Fluorous boronates

The palladium nanoparticle is prepared from the reaction of the stabilizer, 4,4 -bis(perfluorooctyl)dibenzylideneacetone with palladium(II) chloride. The average size of the nanoparticle varied according the ratio of PdCF to the stabilizer, but was typically around 4 or 5 nm. The initial yield observed in the Suzuki coupling reaction was 90%, but decreased to 78% after five consecutive runs. Fluorous boronates (alternative precursors in Suzuki reactions), have also been developed for use in fluorous biphasic processes [12], A generic structure of a fluorous boronate is shown in Figure 10.2. 

The fluorous boronate is highly soluble in fluorous solvents, but when the nonfluorous R-group combines with another nonfluorous R-group the resulting product becomes preferentially soluble in the organic phase into which it is automatically extracted. 

Figure 10.2 General structure of fluorous boronates used in fluorous biphase Suzuki reactions...

Fluorous phase modifications of the Stille reaction were shown by Curran et al. to be accelerated by microwave irradiation.10 Similarly, Hallberg et al. demonstrated that such irradiation gives remarkably fast solid-phase Suzuki reactions, in the generation of biaryl units.9 Their reaction involved the coupling of a tethered (Rink amide TentaGel) aryl iodide or bromide with several boronic acids under 45 W of irradiation at 2450 MHz in sealed... 

Scheme 17 illustrates another fluorous sulfonate-based synthesis of library scaffolds. The tagged substrates were taken through aldol condensation and cycloaddition reactions to form the pyrimidine ring 18. The intermediates were then reacted with boronic acids for Suzuki reactions to form biaryl compounds 19 [31], reacted with HCO2H to give traceless detagged products 20 [34], or reacted with amine to form products 21 [33]. 

Parallel synthesis of a bicyclic proline library 29 has been developed by a two-step synthesis involving 1,3-dipolar cycloaddition of fluorous benzalde-hydes followed by Pd-catalyzed Suzuki coupling reactions with boronic acids (Scheme 20) [43]. Both reactions were conducted under microwave irradiation and the reaction mixtures were purified by F-SPE without the need of performing a following chromatography. 

Heterogeneous reactions lend themselves to continuous flow reactors, which are desirable as they minimise the reacting volume. This reduces operation risks, and allows smaller, more efficient plants to be built. Flow reactors designed for fluorous reactions with both liquid and gaseous substrates have been demonstrated to be effective, at least on a bench scale [49]. Fluorous solvents have also recently found applications as liquid membranes to control the rate of addition of reagents and so control exothermic reactions such as alkene bromination (Fig. 6), and demethylation of anisoles by reaction with boron tribromide [50], This has potential as a clean route as the kinetic control gives improved selectivity. 

Fluorous DEAD was prepared and used in a Mitsunobu reaction.Fluorous triaryl phosphine was used for a Wittig reaction.Fluorous boronates were prepared and used in functional transformations and a Suzuki-Miyaura coupling reaction. 

Water-soluble calix[n]arenes are powerful receptors for non-polar substrates in aqueous solution. These compounds are promising candidates as carrier molecules for the transport of non-polar substrates through bulk water as well as inverse phase-transfer catalysts, as proven for the Suzuki coupling of iodobenzene with phenyl boronic acid [91]. 1.5-bis(4,4 -bis(perfluorooctyl)penta-l,4-dien-3-one (39) stabilizes palladium 0) nanoparticles (transmission electron microscopy) formed in the reduction of palladium dichloride with methanol. These palladium colloids are soluble in perfluorinated solvents, and they are efficient recoverable catalysts for Suzuki crosscoupling under fluorous biphasic conditions (Equation 69) [92]. 

Scheme 8.9 Coupling of aryl bromides and boronic acids with palladium in the presence of a fluorous tagged guanidine ligand in a fluorous-aqueous biphasic system.

A fluorous nano-paUadium catalyst based on pyrrolidine imide 22 was developed for the Suzuki coupling reaction (Scheme 7.12) [21]. The catalyst 22 promoted the coupling of aryl boronic acid and aryl halide with high yield, and the catalyst was recovered by fluorous liquid-liquid extraction and reused for three times. This fluorous nano-paUadium catalyst 22 was also employed in the Heck reaction in water [22]. The catalyst was recovered by fluorous liquid-liquid phase separation and reused for four times with Utde loss of catalytic activity. 

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