TEMPO catalyst, fluorous

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 use of Cu in combination with TEMPO also affords an attractive catalyst [200, 201]. The original system however operates in DMF as solvent and is only active for activated alcohols. Knochel et al. [202] showed that CuBr.Me2S with perfluoroalkyl substituted bipyridine as the ligand and TEMPO as cocatalyst was capable of oxidizing a large variety of primary and secondary alcohols in a fluorous biphasic system of chlorobenzene and perfluorooctane (see Fig. 4.69). In the second example Ansari and Gree [203] showed that the combination of CuCl and TEMPO can be used as a catalyst in l-butyl-3-methylimidazolium hexafluorophosphate, an ionic liquid, as the solvent. However in this case turnover frequencies were still rather low even for benzylic alcohol (around 1.3 h 1). 

Recently, Betzemeier et al. showed that the scope of the copper-catalyzed oxidation reaction could be improved by using Cu Br Me2S instead of Cu Cl 97). The coordination of a perfluoroalkylated bipyridine to the metal centre produced a catalyst which could be used under biphasic fluorous conditions. Typically, 40)imol of perfluoroalkylated bipyridine was dissolved in 2mL of perfluorooctane. Next, 40 pmol of Cu Br Me2S was added, followed by a solution of 2 mmol alcohol and 64 imol TEMPO in 2mL chlorobenzene. The resulting biphasic reaction mixture was heated to 90°C under dioxygen (Fig. 27). 

The Ru-catalyzed epoxidation of tran -stilbene in the presence of NaI04 was carried out using a bipyridyl ligand with a fluorous ponytail at the 4 and 4 positions. As illustrated by the first equation in Scheme 8, a triphasic system comprising water, dichloromethane and perfluorooctane was employed in the reaction. The reaction was complete in 15 min at 0°C and tran -stilbene oxide 5 was obtained from the dichloromethane layer in a 92% yield. The fluorous layer, containing the catalyst, could be recycled for four further runs without any addition of RuCls. The same perfluoroalkyl-substituted bipyridyl ligand was used successfully in the copper(i)-catalyzed TEMPO (2,2, 6,6 -tetramethylpiperidine (V-oxyl)-oxidation of primary and secondary alcohols under aerobic conditions (Scheme 8, second equation). ... 

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