Aerobic allylic alcohol

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... 

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]. 

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). 

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... 

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. 

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). 

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. 

Major trends can be discerned for Pd-catalysts, aimed at increasing the stability and activity. First is the use of palladium-carbene complexes [178]. Although activities are still modest, much can be expected in this area. Second is the synthesis and use of palladium nanoparticles. For example, the giant palladium cluster, Pd561phen6o(OAc)i8o [179], was shown to catalyze the aerobic oxidation of primary allylic alcohols to the corresponding a,/funsaturated aldehydes (Fig. 4.66) [180]. 

The aerobic oxidation of benzylic and allylic alcohols to their corresponding carbonyl compounds in [C4Ciim][PF6] with TEMPO-CuCl (TEMPO = 2,2,6,6-tetramethylpiperidinyl-l-oxy) as catalyst was found to proceed at higher rates than that of aliphatic alcohols, which is in agreement with results in classical solvents.[75] After product extraction with diethyl ether, the ionic liquid was washed with water and dried at 70°C, prior to the next run. In that manner catalyst activity remained relatively stable for 8 cycles. 

The first example of olefin hydrocohaltation and its subsequent oxygenation was reported by Okamoto [39]. Later, Pattenden studied the hydrocohaltation of 1,3-dienes and found that they led exclusively to 1,4-addition. Under aerobic condition, tertiary peroxycobaloximes are produced. After reductive treatment, tertiary allylic alcohols are obtained (Scheme 14, Eq. 14.1). Interestingly, reactions with TEMPO afford primary alkoxyamines and after reductive treatment primary allylic alcohols (Scheme 14, Eq. 14.2). This change in regioselectivity may be attributed to steric effects [40]. 

Minisci reported the first nitroxyl-catalyzed aerobic alcohol oxidation in the presence of precursors in 2001 (Scheme 15.7a) [28]. The optimal reaction conditions included a combination of catalytic Mn(N03)2 and Co(N03)2 with TEMPO (10 mol%) under 1 atm of O2. The authors demonstrated that Mn(NOg)2, Co(N03)2, and Cu(N03)2 were independently effective catalysts, implicating the nitrate anion as an important contributor to the reaction. Primary and secondary benzylic alcohols, primary allylic alcohols, and primary and secondary aliphatic alcohols were oxidized to the corresponding aldehydes/ketones in excellent yields. 

Figure 2.9 Evidence that surface PdO catalyzes the aerobic selective oxidation of allylic alcohols over Pd/Al20j (a) Strong dependence of TOF on surface oxide concentration and (b) in situ reduction of active PdO phase accompanying onstream deactivation. (Adapted from Refs [96] and [144] by permission of the Royal Society of Chemistry.)...

As a further extension, the Kim group very recently developed the aerobic oxidation and [l,5]-hydride transfer/cyclization sequence starting from readily available ortho tertiary amine substituted cinnamyl alcohols 24 (Scheme 4.12). The tetrapropylammonium perruthenate (TPAP) was identified as the competent catalyst for the initial aerobic oxidation of the allylic alcohols. The synthetically useful tetrahydroquinoline derivatives 25 were prepared in moderate yields and high level of enantioselectivity. 

However, these methods suffer from low activities and/or narrow scope. Uemura and coworkers [74,7 5] reported an improved procedure involving the use of Pd(OAc) 2 (5 mol%) in combination with pyridine (20 mol%) and 3 A molecular sieves (500 mg per mmol of substrate) in toluene at 80 °C. This system smoothly catalyzed the aerobic oxidation of primary and secondary aliphatic alcohols to the corresponding aldehydes and ketones, respectively, in addition to benzylic and allylic alcohols. Representative examples are summarized in Table 5.7. The corresponding lactones were afforded by 1,4- and 1,5-diols. This approach could also be employed under fluorous biphasic conditions [76]. 

Semmelhack ef al. [112] reported that the combination of CuCl and 4-hydroxy TEM PO 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). They proposed that the copper catalyzes the reoxidation... 

A nickel-substituted hydrotalcite was also reported as a catalyst for the aerobic oxidation ofbenzylic and allylic alcohols [125]. Analogous to cobalt, nickel is expected to catalyze oxidation via a free-radical mechanism. 

Sheldon and Arends found that the combination RuCl2(PPh3)3-TEMPO affords an efficient catalytic system for the aerobic oxidation of a broad range of primary and secondary alcohols at 100 °C, giving the corresponding aldehydes and ketones, respectively, in >99% selectivity in all cases [86]. The reoxidation of the ruthenium hydride species with TEMPO was proposed in the latter system [86c[. Allylic alcohols can be converted into a,(3-unsaturated aldehydes with 1 atm of molecular oxygen in the presence of RUO2 catalyst [87]. 

More recently, Kagan and coworkers have described the use of ruthenium supported on ceria, CeO, 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 (>140°C). Surprisingly, allylic alcohols, such as geraniol, and some cyclic alcohols, e.g. menthol, are unreactive. The former result suggests that low-valent ruthenium species are possibly involved and that coordination of ruthenium to the double bond inhibits alcohol oxidation. 

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