NO,.-catalyzed aerobic alcohol oxidation

The stepwise reduction of NO2 to NO occurs at standard reduction potentials very close to the standard potential for the reduction of O2 to H2O (Table 15.1, Eqs. (15.1-15.3)). This relationship implies that NO cocatalysts are able to capture nearly the full thermodynamic driving force of O2 as a terminal oxidant [4]. This favorable feature, together with the kinetically facUe oxidation of NO to NO2 (Table 15.1, Eq. (15.4)), contributes to the effectiveness of NO -based cocatalysts in aerobic oxidation reactions. Depending on the reaction conditions, NO2 can equilibrate with other nitrogen oxide species, such as N2O4, and NO, which could also serve as catalytically relevant oxidants in NO -catalyzed aerobic alcohol oxidation reactions (Eq. (15.5)) [5]. 

Iwabuchi demonstrated that sterically less bulky nitroxyls enable increased catalytic activity in nitroxyl/NO -catalyzed aerobic alcohol oxidation reactions. A broad array of densely functionalized and/or sterically bulky alcohol... 

In conclusion, NO -catalyzed aerobic alcohol oxidation is a growing research area and offers the potential for metal-free aerobic oxidation reactions. Applications of nitroxyl/NO -catalyzed oxidation reactions that employ the sterically unhindered bicyclic nitroxyls (e.g., F-AZADO, ABNO, keto-ABNO) are especially effective with a broad range of substrates bearing diverse functional groups, and reactionengineering advances that allow using these reactions in continuous processes should help to enhance reaction efficiency and promote safety. 

Scheme 15.6 General proposed catalytic cycles for (a) NO - and nitroxyl-catalyzed aerobic alcohol oxidation and (b) NOj -, Xj-, and nitroxyl-catalyzed aerobic alcohol oxidation.

The attractive (80) features of MOFs and similar materials noted above for catalytic applications have led to a few reports of catalysis by these systems (81-89), but to date the great majority of MOF applications have addressed selective sorption and separation of gases (54-57,59,80,90-94). Most of the MOF catalytic applications have involved hydrolytic processes and several have involved enantioselec-tive processes. Prior to our work, there were only two or three reports of selective oxidation processes catalyzed by MOFs. Nguyen and Hupp reported an MOF with chiral covalently incorporated (salen)Mn units that catalyzes asymmetric epoxidation by iodosylarenes (95), and in a very recent study, Corma and co-workers reported aerobic alcohol oxidation, but no mechanistic studies or discussion was provided (89). 

Scheme 15.3 Amberlyst-15- and NO -catalyzed aerobic benzylic alcohol oxidation.

The alcohol oxidation reactions described herein use inexpensive O2 and NO sources, and there is potential for their use in large-scale industrial processes. Continuous flow methods provide a particularly strategic opportunity for large-scale applications (see Chapter 23). Hermans and coworkers demonstrated a segmented-flow method for their amberlyst-15/NO -catalyzed aerobic oxidation... 

The direct transformation of alcohols to the corresponding amines is of growing interest because alcohols are easily available or accessible by chemical means. Amination of alcohols is usually catalyzed by transition metals at high temperatures and elevated pressures. Unfortunately, there is no enzyme known today that allows this particular functional group interconversion (FGl) in one step. Consequently, a multi-enzyme cascade was set up for the amination of alcohols as demonstrated for various benzylic and cinnamic alcohols under physiological conditions [24] aerobic alcohol oxidation toward the aldehyde was performed via a galactose oxidase originating from Fusarium (NRRL 2903 [25]) followed by an in situ co-TA-catalyzed reductive amination step (Scheme 4.5). 

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]. 

TEMPO and other organic nitroxyls have been used as catalysts in combination with numerous stoichiometric oxidants, such as sodium hypochlorite [24], PhI(OAc)2 [25], and sodium chlorite [26]. A number of recent studies have shown that NO -based redox cocatalysts enable these reactions to be conducted with O2 as the terminal oxidant [27]. The general catalytic cycle for these aerobic nitroxyl/NO -catalyzed alcohol oxidation reactions is depicted in Scheme 15.6a. A variation of this approach features halides as additives, in which the X2/HX redox couple is believed to mediate the NO2/NO and oxoammonium/hydroxylamine redox couples (Scheme 15.6b). 

