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.
Schütz
Johannes
J
Department of Pharmaceutical Chemistry, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, 6020 Innsbruck, Austria.
Windisch
Petra
P
Kristeva
Elka
E
Wurst
Klaus
K
Ongania
Karl-Hans
KH
Horvath
Ulrike E I
UE
Schottenberger
Herwig
H
Laus
Gerhard
G
Schmidhammer
Helmut
H
D002384:Catalysis; D018360:Crystallography, X-Ray; D015394:Molecular Structure; D009019:Morphinans / Q000138:chemical synthesis / Q000737:chemistry*; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry*
D009019:Morphinans; D009570:Nitriles