ABSTRACT Pyrimidines are aromatic nitrogen‐containing heterocycles with significant applications in medicinal chemistry and materials science. Conventional two‐step strategies for synthesizing 2,5‐disubstituted pyrimidines from 2,5‐dihalopyrimidines often require toxic reagents, transition metal (TM) catalysts, harsh conditions, specialized substrates, or non‐commercially available reagents. Therefore, this study aims to develop a TM‐free synthetic route for producing 2,5‐disubstituted pyrimidines via heterocyclic skeletal editing. This one‐pot tandem reaction sequence integrates nucleophilic aromatic C─O, C─N, and C─S substitutions with an amidine‐based inverse‐electron demand Diels–Alder reaction, providing efficient synthesis of pyrimidine derivatives in moderate to excellent yields. The modular skeletal editing strategy employs 5‐bromo‐1,2,3‐triazine 1 as a molecular platform, facilitating orthogonal coupling with various phenols, thiophenols, and sodium azide, followed by amidines to achieve skeletal editing under mild conditions using only Cs 2 CO 3 . This method offers several advantages, including ready substrate availability, operational simplicity, and high atom economy. To further demonstrate the functional utility of the pyrimidine derivatives, pyrimidine‐based Ru(II) complexes were synthesized for fluorescence imaging in live cells. An alkynylated Ru(II) complex 13 served as a key precursor for the modular incorporation of organelle‐targeting moieties via copper‐catalyzed azide–alkyne cycloaddition. These functionalized metal complexes facilitate selective labeling of the nucleus and mitochondria in live cells.
Wang et al. (Sun,) studied this question.
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