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PreprintCC BY-NCChemRxiv

Ipso-selective pyridine-to-aniline editing through amine-induced fragmentation

  • Benjamin R. Boswell1,2
  • Corey R. J. Stephenson1,2
  1. 1Department of Chemistry
  2. 2University of British Columbia
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Abstract

Skeletal editing enables the remodeling of aromatic frameworks, but pyridine-to-aniline conversions can generate multiple positional isomers, complicating analogue synthesis. Here we report an ipso-selective strategy that separates regiochemical control from diversification of the aniline nitrogen. Pyridines are converted through dearomatization and cycloaddition into stable, isolable bicyclic ketones, which undergo amine-induced condensation–fragmentation to afford anilines with the amino group positioned at the site corresponding to the original pyridine nitrogen. Both primary and secondary amines participate, enabling divergent synthesis from a common intermediate. Notably, regioisomeric intermediates derived from a 3-substituted pyridine converge to a single aniline product. The method also enables preparation of multiple analogues from a tropicamide-derived scaffold, illustrating the potential of this modular approach for medicinal-chemistry scaffold diversification.

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Cite

BibTeXRIS
BibTeX
@misc{boswell2026ipsoselective,
  title = {{Ipso-selective pyridine-to-aniline editing through amine-induced fragmentation}},
  author = {Benjamin R. Boswell and Corey R. J. Stephenson},
  howpublished = {ChemRxiv},
  year = {2026},
  month = oct,
  doi = {10.26434/chemrxiv.15010949/v1},
  url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010949/v1},
  note = {CC BY-NC},
}
RIS
TY  - UNPB
TI  - Ipso-selective pyridine-to-aniline editing through amine-induced fragmentation
AU  - Benjamin R. Boswell
AU  - Corey R. J. Stephenson
PY  - 2026
DA  - 2026/10/23
PB  - ChemRxiv
DO  - 10.26434/chemrxiv.15010949/v1
UR  - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010949/v1
AB  - Skeletal editing enables the remodeling of aromatic frameworks, but pyridine-to-aniline conversions can generate multiple positional isomers, complicating analogue synthesis. Here we report an ipso-selective strategy that separates regiochemical control from diversification of the aniline nitrogen. Pyridines are converted through dearomatization and cycloaddition into stable, isolable bicyclic ketones, which undergo amine-induced condensation–fragmentation to afford anilines with the amino group positioned at the site corresponding to the original pyridine nitrogen. Both primary and secondary amines participate, enabling divergent synthesis from a common intermediate. Notably, regioisomeric intermediates derived from a 3-substituted pyridine converge to a single aniline product. The method also enables preparation of multiple analogues from a tropicamide-derived scaffold, illustrating the potential of this modular approach for medicinal-chemistry scaffold diversification.
ER  -