In this work, we conducted a study of 7‐exo‐trig cyclizations mechanism involving aryl, vinyl, and alkyl radicals on oxime ethers. Initially, the reaction of brominated oxime ether 9 a with (TMS)₃SiH and AIBN gave rise to aryl radicals that underwent a 7‐exo‐trig cyclization on the oxime ether, yielding dibenzoxepine 10 a, and the ipso reaction and reduction products were obtained as well. Approximate rate constants at 80 °C for the 7‐exo‐trig (1.0×10⁸ s⁻¹) and the ipso cyclization (4.3×10⁷ s⁻¹) were determined by competition experiments. DFT calculations showed good agreement with the experimental results. The reduction rate constant of the N‐alkoxyaminyl radical with (TMS)₃SiH was calculated to be 4.1×10⁻¹ M⁻¹ s⁻¹; while the rate constants for the 7‐exo‐trig cyclizations of vinyl and alkyl radicals on the oxime ether were estimated in the ranges of 10⁶ s⁻¹–10⁸ s⁻¹ and 10³ s⁻¹–10⁸ s⁻¹, respectively. The 7‐exo‐trig cyclization reactions involving aryl, vinyl, and alkyl radicals with oxime ethers were found to be an exothermic and irreversible process, with the oximic carbon showing a preference for nucleophilic alkyl radicals. This kinetic study contributes to the deeper understanding of radical‐mediated cyclizations, enabling the efficient design of complex synthetic routes.

The mechanism and kinetic constants of the cascade cyclization involving vinyl, aryl and N-alkoxyaminyl radicals for the formation of 1-azaspiro[4.4]nonanes.

This study reports the synthesis, characterization, and antifungal evaluation of a series of pyridoxal and salicylaldehyde derivatives, using synthetic methodologies such as radical cyclizations and click chemistry. Compounds 6a and 6b, featuring a fused dihydrobenzoxepine-pyridine scaffold, demonstrated effective fungicidal activity with MIC values of 19 µg/mL against Cryptococcus neoformans 2807. Similarly, compound 6b exhibited notable activity with a MIC of 75 µg/mL against Candida auris PUJ-HUSI 537. Both compounds outperformed fluconazole (FLC) in these strains. In silico ADMET profiling revealed favorable pharmacokinetic properties, including blood–brain barrier penetration and drug-likeness parameters consistent with Lipinski’s rule of five. Cytotoxicity assays on human fibroblasts confirmed the low toxicity of compound 6a at the tested concentrations. These results highlight the potential of the fused dihydrobenzoxepine-pyridine scaffold as a promising antifungal candidate for further investigations.