Cyclohexene allylic oxidation

An example of this reaction is the reaction of cyclohexene with t-butyl perbenzoate, which is mediated by Cu(I). " The initial step is the reductive cleavage of the perester. The t-butoxy radical then abstracts hydrogen from cyclohexene to give an allylic radical. The radical is oxidized by Cu(II) to the carbocation, which captures benzoate ion. The net effect is an allylic oxidation. 

The Pacman catalyst selectively oxidized a broad range of organic substrates including sulfides to the corresponding sulfoxides and olefins to epoxides and ketones. However, cyclohexene gave a typical autoxidation product distribution yielding the allylic oxidation products 2-cyclohexene-l-ol (12%) and 2-cyclohexene-1-one (73%) and the epoxide with 15% yield [115]. 

The activity of the FePeCli6-S/tert-butyl hydroperoxide (TBHP) catalytic system was studied under mild reaction conditions for the synthesis of three a,p-unsaturated ketones 2-cyclohexen-l-one, carvone and veibenone by allylic oxidation of cyclohexene, hmonene, and a-pinene, respectively. Substrate conversions were higher than 80% and ketone yields decreased in the following order cyclohexen-1-one (47%), verbenone (22%), and carvone (12%). The large amount of oxidized sites of monoterpenes, especially limonene, may be the reason for the lower ketone yield obtained with this substrate. Additional tests snggested that molecular oxygen can act as co-oxidant and alcohol oxidation is an intermediate step in ketone formation. 

The heterogeneous catalytic system iron phthalocyanine (7) immobilized on silica and tert-butyl hydroperoxide, TBHP, has been proposed for allylic oxidation reactions (10). This catalytic system has shown good activity in the oxidation of 2,3,6-trimethylphenol for the production of 1,4-trimethylbenzoquinone (yield > 80%), a vitamin E precursor (11), and in the oxidation of alkynes and propargylic alcohols to a,p-acetylenic ketones (yields > 60%) (12). A 43% yield of 2-cyclohexen-l-one was obtained (10) over the p-oxo dimeric form of iron tetrasulfophthalocyanine (7a) immobilized on silica using TBHP as oxidant and CH3CN as solvent however, the catalyst deactivated under reaction conditions. 

Catalytic activity. Figure 49.1 shows the catalytic activity of FePcCli6-S for the allylic oxidation of 1, 2, and 3. High olefin conversion was observed the highest ketone yield was obtained with cyclohexene. The lower ketone yields... 

It has been reported that molecnlar oxygen plays an important role in the allylic oxidation of olefins with TBHP (25, 26). Rothenberg and coworkers (25) proposed the formation of an alcoxy radical via one-electron transfer to hydroperoxide, Equation 4, as the initiation step of the allylic oxidation of cyclohexene in the presence of molecnlar oxygen. Then, the alcoxy radical abstracts an allylic hydrogen from the cyclohexene molecnle. Equation 5. The allylic radical (8) formed reacts with molecular oxygen to yield 2-cyclohexenyl hydroperoxide... 

Several catalytic systems based on copper can also achieve allylic oxidation. These reactions involve induced decomposition of peroxy esters (see Part A, Section 11.1.4). When chiral copper ligands are used, enantioselectivity can be achieved. Table 12.1 shows some results for the oxidation of cyclohexene under these conditions. 

Table 12.1. Enantioselective Copper-Catalyzed Allylic Oxidation of Cyclohexene...

It has been pointed out earlier that the anti/syn ratio of ethyl bicyclo[4.1,0]heptane-7-carboxylate, which arises from cyclohexene and ethyl diazoacetate, in the presence of Cul P(OMe)3 depends on the concentration of the catalyst57). Doyle reported, however, that for most combinations of alkene and catalyst (see Tables 2 and 7) neither concentration of the catalyst (G.5-4.0 mol- %) nor the rate of addition of the diazo ester nor the molar ratio of olefin to diazo ester affected the stereoselectivity. Thus, cyclopropanation of cyclohexene in the presence of copper catalysts seems to be a particular case, and it has been stated that the most appreciable variations of the anti/syn ratio occur in the presence of air, when allylic oxidation of cyclohexene becomes a competing process S9). As the yields for cyclohexene cyclopropanation with copper catalysts [except Cu(OTf)2] are low (Table 2), such variations in stereoselectivity are not very significant in terms of absolute yields anyway. 

For the Ti(OiPr)4/silica system, the advantage of MCM-41 (a mesoporous silica) over an amorphous silica is not evident either in terms of activity or selectivity for the epoxidation of cyclohexene with H202 in tert-butyl-alcohol.148 Nevertheless, deactivation of the catalysts seems slower, although the selectivity of the recovered catalysts is also lower (allylic oxidation epoxidation = 1 1). Treatment of these solids with tartaric acid improves the properties of the Ti/silica system, but not of the Ti/MCM-41 system, although NMR,149 EXAFS,150 and IR151 data suggest that the same titanium species are present on both supports. 

When the reactant is cyclohexene, in the first step of Scheme 26, the direct hydrogen abstraction for the allylic oxidation (path 1) competes with the electron transfer (from the alkene to the M-oxo complex) for the epoxidation (path 2). Because the manganese complex is more readily reduced than the chromium... 

