TiCl<sub>3</sub>‐Mediated Synthesis of 2,3,3‐Trisubstituted Indolenines: Total Synthesis of (+)‐1,2‐Dehydroaspidospermidine, (+)‐Condyfoline, and (−)‐Tubifoline
Bastien Delayre, Cyril Piemontesi, Qian Wang, Jieping Zhu
Abstract
-mediated reductive cyclization of tetrasubstituted alkenes bearing a 2-nitrophenyl substituent. The proof of concept is demonstrated firstly by accomplishing a concise total synthesis of (+)-1,2-dehydroaspidospermidine featuring a late-stage application of this key transformation. A sequence of reduction of nitroarene to nitrosoarene followed by 6π-electron-5-atom electrocyclization and a 1,2-alkyl shift of the resulting nitrone intermediate was proposed to account for the reaction outcome. A subsequent total synthesis of (+)-condyfoline not only illustrates the generality of the reaction, but also provides a mechanistic insight into the nature of the 1,2-alkyl shift. The exclusive formation of (+)-condyfoline indicates that the 1,2-alkyl migration follows a concerted Wagner-Meerwein pathway, rather than a stepwise retro-Mannich/Mannich reaction sequence. Conditions for almost quantitative conversion of (+)-condyfoline to (-)-tubifoline by way of a retro-Mannich/1,3-prototropy/transannular cyclization cascade are also documented.