Bis-epoxides

Unsaturated aUphatic endoperoxides form bis(epoxides) and/or epoxy aldehydes upon thermolysis (80,81). Thus 3,5-epidioxycyclopentene [6573-26-8] reacts as follows. 

With certain transition metals, eg, Ru(II)-tertiary phosphine complexes, the principal products are bis(epoxides) (82). 

Similarly, efficient tetracyclization (MeAlCl2-promoted) of the bis-allylic silane/ bis-epoxide 97 constitutes the key step in the synthesis of (+)-a-onocerin. In this case, because of the presence of the bis-allylic silane group, a double bis-annula-tion occurs, with the formation of the ethylene-bridge linked bis-decalin system present in the target compound (Scheme 8.26) [46],... 

Scheme 8.14. Enzyme-catalyzed transformation of bis-epoxide cis.cis.meso-8-51.

In a similar manner, and as shown again by the Faber group, the catalyzed reaction of bis-epoxides led to THFs containing four stereocenters [22]. Thus, treatment of cis,ds,weso-8-51 with the epoxide hydrolase Rhodococcus sp. CBS 71773 predominantly yielded the THF derivative 8-53a in 94% ee and 89% de, whereas the use of other biocatalysts has shown only low to moderate stereoselectivity (Scheme 8.14). As intermediate, the diol 8-52 can be assumed, whereby for the further transformation path A is always favored. 

It should be noted that as early as 1993, Kurth and coworkers investigated the enzymatic transformation of bis-epoxides of type 8-51 using cytosolic epoxide hydrolase from rat liver. However, at that time the regio- and stereochemistry of the obtained THFs had not been investigated. 

Butanediol diglycidyl ether is a viscous liquid having a density of 1.45 at 20°C. It is a hygroscopic, corrosive compound with a displeasing odor that should be handled with care in a fume hood. Aqueous solutions of the bis-epoxide usually possess a characteristic oily film on their surfaces, indicating the limited solubility of the reagent. 

Figure 14.14 Additional hydroxyl-particle activation methods include bis-epoxide modification, tosyl activation, and tresyl activation methods. The tosyl chloride and tresyl chloride activation procedures must be done in dry organic solvent, but the coupling of an amine-containing ligand can be done in either organic solvent or aqueous buffer.

Polyunsaturated (dienes and trienes) lipids found in sediments have been proven to be valuable tools in the determination of palaeo-water temperatures616-18. These C20, C25 and C30 highly branched isoprenoids were investigated analytically by all the tools suggested in this review. We will select one diene to demonstrate the use of the MS, oxidation (bis-epoxidation) MS and H NMR techniques previously discussed. This diene, 2,6,10,14-tetramethyl-7-(3-methylpent-4-enyl)pentadec-5-ene (4), shows the fragmentation pattern given in Scheme 2. 

In very recent work the [6]radialene 95 has been epoxidized with m-chloroperbenzoic acid (MCPBA) to the mono- and the bis -epoxide 168 and 169, respectively, at 0 °C, and to the tris-epoxide 170 at room temperature100. Methylenation with CH2l2/AlMe3 provides the rotaradialenes 171 and 172 (equation 21)101. Again, the relative orientation of the three-membered rings in these adducts follows from X-ray and NMR data100101. 

Ring-opening with heteroatomic nucleophiles is certainly among the most thoroughly studied behavior of epoxides, and this reaction continues to be a versatile workhorse of synthetic utility. This is exemplified in the recent literature by the examples of the p-cyclodextrin-catalyzed aminolysis of simple epoxides by aniline derivatives (i.e., 53 - 54) <00SL339> and the synthesis of oxa-azacrown ethers through the treatment of Ws-epoxides 55 with diamines 56. Yields in the latter synthesis are sensitive to the size of the macrocycle and substitution on the bis-epoxide <00TL1019>. 

Three divinyl carbinol substrates have been chosen as examples. They are good substrates for examination because the vinyl carbinols are known to undergo Sharpless reaction at low reaction rates. The results presented in Table 4-7 clearly show that the ee of 79 improves as the reaction proceeds toward completion. Note that the minor enantiomer 78 can be removed through a second, faster epoxidation that converts enantiomer 78 into an easily destroyed bis-epoxide 80 (Scheme 4-29 and Table 4-7). The same trend is apparent in the second demonstration with diisopropenyl carbinol 81 (Scheme 4-30 and Table 4-8). Similarly, the third reaction is the reaction of (E,E)-divinyl carbinol 82 (Scheme 4-31 and Table 4-9). 

