4-Hydroxy-TEMPO catalyzed oxidation

The reactivity pattern of recyclable hypervalent iodine reagents 65-67,69-71,73,74 and 76 is similar to the common iodobenzene-based reagents [34], For example, the recyclable (diacetoxyiodo)arenes 65,69,73 and 76 can be used instead of (diacetoxyiodo)benzene in the KBr or TEMPO-catalyzed oxidations of alcohols [74-78], while [hydroxy(tosyloxy)iodo]arenes 67, 71 and 74 are excellent reagents for tosyloxylation of ketones (Scheme 5.28) [76]. 

Semmelhack reported that the combination of CuQ and 4-hydroxy TEMPO catalyzes the aerobic oxidation of alcohols. However, the scope was limited to active benzylic and allylic alcohols and activities were low (10mol% of catalyst was needed for smooth reaction). 

SemmeUiack et al. [104] reported that the combination of CuCl and 4-hydroxy TEMPO catalyzes the aerobic oxidation of alcohols. However, the scope was limited to active benzyhc and allylic alcohols and activities were low (10 mol% of catalyst was needed for smooth reaction). They proposed that the copper catalyzes the reoxidation of TEMPO to the oxoammonium cation. Based on our results with the Ru/TEMPO system we doubted the validity of this mechanism. Hence, we subjected the Cu/ TEMPO to the same mechanistic studies described above for the Ru/TEMPO system [105]. The results of stoichiometric experiments under anaerobic conditions, Hammett correlations and kinetic isotope effect studies showed a similar pattern to those with the Ru/TEMPO system, i.e., they are inconsistent with a mechanism involving an oxoammonium species as the active oxidant. Hence, we propose the mechanism shown in Scheme 4.18 for Cu /TEM PO-catalyzed aerobic oxidation of alcohols. 

The mechanistic details of these laccase/mediator catalyzed aerobic oxidations are still a matter of conjecture (51-54). However, experiments with a probe alcohol point towards one-electron oxidation of the mediator by the oxidized (cupric) form of the laccase followed by reaction of the oxidized mediator with the substrate, either via electron transfer (ET), e.g., with ABTS, or via hydrogen atom transfer (HAT), e.g., with N-hydroxy compounds which form N-oxy radicals (55). TEMPO and its derivatives form a unique case one-electron oxidation of TEMPO affords the oxoammonium cation which oxidizes the alcohol via a heterolytic pathway (Fig. 6), giving the carbonyl product and the hydroxylamine. The Tl copper center in fungal laccases has a redox potential of ca. 0.8 V vs. NHE. Consequently, fungal laccases can easily oxidize TEMPO to the corresponding oxoammonium cation, since the oxidation potential of the latter, which was first measured by Golubev and co-workers (55,57), is 0.75 V. This was confirmed by EPR measurements, which showed that laccase is reduced in the presence of TEMPO One equivalent of laccase could oxidize at least three equivalents of TEMPO within a few minutes under anaerobic conditions (58). 

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