Synthesis of epoxides from alkenes

SECTION 10.2. ADDITION OF OXYGEN AT CARBON-CARBON DOUBLE BONDS 

Epoxidation Followed by Ring Opening to an Allyl Alcohol 

Alumina has been found to be a useful catalyst for nucleophilic ring opening of epoxides by amines, alcohols, carboxylic acids, and thiols. These reactions are believed to be concerted processes in which both the alumina and nucleophile participate with the alumina acting as a Lewis acid. In unsymmetrical epoxides, the reactions show a modest (1 2-l 10) selectivity for attack by the nucleophile at the less hindered carbon of the epoxide. 

Double bonds having oxygen and halogen substituents are susceptible to epoxida-tion, and the reactive epoxides that are thereby generated serve as intermediates in some useful synthetic transformations. Vinyl chlorides furnish haloepoxides, which can rearrange to a-haloketones  

3 -epoxypropyl jS-glycoside of di(N-acetyl-D-glucosamine) where R is N-acetyl glucosamine specifically inactivates hen lysozyme and several other bird lysozymes (Maron et al. 1972). The residue of hen lysozyme specifically modified by VIII is asp. 52 (Eshdat et al. 1973). X-ray analysis reveals that the two glucosamine residues of the affinity label occupy subsites B and C of the substrate binding cleft (Moult et al. 1973). The synthesis of the affinity label was accomplished by the most general procedure for the synthesis of epoxides, namely oxidation of alkenes with peroxyacids. 

The starting materials for the synthesis of the various derivatives used in these studies were the appropriate allyl glycosides which have the general structure indicated in (X). Allyl derivatives may be the most general precursor for the synthesis of epoxides. The various allyl glycosides were synthesized by the following procedure of Thomas (1970)forallyl-2-acetamido-3,4-6-tri-0-acetyl-2-deoxy-/ -D-glycopyra- 

As a guide to the stability of epoxides, the procedure used for the deacetylation of the above glycosides is presented. The appropriate epoxypropyl glycoside was suspended in dry methanol (10% w/v) with rapid magnetic stirring, and treated with methanolic barium methoxide to give a final concentration of 0.02 M. After dissolution, precipitation of the 0-deacetylated products began within 5 min. After 12 hr at 3°C, the solids were collected, and crystallized from aqueous acetone. 

Ross (1950) has provided a simple procedure to determine the reactivity of epoxides which may be useful in monitoring their stability if they are to be used in affinity labels. Addition of an epoxide to a neutralized solution of 0.2 M sodium thiosulfate in 50% acetone containing phenolphtalein followed by heating causes the generation of a pink color which can be reversed by addition of 0.2 N acetic acid from a burette. When no further OH is produced upon heating, the volume of acetic acid used is a measure of the titer of epoxide present. 

According to Ross (1950), the half-life of epoxides in water is about 100 hr. Acid catalyzed decomposition reactions do not take place rapidly until the pH is below 4.2. 

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Scheme 12.11. Synthesis of Epoxides from Alkenes Using Peroxy Acids...

Figure 4.20 Continuous removal of product by stripping synthesis of epoxides from alkenes applying a batch process with resting cells or a fermenter connected to absorption, extraction and distillation...

Both chemical and enzymatic synthetic methods for the asymmetric oxidation of the carbon-carbon double bond have been developed [46], but the area of carbon-carbon double bond oxidations has been shaped by the breakthrough discovery of asymmetric epoxidation of allylic alcohols with the Katsuki-Sharpless method [47]. Catalytic asymmetric synthesis of epoxides from alkenes by Jacobsen... 

The most common laboratory method for the synthesis of epoxides from alkenes is oxidation with a peroxycarboxylic acid (a peracid), RCO3H. One peracid used for this purpose is peroxyacetic acid ... 

The reaction between an aldehyde and a carbon nucleophile, such as a sulfur ylide, constitutes an alternative approach to the synthesis of epoxides. Since alkenes, which are the normal epoxidation substrates, are often formed from aldehydes, this approach can be highly efficient. On the other hand, the synthesis of appropriate carbon nucleophiles usually requires additional steps. 

Olefins are very important industrial raw materials, and much effort has been devoted toward using them as substrates in asymmetric synthesis [811, 812, 853], The industrial synthesis of nonracemic a-aminoacids by catalytic hydrogenation was ore of the first important uses of olefins in asymmetric synthesis [859], Today, the Sharpless epoxidation of allylic alcohols [807, 808, 809] is one of the most popular methods in asymmetric synthesis. The importance of pyrethrinoid pesticides, bearing a cyclopropane skeleton, justifies the efforts devoted to the asymmetric synthesis of cyclopropanes from alkenes [811,812, 937],... 

