Radical fluorous phase

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. 

Tris[(2-perfluorohexyl)ethyl]tin hydride has three perfluorinated segments with ethylene spacers and it partitions primarily (> 98%) into the fluorous phase in a liquid-liquid extraction. This feature not only facilitates the purification of the product from the tin residue but also recovers toxic tin residue for further reuse. Stoichiometric reductive radical reactions with the fluorous tin hydride 3 have been previously reported and a catalytic procedure is also well established. The reduction of adamantyl bromide in BTF (benzotrifluoride) " using 1.2 equiv of the fluorous tin hydride and a catalytic amount of azobisisobutyronitrile (AIBN) was complete in 3 hr (Scheme 1). After the simple liquid-liquid extraction, adamantane was obtained in 90% yield in the organic layer and the fluorous tin bromide was separated from the fluorous phase. The recovered fluorous tin bromide was reduced and reused to give the same results. Phenylselenides, tertiary nitro compounds, and xanthates were also successfully reduced by the fluorous fin hydride. Standard radical additions and cyclizations can also be conducted as shown by the examples in Scheme 1. Hydrostannation reactions are also possible, and these are useful in the techniques of fluorous phase switching. Carbonylations are also possible. Rate constants for the reaction of the fluorous tin hydride with primary radicals and acyl radicals have been measured it is marginally more reactive than tributlytin hydrides. ... 

Unfortunately, the appeal of solid phase extractions on small scale fades as the scale increases due to the cost and inconvenience of using large amounts of fluorous silica gel. Here, modified techniques to reduce the tedium of repeated extractions are attractive. For example, Crich has recently introduced the minimally fluorous selenide C6Fi3CH2CH2C6H4SeH[171. This selenol is added in catalytic quantities to tin hydride reductions of reactive aryl and vinyl radicals. The high reducing capacity of the aryl selenide suppresses undesired reactions of product radicals without suppressing the reactions of the aryl and vinyl radicals themselves. After the reaction is complete, the selenol can be recovered by a modified continuous extraction procedure. 

Abstract Increasing reaction speed and simplifying product purification are two major ways to improve the efficiency of organic synthesis. A new technology for high-speed solution-phase synthesis has been developed by combination of microwave heating and fluorous purification. This review describes different techniques for microwave-enhanced fluorous synthesis and their applications in Pd-catalyzed cross-coupling reactions, free-radical reactions, multicomponent reactions, and compound library synthesis. 

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