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

Abstract

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.

Organic Electrosynthesis: Applications in Complex Molecule Synthesis

“…Early studies by the Waldvogel laboratory have demonstrated that phenols can be electro‐oxidatively coupled to produce biphenols as well as polycyclic scaffolds . A related strategy was recently employed by the Opatz and Waldvogel groups in the syntheses of (−)‐thebaine and (−)‐oxycodone . Here, regio‐ and diastereoselective intramolecular anodic coupling of laudanosine derivatives afforded the corresponding morphinandienone motifs, which were further elaborated to the desired target structures (Schemes and ).…”

‐Aminonitriles: From Sustainable Preparation to Applications in Natural Product Synthesis

“…Later, this general route was combined with anodic C−C aryl coupling to provide a biomimetic access to the natural product (−)‐thebaine ( 137 ) and the semisynthetic opioid (−)‐oxycodone (see Scheme ) . As starting materials for these syntheses, bromides 126 and 125 were prepared from methyl gallate 123 .…”

Strategies for the production of biochemicals in bioenergy crops

“…Additionally, gallate can be easily decarboxylated to form pyrogallol, an important platform chemical used as a reducing agent in photography and dyeing agent in cosmetics. Finally, methyl gallate can be used as starting material for the synthesis of the drug precursor thebaine [34].…”