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Updated: Aug 3, 2025

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
Intramolecular Buchwald-Hartwig N-arylation of bicyclic hydrazines: practical access to
Claire Fleurisson1, Nessrine Graidia1, Yann Foricher2
1Université Paris Cité, CNRS, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques, F-75006 Paris, France. erica.benedetti@u-paris.fr.
Abstract:
In recent years, spirocycles have been the focus of medicinal chemistry, and several drugs or drug candidates incorporating these "non-planar" chemical motifs have been developed. Herein, an unusual intramolecular Buchwald-Hartwig N-arylation of bicyclic hydrazines is described. This key reaction gives access to various spiro[indoline-2,3'-piperidine] derivatives after reductive cleavage of a nitrogen-nitrogen bond. Following this strategy, unprecedented spiro compounds can be obtained in up to 42% yields over 5 steps. Our approach widens the chemical space of spirocycles and may be useful to explore new avenues of research in drug discovery.
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