Ruthenium-mediated C-H functionalization of pyridine: the role of vinylidene and pyridylidene ligands

Abstract

A combined experimental and theoretical study has demonstrated that [Ru(η(5)-C(5)H(5))(py)(2)(PPh(3))](+) is a key intermediate, and active catalyst for, the formation of 2-substituted E-styrylpyridines from pyridine and terminal alkynes HC≡CR (R = Ph, C(6)H(4)-4-CF(3)) in a 100% atom efficient manner under mild conditions. A catalyst deactivation pathway involving formation of the pyridylidene-containing complex [Ru(η(5)-C(5)H(5))(κ(3)-C(3)-C(5)H(4)NCH═CHR)(PPh(3))](+) and subsequently a 1-ruthanaindolizine complex has been identified. Mechanistic studies using (13)C- and D-labeling and DFT calculations suggest that a vinylidene-containing intermediate [Ru(η(5)-C(5)H(5))(py)(═C═CHR)(PPh(3))](+) 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(η(5)-C(5)H(5))(C(5)H(4)N)(═C═CHR)(PPh(3))]. 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.