2,3-epoxy alcohols hydride, addition

A synthetically useful diastereoselectivity (90% dc) was observed with the addition of methyl-magnesium bromide to a-epoxy aldehyde 25 in the presence of titanium(IV) chloride60. After treatment of the crude product with sodium hydride, the yy -epoxy alcohol 26 was obtained in 40% yield. The yyn-product corresponds to a chelation-controlled attack of 25 by the nucleophile. Isolation of compound 28, however, reveals that the addition reaction proceeds via a regioselective ring-opening of the epoxide, which affords the titanium-complexed chloro-hydrin 27. Chelation-controlled attack of 27 by the nucleophile leads to the -syn-diastereomer 28, which is converted to the epoxy alcohol 26 by treatment with sodium hydride. 

The overall transformation of alkenes to alcohols that is accomplished by epoxi-dation and reduction corresponds to alkene hydration. Assuming a nucleophilic ring opening by hydride addition at the less-substituted carbon, the reaction corresponds to the Markovnikov orientation. This reaction sequence is therefore an alternative to the hydration methods discussed in Chapter 4 for converting alkenes to alcohols. 

Wharton reaction (1, 439 8, 245). This reaction can also be conducted under free-radical conditions of reduction of thiocarbonylimidazolide derivatives of a,/l-epoxy alcohols with tri-n-butyltin hydride.17 In some cases, inverse addition is necessary to prevent further rearrangement of the allylic alcohol initially formed. Yields are around 50-60%. The modification is not useful in the carbohydrate field, where very complex product mixtures are formed. 

The reverse regiocontrol, giving 1,2-diols, is observed with DIBAL-H (diisobutylaluminum hydride). The remarkable effect of titanium tetraisopropoxide as an additive to lithium borohydride has also been reported. In this reaction benzene is a better solvent than THF, probably because a Ti complex using both oxygens in epoxy alcohols is formed in benzene before the hydride attack. Other metal hydrides used include sodium hydrogen telluride (NaHTe) and an ate complex derived from DIBAL-H and butyllithium, both of which reduce epoxides to alcohols, although they have been tested with only a small number of examples. In the former case the reaction may proceed via a 2-hydroxyalkyltellurol intermediate. 

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... 

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