A novel method for the synthesis of α,α-difluoro-γ-lactam derivatives has been developed using a copper/amine catalyst via a tandem radical cyclization pathway. This protocol provides a convenient and straightforward strategy for the rapid construction of various 3,3-difluoro-γ-lactam moieties from easily available alkenes and N-aryl bromodifluoroacetamide as starting materials under mild reaction conditions.

Isoxazoline derivatives have been disclosed in the art as having acaricidal and insecticidal activity and as potential precursors for the syntheses of natural products. This work first demonstrates the chiral resolution of isoxazoline derivatives that had not been studied before on native cyclodextrin (CD) chiral stationary phases (CSPs). Two structurally well-defined CSPs based on native CD were prepared via different click procedures and applied for the enantioseparation of isoxazolines. Most of the studied isoxazolines were found to be well resolved (Rs > 1.5) under reversed phase mode, especially 4NPh-OPr, which exhibits the best enantioselectivity and resolution (α = 2.22; Rs = 4.16). Optimal resolutions were achieved by evaluating the influences of mobile phase composition, substitution moieties and CSP linkages on the separation. This contribution verifies that excellent enantioseparation of isoxazolines can be accomplished on smartly designed native CD-CSP, which provides a facile and economic way to obtain enantiopure isoxazoline derivatives.