Dearomative Spirocyclization of Tryptamine-Derived Isocyanides via Iron-Catalyzed Carbene Transfer

The Journal of Organic Chemistry
2023.0

Abstract

Tryptamine-derived isocyanides are valuable building blocks in the construction of spirocyclic indolenines and indolines via dearomatization of the indole moiety. We report the Bu(4)N[Fe(CO)(3)NO]-catalyzed carbene transfer of alpha-diazo esters to 3-(2-isocyanoethyl)indoles, leading to ketenimine intermediates that undergo spontaneous dearomative spirocyclization. The utility of this iron-catalyzed carbene transfer/spirocyclization cascade was demonstrated by its use as a key step in the formal total synthesis of monoterpenoid indole alkaloids (+/-)-aspidofractinine, (+/-)-limaspermidine, (+/-)-aspidospermidine, and (+/-)-17-demethoxy-N-acetylcylindrocarine.

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