Room-Temperature Ring-Opening of Quinoline, Isoquinoline, and Pyridine with Low-Valent Titanium

The complex (PNP)Ti═CH^tBu(CH₂^tBu) (PNP = N[2-PⁱPr₂-4-methylphenyl]₂^-) dehydrogenates cyclohexane to cyclohexene by forming a transient low-valent titanium-alkyl species, [(PNP)Ti(CH₂^tBu)], which reacts with 2 equiv of quinoline (Q) at room temperature to form H₃C^tBu and a Ti(IV) species where the less hindered C₂═N₁ bond of Q is ruptured and coupled to another equivalent of Q. The product isolated from this reaction is an imide with a tethered cycloamide group, (PNP)Ti═N[C₁₈H₁₃N] (1). Under photolytic conditions, intramolecular C-H bond activation across the imide moiety in 1 occurs to form 2, and thermolysis reverses this process. The reaction of 2 equiv of isoquinoline (Iq) with intermediate [(PNP)Ti(CH₂^tBu)] results in regioselective cleavage of the C₁═N₂ and C₁-H bonds, which eventually couple to form complex 3, a constitutional isomer of 1. Akin to 1, the transient [(PNP)Ti(CH₂^tBu)] complex can ring-open and couple two pyridine molecules, to produce a close analogue of 1, complex (PNP)Ti═N[C₁₀H₉N] (4). Multinuclear and multidimensional NMR spectra confirm structures for complexes 1-4, whereas solid-state structural analysis reveals the structures of 2, 3, and 4. DFT calculations suggest an unprecedented mechanism for ring-opening of Q where the reactive intermediate in the low-spin manifold crosses over to the high-spin surface to access a low-energy transition state but returns to the low-spin surface immediately. This double spin-crossover constitutes a rare example of a two-state reactivity, which is key for enabling the reaction at room temperature. The regioselective behavior of Iq ring-opening is found to be due to electronic effects, where the aromatic resonance of the bicycle is maintained during the key C-C coupling event.