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

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

Fingerprint

Quinazolines
Palladium
Cyanides
Application programming interfaces (API)
Carbon Dioxide
Carbon dioxide
Labeling
Catalysis
Transition metals
Thermodynamic stability
Substitution reactions
Kinetics
3-bromoaniline

Keywords

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

Cite this

Mampuys, Pieter ; Neumann, Helfried ; Sergeyev, Sergey ; Orru, Romano V.A. ; Jiao, Haijun ; Spannenberg, Anke ; Maes, Bert U.W. ; Beller, Matthias. / Combining Isocyanides with Carbon Dioxide in Palladium-Catalyzed Heterocycle Synthesis : N3-Substituted Quinazoline-2,4(1H,3H)-diones via a Three-Component Reaction. In: ACS Catalysis. 2017 ; Vol. 7, No. 8. pp. 5549-5556.
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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.",
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Combining Isocyanides with Carbon Dioxide in Palladium-Catalyzed Heterocycle Synthesis : N3-Substituted Quinazoline-2,4(1H,3H)-diones via a Three-Component Reaction. / Mampuys, Pieter; Neumann, Helfried; Sergeyev, Sergey; Orru, Romano V.A.; Jiao, Haijun; Spannenberg, Anke; Maes, Bert U.W.; Beller, Matthias.

In: ACS Catalysis, Vol. 7, No. 8, 04.08.2017, p. 5549-5556.

Research output: Contribution to JournalArticleAcademicpeer-review

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AU - Neumann, Helfried

AU - Sergeyev, Sergey

AU - Orru, Romano V.A.

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AU - Maes, Bert U.W.

AU - Beller, Matthias

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