Fluorous scavengers

An interesting approach involving the use of a fluorous dienophile as a diene scavenger under microwave conditions has been investigated by Werner and Curran [101]. The classical Diels-Alder-type cydoaddition of diphenylbutadiene with maleic anhydride as dienophile was accelerated under microwave heating, such that it... 

Scheme 7.88 Diene scavenging utilizing a fluorous dienophile.

Fluorous Technologies Bulletin on Fluorous Scavenging, www.fluorous.com/html. 

Recently, the fluorous biphasic separation technique has been enriched with two new developments, both of which were demonstrated in hydrogenation. The need for a fluorous solvent can be eliminated by using fluorous silica as a fluorous catalyst scavenger. In liquid-liquid biphasic systems, reversible expan-... 

B. Linclau, A. K. Singh, D. P. Curran, Organic-Eluorous Phase Switches A Fluorous Amine Scavenger for Purification in Solution Phase Parallal Synthesis , J. Org. Chem 1999, 64, 2835. 

At the time of writing, neither ionic liquids nor fluorous solvents have been used as solvents for commercial processes, although BASF use an ionic liquid as a proton scavenger in phosphine manufacture [36], These are relatively new technologies and time will tell whether or not they will fulfil current high expectations. 

The most important characteristics that make fluorous synthesis superior to solid-supported synthesis is the favorable reaction kinetics associated with the solution-phase reactions. Comparison reactions using fluorous vs. solid-supported thiols to scavenge a bromide are shown in Fig. 1 [16]. Using 1.5equiv of F-thiol 1, more than 95% bromide was quenched in less than 40 min (top line). Under the same conditions and using 1.5 equiv PS-thiol 2, only 50% of the halide was quenched after 80 min (bottom line). By doub-... 

In the synthesis of a compound library of allosteric Akt kinase inhibitors 39, Lindsley and coworkers employed different HTS techniques (Scheme 24) [54]. A polymer-supported base and a fluorous thiol scavenger were used in the alkylation reaction of 40. F-SPE purified intermediate was then used for microwave-assisted cycloaddition of 41. Similar intermediates have been used for generation of an unnatural canthine alkaloid library 42 by performing cycloaddition reactions with an indo-tethered acyl hy-drazide [55]. 

A tempting comparison is that between standard solid-phase chemistry and fluorous chemistry. Both of these techniques have several attributes in common, including the use of linkers, frequent use of scavengers, and utility in many similar applications. Even though the use of standard solid-phase chemistry has many advantages, some aspects of polymer-supported synthesis strategies have drawbacks. Eluorous chemistry has in many ways marketed itself as an alternative to solid-sup-port chemistry due to its superior performance in a number of respects. ... 

Microwave-assisted fluorous Ugi reactions were presented where the reaction times and convenient separation techniques appeared more attractive than the corresponding room temperature methods with traditional scavenging techniques. ... 

One of the first examples of the use of fluorous solvents in reactions was their use in the extraction of photodegraded solid and liquid wastes contaminated with polychlorinated biphenyls (PCBs). Fluorinated ligands and scavengers... 

Linclau B, Sing AK, Curran DP. Organic-Fluorous phase switches a fluorous amine scavenger for purification in solution phase parallel synthesis. J Org Chem. 1999 64 2835-2842. Parlow JJ. Polymer-assisted solution-phase chemical library synthesis. Curr. Opin. Drug Discov. Devel. 2005 8 757-775. 

Fluorous scavengers facilitate removal of excess reagents from complex reaction mixtures [28] (Scheme 3.25). Thus, the fluorous anhydrides 55 and isocyanates 56 enable the removal of excess amine reagents. Several custom-tailored fluorous scavengers with complementary reactivity are available for removal of other reactive species. 

Scheme 3.25 Examples of fluorous scavengers enabling simple removal of excess reagents from complex reaction mixtures [28].

Fluorous scavengers do not necessarily need to form a covalent bond with the species they have to remove into the fluorous phase. For example, lightly fluorous N,N -dialkyl ureas can bind to perfluorocarboxyl ic acids by hydrogen... 

Zhang and coworkers have developed the use of fluorous-tagged isocyanate as well as isatoic anhydride and acid chloride for the scavenging of amines for use in combinatorial as well as conventional chemistry (Figure 8.3) [30]. All reagents were readily prepared from commercially available sources, and the F-isatoic anhydride was prepared via a simple NaH-mediated alkylation of isatoic anhydride with per-fluoroalkyl halide. 

Figure 8.3 Fluorous-tagged isocyanate, isatoic anhydride and acid chloride for the scavenging of amines.

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