Catalytic Synergy Drives Triazole-Directed ortho-C(sp²)-H Functionalization

Triazole motifs, ubiquitous in therapeutic agents and bioactive molecules, represent privileged scaffolds for late-stage functionalization and drug diversification. Transition-metal-catalyzed direct C(sp²)-H functionalization offers an atom-economical and regioselective strategy to access such modifications, yet existing methods often lack catalytic adaptability and synthetic versatility. Here, we disclose a tunable ortho-C(sp²)-H functionalization protocol that employs triazole as a directing group. Leveraging catalyst-substrate synergy, diverse aryl triazoles─including the marketed neuropsychiatric drug suvorexant─were efficiently acylmethylated with sulfoxonium ylides. The resulting products served as versatile intermediates for further transformations, such as aerobic oxidation, triazole ring-opening, cyclization, and Wittig-type reaction, thus enabling rapid access to structurally diverse heterocycles and drug-like molecules. Mechanistic insights reveal that metal-triazole coordination governs the rate-determining step, with the metal identity decisively controlling both reactivity and selectivity.