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A Four-Component Reaction Strategy for Pyrimidine Carboxamide Synthesis
Wei Guo1,2, Jianhua Liao1, Dongqing Liu1
1Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, P.R. China.
Angewandte Chemie (International Ed. in English)
|December 15, 2016
Summary
A novel palladium-catalyzed reaction efficiently synthesizes pyrimidine carboxamides using readily available starting materials. This method uniquely utilizes N,N-dimethylformamide (DMF) as a dual synthon, offering a greener and more economical approach.
Area of Science:
- Organic Chemistry
- Catalysis
- Synthetic Methodology
Background:
- Pyrimidine carboxamides are important scaffolds in medicinal chemistry.
- Efficient and economical synthesis of complex organic molecules is a key challenge.
Purpose of the Study:
- To develop a novel, highly effective multi-component reaction for synthesizing pyrimidine carboxamides.
- To explore the use of N,N-dimethylformamide (DMF) as a dual synthon in palladium-catalyzed reactions.
Main Methods:
- A palladium-catalyzed 3 starting materials-4 component reaction (3SM-4CR) strategy was employed.
- The reaction involved amidines, styrene, and N,N-dimethylformamide (DMF).
- Isotope-labeling experiments confirmed the role of DMF as a dual synthon.
Main Results:
- The developed 3SM-4CR strategy successfully synthesized pyrimidine carboxamides.
- N,N-dimethylformamide (DMF) was demonstrated to act as both a one-carbon-atom and an amide synthon.
- The reaction combined C-H bond functionalization and cross-dehydrogenative coupling, forming four chemical bonds.
Conclusions:
- This novel sequential 3SM-4CR strategy offers an atom and step-economical route to pyrimidine carboxamides.
- The method utilizes inexpensive starting materials and green oxidants.
- The synthesized pyrimidine carboxamides have potential applications in the pharmaceutical industry.
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