Application of the Palladium-Catalysed Norbornene-Assisted Catellani Reaction Towards the Total Synthesis of (+)-Linoxepin and Isolinoxepin.

Our ongoing effort towards the development of highly selective transition-metal-catalysed C-H activation processes has led to the expansion of the Catellani reaction. In a Pd⁰/Pd^II/Pd^IV-catalysed domino reaction, an aryl iodide, alkyl iodide and tert-butyl acrylate were combined to synthesize the carbon framework of the novel lignan (+)-linoxepin. The enantioselective synthesis highlights the work accomplished in our group and provides an excellent procedure for the reliable and scalable synthesis of architecturally complex scaffolds. This report outlines the synthetic approaches towards this interesting class of biologically active molecules. After the key Catellani/Heck reaction, our synthesis features a Leimeux-Johnson oxidation and a titanium tetrachloride mediated aldol condensation. Finally, a tuneable Mizoroki-Heck reaction was performed to furnish not only the natural product (+)-linoxepin but also its isoform, which we have named isolinoxepin. [ABSTRACT FROM AUTHOR]