Asymmetric Total Synthesis of Indole Diterpenes Paspalicine, Paspalinine, and Paspalinine‐13‐ene

Abstract Paspaline‐derived indole diterpenes (IDTs) are structurally complex mycotoxins with unique tremorgenic activity. Reported are asymmetric total syntheses of three paspaline‐derived IDTs paspalicine, paspalinine and paspalinine‐13‐ene. Our synthesis features a green Achmatowicz rearrangement/bicycloketalization for the efficient construction of FG rings (75 % yield) and a cascade ring‐closing metathesis of dienyne for highly regioselective formation of CD rings (72 % yield). Other highlights include four palladium‐mediated reactions (Stille, aza‐Wacker, Suzuki, and Heck) to forge the BE rings and the installation of two continuous all‐carbon quaternary stereocenters via reductive ring‐opening of cyclopropane and α‐methylation of the conjugate ester. Our new synthetic strategy is expected to be applicable to the chemical synthesis of other paspaline‐derived IDTs and will facilitate the bioactivity studies of these agriculturally and pharmacologically important IDTs.