Efficient Access to Enantioenriched gem-Difluorinated Heterocycles via Silver-Catalyzed Asymmetric Cycloaddition Reaction

Abstract

gem-Difluorinated alkenes represent versatile building blocks to divergently access functional molecules containing gem-difluorinated methyl groups; however, little advances have been made on the transformations of gem-difluoro-1,3-dienes, particularly for the enantioselective versions. In this paper, we introduced an enantioselective [4 + 2] cycloaddition of gem-difluoro-1,3-butadienes with azodicarbonates catalyzed by AgSF 6 and (S)-MOP at a low catalyst loading that enables the generation of enantioenriched hydropyridazine derivatives in high yields and enantioselectivities (up to 98% yield, 98% ee). Control experiments and DFT analysis revealed that the cycloaddition reactions probably undergo a cascade reaction pathway, and azodicarbonates are activated by the chiral silver-(S)-MOP complex to control the enantioselectivities of the reactions.