Ruthenium TEMPO

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. 

On the basis of the results discussed earlier the detailed catalytic cycle depicted in Fig. 16 is proposed for the ruthenium/TEMPO-catalysed aerobic oxidation of alcohols. 

Dijksman, A., Marino-Gonzalez, A., Payeras, A.M., Arends, W., and Sheldon, R.A. 2001. Efficient and selective aerobic oxidation of alcohols into aldehydes and ketones using Ruthenium/TEMPO as the catalytic system. Journal of the American Chemical Society, 123 6826-33. 

Table 5.3 Ruthenium-TEMPO-catalyzed oxidation of primary and secondary alcohols to the corresponding aldehyde using molecular oxygen. ...

Figure 5.9 Ruthenium/TEMPO-catalyzed aerobic oxidation of alcohols.

Figure 5.10 Proposed mechanism for the ruthenium/TEMPO-catalyzed oxidation of alcohols.

Table J. Ruthenium-TEMPO catalysed oxidation of primary alcohols to the corresponding...

Figure 4. Ruthenium/tempo catalyzed aerobic oxidation of alcdtols...

Dijksman, A., Arends, I. and Sheldon, R. (1999). Efficient Ruthenium-TEMPO-Catalysed Aerobic Oxidation of Aliphatic Alcohols into Aldehydes and Ketones, Chem. Commun., 16, pp. 1591-1592 Dijksman, A., Marino-Gonzalez, A., Mairati i Payeras, A., et al. (2001). Efficient and Selective Aerobic Oxidation of Alcohols into Aldehydes and Ketones Using Ruthenium/TEMPO as the Catalytic System, J. Am. Chem. Soc., 123, pp. 6826-6833. 

Sheldon et al. have combined a KR catalyzed by CALB with a racemization catalyzed by a Ru(II) complex in combination with TEMPO (2,2,6,6-tetramethylpi-peridine 1-oxyl free radical) [28]. They proposed that racemization involved initial ruthenium-catalyzed oxidation of the alcohol to the corresponding ketone, with TEMPO acting as a stoichiometric oxidant. The ketone was then reduced to racemic alcohol by ruthenium hydrides, which were proposed to be formed under the reaction conditions. Under these conditions, they obtained 76% yield of enantiopure 1-phenylethanol acetate at 70° after 48 hours. 

Our initial work on the TEMPO / Mg(N03)2 / NBS system was inspired by the work reported by Yamaguchi and Mizuno (20) on the aerobic oxidation of the alcohols over aluminum supported ruthenium catalyst and by our own work on a highly efficient TEMP0-[Fe(N03)2/ bipyridine] / KBr system, reported earlier (22). On the basis of these two systems, we reasoned that a supported ruthenium catalyst combined with either TEMPO alone or promoted by some less elaborate nitrate and bromide source would produce a more powerful and partially recyclable catalyst composition. The initial screening was done using hexan-l-ol as a model substrate with MeO-TEMPO as a catalyst (T.lmol %) and 5%Ru/C as a co-catalyst (0.3 mol% Ru) in acetic acid solvent. As shown in Table 1, the binary composition under the standard test conditions did not show any activity (entry 1). When either N-bromosuccinimide (NBS) or Mg(N03)2 (MNT) was added, a moderate increase in the rate of oxidation was seen especially with the addition of MNT (entries 2 and 3). 

Chloromethyl polystyrene can be converted to a free-radical initiator by reaction with 2,2,6,6-tetramethylpipcridinc-/V-oxyl (TEMPO). Radical polymerization of various substituted alkenes on this resin has been used to prepare new types of polystyrene-based supports [123]. Alternatively, cross-linked vinyl polystyrene can be copolymerized with functionalized norbornene derivatives by ruthenium-mediated ringopening metathesis polymerization [124],... 

Oxidation of the crude product mixtures containing both regioisomers 44 and 45 gave Cbz-protected amino acid 46 and amino ketone 47, which could then be separated by simple acid-base-extraction. As oxidizing reagents, periodic acid and a catalytic amount of ruthenium trichloride were found to be suitable. For some cases in which chemical yields were low, a TEMPO-catalyzed oxidation with bleach as oxidant was more effective. 

Table 2 Ruthenium/2,2, 6,6 -tetramethylpiperidinyl-W-oxyl (TEMPO) catalysed oxidation of primary and secondary alcohols to the corresponding aldehyde using molecular oxygen. 15 mmol substrate, 30 ml chlorobenzene, RuCl2(PPh3)3/TEMPO ratio of 1/3, 10 ml mur1 02/N2 (8/92 v/v), P=10 bar, T=100 °C...

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). 

If a secondary alcohol is not easily oxidized by other methods the ruthenium(Vin) oxide catalyzed procedure is often recommended. As mentioned previously, this is a strong oxidation method which is not compatible with a number of functional groups. Sodium periodate usually serves as the stoichiometric oxidant, but sodium hypochlorite has also been used in the oxidation of secondary alcohols [94]. Because of the cheap oxidants and a straightforward work-up this reaction is well suited for large-scale oxidations [95]. The TEMPO procedure also employs a cheap stoichiometric oxidant and has been applied in the oxidation of 23 on a kilogram scale [87]. The TPAP-catalyzed method is a milder procedure and many functional groups are stable to these conditions. However, secondary alcohols are still oxidized to ketones in high yield with NMO as the co-oxidant [24]. 

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