Enantioselective Total Synthesis of (−)-Daphenylline
Bing-Lu Wu, Jian-Neng Yao, Xiang-Xi Long, Zong-Qin Tan, Liang Xiao, Li Feng, Kun Wei, Yu‐Rong Yang
Abstract
A concise enantioselective total synthesis of (−)-daphenylline, a hexacyclic Daphniphyllum alkaloid with a unique benzene ring, was achieved in 14 steps. The synthesis commences with two chiral stereocenters, C2 and C18, readily installed via Carreira’s Ir/amine dual-catalyzed allylation. The allylic bridgehead amine 6 was rapidly prepared through Wickens’ photoredox-catalyzed hydrocarboxylation of olefin and CuBr 2 -catalyzed α-amination of ketone. The tetracycle 4 was formed via Pd-catalyzed reductive Heck reaction or, more concisely, by Krische’s Rh-catalyzed reductive 1,6-enyne cyclization. In this synthesis, newly reported Wickens’ photoredox-catalyzed hydrocarboxylation was used twice, and Friedel–Crafts acylation thrice.