Enantioselective Defluorinative C(sp2)–H Allylation of Acrylamides Enabled by CpxRh(III) Catalysis

Abstract Chiral fluoroalkenes are high-value synthetic targets; however, the development of efficient catalytic asymmetric methods for their assembly from abundant precursors remains a formidable challenge. Herein, we report a convergent strategy that merges asymmetric alkenyl C(sp2)–H functionalization with defluorinative coupling, enabling the direct, enantioselective synthesis of fluorinated skipped 1,4-dienes from readily available starting materials. Facilitated by a chiral CpxRh(III) catalyst, this enantioselective olefin–olefin cross-coupling leverages abundant acrylamides and amide-substituted allylic difluorides to provide streamlined access to a structurally diverse array of enantioenriched fluorinated 1,4-dienes with high efficiency and excellent stereocontrol (up to 99% yield, 99% ee). Mechanistic studies suggest that the transformation proceeds via a sequence of site-selective alkenyl C–H activation, enantioselective migratory insertion, and β-fluoride elimination. Remarkably, ester-derived allylic difluorides induce divergent cascade reactivity, allowing efficient construction of valuable chiral 2-piperidones with excellent enantio- and diastereoselectivity. This step-economical protocol offers a versatile platform for the rapid construction of complex fluorinated motifs from simple chemical feedstocks.