Alkene Sharpless epoxidation

Fig. 12.4. Successive models of the transition state for Sharpless epoxidation. (a) the hexacoordinate Ti core with uncoordinated alkene (b) Ti with methylhydroperoxide, allyl alcohol, and ethanediol as ligands (c) monomeric catalytic center incorporating t-butylhydroperoxide as oxidant (d) monomeric catalytic center with formyl groups added (e) dimeric transition state with chiral tartrate model (E = CH = O). Reproduced from J. Am. Chem. Soc., 117, 11327 (1995), by permission of the American Chemical Society. 

Schreiber s model has also proved to be a general approach to a series of oxygenated metabolites of arachidonic acid, such as lipoxin A and lipoxin B.50 The family of linear oxygenated metabolites of arachidonic acid has been implicated in immediate hypersensitivity reactions, inflammation, and a number of other health problems. Among these metabolites, several compounds, such as lipoxin A, lipoxin B, 5,6-diHETE, and 14,15-diHETE possess 1-substituted (/ )-1 -alken-3.4-diol 84 as a common substructural moiety. Therefore, the car-binol 83 is an ideal substrate for generating compound 84 by applying Sharpless epoxidation reaction.50... 

It should be added that many other groups have contributed to the predevelopments of these inventions and also to later developments. All four reactions find wide application in organic synthesis. The Sharpless epoxidation of allylic alcohols finds industrial application in Arco s synthesis of glycidol, the epoxidation product of allyl alcohol, and Upjohn s synthesis of disparlure (Figure 14.4), a sex pheromone for the gypsy moth. The synthesis of disparlure starts with a Ci3 allylic alcohol in which, after asymmetric epoxidation, the alcohol is replaced by the other carbon chain. Perhaps today the Jacobsen method can be used directly on a suitable Ci9 alkene, although the steric differences between both ends of the molecules are extremely small ... 

Since the epoxidation of alkenes with peracids was discovered by Prilezajew in 1909 [29], epoxides have played a major role in organic chemistry and industry, providing important intermediates for the synthesis of more complex molecules. Metal-catalyzed epoxidation reactions have received much attention in recent decades since the discovery of the Sharpless epoxidation [30, 31], but most epoxides were prepared from alkenes primarily by their interaction with peracids. 

Asymmetric epoxidation of olefins is an effective approach for the synthesis of enan-tiomerically enriched epoxides. A variety of efficient methods have been developed [1, 2], including Sharpless epoxidation of allylic alcohols [3, 4], metal-catalyzed epoxidation of unfunctionalized olefins [5-10], and nucleophilic epoxidation of electron-deficient olefins [11-14], Dioxiranes and oxazirdinium salts have been proven to be effective oxidation reagents [15-21], Chiral dioxiranes [22-28] and oxaziridinium salts [19] generated in situ with Oxone from ketones and iminium salts, respectively, have been extensively investigated in numerous laboratories and have been shown to be useful toward the asymmetric epoxidation of alkenes. In these epoxidation reactions, only a catalytic amount of ketone or iminium salt is required since they are regenerated upon epoxidation of alkenes (Scheme 1). 

The development of asymmetric cyclopropanation protocols has been actively studied and in recent years remarkable progress has been made. The extent of chiral induction that can now be obtained in these reactions approaches the level of other classic catalytic asymmetric reactions on alkenes, such as catalytic hydrogenation and the Sharpless epoxidation.37... 

Sharpless epoxidation of (E)-(l,2-dialkyl)vinylsilanols 13, prepared from hydrolysis of ( )-( 1,2-dialkyl )vinyldimethylbutoxysilanes 12, gave silylepoxides 14, which were treated with Et4NF in MeCN to afford epoxides 15 in 62-70% overall yield and 44-70% ee (Scheme 6AA.6).7 The overall transformation can be considered as asymmetric epoxidation of simple internal alkenes. This approach was applied to the synthesis of a naturally occurring insect sex pheromone (+)-disparlure.7... 

The most important catalytic asymmetric syntheses include addition reactions to C=C double bonds. One of the best known is the Sharpless epoxidations. Sharpless epoxidations cannot be carried out on all alkenes but only on primary or secondary allylic alcohols. Even with this limitation, the process has seen a great deal of application. 

Thus, in cw-vic-dihydroxylations of alkenes with 0s04 tertiary amines, like pyridine, have ligand acceleration effects (this term was introduced in Section 3.4.6, using the Sharpless epoxidation as an example). 

