Cyclohexene epoxides from

Singh J, Dhar K L, Atal C K 1970 Studies on the genus Piper. X. Structure of pipoxide. A new cyclohexene epoxide from P. hookeri Linn. Tetrahedron 26 4403-4406... 

The epoxidation method developed by Noyori was subsequently applied to the direct formation of dicarboxylic acids from olefins [55], Cyclohexene was oxidized to adipic acid in 93% yield with the tungstate/ammonium bisulfate system and 4 equivalents of hydrogen peroxide. The selectivity problem associated with the Noyori method was circumvented to a certain degree by the improvements introduced by Jacobs and coworkers [56]. Additional amounts of (aminomethyl)phos-phonic acid and Na2W04 were introduced into the standard catalytic mixture, and the pH of the reaction media was adjusted to 4.2-5 with aqueous NaOH. These changes allowed for the formation of epoxides from ot-pinene, 1 -phenyl- 1-cyclohex-ene, and indene, with high levels of conversion and good selectivity (Scheme 6.3). 

Fig. 34. Ratio of product concentrations [sum of epoxide and secondary products (a) from oct-1 -ene and (b) from cyclohexene] obtained with mesoporous and conventional TS-1 as a function of the contact time. The results show that the mesoporous TS-1 has a similar activity for oct-1 -ene epoxidation as conventional TS-1. However, the mesoporous TS-1 is significantly more active for cyclohexene epoxidation [Reproduced from Schmidt et al. (188) by permission of the Royal Society of Chemistry].

The mesoporous materials reported above are usually prepared from relatively expensive surfactants. Some of them have poor hydrothermal stability. Furthermore, the MCM-41 host structure has a one-dimensional pore system with consequent pore blockage and diffusion limitations. Shan et al. (52) reported the synthesis of a three-dimensional and randomly connected mesoporous titano-silicate (Ti-TUD-1, mesopore wall thickness = 2.5-4 nm, surface area — 700-1000 m2/g, tunable pore size —4.5-5.7 nm) from triethanolamine (TEA). Ti-TUD-1 showed higher activity (about 5.6 times) for cyclohexene epoxidation than the framework-substituted Ti-MCM-41. Its activity was similar to that of the Ti-grafted MCM-41 (52). 

In the synthesis of cyclohexene oxide from cyclohexene shown, this does implicate the less favourable diaxial conformer in the epoxide-forming step. Cyclohexene oxide contains a c/s-fused ring system, the only arrangement possible, since the three-membered ring is necessarily planar (see Section 3.5.2). 

The desymmetrization of meso-e poxides such as cyclohexene epoxide (55, Scheme 13.27) has been achieved both by enantioselective isomerization, e.g. to allylic alcohols (56, path A, Scheme 13.27) or by enantiotopos-differentiating opening by nucleophiles, affording trans-/ -substituted alcohols and derivatives (57, path B, Scheme 13.27). As indicated in Scheme 13.27, the allylic alcohols 56 can also be prepared from the ring-opening products 57 by subsequent elimination of the nucleophile. 

They found that the erythrolthreo-% i,cX N Xtj is X-substituent dependent, acting through H-bonding, which was demonstrated by the TFDO Ic epoxidation of 73. An example of cyclohexene epoxidation by dioxiranes derived from various ketones grafted on solid supports has also appeared <1996MI273>. Shi and co-workers reported <1996JA9806> excellent ee s of asymmetric epoxidation of different /ra t-olefms by fructose-derived ketones 74 before then, only low enantioselectivities (9-20%) have been reported on this type of reaction. 

Epoxides are possibly the most studied of the three-membered heterocycles. While a host methods for the synthesis of epoxides have been developed, work continues, especially in the development of more chemo-, regio-, and stereoselective methods. The development of new metal-based epoxidation catalysts continues to garner significant levels of activity. The use of the Mn-based catalyst, I, with a water-soluble ligand provides excellent yields of the corresponding epoxides <06MI139>. A Mn-salen complex was modified by the addition of phosphonium groups at either end to render it water-soluble. The use of 5 mol% of this catalyst with NalO as the oxidant provided a quantitative yield of cyclohexene oxide from cyclohexene. 

