Natural products inspired [3+2] cycloaddition enables efficient construction of hydroxylated tetrahydrofuran acetals and concise syntheses of lignans

Mimicking biosynthetic pathways of hongkonoids led to the development of a new Cu(I)-catalyzed [3 + 2] cycloaddition of alpha-hydroxyketone and beta-keto enol ethers, affording tetrahydrofuran acetals in a highly diastereoselective manner and 100% atom economy. Computational studies on the mechanism disclosed a concerted but asynchronous Michael addition/aldol reaction. Of the same importance, this methodology provides a practical biomimetic approach for one-step construction of the dibenzylbutyrolactol lignan backbone starting from two phenyl propane derivatives, opening up a powerful new approach for lignan synthesis, which is showcased by succinct total syntheses of two biologically important aryltetralin-type lignans, beta-apopicropodophyllin and cycloolivil. Given the mild and operationally simple conditions, the developed chemistry might have a promising prospect in potential industrial applications.