Fluorous solvents partition coefficients

The distribution of solutes between the two phases can be estimated by measurement of the relative solubility of the reagent in each phase of the system under given physical conditions. Water and 1-octanol have become a standard solvent mixture for this [21], although other pairs of solvents may be used to produce, for example, a scale of preference for fluorous versus organic solvents, as described below. The quantity P, known as the partition coefficient, is defined as... 

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. 

C4F9C2H4), are highly fluorophilic and exhibit large partition coefficients in favor of fluorocarbon solvents over common organic solvents due to a double-layered structure where the stannoxane core is covered by fluoroalkyl groups. Fluorous technology allows transesterification and esterification in which 100% yield of the desired esters is achievable with reactants in a strict 1 1 ratio. The tin catalysts are recovered from the fluorous phase quantitatively (Equation (95)).260... 

The value of perfluoroalkyl-derivatised ligands in FBS catalysis depends on the preferential solubility of the catalyst in a fluorous solvent. Initially, this was established, qualitatively, by 31P NMR spectroscopic studies [37,49], but very recently [52] the fluorous partition coefficients of metal complexes of the trialkyl phosphine (la) have been measured analytically, from which both a fluorine content of > 60% and the number of perfluoroalkyl groups, which shield the hydrocarbon domain of the complex, are crucial for a high fluorous partition. 

This can be exploited for the extractive separation of fluorous-tagged compounds from other substances. The partition coefficient depends on the size of the fluorous tag and on the organic solvent. The preference for the fluorous phase increases with increasing fluorine content and polarity of the organic phase. As the fluorous solvent, FC-72 (a mixture of CeFu isomers) is often used. At room temperature, it forms biphasic systems with solvents such as toluene, dichloromethane or acetonitrile and with aqueous media. Somewhat surprisingly, diethyl ether and tetrahydrofuran are good solvents for fluorous molecules and are miscible with FC-72 at... 

Here, the water has a big 8 (around 48) [24], the organic solvent has a medium 8 (around 20), and the fluorous solvent has a small 8 (around 12). The introduction of some perflu-oroalkylated moiety with small 8 into a highly hydrophilic molecule with a big 8 would result in lowering the 8 of the partially fluorinated molecule to a medium 8 value. This suppression of 8 would result in higher partition coefficient toward the organic phase, i.e. higher lipophilicity [24],... 

Pozzi, Sinou, and co-workers prepared a fluorous chiral phosphine, (R)-2- bis[4-(1 H,1 H-perfluorooctyloxy)phenyl]phosphino -2 -(l H,1 H-perfluorooctyloxy)-l, 1 -binaphthyl (F content = 52%, partition coefficient n-perfluorooctane/toluene = 0.23, n-perfluorooctane/CHjOH = 7.42) and used for a chiral ligand of palladium complex in an asymmetric aUyHc alkylation of 1,3-diphenylprop-2-enyl acetate [8]. The reaction was carried out at room temperature in BTF or toluene and gave the corresponding product in 99% and 88% chemical yields and 81% ee and 87% ee, respectively after the nonfluorous MOP complex gave the product in 95% yield and 99% ee in toluene at 0 °C [9]) [Eq. (1)]. When toluene was used as a solvent, the simple extraction of the reaction mixture with n-perfluorooctane (twice) allowed the complete removal of the ligand and of the palladium complex. However, the recovered palladium complex did not have catalytic activity for the reachon. 

In order to extract non-fluorous products from reactions involving fluorous solvents in a rational way, partition coefficients must be known. The design and optimization of fluorous catalysts and reagents require analogous data. In 1999, only a few partition coefficients involving fluorous and organic phases had been... 

Entries VI-22 through VI-25 feature monoiodide derivatives of some of the preceding fluorous benzenes. In all cases, the fluorophilicities decrease. Only for entry VI-25, a triply ponytailed eompound, is a highly biased partition coefficient maintained (2.0 98.0). When a more polar non-fluorous solvent, such as methanol, is employed, fluorous phase affinities increase. Nevertheless, it is clear that with monofunctional arenes, at least three ponytails of formula Rfs(CH2)3 are required for high degrees of fluorous phase immobilization. Entries III-4, IV-9 and V-3 show that two ponytails of formula Rfg (i.e. without spacers) are essentially as effective (1.4 98.6,2.6 97.4 and 1.2 98.8). 

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