MsOH Promoted Divergent Synthesis of 4-Arylidene Isoxazolidines and Isoxazolines from O-Propargyl Hydroxylamines and Aldehydes

Temperature-dependent, Brønsted-acid-mediated divergent synthesis of 4-arylidene isoxazolidines and isoxazolines from O-propargyl hydroxylamines is developed. A series of control and crossover experiments have been carried out, revealing that the formation of 4-arylidene isoxazoline proceeds through an alkyne-oximium cyclization, ring-opening reaction, and subsequent condensation. Synthetic versatility of the developed methodology was highlighted in the synthesis of 3-aminoacrylaldehyde, β-hydroxy ketone, and isoxazole derivatives.