Synthesis of 1,2,4-Oxadiazolines through Deoxygenative Cyclization of N-Vinyl-α,β-Unsaturated Nitrones with in Situ Generated Nitrile Oxides from Hydroxamoyl Chlorides

A variety of 1,2,4-oxadiazoline derivatives were synthesized in moderate to good yields through a deoxygenative cyclization cascade reaction of N-vinyl-alpha,beta-unsaturated nitrones and hydroxamoyl chlorides. Mechanistic studies revealed that the reaction underwent double additions of nitrile oxides to N-vinyl-alpha,beta unsaturated nitrones, sequential elimination, and intramolecular cyclization to afford 1,2,4-oxadiazolines. Alternatively, 1,2,5-oxadiazolines were also obtained as major products in i-PrOH solvent through [3 + 3] cycloaddition and selective [3,3]-rearrangement. Moreover, the prepared 1,2,4-oxadiazolines were easily converted to polysubstituted pyrroles under thermal conditions.

Automated summary

A series of 1,2,4-oxadiazoline derivatives were successfully synthesized through a deoxygenative cyclization reaction of N-vinyl-alpha,beta-unsaturated nitrones and hydroxamoyl chlorides. The reaction proceeded through double additions of nitrile oxides, sequential elimination, and intramolecular cyclization. Additionally, 1,2,5-oxadiazolines were also obtained in specific solvents. The prepared 1,2,4-oxadiazolines could be easily transformed into polysubstituted pyrroles under thermal conditions.