Kinetic Resolution of Racemic 2-Isoxazolines by Asymmetric Reduction

摘要

2-Isoxazolines and isoxazolidines are easily transformed to 1,3-amino alcohols, which are often used as intermediates for preparation of biologically active alkaloids and β-lactams. Our attempts for obtaining optically active isoxazolidines by metal-catalyzed asymmetric 1,3-dipolar cycloaddition of nitrones with olefins have applied to limited substrates, which have substituents coordinating to metals. On the other hand, substrates with no functionality for coordination to the metal in a bidentate fashion gave the products with poor enantioselectivity. Therefore, we tried palladium-catalyzed decomposition reaction of isoxazolidines in kinetic resolution as a new pathway to obtain optically active isoxazolidines. Here, we wish to describe the next trail, reduction of 2-isoxazolines to 1,3-amino alcohols directly and to isoxazolidines in kinetic resolution fashion (Scheme 1). Our aim is kinetic resolution by asymmetric reduction of the C=N double bond using chiral oxazaborolidine generated from 1,2-amino alcohols and borane, because the chiral oxazaborolidine-mediated reduction of oxime ethers, which is similar in structure to 2-isoxazolines, afforded optically active amines with high enantioselectivity.