Cyclic 2,3-disubstituted epoxides

Reductive cleavage of epoxides is successful primarily for terminal epoxides 1,2-disubstituted epoxides give alkenes by elimination of Li20, unless they are cyclic, in which case the secondary organolithium may be trapped with stereoselectivity at the former C-0 bond ... 

As expected on the basis of the epoxy halide results just discussed, die displacement of a primary tosyl-ate can be smoothly accomplished in the presence of an adjacent disubstituted epoxide,and this reaction has been utilized in syntheses of disparlure and of other insect pheromones. On the other hand, a recently reported reaction of a cyclic glucopyranose-derived epoxide with either Me2CuLi or MeMgCl-CuBr afforded in high yield the desired ring-opened product, leaving intact an exocyclic primary mesylate. 

Terminal epoxides react slowly with sulfonyl carbanions such as the homoenolate equivalent (1) (eq 4). With disubstituted epoxides and cyclic epoxides the reactions are slower still. For example, reaction of the lithio derivative of ethyl phenyl sulfone with cyclopentene oxide occurs in excellent yield (98%) after 10 h reflux in toluene. It has been reported that, in some cases, the addition of a Lewis acid (magnesium bromide, boron trifluoride etherate, 4 titanium tetraisopropoxide, MeOAl(i-Bu)2 ) or HMPA iirproves the yield dramatically. 

Terashima et al. 231) reported an asymmetric halolactonization reaction. This highly stereoselective reaction permits the synthesis of intermediates for the preparation of chiral a,a-disubstituted a-hydroxycarboxylic acids (227)231c), a-hydroxyketones (228) 231c), functionalized epoxides (229) 231d,e) and natural products 231h,j). Only amino acids have so far been used as a source of the chiral information in the asymmetric halolactonization reaction. Again, the best results have been obtained by using cyclic imino acid enantiomers, namely proline. 

The alicyclic epoxide, limonene oxide, which is obtained from a renewable resource has shown modest activity compared to CHO for reaction with C02 to provide a copolymer. This significant decrease in reactivity is presumably due to the steric influence of a disubstitution at one of the ipso carbon centers. Of course, in either highly selective reaction, where complete formation of copolymer or cyclic carbonate occurs, the process displays 100% atom economy. The environmental attractiveness of this process is further enhanced by the fact that reactions are generally carried out in the absence of an organic cosolvent, that is, in C02-swollen epoxide solutions. 

The cyclic substrate 32 and other disubstituted olefins such as 35a were oxidized in sc C02 to give the corresponding epoxides with reasonable rates (>95% conversion in less than 18 h) and excellent selectivities (>98%) under otherwise similar reaction conditions (Loeker and Leitner, 2000). It is important to note, however, that no addition of a metal catalyst was required in the supercritical reaction medium. Detailed control experiments revealed that the stainless steel of the reactor walls served as efficient initiator for the epoxidation under these conditions. Terminal olefins 35b,c were oxidized with somewhat reduced rates and either epoxidation or vinylic oxidation occurred as the major reaction pathway depending on the substrate (eq. 5.11). Apart from providing the first examples for efficient and highly selective oxidation with 02 in sc C02 (earlier attempts Birnbaum et al., 1999 Loeker et al., 1998 Wu et ah, 1997), this study points to the possible importance of wall effects during catalytic reactions in this medium (see also Christian et ah, 1999 Suppes et ah, 1989). 

It was shown that cyclization of the hydroxy epoxides promoted by Eu(fod)3 (fod = 6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato) proceeds via an exo-mode, providing the corresponding disubstituted eight- and nine-membered cyclic ethers in excellent yields <2003TL2709>. This method was used for the stereoselective total synthesis of (+)-laurallene, as indicated in Scheme 19 <2003TL3175>. 

Disubstituted peroxides are cleaved reductively by the same reagents as are used for hydroperoxides. The usual products are alcohols derived from the two substituents, but considerable selectivity is possible with some substrates. This is illustrated by the reduction of cyclic endoperoxides of the general formula (50) these compounds are available from the cycloaddition of singlet oxygen to cyclic conjugated dienes. The reduction of such compounds provides a good method of synthesis of cis-1,4-diols, which can be formed with retention of the double bond or with reduction of it (Scheme 29). It is also possible to prepare unsaturated epoxides by reduction with triphenylphosphine or other phosphorus(III) reagents. 

Cyclic and acyclic cfs-disubstituted olefins have traditionally been the best substrates for the [Mn(salen)]-catalyzed epoxidation reaction. A predictive stereochemical mnemonic for the epoxidation of ds-olefins by catalyst 8 is provided in Fig. 10 [19]. Especially high enantioselectivity is observed in the epoxidation of... 

The cyclic sulfites or sulfates thus obtained can be employed as synthetic equivalents of epoxides, which can react with a number of nucleophiles often, they are more reactive than the oxirane analogs and thus can lead to disubstitution products <1997AHC89, 1994CRV2483>. The cyclic sulfate 42, for example, has been used as a double electrophile in a [3+3] annulation procedure, which combines C-C-C and N-C-C moieties (Scheme 14)... 

In 2010, Tanaka s group investigated whether a chiral cyclic a-amino acid included in an oligopeptide chain could catalyze the epoxidation of different enones with high enantiomeric excess. They demonstrated that the a-helical secondary structure of the peptide catalyst is directly related to the chosen a,a-disubstituted amino acid [134]. Thus, they found that 5 mol% of a-helical nonamer 92 with urea-H2O2 as oxidant can catalyze the reaction with ee > 95% (Scheme 12.18). 

This catalytic system provides high enantioselectivities for a range of epoxides (Figure 19.2), including those derived from trisubstituted and traus-1,2-disubstituted alkenes, with complete stereospecificity (retention of the alkene geometry in the epoxide product) [17]. The reaction has been shown to be chem-oselective for the alkene of enynes [18], provided monoepoxides upon reaction with conjugated trans-dienes [19] and afforded up to 93% ee for the asymmetric epoxidation of fluoro-olefins [20]. However, decreased enantioselectivity was observed for both cis- and terminal alkenes. The catalytic system has also been applied to the resolution and desymmetrization of cyclic trisubstituted alkenes [21]. 

Pathak et al. developed a metal-free route to 1,5-disubstituted 1,2,3-triazolylation at Cl, C2, C3, C4, andC6 of pyranosidesgenerating 1,5-triazolylated monosaccharides and 1,5-triazole-linked disaccharides for the first time. Exo-cyclic vinyl sulfones 117 and 118 derived from styrene epoxide and monotosylated glycerol were reacted with six different azidopyranosides 116 to generate 1,5-disubstituted 1,2,3-triazoles 119 and 120 (Scheme 4.45) [46]. The reaction was... 

---