Epoxidations of chiral allenylsilanes are also highly stereoselective, especially if the silyl group is spatially demanding (Eq. 9.54) [60]. A bis-epoxide intermediate is formed which rearranges to an a,/8-unsaturated a -hydroxy ketone. Such products are of interest as branched carbohydrate analogues. 

Photooxygenation of a-terpinene 155 in the presence of eosin (equation 87) produces ascaridole 156, a constituent of the essential oil Chenopodium ambrosioides L 1. The ewrfo-peroxide 157 derived from cyclopentadiene is a crystalline solid, stable at —100 °C78 above this temperature it rearranges to a mixture of the bis-epoxide 158 and the epoxyaldehyde 159 (equation 88)79,80. 

The tetraphenylcyclopentadiene 160 affords the peroxide 161, which rearranges on heating to the bis-epoxide 162 (equation 89)81. In the case of the photooxygenation of the fulvene 163, only the rearrangement product 164 could be isolated (equation 90)81. 

The arene (5 mmol) in CHCl3 (100 ml) is added to aqueous NaOCl (0.6 M, 250 ml) and the pH is adjusted to 8-9 by the addition of cone. HCl. TBA-HS04 (0.34 g, l mmol) is added and the mixture is stirred until TLC analysis shows complete conversion of the arene. The organic phase is separated, washed well with H20, dried (K2CO ), and evaporated to yield the epoxide (e.g. 90% from phenanthrene, 76% from 1,2-benz-anthracene, 70% from acenaphthene, 19% 2,3 4,5-bis-epoxide from naphthalene). 

Fortunately, nature provides an alternative nucleophile whose role is to mop up dangerous electrophiles such as aflatoxin Bi epoxide before they can do damage, and to remove them from the body. This compound is glutathione (see Box 6.6), a tripeptide composed of glutamic acid, cysteine, and glycine. 

The importance of hydrolytic kinetic resolution (HKR) in providing a wide range of highly enantiomerically enriched terminal mono- and bis epoxides has been showed by the conversion of such epoxides efficiently to some important insect pheromones. 1 51... 

Hendry JA, Homer RF, Rose FL, et ah Cytotoxic agents. II. Bis-epoxides and related compounds. BrJ Pharmacol 6 235-255, 1951... 

Upon reaction of Cjq with Meli a bis-epoxide bridged derivative of this cyclo-pentadiene adduct type has been isolated and characterized by single-crystal X-ray analysis [55]. Both epoxide groups bridge [5,6]-bonds in the same pentagon. 

A detailed account of the chemical and spectroscopic evidence for the structures of cochlioquinone-A (18a) and -B (18b) has been published. These compounds are metabolites of Cochliobolus miyabeanus, a parasitic mould which grows on rice, and their unusual cyclofarnesane structure is probably derived in nature by introduction of a farnesyl unit into an aromatic precursor followed by cyclization of an intermediate bis-epoxide. 

A related series of cycloadducts has been produced employing a 1,3-dipolar cycloaddition approach <2000EJ03363, 2001TL465>. Thus, the 1,3-dipole formed from bis-epoxides on heating at high temperatures in a sealed tube undergoes cycloaddition to benzonorbornadienes to produce cycloadducts in a highly stereoselective exo,aco-fashion (Equation 101). 

Although the same sequence of conversions was found to be successfully applied to the c/ v-bis-epoxide 66b, yielding the (Z)[10.10] isomer, mp 136-138 °C, this method... 

Oxepane (159) was obtained in high yield as an unexpected product of rearrangement from the peroxyacid oxidation of the substituted furan shown in equation (45) (81JOC2589). The isomerization of a bis-epoxide intermediate to the ring expansion product (159) occurs in the final step of the latter reaction. ... 

The preparation of the allene bis-epoxide 1 started with isovaleraldehyde 9. Addition of the protected propargyl alcohol 10 under the Carreira conditions led to 11 in > 95% . Mesylation followed by displacement with methyl cuprate provided the allene without loss of enantiomeric excess. Oxidation of the allene 12 with dimethyldioxirane could have led to any of the four diastereomers of the spiro bis epoxide. In the event, only two diastereomers were observed, as a 3 1 mixture. That 1 was the major diastereomer followed from its conversion to 3. The configuration of the minor diastereromer was not noted. Exposure of 1 to nucleophilic azide then gave the easily-purified 2. 

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