Ruthenium-Mediated C–H Functionalization of Pyridine: The Role of Vinylidene and Pyridylidene Ligands

A combined experimental and theoretical study has demonstrated that [Ru­(η⁵-C₅H₅)­(py)₂(PPh₃)]⁺ is a key intermediate, and active catalyst for, the formation of 2-substituted <i>E</i>-styrylpyridines from pyridine and terminal alkynes HCCR (R = Ph, C₆H₄-4-CF₃) in a 100% atom efficient manner under mild conditions. A catalyst deactivation pathway involving formation of the pyridylidene-containing complex [Ru­(η⁵-C₅H₅)­(κ³-<i>C</i>₃-C₅H₄NCHCHR)­(PPh₃)]⁺ and subsequently a 1-ruthanaindolizine complex has been identified. Mechanistic studies using ¹³C- and D-labeling and DFT calculations suggest that a vinylidene-containing intermediate [Ru­(η⁵-C₅H₅)­(py)­(CCHR)­(PPh₃)]⁺ is formed, which can then proceed to the pyridylidene-containing deactivation product or the desired product depending on the reaction conditions. Nucleophilic attack by free pyridine at the α-carbon in this complex subsequently leads to formation of a C–H agostic complex that is the branching point for the productive and unproductive pathways. The formation of the desired products relies on C–H bond cleavage from this agostic complex in the presence of free pyridine to give the pyridyl complex [Ru­(η⁵-C₅H₅)­(C₅H₄N)­(CCHR)­(PPh₃)]. Migration of the pyridyl ligand (or its pyridylidene tautomer) to the α-carbon of the vinylidene, followed by protonation, results in the formation of the 2-styrylpyridine. These studies demonstrate that pyridylidene ligands play an important role in both the productive and nonproductive pathways in this catalyst system