Fluorous partition coefficients

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. 

A similar quantitative theory enabling prediction of the fluorophilicity (a substance is considered fluorophilic if fi > 0) or the fluorous partition coefficients P for fluorous reagents [11] is, unfortunately, not available. 

The fluorous alkylphosphines 2 [8, 12] and 3 [8, 13], containing one or two perfluoroalkyl tails, respectively, have also been prepared. Partition coefficients of the chiral fluorous monophosphines 3a-b were found to be lower than the values measured for the corresponding phosphines 1, which contain one extra perfluoroalkyl tail [13], In addition, fluorous phosphinites, phosphonites and phosphites 4a-e and diphosphonite 5 have become available [8, 14]. 

The discussion is oversimplified since increasing the number of fluorines does not always increase the partition coefficient into a fluorous phase. 

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... 

Table 3.4 Partition coefficients for selected fluorous compounds in the (I 3 Cf, 11 ) 1 /(113 Cg H5 biphase system [25]...

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. 

Fluorous biphase reactions have been reviewed extensively in the past few years, and most important types of reaction may now be conducted under fluorous conditions [46,51], However, partitioning of catalysts and reagents into the fluorous phase is seldom perfect - even a loss of 1-2% of an expensive catalyst may be unacceptable. Solubility and partitioning between phases relies on a complex balance of properties and interactions, and rather than simply adding more fluorocarbon chains to a catalyst (which is a common approach to the problem of leaching of catalyst from the fluorous phase), studies have indicated that the partition coefficients of fluorous compounds may better be optimised by... 

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... 

Table 1 Partition Coefficients of Phosphines in Organo-Fluorous Phases a...

A fluorous version of the chiral bis-phosphine BINAP has been developed for asymmetric Heck reactions [5]. Several flnorous-derivatized binaphthols and BINAP derivatives have been reported, (Scheme 10.4) [6]. The silane spacer gronp present in one of the ligands was nsed to maximize the percentage fluorine on the molecnle. Even so, the partition coefficient between FC-72 (see Chapter 3) and benzene was only 2.85, and not surprisingly, the reuse of the catalyst was poor. 

Table 7.3 Partition coefficients for some organic and fluorous compounds in FBS. ...

Fluorous catalysts are best suited for converting apolar substrates into products of higher polarity, as the partition coefficients of the substrates and products will be higher and lower, respectively, in the fluorous phase. 

At least 60wt% fluorine is required to obtain fluorous molecules that are preferentially soluble in the fluorous phase (partition coefficient P> 1). 

The most appealing feature of fiuorous chiral catalysts is their easy separation from the reaction products, and possible recycling. To this end, emphasis was initially placed on the FBS approach, which is only effective for heavy fluorous catalysts with high or at least moderate partition coefficients in perfluorocarbons. Besides being synthetically demanding, heavy fiuorous chiral catalysts can exhibit unpre-dictably low activities and stereoselectivities, even after careful optimization of the FBS reaction conditions. These seem to be less-compelling issues for relatively simple hght fiuorous chiral catalysts that can be quickly evaluated under the... 

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