TEMPO system

In a review by Bragdt et al. (2004) results and perspectives are given to change the salt-based oxidative systems for cleaner oxygen or hydrogen peroxide enzyme-based Tempo systems. Moreover, several immobilized Tempo systems have been developed [129]. 

FIGURE 4. Hammett plot for the oxidation of 4-X-substituted benzyl alcohols with the laccase/ TEMPO system, in competition experiments vs. benzyl alcohol. Reprinted with permission from Reference 156. Copyright (2004) John Wiley Sons Limited... 

As anticipated, Sheldon and coworkers attempted to revise the Cu/TEMPO system, and suggested that a piperidinyloxycopper(II) adduct, rather than the oxoammonium ion, is instead formed as an intermediate species that adduct would be responsible for turning the alcohol into the carbonyl product. Sheldon and coworkers proposed the radical mechanism outlined in Scheme 17, and supported it with a Hammett p value of —0.16 (vs. a) and with a KIE of 5.4 . They also suggested that steric hindrance arising from interaction of secondary alcohols with the active-TEiMPO species, whatever it can be, are possibly responsible for the lower, or lack of, reactivity displayed by these substrates . Accordingly, a novel TEMPO-like system has been recently developed in order to specifically bypass this steric interference , as we are going to see below. 

TABLE 14. Aerobic oxidations with the Lc/TEMPO system, at room temperature... 

Although, in separate experiments, secondary alcohols are oxidized faster than primary ones, in competition experiments the ruthenium/TEMPO system displayed a preference for primary over secondary alcohols. This can be explained by assuming that initial complex formation between the alcohol and the ruthenium precedes rate-limiting hydrogen transfer and determines substrate specificity, i.e. complex formation with a primary alcohol is favoured over a secondary one. 

Although only a small amount of catalyst is used, recyclability is an issue and several heterogeneous TEMPO systems have been reported. For example, MCM-4112 and silica-supported TEMPO13,14 were applied in oxidation reactions using hypochlorite as the oxidant. The preparation of these catalysts involves initial functionalisation of the support followed by covalent attachment of a 4-substituted TEMPO via an amide, amine or ether linker (figure 2). 

In addition to primary and secondary aliphatic alcohols (entries 2-7), benzylic alcohols were also efficiently oxidised (entries 9 and 10), complete conversion being observed within 30 minutes. In competition experiments, the catalyst showed a marked preference for primary alcohols (entries 8 and 11). This is analogous to the already reported homogeneous3 and heterogeneous13 TEMPO systems. A stereogenic centre at the a-position is not affected during oxidation as shown by the selective oxidation of (S)-2-methylbutan-l-ol to (S)-2-methylbutanal (entry 12).20... 

For comparison, the previously described silica and MCM-41 supported TEMPO catalysts were also employed in the bleach-oxidation of octan-2-ol under the chlorinated hydrocarbon solvent- and bromide-free conditions. As shown in figure 4, PIPO is the most active catalyst under these conditions. All silica and MCM-41 supported TEMPO systems gave comparable conversions and are more active than homogeneous TEMPO. On the other hand, the activities obtained under these environmentally benign conditions were lower than in the case of dichloromethane/bromide. 

For PIPO, the time for complete conversion increased from 20 to 45 minutes. The silica-supported TEMPO system reported by Bolm et al.13 gave 74% conversion in 2 hours, whereas using the Anelli protocol (dichloromethane/bromide) this activity was already reached within 30 minutes. With homogeneous TEMPO, the differences were even more dramatic, i.e. complete conversion was reached within 10 minutes using the Anelli protocol,3 whereas only 45% conversion was observed in 2 hours under the chlorinated hydrocarbon solvent- and bromide-free conditions. 

Besides hypochlorite, oxygen can also be used as the oxidant.9,10 Unfortunately, in contrast to homogeneous TEMPO the combination of PIPO and RuCl2(PPh3)3 in chlorobenzene10 is not able to catalyse the aerobic oxidation of octan-2-ol, probably owing to coordination of ruthenium to the polyamine. On the other hand, in combination with CuCl in DMF,9 it catalyses the aerobic oxidation of benzylalcohol to benzaldehyde within 1.5 hours (entry 2 table 4).24 The activity of PIPO is comparable to that of TEMPO (entries 4 and 5) and is superior to that of the previously described heterogeneous TEMPO systems (entries 6,7 and 8). CuCl/PIPO also catalyses the aerobic oxidation of benzylalcohol under solvent-free conditions (entry 3). 

The differences displayed above are probably caused by coordination/bonding of copper to the free silanol groups on the surface of MCM-41 and silica. Besides these free silanol groups, the silica supported TEMPO system reported by Brunei et al.14 also contains unreacted amine linkers, which inactivate the catalyst almost completely (entry 8). Therefore, the activity of the MCM-41 and silica supported TEMPO systems may be improved by blocking the free silanol groups and amine linkers on the surface. 

We gratefully acknowledge IOP (Innovation-Oriented Research Program) for financial support and C. Bolm, D. Brunei and H. van Bekkum for the kind donation of their supported TEMPO systems. We thank M. Verhoef for valuable discussions. 

