Synthesis of (-)-Monoterpenylmagnolol and Magnolol

Article abstract of DOI:10.1021/jo00111a052

(-)-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(0)-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.