjCN/... 

Scheme 3.22 Fluorous synthesis of a library of substituted quinazoline-2,4-diones (46) [22]. The key to this approach is a fluorous benzyloxycarbonyl group on which the target molecules are stepwise constructed and which keeps the different synthetic intermediates bound to fluorous reversed-phase silica gel (FRPSG) during the purification cycles. The structural diversity of the target compound library (46) is introduced by the different anthranilic acid derivatives and primary amines in boxes) (TBTU = 0-(benzotriazol-1-yl)-N,/ /,N, N -tetramethyluronium tetrafluoroborate).

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. 

Bannwarth and co-workers have recently developed new protocols for the separation and recycling of perfluoro-tagged catalysts without the need for fluorous solvents [25]. They have employed Pd complexes 11c, lid, and 17, immobilized by adsorption on fluorous reversed-phase silica gels (FRPSG) 18 and 19, and demonstrated the application to Suzuki couplings in organic solvents. Coarse-grained... 

Fluorous reverse-phase silica gel (FRPSG)-supported Lewis acids are new and effective catalysts of Baeyer-Villiger and Diels-Alder reactions in water. FRPSG-supported Sc[C(S02C4F9)3]3 (5 mol%) catalyzes the Diels-Alder cycloaddition of 2,3-dimethyl-butadiene with methyl vinyl ketone in water at room temperature (16 h, 91%) and can be recycled by simple filtration after the reaction. ... 

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