Two-stage catalysis in the Pd-catalyzed formation of 2,2,2-trifluoroethyl-substituted acrylamides: oxidative alkylation of PdII by an IIII reagent and roles for acetate, triflate, and triflic acid

In the synthesis of 2,2,2-trifluoroethyl-substituted acrylamides, two-stage palladium-catalysis is indicated experimentally, including oxidative alkylation of Pd^II to Pd^IV by [I^IIIMes(CH₂CF₃)]⁺ (Besset et al., Chem. Commun., 2021, 57, 6241). For N-(quinolin-8-yl)-2-(phenyl)acrylamide [LH₂ = H₂C═C(Ph)–C(O)–NH∼N], studied by density functional theory herein, the first stage involves palladium acetate-promoted NH-deprotonation and concerted metalation-deprotonation CH-activation for Pd(OAc)₂(LH₂), followed by the transfer of [CH₂CF₃]⁺ from I^III to give a Pd^IV intermediate that undergoes reductive elimination to form the acrylamide-CH₂CF₃ linkage. The second stage employs [Pd(LH)(NCMe)]⁺ as the catalyst, with steps including outer-sphere CH-activation by triflate and crucial roles for Pd^IV, acetonitrile solvent, and N-protonation of the product by triflic acid to form [LH₂(CH₂CF₃)]⁺. In an apparently unique process, the first stage is faster than the second and produces the catalyst, but the second stage is catalytic to provide high yields of the product.