Formic acid catalyzed rearrangement of thevinols (=4,5-epoxy-3,6-dimethoxy-α,17-dimethyl-6,14-ethenomorphinan-7-methanols) and their vinylogous analogues: Effects of 5β-methyl substitution

In a limited number of cases, 14-alkenylcodeinones (=14-alkenyl-7,8-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ones) can be obtained by formic acid treatment of thevinols (=4,5-epoxy-3,6-dimethoxy-α,17-dimethyl-6,14-ethenomorphinan-7-methanols), but under these conditions the equivalent 14-alkenyl-7,8-dihydrocodeinones undergo further rearrangement (Scheme 1 and Table). Introduction of a 5β-methyl group allows the 18,19-dihydrothevinol precursors to be rearranged to 14-alkenyl-7,8-dihydrocodeinones, but similar manipulation of the vinylogues of these thevinols is generally unable to prevent full rearrangement to 5,14-bridged thebainone derivatives.