Total Synthesis of Euphane Triterpenoids Using Metal-Catalyzed Hydrogen Atom Transfer

Abstract

Euphane triterpenoids are widely distributed in nature and show various intriguing bioactivities, but relatively few synthetic routes to them have been described. Here, we report asymmetric convergent total syntheses of euphanes involving two triterpenoids and two nortriterpenoids: euphol, 25,26,27-trisnor-3β-hydroxy-euphan-24-al, euphorbiumrin D, and 3-oxo-tirucall-7-ene-3,20-dione. The syntheses employ an enantioselective Antilla allylboration and intramolecular radical cyclization to construct ring A, a palladium-catalyzed Liebeskind stannane-thioester coupling to connect ring A with the bicyclic CD system, and a novel radical cascade with metal-catalyzed hydrogen atom transfer (MHAT) to complete the polycyclic architecture. The late-stage syntheses of both triterpenoids feature a diimide reduction and a MHAT/1,5-hydrogen transfer cascade to diastereoselectively forge the C20 and C17 stereogenic centers.