Ruthenium-Catalyzed Selective C4 C-H Phosphorylation of Indoles and Mechanistic Insights

Phosphorylated indoles are valuable motifs in medicinal chemistry and functional materials, attracting considerable attention for their efficient and selective synthesis. We report the first ruthenium-catalyzed direct C-H phosphorylation at C4 of indoles, without preprotection of C2 and C3. This strategy enables the efficient construction of structurally diverse phosphorylated indole derivatives and delivers N-H-free phosphorylated indoles in high yields via a one-pot deprotection sequence. Density functional theory (DFT) studies revealed that steric effects from bulky N-substituents are the key driving force for C4 selectivity, effectively suppressing competing activation pathways at C2 and C3 and thus enabling excellent regioselective control.