Supported TEMPO

polystyrene-supported TEMPO, sol-gel TEMPO, PEG-TEMPO, supported oxammoium salts, etc.). These catalysts have shown good activity and selectivity, and were also readily recyclable. The aerobic oxidation of alcohols with supported TEMPO employing oxygen as co-oxidant has been explored [19k, 191, 20], either in the presence of Co(N03)2 and Mn(N03)2 (Minisci s conditions) or in the presence of Cu(II), giving interesting results. 

---

Figure 5.13 Yields in the Montanari-Anelli oxidation of 1-nonanol to give nonanal in the presence of silica-supported TEMPO (SG-TMP-O, front row), and in the presence of sol gel ORMOSIL doped with TEMPO [SG-TEMPO-1 is 25% and SG-TEMPO-2 is 100% methylated (middle and back row, respectively)]. (Reproduced from ref. 25, with permission.)...

Some successful attempts to immobilize catalysts for the oxidation of alcohols to carbonyl compounds involve the attachment of TEMPO-derivatives to a solid phase. Bolm et al. were the first to immobilize l-hydroxy-2,2,6,6-tetramethylpiperi-dine to modified silica gel (SG-TMP-OH) (11) and applied in the oxidation of multifunctional alcohols [68]. Other groups further investigated the use of polymer-supported TEMPO [69]. This system allowed the oxidation of alcohols to aldehydes and ketones, respectively, using bleach to regenerate the immobilized ni-troxyl radical (Scheme 4.6). 

Scheme 4.6 Solid-phase supported TEMPO-species.

Wu et alP have synthesized a TSIL having 2,2,6,6-tetramethylpiper-idine-l-oxyl (TEMPO) appended to an imidazolium cation for the oxidation of alcohols to corresponding carbonyl compounds. These reactions have shown high yields similar to non-supported TEMPO, but with the additional advantage of easy separation of products. 

Additionally, the use of unsymmetrical TEMPO analogues, able to perform enantioselective alcohol oxidations22 and silica-supported TEMPO,23 must be mentioned. 

The chemical selectivity of reactions catalyzed by supported TEMPO closely resembles the patterns observed for homogeneous reactions. Primary alcohols are strongly preferred over secondary alcohols. Especially in liquid biphasic systems, high aldehyde yields can be achieved with as little as 0.1 mol% of the immobilized catalyst (412) ... 

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. 

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. 

However, PEG supported metal-free catalysts have also been shown to perform well in water. For example the synthesis of a PEG-supported TEMPO (2,2,6,6-tetramethyl-piperidine-l-oxyl), and its use as a highly efficient, recoverable and recyclable catalyst in oxidation reactions was described (Pozzi et al. 2004). 

As mentioned before a PEG-supported TEMPO proved to be very efficient in the oxidation of 1-octanol to octanal not only with sodium hypochlorite, but also in combination with different terminal oxidants such as bis(acetoxy)iodobenzene and trichloroisocyanuric acid. This reaction could be extended to acyclic and cyclic primary and secondary alcohols with excellent results. It is remarkable that the PEG-supported TEMPO maintained the good selectivity for primary vs secondary ben-zylic alcohol oxidation typical of non-supported TEMPO. 

Pozzi G, Cavazzini M, Quid S, Benaglia M, Dell Anna G (2004) Poly(ethylene glycol)-supported TEMPO an efficient, recoverable, metal-free catalyst for the selective oxidation of alcohols. Org Lett 6 441-443... 

Pozzi G, Quid S, Benaglia M, Puglisi A, Holczknecht O (2005) Aerobic oxidation of alcohols to carbonyl compounds mediated by poly(ethylene glycol-supported TEMPO radicals. Tetrahedron 61 12058-12064... 

Polymer-supported TEMPO is a metal-free catalyst for chemoselective oxidations. It is readily removed from the reaction mixture and can be reused several times. ... 

Fig. 21 Supported TEMPO and carboxylic acid used as reagents for oxidation of alcohol and epoxide ring opening respectively...

