Asymmetric difluoroalkylation via Michael addition of in situ generated difluoroenol intermediate

Abstract

A dirhodium and chiral Zn-complex co-catalyzed asymmetric difluoroalkylation of isatylidene malononitriles via Michael-type interception of α,α-difluoroenol species, which generated in situ from trifluoromethyl diazo compounds and water in the presence of Rh2(esp)2, has been disclosed. This reaction provides an efficient approach for the synthesis of fluorinated oxindoles incorporating a chiral quaternary carbon center in generally good yields and excellent stereoselectivity (91%–99% ee). Comparion with difluoroenoxysilane, this difluoroenol intermediate demonstrated higher reactivity and enantioselectivity under mild conditions.