Mechanistic Diversity of the van Leusen Reaction Applied to 6-Ketomorphinans and Synthetic Potential of the Resulting Acrylonitrile Substructures

Tosylmethyl isocyanide was used to convert 7,8-didehydro-6-ketomorphinans to 6,7-didehydromorphinan-6-carbonitriles with retainment of the 4,5-epoxy ring. However, ring
opening occurred in the presence of NaH giving 5,6,7,8-tetradehydromorphinan-6-carbonitriles. Addition of nucleophiles such as Li diisopropylamide or Grignard reagents to
the acrylonitrile substructure yielded ring-opened 5,6-didehydro products. Seven products were characterized by X-ray
crystal structure analysis and revealed insight into the
mechanistic diversity of the van Leusen reaction.