Expeditious and Divergent Total Syntheses of Aspidosperma Alkaloids Exploiting Iridium(I)-Catalyzed Generation of Reactive Enamine Intermediates

A new approach for the divergent total syntheses of (+/-)-vincaminorine, (+/-)-N-methylquebrachamine, (+/-)-quebrachamine, (+/-)-minovine and (+/-)-vincadifformine, each in less than 10 linear steps starting from a single -lactam building block, is reported. Key to our route design is the late-stage generation of reactive enamine functionality from stable indole-linked -lactams via a highly chemoselective iridium(I)-catalyzed reduction. The efficiently formed secodine intermediates subsequently undergo either a formal Diels-Alder cycloaddition or a competitive Michael addition/reduction to access aspidosperma-type alkaloids in excellent diastereoselectivities. Product selectivity could be controlled by changing the indole N-protecting group in the reductive cyclization precursors. An asymmetric variant of this synthetic strategy for the synthesis of (+)-20-epi-ibophyllidine is also described.