Fluorous switching techniques

Finally, in our 1997 Science paper,1451 we introduced a number of fluorous phase switching techniques, and one of these is illustrated in Figure 12. Cycloaddition of nitriles with fluorous tin azide 20 provides... 

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. ... 

Fluorous tagging can facihtate separation by standard purification methods, but more specific methods are available. A particularly useful technique is SPE onto fluorous silica gel, which contains a fluorinated chain bonded to the silica. The non-fluorous components are washed off with a fluorophobic solvent then the fluorous component is eluted with a fluorophilic solvent. Note that ordinary organic solvents are used fluorinated solvents are seldom required. Many organic solvents are fluorophilic, but can be switched dramatically, in the case of water-miscible solvents, by the addition of relatively small amounts of water, into fluorophobes. The selectivity is such that the fluorophobic solvent can be 20% water in methanol, followed, as the fluorophilic solvent, by pure methanol. 

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