Highly Efficient Formal [2+2+2] Strategy for the Rapid Construction of Polycyclic Spiroindolines: A Concise Synthesis of 11‐Demethoxy‐16‐epi‐myrtoidine

Abstract

A novel formal [2+2+2] strategy for the stereoselective elaboration of polycyclic indole alkaloids is described. Upon treatment with the catalyst InCl3 (5 mol %), tryptamine‐derived enamides reacted readily with methylene malonate, thus enabling rapid and gram‐scale access to versatile tetracyclic spiroindolines with excellent diastereoselectivity (21 examples, up to 95 % yield, up to d.r.>95:5). This strategy provides a concise approach to alkaloids isolated from Strychnos myrtoides, as demonstrated by a short synthesis of 11‐demethoxy‐16‐epi‐myrtoidine.

Synergetic Tandem Enantiomeric Enrichment in Catalytic Asymmetric Multi-Component Reactions (AMCRs): Highly Enantioselective Construction of Tetracyclic Indolines with Four Continuous Stereocenters

“…5 Later, we developed an efficient three-component formal [2 + 2 + 2] protocol for rapid access to polycyclic spiroindolines from tryptamine-derived enamides and methylene malonates. 6 Very recently, we disclosed an intermolecular [4 + 2] annulation of D−A cyclobutanes 1 with substituted indoles 2, which provides a facile construction of hydrocarbazoles 3 bearing three continuous stereocenters with good diastereoselectivities. 7 However, the enantioselection of this annulation is very sensitive to the donor substituents of the D− A cyclobutanes.…”