Synthesis of 5β‐methyl‐6‐demethoxythebaine and its Diels‐Alder reaction to 6α,14α‐ethenoisomorphinans and 6β,14β‐ethenomorphinans (Chemistry of Opium Alkaloids, Part XXXV

Deprotonation of 6‐demethoxythebaine (1) with butyllithium, followed by reaction of the anion with dimethyl sulfate, gave the non‐conjugated diene 4 as the major product and title compound 5β‐methyl‐6‐demethoxythebaine (5) only in low yield. Therefore, 5 was prepared from 5β‐methylthebaine (6), which was converted into 5β‐methylcodeinone (7) and then reduced to 5β‐methylcodeine (8). Mesylation of 8 yielded 6‐O‐mesyl‐5β‐methylcodeine (9). Reaction of 9 with lithium bromide gave 5β‐methyl‐bromocodide (10) as the major product, together with 5. When 10 was treated with potassium tert‐butoxide, the desired 5 was obtained in good yield. Short treatment of 10 gave the intermediate 8‐bromo‐5‐methyl‐desoxycodeine‐A (11), which reacted further to 5 after prolonged treatment. Diels‐Alder reaction of 5 with ethyl acrylate yielded two products, ethyl 6α,14α‐ethenoisomorphinan‐7α‐carboxylate 13 and ethyl 6β,14β‐ethenomorphinan‐8β‐carboxylate 14, due to β‐face and α‐face approach, respectively. Similarly, with 3‐buten‐2‐one as the dienophile, a mixture of 7α‐acetyl‐6α,l4α‐ethenoisomorphinan 15 and 8β‐acetyl‐6β,14β‐ethenomorphinan 16 was obtained. Diels‐Alder reaction of 5 with maleic anhydride, followed by esterification of the adducts, yielded dimethyl 6α,l4α‐ethenoisomorphinan‐7β,8β‐dicarboxylate 19 and dimethyl 60,140‐ethenomorphinan‐7β,8β‐dicarboxylate 20 in a 7 : 3 ratio. The results of the Diels‐Alder reaction are discussed in connection with the substituents in the 5β‐ and 6‐position.