STUDIES ON THE SYNTHESIS OF ACANTHODORAL AND NANAIMOAL - EVALUATION OF CATIONIC CYCLIZATION ROUTES

Intramolecular Lewis acid-promoted reactions of alpha,beta-unsaturated ketone 6 and aldehydes 7 and 8 were examined as potential routes to a canthodoral (1), a structurally interesting natural product. Ketone 6 afforded ene product 22 exclusively, and both 7 and 8 gave mixtures of bicyclic aldehydes 3 and 26 and tricyclic aldehyde 25. The latter mos t likely results from 7 by intramolecular cyclization of the alkene on to the Lewis acid-activated carbonyl moiety affording carbocation 31 f ollowed by a 1,2-hydride shift and ring closure. Starting from 8, tric yclic aldehyde 25 apparently forms by cyclization to cation 35 and rin g closure to cyclobutane 36, followed by ring opening to 31, the same cation as formed in reactions of 7. Nanaimoal (3) results from loss of H+ from 31, and bicyclic aldehyde 26 may be formed in a similar manne r or by a concerted ene reaction. The configuration of 25 establishes that the stereochemistry of the initial cyclization to 31 precludes th e possible use of this strategy for the synthesis of acanthodoral. How ever, acid-promoted cyclization of allylic alcohol 23 efficiently give s diene 29 which undergoes selective hydroboration/oxidation to afford nanaimoal.