Cyclohexene oxidative cleavage

Oxirane on thermolysis or photolysis suffers C—O homolysis to give a plethora of products (Scheme 2). Substituted oxiranes behave similarly on thermolysis although some C—C cleavage is observed (Scheme 3). Cyclopentene and cyclohexene oxides undergo only C—O cleavage (Scheme 4). 

Conversion of epoxides into /3-hydroxy isocyanides—preparation of trans-2-isocyanocyclohexanol, using TMSCN to open cyclohexene oxide with trans stereochemistry, followed by KF/MeOH cleavage of the intermediate silyl ether. 

It not tertiary, the product yield is lowered by transfer of the carbinol hydride ion to the aldehyde to produce a new alkoxide and an enolate ion. Thus, propylene oxide, after reductive cleavage with LDBB and trapping with isobutyraldehyde or p-anisaldehyde, provided 5-methyl-2,4-hexanediol in 40-50% yield or 1-p-anisyl-1,3-butanediol in 44% yield, respectively (in both cases about equal mixtures of diastereoisomers were obtained). The cyclohexene oxide-derived dianion, when trapped with isobutyraldehyde, gave 2-(1-hydroxy-2-methylpropyl)cyclohexanol in 71% yield as a mixture of only partially separable isomers in the ratio 15 11 39 35. 

No atoms are lost in the cleavage reaction so that cheap cyclohexene 6 is used to make adipic acid 7 for nylon manufacture. Any of the oxidative cleavage methods from the last chapter could be used Vogel1 has a recipe using concentrated nitric acid on cyclohexanol 8 that presumably goes by dehydration to the alkene 6 followed by oxidation, and other methods are probably used industrially. 

The synthesis of 18 is discussed in the next chapter. The synthesis of 14 is a classic of its kind the alcohol 17 is not isolated but dehydrated directly to the cyclohexene 16 and the oxidative cleavage is done by ozone. The intramolecular aldol is unambiguous as the alternative is a seven-membered ring.2... 

This last example makes it clear that we shall normally have to make the cyclohexenes we need for oxidative cleavage and one of the best routes to such compounds is the Diels-Alder reaction (Chapter 17). A generalised example would be ozonolysis of the alkene 21, the adduct of butadiene and the enone 20. The product 22 has a 1,6-relationship between the two carboxylic acids. Since Diels-Alder adducts have a carbonyl group outside the ring (the ketone in 21) the cleavage products 22 also have 1,5- and 1-4-diCO relationships and would be a matter for personal judgement which of these should be disconnected instead if you choose that alternative strategy. 

To access 5a-carba-L-gulopyranose derivatives 119 and 121, Stork cyclization clearly transformed cyclohexene 116 into cyclic silylether 117 which, after oxidative cleavage of the C-Si bond, led to 118, the direct precursor of p-L-configured carbahexose 119. The a-L-anomeric counterpart 121 was obtained from the common intermediate 118 by a short sequence centered upon inversion of configuration of the pseudoanomeric carbon. Inversion of the configuration at Ci in 116 and application of the same protocol ensured preparation of both anomers of the D-talo-configured carbasugars. 

Cleavage and resolution of epoxides.1 The aluminum reagent obtained by reaction of (R)-l with diethyl- or dimethylaluminum chloride shows slight reactivity in reactions with epoxides, but the ate complex (2), prepared from 1, (C2H5)2A1C1, and lithium butoxide, converts cyclohexene oxide into the chlorohydrin (3) in 40% ee. 

Fig. 4.23 Oxidative cleavage of cyclohexene using tungstate catalyst.

Another possibility is the use of tungsten, which has led to excellent results for the conversion of cyclohexene to adipic acid (see Fig. 4.23) [48]. For linear olefins using the Venturello-system, oxidative cleavage products can be obtained in around 80% yield [96]. 

In contrast to other cleavage reagents, this anodic oxidation does not show stereochemical preference. In addition, ether derivatives are oxidized in similar current efficiencies to those of the parent 1,2-diols. Cyclohexene oxide is oxidized via the corresponding hydroxy edier. 

Lead acetate azides, Pb(OAc)4 (N3)n, prepared in situ from lead tetraacetate and azidotrimethylsilane, react with alkenes to yield a variety of products, depending on the structure of the alkene 1,2-diazides. 1,2-acetoxy azides, a-azido ketones, allylic azides, and <5-oxo nitriles (by the oxidative cleavage of cyclohexene rings)97. The diazides and acetoxy azides are formed by preferential syn addition, but the diastereoselectivity (up to 3 1) is far from satisfactory with both acyclic and cyclic alkenes98,99. 

The literature of this reaction to 1940 has been adequately reviewed. The emphasis up to that time was placed on obtaining higher yields of carbonyl compounds by hydrolysis of the ozonides. Several methods have been described for the oxidative cleavage of ozonides to acids. These procedures may prove valuable in the synthesis of certain acids. By adding the ozonide of 1-tridecene to an alkaline silver oxide suspension at 95°, a 94% yield of lauric acid is obtained. Decomposition of ozonides with 30% hydrogen peroxide is described for the preparation of 5-methyl-hexanoic acid (67%) from 6-methyl-l-heptene and of adipic acid (60%) from cyclohexene. A study of solvents for ozonolysis has been made. ... 

Cleavage of the triphenylphosphine complex with iodine in methanol led to the formation of an ester. Surprisingly, cyclohexene oxide... 

Examples of intramolecular trapping of carbonyl ylide dipoles by alkenes have now been reported.These include, for example, the conversion of the oxirane (172) into the tetrahydrofuran (173). Carbonyl ylides have also been prepared by irradiation of 2,3-bis-(p-methoxyphenyl)oxirane in the presence of dicyanoanthracene as electron-transfer sensitizer direct or triplet-sensitized irradiation, however, leads mainly to rearrangement via carbon-oxygen bond cleavage. In contrast, cyclohexene oxide and styrene oxide, on naphthalene-sensitized irradiation in alcohols, undergo solvolysis via oxide anion-radical intermediates. ... 

Flowers et al. have dealt with the thermal gas-phase reactions of methyl-oxirane, other methyl-substituted oxiranes, and ethyloxirane. The kinetics of the processes have been compared. Pyrolysis of these compounds is a first-order, homogeneous, nonradical process the reaction rate is not affected by radical scavengers. A biradical mechanism holds. The thermochemical behavior of cyclopentene oxide and cyclohexene oxide is similar. The primary products are the corresponding carbonyl compounds and unsaturated alcohols. Two mechanistic possibilities have been discussed they are obtained from a common biradical intermediate or the alcohol is formed directly from the oxirane in a concerted manner. Thermolysis of spirooxiranes leads to ketone derivatives via biradicals with homolytic bond cleavage (Eqs. 376, 377). ... 

Oxidation. Oxidation of cyclohexene and norbomene with Mo(CO) -r-BuOOH in supercritical carbon dioxide gives vic-diols. Some alkenes (e.g., cyclooctene) afford epoxides but vinylnaphthalenes and cii-stilbene undergo oxidative cleavage to the aromatic aldehydes. 

Scheme 7.13 Reaction network in the direct oxidative cleavage of cyclohexene to AA. Source elaborated from [34h].

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