TEMPO oxidations with a silica-supported catalyst Carsten Bolm* and Thomas Fey Institut für Organische Chemie der RWTH Aachen, Professor-Pirlet-Straße 1, D-52056 Aachen, Germany. E-mail: carsten.bolm@oc.rwth-aachen.de Received (in Cambridge, UK) 14th July 1999, Accepted 29th July 1999 Silica-supported 1-hydroxy-2,2,6,6-tetramethylpiperidine (SG-TMP-OH) was successfully applied as a recyclable catalyst in the oxidation of various alcohols. Aminoxyl† radicals are well-established catalysts for the oxidation of alcohols. 1 Typically, such oxidations are carried out in the presence of 1 mol% of catalyst and a stoichiometric amount of a terminal oxidant such as bleach, 2 sodium chlorite, 3 sodium bromite, 4 tert-butyl hypochlorite, 5 N-chlorosuccini- mide, 6 MCPBA, 7 [bis(acetoxy)iodo]benzene, 8 or oxygen in combination with a high-valent metal salt. 9 Furthermore, electrochemical reoxidation of the catalyst is possible. 10 Especially for large scale oxidations, the TEMPO–bleach protocol introduced by Anelli et al. 2 appears most useful. 11 Although usually a small quantity of the catalyst is sufficient for an efficient transformation, it is still desirable to develop improved work-up conditions which allow simple product isolation as well as catalyst separation and recycling. 12 We envisaged that both requirements could be realised by using a polymer-supported aminoxyl radical. Usually TEMPO-cata- lysed reactions afford the desired carbonyl compounds in high yields without the formation of significant amounts of by- product, and thus catalyst separation and product isolation could easily be accomplished by simple filtration and phase separation followed by evaporation of the organic solvent (Scheme 1). Although several polymer-bound aminoxyl radicals have already been synthesised, 13 only a very few of them were applied as oxidation catalysts. 13a–d To the best of our knowl- edge, none of them has been studied under the conditions mentioned above. Due to several publications concerning the application of polymer-supported oxidation reagents and cata- lysts, 14 and based on our own expertise in the use of heterogenised alkaloids in the Sharpless dihydroxylation re- action, 14g,15 we focused our attention on the attachment of the TEMPO precursor 1-hydroxy-4-oxo-2,2,6,6-tetramethylpiper- idine (2) 16 onto silica. The synthesis of 3 (SG-TMP-OH) was accomplished by reductive amination of 2 with commercially available aminopropyl-functionalised support (Scheme 2). 17 ‡ The resulting solid was carefully washed with hot MeOH using a Soxhlet extractor for several days in order to ensure complete removal of non-chemically bounded hydroxypiperidine deriva- tives from the surface. SG-TMP-OH 3 was then applied as catalyst in the oxidation of various alcohols according to the Anelli protocol (Table 1). 2a § As shown by quantitative GC analysis, aldehydes and ketones were formed in high yields from the corresponding primary and secondary alcohols, respectively. Both benzylic and aliphatic substrates react equally well. In order to study the selectivity profile in the oxidation of primary and secondary alcohols, we performed competition experiments using equimolar mixtures of both. Entries 8 and 9 of Table 1 show a high selectivity towards the oxidation of the primary alcohols, which resembles the known behaviour of the unsupported TEMPO catalyst. 19 Thus, the corresponding aldehydes of nonan-1-ol and benzyl alcohol were formed in 96 and 92% yield, respectively, whereas the oxidation of the secondary alcohols nonan-2-ol and 1-phenylethanol occured in low yield only (1 and 3%, respectively). In addition, as in catalysed oxidations with TEMPO itself, 2c no racemisation of optically active compounds occured (entry 10). We finally investigated the possibility of recycling the catalyst. Therefore, the silica-bound TEMPO derivative was recovered by filtration after the reaction and reapplied in a sequence of oxidations using nonan-1-ol as substrate. The results illustrated in Fig. 1 show that even after 10 subsequent runs the catalyst activity remained high. In both substrate conversion and product yield only a minor decrease was observed, proving the high efficiency of the catalyst recovery. In conclusion, we have demonstrated that silica-supported TEMPO is an excellent catalyst for the oxidation of alcohols, affording the corresponding carbonyl derivatives in high yields. Primary alcohols are selectively oxidised in the presence of Scheme 1 Scheme 2 Table 1 TEMPO oxidation of various alcohols to the corresponding aldehydes and ketones with silica-supported catalyst 3 a Entry Substrate Yield (%) b 1 Benzyl alcohol 92 (75) 2 Heptan-1-ol 90 3 Octan-1-ol 88 4 Nonan-1-ol 90 (85) 5 Dodecan-1-ol 81 6 Nonan-2-ol 65 7 1-Phenylethanol 91 8 Nonan-1-ol/nonan-2-ol 96/1 9 Benzyl alcohol/1-phenylethanol 92/3 10 (S)-2-Methylbutan-1-ol c 60 a Oxidation experiments conducted following the protocol in note §. b Yields were determined by quantitative GC analysis using decane or dodecane as internal standard. Values in parentheses are isolated yields. c The ee of 95% remained unchanged (ref. 18). Chem. Commun., 1999, 1795–1796 1795