Allylic aerobic

Hydroxylation and Baeyer-Villiger reactions carried out by monooxygenation are important in the degradation of a range of terpenoids and steroids. The aerobic degradation of limonene can take place by a number of reactions several of which involve hydroxylation at allylic positions... 

Ishii and co-workers [109] reported the aerobic oxidation of various organic compounds catalyzed by (NH4)5H6[PV8Mo4O40] supported on active carbon. The catalyst showed high activity for oxidative dehydrogenation of various benzylic and allylic alcohols to give the corresponding carbonyl compounds in moderate to high yields. The catalyst can be recycled without loss of activity for the... 

Aconitase [citrate(isocitrate) hydro-lyase, EC 4.2.1.3] is the second enzyme of the citric acid cycle, which plays a central role in metabolism for all aerobic organisms. This enzyme catalyzes a dehydration-rehydration reaction interconverting citrate and 2R,3S-isocitrate via the allylic intermediate ds-aconitate. 

Such a reaction may occur on treatment of the benzo-fused bicyclic sulfonium salt 37 with various bases under aerobic conditions. The incipient allylic diradical 39 is trapped as 1,3-diradical by molecular oxygen to give a mixture of up to 35% diastereomeric Spiro-1,2-dioxolanes 40. The spirocyclopentene 41 is obtained in a competing path in which allylic diradical 39 is cyclized as a 1,5-carbon-centered diradicaE . 

Aerobic Co(II) catalysed hydroperoxysiiyiation of allylic alcohols provides silyl peroxides that can be condensed with ketones to produce 1,2,4-trioxanes or 1,2,4-trioxepanes by a simple one-pot procedure (Scheme 35A). A recent improvement in the use of Co(acac)2 is the use of Co(thd)2 (thd = bis (2,2,6,6-tetramethyl-3,5-heptanedionato)). This more reactive catalyst allows cyclic allylic alcohols to be oxygenated and the resulting peroxysilyl alcohol can be transformed to spiro trioxanes, some of which have potent in vitro antimalarial activity (Scheme 35B). For example, compound 87 expresses activity around 20 nM (artemisinin = 10 nM). 

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]. 

These multicomponent catalyst systems have been employed in a variety of aerobic oxidation reactions [27]. For example, use of the Co(salophen) cocatalyst, 1, enables selective allylic acetoxylation of cyclic alkenes (Eq. 6). Cyclo-hexadiene undergoes diacetoxylation under mild conditions with Co(TPP), 2 (Eq. 7), and terminal alkenes are oxidized to the corresponding methyl ketones with Fe(Pc), 3, as the cocatalyst (Eq. 8). 

Toyota, Ihara, and coworkers demonstrated that silyl enol ethers undergo Pd -promoted intramolecular nucleophilic attack on alkenes [18]. Allhough early examples required stoichiometric Pd [167], they have also shown that Pd(OAc)2 in DMSO is an effective catalyst in the presence of an aerobic atmosphere (Eq. 38) [168-170]. The reaction is proposed to proceed through an oxo-jt-allyl intermediate that can undergo competitive alkene insertion or P-hydride elimination (Scheme 11). The latter reaction is the basis for the synthetically useful conversion of silyl enol ethers to a,P-unsaturated carbonyl compounds (see below). Efforts to use BQ as an oxidant were not described. 

The mechanistic role of BQ in the allylic acetoxylation of alkenes suggests that it may not be possible to achieve direct dioxygen-coupled turnover. Recently, however, Kaneda and coworkers reported BQ-free conditions for aerobic allylic acetoxylation that feature a solvent mixture of acetic acid and M,M-dimethylacetamide (DMA) and O2 as the sole oxidant for the Pd catalyst (Eq. 55) [209]. The reactions are highly selective for C-1 acetoxylation (C-1 C-3 = 7-45 1). High pressures of O2 (6 atm) are required to achieve these results. 

H. Spirotrioxanes via Mukaiyama Co(ll) Mediated Aerobic Hydroperoxysilylation of Allylic Alcohols (Use of Triplet Oxygen)... 