Epoxy alcohols. A few years ago Mihelich1 was granted a patent for preparation of epoxy alcohols by photooxygenation of alkenes in the presence of titanium or vanadium catalysts. Adam et al.2 have investigated this reaction in detail and find that Ti(IV) isopropoxide is the catalyst of choice for epoxidation of di-, tri-, and tetrasubstituted alkenes, acyclic and cyclic, to provide epoxy alcohols. When applied to allylic alcohols, the reaction can be diastereo- and enantioselective. The reaction actually proceeds in two steps an ene reaction to provide an allylic hydroperoxide followed by intramolecular transfer of oxygen catalyzed by Ti(0-i-Pr)4. The latter step is a form of Sharpless epoxidation and can be highly stereoselective. 

The conversion of alkenes into epoxides is important not only because it is one of the most reliable routes leading from oxidation level 1 to level 2, but also because reactions of non-symmetrical epoxides with nucleophiles invariably proceed as an attack at the less substituted carbon with inversion of configuration. Thus, hydride reduction of epoxides represents an additional option for the preparation of alcohols (Scheme 2.62), especially valuable for the synthesis of optically pure isomers from epoxides obtained by the Sharpless oxidation. It is also of merit that as a result of alkene-epoxide conversion, a nucleophilic moiety (double bond) is transformed into an electrophilic epoxy ring. The latter... 

The Sharpless asymmetric epoxidation is an enantioselective reaction that oxidizes alkenes to epoxides. Only the double bonds of allylic alcohols—that is, alcohols having a hydroxy group on the carbon adjacent to a C=C —are oxidized in this reaction. 

The conversion of alkenes to epoxides is covered in most introductory organic chemistry texts, often exemplified by the use of m-chloroperoxybenzoic acid (MCPBA) as the epoxidizing reagent. Bradley et al. compared the enantioselective Sharpless epoxidation of geraniol with the classical MCPBA method, which gives a racemic product 21). Hoye and Jeffrey have illustrated a... 

There are many possible answers here. What we had in mind was some sort of asymmetric Die Alder reaction for the first (pp. 1228-31), an asymmetric aldol reaction for the second or e i opening an epoxide made by the Sharpless epoxidation (pp. 1239-41), asymmetric dihydroxylat on an -alkene for the third (pp. 1241-3), and perhaps asymmetric dihydroxylation on a Z-alker for the fourth. Of course, you might have used resolution or catalytic hydrogenation, or the ch pool, or any other strategy you could devise. 

Should the starting material 53 be enantiomerically pure Yes, as there is virtually no kinetic resolution. The asymmetric centre in 53 is evidently too far from the alkene that reacts by AE to have more than a minor effect on the stereoselectivity. Enantiomerically pure alcohol 53 was already available from asymmetric reduction (using CBS, see chapter 26) of the corresponding enone. Sharpless epoxidation does have limitations but it is supremely practical. 

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],... 

Neighboring group effects are important in reactions of peroxyacids, as they were with reactions of hydroperoxides. Reexamination of the epoxidation of 171 using MCPBA rather than TBHP reveals that the peroxyacid gave a 95 5 mixture of 172 and 173. Using MCPBA rather than TBHP led to a slight increase in diastereoselectivity for the reaction, although this depends on the substitution pattern of the alkene. Sharpless... 

Diaminocyclohexane [(R,R)- and ( S, S)-enantiomer] forms an imine (SCHIFF base) with 2,5-di-/ rr-butylsalicylaldehyde, which gives a chiral Mn(III) (salen) complex with Mn(II)acetate and oxygen. In contrast to the Sharpless-Katsuki protocol (p 20), this complex effects the stereoselective oxygen transfer (from oxidants, e.g. monopersulfate or NMO) to unfunctionalized alkenes (Jacobsen epoxidation [1], extended by Katsuki [2]) giving rise to enantiomeric oxiranes with 90-98% ee. 

The asymmetric epoxidation of functionalized alkenes still attracts considerable attention. Synthetic chemists continue to be in search of new and improved routes to epoxides, since they provide versatile intermediates for natural product synthesis. The topic of preparative techniques for chiral epoxides is seldom broached without the mention of the Sharpless epoxidation. Indeed, the impact of this protocol cannot be overestimated, as new applications continue to be reported. For example, linear poly(tartrate ester) ligands have been used this past year to generate a solid-supported Sharpless-type catalyst <97CC123>. 

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