Total synthesis of the alkoxydioxines (+)- and (-)-chondrillin and (+)- and (-)-plakorin via singlet oxygenation/radical rearrangement

The sequential application of singlet oxygenation and peroxyl radical rearr angement provides an asymmetric entry to 4-peroxy-2-enols and 4-peroxy-2-en ones, Enantiomerically enriched 2-hydroperoxy-3-alkenols, obtained via hydr oxyl-directed addition of O-1(2) to Z-allylic alcohols, undergo stereospeci fic radical rearrangement Do form 4-hydroperoxy-2-alkenols. The yields of t he rearrangement are improved in the presence of excess tert-butyl hydroper oxide, which limits dimerization of the substrate peroxyl radicals. However , the rearrangement equilibrium is unaffected by the presence of polar co-s olvents or by the incorporation of a group able to selectively hydrogen bon d to the product hydroperoxide. Photoisomerization of the (E)-4-hydraperoxy -2-enone rearrangement products results in irreversible ring closure to fur nish diastereomeric mixtures of enantiomerically enriched dioxinols. The st rategy is applied to the total synthesis of the alkoxydioxine natural produ cts chondrillin and plakorin. Comparison of the optical rotation of the syn thetic material against literature reports indicates that the natural produ cts are either enantiomerically pure or highly enriched in one enantiomer. In addition, our results conclusively demonstrate that the reported configu ration of chondrillin is in error.