Synthesis of Epoxides from Haiohydrins (Section 11.8C) Formation of the halohydrin and the following intramolecular Sf 2 reaction are both stereoselective (the configuration of the alkene is retained in the epoxide) and stereospecific (for alkenes that show ds, trans isomerism, the configuration of the epoxide depends on the configuration of the alkene). 

Historically, the asymmetric synthesis of epoxides derived from electron-poor alkenes, for example a, (3-unsaturated ketones, has not received as much attention as the equivalent reaction for electron-rich alkenes (vide supra). However, a recent flurry of research activity in this area has uncovered several... 

The formation of epoxides is a well-investigated synthetic problem and two approaches, either from a double bond system by transfer of oxygen starting from an alkene, or carbene transfer to a carbonyl group, have attracted much interest. The use of the CpFe(CO)2+ fragment was also investigated by Hossain and coworkers with a view to its use for the synthesis of epoxides (Scheme 9.15) [30, 31]. However, the CpFe(CO)2+ fragment not only catalyzes the carbene transfer, but also acts as... 

Ylide (1) adds selectively to the least hindered side of a spirocyclic cyclobutanone to afiord epoxide (10) as the sole product in 65% yield (Scheme 3). Where only steric factors are likely to be important, complementary stereochemical results are often possible by methylene addition to a carbonyl group or alternatively, by carrying out an epoxidation reaction on the derived alkene. In each case, the reagent approaches a double bond from the same stereochemical face. This point is nicely illustrated by the synthesis of epoxide (11). 

The peroxy intermediate (1) is an excellent reagent for the synthesis of acid-sensitive benzylic epoxides from alkenes, the oxidation of benzylic CH2 to C=0, and the chemoselective oxidation of alkene sulfoxides to alkene sulfones. It is noteworthy that the reactions are carried out under mild conditions (—35 °C). 

The most important oxirane syntheses are by addition of an oxygen atom to a carbon-carbon double bond, i.e. by the epoxidation of alkenes, and these are considered in Section 5.05.4.2.2. The closing, by nucleophilic attack of oxygen on carbon, of an OCCX moiety is dealt with in Section 5.05.4.2.1 (this approach often uses alkenes as starting materials). Finally, oxirane synthesis from heterocycles is considered in Section 5.05.4.3 one of these methods, thermal rearrangement of 1,4-peroxides (Section 5.05.4.3.2), has assumed some importance in recent years. The synthesis of oxiranes is reviewed in (B-73MI50500) and (64HC(19-1U). 

In a formal synthesis of fasicularin, the critical spirocyclic ketone intermediate 183 was obtained by use of the rearrangement reaction of the silyloxy epoxide 182, derived from the unsaturated alcohol 180. Alkene 180 was epoxidized with DMDO to produce epoxy alcohol 181 as a single diastereoisomer, which was transformed into the trimethyl silyl ether derivative 182. Treatment of 182 with HCU resulted in smooth ring-expansion to produce spiro compound 183, which was subsequently elaborated to the desired natural product (Scheme 8.46) [88]. 

The application of 1,3-dipolar cycloaddition processes to the synthesis of substituted tetrahydrofurans has been investigated, starting from epoxides and alkenes under microwave irradiation. The epoxide 85 was rapidly converted into carbonyl ylide 86 that behaved as a 1,3-dipole toward various alkenes, leading to quantitative yields of tetrahydrofuran derivatives 87 (Scheme 30). The reactions were performed in toluene within 40 min instead of 40 h under classical conditions, without significantly altering the selectivi-ties [64]. 

Synthesis of cyclic carbonates from alkenes epoxidation-cum-cycloaddition... 

To date, the most frequently used ligand for combinatorial approaches to catalyst development have been imine-type ligands. From a synthetic point of view this is logical, since imines are readily accessible from the reaction of aldehydes with primary or secondary amines. Since there are large numbers of aldehydes and amines that are commercially available the synthesis of a variety of imine ligands with different electronic and steric properties is easily achieved. Additionally, catalysts based on imine ligands are useful in a number of different catalytic processes. Libraries of imine ligands have been used in catalysts of the Strecker reaction, the aza-Diels-Alder reaction, diethylzinc addition, epoxidation, carbene insertions, and alkene polymerizations. 

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