Thioiminium Salt Catalyzed Chemoselective Late Stage Halogenation Using N-Halosuccinimides
Abstract
C−H halogenation plays a central role in drug discovery. It enables rapid molecular diversification and provides a direct means to tune the metabolic and biological properties of drug candidates. However, selective halogenation of less reactive arenes remains challenging, particularly when aromatic and benzylic C−H bonds coexist in the same molecule. Here, we introduce a thioiminium salt-based Lewisbase catalyst that activates readily available N-halosuccinimides for selective aromatic and benzylic halogenation with complementary control. Notably, the method enables late-stage aromatic bromination of natural products, pharmaceuticals, peptides and heterocycles and can be extended to aromatic chlorination using N-chlorosuccinimide. The practicality of this method is demonstrated by four gramscale syntheses, catalyst recycling and post-synthetic diversification. Mechanistic and computational studies reveal distinct electrophilic and radical pathways, with the catalyst counter anion acting as a molecular switch for chemoselectivity between aromatic and benzylic bromination.
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BibTeX
@misc{sahoo2026thioiminium,
title = {{Thioiminium Salt Catalyzed Chemoselective Late Stage Halogenation Using N-Halosuccinimides}},
author = {Debasis Sahoo and Upasi Goswami and Haren Konwar and Arnab Mondal and Avijit Maiti and Tuhin Patra},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15010130/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010130/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Thioiminium Salt Catalyzed Chemoselective Late Stage Halogenation Using N-Halosuccinimides
AU - Debasis Sahoo
AU - Upasi Goswami
AU - Haren Konwar
AU - Arnab Mondal
AU - Avijit Maiti
AU - Tuhin Patra
PY - 2026
DA - 2026/10/08
PB - ChemRxiv
DO - 10.26434/chemrxiv.15010130/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010130/v1
AB - C−H halogenation plays a central role in drug discovery. It enables rapid molecular diversification and provides a direct means to tune the metabolic and biological properties of drug candidates. However, selective halogenation of less reactive arenes remains challenging, particularly when aromatic and benzylic C−H bonds coexist in the same molecule. Here, we introduce a thioiminium salt-based Lewisbase catalyst that activates readily available N-halosuccinimides for selective aromatic and benzylic halogenation with complementary control. Notably, the method enables late-stage aromatic bromination of natural products, pharmaceuticals, peptides and heterocycles and can be extended to aromatic chlorination using N-chlorosuccinimide. The practicality of this method is demonstrated by four gramscale syntheses, catalyst recycling and post-synthetic diversification. Mechanistic and computational studies reveal distinct electrophilic and radical pathways, with the catalyst counter anion acting as a molecular switch for chemoselectivity between aromatic and benzylic bromination.
ER -