Extraction fluorous

To take advantage of the fluorous extraction procedure, or the use of the preparatively simple filtration, the use of highly fluorous reagents is crucial. The usefulness of the microwave heating technique is obvious in these examples. 

An in situ carbonylation procednre was shown by Larhed to be compatible with recycling of the flnorons catalyst nsed in the reaction (Reaction Scheme 12). The catalyst was collected five times by a two-phase liquid fluorous extraction. The yields were shown to vary only slightly between the experiments. 

Ryu, Curran and their co-workers have achieved the fluorous hydroxymethyla-tion of organic halides using a catalytic quantity of a fluorous tin hydride [8] in the presence of sodium cyanoborohydride [10]. Interestingly, this fluorous reagent, as is usually the case for the related fluorous reactions [18], permits simple purification by a three-phase (aqueous/organic/fluorous) extractive workup. An example is given in Scheme 4-5. It should be noted that, unlike the cyclization-for-mylation sequence shown in the fourth equation in Scheme 4-3, the cyclization-hydroxymethylation sequence of the same substrate using a catalytic system was... 

The fluorous tag can be attached to catalysts, reagents, or the substrate itself. Several fluorous-tagged transition metal complexes have been developed, which can be recovered from reaction mixtures by fluorous extraction and then reused. Examples of fluorous transition metal complexes are shown in Fig. 3. 

Fluorous-tagged reagents are very attractive for reactions in which a stoichiometric by-product is formed that is difficult to separate. An example is perfluor-oalkylated triphenylphosphane for use in Wittig and aza-Wittig reactions, where the corresponding phosphane oxide is removed by fluorous extraction [22, 23]. Similarly, fluorous sulfoxide has been employed in Swern oxidations, and fluorous carbodiimide has been used as a coupling reagent [24, 25]. 

Preparation of 26 [14] Allyl alcohol 22 (0.91 mmol) and triethylamine (1 equiv.) were dissolved in dry tetrahydrofuran (THF) (2 mL) under argon. A solution of bromo tris(2-perfluorohexylethyl)silane 23 (0.25 equiv) in THF (2 mL) was slowly added to the reaction mixture at 25 °C. The resulting mixture was stirred at 25 °C for 3 h. After removal of the solvent, the residue was purified by three-phase extraction with FC-72 (10 mL), dichloromethane (10 mL), and water (10 mL). The organic/aqueous biphase was extracted twice more wdth FC-72 (10 mL). After concentration of the combined fluorous extracts, the residue was purified by flash chromatography (hexane/diethyl ether, 50 1) to yield a colorless oil. 

An unavoidable by-product of the Swem reaction is the volatile dimethylsulphide which, on account of its unpleasant smell, is a reagent regulated by offensive odour control laws. This makes large scale chemistry problematic, especially in industry. To overcome this, several methods exist to perform the Swem oxidation under odourless conditions. For example, Node et al. outline a protocol for the Swem oxidation which uses dodecyl methyl sulfoxide in place of methyl sulfoxide,12 while Crich and co-workers have developed a fluorous Swem oxidation reaction that uses tridecafluorooctylmethyl sulfoxide 17,l3a,b This reagent can be recovered via a continuous fluorous extraction procedure and recycled by reoxidation with hydrogen peroxide. Additionally, the fluorous DMSO is crystalline, odourless and soluble in CH2CI2 to —45 °C. 

When ketones are converted to enones by reaction with p-perfluorohexylbenzene-selenenyl chloride and subsequent oxidative elimination, the spent reagent can be recovered in the form of the diselenide by reduction and continuous fluorous extraction. 

Examples of using functionalized, fluorinated carboxylates as alternative X-type ligands for the generation of supported catalyst analogs were previously introduced in section The Attachment of Grubbs-Type Catalysts via the X-Type Ligand . However, the introduction of fluorous functionalities within the catalyst architecture can also be employed to aid in product isolation and to effectively recover/recycle a catalyst via fluorous extraction [141]. Although similar to the IL systems that were discussed in the previous section, this approach instead uses... 

Yao and coworkers [ 142] were the first to report a fluorous-functionalized olefin metathesis catalyst. A random, bifunctional, fluorous polyacrylate material, containing both a perfluoroalkyl section and a styrenic Hoveyda ligand section in a 10 1 ratio, was prepared. This was then treated with catalyst 4 to generate the heavy fluorous catalyst 156. This catalyst was then effectively used in a variety of RCM reactions at 50 C, employing a solvent mixture of PhCFj/CHjClj (1 19 v/v). This catalyst system was shown to be efficiently recycled a total of 20 times using a fluorous extraction technique. Unfortunately, no results were reported pertaining to any residual Ru contamination within the organic fractions. 

Huang and coworkers have also used the fluorous extraction to efficiently purify desired oligosaccharides from the mixtures of their one-pot products (Scheme 16.30). Thus, after... 

Scheme 16.34. Microfluidic and fluorous extraction techniques for oligosaccharide synthesis.

Curran has used fluorous tin reactants (45) to facilitate the separation of the desired product from tin by-products via a three-phase (aqueous/organic/fluorous) extraction protocol as presented below. This also allows for easy isolation and recycling of the tin fluorous compound. 

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