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.