Mechanisms of C(sp3)-H Functionalization of Acetonitrile or Acetone with Alkynes: A DFT Investigation.

The mechanisms for the C(sp³)-H activation and addition reactions between acetonitrile (or acetone) and alkynes have been investigated with the M06-2X-D3/ma-def2-TZVP method and basis set. The SMD (solvation model based on solute electron density) model was applied to simulate the solvent effect. In the first and second reactions, 2-phenylbut-3-yn-2-ol reacted with acetonitrile and acetone, respectively. First, the C(sp³)-H activations of acetonitrile and acetone could be achieved by PhCOO^• and t-BuO^• radicals. Then, addition reactions converted 2-phenylbut-3-yn-2-ol into final products P1 and P2. Gibbs free energy surfaces of these two reactions suggest that blue lines would be the favorable paths with lower Gibbs energy barriers, and the terminal C atom of the C≡C bond is the best reactive site. Moreover, the analysis of the IRI (Interaction Region Indicator) reveals the Z- and E-configuration transformations. While in the third and fourth reactions, methyl(2-(phenylethynyl)phenyl)sulfane has interactions with acetonitrile and acetone via some paths, respectively. Gibbs free energy profiles show that the C10 atom, rather than the C11 atom, has priority, and the blue lines are favorable. Furthermore, the action mode of Na₂HPO₄ could reduce the energy barrier and benefit the reaction. vdW (van der Waals) interactions play an important role in the choice for the reactive site. In the fifth (or sixth) reaction, it happened between 1-(2-(methylthio)phenyl)-3-phenylprop-2-yn-1-one and acetontrile (or acetone) to yield the final product P5 (or P6). The computational results uncovered the blue line is the best path, and the choice for the reactive site depends on the vdW interactions, which reveals the origin of selectivity. In addition, the investigation for the byproducts have been carried out, and these can explain the reason that only the main product is produced. Both of those can agree with the experimental results. The localized orbital locator (LOL) isosurfaces, Laplacian bond order (LBO), electron density of the bond critical point (ρ_BCP), electron spin density isosurface graphs, and IRI graphs can be used to analyze the structure and reveal the reaction substances.