Preparation of 6‐demethoxy‐N‐formyl‐N‐northebaine and its Diels‐Alder reactions with methyl vinyl ketone and nitroethene; novel 8‐nitro‐substituted 6α,14α‐ethenoisomorphinans and 6β,14β‐ethenomorphinans (chemistry of opium alkaloids, part XXVIII)

Abstract

AbstractThe synthesis of 6‐demethoxy‐N‐formyl‐N‐northebaine (5) and its Diels‐Alder reactions with methyl vinyl ketone and nitroethene are described.N‐Demethylation of 6‐demethoxythebaine (3) with diethyl azodicarboxylate, followed by hydrolysis, gave 6‐demethoxy‐N‐northebaine (4) which was N‐formylated with ethyl formate in DMF to give 5, using “Ketjencat LA‐LPV Steamed” as a catalyst.Reaction of 5 with methyl vinyl ketone using microwave heating gave the expected 7α‐acetyl‐6α,14α‐ethenoisomorphinan 9 by direct crystallization from the reaction mixture. On the other hand, Diels‐Alder reaction of 5 with nitroethene afforded the 7α‐nitro‐6α,14α‐ethenoisomorphinan 12 as a minor product (10%). The major products were 8α‐nitro‐6α,14α‐ethenoisomorphinan (10) (50%) and 8β‐nitro‐6β, 14β‐ethenomorphinan (11) (30%). The structure of the new adducts was elucidated by 1H NMR.Factors which may influence the course of the Diels‐Alder reaction of morphinan‐6,8‐dienes are discussed. The surprising change in selectivity seems to be governed mainly by steric effects.