Synthesis of α-aminooxy amides through [3 + 3] cycloaddition and Sc(OTf)3-catalyzed double C–N bond cleavage in a one-pot reaction

Abstract

Various α-aminooxy amides bearing a quaternary carbon at the α-position were prepared in good to excellent yields under mild reaction conditions from N-vinyl nitrones and α-bromohydroxamates. The N-vinyl nitrones tolerate a wide range of N-vinyl fluorenone nitrones and N-vinyl isatin nitrones. Mechanistic studies show that the reaction initially proceeds through [3 + 3] cycloaddition between N-vinyl nitrones and aza-oxyallyl cations generated from α-bromohydroxamates to afford six-membered N,O-heterocycles, followed by double C–N bond cleavage in the presence of the Sc(OTf)₃ catalyst. A selective N–O bond cleavage of the obtained α-aminooxy amides is also realized under Fe/NH₄Cl conditions. Furthermore, gram-scalable preparations of α-aminooxy amides are easily achieved.