Unified Mechanistic Concept of the Copper-Catalyzed and Amide-Oxazoline-Directed C(sp²)-H Bond Functionalization

Density functional theory calculations have been performed to provide the unified mechanism of Cu(II)-catalyzed and amide-oxazoline (Oxa)-directed C(sp²)-H functionalization reactions. The common steps of the studied seven reactions (such as C-H bond vinylation, phenylation, trifluoromethylation, amination, alkynylation, and hydroxylation) are complexation, N-H and C-H bond deprotonation, and Cu(II)/Cu(II) → Cu(I)/Cu(III) disproportionation, leading to the Cu(III) intermediate. The mechanism of the studied C-H functionalization reactions, initiated from the Cu(III) intermediate, depends on the nature of coupling partners. With vinyl- or phenyl-Bpin, which bear no acidic proton (called as a Type-I reaction), the coupling partners are thein situgenerated (by addition of anions) anionic borates, which coordinate to the Cu(III) intermediate and undergo concerted transmetalation and reductive elimination to form a new C-C bond. In contrast, with imidazole, aromatic amines, terminal alkyne, and water (called as a Type-II reaction), which bear an acidic proton, the real coupling partners are theirin situgenerated deprotonated derivatives, which coordinate to copper and lead to a final product with the C-Y bond (Y = C, N, and O) via the reductive elimination pathway. The C(sp²)-H bond trifluoromethylation with TMSCF₃is identified as a special case, positioned between the Type-I and Type-II reaction types. The real coupling partner of this reaction is thein situgenerated (via the CF₃^--to-OH^-ligand exchange) CF₃^-anion that binds to the Cu(III) intermediate and undergoes the C-CF₃reductive elimination. Our calculations, consistent with the experimental KIE study, have established C-H bond activation as a rate-limiting step for all reactions.