Pfaltz and co-workers (108) reported that the allylic oxidation of cyclohexene proceeds in moderate selectivity using stoichiometric amounts of semicorrin-Cu(II) complexes. In catalytic reactions, the enantioselectivity decreased drastically. Better results were realized using bis(oxazolines) as ligands. Upon... 

Tris(oxazoline) complexes have also been investigated as ligands in the allylic oxidation reaction. Katsuki and co-workers (116) observed that Cu(OTf)2 com-plexed to the tris(oxazoline) 160 is a more selective catalyst than one derived from CuOTf, Eq. 99, in direct contrast to results observed with bis(oxazohnes) or pyridyl bis(oxazohnes) as ligands (cf. Section III.A.3). When the reaction is conducted at -20°C, the cyclopentenyl benzoate is delivered in 88% ee albeit in only 11% yield after 111 h. Larger cycloalkenes are less selective (cyclohexene 56% ee, cyclohep-tene 14% ee, cyclooctene 54% ee). 

The application of dinuclear metal catalysts to the Kharasch-Sosnovsky reaction is mechanistically intriguing due to their illustrated role in mediating biological oxidations (119). Fahmi (120) examined a variety of dinucleating ligands with Cu(MeCN)4PF6 as catalysts in the allylic oxidation of cyclohexene, Eq. 102. In these studies, early results have been inferior to those obtained from bis(oxa-zoline)-copper catalysts. 

The ring-opening of the cyclopropane nitrosourea 233 with silver triflate followed by stereospecific [4 -i- 2] cycloaddition yields 234 [129]. (Scheme 93) Oxovanadium(V) compounds, VO(OR)X2, are revealed to be Lewis acids with one-electron oxidation capability. These properties permit versatile oxidative transformations of carbonyl and organosilicon compounds as exemplified by ring-opening oxygenation of cyclic ketones [130], dehydrogenative aroma-tization of 2-cyclohexen-l-ones [131], allylic oxidation of oc, -unsaturated carbonyl compounds [132], decarboxylative oxidation of a-amino acids [133], oxidative desilylation of silyl enol ethers [134], allylic silanes, and benzylic silanes [135]. 

Sheldon and coworkers have developed chromium-substituted molecular sieves (CrAPO-5) as recyclable solid catalysts for several selective oxidations, among them also the allylic" and benzylic ° " ° " ° oxidations using TBHP or O2 as the terminal oxidants (equation 63), which yielded the corresponding benzylic ketones in moderate yield (conv. 13-70%) and moderate to good selectivity (41%, 65-97%). The benzylic alcohols were formed as side products. Allylic oxidation also proceeded with good conversions, while selectivities were lower and both possible products, the allylic ketone (31-77% selectivity) and the allylic alcohol (0-47% selectivity), were formed. Chromium sUicalite showed activity for selective benzylic oxidation in the presence of TBHP as well as giving mainly the allylic ketone (2-cyclohexen-l-one with 74% selectivity) and the allylic alcohol as minor product (2-cyclohexen-l-ol with 26% selectivity) -. ... 

Other examples of this type of reaction include those conducted by Andrus and co-workers using the copper(I) complex of ligand 224 in the allylic oxidation of cyclohexene.As shown in Figure 9.65, this reaction afforded the oxidation product, (15)-2-cyclohexen-l-yl 4-nitrobenzoate 225 in 76% yield and 73% ee. Clark and co-workers also experimented with the allylic oxidation of cyclohexene using inda-box ent-9h to afford the oxidation product, (15)-2-cyclohexen-l-yl benzoate, 223b in 76% yield (71% ee). ... 

The related dirhodium(II) a-caprolactamate (cap) complex [Rh2(p--cap)4] undergoes a one-electron oxidation process at quite a lower potential (11 mV) than the acetate complex (1170 mV). In agreement with the Kochi hypothesis, the a-caprolactamate complex has recently been found to be an exceptional catalyst for the allylic oxidation of alkenes under mild conditions. A wide range of cyclohexenes, cycloheptenes, and 2-cycloheptenone (Eq. 5) are rapidly converted to enones and enediones in 1 h with only 0.1 mol % of [Rh2( x-cap)4] and yields ranging from 60 to 90%, in the presence of potassium carbonate [34]. 

In 1989, Isobe and coworkers reported on an organometallic polyoxometalate cluster (Rhcp )4V60i9] (cp = r/2-C4Me5) that catalyzes the oxidation of cyclohexene with TBHP as oxidant to give mainly allylic oxidation products (l-tm-butylperoxycyclohex-2-ene 42% and cyclohex-2-en-l-one 21%) and only httle epoxide (15%) (equation 62)432. The yield of 1-tm-butylperoxy cyclohex-2-ene increased with decreasing molar ratio of cyclohexene to TBHP, while the yield of cyclohex-2-en-l-one has a maximum at the ratio of 0.2. 

SCHEME 129. Yields and enantiomeric excesses of the enantioselective allylic oxidation (Kha-rasch-Sosnovsky reaction) of cyclohexene using different chiral ligands... 

C>2 is known to react with olefins to form allylic hydroperoxides via the Schenck reaction. Even if cyclohexene has a rather low reactivity towards 02 [19], it is likely that at least part of the allylic oxidation products (enylOOH, enol, enone) arise from a 02 reaction, rather than from a free radical chain process. 

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