The hepatocytes, or parenchymal cells, represent about 80% of the liver by volume and are the major source of metabolic activity. However, this metabolic activity varies depending on the location of the hepatocyte. Thus, zone 1 hepatocytes are more aerobic and therefore are particularly equipped for pathways such as the p-oxidation of fats, and they also have more GSH and GSH peroxidase. These hepatocytes also contain alcohol dehydrogenase and are able to metabolize allyl alcohol to the toxic metabolite acrolein, which causes necrosis in zone 1. Conversely, zone 3 hepatocytes have a higher level of cytochromes P-450 and NADPH cytochrome P-450 reductase, and lipid synthesis is higher in this area. This may explain why zone 3 is most often damaged, and lipid accumulation is a common response (see "Carbon Tetrachloride," for instance, chap. 7). 

Pd-catalyzed aerobic oxidations with hidroquinone-Cu(OAc)2701 and hydroqui-none-iron phthalocyanine529 were also achieved. On the basis of the transformation of 1,2-dideuterocyclohexene, conclusive evidence for the involvement of the ir-allyl intermediate in the quinone-based system has been reported 702... 

Owing to their relevance in steroid chemistry Okamoto et al. investigated aerobic allylic hydroxylations of octahydronaphthalene derivatives such as lc in the presence of Fe(III) picolinate complexes Fe(PA)3H20 (Scheme 3.21) [108]. The combination of electrolysis and the Fe(PA)3-02-MeCN system suppressed epoxidation almost completely, leading exclusively to the oxidation products 2c and 3c, albeit with low yields. In contrast, when alkene lc was submitted to chemical oxidation using the... 

In comparison with metal porphyrins, the corresponding metal phthalocyanines are much more stable against oxidative decomposition. Murahashi et al. reported that chlorinated Fe(II) phthalocyanine is particularly well suited for aerobic allylic oxidation employing acetic aldehyde as a cofactor (Scheme 3.27) [118]. Under these conditions, cyclohexene la is converted to a mixture of 2a and 3a in 70% overall yield and the epoxide 4a as byproduct (30%). Acetic aldehyde is proposed to autoxidize by... 

An efficient and convenient methodology for the aerobic oxidation of alcohols catalysed by sol-gel trapped perruthenate and promoted by an encapsulated ionic liquid in supercritical carbon dioxide solution has been reported. The reaction is highly selective and useful for substrates otherwise difficult to oxidize.263 A four-component system consisting of acetamido-TEMPO-Cu(C104)2-TMDP-DABCO has been developed for aerobic alcohol oxidation at room temperature. The catalytic system shows excellent selectivity towards the oxidation of benzylic and allylic alcohols and is not deactivated by heteroatom-containing (S, N) compounds. The use of DMSO as the reaction medium allows the catalysts to be recycled and reused for three runs with no significant loss of catalytic activity.264... 

Pd(II) catalysts have been widely used for aerobic oxidation of alcohols. The catalytic systems Pd(OAc)2-(CH3)2SO [14] and Pd(OAc)2-pyridine [15] oxidize allylic and benzylic alcohols to the corresponding aldehydes and ketones. Secondary aliphatic alcohols, with relatively high water solubility, have been oxidized to the corresponding ketones by air at high pressure, at 100 °C in water, by using a water-soluble bathophenanthroline disulfonate palladium complex [PhenS Pd(OAc)2] [5d]. The Pd catalyst has also been successfully used for aerobic oxidative kinetic resolution of secondary alcohols, using (-)-sparteine [16]. 

Such a simple mechanistic proposal accomodated the observation that highly activated, benzylic alcohols were good substrates due to the enhanced lability of their a-hydrogen atoms. In contrast, aliphatic alcohols are far less reactive towards H-radical abstraction and, accordingly, poor conversions should ensue. However, it was rather disturbing to note that allylic alcohols, such as geraniol and nerol, displayed poor reactivity in this system. Furthermore, it was observed that the aerobic oxidation of aliphatic alcohols invariably resulted in the rapid formation of a green copper(II) salt, with concomitant deactivation of the catalyst. 

