Synfacts 2020; 16(08): 0875
DOI: 10.1055/s-0040-1707081
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of (+)-1,2-Dehydroaspidospermidine, (+)-Condyfoline, and (–)-Tubifoline

Erick M. Carreira
Manuel Freis
Delayre B, Piemontesi C, Wang Q, Zhu J. * École Polytechnique Fédérale de Lausanne, Switzerland
TiCl3-Mediated Synthesis of 2,3,3-Trisubstituted Indolenines: Total Synthesis of (+)-1,2-Dehydroaspidospermidine, (+)-Condyfoline, and (−)-Tubifoline.

Angew. Chem. Int. Ed. 2020;
DOI: 10.1002/anie.202005380.
Further Information

Publication History

Publication Date:
21 July 2020 (online)



Zhu and co-workers report the synthesis of 2,3,3-trisubstituted indolenines through a TiCl3-mediated reductive cyclization of tetrasubstituted alkenes bearing a 2-nitrophenyl substituent. An unprecedented sequence of reduction of nitro­arene, 6π electrocyclization, 1,2-alkyl shift, and final nitrone reduction resulted in the syntheses of (+)-1,2-dehydroaspidospermidine, (+)-condyfoline, and (−)-tubifoline.



Palladium-catalyzed decarboxylative cross-coupling between enantioenriched vinyl triflate A and racemic potassium carboxylate B furnished cyclopentene C. Epoxidation, deprotection, and subsequent transannular epoxide ring opening provided E which was converted into (+)-1,2-de­hydroaspidospermidine through reductive cyclization. Isomerization of (+)-condyfoline to (−)-tubi­foline occurred by a retro-Mannich/Mannich reaction.