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Synthesis of Spirocyclic 1‐Pyrrolines from Nitrones and Arynes through a Dearomative [3,3′]‐Sigmatropic Rearrangement

Abdullah S. Alshreimi, Guanqun Zhang, Tyler W. Reidl, Ricardo L. Peña, Nicholas‐George Koto, Shahidul M. Islam, Donald J. Wink, Laura L. Anderson

2020Angewandte Chemie International Edition35 citationsDOI

Abstract

A dearomative [3,3']-sigmatropic rearrangement that converts N-alkenylbenzisoxazolines into spirocyclic pyrroline cyclohexadienones has been developed by using the dipolar cycloaddition of an N-alkenylnitrone and an aryne to access these unusual transient rearrangement precursors. This cascade reaction affords spirocyclic pyrrolines that are inaccessible through dipolar cycloadditions of exocyclic cyclohexenones and provides a fundamentally new approach to novel spirocyclic pyrroline and pyrrolidine motifs that are common scaffolds in biologically-active molecules. Diastereoselective functionalization processes have also been explored to demonstrate the divergent synthetic utility of the unsaturated spirocyclic products.

Topics & Concepts

Sigmatropic reactionAryneChemistryCombinatorial chemistryMedicinal chemistryStereochemistryCyclization and Aryne ChemistryAsymmetric Synthesis and CatalysisChemical synthesis and alkaloids