Experiments directed towards the synthesis of anthracyclinones. XXXVI - Asymmetric dihydroxylations of alkylidene anthracyclinones

The methylidene tetracycle (2) has been synthesized in 11 steps from quinizarin (5) in an overall yield of 38% by using a highly efficient selective dihydroxylation step and an intramolecular ene cyclization. Also prepared with the selective dihydroxylation methodology were the silyloxy alkene (3) and the 6-demethoxy alkene (4). A mixture (1 : 2) of the (E)- and (Z)-isomers of the ethylidene compound (6) has been prepared by similar methods. The products resulting from the reactions of AD-mix-alpha and AD-mix-beta on the alkenes (1)-(3) and (6) have been investigated and their stereochemistries assigned by using H-1 n.m.r. and NOESY experiments, and molecular modelling of acetonide derivatives. An X-ray crystal structure of the acetate (64) has confirmed the relative stereochemical assignments.