Approach towards an EPC synthesis of nodusmicin. Part 5: Stereoselective introduction of a side chain at the cis-decalin part of nodusmicin

The introduction of the side chain at C-4 of cis-decalin 2 and closure of the oxygen bridge are reported. Partial dehydrogenation of 2 was followed by oxymercuration and halogen–mercury exchange. Intermolecular radical addition to acrylic ester occurred from the convex face of the tricyclic compounds 7a and 7b. Consecutive epimerization failed. Therefore, two methods using intramolecular attachment of the side chain were developed. Formation of the β-iodoacetal of the cyclic allylic alcohol 21 permitted intramolecular radical addition generating the desired configuration at C-4 of the decalin. Likewise formation of the β bromoacetal with the exo-cyclic hydroxy group of tricycle 12 led via SN2-reaction to tetrahydropyrans with the desired configuration at C-4. The oxygen bridge was introduced by dehydration of the exo-cyclic alcohol and consecutive oxymercuration. Mercury–oxygen exchange completed the reaction sequence.