Catalytic asymmetric synthesis of (−)-arctigenin using a chiral Ir complex

Abstract

The catalytic asymmetric synthesis of (−)-arctigenin is reported. The central optically pure lactone intermediate is obtained either from an Ir-catalyzed asymmetric Tishchenko reaction or an asymmetric oxidative lactonization and subsequently converted to β-iodomethyl-α-methylene-γ-butyrolactone. Several recent Negishi coupling protocols were investigated for the introduction of an aryl unit in the presence of the α-methylene-γ-butyrolactone. The introduction of a second aryl unit was achieved using a diastereoselective Rh-catalyzed conjugate addition and protonation under protecting-group-free conditions.