Fluorous azide

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... 

D. P. Curran, S. Hadida, S. Y. Kim, Tris(2-Perfluorohexyl-ethyfltin Azide A New Reagent for Preparation of 5-Substituted Tetrazoles from Nitriles with Purification by Fluorous Organic Liquid-Liquid Extraction , Tetrahedron 1999, 55, 8997. 

The substituted furo[3,2-3]indole-2-carbonitrile 228 with a fluorous tin azide (C6F]3CH2CH2)3SnN3) gave the corresponding tetrazole derivative 229 (Equation 4) <1999T8997>. 

A copper catalysed click (azide-alkyne cycloaddition) reaction has been used to prepare a fluorous-tagged TEMPO catalyst (Figure 7.20). TEMPO is a stable organic free radical that can be used in a range of processes. In this case, its use in metal-free catalytic oxidation of primary alcohols to aldehydes using bleach as the terminal oxidant was demonstrated. The modified TEMPO can be sequestered at the end of the reaction on silica gel 60 and then released using ethyl acetate for reuse in further reactions in this way the TEMPO was used four times with no loss in activity. 

The tin azide 11 (Scheme 16) is an example of a fluorous reagent that, unlike the fluorous tin hydride 1, transfers the fluorous tag to the product. This type of phase switch is very powerful only the nitrile that reacts with 11 is switched to the fluorous phase whereas any unreacted nitrile or impurities are left behind in the organic phase. Cycloaddition reaction of 11 with excess nitrile leads to fluorous tetrazoles 12. Again, BTF is a unique reaction solvent that serves to dissolve all reactants. Purification is effected in the usual way via fluorous-organic extraction. Deprotection yields the tetrazoles 13 in good yields and purities. 

The Finnegan tetrazole synthesis has also provided an opportunity to showcase fluorous chemistry. In this instance, a polyfluorinated tin azide 64 was used in excess and reacted with electron-rich nitrile 63 to provide excellent yield of the tetrazole 65. This procedure was quite general, providing yields of tetrazoles in modest to excellent yield. 

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