Synthetic approaches to cularines. I. Phenolic oxidative coupling

Ferricyanide-promoted biogenetic-type phenolic oxidative coupling of an 8,3′-dihydroxytetrahydrobenzyl-isoquinoline 19a afforded the isomeric phenolic cularines 5 and 21. Vanadium oxytrifluoride oxidation of the N-borane complex of 19a afforded, regioselectively, the para-coupled product 21. Moreover, when this reagent was used on the monophenolic tetrahydrobenzylisoquinoline 19b protected as its N-borane complex, cularine 1 was regioselectively obtained in good yield. Other structural modifications and reagents were not successful.