Fluorine-Activated and -Directed Allene Cycloadditions with Nitrile Oxides and Imine Oxides: Synthesis of Ring-Fluorinated Isoxazole Derivatives

In this study, 1,1-difluoroallenes underwent a regioselective [2+3] cycloaddition with nitrile oxides and imine oxides in the presence of a AuCl catalyst. (E)-4-Alkylidene-5,5-difluoroisoxazolines and -isoxazolidines were obtained in regioselective and diastereoselective manners by employing aurated difluoroallylic cation intermediates. The synthesized 5,5-difluoroisoxazolines were readily aromatized through dehydrofluorination or allylic fluorine substitution to provide 5-fluoroisoxazoles.

Automated summary

In this study, a regioselective [2+3] cycloaddition reaction of 1,1-difluoroallenes with nitrile oxides and imine oxides was achieved in the presence of an AuCl catalyst. The reaction produced (E)-4-alkylidene-5,5-difluoroisoxazolines and -isoxazolidines in a regioselective and diastereoselective manner using aurated difluoroallylic cation intermediates. The synthesized 5,5-difluoroisoxazolines could be easily aromatized into 5-fluoroisoxazoles through dehydrofluorination or allylic fluorine substitution.