Catalytic Asymmetric Chlorination of Isoxazolinones

Abstract

Organic compounds featuring a chlorine substituted stereocenter are frequently found in nature and are interesting for pharmaceutical applications and as synthetic building blocks. Catalytic methods to generate such stereocenters by C,H bond functionalization are still relatively rare. Here we report the first catalytic asymmetric chlorination of isoxazolinones, a synthetically and biologically interesting class of heterocycles, which can be considered as precursors for β-aminoacids. The title reaction was catalyzed with high enantioselectivity by a planar chiral ferrocene based palladacycle in high to excellent yields. It is showcased that the products are valuable for post-synthetic transformations. An SN2 reaction proceeded with smooth inversion of the absolute configuration. The substitution product could then be transformed into an α-azido β-aminoacid derivative via a reductive, diastereoselective ring opening.