Synthesis of Unsymmetrical C2,3-Bis-sulfenylated Indoles via Bimetallic Cu/Fe Relay Catalysis

The synthesis of unsymmetrical C2,3-bis(sulfenyl)indoles represents a significant challenge in heterocyclic chemistry due to the difficulty in controlling site-selective sequential functionalization. Herein, we report an efficient bimetallic Cu/Fe relay catalysis strategy for the one-pot construction of these privileged scaffolds starting from indole-2-thiones, disulfides, and halides. This protocol features a sequential dual-catalytic pathway: a copper-catalyzed C-S coupling installs the C2-sulfenyl motif, followed by an iron-mediated regioselective electrophilic sulfenylation at the C3 position. The reaction proceeds with high step economy and broad substrate scope, tolerating a wide range of functional groups including heteroaryl and alkyl moieties. Notably, this method obviates the need for intermediate isolation, offers excellent scalability (gram-scale), and enables the late-stage functionalization of complex bioactive molecules, providing a robust platform for accessing structurally differentiated bis-sulfenylated indoles.