Fluorous Biphase Systems FBS

The concept of fluorous biphase hydroformylation of heavy olefins was introduced by Horvath at Exxon in 1994 [42, 43]. Fluorocarbon-based solvents, especially perfluorinated alkanes and ethers, are of modest cost, chemically inert, and nonpolar and show low intermolecular forces. Most of them are immiscible with water and can be therefore used as the nonaqueous phase. Moreover, their miscibility with organic solvents such as toluene, THF, or alcohols at room temperature is quite low. Only at elevated temperature miscibility occurs. These features allow hydroformylation at smooth reaction conditions at 60-120 °C in a homogeneous system [44]. Upon cooling, phase separation takes place. The catalyst is recovered finally by simple decantation. One of the last summaries in this area was given by Mathison and Cole-Hamilton in 2006 [45]. 

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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. 

More recent conceptual advances in the liquid/liquid biphasic systems include the novel fluorous biphase system (FBS)12-14,70-73 and the use of ionic liquids15-22... 

Figure 5.1. Separation scheme to recycle a homogeneous metal catalyst in a typical fluorous biphasic system (FBS).

This new experimental technique, using fluorous solvents or fluorous biphasic systems (FBS) with fluorous biphase catalysis (FBC), was developed by Vogt and Kaim [884] and by Horvath and Rabai [885] in 1991 and 1994, respectively. Since then, this method has found many applications in synthetic organic chemistry and has already been reviewed repeatedly [886-893]. Incidentally, temperature-dependent two-phase one-phase transitions are not limited to combinations of fluorous solvents with organic solvents. For example, certain mixtures of water and l-cyclohexylpyrrolidin-2-one form one phase at ambient temperature and a two-phase system at higher temperatures >ca. 50 °C), also allowing interesting separation possibilities. 

In addition to aqueous biphasic systems a number of alternative two phase processes using non-aqueous hquid/hquid systems are emerging. One example is Horvath s proposal of a fluorous biphase system (FBS) using the immiscibihty of a fluorinated compound with organic solvents. 

The Sonogashira coupling reaction of terminal alkynes with aryl or vinyl halides is a useful tool for carbon—carbon bond formation, and has found wide employment in areas such as natural product synthesis, the pharmaceutical industry, and material sciences. Novel recyclable Pd catalysts with fluorous ponytails in the ligand 2,2 -bipyridine were reported in a copper-free Pd-catalyzed Sonogashira reaction in a fluorous biphasic system (FBS) (Equation 4.19). The catalysts are only soluble in perfluorinated solvents at room temperature [41],... 

Some further studies still deal with the Friedel-Crafts acylation in fluorous fluids. These fluids all have very unusual properties such as high density and high stability, low solvent strength and extremely low solubility in water and organic compounds, and, finally, nonflammability. These properties allow their easy handling and reuse. Friedel-Crafts acylation of electron-rich aromatic substrates can be very efficiently performed in a fluorous biphasic system (FBS), which represents a benign technique for phase separation, and catalyst immobilization and recycling. 

The most severe dra wback in homogeneous catalysis is the separation of the catalyst from the reaction mixture. The industrial success of the aqueous two-phase hydroformylation ofpropene to n-butanal [1] in Ruhrchemie AG in 1984 represents the considerable progress in this field. However, aqueous/organic biphasic catalysis has its limitations when the water solubility of the starting materials proves too low, as in hydroformylation of higher olefins (see Chapter 1). To solve this issue, a variety of approaches have been attempted. Additions of co-solvents [2] or surfactants [3, 4] to the system or application of tenside ligands [5, 6] and amphiphilic phosphines [7, 8] are ways to increase the reaction rates. Other approaches such as fluorous biphase system (FBS see Chapter 4) [9], supported aqueous phase catalysis (SAPC see Section 2.6) [10], supercritical CO2 (cf. Chapter 6) [11] and ionic liquids (cf Chapter 5) [12] have also been introduced to deal with this problem. 

Another useful solvent system is made of THF and a perfluorinated solvent (fluorous biphasic system, FBS). Ligands bearing long polyfluorinated chains are required in order to solubilize the metal complexes in fluorous phases. ... 

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