Combining Isocyanides with Carbon Dioxide in Palladium-Catalyzed Heterocycle Synthesis: N3-Substituted Quinazoline-2,4(1H,3H)-diones via a Three-Component Reaction

Pieter Mampuys, Helfried Neumann, Sergey Sergeyev, Romano V.A. Orru, Haijun Jiao, Anke Spannenberg, Bert U.W. Maes*, Matthias Beller

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

We report a Pd-catalyzed three-component reaction of 2-bromoanilines, carbon dioxide, and isocyanides. The combination of these two readily available C1-reactants, featuring a huge difference in kinetic and thermodynamic stability, is hitherto unprecedented in transition-metal catalysis. With this one-pot three-component reaction, N3-substituted quinazoline-2,4(1H,3H)-diones are obtained in moderate to high yields in a completely regio- and chemoselective manner. Our approach easily allows variation of the arene and N3-substitution pattern of the desired heterocycle. The formal synthesis of different APIs illustrates its practical applicability. In addition, the methodology also allows for a convenient and selective 13C-labeling through the use of 13CO2. This is illustrated for [2-13C]-2,4-dichloro-6,7-dimethoxyquinazoline synthesis, a key intermediate for several APIs.

Original languageEnglish
Pages (from-to)5549-5556
Number of pages8
JournalACS Catalysis
Volume7
Issue number8
DOIs
Publication statusPublished - 4 Aug 2017

Keywords

  • C-labeling
  • C-reactants
  • carbon dioxide
  • isocyanide
  • Pd-catalysis

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