Scheme 8.3 PEG-supported TEMPO as a catalyst for oxidation reactions.

The TEMPO-catalyzed oxidation of alcohols to carbonyl compounds with buffered aqueous NaOCl has found broad apphcation even in large-scale operations. Indeed, this selective methodology involves the use of safe and inexpensive inorganic reagents under mild reachon condihons. A supported TEMPO 7, which is soluble in CH2CI2 and acetic acid but insoluble in ethers and hexane, was prepared and proved to be an effective catalyst for the selective oxidahon of 1-octanol with various stoichiometric oxidants. When 7 was employed at 1 mol% as a catalyst with a stoichiometric amount of NaOCl, the aldehyde was obtained in 95% yield after only 30 min of reaction. The recycling of catalyst 7 was shown to be possible for seven reaction cycles in the oxidahon of 1-octanol, that occurred in undiminished conversion and selectivity under similar reachon conditions. 

Another option is the use of both solid-supported versions of the catalyst and the co-oxidant. The Toy group in Hong-Kong has developed a multipolymer system for the TEMPO-catalyzed alcohol oxidation in which both the pre-catalyst and the co-oxidant are attached to a polymer. As it was clearly impossible to use two insoluble supported reagents, the idea was to use an insoluble polymer in conjunction with a soluble one. An insoluble polymer-supported diacetoxyiodosobenzene (PSDIB), an analog of 10, and a soluble polymer-supported TEMPO were used,... 

Notably, the co-oxidant problem also occurs for TEMPO-catalyzed oxidations. For the aerobic oxidation of alcohols with supported TEMPO see the end of Section 4.3.1.2. 

Oxidations. The oxidation of primary alcohols to acids with sodium chlorite is catalyzed by TEMPO and bleach. On the other hand, when the oxidation is carried out at 0° with a silica-supported TEMPO in the presence of KBr and in a biphasic solvent system (aqueous phase pH 9.1) primary alcohols afford aldehydes. ... 

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],... 

Likewise, efficient recyclable bifunctional catalysts 112 and 113 (Eigure 4.3) bearing ionic liquid-supported TEMPO and iodoarene moieties have been developed and used for the environmentally benign catalytic oxidation of alcohols [92]. Compounds 112 and 113 have been tested as catalysts for the oxidation of alcohols to the corresponding carbonyl compounds using peracetic acid as a green and practical oxidant. Ion-supported catalysts 112 and 113 can be conveniently recovered from the reaction mixture and reused without any loss of catalytic activity (Section 5.5). 

Various primary and secondary alcohols can be oxidized to aldehydes and ketones with the ion-supported [bis(acyloxy)iodo]arene 99 in the ionic liquid [emim]+[BF4] (l-ethyl-3-methylimidazolium tetrafluorobo-rate) in the presence of bromide anion [94], or in water in the presence of ion-supported TEMPO [97]. Under similar conditions reagent 99 can be used for mild, efficient, highly selective and environmentally friendly oxidation of aliphatic and aromatic sulfides to sulfoxides in excellent yields [98]. This reaction is compatible with hydroxyl, nitrile, methoxy, carbon-carbon double bonds and ester functionalities. The analogous pyrrolidinium-derived ion-supported [bis(acyloxy)iodo]arenes are efficient oxidants of alcohols to carbonyl compounds in the presence of TEMPO [99]. 

The use of ion-supported [bis(acyloxy)iodo]arene in the ionic liquid [emim]+[BF4] (l-ethyl-3-methylimidazolium tetrafluoroborate) in the presence of bromide anion or ion-supported TEMPO for the oxidation of primary and secondary alcohols is discussed in Section 5.3.3 [52,53],... 

Recently, a so-called ion-supported TEMPO was synthesized bybuilding a TEMPO moiety into the side chain of a dialkylimidazolium salt (Fig. 7.19). The resulting material catalyzed the oxidation of alcohols with NaOCi or I2 in water or an ionic liquid/water mixture. ... 

Scheme 23.70. Oxidation of alcohols with air using a SBA-15-supported TEMPO catalyst.

---