Enantioselective synthesis of (-)-dihydrocodeinone: a short formal synthesis of (-)-morphine.
[reaction: see text] The radical cyclization approach to the morphine alkaloids has been applied in an asymmetric synthesis of (-)-dihydrocodeinone. A chiral cyclohexenol (R-32), from the CBS reduction of the enone, is the source of chirality. The first key step, tandem closure in which stereochemistry is controlled by geometric constraints, (-)-15b --> (+)-16, was followed by an unprecedented reductive hydroamination, completing the synthesis of (-)-dihydroisocodeine ((-)-17) in 13 steps from commercially available materials.
Parker
Kathlyn A
KA
Department of Chemistry, Brown University, Providence, Rhode Island 02912, USA.
Fokas
Demosthenes
D
D006853:Hydrocodone / Q000138:chemical synthesis* / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D009020:Morphine / Q000737:chemistry*; D009022:Morphine Derivatives / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
D009022:Morphine Derivatives; D006853:Hydrocodone; D009020:Morphine