Synthesis of Pyridinyl-Pyrimidines via Pd-Catalyzed Cross-Coupling Reactions: A Comparison of Classical Thermal and Microwave Assisted Reaction Conditions

Abstract

The Negishi cross-coupling reaction was used for the synthesis of pyridinyl-pyrimidines utilizing classical thermal or microwave assisted conditions. The organozinc substrates were prepared from 2-fluoro-4-iodopyridine by conventional lithiation chemistry and subsequent transmetalation with ZnCl₂ or ZnI₂. Two different catalysts - Pd(PPh₃)₄ and Pd/C - were investigated for their ability to facilitate the cross coupling process with 2,4-dichloropyrimidine. We found that distribution and yield of desired compoun­ds and possible by-products highly depend on the type of energy input. In contrast to thermal conditions, the microwave assisted method allowed efficient access to di-coupled compounds.

Keywords

palladium catalyzed cross-coupling reactions - Negishi-reaction, microwave assisted reactions - homogeneous catalysis - heterogeneous catalysis

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