Synthesis of racemic and optically active codeine and morphine via the N‐formylnordihydrothebainones: (Chemistry of opium alkaloids, part X)

Starting from 3,4,5-trihydroxybenzoic acid (gallic acid), racemic 1-(3,5-dibenzyloxy-4-methoxybenzyl)-1,2,3,4-tetrahydro-6-methoxyisoquinoline (3, Scheme) was synthesized. Resolution with (-)-(S)-malic acid yielded (+)-(R)-3. By a Birch reduction, followed by N-formylation, and by acid-catalysed cyclization, we obtained racemic and optically active N-formyl-2-hydroxynordihydrothebainone (6). 6 Was selectively converted into N-formyl-2-(1-phenyltetrazol-5-yloxy)nordihydrothebainone (7). Hydrogenolysis of (-)-7 and of racemic 7 yielded (-)-N-formylnordihydrothebainone (8) and racemic 8, respectively. Previously we had converted the N-formyl derivative (8) in various ways into dihydrothebainone. The conversion into (-)-codeine and (-)-morphine is known.