Taming the radical cation intermediate enabled one-step access to structurally diverse lignans

Lignans, in spite of their structural diversity, are all biosynthetically derived from coniferyl alcohol. We report herein a divergent synthesis of lignans from biomass-derived monolignols in a short synthetic sequence. Blue LED irradiation of a dichloromethane solution of dicinnamyl ether derivatives in the presence of Cu(TFA)(2), an alcohol (2.0 equiv) and a catalytic amount of Fukuzumi's salt affords the C7-alkoxylated aryltetralin cyclic ethers. Increasing the amount of alcohol under otherwise identical conditions diverts the reaction course to furnish the C7,C7'-dialkoxylated dibenzyltetrahydrofurans, while replacing Cu(TFA)(2) with diphenyl disulfide (PhSSPh) provides selectively the C7-monoalkoxylated dibenzyltetrahydrofurans. Aza-, thia- and carba-analogues of lignans are equally accessible by simply changing the tethering atom of the allylic alcohols. Concise total syntheses of aglacins A, E, F, brassilignan, and dehydrodimethylconidendrin are documented featuring these transformations. Lignans, in spite of their structural diversity, are all biosynthetically derived from coniferyl alcohol. Here, the authors describe a divergent and stereoselective chemical synthesis of three types of lignans from biomass-derived monolignols, exploiting the different reaction manifolds of highly reactive radical cation intermediate.

Automated summary

In this study, a divergent and stereoselective chemical synthesis of three types of lignans from biomass-derived monolignols was described. This synthesis method exploits the different reaction manifolds of highly reactive radical cation intermediate, allowing concise total syntheses of several lignan compounds.