Catalysis fluorous biphase

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Easy recycling of gold hydrosilation catalysts has also been achieved using a fluorous approach.Conversions varied from moderate to excellent for the reaction of dimethylphenylsilane with benzaldehyde. However, the mechanism is not clear at this stage. The catalyst could not be recycled in the absence of fluorous solvents under thermomorphic conditions and the formation of 

Catalytic gold nanoparticles (a) TEM image, (b) particle size distribution of particles distribution (%) vs diameter of particles (nm) [Reprinted with permission from QSAR Comb. Sci., 2006, 25, 719-722. Copyright 2006 Wiley-VCH.] 

Fluor OUS Sonogashira reactions (a) using a fluorous support and no fluorous solvent, (b) using perfluorodecaline under phosphine- and copper-free conditions. 

Another recent addition to the fluorous biphase toolbox is the discovery of fluorous phase transfer catalysts for halide substitution reactions in aqueous-fluorous systems.This class of reactions is academically intriguing, as an ionic displacement reaction has taken place in one of the least polar solvents known. They make use of fluorous phosphonium salts under biphasic conditions but can also make use of non-fluorous phosphonium salts in a triphasic system. Further information and reactions using such systems will no doubt be reported in the next few years. 

Reagents with very high fluorine content ( 60 % fluorine by weight) tend to dissolve well in fluorous solvents. In a biphasic fluorocarbon-hydrocarbon system they have a strong preference for the fluorous phase. Thus, by simple temperature cycling, such a solvent system can be reversibly switched between a biphasic and a homogeneous state. In the biphasic state, fluorous reagents are exclusively present 

Copyright 2004 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-30691-9 

The temperature-dependent miscibility of fluorous biphasic systems [1] can be predicted by use of the Hildebrand-Scratchard or regular solution theory [2, 9]. According to this theory the critical temperature (T). above which the two liquids of a biphasic system mix in all ratios is dose to the phase-separation temperature of a biphasic system consisting of equal volumes of each phase  

A similar quantitative theory enabling prediction of the fluorophilicity (a substance is considered fluorophilic if fi 0) or the fluorous partition coefficients P for fluorous reagents [11] is, unfortunately, not available. 

Nevertheless, for general design of fluorous compounds some rules have been derived by combination of empirical and computational methods (QSAR, neural network simulation) [12[. These rules are illustrated by the data in Table 3.1 and can be summarized as follows  

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Several reviews and overviews survey the development and current state of fluorous biphasic catalysis,122"251 and a recent application by Gladysz and... 

These examples reveal the attractive features of fluorous biphasic catalysis methods for chemical processes. Reactions occur in the liquid phase and can be either homogeneous or biphasic. In either case, biphasic conditions are established at the end of the reaction so the separation is easy. Fluorous sol-... 

Despite their vast untapped potential, techniques like fluorous biphasic catalysis still have limitations. These limitations center on solubility and emanate directly from the strengths of the technique heavily fluorous compounds tend to be highly insoluble in organic solvents while organic compounds (especially polar ones) tend to be highly... 

The technique now called fluorous biphasic catalysis was apparently first described in the Ph.D. thesis of M. Vogt in 1991 however, these studies did not become known to the community until sometime later. W. Keim, M. Vogt, P. Wasserscheid, B. Driessen-Holscher, Perfluorinated polyethers for the immobilization of homogeneous nickel catalysts , J. Mol. Catal A Chem. 1999,139,171. 

R. H. Fish, Fluorous Biphasic Catalysis A New Paradigm for the Separation of Homogeneous Catalysts from their Reaction Substrates and products , Chem. Fur. J. 1999, 5,1677. 

These critical aspects of the classical fluorous biphasic catalysis led in recent works to the development of protocols for the conversions with modified catalyst systems in non-fluorinated hydrocarbons as solvents. As part of the BMBE lighthouse project, Gladyzs and coworkers appHed this concept to C - C coupHng reactions (Suzuki reaction) and other metal-catalyzed addition reactions (hydrosilylation, selective alcoholysis of alkynes), which have direct relevance for the synthesis of fine chemicals and specialties [74]. 

Following the publication of the first example of fluorous biphase catalysis by Horvath and Rabai in 1994 [1], the immediate focus was to develop catalysts that would exhibit very biased partition coefficients with respect to fluorous and organic solvents. Such liquids are normally immiscible at room temperature. This was done by attaching ponytails of the formula (CH2)m(CF2) -iCF3 (abbreviated (CH2)mRf )> including arrays emanating from silicon atoms [2]. Catalysis was then effected at elevated temperatures, where fluorous and organic solvents are commonly miscible, with prod-uct/catalysis separation at the low-temperature two-phase limit. 

Fig. 22. Schematic illustration of the approach used to carry out fluorous biphasic catalysis using dendrimer-encapsulated metal nanoparticles modified on their exterior with perfluoroether ponytails. Note that the ponytails can be attached by either electrostatic or covalent means. Reprinted with permission from Ref. 103 Copyright 2000 American Chemical Society...

The major problem associated with aqueous catalysis is the limited and often very low solubility of certain organic reactants in water. Much work is needed to find practical solutions for these hydrophobic reactants. Possibilities deserving further attention include the application of fluorous biphasic catalysis or nonaqueous ionic liquid catalysis. The potential of organic reactions compatible with or even promoted by water is not yet fully exploited. 

A chapter written in 1996 covers hydroformylation catalyzed by organometallic complexes in detail,219 whereas a review written 5 years later gives a summary of the advances on hydroformylation with respect to synthetic applications.220 A selection of papers in a special journal issue has been devoted to carbonylation reactions.221 A major area of the research has been the development of fluorous biphasic catalysis and the design of new catalysts for aqueous/organic biphasic catalysis to achieve high activity and regioselectivity of linear or branched aldehyde formation. 

Because of their low solubilities in the aqueous phase, the hydroformylation of higher alkenes (>C2) is still a challenging problem. In addition to fluorous biphasic catalysis, possible solutions, which have been addressed, include the addition of surfactants240,241 or the use of amphiphilic ligands242-244 to enhance mutual solubility or mobility of the components across the phase boundary and thereby increase the rate of reaction. The use of polar solvents such as alcohols,245 p-cyclodextrin,246 cyclodextrin ligands,247 248 thermoregulated phase-transfer... 

Fluorous biphase catalysis was also applied in Friedel-Crafts acylation with Yb tris(perfluoroalkanesulfonyl)methide catalysts with acid anhydrides.59 Of the aromatics studied, activated compounds and naphthalene (95% conversion) showed satisfactory reactivity. 

Figure 14.2. Phase changes in a fluorous biphasic catalysis system.

The fluorous biphasic catalysis concept was successfully demonstrated first by hydroformylation of 1-decene carried out in perfluoromethylcyclohexane and toluene, which forms a homogeneous liquid phase at 100°C in the presence of catalyst 2 prepared in situ according to Eq. (14.1) 125,133... 

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