Fluorous phase chemistry

In fluorous synthesis, the possibility for separation on a fluorous solid phase allows for reduction of the fluorine content in the tags. Fluorous resins offer a way to confront the high molecular weight problem resulting from fluorous tagging and therefore the problem of atom economy in fluorous-phase chemistry. 

For commercial use of fluorous phase chemistry see the following internet pages http //www.fluorous.com and http //www.ict-inter.net. 

The strategy best developed to date consists in the use of new types of solvents ionic liquids, fluorous phase chemistry, supercritical carbon dioxide, and biosolvents. Other technologies include the use of water as solvent, and the solventless approach which avoids the use of such substances. 

A.P. Dobbs and M.R. Kimberley (2002) Journal of Fluorine Chemistry, vol. 118, p. 3 - Fluorous phase chemistry A new industrial technology . 

Choosing fluoiinated substrates, soluble in fluorinated solvents, Curran et al. have used fluorous-phase chemistry toward the synthesis of DHPMs. The reaction mixture was purified by a liquid-liquid extraction method because by-products were not soluble in fluorinated solvents. Reaction of fluorinated urea 16 with alkyl acetoacetate and an aldehyde. 

More recently we have also described another approach to using polymer in phase separation and catalyst recovery. This approach (equation 7) is similar to the fluorous phase chemistry shown in Figure 5 but uses less expensive solvents. For example, we showed that we can make a polymeric catalyst like 5 or 6 and that... 

Scheme 10.8 Synthesis of/8- l —>6) linked D-glucopyranoside homotetramer via iterative glycosylation in a combined system of microreactor and fluorous phase chemistry [27]. Source Copyright 2007 American Chemical Society.

Abstract Current microwave-assisted protocols for reaction on solid-phase and soluble supports are critically reviewed. The compatibility of commercially available polymer supports with the relatively harsh conditions of microwave heating and the possibilities for reaction monitoring are discussed. Instrmnentation available for microwave-assisted solid-phase chemistry is presented. This review also summarizes the recent applications of controlled microwave heating to sohd-phase and SPOT-chemistry, as well as to synthesis on soluble polymers, fluorous phases and functional ionic liquid supports. The presented examples indicate that the combination of microwave dielectric heating with solid- or soluble-polymer supported chemistry techniques provides significant enhancements both at the level of reaction rate and ease of purification compared to conventional procedures. 

Some of the disadvantages of the Stille reaction, e. g. the low reactivity of some substrates, separation difficulties in chromatography, and the toxicity of tin compounds, have been ameliorated by recent efforts to improve the procedure. Curran has, in a series of papers, reported the development of the concept of fluorous chemistry, in which the special solubility properties of perfluorinated or partly fluorinated reagents and solvents are put to good use [45]. In short, fluorinated solvents are well known for their insolubility in standard organic solvents or water. If a compound contains a sufficient number of fluorine atoms it will partition to the fluorous phase, if such a phase is present. An extraction procedure would thus give rise to a three-phase solution enabling ready separation of fluorinated from nonfluorinated compounds. 

On the heels of work by Zhu and Horvath and Rabai, perfluorocarbon solvents and fluorous reagents have been used increasingly in organic syntheses. Ruorous compounds often partition preferentially into a fluorous phase in organic/fluorous liquid-liquid extraction, thus providing easy separation of the compounds. Tris[(2-perfluorohexyl)ethyl]tin hydride combines the favorable radical reaction chemistry of trialkyltin hydrides with the favorable separation features of fluorous compounds. 

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