Abstract
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 Ag(3)PO(4) as the oxidant, Rh promotes the formation of indoline radical cations stabilized by SbF(6) (-), enabling remote C5 thiolation via a single-electron transfer (SET) mechanism, as supported by the Fukui function. In contrast, Ag(2)O 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.