Phenol oxidation. Part IV. Synthesis and novel ring-opening of spirocyclic dienones related to the benzylisoquinoline alkaloid cularine

Abstract

1,2,3,4-Tetrahydro-1-(4-hydroxy-3-methoxybenzyl)-7-methoxy-N-methylisoquinolin-8-ol was oxidatively coupled with potassium ferricyanide to give a mixture of diastereoisomeric dienones. Treatment of the mixture with hydrochloric acid in glacial acetic acid gave a product tentatively identified as 1-(4,6-dihydroxy-3-methoxy-benzyl)-1,2,3,4-tetrahydro-7-methoxy-N-methylisoquinolin-8-ol, whereas treatment of the dienones with hydrogen chloride in methanol gave 1,2,3,4-tetrahydro-7-methoxy-N-methyl-1-(3,4,6-trimethoxybenzyl)-isoquinolin-8-ol, whose structure was confirmed by unambiguous synthesis. Two essentially different mechanisms for the formation of the latter product were differentiated by carrying out the ring opening in ethanol instead of methanol: the product was then 1-(4,6-diethoxy-3-methoxybenzyl)-1,2,3,4-tetrahydro-7-methoxy-N-methylisoquinolin-8-ol.