Epoxides 5-alkyl-substituted

In Pd(0)-catalyzed isomerization reaction of epoxides, alkyl-substituted epoxides afford methyl ketones (path a, Scheme 11), whereas aryl-substituted epoxides give aldehydes or ketones via cleavage of the benzylic C-O bond (path b) [94]. 

Epoxide formation from chlorohydrins is marked by an increase in rate with alkyl substitution (28) as shown in Figure 1. This phenomenon has been explained on the basis that steric crowding ia the chlorohydrin is somewhat reheved as the epoxide is formed, so that the greatest rehef of strain results from ring closure of the most crowded chlorohydrin (28). 

The first step in this preparation, the epoxidation of 1,4,5,8-tetra-hydronaphthalene, exemplifies the well-known selectivity exerted by peracids in their reaction with alkenes possessing double bonds that differ in the degree of alkyl substitution.12 As regards the method of aromatization employed in the conversion of ll-oxatricyclo[4.4.1.01-6]-undeca-3,8-diene to l,6-oxido[10]annulene, the two-step bromination-dehydrobromination sequence is given preference to the one-step DDQ-dehydrogenation, which was advantageously applied in the synthesis of l,6-metliano[10]annulene,2,9 since it affords the product in higher yield and purity. 

The rate also decreases with an increase in the chain length of the alkene molecule (hex-l-ene > oct-1-ene > dodec-l-ene). Although the latter phenomenon is attributed mainly to diffusion constraints for longer molecules in the MFI pores, the former (enhanced reactivity of terminal alkenes) is interesting, especially because the reactivity in epoxidations by organometallic complexes in solution is usually determined by the electron density at the double bond, which increases with alkyl substitution. On this basis, hex-3-ene and hex-2-ene would be expected to be more reactive than the terminal alkene hex-l-ene. The reverse sequence shown in Table XIV is a consequence of the steric hindrance in the neighborhood of the double bond, which hinders adsorption on the electrophilic oxo-titanium species on the surface. This observation highlights the fact that in reactions catalyzed by solids, adsorption constraints are superimposed on the inherent reactivity features of the chemical reaction as well as the diffiisional constraints. 

T. Watabe, K. Akamatsu, Enzymatic Hydrolysis of Mono-n-alkyl Substituted Ethylene Oxides and Their Inhibitory Effects on Hepatic Microsomal Epoxide Hydrolase , Chem. Pharm. Bull. 1974, 22, 2155 - 2158. 

Alkyl-substituted olefins are also epoxidized by CPO. The oxidation of functionalized terminal olefins by CPO catalysis with fBuOOH as oxygen donor affords the corresponding epoxides in good ee values (entries 20, 22, 24-26). While cz5-substituted olefins were epoxidized by CPO with H2O2 in good to excellent enantiomeric excesses (entries 32-35), the trans compounds were poorly converted. The enantioselective CPO-catalyzed epoxidation has been intensively investigated, although examples of diastereoselective oxidations (entries 43-45) are rare. 

The epoxidation is accelerated by increasing alkyl substitution and is stereospecific as demonstrated by the retained configuration of the olefinic bond. 

In conclusion, the ability to abstract the -proton is correlated to its degree of substitution. However, substituents other than simple aUcyl groups may modify this facility of proton removal and influence the course of the -elimination. As anticipated, the presence on the adjacent carbon of the epoxide of an ally lie or benzylic group results in a dramatic enhancement of the -elimination rate and modifies its regioselectivity . As shown in Scheme 19, the rearrangement of the phenyl-substituted epoxide 34 is complete within a few minutes, whereas several hours are required in the case of the corresponding alkyl-substituted epoxide 35. 

In 1996, Enders and coworkers reported the asymmetric epoxidation of ( )-enones 91 in the presence of stoichiometric amounts of diethylzinc and (lR,2R)-A-methylpseudo-ephedrine (120) under an oxygen atmosphere to give fraw -epoxides 92 with excellent yields (94-99%), almost complete diastereoselectivity (>98% de) and with very good enantioselectivities (61-92%) (Scheme 54) . For the same reaction Pu and coworkers utilized achiral polybinaphthyl 121 as ligand (in excess) instead of the chiral aminoalcohol. For each substrate, only one diastereomer was formed, but in most cases yields were lower than observed with the Enders system. Enders catalyst shows high asymmetric induction for alkyl-substituted enones (ee 82-92%), but for substrates bearing only aromatic substituents only modest enantioselectivity was obtained (R = R = Ph ... 

