Fluorous biphasic condition

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dependent miscibility of fluorinated solvents (organic solvents in which most or all of the hydrogen atoms have been replaced by fluorine atoms) with normal organic solvents, to provide a possible answer to the biphasic hydroformylation of long-chain alkenes.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

Figure 6.6. Hydrosilation of alkenes under fluorous biphasic conditions.[34]...

Figure 6.28. Acetylation of cyclohexanol carried out continuously under fluorous biphasic conditions for 500...

In a similar fashion, 2 a, 2 c, 4 a and 4 c were also tested in the hydrogenation of 1-hexene under fluorous biphasic conditions (l-hexene/PFMCH = l 2 (v v)) [12, 14]. Relatively low activities were found for all catalysts, with activities increasing in the order 4a<4c<2a<2c. 

A similar reaction has been conducted under fluorous biphasic conditions, using a perfluoroalkylated bipyridine as ligand to ensure that the copper species resides in the fluorous phase [22], The oxidation of a range of primary alcohols to the corresponding aldehydes was found to be possible, an example of which is shown in Scheme 9.11. The catalyst could be successfully recycled by phase separation, with analytically pure products being isolated even after... 

The key result from this study is that the Pd/dendrimer nanocomposites are catalytically active under fluorous biphasic conditions. Indeed, one catalyst was... 

The possibility of asymmetric induction under the fluorous biphase conditions was first speculated upon by Horvath and Rabai [10], and this year has seen the first report of asymmetric catalysis in a fluorous biphase [69]. Two, C2 symmetric salen ligands (29a, b) with four C8Fi7 ponytails have been prepared (Scheme 5) and their Mn(II) complexes evaluated as chiral catalysts for the aerobic oxidation of alkenes under FBS-modified Mukaiyama conditions. Both complexes are active catalysts (isolated yields of epoxides up to 85%) under unusually low catalyst loadings (1.5% cf. the usual 12%). Although catalyst recovery and re-use was demonstrated, low enantioselectivities were observed in most cases. 

It was therefore reasonable for us to postulate that replacement of surface alkyl groups on the distan-noxanes with fluoroalkyl groups should render the molecules fluorophilic, and that mild catalysts would be accessible and workable under fluorous biphasic conditions. 

The second generation of catalysts for this transformation was based on fully fluorinated trisindazolylborates, leading to highly electrophilic metal centers. A series of five new ligands were prepared (Scheme 13) and their silver complexes synthesized and tested as catalysts for the alkane functionalization reaction. In addition to excellent activities, they were employed in fluorous biphasic conditions, allowing a ready separation of products from the catalyst, and the subsequent recycling of the latter. 

A similar triarylphosphane was introduced by Leitner for the performance of transition metal catalyzed reactions in supercritical CO2 [24]. Recently, this phosphane was used for palladium catalyzed substitutions of allylic substrates in perfluorinated solvents under fluorous biphase conditions [25], Therefore, the reaction of cinnamyl methylcarbonate (36) with several nucleophiles (Nu-... 

The direct condensation of carboxylic acids with aliphatic alcohols has been investigated by the use of fluorous ammonium salts as metal-free catalysts (Equation 4.24). Esterification reactions were carried out under mild fluorous biphasic conditions, in the presence of 1 mol% of fluorous ammonium triflate and without any water removal techniques. In the case of primary and secondary aliphatic alcohols, good to excellent ester yields were obtained. The fluorous ammonium triflate salt was easily recovered by simple phase separation and reused at least three times without any significant loss of activity [45],... 

Reagents involved in the oxidation of alcohols to aldehydes-ketones by oxygen under fluorous biphasic conditions are TEMPO, CuBr-SMe2, and 4,4 -bis[heptadecafluoro)-dodecyl]-2,2 -bipyridyl. The Mn(salen) complexes that mediate epoxidation of alkenes have been modified to bear polyfluoroalkyl substituents in the aromatic rings. Oxyfunc-tionalization of unactivated C—H sites is achieved with perfluorinated oj-2-butyl-3-propyloxaziridine. "... 

Oxidations. Benzylic alcohols undergo aerial oxidation to aromatic aldehydes in the presence of many different catalysts OsOVCuCl-pyridine (for benzylic alcohols only OSO4 is needed)," Ru-on-hydroxyapatite, hydrotalcite-supported Pd(II)," and CuBr-SMe2 under fluorous biphasic conditions. ... 

FI. [Cu Br Me2S-hipyridine] under Fluorous Biphasic Conditions (97,98)... 

Fig. 27. [Cu -TEMPO]-catalyzed aerobic oxidation of alcohols using fluorous biphasic conditions 97,98).

Table 1 Hydroformylation of higher aikenes under fluorous biphasic conditions with phosphites 1-6.

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