Metal-Free, Regiodivergent N-Alkylation of 1H-Indazoles Enabled by Brønsted Acid Catalysis

The catalytic N-selective functionalization of indazoles is pivotal in medicinal chemistry; however, achieving regiodivergent N-alkylation remains challenging due to the aromatic stabilization and tautomeric equilibrium of indazoles. Herein, we report a metal-free, Brønsted acid-catalyzed alkylation of 1H-indazoles using sulfoxonium ylides, which affords excellent N2-selectivity and good yields. Modulation of the catalyst enables switchable N1/N2-alkylation. This protocol facilitates the efficient synthesis of pharmaceutical analogues, including anti-lung cancer agents with significant efficacy.