KHMDS-Mediated Direct Heteroarylation of C(sp ³ )-H Bonds of 9,10-Dihydroacridines and Analogues for Discovery of Potent Antimicrobial Agents

Acridine scaffolds are key pharmacophores in bioactive molecules and functional materials that exhibit diverse biological activities. Although C9-functionalization methods of 9,10-dihydroacridines have advanced, the development of efficient and transition-metal-free strategies for direct heteroarylation of sp³ C-H bonds to access structurally diverse acridines is highly demanding. Herein, we report a KHMDS-mediated direct coupling of 9,10-dihydroacridines with readily available heteroaryl halides under mild and simple conditions. This approach enables rapid and modular access to 9-heteroaryl dihydroacridine derivatives. The resulting functionalized products can be readily transformed into a diverse set of (hetero)aryl-substituted acridinium salts, which shall inspire future applications in the design of photocatalysts and fluorescent dyes. Biological tests demonstrated potent and wide-ranging antifungal activity, underscoring the potential of these products as fungicide leads for agrochemical development.