Epoxides ring synthesis

Oxirans.—Many examples of epoxide ring synthesis have appeared this year. Without doubt a great deal of effort has gone into the stereoselective syntheses of chiral epoxides, and many of the methods described may be useful for future natural product synthesis. 

The asymmetric epoxidation of electron-poor cinnamate ester derivatives was highlighted by Jacobsen in the synthesis of the Taxol side-chain. Asymmetric epoxidation of ethyl cinnamate provided the desired epoxide in 96% ee and in 56% yield. Epoxide ring opening with ammonia followed by saponification and protection provided the Taxol side-chain 46 (Scheme 1.4.12). 

In the synthesis of the bromo derivative 12 from diepoxide 11, an interesting epoxide ring-opening-ring-closure reaction is involved.5... 

The potential of such reaction sequences for the generation of molecular diversity was also demonstrated by the synthesis of a library of heterocycles. Epoxide ring-opening with hydrazine and subsequent condensation with (3-diketones or other bifunctional electrophiles gave rise to a variety of functionalized heterocyclic structures in high purity [34]. A selection based on the substrate derived from cyclohexene oxide is shown in Scheme 12.12. 

Scheme 4.10 gives some examples of application of alkyne carboalumination in synthesis. The reaction in Entry 1 was carried out as part of a synthesis of the immunosuppressant drug FK-506. The vinyl alane was subsequently transmetallated to a cuprate reagent (see Chapter 8). In Entry 2, the vinyl alane was used as a nucleophile for opening an epoxide ring and extending the carbon chain by two atoms. In Entries 3 to 5, the vinyl alane adducts were converted to vinyl iodides. In Entry 6, the vinyl alane was converted to an ate reagent prior to reaction with formaldehyde. 

Some additional examples are given in Scheme 8.6. The electrophiles that have been used successfully include iodine (Entries 2 and 3) and cyanogen chloride (Entry 4). The adducts can undergo conjugate addition (Entry 5), alkylation (Entry 6), or epoxide ring opening (Entries 7 and 8). The latter reaction is an early step of a synthesis of epothilone B. 

An alternative disconnection of homopropargylic alcohols substrates for intramolecular hydrosilylation is the opening of an epoxide with an alkynyl anion. This strategy was employed in a total synthesis of the macrolide RK-397 (Scheme 20). Epoxide ring opening serves to establish homopropargylic alcohol C with the appropriate stereochemistry. A hydrosilylation/oxidation protocol affords the diol E after liberation of the terminal alkyne. The... 

The sole synthesis (to date) offucoxanthin (5) [11,12] by Ito and co-workers [58] relied on the opposite building block scheme, i.e. the C10-dialdehyde 50 was linked with the two C15-phosphorane termini 51 and 52 (Scheme 18.17). However, several steps of this synthetic approach are hardly efficient for example, the introduction of the epoxide ring carried out in the last step furnishes mainly the non-natural diastereomer. 

Epoxide ring-opening with transfer of an sp carbon moiety was applied in a short synthesis [44] of eicosanoid 56 [45], relevant in marine prostanoid biosynthesis (Scheme 9.13). Homoallyl alcohol 55 was obtained in good yield from 54 by use of a cyano-Gilman alkenylcuprate [46]. 

Epoxides are extremely useful intermediates in organic synthesis since they react with a variety of nucleophiles suffering opening of the epoxide ring with retention or inversion of configuration at the carbon undergoing attack. Thus, the development of highly stereoselective methods for the synthesis of certain chiral epoxides, such as the methods under discussion, has enabled the asymmetric synthesis of a wide variety of 1,2-bifunctional compounds. 

The synthesis of fluoroazoles usually involves a chiral epoxide ring opening by the azole, as exemplified by the synthesis of albaconazole (Figure 8.24). 

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