TANDEM [3,3]-SIGMATROPIC REARRANGEMENTS IN AN ANSAMYCIN - STEREOSPECIFIC CONVERSION OF AN (S)-ALLYLIC ALCOHOL TO AN (S)-ALLYLIC AMINE DERIVATIVE

Ansamycin ring modifications in the geldanamycin oncogene inhibitor se ries were investigated. A carbamate to urea interchange was accomplish ed with net retention at the 7(S)-center of a geldanamycin analog. Thi s chirally specific transformation was efficiently accomplished by emp loying tandem [3,3]-sigmatropic rearrangements involving first, the co nversion of the allylic 7(S)-alcohol 2b to an allylic 9(S)-thiol, 4b, and then the rearrangement to the allylic 7(S)-isothiocyanate 6, which was carried on to allylic 7(S)-amine derivatives 1a and 1b. This tand em rearrangement strategy may have wide applicability for the preparat ion of chiral allylic amines from the large array of readily available chiral allylic alcohols.