Synthetic and mechanistic studies of the ring opening and denitrogenation of pyridine and picolines by Ti-C multiple bonds

The neopentylidene-neopentyl complex (PNP)Ti=CH^tBu(CH ₂^tBu) (1; PNP^- = N[2-P(CHMe₂) ₂-4-methylphenyl]₂) extrudes neopentane in neat pyridine or picoline (3-or 4-picoline) under mild conditions (25 °C), to generate the transient titanium alkylidyne intermediate (PNP)Ti≡C^tBu (A), which subsequently ring-opens the pyridine by ring-opening metathesis of the aromatic N=C bond across the Ti≡C linkage, generating the metallaazabicycles (PNP)Ti(C(^tBu)C₅H₃RNH) (R = H (2), 3-Me (3), 4-Me (4)). Kinetic studies suggest that the C-N activation process obeys a pseudo-first-order process in titanium, with α-hydrogen abstraction being the rate-determining step (the KIE for 1/1-d₃ conversion to 2 was 3.8(3) at 25 °C). The activation parameters are ΔH^‡ = 23(3) kcal/mol and ΔS^‡ = -4(3) cal/(mol K). The intermolecular k_H/k_D ratio is close to unity, 1.07(3) at 25 °C, for the conversion of 1 to 2 in pyridine versus pyridine-d₅. Detailed theoretical studies suggest the 1 → 2 transformation proceeds in the following order: (i) formation of A in an overall endergonic step by α-hydrogen abstraction, (ii) an exergonic binding of pyridine, and (iii) concerted, exergonic [2 + 2] cycloaddition followed by (iv) exergonic ring-opening metathesis and finally (v) a concerted hydrogen atom migration. Complexes 2-4 can denitrogenate, that is, completely remove N of the heterocycle at 65 °C over 72 h, when treated with silyl chlorides such as ClSiR₃ (R = Me, ⁱPr, Ph) to cleanly afford the titanium silylimides (PNP)Ti=NSiR₃(Cl) (R = Me (8), ⁱPr (9), Ph (10)) and the corresponding ^tBu-arene organic byproduct. [Et ₃Si][B(C₆F₅)₄] also promotes denitrogenation of 2 to yield ^tBu-benzene, but the metal complex could not be characterized from such a reaction. The conversion 2 → 8 was found to have activation parameters ΔH^‡ = 30(6) kcal/mol and ΔS^‡ = 10(2) cal/(mol K), therefore yielding ΔG^‡ ≈ 27 kcal/mol at 298.15 K. A KIE of 1.6(2) at 85 °C was observed when 2/2-d₅ were denitrogenated to 8 in the presence of ClSiMe₃, with the rate of the reaction being insensitive to both the steric nature and concentration of the trialkylsilyl chloride. Denitrogenation leading to 8-10 is proposed to occur via a series of steps including a 1,3-hydrogen migration, an electrocyclic rearrangement, a retrocycloaddition, and a Si-Cl addition. The transformations 1 → 2/3/4 and 2/3/4 → 8 can be made cyclic by a series of steps such as deimination of the imide moiety in 8 with 2 equiv of MoCl₅, followed by reduction and transmetalation with LiCH₂^tBu and then oxidatively induced α-hydrogen abstraction. The reactivity of 1 with other heterocycles such as THF, thiophene, and piperidine is also discussed.