Biphasic catalysis fluorous

The fluorous biphasic concept was introduced by the Hungarian chemists Istvan Horvath and Jozsef Rabai in 1994 [148], A fluorous biphasic system consists of a fluorous phase (a perfluoroalkane-, perfluorodialkyl ether-, or perfluorotrialkylamine-rich phase) containing a fluorous-soluble reagent or catalyst, and a second phase, 

Horvath and Rabai demonstrated the efficiency of their fluorous-soluble RhP[CH2CH2(CF2)5CF3]3 catalyst in the hydroformylation of 1-decene at 100 °C, usingaSOiSOvol toluene/CgFnCFsSolventmixtureandllbarofl 1 CO/H2[148]. 

Interestingly, the first experiments demonstrating the fluorous biphasic concept were actually made in 1991 by M. Vogt, a German PhD student at the Rheinisch-Westfalischen Technischen Hochschule in Aachen. Unfortunately, Vogt (and his supervisor ) never published these results except as a PhD thesis hidden at the technical school library in Aachen, so their work remained secret. It came to light only some years after the field of fluorous biphasic chemistry was established internationally [151]. 

In the Kuraray process for the production of nonane-1,9-diol two steps involve the use of aqueous biphasic catalysis Pd/tppms catalyzed telomerization of butadiene with water as a reactant and Rh/tppms catalyzed hydroformylation (Fig. 7.14) [51]. 

The palladium(II) complex of sulfonated bathophenanthroline was used in a highly effective aqueous biphasic aerobic oxidation of primary and secondary alcohols to the corresponding aldehydes or carboxylic acids and ketones respectively (Fig. 7.15) [52, 53]. No organic solvent was necessary, unless the substrate was a solid, and turnover frequencies of the order of 100 h-1 were observed. The catalyst could be recovered and recycled by simple phase separation (the aqueous phase is the bottom layer and can be left in the reactor for the next batch). The method constitutes an excellent example of a green catalytic oxidation with oxygen (air) as the oxidant, no organic solvent and a stable recyclable catalyst. 

Fluorous biphasic catalysis was pioneered by Horvath and Rabai [54, 55] who coined the term fluorous , by analogy with aqueous , to describe highly fluori-nated alkanes, ethers and tertiary amines. Such fluorous compounds differ markedly from the corresponding hydrocarbon molecules and are, consequently, immiscible with many common organic solvents at ambient temperature although they can become miscible at elevated temperatures. Hence, this provides a basis for performing biphasic catalysis or, alternatively, monophasic catalysis at elevated temperatures with biphasic product/catalyst separation at lower temperatures. A number of fluorous solvents are commercially available (see Fig. 7.16 for example), albeit rather expensive compared with common organic 

In order to perform fluorous biphasic catalysis the (organometallic) catalyst needs to be solubilized in the fluorous phase by deploying fluorophilic ligands, analogous to the hydrophilic ligands used in aqueous biphasic catalysis. This is accomplished by incorporating so-called fluorous ponytails . 

EaStCHEM, School of Chemistry, University of St Andrews, St Andrews,Fife, KYI 6 9ST, Scotland 

Biphasic systems, in which the catalyst is designed to be dissolved in a liquid phase which is immiscible with the product (either with or without a separate solvent) potentially provide some of the most attractive solutions to the problem of product 

Various other biphasic solutions to the separation problem are considered in other chapters of this book, but an especially attractive alternative was introduced by Horvath and co-workers in 1994.[1] He coined the term catalysis in the fluorous biphase and the process uses the temperature dependent miscibility of fluorinated solvents (organic solvents in which most or all of the hydrogen atoms have been replaced by fluorine atoms) with normal organic solvents, to provide a possible answer to the biphasic hydroformylation of long-chain alkenes. At temperatures close to the operating temperature of many catalytic reactions (60-120°C), the fluorous and organic solvents mix, but at temperatures near ambient they phase separate cleanly. Since that time, many other reactions have been demonstrated under fluorous biphasic conditions and these form the basis of this chapter. The subject has been comprehensively reviewed, [2-6] so this chapter gives an overview and finishes with some process considerations. 

Fluorous biphasic systems operate on the premise that the catalyst complex is preferentially soluble in the fluorous phase. This is achieved by synthesising fluorinated ligands that have a high weight-percentage of fluorine. It has been reported that for a complex to be preferentially soluble in fluorous solvents it must contain 60 

J Cole-Hamilton and R. P. Tooze (eds.), Catalyst Separation, Recovery and Recycling, 145-181. 2006 Springer. Printed in the Netherlands. 

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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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