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

Abstract

A variety of 1,2,4-oxadiazoline derivatives were synthesized in moderate to good yields through a deoxygenative cyclization cascade reaction of N-vinyl-α,β-unsaturated nitrones and hydroxamoyl chlorides. Mechanistic studies revealed that the reaction underwent double additions of nitrile oxides to N-vinyl-α,β-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.

Desymmetric [3+3] Cyclization of p-Quinamines for the Synthesis of 1,2,4-Oxadiazines and Hydroquinoxalines

“…We anticipated that p -quinamines might be general precursors for the construction of 1,2,4-oxadiazine and hydroquinoxaline skeletons to realize [3+3] cyclization with suitable three-atom units. 1,3-Dipole surrogates such as hydroximoyl halides and α-halohydroxamates have been used as three-atom synthons in recent years to synthesize nitrogen-containing heterocycles. Under base treatment, a nitrile oxide intermediate could be generated from hydroximoyl halide, and an azaoxyallyl cation intermediate could be generated from α-halohydroxamate.…”