Recently, an alternative to the catalytic system described above was reported [204]. The new catalytic procedure for the selective aerobic oxidation of primary alcohols to aldehydes was based on a CunBr2(Bpy)-TEMPO system (Bpy=2,2 -bipyridine). The reactions were carried out under air at room temperature and were catalyzed by a [copper11 (bipyridine ligand)] complex and TEMPO and base (KOtBu) as co-catalysts (Fig. 4.70). 

Fig. 4.69 Fluorous CuBr2-bipy-TEMPO system for alcohol oxidation.

Alternatively TEMPO can be reoxidized by metal salts or enzyme. In one approach a heteropolyacid, which is a known redox catalyst, was able to generate oxoammonium ions in situ with 2 atm of molecular oxygen at 100 °C [223]. In the other approach, a combination of manganese and cobalt (5 mol%) was able to generate oxoammonium ions under acidic conditions at 40 °C [224]. Results for both methods are compared in Table 4.9. Although these conditions are still open to improvement both processes use molecular oxygen as the ultimate oxidant, are chlorine free and therefore valuable examples of progress in this area. Alternative Ru and Cu/TEMPO systems, where the mechanism is me-... 

Schmidt-Naake and Butz investigated the copolymerization of St with N-cy-clohexylmaleimide (CMI) using the BPO/TEMPO system [102] and found that the rate of copolymerization was faster than the rate of either homopolymerization using the same system. They concluded that the electron-donating St and... 

ATRP is a useful tool for preparing statistical copolymers with various monomer combinations. Unlike the TEMPO systems detailed above, the ATRP systems can be used to copolymerize styrene, acrylate, or methacrylate based combinations, potentially leading to materials with better and/or different physical and mechanical properties than the corresponding homopolymers or block copolymers. This may also include monomers which cannot yet be homopolymer-ized by ATRP such as isobutene or vinyl acetate [86,130]. Table 2 summarizes statistical copolymers prepared using ATRP systems. 

Barbosa and Gomes used the AIBN/TEMPO system to homopolymerize a side-chain LC acrylate monomer, 4 -ethylbiphenyl-4-(4-propenoyloxy-buty-loxy)benzoate (EBPBB, Fig. 11) [154]. The polymerization was carried out at 135 °C for 48 h, resulting in a monomer conversion of 78% and a polymer Mn=... 

The field of living free-radical polymerizations (e.g. ATRP, TEMPO systems) has been growing in recent years. Yet, no living rascal polymerizations have thus far been reported for a-olefins. Further developments may include the design of functional initiators for living polymerization. Also, ATRP may benefit from the design of homogeneous redox systems that can be easily removed from the polymerization mixture. 

The laccase/TEMPO system was the subject of further investigations by Galli and Gentili and co-workers (47,51) and Sheldon and co-workers... 

Oxidations with Dioxygen Using a Laccase/TEMPO System (47,58)... 

A similar oxidative protocol has been used for the oxidation of (fluoroalkyl)alkanols, Rf(CH2) CH20H, to the respective aldehydes [146], in the one-pot selective oxidation/olefination of primary alcohols using the PhI(OAc)2-TEMPO system and stabilized phosphorus ylides [147] and in the chemo-enzymatic oxidation-hydrocyanation of 7,8-unsaturated alcohols [148]. Other [bis(acyloxy)iodo]arenes can be used instead of PhI(OAc)2 in the TEMPO-catalyzed oxidations, in particular the recyclable monomeric and the polymer-supported hypervalent iodine reagents (Chapter 5). Further modifications of this method include the use of polymer-supported TEMPO [151], fluorous-tagged TEMPO [152,153], ion-supported TEMPO [154] and TEMPO immobilized on silica [148],... 

Based on the ability of the PhI(OAc)2-TEMPO system to selectively oxidize primary alcohols to the corresponding aldehydes in the presence of secondary alcohols, Forsyth and coworkers have developed the selective oxidative conversion of various highly functionalized l°,2°-l,5-diols into the corresponding 8-lactones [155]. A representative example, showing the conversion of substrate 127 into the 8-lactone... 

An efficient and mild procedure has been described for the oxidation of different types of alcohols to carbonyl compounds using TEMPO as the catalyst and (dichloroiodo)benzene as a stoichiometric oxidant at 50 °C in chloroform solution in the presence of pyridine [157]. Under these conditions, 1,2-diols are oxidized to p-hydroxyketones or p-diketones depending upon the amount of PhICh used. Interestingly, a competitive study has shown that this system preferentially oxidizes aliphatic secondary alcohols over aliphatic primary alcohols [157], while the PhI(OAc)2-TEMPO system selectively converts primary alcohols into the corresponding aldehydes in the presence of secondary alcohols. 

The diazidation reaction leading to vicinal trans-diazides (Scheme 3.187) has also been utilized in organic synthesis [567]. Dihydropyrans 479 react with the (PhIO) /TMSN3/TEMPO system to give 2,3-bis-azido adducts 480 (Scheme 3.190), which can be further elaborated into amino-pyrans [567]. 

While the oxidation-induced mieellization was based on the OAC/TEMPO system using chlorine as the oxidizing agent, the reduetion-induced was attained through the TEMPO/HA system using phenylhydrazine as the redueing agent [49]. 

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