APPLICATION AND MECHANISTIC STUDIES OF THE [2,3]-WITTIG REARRANGEMENT - AN APPROACH TO THE BICYCLIC CORE STRUCTURE OF THE ENEDIYNE ANTITUMOR ANTIBIOTICS CALICHEAMICIN GAMMA(1)(I) AND ESPERAMICIN-A(1)

Starting from readily available beta,gamma-unsaturated cyclohexenone precursors the 13-membered bicyclic enediyne 8 was prepared as well as the corresponding ''dihydro'' analogs 11 and 42 lacking the C4-C5 double bond. [2,3]-Wittig ring contraction fo 8 to 9, possessing the bicyclo [7.3.1] tridecadiynene system, characteristic of the enediyne antibiotics calicheamicin and esperamicin,was obstructed by competing electron transfer reactions involving the planar enediyne system. However, [2,3]-Wittig rearrangement of the 1,5-diynes 11 and 42 proved efficient. Under mild base conditions (DBU, 20 degrees C) the 10-membered bicyclic 1,5-diyne 57, bearing a OMs group at C-4, was converted to enediyne 9. This product underwent spontaneous Bergman cyclization giving a series of products, several of which lacked the O-Me substituent which was introduced at C-8. These results, confirmed by deuterium labeling studies, brought to light the occurrence of an internal quenching process involving 1,5-radical translocation.