Biphasic fluorination

With thin-film nickel reactors, Chambers and co-workers demonstrated the biphasic fluorination of numerous organic substrates including diketones [70], substituted toluenes [71], and more recently benzaldehyde derivatives [72], using... 

Compounds lb and 2b were the Urst fluorinated ligands tested in Mn-catalyzed alkene epoxidation [5,6]. The biphasic Uquid system perfluorooc-tane/dichloromethane led to excellent activity and enantioselectivity (90% ee) in the epoxidation of indene with oxygen and pivalaldehyde (Scheme 1, Table 1). In addition, the fluorous solution of the catalyst was reused once and showed the same activity and selectivity. This represents a considerable improvement over the behavior in the homogeneous phase, where the used catalyst was bleached and reuse was impossible. Unfortunately, indene was the only suitable substrate for this system, which failed to epoxidize other alkenes (such as styrene or 1,2-dihydronaphthalene) with high enantioselectivity. The system was also strongly dependent on the oxidant and only 71% ee was obtained in the epoxidation of indene with mCPBA at - 50 °C. 

Table 1 Results of the alkene epoxidation reactions with fluorinated (salen)Mn complexes under biphasic conditions ...

In contrast with salen ligands, ionic liquids were used earlier than fluorinated solvents for biphasic liquid systems with bis(oxazoline)-based complexes. In... 

The term fluorous biphase has been proposed to cover fully fluorinated hydrocarbon solvents (or other fluorinated inert materials, for example ethers) that are immiscible with organic solvents at ambient conditions. Like ionic liquids the ideal concept is that reactants and catalysts would be soluble in the (relatively high-boiling) fluorous phase under reaction conditions but that products would readily separate into a distinct phase at ambient conditions (Figure 5.5). 

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dependent miscibility of fluorinated solvents (organic solvents in which most or all of the hydrogen atoms have been replaced by fluorine atoms) with normal organic solvents, to provide a possible answer to the biphasic hydroformylation of long-chain alkenes.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

Pozzi and co-workers have also reported a fluorous soluble cobalt complex, which is active in the aerobic epoxidation of alkenes in a fluorous biphasic system (FBS).[50] The ligand used in this complex was a fluorinated tetraarylporphyrin, with eight perfluorooctyl chains shown in Figure 6.13. The cobalt complex was dissolved in perfluorohexane and added to a solution of the alkene with 2-methylpropanal (aldehyde substrate — 2 1) at room temperature. 

M. Cavazzini, F. Montanari, G. Pozzi, S. Quia, Perfluorocarbon-Soluble Catalysts and Reagents and the Application of FBS (Fluorous Biphase System) to Organic Synthesis , J. Fluorine Chem. 1999, 94,183. 

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]. 

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