TEMPO catalyzing reactions

Although these reactions are formulated as ionic reactions via 947 and 949, because of the apparent partial formation of polymers and inhibition of the fluoride-catalyzed reaction of pyridine N-oxide 860 with aUyl 82 or benzyltrimethylsilane 83 by sulfur or galvinoxyl yet not by Tempo, a radical mechanism caimot be excluded [61, 62]. The closely related additions of allyltrimethylsilane 82 (cf. Section 7.3) to nitrones 976 are catalyzed by TMSOTf 20 to give, via 977, either o-unsatu-rated hydroxylamines 978 or isoxazoHdines 979 (cf also the additions of 965 to 962a and 969 in schemes 7.20 and 7.21). 

Inhibition by radical traps, such as TEMPO 17, was used to explain the involvement of radicals in the course of transition metal-catalyzed reactions (Fig. 7). Typical cross-coupling reactions, such as Heck or Suzuki-Miyaura reactions, proceeded even with nitroxyls as substrates, although the yields were sometimes low. Thus, nitroxyls do not necessarily interfere very much with the course of two-electron catalytic processes [79-81]. However, it must be critically mentioned that 17 and related nitroxides are both oxidants and reductants for metal species. 

The reaction appears to be well suited for selective conversion of biomass carbohydrates into their corresponding oxidized derivatives. This system serves to oxidize several polymeric carbohydrates including starches and pullulan.445 49 More recent work has described the TEMPO-catalyzed introduction of carboxyl groups in native cellulose and its different morphological forms,45(M52 cellulose derivatives,453 and the surface of cellulose nanocrystals.454 The related biopolymer, chitin, also is oxidized under these conditions.455... 

For the sake of completeness we also note that oxygen transfer processes can be mediated by organic catalysts which can be categorized on the same basis as metal catalysts. For example, ketones catalyze a variety of oxidations with mono-peroxysulfate (KHS05) [14]. The active oxidant is the corresponding dkmrane and, hence, the reaction can be construed as involving a peroxometal pathway. Similarly, TEMPO-catalyzed oxidations of alcohols with hypochlorite [15, 16] involve an oxoammonium salt as the active oxidant, i.e. an oxometal pathway. 

In TEMPO-mediated oxidations, bromide ions are key to the efficient catalytic cycle (Figure 9.10) [29, 30]. Rychnovsky found thatTEMPO-catalyzed oxidation of alcohols using m-CPBA was also dependent on bromide ions for rapid reaction [31]. Any compounds that sequester bromide ions in these catalyzed reactions should be avoided. 

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. 

Recently, Giacomelli and co-workers have reported an efficient oxidation of primary alcohols to carboxylic acids through a TEMPO-catalyzed procedure. The procedure is based on the addition of 2 molar equiv of TCCA to an acetone solution of the alcohol followed by catalytic amounts (0.1 equiv) of TEMPO, NaBr, and then 1 equiv of aq. NaHCOs (Equation 65). This system operates at room temperature, the oxidation of the primary alcoholic group being practically quantitative. Secondary alcohols are oxidized to ketones. The mild conditions of this procedure and the total absence of any transition metal make this reaction suitable for safe laboratory use <2003JOC4999>. 

A similar TEMPO-catalyzed system for the oxidation of alcohols using l-chloro-l,2-benziodoxol-3(l//)-one (130) (Section 2.1.8.1.1) as the terminal oxidant in ethyl acetate in the presence of pyridine at room temperature has been reported [158], Various alcohols 129 can be oxidized to the corresponding carbonyl compounds in high to excellent yields under these conditions (Scheme 3.55). The oxidation of primary alcohols (129, = H) in this reaction proceeds generally faster compared to the secondary alcohols. 

The intermediate hydridoruthenium species is most probably RuHzCPhjP), as was observed in RuCl2(PhjP)rcatalyzed hydrogen transfer reactions. The observation that RuH2(PhjP)4 exhibits the same activity as RuCl2(PhjP)3 in the Ru/TEMPO catalyzed aerobic oxidation of 2-octanol is consistent with this notion. 

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). 

The first example of vanadium as the sole metallic component in TEMPO-catalyzed aerobic alcohol oxidation in acetonitrile was recently reported. Flowever, the catalyst did not perform well with secondary aliphatic alcohols, even with extended reaction times. 

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. 

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. 

The application of ionic liquids as a reaction medium for the copper-catalyzed aerobic oxidation of primary alcohols was reported recently by various groups, in attempts to recycle the relatively expensive oxidant TEMPO [150,151]. A TEMPO/CuCl-based system was employed using [bmim]PF6 (bmim = l-butyl-3-methylimodazolium) as the ionic liquid. At 65 °C a variety of allylic, benzylic, aliphatic primary and secondary alcohols were converted to the respective aldehydes or ketones, with good selectiv-ities [150]. A three-component catalytic system comprised of Cu(C104)2, dimethylaminopyridine (DMAP) and acetamido-TEMPO in the ionic liquid [bmpy]Pp6 (bmpy = l-butyl-4-methylpyridinium) was also applied for the oxidation of benzylic and allylic alcohols as well as selected primary alcohols. Possible recycling of the catalyst system for up to five runs was demonstrated, albeit with significant loss of activity and yields. No reactivity was observed with 1-phenylethanol and cyclohexanol [151]. 

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) ... 

Researchers at Tibotec patented a synthesis of racemic bis-THF alcohol ll.33 This synthesis used the multicomponent reaction developed by Ghosh and co-workers.34 As shown in Scheme 7, multicomponent reaction of dihydrofuran 12 and glyoxalate 28 provided 29 in 70-92% yield by GC. Reduction of 29 by NaBH4 gave 30 in 76% yield, which underwent an acid-catalyzed cyclization to give ( )-ll. This was subjected to a three-step process that included a TEMPO oxidation, NaBH4 reduction, and lipase resolution to provide optically active bis-THF (-)-ll. 

---