The results of the dioxirane epoxidation of some 3-alkyl-substituted cyclohexenes and of 2-menthene indicate that the diastereoselectivity control is subject to the steric interactions of the dioxirane with the substituents of the substrate, while the size of the dioxirane substituents has only a minimal effect . In the favored transition structure, the alkyl groups of the dioxirane cannot interact effectively with the substituents at the stereogenic center of the chiral alkene . ... 

Epoxides also participate in the Ritter reaction with nitriles. An investigation of the ring opening of several alkyl-substituted glycidic esters and amides 181 showed that this transformation occurs with inversion and is completely regiospecific. ° Esters appeared to be somewhat more reactive than amides. However, phenyl-substituted glycidic esters and amides 184 are almost totally nonstereoselective. In addition, the oxazolines 186 are isolated in low yield due to the propensity of intermediate 185 to generate an aldehyde byproduct 187 (Scheme 8.53). 

Generally monosubstituted and dx-l,2-disubstituted epoxides are good substrates for EH while tri-, tetra or tra s-l,2-disubstituted ones are poor or non-substrates. Resolutions of epoxides using microsomal epoxide hydrolases, mEHs show that cis-2-alkyl substituted styrene oxides gave very high E-values when R=Me or Et (Figure 2.18a). A series of cis-... 

Table 6.12 Enantioselective catalytic epoxidation of aryl- and alkyl-substituted a,/l-enones using a (i )-BINOL-zinc catalyst (see Figure 6.13).

Asymmetric epoxidation.1 Simple, unfunctionalized olefins are epoxidized at 20 in nitrobenzene to (R)-cpoxidcs with 15-35% ce. Chemical yields are 70%. Alkyl substitution increases the rate of epoxidation, but steric hindrance decreases the asymmetric induction. 

Oxidation of Other Arenes. Aromatic compounds with longer alkyl side chains can be converted to ketones or carboxylic acids. All the previously discussed reagents except Cr02Cl2 usually afford the selective formation of ketones from alkyl-substituted arenes. Oxidation with Cr02Cl2 usually gives a mixture of products. These include compounds oxidized in the P position presumably formed via an alkene intermediate or as a result of the rearrangement of an intermediate epoxide.110,705... 

Among the many alkyl-substituted epoxides that have hi n reported to undergo hydration under various conditions are propylnm oxide, isobutylene oxide, 1,2-epoxybutone, trimethylethylene oxide, and others-. . . , jtf, i w. . shown in JSq, (50 ). 

Several simple alkyl-substituted epoxides containing one c more polar atomB in the vicinity of the epoxide ring (Eqs. BIG and 818) have been hydrated to corresponding i)2-diolB.2. . .wMi>M - 1M1 Two of these in particular, epichlorohydrin and glycidol, have figured prominently in the now classic kinetic study of Breasted and co-workers,24 and in the more recent investigation of Rosa.14 1... 

The Htereoohemic Uy specific character of the reaction of amimv. with simple alkyl-substituted epoxides was established by Dickey and co-workers in an investigation of ammonia addition to ci - ami fraiw-2,3- poxybutane. Products of this condensation were found to tv threo- and eryiW3-amino-2-butanol respectively (Eq. 618). 

Among alkyl-substituted ethylene oxides known to umletrn cleavage on treatment with sodium sulfite are propylene oxide, isobutylene oxide, 1,2-epoxybutane, 1,2-epoxyoctane, and 2,3-cpow-butane.1 75 These reactions with sodium sulfite constitute the bani-, ffrail analytical method developed by Swan1875 for the estimation <[Pg.179]

Among other simple alkyl-substituted epoxides eithct cleaved directly with acetic acid, or assumed to exist as intermediates in the conversion of corresponding olefins into 1,2-dkit... 

Variously alkyl-substituted acyclic olefins (Eq. fij have been reported to yield epoxides on treatment with perbcnxoic arid, snob as ethylene itself,17" l-heptene,10 3-hcptene, 2,4.4-frimethyl-1 -pentene174 2,4,4-t7imethyl 2pcntene)873 2,3-djmethy)-2-bntene,14"- 774 and 1,1-dineopentylethylene ... 

Condensation of Grignard reagents with alkyl-substituted ethylene oxides is fairly complex, particularly if the epoxides involved are asymmetric and massively substituted. The reaction course depends also on the structure of the Grignard reagent, and obviously on experimental conditions used for the condensation. 45 ... 

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