Mechanistic diversity of the van Leusen reaction applied to 6-ketomorphinans and synthetic potential of the resulting acrylonitrile substructures

Johannes Schütz; Petra Windisch; Elka Kristeva; Klaus Wurst; Karl-Hans Ongania; Ulrike E I Horvath; Herwig Schottenberger; Gerhard Laus; Helmut Schmidhammer

doi:10.1021/jo050362v

Mechanistic diversity of the van Leusen reaction applied to 6-ketomorphinans and synthetic potential of the resulting acrylonitrile substructures

J Org Chem. 2005 Jun 24;70(13):5323-6. doi: 10.1021/jo050362v.

Authors

Johannes Schütz¹, Petra Windisch, Elka Kristeva, Klaus Wurst, Karl-Hans Ongania, Ulrike E I Horvath, Herwig Schottenberger, Gerhard Laus, Helmut Schmidhammer

Affiliation

¹ Department of Pharmaceutical Chemistry, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, 6020 Innsbruck, Austria.

PMID: 15960541
DOI: 10.1021/jo050362v

Abstract

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.

MeSH terms

Catalysis
Crystallography, X-Ray
Molecular Structure
Morphinans / chemical synthesis
Morphinans / chemistry*
Nitriles / chemical synthesis
Nitriles / chemistry*

Substances

Morphinans
Nitriles