New model compounds were investigated within our efforts to synthesize
the natural product heliquinomycin. We could provide good evidence
that electronic effects prevent the spiroketal formation of compounds
such as 5 incorporating an isocoumarin moiety.
As a consequence, precursors 16 and 26 were prepared, which do not exert the
strong electron-withdrawing effect of the methoxycarbonyl group
present in 5. Dihydroisocumarin derivative 10 and phthalide 25 were
coupled by Heck reactions with enone 4 to
provide the required precursors 16 and 26. After reductive debenzylation the resulting
intermediates were treated with anhydrous hydrochloric acid in alcohols
to give spiroketals 18-20 and 28, 29 in reasonable yields. The spiroketalizations
occur under thermodynamic control affording products with the hydroxyl
group in a trans-relationship with respect
to the pyran oxygen atom. Attempts to oxidatively convert dihydroisocumarin 19 into an isocoumarin derivative failed.
In one attempt a ring contraction to new spiroketal 24 was
observed.
acetals - spiro compounds - Heck reaction - natural products - heliquinomycin
