Fluorous silica

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... 

Recently, the fluorous biphasic separation technique has been enriched with two new developments, both of which were demonstrated in hydrogenation. The need for a fluorous solvent can be eliminated by using fluorous silica as a fluorous catalyst scavenger. In liquid-liquid biphasic systems, reversible expan-... 

Figure 3. Solid phase extraction over fluorous reverse phase silica...

Unfortunately, the appeal of solid phase extractions on small scale fades as the scale increases due to the cost and inconvenience of using large amounts of fluorous silica gel. Here, modified techniques to reduce the tedium of repeated extractions are attractive. For example, Crich has recently introduced the minimally fluorous selenide C6Fi3CH2CH2C6H4SeH[171. This selenol is added in catalytic quantities to tin hydride reductions of reactive aryl and vinyl radicals. The high reducing capacity of the aryl selenide suppresses undesired reactions of product radicals without suppressing the reactions of the aryl and vinyl radicals themselves. After the reaction is complete, the selenol can be recovered by a modified continuous extraction procedure. 

As would be expected, fluorous compounds are preferentially retained on fluorous silica gel [62]. Similarly, fluorous catalysts can be adsorbed on fluorous silica gel. These materials have been applied to reactions in organic solvents and water, both at room temperature and above [63-69]. The investigators have usually interpreted the transformations as bonded fluorous phase catalysis , which corresponds to sequence B-II in Fig. 1. However, there remains the possibility that at least some catalysis proceeds under homogeneous conditions via desorbed species. To our knowledge, fish-out experiments analogous to that conducted with the Teflon tape in Fig. 8 have not been conducted. 

To date, reports have involved palladium catalysts for Suzuki and Sono-gashira coupling reactions [63-66], rhodium catalysts for silylations of alcohols by trialkylsilanes [67,68], and tin-, hafnium-, and scandium-based Lewis acid catalysts for Baeyer-Villiger and Diels-Alder reactions [69]. Regardless of exact mechanism, this recovery strategy represents an important direction for future research and applications development. Finally, a particularly elegant protocol where CO2 pressure is used instead of temperature to desorb a fluorous rhodium hydrogenation catalyst from fluorous silica gel deserves emphasis [28]. 

Although the imidazolidinone catalysts used within these transformations are simple, cheap, readily accessible and in some cases recyclable using acid/base extraction, considerable efforts have been made to examine alternative methods to separate and recycle the catalyst with good success. Examination of the structure of imidazolidinone 22 shows two convenient points for the introduction of a polymer or fluorous support, R and R, both of which have been examined (Fig. 4). Curran has shown that identical reactivity, diastereoselectivity and enantioselectivity can be obtained using a fluorous tag (23) [53]. The catalyst can easily be recovered and recycled using F-SPE with excellent yield, purity and levels of activity. Polymer- (24) and silica-supported (25) imidazolidinones reported by Pihko [54] (R substitution)... 

Recently, the submitters have developed new separation procedures based on fluorous silica gel, and the separation of fluorous compounds by solid phase extraction... 

The fluorous silica concept involves the selective partitioning of a fluorous-modified catalyst between an organic liquid phase and the fluorinated surface phase. In the absence of CO2, the fluorinated catalyst prefers the fluorous surface phase and remains partitioned onto the silica. When CO2 pressure is added, the catalyst will partition off of the silica and into the GXL phase (containing reactants), where homogeneous reaction can take place. After the reaction is completed, the CO2 is removed and the catalyst will partition back onto the fluorous silica surface, which can be easily recovered by filtration. A cartoon schematic is shown as Figure 2. 

Figure 2. Schematic representation of the fluorous silica concept. In the absence of CO2 the catalyst partitions onto the fluorous silica surface. In the presence of CO2 the catalyst partitions into the bulk liquid phase where reaction takes place (14).

Our fluorous silica technology was also tested (1) on the catalytic hydrogenation of styrene. The fluorous silica phase contained a fluorinated version of Wilkinson s catalyst (Figure 3) deposited onto the surface of the fluorous silica. The organic phase consisted of styrene dissolved in cyclohexane. No fluorous solvent was used. 

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. 

Another elegant technique in fluorous synthesis is the use of reverse-phase fluorinated silica gel as a solid separation phase. Such fluorinated solids allow the separation of fluorous from nonfluorous materials by selective adsorption, and can even be used for chromatographic separations by degree of fluorination (Kainz et al., 1998). These techniques require a considerably lower content of fluorine for efficient separation and have been referred to as light fluorous synthesis (Curran and Luo, 1999). 

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].

Curran DP (2004) Separation with fluorous silica gel and related materials. In Gladysz JA, Curran DP, Horvath IT (eds) Handbook of Fluorous Chemistry. Wiley, Weinheim, p 101... 

Systems have been developed that allow the recycling of catalysts. The first case study involved simple adsorption of proline onto silica gel [6], but the system suffered from a loss in enantioselectivity. More recently, promising results have been obtained with fluorous proline derivatives [64] used for aldol reactions the recycling of fluorous catalysts has been demonstrated using fluorous solid-liquid extraction. Solid phase-supported catalysts through covalent bonds [65] and through noncovalent interactions [66] were also used for aldol reactions. Proline and other catalysts can be recycled when ionic liquids or polyethylene glycol (PEG) were used as reaction solvents [67]. 

Hyperbranched polymers can also be used for supramolecular immobilization (Scheme 15). Yet another approach for the noncovalent immobilization has been presented by Tzschucke and coworkers who used interactions between fluorous phase silica (FPS) and perfluoro-tagged palladium... 

This supramolecular dendritic assembly serves as a valuable soluble model for the interaction of perfluoro-tagged catalysts with insoluble supports such as fluorous silica gel and clearly reveals the ligand diffusion from the complex at elevated temperatures. This behavior can also explain the high catalytic activity of the heterogeneous FPS system. 

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