Synthesis of 3‐alkoxy‐7,8‐didehydro‐4‐hydroxy‐N‐methylmorphinan‐6‐ones from morphine. Intermediates for novel A‐ and C‐ring‐functionalized morphinans. (Chemistry of opium alkaloids, Part XXII)

Abstract

AbstractCesium‐assisted benzylation of morphine (1) gave 3‐O‐benzylmorphine (3) in high yield, leading to a convenient synthesis of 3‐benzyloxy‐7,8‐didehydro‐4‐methoxy‐N‐methylmorphinan‐6‐one (8). This was accomplished by Oppenauer oxidation of 3, followed by 4,5α‐epoxy ring opening and methylation, respectively. The key step in this sequence, viz. the reductive epoxy ring opening with retention of the 7,8‐double bond, could also be applied to codeinone (4) giving quantitatively thebainone‐A (6). The low‐yield synthesis of 3 involving a classical procedure can be explained by the Hofmann degradation products 16 and 17.The morphinan‐5,7‐diene 14 was obtained from 8 via the p‐toluenesulfonylhydrazone 13. Morphinan‐6,8‐dienes are accessible from 8 using known procedures.