Aerobic oxidation is not going to be limited to alcohol oxidation. Apparently we are closer to finding suitable catalysts for alcohol oxidation, but oxidation of alkenes, aromatic hydrocarbons, alkylaromatics, imines, amines, sulfur compounds etc. will require much work in the forthcoming years. In some cases, the presence of radical initiators, even though in minor quantities, may serve to promote the oxidation catalyzed by noble metal nanopartides, and gold in particular [56, 108]. Thus, there is no doubt that the next years will witness exciting developments in the field of metal nanopartides for aerobic oxidation. 

The enantioselective oxidative coupling of 2-naphthol itself was achieved by the aerobic oxidative reaction catalyzed by the photoactivated chiral ruthenium(II)-salen complex 73. 2 it reported that the (/ ,/ )-chloronitrosyl(salen)ruthenium complex [(/ ,/ )-(NO)Ru(II)salen complex] effectively catalyzed the aerobic oxidation of racemic secondary alcohols in a kinetic resolution manner under visible-light irradiation. The reaction mechanism is not fully understood although the electron transfer process should be involved. The solution of 2-naphthol was stirred in air under irradiation by a halogen lamp at 25°C for 24 h to afford BINOL 66 as the sole product. The screening of various chiral diamines and binaphthyl chirality revealed that the binaphthyl unit influences the enantioselection in this coupling reaction. The combination of (/f,f )-cyclohexanediamine and the (R)-binaphthyl unit was found to construct the most matched hgand to obtain the optically active BINOL 66 in 65% ee. 

Recently two heterogeneous TPAP-catalysts were developed, which could be recycled successfully and displayed no leaching In the first example the tetra-alkylammonium perruthenate was tethered to the internal surface of mesopor-ous silica (MCM-41) and was shown [153] to catalyze the selective aerobic oxidation of primary and secondary allylic and benzylic alcohols. Surprisingly, both cyclohexanol and cyclohexenol were unreactive although these substrates can easily be accommodated in the pores of MCM-41. The second example involves straightforward doping of methyl modified silica, denoted as ormosil, with tetra-propylammonium perruthenate via the sol-gel process [154]. A serious disadvantage of this system is the low-turnover frequency (1.0 and 1.8 h-1) observed for primary aliphatic alcohol and allylic alcohol respectively. 

Metal nanoparticles embedded in thermosensitive core-shell microgel particles can also work efficiently as catalyst for this reaction. Figure 13 shows the oxidation reaction of benzyl alcohol to benzaldehyde in aqueous media by using microgel-metal nanocomposite particles as catalyst. All reactions were carried out at room temperature using aerobic conditions. It is worth noting that the reaction conditions are very mild and no phase transfer catalyst is needed. It has been found that microgel-metal nanocomposites efficiently catalyze the aerobic oxidation of benzyl alcohol at room temperature. No byproducts have been detected by GC after the reaction, and water is the only product formed besides the aldehyde. 

A heterogeneous TPAP-catalyst was developed, which could be recycled successfully and displayed no leaching, by tethering the tetraalkylammonium perruthenate to the internal surface of mesoporous silica (MCM-41). It was shown [56] to catalyze the selective aerobic oxidation of primary and secondary allylic and benzylic alcohols (Figure 5.11). Surprisingly, both cyclohexanol and cyclohexenol were unreactive. 

More recently. Repo and coworkers [117] showed that the selective aerobic oxidation of benzyl alcohol to benzaldehyde could be performed with TEMPO in combination with Cu(II) /phenanthroline in aqueous alkaline with no added organic solvent. Finally, an interesting recent development in copper-catalyzed oxidation of alcohols is the use of copper nanoparticles on hydrotalcite as a heterogeneous catalyst for the liquid phase dehydrogenation of alcohols in the absence of an oxidant [118]. 

Usually the stable nitroxyl radicals alone cannot directly catalyze the oxidation of alcohols with dioxygen or peroxide, so they rely on the assistance of various cocatalysts that play an important role in activating the oxidation agent. The most used cocatalysts are first row transition-metal complexes where Cu compounds with various N-donor ligands account for the prime ones. In many instances this combination serves as some kind of model to compare catalytic properties of copper compounds. For example, the performances of two asymmetric tetranuclear (with the Cu4(p—0)2(p — 0)2 404 core) and dinuclear (with the Cu2(p-0)2N202 core) copper(II) complexes were compared in the catalytic TEMPO-mediated aerobic oxidation ofbenzylic alcohols. In spite of their similarity, the complexes perform differently the tetranuclear copper(II) (R) complex is highly active leading to yields up to 99% and TONs up to 770, while the (S,R)-2 dinuclear complex is not so efficient under the same conditions. However, no solid explanation of the activity differences was proposed. 

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