Cyclohexene derivatives, cleavage

The most common procedure is ozonolysis at -78 °C (P.S. Bailey, 1978) in methanol or methylene chloride in the presence of dimethyl sulfide or pyridine, which reduce the intermediate ozonides to aldehydes. Unsubstituted cydohexene derivatives give 1,6-dialdehydes, enol ethers or esters yield carboxylic acid derivatives. Oxygen-substituted C—C bonds in cyclohexene derivatives, which may also be obtained by Birch reduction of alkoxyarenes (see p. 103f.), are often more rapidly oxidized than non-substituted bonds (E.J. Corey, 1968 D G. Stork, 1968 A,B). Catechol derivatives may also be directly cleaved to afford conjugated hexa-dienedioic acid derivatives (R.B. Woodward, 1963). Highly regioselective cleavage of the more electron-rich double bond is achieved in the ozonization of dienes (W. KnOll, 1975). 

Correspondingly, 1,6-difunctionalized molecular skeletons can be derived by oxidative cleavage of cyclohexene derivatives. This is a widely used method, as it allows for differentiation of the functionalihes at the 1- and 6-positions. Detailed methods for doing this can be found in reference [107] (Scheme 2.58). 

Scheme 2.58 Oxidative cleavage of cyclohexene (derivatives) to generate end group differentiated i,6-difunctionalized molecular skeletons...

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. 

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 of epoxides. As with simpler haloboranes, these reagents cleave epoxides of cycloalkenes to give, after nonoxidative workup, halohydrins in 65-90% yield. When carried out at -78 to -100°, the cleavage can show high en-antioselectivity. Thus the halodiisopinocampheylboranes derived from (+ )-pinene react with the oxide of cyclohexene or of cyclopentene to furnish (1R,2R) halo-... 

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. 

One of the most popular ways of using the double bond cleavage sequence envisages its utilization for the preparation of l, -dicarbonyl compounds via oxidation of the respective cycloalkene derivatives. Thus oxidation of cyclohexene represents the easiest way to prepare the 1,6-dialdehyde 460. Intramolecular aldol condensation of460 proceeds with ease to give the respective cyclopentene derivatives 461 or 462 (Scheme 2.149). 

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). ... 

PIFA easily converts succinic acid derivatives (32) to -alanine derivatives (33). Limited use of PIFA (1 equiv.) allows the rearrangement of 3-cyclohexene-1-carboxamide (34) without oxidation of the double bond, as shown in Scheme 12. Cyclohexanone is obtained by the PIFA oxidation of 1-cyclohex-enecarboxamide (35). Selective oxidation of the primary amide (36) occurs without effect on secondary or tertiary amides in the same molecule. The rearrangement of the cyclopropane derivative (37) accompanies the ring cleavage to give the -alanine derivative (38) after treatment with benzyloxycarbonyl chloride. ... 

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