Direct Metal-Free Transformation of Alkynes to Nitriles: Computational Evidence for the Precise Reaction Mechanism.

Density functional theory calculations elucidated the precise reaction mechanism for the conversion of diphenylacetylenes into benzonitriles involving the cleavage of the triple C≡C bond, with -iodosuccinimide (NIS) as an oxidant and trimethylsilyl azide (TMSN) as a nitrogen donor. The reaction requires six steps with the activation barrier Δ = 33.5 kcal mol and a highly exergonic reaction free-energy Δ = -191.9 kcal mol in MeCN. Reaction profiles agree with several experimental observations, offering evidence for the formation of molecular I, interpreting the necessity to increase the temperature to finalize the reaction, and revealing thermodynamic aspects allowing higher yields for alkynes with para-electron-donating groups. In addition, the proposed mechanism indicates usefulness of this concept for both internal and terminal alkynes, eliminates the option to replace NIS by its Cl- or Br-analogues, and strongly promotes NaN as an alternative to TMSN. Lastly, our results advise increasing the solvent polarity as another route to advance this metal-free strategy towards more efficient processes.