An Asymmetric Approach towards (–)‐Aphanorphine and Its Analogues

• Published in: European Journal of Organic Chemistry Vol. 2009; no. 6; pp. 793 - 796
• Main Authors: Donets, Pavel A., Goeman, Jan L., Van der Eycken, Johan, Robeyns, Koen, Van Meervelt, Luc, Van der Eycken, Erik V.
• Format: Book Review Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01-02-2009
• Subjects: Alkaloids; Asymmetric catalysis; Cyclization; Heck reaction; Radical reactions
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.200801175

A short enantioselective approach towards the alkaloid(–)‐aphanorphine and its substituted analogues is described. The enantiomerically pure starting material for the synthesis was obtained by asymmetric hydrogenation in the presence of the Rh–(S)‐PipPhos complex. Microwave‐assisted Heckcyclization selectively provided the seven‐membered 3‐benzazepine ring. Further, the assembly of the tricyclic core of the alkaloid was accomplished by intramolecular radical cyclization. The X‐ray structure confirming the absolute configuration of the obtained products is described. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
The synthesis of compounds 1 was developed on the basis of steps involving asymmetric hydrogenation, reductive Heck cyclization and intramolecular radical cyclization.