Asymmetric difluoroalkylation via Michael addition of an in situ generated difluoroenol intermediate†

Abstract

A dirhodium and chiral Zn-complex co-catalyzed asymmetric difluoroalkylation of isatylidene malononitriles via a Michael-type interception of α,α-difluoroenol species, which are 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 containing a chiral quaternary carbon center in generally good yields and with excellent stereoselectivities (91%–99% ee). Compared with difluoroenoxysilane, this difluoroenol intermediate showed higher reactivity and enantioselectivity under mild conditions.