Stereoselective Epoxide Synthesis

The ability to access stereochetnically pure products from epoxide cascade reactions is critically dependent upon the capacity to prepare stereochemically pure epoxides. This section details the advances that make stereoselective synthesis through epoxide cascade reactions possible. 

This utility of this procedure was substantially enhanced by the observation that adding tartrate esters to the reaction mixture enhances the rate of the oxidation (ligand-accelerated catalysis) [45]. This also makes the oxidant chiral and enantiomerically pure, creating the possibility of directed asymmetric oxidation. This was realized by using 

SCHEME 4.17 Henbest s hydrogen-bonding directed epoxidation. 

Yamamoto took a similar approach for the epoxidation of allyUc and homoallyhc alcohols (Schane 4.20). This process employed chiral hydroxamic acid ligand 101 to induce stereocontrol and VO(OtPr)3 to serve as the Lewis acid [49]. ( )-HomoaIlyhc alcohol 102 was converted to epoxide 103 

SCHEME 4.20 Directed asymmetric homoallylic alcohol epoxidation. 

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Scheme 28 shows a stereoselective epoxide synthesis, which proceeds by way of a tin enolate. Similarly, the tin enolates derived from triphenyltin chloride and lithium enolates, R HC=C(OLi)R react with alkyl and aryl aldehydes R CHO without the necessity for a catalyst to give mainly the erythro-products (139) in good yield. ... 

The numerous methods for stereoselective epoxide synthesis and the extensive base of knowledge regarding regiocontrol in intramolecular opening reactions combine to create numerous opportunities for natural product synthesis. This section will illustrate many of the routes that have exploited this approach. These routes are often called biomimetic syntheses due to... 

A stereoselective total synthesis of dendrobatide toxin 251 D was developed by Overman et al.237) involving an epoxidation of the (S)-proline derivative (237) to furnish the oxirane (238) as major product. In their approach towards the total synthesis of the same natural product Thomas et al.238) investigated the stereoselectivity of the epoxide formation from (S)-5-acetylpyrrolidin-2-one and dimethyloxosulfonium methylide. A diastereoselectivity of d.s. 50-60% was achieved 238. ... 

Preparation of nonracemic epoxides has been extensively studied in recent years since these compounds represent useful building blocks in stereoselective synthesis, and the epoxide functionality constitutes the essential framework of various namrally occurring and biologically active compounds. The enantiomericaUy enriched a-fluorotropinone was anchored onto amorphous KG-60 silica (Figure 6.6) this supported chiral catalyst (KG-60-FT ) promoted the stereoselective epoxidation of several trans- and trisubstituted alkenes with ees up to 80% and was perfectly reusable with the same performance for at least three catalytic cycles. 

The key step in a total synthesis of cycloeudesmol (6) is a highly stereoselective epoxidation of 3 to provide 4, which can be converted into the cyclopropane 5 in quantitative yield by treatment with 3 equiv. of LDA at -780°.2... 

Because of their suitable skeletal structure trans-CHD are applicable in the synthesis of compound classes of chemical, biological, and pharmaceutical interest. Regio- and stereoselective epoxidation of either one or two double bonds of 2, for example, opens up an approach to a group of naturally occurring cyclohexane epoxides which have attracted considerable attention because of their unusual structures, biogenesis, and biological activity [15]. 

Indolines and indoles were prepared by a direct electrochemical reduction of arenediazonium salts. As a result, radical intermediates were generated from which 3,4-disubstituted tetrahydrofuran skeleta were constructed <02OL2735>. A short and stereoselective total synthesis of furano lignans was realized by radical cyclization of epoxides using a transition-metal radical source <02JOC3242>. Other preparations of tetrahydrofurans using radical cyclization include the synthesis of novel amino acids L-bis-... 

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>. 

Because it is often possible to control the stereochemical orientation of substituents on a cyclic array, Baeyer-Villiger cleavages of substituted cyclic ketones have been used extensively in the stereocon-trolled syntheses of substituted carbon chains. An asymmetric synthesis of L-daunosamine intermediate (30) from a noncarbohydrate precursor employed the cyclopentenol (28), prepared in optically pure form (95% ee) from 2-methylcyclopentadiene using asymmetric hydroboration (Scheme 8). Stereoselective epoxidation, conversion to Ae ketone and regioselective Baeyer-Villiger oxidation afforded lactone (29). 

For the synthesis of oxiranes with more complex structures, the peracid method is combined with other epoxidation procedures examples are the syntheses of ( )-crotoxirane, ( )-epicrotoxirane, and ( )-isocrotoxirane ° or the preparation of cis-trioxatris-(a)homotropylidene. o-Sulfoperbenzoic acid has been used for the stereoselective epoxidation of cholesterol. The selective epoxidation of cholest-5-en-3-one too has been examined. In the synthesis of 25-hydroxycholesterol selective epoxidation occurs on and 26 is formed. The epoxidation of olefin propellanes 27 and 28 can be achieved with MCPBA. As a consequence of the secondary orbital interaction, syn-attack is more marked in the case of 28. ° Epoxypropelladiene can be synthesized in accordance with Eq. 12. ... 

The main features of the Shirahama synthesis include the tetrahydrofuran ring expansion to afford the ring B and his incorporation of stereoselective epoxide cyclizations in accord with the... 

Next, the process chemistry for a large-scale synthesis of (+)-6a (MGS0008) is presented (see Scheme 3.2) [41], The reaction of racemic (+)-16 with TMSC1 and LHMDS, followed by dehydrosilylation with palladium acetate afforded enone ( )-2 (90% yield), which was stereoselectively epoxidized using tert-butyl hydroperoxide (TBHP) in the... 

The key steps were the same as those used for the synthesis of dolicholide (31) and dolichosterone (34) (i) chain elongation by means of organoaluminum chemistry, (ii) stereoselective epoxidation of the resulting allylic alcohol, and (iii) regio- and stereoselective cleavage of the epoxy ring. 

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