Year: 2025
Type: preprint
Abstract: Skeletal and peripheral editing of pyridines is a powerful strategy for late-stage functionalisations of N-heterocycles, in particular pyridines. While pyridines inherently exhibit high reactivity at the C2 and C4 positions due to their electronic structure, functionalization at the C3 position is significantly more challenging and less explored. Herein, we report a distinct dearomatization–rearomatisation strategy that transforms 2-substituted pyridines into synthetically challenging 3-acylpyridines via an unprecedented rearrangement of a Zincke imine. This intermediate first undergoes a regioselective formylation followed by an isomerisation–hydrolysis cascade to deliver the desired pyridine derivatives in good to excellent yields. Notably, an operationally simple one-pot variant circumvents the need to isolate Zincke imines –a bottleneck in related methodologies. In contrast to traditional electrophilic formylation, our strategy proceeds under mild conditions and exhibits high selectivity for the electron-deficient triene fragment, leaving electron-rich aromatic motifs untouched.
Source: ChemRxiv
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Award: G4911666105
OpenAlex ID: W4413376835