SYNTHESIS OF (-)-MONOTERPENYLMAGNOLOL AND MAGNOLOL

(-)-Monoterpenylmagnolol (3) was synthesized in eight steps from (+)-3,9-dibromocamphor (4) and the bis(methoxymethyl) ether (22) of 3-(4-hydroxyphenyl)-1-propanol. Fragmentation of an endo-3-aryl-9-bromocamphor (27) provided the correct absolute stereochemistry. In this total synthesis, dissolving metal conditions were developed to reduce enol phosphate and isopropenyl functions without concomitant reduction of an attached phenol. Palladium(O)-catalyzed cross-coupling of an arylzinc chloride with 4-allyl-2-iodophenyl methoxymethyl ether (34) provided the desired tricyclic 1,2,3,5-tetrasubstituted biaryl 41 in fair yield without optimization and with little isomerization of the allyl group. Magnolol (1) was also synthesized by aryl coupling of 34 and the methoxymethyl ether of 4-allyl-2-lithiophenol via the zinc chloride method as above, as well as from 5,5'-dibromo-2,2'-dimethoxybiphenyl (37) by allylation with allyltributylstannane followed by ether cleavage.