Asymmetric 1,3‐Dipolar Cycloaddition Reactions of Benzonitrile Oxide Mediated by a Chiral Lewis Acid

Abstract

Abstract In this paper we report on the asymmetric 1,3‐dipolar cycloaddition reactions of nitrile oxides mediated by pybox/ytterbium triflates, ‐/magnesium bromide, and ‐/magnesium perchlorate. It was confirmed that the reactions proceed smoothly to give isoxazoline derivatives in high enantiomeric excesses with Mg 2+ or Yb 3+ complexes and acrylamide dipolarophiles bearing an oxazolidinone or imidazolidinone coordination auxiliary as well as a pybox ligand. In reactions with a dipolarophile bearing 4,4‐dimethyloxazolidinone as the coordination auxiliary, an enantiomeric excess (59 % ee ) of the corresponding cycloaddition product was achieved by using a slow addition technique to generate nitrile oxides in the presence of Yb(OTf) 3 /ph‐pybox. The cycloaddition reaction of a dipolarophile with an unsubstituted oxazolidinone group in the presence of Yb(OTf) 3 /ph‐pybox at a relatively high temperature (35 °C) produced a higher enantiomeric excess. A relatively low temperature (–78 °C) was required to obtain enantiomeric excesses such as 69 and 87 % ee in the reactions of a dipolarophile bearing an imidazolidinone group to afford cycloadducts in the presence of MgBr 2 /ip‐pybox.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)