Synthetic Studies on Enantioselective Total Syntheses of Tabercarpamines and Voacangine‐Type Indole Alkaloids

The proposed post‐iboga natural products, (+)‐tabercarpamines G and I, along with their corresponding C20 stereoisomers and C10‐methoxy‐regioisomers were synthesized. An extensive NMR spectroscopic study showed that the spectral data of these synthetic compounds were not consistent with the proposed (+)‐tabercarpamines G and I in isolation report, indicating that the proposed structures were misassigned. Subsequently, from the advanced intermediates for the synthesis of the proposed (+)‐tabercarpamines G and I, the unified enantioselective syntheses of six iboga‒type natural products including (‐)‐isovoacangine and (‐)‐voacangine, (‐)‐3‐oxo‐isovoacangine and (‐)‐3‐oxo‐voacangine, and (‐)‐(3S)‐cyanoisovoacangine and (‐)‐(3S)‐cyanovoacangine were accomplished via a divergent manner. The synthetic route provided the first catalytic asymmetric approach to access these three types of iboga‒type natural products and achieved the first enantioselective syntheses of (3S)‐cyano(iso)voacangines. Our synthesis hinged on a catalytic asymmetric Michael/aldol reaction for the construction of chiral aza‐[3.3.1]‐bridged bicyclic framework at the early stage and a ring reorganization process from [3.3.1]‐ to [2.2.2]‐bicyclic ring system―a pathway opposite to the proposed biogenic synthesis―at the late stage.