Epoxide opening hydroxyester

It is generally accepted that the NCS chromophore intercalates into DNA via its naphthoate side chain, which positions the rest of the molecule within the minor groove [58-60]. Another role for the a-hydroxynaphthoate has been suggested in the activation of NCS chromophore (Scheme 7-9) [61]. Here, the hydroxyester participates in epoxide opening and cumulene formation. Again, the three-dimensional solution structure of intact NCS provides invaluable information, showing that this naphthoate is kept well away from the bicyclic core until the chromophore is released from the apoprotein [42]. 

When the epoxyester 73 - prepared from the standard epoxyalcohol by oxidation and Wittig-Horner chain elongation - was treated with trimethylalu-minum, a regioselective opening of the epoxide yielded hydroxyester 74, which after protection and DIBAH reduction was ready for a Sharpless-epoxidation... 

A new epoxide inversion method has been developed which uses cesium propionate as a key reagent to promote nucleophilic ring opening, initially providing a mixture of regio-isomeric hydroxyesters (e.g. 70 71). Subsequent mesylation of the hydroxylic groups in the crude reaction mixture, followed by treatment with potassium carbonate, provides the inverted epoxide (R.K-69) <02TL4111 >. 

In the presence of ethanol, butanolides 149 or 150 undergo mild cleavage with tri-methylsilyl iodide to form the iodohydrin 159 in good yield. Cyclization of 159 to epoxide 160 under basic conditions (e.g., sodium carbonate) leads to isomerization within 5 min, but use of silver oxide affords 160 with no racemization. Opening the epoxide with cuprates furnishes j -hydroxyesters 161 with >99% ee (Scheme 21) [57]. The scope of this reaction can be extended to include cuprates derived from substituted vinyl halides. 

Heterocycles may also be carbonylated, to give either ring-expanded heterocycles, or ring-opened products. These include epoxides (Scheme 4.29), aziridines (Scheme 4.30), ° oxetanes (Scheme 4.31) and azetidines (Scheme 4.32). The cobalt-catalysed carbonylation of epoxides provides a short route to (3-hydroxyesters 4.73 (Scheme 4.29). These useful synthetic building blocks are often obtained in enan-tiomerically enriched form by the asymmetric reduction of P-ketoesters. As many epoxides are readily available in very high e.e., the carbonylation chemistry provides a useful alternative route. 

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