Precise Editing of Indolines at Different Positions via SET and CMD Pathways

In drug discovery, the pursuit of concise and specific synthetic methods is driving the development of new strategies. Particularly during the late stages of a synthetic sequence, when the substrate molecule contains multiple highly similar C–H bonds, the ability to achieve selective “molecular editing” using mild and precise transformations has become a crucial capability. Here, we report Rh-catalyzed molecular editing of indoline derivatives at different positions via a single, oxidant-tunable catalytic system. Using Ag3PO4 as the oxidant, Rh promotes the formation of indoline radical cations stabilized by SbF6–, enabling remote C5 thiolation via a single-electron transfer (SET) mechanism, as supported by the Fukui function. In contrast, Ag2O suppresses the SET pathway, as confirmed by the ABTS assay, and enables C7-selective thiolation through a concerted metalation–deprotonation (CMD) process mediated by a Rh(III)/MPAA ligand system. Mechanistic experiments and Fukui indices calculation elucidate the origin of the observed regiodivergence, highlighting the dual reactivity of Rh(III) and offering new conceptual insights into oxidant-controlled C–H functionalization.