Substrate-Assisted Reductive Elimination Determining the Catalytic Cycle: A Theoretical Study on the Ni-Catalyzed 2,3-Disubstituted Benzofuran Synthesis via C–O Bond Activation

2,3-Disubstituted benzofurans with potential for pharmaceutical applications are effectively synthesized by Ni complexes via intramolecular C–O bond activation. The reaction pathway for the full catalytic cycle has been investigated using density functional theory (DFT) calculations. The rate-determining step is the reductive elimination of the product. A key result is that coordination to an alkynyl group of another substrate co-occurs with elimination, which not only improves thermodynamic stability of the product but also determines the reaction pathway of the catalytic cycle. The reductive elimination assisted by the solvent molecules or free ligand results in an endergonic reaction. This result is related to the enhancement of reductive elimination of C–C coupling products by the addition of olefins or alkynes and can be recognized as a self-cocatalytic effect of the substrate. The result adds another viewpoint in the design of catalytic reaction systems with effective catalytic cycles.