Pyridyl Radical-Induced Catalytic Reconstruction of Cyclic Sulfides
Abstract
Ring-expansion editing offers a transformative strategy that could reshape the landscape of ring scaffold construction in synthetic chemistry. The introduction of three-dimensionality ring into flat aromatic systems could afford important semisaturated fused heterocycles, yet efficient method to access sulfur-containing semisaturated fused pyridines (SSFPs) remains scarce. Herein, we report a pyridyl radical-driven catalytic strategy for the direct two-carbon ring expansion of readily available cyclic thioethers, providing efficient access to synthetically challenging SSFPs. This transformation is enabled by synergistic dual photoredox cycles that orchestrate a cascade of radical cross-coupling, C(sp 3 )–S bond cleavage, and intramolecular cyclization between commercial bromopyridines and cyclic sulfides. The protocol demonstrates broad functional-group tolerance and substrate generality. Gram-scale synthesis and extensive downstream derivatizations, including late-stage semisaturation of pharmaceutical cores, highlight its synthetic utility. Mechanistic studies support a stepwise radical process involving discrete pyridyl and carbon-centered radical intermediates. This method offers a step-economical and modular alternative to conventional de novo synthesis for the rapid construction of complex, drug-like heterocyclic architectures.
Fields of Study & Subjects
Radical Photochemical Reactions
Sulfur-Based Synthesis Techniques
Catalytic C–H Functionalization Methods
Publication details
- Journal / source
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Volume
- 148
- Issue
- 27
- Pages
- 29408–29418
- Publication date
- 27 June 2026
- Language
- EN