Sulfonylation of anilines through photocatalytic activation of N-hydroxymethylphthalimide sulfones
Sulfones, sulfonamides, and sulfonyl fluorides are valuable motifs in drug discovery and organic chemistry, yet their synthe-sis often relies on pre-functionalized substrates or harsh oxidants, limiting their applicability in complex settings. The genera-tion of sulfinyl radicals through photocatalytic means is one method to affect C-H sulfonylation chemistries. In this study, we have developed a N-hydroxymethylphthalimide (NHMP) sulfone functionality as a precursor to the sulfinyl radical after single electron reduction. The utility of the NHMP sulfone is demonstrated through the sulfonylation of aniline substructures including complex and biologically relevant scaffolds. The NHMP group was joined with a sulfinate protecting group (SPG) to yield a bifunctional reagent capable of delivering additional sulfur-(VI) functionalities such as sulfonamides and sulfonyl fluorides. Together, this work introduces a modular and operationally simple strategy for sulfone synthesis and offers a new avenue for late-stage diversification of aniline-based pharmaceuticals.
Authors
- Matthew J. Moschitto (ORCID: https://orcid.org/0000-0002-6758-7892)
- Twinkle I. Patel
- Sakshi Shah
- Malik Williams
- Jessica Linder
Institutions
- Rutgers, The State University of New Jersey (US)
Publication Details
- Journal
- ChemRxiv
- Published
- 2025-08-19
- DOI
- https://doi.org/10.26434/chemrxiv-2025-ql10s
- Primary Topic
- Sulfur-Based Synthesis Techniques
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- New Jersey Health Foundation