Radical substitution reactions involving allylic tin derivatives could be accompanied by a photoinduced 1,3-rearrangement54,55. A photostationary mixture of cinnamyl(tri-phenyl)stannane with its regioisomer l-phenylprop-2-enyl(triphenyl)stannane has been shown to form in the photolysis of ( )-cinnamyl(triphenyl)stannane in benzene under aerobic conditions, or in the presence of halogenated organic compounds or radicaltrapping reagents (equation 21). 

Recently two heterogeneous TPAP catalysts were developed which could be recycled successfully and displayed no leaching In the first example the tetraalkylammonium perruthenate was tethered to the internal surface of mesoporous silica (MCM-41) and was shown [ 101] to catalyse the selective aerobic oxidation of primary and secondary allylic and benzylic alcohols (Fig. 17). Surprisingly, both cyclohexanol and cyclohexenol were unreactive although these substrates can easily be accommodated in the pores of MCM-41. No mechanistic interpretation for this surprising observation was offered by the authors. 

Both Ru02 and 5% ruthenium-on-charcoal catalyse the aerobic oxidation of activated alcohols such as allylic alcohols [109] and a-ketols [110] (Eq. 27). 

Vocanson et al. [ 111 ] have described the use of ruthenium supported on ceria, Ce02, as a catalyst for the aerobic oxidation of alcohols. Primary and secondary alcohols are oxidized to the corresponding aldehydes (carboxylic acids) and ketones, respectively, at elevated temperatures (above 140 °C). Surprisingly, allylic... 

Allylation of carbonyl and imino groups is one of the most convenient methods for the introduction of allylic functions.107-110 Allylic tin compounds have high interaction between C=C and C-Sn bonds which makes them more reactive than the corresponding silicon derivatives.111,112 In spite of their high reactivity, tin compounds are stable enough to be isolated and to react at ambient temperature under aerobic conditions. These factors allow them to be applicable to various types of reactions, for example, thermal,113 high-pressure,116 transition metal-catalyzed,117,118 radical,119,120 photochemical,121,122 tin-lithium exchange reactions,108,113 and so on. A broad... 

In aerobic cells, polyunsaturated fatty acids of membrane phospholipids easily undergo such oxidative chain reactions [111,112]. This is because the double bonds of the polyunsaturated structure are repeatedly connected to each other by c/s-methylene units. Such bis-allylic structures enable electron delocalization on five carbon atoms, making the initial hydrogen abstraction on... 

Another improvement is the use of a Ru/TEMPO catalyst combination for the selective aerobic oxidations of primary and secondary alcohols to the corresponding aldehydes and ketones, respectively (Fig. 1.22) [72]. The method is effective (>99% selectivity) with a broad range of primary and secondary aliphatic, allylic and benzylic alcohols. The overoxidation of aldehydes to the corresponding carboxylic acids is suppressed by the TEMPO which acts as a radical scavenger in preventing autoxidation. 

Ruthenium-exchanged hydrotalcites were shown by Kaneda and coworkers [156], to be heterogeneous catalysts for the aerobic oxidation of reactive allylic and benzylic alcohols. Ruthenium could be introduced in the Brucite layer by ion exchange [156]. The activity of the ruthenium-hydrotalcite was significantly enhanced by the introduction of cobalt(II) in addition to ruthenium(III), in the Brucite layer [157 ]. For example, cinnamyl alcohol underwent complete conversion in 40 min in toluene at 60 °C, in the presence of Ru/Co-HT, compared with 31% conversion under the same conditions with Ru-HT. A secondary aliphatic... 

Much effort has been devoted to finding synthetically useful methods for the palladium-catalyzed aerobic oxidation of alcohols. For a detailed overview the reader is referred to several excellent reviews [163]. The first synthetically useful system was reported in 1998, when Peterson and Larock showed that simple Pd(OAc)2 in combination with NaHC03 as a base in DMSO as solvent catalyzed the aerobic oxidation of primary and secondary allylic and benzylic alcohols to the corresponding aldehydes and ketones, respectively, in fairly good yields [164, 165]. Recently, it was shown that replacing the non-green DMSO by an ionic liquid (imidazole-type) resulted in a three times higher activity of the Pd-catalyst [166]. 

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