Cyclohexane epoxides

The vinyloxirane reaction was later extended to methylidene cyclohexene oxide and to related meso derivatives [53]. The effects of the diastereomeric ligands 42 and 43 (Fig. 8.5), derived from (S)-binaphthol and (S, S)- or (R, R)-feis-phenylethyl-amine respectively, were investigated. In the case of kinetic resolution of racemic methylidene cyclohexane epoxide 45 with Et2Zn, ligand 42 produced better yields, regioselectivity, and enantioselectivity than 43 (Scheme 8.27). 

J. Marco-Contelles, Cyclohexane epoxides—Chemistry and biochemistry of (+)-cyclophellitol, Eur. J. Chem. (2001) 1607-1618. 

Through the NN-GA optimisation process, an important improvement in the activity and selectivity of the starting materials has been achieved (Fig. 5.5). The figure shows the cyclohexane epoxide yields for the eight evolved generations (8x21 samples). The best materials have low titanium contents, and were extracted and silylated. These materials have a Ti-MCM-41 structure and a very hydrophobic surface. 

The presence of hydroxyl groups, both adjacent and remote from the epoxide group, have been found to control the regio- and stereo-specificity of the tetracyanoethylene-catalysed methanolysis of cyclohexane epoxides.44 Because the nucleophilic attack occurs at the carbon remote from the hydroxyl group with inversion of configuration, it was suggested the hydroxyl group participates in the reaction. 

Because of their suitable skeletal structure trans-CHD are applicable in the synthesis of compound classes of chemical, biological, and pharmaceutical interest. Regio- and stereoselective epoxidation of either one or two double bonds of 2, for example, opens up an approach to a group of naturally occurring cyclohexane epoxides which have attracted considerable attention because of their unusual structures, biogenesis, and biological activity [15]. 

Scheme 6.4.4. 2,3-trans-CHD 2 as a precursor of cyclohexane epoxides and (amino-) carbasugars. 

Reaction with 1,2-glycols. This redox system converts trafis-l,2-cyclo-hexanediol into cyclohexane epoxide with no indication of a phosphorus-containing intermediate. The reaction with cm-1,2-cyclohexanediol results in a phosphorane. This differing behavior was first observed in reactions of the nucleosides 1 and 3. 

Normally, axial attack occurs on cyclohexane epoxides as explained in Chapter 18 but the mle is not rigid as you can see here. Equatorial attack occurs here because the transition state already has much of the stability of the product. You should continue to assume axial attack unless told otherwise. 

The enantiospecific synthesis of naturally occurring cyclohexane epoxides such as (+)-crotepoxide and (+)-boesenoxide was accomplished by T.K.M. Shing et al. The key Intermediate 1,3-cyclohexadlene was prepared using the Corey-Winter protocol on a c/s-vicinal diol. The resulting diene was then converted to the natural product after several steps. 

Sources, biological activities, and syntheses of naturally occurring cyclohexane epoxides 04CRV2857. 

Cyclohexane epoxides—chemistry and biochemistry of (+ )-cyclophellitol 01EJ01607. 

Entry 6 is one of several examples demonstrating enantioselectivity for both the cis and trans isomers of heptane-2,3-epoxide. Entry 7 shows the kinetic resolution of an exocyclic cyclohexane epoxide. The two stereoisomeric monomethyl analogs were only partially resolved and the 3-methyl isomer showed no enantioselectivity. This shows that the steric or hydrophobic effect of the dimethyl substiments is critical for selective binding. 

The reaction of malonate enolates with cyclohexane epoxides leads to mixtures of the two possible lactones (87) and (88)," convertible into the corresponding a-methylene-lactones by now relatively standard procedures. In a similar vein, the bis-spirolactone (90) can be obtained from epoxide (89). Spirolactones can also be prepared from cyclic ketones by condensation with ethyl a-bromomethylacrylate in the presence of zinc, and cyclization of the adduct in cold, dilute acid." ... 

The mechanism of dehydrohalogenation under basic conditions of trons-fused bicyclo[4,n,0]alkane halohydrins (563)—(565) has been studied. Three reaction types are noted (i) epoxide formation, (ii) ketone formation, and (iii) ring contraction. trans-Diaxial chlorohydrins corresponding to (563)—(565) gave epoxides (566)—(568) with relative rates (derived from bimolecular rate constants) of 1 3 17. This rate sequence was rationalized in terms of deformation of the cyclohexane ring brought about by the nature of the fused ring. In particular, deformation is probably towards the half-chair conformation favoured by the cyclohexane epoxide which is formed in the slow step. trans-Diequatorial chlorohydrins represented by (563)—(565)... 

The hydrolysis of epoxides to give 1 -diols is an area that is ripe for development. Some work has been published showing that epoxides such as cyclohexane epoxide (36) form optically active diols, in this case cyclo-hexane-(lR,2i )-diol (37). The research has concentrated on the use of enzymes present in liver microsomes, and while this elegant work has indicated what can be achieved, it is clear that rapid progress and the involvement of non-experts in this particular area must await the discovery of readily available epoxide hydrolase enzyme(s) from microbial sources. 

This intermediate is available by an interesting detour, the reaction of cyclohexane epoxide with phenyl-Grignard reagent, followed by oxidation of sec alcohol. The reader should propose a synthetic scheme to TM 8.8 and suggest workable reaction conditions. 

These compounds will be described in the order of y- and J-lactones, cyanogenic glycosides, cyclohexane epoxides, cyclohexane diols, polycyclic compounds, and miscellaneous. 

These compounds are not aromatic, because the aromatic ring has been oxidized to an epoxide (67). The biogenesis of these cyclohexane-epoxides remains to be solved, although hypothetical pathways involving an arene oxide have been proposed (43, 57). 

Sutherland and his co-workers have established that tetrasubstituted cyclohexane epoxides can fulfil a useful role as cationic cyclization initiators." Several alk-3-enyl-2,3-epoxy-3-methylcyclohex-2-enones, e.g. (177), have been successfully cyclized to decalone derivatives, e.g. (178), in good yield on treatment with Lewis acids, and the acetylenic epoxides (179) and (181) have been cyclized in excellent yields to the expected decalin (180) and hydrindane (182) derivatives respectively." ... 

In the present work, we have tested MIL-47 for its catalytic performance in the oxidation of cyclohexene. Amongst the various oxidation products of cyclohexene, cyclohexane epoxide is a highly reactive and selective organic intermediate which is widely used in the synthesis of enantioselective dmgs, epoxy paints and mbber promoters [11]. Furthermore the catalytic activity of MIL-47 is compared to VAPO-5, V0x/Si02 and the homogeneous catalyst VO(acac>2. 

Alkylation Reactions. DMF dialkyl acetals undergo a variety of reactions with 1,2-diols. For example, the reaction of trans-cyclohexane-l,2-diol with DMF dimethyl acetal leads to the formation of cyclohexane epoxide (eq 2) with inversion of configuration. Similarly, wej 0-l,2-diphenyl-l,2-ethanediol gives trans-stilbene epoxide stereospecifically (eq 3). This method has also been applied in the synthesis of cholestane epoxide from vicinal diols. If the intermediate 2-dimethylamino-1,3-dioxolane is treated with Acetic Anhydride, reductive elimination to the alkene occurs with retention of stereochemistry (eq 4). " ... 

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