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 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.

Xylochemistry--Making Natural Products Entirely from Wood.

The first total synthesis of the dimeric berberine alkaloid ilicifoline (ilicifoline B) is reported. Its carbon skeleton is constructed from ferulic acid, veratrole, and methanol. The synthesis reported herein employs starting materials solely derived from wood. The natural product is thus constructed entirely from renewable resources. The same strategy is applied to a formal total synthesis of morphinan alkaloids. The use of wood-derived building blocks (xylochemicals) instead of the conventional petrochemicals represents a sustainable alternative to classical synthetic approaches.

Enantioselective synthesis of (-)-dihydrocodeine and formal synthesis of (-)-thebaine, (-)-codeine, and (-)-morphine from a deprotonated α-aminonitrile.

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.

Chromatographically separable rotamers of an unhindered amide.

Surprisingly stable formamide rotamers were encountered in the tetrahydroisoquinoline and morphinan series of alkaloids. We investigated the hindered rotation around the amide bond by dynamic high-performance liquid chromatography (DHPLC) and kinetic measurements of the interconversion of the rotamers which can readily be separated by HPLC as well as TLC. The experimental results of the different methods were compared to each other as well as to results obtained by DFT calculations.

4-[2-(Benzyl-amino)-phen-yl]-2,6-dimethyl-quinoline N-oxide.

The title compound, C(24)H(22)N(2)O, was obtained in a two-step procedure from the corresponding 4-(2-iodo-phen-yl)quinoline. The quinoline system is approximately planar [maximum deviation from the least-squares plane = 0.021 (2) Å]. The planes of the quinoline system and the phenyl ring subtend a dihedral angle of 78.08 (8)°. In the crystal, pairs of mol-ecules are connected via a center of symmetry and linked by a pair of angular N-H⋯O hydrogen bond. These dimers form columns oriented along the c axis.