A study of Cascade N-Allylation/Dearomative Hydrolysis of Halogenated Pyridazines via Vinylcarbene Ylides. Chongchong Yan et al
Description
Research Hypothesis We hypothesized that a vinylcarbene metal complex generated from a cyclopropene could react with a halogenated pyridazine to form a pyridazine ylide intermediate, altering the electronic properties of the azaarene and facilitating SNAr-type hydrolysis and subsequent N-allylation under mild conditions in a one-pot cascade process. Data Overview This dataset contains raw NMR (¹H/¹³C), HRMS, GC/HPLC chromatograms, SC-XRD structure files, and anti-PVY antiviral activity data, organized into figure-corresponding compressed folders. Data Acquisition Methods NMR: Bruker Avance III 400/600 MHz, CDCl₃/DMSO-d₆/acetone-d₆, TMS internal standard, 298 K. HRMS: ESI-Q-TOF-MS. Yields: Isolated yields after column chromatography; E/Z ratios by ¹H NMR of crude mixtures. Antiviral assays: Half-leaf lesion method with ribavirin as positive control; performed in triplicate. Key Findings and Data Interpretation Optimal conditions (Table 1): Rh₂(esp)₂ (2.0 mol%), TFA (1.0 equiv.), EtOAc, 1.5 equiv. H₂O, rt, 24 h → product 3aa in 85% yield. Substrate scope: Halogenated pyridazines gave 52%–88% yields; EWG-substituted performed better (72%–88%), EDG gave 57%–63%. Cyclopropenes with aryl, alkyl, and spirocyclic groups reacted efficiently (51%–86%). Late-stage functionalization: Natural product and peptide-tethered substrates yielded 52%–76%, showing excellent amide bond compatibility. Derivatization and bioactivity: Gram-scale (7.0 mmol) gave 81%. Products underwent hydrogenation, amination, thionation, etc. Compounds 3Va, 3Wa, and 3Xa showed anti-PVY activity comparable to ribavirin. Mechanism: Isotope labeling (D₂O, H₂¹⁸O) confirmed water as H⁺ and O source. Control experiments confirmed the N-ylide pathway over pre-hydrolysis. Interpretation summary: This Rh-catalyzed one-pot cascade provides a mild, step-economical route to N-allyl pyridazinones, avoiding harsh conventional conditions and offering a versatile platform for drug discovery and agrochemical exploration. Raw data are available for validation and further analysis.
Files
Institutions
- Guizhou UniversityGuizhou, Guiyang