Acetonide from carbonate group

In all cases examined the ( )-isomers of the allylic alcohols reacted satisfactorily in the asymmetric epoxidation step, whereas the epoxidations of the (Z)-isomers were intolerably slow or nonstereoselective. The eryfhro-isomers obtained from the ( )-allylic alcohols may, however, be epimerized in 95% yield to the more stable tlireo-isomers by treatment of the acetonides with potassium carbonate (6a). The competitive -elimination is suppressed by the acetonide protecting group because it maintains orthogonality between the enolate 7i-system and the 8-alkoxy group (cf the Baldwin rules, p. 316). 

Unique chemistry is associated with the cyclopentenone all five carbon atoms can be functionalized, and the endo-methyl groups of the acetonide assure clean stereoselective addition of the alkenylcopper reagent from the convex side. The use of the acetonide group to control enolate regioselectivity and to mask alcohols should be generally applicable. 

Compatibility of asymmetric epoxidation with acetals, ketals, ethers, and esters has led to extensive use of allylic alcohols containing these groups in the synthesis of polyoxygenated natural products. One such synthetic approach is illustrated by the asymmetric epoxidation of 15, an allylic alcohol derived from (S)-glyceraldehyde acetonide [59,62]. In the epoxy alcohol (16) obtained from 15, each carbon of the five-carbon chain is oxygenated, and all stereochemistry has been controlled. The structural relationship of 16 to the pentoses is evident, and methods leading to these carbohydrates have been described [59,62a]. 

In the laboratory of F.E. Ziegler, the synthesis of the core nucleus of FR-900482 was accomplished. In the final stages of the synthetic effort, the removal of the formyl group from the C7 quaternary center was necessary. The authors chose the Tsuji-Wilkinson decarbonylation protocol to effect the transformation. The 1,3-diol functionality was protected as the acetonide prior to the decarbonylation. Usually the rate of decarbonylation is slowest for aldehydes that have the formyl group attached to a quaternary carbon, so it was necessary to use more than two equivalents of the catalyst to effect the decarbonylation at the reflux temperature of xylene. 

The stereochemistry of sy/i- and a/fr/-13 diols in the polyene macrolide antibiotics and polyketides can be determined from the chemical shifts of the acetal carbons and methyl carbons of the corresponding acetonides. The acetonides of jy/i-l,3-diols [Scheme 3.36] occupy a low energy chair conformation displaying an acetal resonance at b 98.5 and methyl resonances at 6 30.0 (equatorial) and b 19.6 (axial). In both possible chair conformations of the a/i/i-l,3-dioI acetonides. there are severe 13-diaxiaI interactions that are relieved in the corresponding twist-boat. In the twist-boat conformation, the acetal carbon resonates at 6 100.6 whereas both methyl groups resonate at b 24.6 because the methyl groups are in nearly identical environments. The twist-boat conformation is more stable than the corresponding chair conformations by about 2 kcal/mole. 

The enantioselective synthesis of monoprotected fra 5-2,5-pyrrolidine dialcohol 1119, a potentially useful intermediate for the construction of pyrrolizidine alkaloids, uses ( S)-malic acid as the chiral source and radical cyclization to fabricate the heterocycle (Scheme 164) [236]. The crucial intermediate 1112 is prepared from acetonide 454b by a Mitsunobu reaction of 1110 with oxazolidine-2,4-dione, resulting in inversion of configuration at the hydroxyl-bearing carbon. Reduction of the 4-carbonyl group of heterocycle 1111 with sodium borohydride followed by dehydration of the resulting alcohol furnishes 1112. 

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