Epoxide, reductive opening

Xiong used an acid-mediated epoxide-opening cascade to prepare a penta-tetrahydrofuran structure for the synthesis of the tetra-tetrahydrofuran natural product omaezakianol (152 Scheme 4.31) [66]. This allowed for the synthesis of cyclization precursor 153 from squalene. Exposing 153 to CSA provided pentacycle 154 in a 21% yield that includes the formation of the epoxides. Reductive opening resulted in... 

Reductive Opening of a 17a,20-Epoxide 17a,20-Oxidopregn-4-en-3-one (0.7 g) in 90 ml of dioxane (previously distilled over sodium) is added gradually to a solution of 1 g of lithium aluminum hydride in 50 ml of dry ether. 

The procedure is outlined in Scheme 8.33, starting from the generic allylic alcohol 125. SAE on 125 would provide epoxide 126, which could easily be transformed into the unsaturated epoxy ester 127 by oxidation/Horner-Emmonds olefmation (two-carbon extension). This operation makes the oxirane carbon adjacent to the double bond more susceptible to nucleophilic attack by a hydride, so reductive opening (DIBAL) of 127 provides, with concomitant ester reduction, diol 128. Pro-... 

Reductive opening of the oxirane ring of 193 with lithium aluminum hydride, and acetylation, provided compound 194. Epoxidation of 194 with mCPB A gave the epoxide 195. Opening of the oxirane ring with acetate ions, followed by acetylation, gave the tetraacetate 196, or, by exhaustive acetylation with acetic anhydride-DMAP, the pentaacetate 189. Compounds 196 and 189 were readily transformed into 190 by hydrolysis. " ... 

Scheme 5.7 illustrates these and other applications of the hydride donors. Entries 1 and 2 are examples of reduction of alkyl halides, whereas Entry 3 shows removal of an aromatic halogen. Entries 4 to 6 are sulfonate displacements, with the last example using a copper hydride reagent. Entry 7 is an epoxide ring opening. Entries 8 and 9 illustrate the difference in ease of reduction of alkynes with and without hydroxy participation. 

Epoxides can also be reductively opened to form a radical. An example of an intramolecular cyclization of such a radical has recently been reported <06TL7755>. Treatment of 40 with Cp2TiCl generates an intermediate alkoxy radical, which then adds to the carbonyl of the formate ester. The product, 41, is formed as a 2 1 mixture of isomers at the anomeric carbon. This reaction is one of the first examples of a radical addition to an ester. The major byproduct of this reaction is the exo-methylene compound, 42, arising from a P-hydrogen elimination. 

With an operating catalytic cycle for the reductive opening of epoxides at hand, we decided to investigate the preparatively more important formation of carbon—carbon bonds. Inter-molecular addition reactions to a,(3-unsaturated carbonyl compounds have been described for the stoichiometric process of Nugent and RajanBabu [5], The general concept behind the catalytic conditions is outlined in Scheme 12.16. 

Table 12.2. Reductive opening of epoxide 1 with various titanocene complexes.

To confirm the trends observed with 10, we also investigated the behavior of epoxide 17 under ET conditions. Here, a tertiary radical would be formed after reductive opening that is more persistent than the secondary radical obtained from 10, as depicted in Scheme 8. The results of the opening reactions are summarized in Table 3. 

In summary, our studies have revealed that Sml2 is not a suitable reagent for the reductive opening of epoxides. The high Lewis acidity of this metal combined with the high nucleophilicity of the iodide ions leads to the for-... 

Using the reductive epoxide ring opening of the intermediate hydroxyepoxides with Red-Al the sequence leads then to polyols 10 and IT. On the other hand, since... 

Treatment of the /3-keto ester 220 with sodium ethoxide at elevated temperature triggered off an epoxide ring opening by / -elimination that was followed by the desired Knoevenagel condensation to afford the tricyclic product 206 (Scheme 34). The enone moiety in the intermediate 221 did not show a propensity for deprotonation and, therefore, the ketone carbonyl function of the enone moiety was available for a Knoevenagel condensation. The reduction of the p-keto ester (206) to the corresponding diol was the next objective. Treatment of the TES-protected -keto ester (TES-206) with DIBAH afforded the diastereomeric diols 222 and 223 in a moderate diastereoselec-tivity in favour of the undesired diastereomer 222. The diastereomers were separated and the undesired diastereomer 222 was epimerized to 223 by a sequence that consists of Mitsunobu inversion and benzoate ester reduction [98, 99]. 

Lactol 128 has been converted into a variety of racemic C-nucleosides. The unstable aldehyde 130 was prepared from 128 by way of oxazolidine 129. Lactone 131 was also derived from 128 and used as starting material in the synthesis of racemic C-nucleosides. Adducts 77 + 77 were transformed into epoxide 132. Opening of the epoxide, followed by ozonolysis and reduction allowed one to... 

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