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.
Bibliographical noteFunding Information:
This work was supported by the National Science Foundation under the CCI Center for Selective C–H Functionalization (CHE-1700982). The authors gratefully acknowledge the use of the resources of the Cherry Emerson Center for Scientific Computation at Emory University. L.-P. Xu acknowledges the Natural Science Foundation of China (NSFC 21702126) and the China Scholarship Council for support.
© 2021 American Chemical Society
- CH functionalization
- DFT calculations
- directing group assisted
- reaction mechanism
ASJC Scopus subject areas