In 2006 Fukuyama published a total synthesis of racemic morphine starting from isovanillin and a cyclohexene-epoxide [16, 17]. The key features in their synthesis are (1) a construction of the ether linkage between A and C rings by Tsuji-Trost coupling, (2) an intramolecular Heck reaction to construct A-C-E tricyclic system, and (3) an intramolecular Mannich-type reaction of a ketone with an aminal to provide the pentacyclic structure of morphine in a one-step reaction by double cyclization. 

Epoxides from vic-diols. trans-1,2-Dihydroxycyclohexane (1) reacts with dimethylformamide dimethyl acetal at 75° (24 hours) and then at 130° (24 hours) to give <7.f-cyclohexene oxide (2) in 88% yield. The analogous reaction with cis-dihydroxycyclohexune (3) yieIJs dimethylformamide cyclohexane acetal (4). 

It seems that practical implementation of this type of selective catalysts will require a medium in which (very) polar products can be removed from the zeolite phase. Unfortunately, no attention has been paid in literature to such issues. On the contrary, some attention has been devoted to host modification after exchange of NaY with other alkali metal cations [37]. The cyclohexene epoxidation activity increases with decreasing size of the charge compensating cation pointing to the influence of steric effects or of electrostatic effects on the activity. In competitive experiments using cyclohexene and 1-octene as feed, the reactivity of the smaller substrate is suppressed, indicating that competitive sorption is involved as well [37],... 

Evidence for the formation of singlet oxygen from Posner was based on chemical trapping. Photolysis of dibenzothiophene sulfoxide in a 90 10 mixture of cyclohexene and acetic acid provided a sample that tested positive for peroxides. After reduction with Nal, 2-cyclohexenol was obtained in 22-34% yield. The authors noted a lack of cyclohexanone and cyclohexene epoxide. This was rationalized as outlined below [97]. 

Acetylenes, few of which are biologically active, have also been isolated from microorganisms and marine organisms, such as the antifungal acetylenic cyclohexene-epoxide derivative asperpentyn isolated from Aspergilus and dactylyne, an acetylenic dibromochloro-ether, isolated from sea hare. Dactylyne was shown to be a very potent inhibitor of drug metabolism... 

The opening of cyclohexene epoxides is controlled by the need to get the trans diaxial products. To get the right answer we need merely to draw the only possible trans diaxial (i.e with CN and O" diaxial) product from each of these conformationally fixed trans decalins. Cyanide must, of course, open the epoxide with inversion so the OH group in the products is on the same side as the oxygen atom in the original epoxides. 

The formation of P-bromohydrins and p thioalcohols from epoxides has also been reported. For example, Shibasaki has shown that the heterobimetalhc gallium lithium BINOL complex (12.138) is a good catalyst for nucleophilic ringopening of epoxides, including the use of thiols. Cyclohexene epoxide (12.116) is converted into the sulfide (12.141) with very good enantioselectivity. Indium complexes of bipyridine (12.126) are very active catalysts in the thiolysis of meso-epoxides providing between 92 and 96% ee in the reaction of ds-stilbene oxides with a range of aromatic and aliphatic sulfides. ... 

The PW4O2J anion turned out to be a valuable catalyst for a number of oxidations of organic substrates with hydrogen peroxide, including the epoxidation of olefins and their cleavage, e.g. to get adipic acid from cyclohexene or from the intermediate 1,2-cyclohexanediol. " ... 

Jerina e( al. (1968) have shown that an epoxide hydrase of rabbit liver microsomes, or the. soluble fraction of liver homogenate, convert benzene epoxide to the dihydrodiol (see Fig. 4). The reaction was also demonstrated with styrene epoxide, indene epoxide, and cyclohexene epoxide. A soluble dehydrogenase from the liver preparation oxidized dihydrodiols to catecliols. The conversion of the epoxide to phenol was considered to be a nonenzymic isomerization. In the presence of glutathione and glutathione-iS-epoxide transferase, a glutathione conjugate was formed. 

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