Stereoselective Synthesis of Lignans of Three Structural Types from a Common Intermediate, Enantioselective Synthesis of (+)-Yangambin

Enantioselective total synthesis of (+)-yangambin was achieved. The key transformation is one-pot conjugate addition/aldol reaction that involves an enantioenriched benzyl tert-butyl sulfoxide, an enone, and gaseous formaldehyde to construct the bis(phenylpropanoid) backbone with excellent stereoselectivity and in good yield. Reduction of the ketone with diisobutylaluminium hydride and acid-catalysed cyclisation in EtOH furnished (+)-yangambin in good yield. The resulting synthesis is short, efficient and highly selective. Formation of 2,5-diaryltetrahydrofuran lignans was observed as a side reaction in the final step of yangambin synthesis. Acid-catalysed cyclisation of the aldol intermediate gave a completely different outcome. Dehydration to give an enone was followed by two electrophilic aromatic substitution reactions to furnish a derivative of the lignan lirionol.