Year: 2026
Type: preprint
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.
Source: ChemRxiv
Institution: University of British Columbia
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7223378042