Oxirane from 1,2-diol

Industrial interest has been shown in the generation of oxirans from vicinal hydroxy-acetates (by elimination of acetic acid at temperatures of around 400 or from vicinal diols (through conversion into hydroxy-esters in situ... 

Oxiranes from yic-dioh. Epoxidation with a peracid of a double bond in the presence of a triple bond is often not successful. However, 1 -alkynylOxiranes can be obtained in yields of about 80% by treatment of t /c-diols of type 1 with 1 equiv. of tosyl chloride in monoglyme followed by reaction with powdered sodium... 

The addition of acetylides to oxiranes yields 3-alkyn-l-ols (F. Sondheimer, 1950 M.A. Adams, 1979 R.M. Carlson, 1974, 1975 K. Mori, 1976). The acetylene dianion and two a -synthons can also be used. 1,4-Diols with a carbon triple bond in between are formed from two carbonyl compounds (V. Jager, 1977, see p. 52). The triple bond can be either converted to a CIS- or frans-configurated double bond (M.A. Adams, 1979) or be hydrated to give a ketone (see pp. 52, 57, 131). 

Treatment of cyclic carbonates of 1,2-diols with thiocyanate ion at temperatures of 100 °C or higher yields thiiranes (Scheme 145) (66CRV297, 75RCR138). Thiourea cannot replace thiocyanate satisfactorily, and yields decrease as the carbonate becomes more sterically hindered. The reaction mechanism is similar to the reaction of oxiranes with thiocyanate (Scheme 139). As Scheme 145 shows, chiral thiiranes can be derived from chiral 1,2-diols (77T999, 75MI50600). 

An oxirane formed by the direct epoxidation, which usually occurs from the sterically least hindered side of the molecule, can be converted into its stereoisomer by a reaction sequence which involves the diaxial opening (in acetic acid at 100° for 2 hr) of the epoxide to a diol mo noacetate. Subsequent mesylation followed by treatment with base gives the inverted oxirane, as shown for the sequence (69) (70) (71) (72). ... 

The procedure is outlined in Scheme 8.33, starting from the generic allylic alcohol 125. SAE on 125 would provide epoxide 126, which could easily be transformed into the unsaturated epoxy ester 127 by oxidation/Horner-Emmonds olefmation (two-carbon extension). This operation makes the oxirane carbon adjacent to the double bond more susceptible to nucleophilic attack by a hydride, so reductive opening (DIBAL) of 127 provides, with concomitant ester reduction, diol 128. Pro-... 

Pyridyl oxiranes (Figure 6.64) were stereoselectively hydrolyzed by EH from A. niger to give the (S)-epoxide and the (R)-diol [183]. The reactions proceed with high regio- and enantioselectivity on the least hindered carbon atom of the... 

Epoxides (oxirans) and 1,2-diols can also be looked upon as disguised ketones capable of being unmasked by acids. Since its development by Spencer et al49 the idea has been utilized by several other groups who used protic acids in work aimed at syntheses of methyl lambertianate,50 a rare furanoid fatty acid from an Exocarpus species,51 and a terpenoid furan,... 

When 1,2-diols are subjected to the same reaction conditions required for the formation of sulphonic esters, oxiranes are produced [27]. Presumably, the mono ester is initially formed and, under the basic conditions, intramolecular elimination occurs to produce the oxirane. Partial hydrolysis and ring-closure of a,p-di(tosyloxy) compounds under basic phase-transfer catalytic conditions provides a convenient route to carbohydrate oxiranes [e.g. 28, 29]. Oxiranes have been produced by an analogous method via carbonate esters from partially protected carbohydrates [30],... 

Turning to enzymatic hydration, we see from the data in Table 10.1 that phenanthrene 9,10-oxide Fig. 10.10, 10.29) is an excellent substrate for epoxide hydrolase. Comparison of enzymatic hydration of the three isomeric phenanthrene oxides shows that the Vmax with the 9,10-oxide is greater than with the 1,2- or the 3,4-oxide the affinity was higher as well, as assessed by the tenfold lower Km value [90]. Furthermore, phenanthrene 9,10-oxide has a plane of symmetry and is, thus, an achiral molecule, but hydration gives rise to a chiral metabolite with high product enantioselectivity. Indeed, nucleophilic attack by epoxide hydrolase occurs at C(9) with inversion of configuration i.e., from below the oxirane ring as shown in Fig. 10.10) to yield the C-H9.S, 10.S )-9,10-dihydro-9,10-diol (10.30) [91],... 

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]. 

One of the first applications of the microbial hydrolysis of epoxides for the synthesis of a bioactive compound is based on the resolution of a 2,3-disub-stituted oxirane having a cis-configuration (Scheme 14). Thus, by using an enzyme preparation derived from Pseudomonas sp., the (91 ,10S)-enantiomer was hydrolyzed in a frans-specific fashion (i.e. via inversion of configuration at C-10) yielding the 9R,10R)-threo-diol. The remaining (9S,101 )-epoxide was converted into (-1-)-dispar lure, the sex pheromone of the gypsy moth in >95% ee [101]. 

Another illustration of the use of such a biocatalytic approach was the synthesis of either enantiomer of a-bisabolol, one of these stereoisomers (out of four) which is of industrial value for the cosmetic industry. This approach was based on the diastereoselective hydrolysis of a mixture of oxirane-diastereoiso-mers obtained from (R)- or (S)-limonene [68]. Thus,starting from (S)-hmonene, the biohydrolysis of the mixture of (4S,81 S)-epoxides led to unreacted (4S,8S)-epoxide and (4S,8i )-diol. The former showed a diastereomeric purity (> 95%) and was chemically transformed into (4S,8S)-a-bisabolol. The formed diol... 

The endiol-cyclic sulfite 19 obtained by oxidation of the dihydropyran 18 affords a trans-fused bipyran <99TL2235> and this system is also accessible from the sulfonyl-stabilised oxirane 20 (Scheme 6) <99TL8019>. 

Cyclic cyanohydrin ethers, 6-alkyl-2,2-dimethyl-l,3-dioxane-4-carbonitriles 1, are easily available from silylated aldols. Deprotonation of 1 and subsequent alkylation gives, v+ -4,6-disubsti-tuted 2,2-dimethyl-l,3-dioxane-4-carbonitriles 2 in good yields in a highly diastereoselective reaction48. Primary bromoalkanes and oxiranes have been used as alkylating reagents. Reduction of the alkylation products 2 afforded the protected, vj. -l,3-diols 3 with complete retention of configuration (see Section D.2.I.). 

On treatment with sodium bis (2-methoxyethoxy)aluminium hydride (Scheme 16), 122 gave the aldehyde 123, which was converted by standard synthetic operations, into the methyl-O-benzylester 124. Acid hydrolysis of 124 followed by allylic epoxidation of the diol furnished the p-oxirane 125. On heating 125 in water containing sodium benzoate a remarkable chain of chemical events took place that resulted in the generation of (+)-pancratistatin (94) in 2% overall yield starting from bromobenzene. 

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