The Facility of Formation of a Δ⁶Bond in Dihydromorphinone and Related Opiates

Treatment of naltrexone, dihydromorphinone, or related opiates that contain a 6-keto group with acetic anhydride or tert-butyldimethylsilyl chloride under mild conditions afforded enol derivatives having a Δ⁶bond. Naltrexone also was found to undergo the Robinson annelation reaction with methyl vinyl ketone with facility and in high yield to give the β-hydroxy ketone 3, whose stereochemistry was determined by means of 2D NMR spectroscopy. Upon acid treatment, 3 was dehydrated to the α,β-unsaturated ketone 4. Acid-catalyzed equilibration of 4 afforded the unconjugated olefin 5. These studies suggest that the Δ⁶bond is more stable than one that is exocyclic to ring C of the opiate because it permits ring flattening which may partially relieve torsional ring strain. The Δ⁶bond also may relieve an eclipsing interaction between a C-6 exocyclic substituent and the vicinal furan oxygen.