Two-Stage Catalysis in the Pd-Catalyzed Formation of 2,2,2-Trifluoroethyl-Substituted Acrylamides: Oxidative Alkylation of Pd^IIby an I^IIIReagent and Roles for Acetate, Triflate, and Triflic Acid

Abstract

In the synthesis of 2,2,2-trifluoroethyl-substituted acrylamides, two-stage palladium-catalysis is indicated experimentally, including oxidative alkylation of PdII to PdIV by [IIIIMes(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 IIII to give a PdIV 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 PdIV, 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.