Fluorous, hydroformylation reaction

An application of the fluorous two-phase system to catalytic reactions is the hydro-formylation of terminal olefins with CO and H2 [5]. Aldehydes 1 can be isolated, together with the branched side products 2. In the Q,FiiCF3/toluene solvent mixture, the catalyst [HRh(CO) P[CH2CH2(CF2)5CF3]3 3] is obtained in situ. It acts in the hydroformylation reaction at 100 °C and can be separated afterwards in the fluorous phase. In this process, however, approximately 0.5% of the catalyst remains in the organic phase. Furthermore, the lower solubility of CO and H2 in the fluorous phase produces a lower catalyst activity. Accordingly, the hydroformylation of ethene can be conducted in a continuous process in an autoclave. 

Fluorous biphasic catalysis was first reported with the hydroformylation reaction depicted in Figure 12.16 (Curran and Lee, 2001). 

A highly fluorous C02-philic rhodium catalyst was effectively immobilized in an inverted H20/scC02 system for the prototypical hydroformylation reaction shown in Eq. (5) [57]. Emulsion-type mixtures are formed under the reaction conditions upon stirring, which separate rapidly when stirring is stopped. After removal of the aqueous phase from the bottom of the reactor, a clear supercritical catalyst phase remains in the reactor that can be re-used for subsequent reactions. Recycling is very efficient at moderate catalyst loadings, but noticeable deactivation occurs at very low rhodium concentrations, probably caused by the low pH of the aqueous solution in the presence of C02. 

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dependent miscibility of fluorinated solvents (organic solvents in which most or all of the hydrogen atoms have been replaced by fluorine atoms) with normal organic solvents, to provide a possible answer to the biphasic hydroformylation of long-chain alkenes.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. 

The fluorous solvent alone had a minimal effect on the outcome of the reaction. However, with the fluorinated ligand, the rr.iso ratio was found to increase with increasing phosphine concentration, reaching a value of almost 8 1 at a phosphine to rhodium ratio of 103 1. The beauty of this system was demonstrated by its use in a semicontinuous hydroformylation experiment. After each... 

Modified cobalt complexes of the type frans-Co2(CO)6(phosphine)2 are promising candidates for certain transition metal-catalyzed reactions, in particular for the hydroformylation of long-chained olefins [117]. A series of complexes Co2(CO)6[P(alkyl) (aryl)m]2 (n 0,1,2,3 m S - n) was synthesized and used for solubility measurements. Since the basicity of phosphines affects the catalytic activity, use of fluorous substituents might induce unexpected changes in the activity. Therefore, also derivatives with an additional ethyl spacer between the fluorous group and the phosphine moiety were examined (Sect. 3.1). 

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... 

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