Mono-epoxides

The method has been applied in asymmetric and regioselective syntheses of several natural compounds. Two simple examples are the commercial syntheses of the gipsy moth hydrophobic sex attractant, disparlure (RE. Rossiter, 1981, 1985) and < mono-epoxidation of a diene in a leukotriene B4 synthesis (L.S. Mills, 1983). 

Styrene was successfully oxidized to the S-product both by xylene monooxygenase from P. putida mt-2 [113] and styrene monooxygenase from Pseudomonas sp.VLB120 [114] (Scheme 9.13), with the latter enzyme displaying a particularly large substrate tolerance with excellent stereoselectivity (>99% ee). In this context it is interesting to note that both xylene monooxygenase as well as chloroperoxidase are very selective for mono-epoxidation in case of presence of multiple alkene functionalities [115]. 

The 3-hydroxyl P-rings of zeaxanthin are further oxygenated by the introduction of 5,6-epoxy moieties by zeaxanthin epoxidase (ZEP). A mono-epoxidated intermediate, antheraxanthin is produced, followed by the di-epoxy xanthophyU, violaxanthin, as shown in Figure 5.3.3B. 

On a capillary GC analysis, the separation of positional isomers of epoxy compounds is generally well accomplished by a high polar column, such as DB-23, rather than by a low polar column, such as DB-1. For the positional isomers, a different elution order depending on the kinds of column has not been reported. In the case of two mono epoxides derived from Z6,Z9-dienes, 6,7-epoxides elute slightly faster than 9,10-epoxides [72,170],but the separation is insufficient even on the high polar column. Three monoepoxides derived from Z3,Z6,Z9-trienes elute in the order of 6,7-, 3,4-, and 9,10-epoxides [9]. The former two isomers are sufficiently separated on the high polar column, while the elution of the latter two isomers overlaps [71]. For each positional isomer of diepoxides derived from the Z3,Z6,Z9-trienes, two diastereomeric... 

Vinyl epoxides are highly useful synthetic intermediates. The epoxidation of dienes using Mn-salen type catalysts typically occurs at the civ-olefin. Epoxidations of dienes with sugar-derived dioxiranes have previously been reported to react at the trans-olefin of a diene. A new oxazolidinone-sugar dioxirane, 9, has been shown to epoxidize the civ-olefin of a diene <06AG(I)4475>. A variety of substitution on the diene is tolerated in the epoxidation, including aryl, alkyl and even an additional olefin. All of these substitutions provided moderate yields of the mono-epoxide with good enantioselectivity. 

In contrast to the relative chemical stability of mono-epoxides, diol epoxides of fatty acids (10.52), which are formed from di-epoxides by EH, are subject to a different fate. In such metabolites, intramolecular nucleophilic substitution may occur, such that oxirane opening is accompanied by formation of a tetrahydrofuran ring [134], Such reactions of intramolecular nucleophilic substitution are discussed in detail in Sect. 11.9. In the case of diol epoxides of fatty acids, the resulting tetrahydrofuran-diols (10.53) are part of a much larger ensemble of oxygenated metabolites of fatty acids, the potential cytotoxicities of which are being evaluated [135]. 

A number of heterogeneous systems have been developed for oxidation reactions using H2O2 as oxygen source . In 1981, Taramasso, Notari and collaborators at Enichem opened new perspectives in this field with the discovery of the Ti-silicalite (TS-1) ° , a new synthetic zeolite of the ZSM family. In the TS-1 zeolite, titanium atoms are located in vicariant positions in the place of Si atoms in the crystalline framework . The remarkable reactivity of TS-1 is likely ascribable to the site-isolation of tetrahedral Ti(IV) in a hydrophobic environment. TS-1 has proved to be an efficient catalyst for the epoxidation of unfunctionalized short-chain olefins, especially terminal ones (equation 28). In addition, polyunsaturated compounds are mainly converted into the mono epoxides (equation 29). 

Various mono- or di-olefins were oxidized regioselectively to their epoxides in high yield with the 2-nitrobenzenesulfonylperoxy intermediate 51 generated in situ from 2-nitrobenzenesulfonyl chloride and KO2 at —35 °C in CH3CN (equation 78)226. Thus /J-ionone was oxidized using 51 to the corresponding mono epoxide product in high yield (83%). That the electron-deficient double bonds remain intact under the reaction conditions shows the electrophilic character of 51. 

