Rhodium-Catalyzed Enantioselective Defluorinative α-Arylation of Secondary Amides

Abstract

We exploited the reactivity of an electronically biased Michael acceptor to perform a defluorinative α-arylation reaction using a chiral diene(L*)-rhodium catalyst. Through this methodology, we are able to obtain various secondary amides, containing a tertiary α-stereocenter and a β,γ-unsaturated gem-difluoro olefin, with excellent enantioselectivities. This methodology addresses the limitations of the previously described α-arylation methods to construct stereo-labile tertiary α-stereocenters. Further investigation of the reaction via in situ ¹⁹ F NMR monitoring suggests that the formation of the product leads to the inhibition of the active rhodium catalyst.

Keywords: asymmetric catalysis; defluorinative arylation; rhodium catalysis.