Green C3-Aminomethylation of Indoles

The 3-aminomethylindole motif serves as a privileged scaffold widely present in natural products and pharmaceuticals, creating an urgent demand for efficient synthetic pathways. Herein, we report a catalyst-free, regioselective C3-aminomethylation of indoles employing N,O-acetals under mild conditions. This method yields products with good to excellent yields, exhibiting a broad substrate scope and outstanding tolerance to various functional groups. Mechanistic investigations indicate the <i>in situ</i> generation of a methyleniminium ion from N,O-acetals, which promotes nucleophilic addition at the C3 position of indoles. The scalability of the process and successful downstream derivatizations further underscore the synthetic value of this strategy.