We have achieved a novel effective approach to chiral cyclobutanones(3) via Sharpless asymmetric dihydroxylation of cyclopropylidene derivatives followed by 1,2-rearrangement. The results show that the disubstituted derivatives are better substrates than the monosubstituted ones. Of these disubstituted cyclopropylidene derivatives, (1e) having bulky substituent on ortho position of aromatic ring, showed moderate enantioselectivity to give the optically active cyclobutanone (3e) in high yield, which constitutes a total formal synthesis of (-)-filiformin. Furthermore, we examined a synthesis of trichothecane antibiotics along with this cyclobutane strategy. A synthesis of A-ring aromatic trichothecane (13) was achieved via palladium mediated ring expansion of (9) and regiocontrolled cyclization of (12) as key steps. The compound (13) thus preprared was controlled into functionalized diene (16) via diol (14) and acetonide (15). The studies for the conversion of (16) into scirpene are now under progress.
