Asymmetric Total Synthesis of (–)-trans-Blechnic Acid via Rhodium(II)-Catalyzed C–H Insertion and Palladium(II)-Catalyzed C–H Olefination Reactions

Abstract

An asymmetric total synthesis of (–)-<i>trans</i>-blechnic acid, a dihydrobenzofuran neolignan, has been achieved. The key steps involve an elaboration of the <i>cis</i>-2,3-dihydrobenzofuran core structure by enantio- and diastereoselective intramolecular C–H insertion using dirhodium(II) tetrakis[<i>N</i>-phthaloyl-(<i>R</i>)-<i>tert</i>-leucinate] [Rh₂(<i>R</i>-PTTL)₄] and a direct coupling of an acrylate unit with the core structure employing Yu’s palladium(II)-catalyzed intermolecular C–H olefination.