Photoredox-Mediated Radical Smiles-Truce Rearrangement: From Aryl Migration to Molecular Complexity Generation.

The Smiles-Truce rearrangement represents a uniquely powerful but historically underutilized strategy for arene functionalization, enabling intramolecular C-C bond formation through controlled molecular reorganization. Despite its conceptual appeal as a strategic disconnection, its traditional implementation as a two-electron SNAr process has relied on strong bases and polarized reaction manifolds, which restrict functional group tolerance, limit substrate scope, and thus confine its use to relatively simple molecular settings. The emergence of radical Smiles-Truce rearrangements, particularly those enabled by visible-light photoredox catalysis, has fundamentally altered how this transformation can be deployed in synthesis. Rather than functioning only as a specialized SNAr variant, the Smiles-Truce rearrangement can be redeployed as a general radical relay for ipso-selective arene functionalization and framework reorganization. Photoredox catalysis enables mild, catalytic access to tethered radical intermediates that engage arenes intramolecularly, bypassing the constraints of polar reactivity and allowing the rearrangement to be applied in complex, functionalized environments. Photoredox-mediated Smiles-Truce rearrangements proceed through the generation of carbon-centered radicals that add intramolecularly to (hetero)arenes, forming transient spirocyclic radical Meisenheimer intermediates. Fragmentation of sulfur-based leaving groups then forges new C-C bonds in a single, efficient sequence. This radical framework enables the direct conversion of simple, abundant building blocks, including sulfonyl chlorides, alcohols, amines, and olefins, into architecturally complex products. Importantly, multiple photoredox activation modes, such as single-electron transfer, proton-coupled electron transfer, and deprotonation-oxidation pathways, expand the strategic reach of this rearrangement and highlight its modularity. In this Account, we illustrate how photoredox-enabled Smiles-Truce rearrangements can be strategically leveraged to achieve diverse synthetic objectives, including arene dearomatization, alcohol-derived framework reorganization, and olefin aminoarylation with high diastereocontrol. We further highlight the robustness and scalability of these reactions, as well as their application to the concise synthesis of bioactive targets. Finally, we demonstrate how transitioning from S(VI) to S(IV) intermediates enables enantiospecific variants of the Smiles-Truce rearrangement, introducing stereochemical control into a transformation long considered stereochemically agnostic. Together, these studies show how photoredox catalysis transformed the Smiles-Truce rearrangement from a specialized aryl-migration reaction into a programmable platform for molecular reorganization and C-C bond construction. By coupling radical logic with photoredox catalysis, this transformation enables direct reorganization of molecular frameworks from simple precursors under mild conditions, significantly expanding its utility in modern synthetic and medicinal chemistry.