One-pot conversion of thebaine to hydrocodone and synthesis of neopinone ketal.

The ethylene glycol ketal of neopinone was prepared in a one-pot procedure by the reaction of thebaine with ethylene glyocol in the presence of p-toluenesulfonic acid. The ketal is also an intermediate in the conversion of thebaine to hydrocodone with ethylene glycol and Pd(OAc)(2), followed by hydrogenation. Additionally, a one-pot procedure for the conversion of thebaine to hydrocodone was achieved by employing palladium catalysis in aqueous medium. Palladium serves a dual purpose in this transformation, first for the activation of the dienol ether of thebaine and second as a hydrogenation catalyst. This procedure was found to be comparable to the two-step protocol which employs diimide reduction of thebaine followed by acid-catalyzed hydrolysis of the resulting 8,14-dihydrothebaine to hydrocodone. Experimental and spectral data are provided for all compounds.