Synthetic and Mechanistic Studies of the Ring Opening and Denitrogenation of Pyridine and Picolines by Ti-C Multiple Bonds

Abstract

The neopentylidene-neopentyl complex (PNP)Ti=CH(t)Bu(CH(2)(t)Bu) (1; PNP(-) = N[2-P(CHMe(2))2-4-methylphenyl]2) extrudes neopentane in neat pyridine or picoline (3- or 4-picoline) under mild conditions (25 degrees C), to generate the transient titanium alkylidyne intermediate (PNP)Ti C(1)Bu (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((t)Bu)C(5)H(3)RNH) (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 a-hydrogen abstraction being the rate-determining step (the KIE for 1/1-d(3) conversion to 2 was 3.8(3) at 25 degrees C). The activation parameters are Delta H* = 23(3) kcal/mol and Delta S* = -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-d(5). Detailed theoretical studies suggest the 1 -> 2 transformation proceeds in the following order: (i) formation of A in an overall endergonic step by a-hydrogen abstraction, (ii) an exergonic binding of pyridine, and (iii) concerted, exergonic 1,2 + 21 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 7211, when treated with silyl chlorides such as ClSi R(3) (R = Me, (i)Pr, Ph) to cleanly afford the titanium silylimides (PNP)Ti=NSiR(3)(Cl) (R = Me (8), (i)Pr (9), Ph (10)) and the corresponding (1)Bu-arene organic byproduct. [Et(3)Si][B(C(6)F(5))(4)] also promotes denitrogenation of 2 to yield (t)Bu-benzene, but the metal complex could not be characterized from such a reaction. The conversion 2 -> 8 was found to have activation parameters Delta H* = 30(6) kcal/mol and Delta S* = 10(2) cal/(mol K), therefore yielding activation parameters Delta H* = 30(6) kcal/mol and Delta S* = 10(2) cal/(mol K), therefore yielding Delta G*approximate to kcal/mol at 298.15 K. A KIE of 1.6(2) at 85 degrees C was observed when 2/2-d(5) were denitrogenated to 8 in the presence of ClSiMe(3), 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 MoCl(5), followed by reduction and transmetalation with LiCH(2)(t)Bu and then oxidatively induced a-hydrogen abstraction. The reactivity of 1 with other heterocycles such as THF, thiophene, and piperidine is also discussed.