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Updated: Jun 23, 2026

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Complex polycyclic lactams from pericyclic cascade reactions of Zincke aldehydes
Sarah E Steinhardt1, Christopher D Vanderwal
1Department of Chemistry, University of California, Irvine, California 92697-2025, USA.
Abstract:
In the course of a simple mechanistic study on the rearrangement of Zincke aldehydes to Z-alpha,beta,gamma,delta-unsaturated amides, a thermally induced pericyclic cascade rearrangement that converts Zincke aldehydes derived from allylic and homoallylic amines into polycyclic lactams was discovered. The key reaction involves an E-Z alkene isomerization, a 6pi electrocyclic ring closure, a [1,5]-sigmatropic shift of hydrogen, a 6pi electrocyclic ring-opening, and a Diels-Alder cycloaddition, and proceeds with excellent stereoselectivity. The unusual observation that furans and an indole serve as dienophiles in this cascade reaction permitted the synthesis of complex, functional group-rich tri- and tetracyclic lactams. In all cases, the rigid polycyclic products are available in only two steps from pyridinium salts and the allylic or homoallylic secondary amines.
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