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

Key words

indole alkaloids - decarboxylative cross-coupling - 6π electrocyclization - 1,2-alkyl shift - retro-Mannich/Mannich reaction

Significance

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.

Comment

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.