A in Rah-liver oil and other sources. 0 Also believed to be a genuine naturally-occurring epoxide the substance o-carotene mono-epoxide [Pg.343]

The three mono-epoxides of humulene 1 are naturally occurring, and it is believed that they are in vivo precursors of other bicyclic and tricyclic sesquiterpenes. In vitro experiments have demonstrated that the 1,2- and 4,5-epoxides undergo facile acid-catalysed rearrangement, and it has been shown recently that treatment of a chloroform solution of the 8,9-epoxide with tin(IV) chloride at -60°C for 15 minutes gives a variety of hydrocarbons and one major product (25%), the alcohol 2. 

The regioselectivity of this reaction in the case of certain dienes is of interest, since it has been found that the most highly substituted double bond is preferentially attacked, for example as in the mono-epoxidation of 1,2-dimethylcyclo-hexa-1,4-diene9 (formed by the Birch reduction of o-xylene, Section 7.5, p. 1114). 

However the epoxidation of olefins lacking allylic and other reactive C-H bonds with molecular oxygen has recently been achieved on silver catalysts (Table 1). In 1997 the Eastman Chemical Company started the manufacture of 3,4-epoxy-1-butene, the product of mono-epoxidation of butadiene, on a semiworks production scale (entry 1). Remarkably enough the presence of benzylic hydrogen, as in / -methyl styrene (entry 5), drives the oxidation towards combustion, while sterically hindered allylic C-H s, as in norbornene (entry 6), are inert to oxidation. 

In considering the mono-epoxidation of geraniol there are four possible products, as shown in Figure 9.10. Because the olefinic protons on C6 and C2 of the products have different chemical shifts, the two sets of regioisomers are easily distinguished using NMR spectroscopy. The hydrogen on C2 has a chemical shift of 5.404 ppm while that on C6 is... 

Direct methods of converting humulene (332) into its 8,9-monoepoxide (337)t and into zerumbone (338) have proved to be very inefficient. Shirahama et al. have now brought about these conversions by indirect means. Thus, for the epoxide (337),169 humulene is first transformed to the acetate (339) by treatment with boron trifluoride etherate in glacial acetic acid followed by mono-epoxidation. Reduction of this acetate with LiAlH, followed by elimination with mesyl chloride in pyridine gives the epoxide (337). In the case of zerumbone (338),170 the readily... 

The starting material for the next desymmetrisation comes from an interesting reaction first described in chapter 19. The Pd-catalysed attack of AcOH on the mono-epoxide ( )-35 gives the racemic monoester 36. In order to convert this to a single enantiomer it is first made into the meso diester13 37. 

AE of the meso-bisallylic alcohol 17 has also been examined [54]. In this class of substrate, the first epoxidation occurs smoothly in a highly enantiotopic selective manner to give the mono-epoxide 18 preferentially but the second epoxidation of 18 is slow. Therefore, the mono-epoxide 18 can be obtained as a major product in a highly enantiopure form (98% ee) together with a small amount of the diepoxide. 

The enhancement of the enantiomeric excess of the mono-epoxide can be expected also in the epoxidation of the meso-secondary diallylic alcohol 31. Epoxidation of 32 gives the desired anfi-epoxide of high enantiomeric excess in good yield [72]. However, some meso-substrates bearing two hydroxy groups in close vicinity to each other may show unusual stereochemistry as discussed in the preceding section. 

Allene epoxides. Synthesis of allene epoxides is difficult because of the tendency to undergo further epoxidation and to isomerize to the corresponding cyclopropanone (2, 308-309). The first known one was obtained by Camp and Green (2, 309, ref. 3g) by oxidation of 1,3-di-f-butylallene with m-chloroper-benzoic acid. Crandall and Machlcdcr 1 have now reported successful mono-epoxidation of 1,1,3-tri-t-butvlallene (1), also using m-chloroperbenzoic acid. The epoxide (2) is the main product but is accompanied by an oxetanone (3), undoubtedly formed via an intermediate diepoxide. The epoxide (2) is extraordinarily stable and shows no tendency to isomerize to a cyclopropanone. 

Epoxidation of 1,3-dienes with NaOCI catalyzed by S,S-2 provides only mono-epoxides with only moderate enantioselcctivity ( 45% ee). In the case of (Z,E)-dienes, epoxidation occurs with high selectivity (10 1) at the (Z)-alkenc (equation I). In contrast, high enantioselectivity can be obtained with ct. s-enynes (equation II). 

Epoxides. Details for preparation of epoxides from carbpnyl compounds with this reagent are available. Diepoxides can be obtained with this reagent from unhindered 1,2-, 1,3-, or 1,4-diketones in which enolization is not possible. Hindered ketones [c.g., (CHj)3CCO—COC(CH3)3] form only mono-epoxides. ... 

Squalene is very important in nature as it is the precursor of steroids, a family of molecules that serve as hormones in numerous organisms. The formation of the steroid framework from the mono-epoxide of squalene is shown in Figure 2.15. 

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