Stereoselective Isoxazolidine Synthesis Via Copper-Catalyzed Alkene Aminooxygenation

摘要

Isoxazolidines are useful in organic synthesis, drug discovery, and chemical biology endeavors. A new stereoselective synthesis of methyleneoxy-substituted isoxazolidines is disclosed. The method involves copper-catalyzed aminooxygenation/cyclization of N-sulfonyl-O-butenyl hydroxylamines in the presence of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl radical (TEMPO) and O2 and provides substituted isoxazolidines in excellent yields and diastereoselectivities. We also demonstrate selective mono N–O reduction followed by oxidation of the remaining N–O bond to reveal a 2-amino-γ-lactone. Reduction of the γ-lactone reveals the corresponding aminodiol.