DDQ promoted metal-free oxidative cascade synthesis of acridinyl ketones and 4-benzoylacridinones from C4-functionalized 1,2,3,4-tetrahydroacridines

Abstract

Herein, we report a DDQ-mediated, metal-free oxidative cascade protocol for the synthesis of acridin-4-yl(aryl)methanones and 4-benzoylacridin-9(10H)-ones (acridones) through sequential dehydrogenative aromatization and C(sp²)–H oxidation of C4-substituted 1,2,3,4-tetrahydroacridines. With operational simplicity, mild reaction conditions, and no transition metals, this cascade offers a step-economical and metal-free approach to access acridine scaffolds. This method exhibits broad functional group tolerance in delivering the desired products in good yields. Mechanistic investigations, including radical-trapping and nucleophile-probing experiments, support a pathway initiated by hydrogen atom transfer (HAT), followed by a single electron transfer (SET), forming the key benzyl carbocation intermediates that undergo subsequent oxidation to the final products. Notably, the formation of acridone products involves an integrated oxidative dechlorination step.