A Regio‐ and Diastereoselective Anodic Aryl–Aryl Coupling in the Biomimetic Total Synthesis of (−)‐Thebaine

The biosynthesis of thebaine is based on the regioselective, intramolecular, oxidative coupling of (R)‐reticuline. For decades, chemists have sought to mimic this coupling by using stoichiometric oxidants. However, all approaches to date have suffered from low yields or the formation of undesired re...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2018-08, Vol.57 (34), p.11055-11059
Main Authors: Lipp, Alexander, Ferenc, Dorota, Gütz, Christoph, Geffe, Mario, Vierengel, Nina, Schollmeyer, Dieter, Schäfer, Hans J., Waldvogel, Siegfried R., Opatz, Till
Format: Article
Language:English
Subjects:
alkaloids
Aromatic compounds
biomimetic synthesis
Biomimetics
Biosynthesis
Chemists
Coupling
Electrochemistry
morphine
Organic chemistry
Oxidants
Oxidizing agents
Stereoselectivity
thebaine
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Summary:The biosynthesis of thebaine is based on the regioselective, intramolecular, oxidative coupling of (R)‐reticuline. For decades, chemists have sought to mimic this coupling by using stoichiometric oxidants. However, all approaches to date have suffered from low yields or the formation of undesired regioisomers. Electrochemistry would represent a sustainable alternative in this respect but all attempts to accomplish an electrochemical synthesis of thebaine have failed so far. Herein, a regio‐ and diastereoselective anodic coupling of 3′,4′,5′‐trioxygenated laudanosine derivatives is presented, which finally enables electrochemical access to (−)‐thebaine. Enforcement of selectivity through a combination of electrochemistry and substrate design was used as an elegant strategy to solve a long‐standing electrosynthetic challenge. A regio‐ and diastereoselective anodic coupling of 3′,4′,5′‐trioxygenated laudanosine derivatives is presented which enables biomimetic, electrochemical access to (−)‐thebaine.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201803887