6533b7d5fe1ef96bd1264854

RESEARCH PRODUCT

Enantioselective Synthesis of (−)-Dihydrocodeine and Formal Synthesis of (−)-Thebaine, (−)-Codeine, and (−)-Morphine from a Deprotonated α-Aminonitrile

Till OpatzMario Geffe

subject

MorphinanThebaineMolecular StructureMorphineBicyclic moleculeCodeineStereochemistryOrganic ChemistryEnantioselective synthesisStereoisomerismStereoisomerismTransfer hydrogenationBiochemistryThebainechemistry.chemical_compoundDeprotonationchemistryYield (chemistry)NitrilesmedicineHydrogenationPhysical and Theoretical Chemistrymedicine.drug

description

The α-benzylation of a deprotonated bicyclic α-aminonitrile, followed by Noyori's asymmetric transfer hydrogenation combined with the Grewe cyclization onto a symmetrical A-ring precursor, are the key steps of a short and high-yielding enantioselective synthesis of the morphinan (-)-dihydrocodeine. This compound can be converted to (-)-thebaine in high yield by known transformations, while (-)-codeine and (-)-morphine are available from an advanced intermediate.

yearjournalcountryeditionlanguage
2014-10-02Organic Letters
https://doi.org/10.1021/ol5023849