Michael K. Whittlesey

Ruthenium-catalyzed meta sulfonation of 2-phenylpyridines

A selective catalytic meta sulfonation of 2-phenylpyridines was found to occur in the presence of (arene)ruthenium(II) complexes upon reaction with sulfonyl chlorides. The 2-pyridyl group facilitates the formation of a stable Ru-C(aryl) σ bond that induces a strong para-directing effect. Electrophilic aromatic substitution proceeds with the sulfonyl chloride to furnish a sulfone at the position meta to the chelating group. This new catalytic process offers access to atypical regioselectivity for reactions involving chelation-assisted cyclometalation.

Synthesis, Electronic Structure, and Magnetism of (Ni(6-Mes) 2 ) + :A Two-Coordinate Nickel(I) Complex Stabilized by Bulky N‑Heterocyclic Carbenes

The two-coordinate cationic Ni(I) bis-N-heterocyclic carbene complex [Ni(6-Mes)2]Br (1) [6-Mes =1,3-bis(2,4,6-trimethylphenyl)-3,4,5,6-tetrahydropyrimidin-2-ylidene] has been structurally characterized and displays a highly linear geometry with a C-Ni-C angle of 179.27(13)°. Density functional theory calculations revealed that the five occupied metal-based orbitals are split in an approximate 2:1:2 pattern. Significant magnetic anisotropy results from this orbital degeneracy, leading to single-ion magnet (SIM) behavior.

Catalytic Hydrodefluorination of Aromatic Fluorocarbons by Ruthenium N-Heterocyclic Carbene Complexes

The catalytic hydrodefluorination (HDF) of hexafluorobenzene, pentafluorobenzene, and pentafluoropyridine with alkylsilanes is catalyzed by the ruthenium N-heterocyclic carbene (NHC) complexes Ru(NHC)(PPh(3))(2)(CO)H(2) (NHC = SIMes (1,3-bis(2,4,6-trimethylphenyl)imidazolin-2-ylidene) 13, SIPr (1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene) 14, IPr (1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) 15, IMes (1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene) 16). Catalytic activity follows the order 15 > 13 > 16 > 14, with 15 able to catalyze the HDF of C(6)F(5)H with Et(3)SiH with a turnover number of up to 200 and a turnover frequency of up to 0.86 h(-1). The catalytic reactions reveal (i) a novel selectivity for substitution at the 2-position in C(6)F(5)H and C(5)F(5)N, (ii) formation of deuterated fluoroarene products when reactions are performed in C(6)D(6) or C(6)D(5)CD(3), and (iii) a first-order dependence on [fluoroarene] and zero-order relationship with respect to [R(3)SiH]. Mechanisms are proposed for HDF of C(6)F(6) and C(6)F(5)H, the principal difference being that the latter occurs by initial C-H rather than C-F activation.

Ni(I) and Ni(II) ring-expanded N-heterocyclic carbene complexes: C–H activation, indole elimination and catalytic hydrodehalogenation

Reaction of the bulky 6-membered N-heterocyclic carbene 6-Mes with Ni(cod)(2) gives a C-H activated 6-Mes nickel(II) complex, but the novel three-coordinate Ni(I) species Ni(6-Mes)(PPh(3))Br if the reaction is performed in the presence of Ni(PPh(3))(2)Br(2). The Ni(I) complex is a precursor for the catalytic hydrodehalogenation of aryl halides.

Three-coordinate nickel(I) complexes stabilised by six-, seven- and eight-membered ring n-heterocyclic carbenes: synthesis, EPR/DFT studies and catalytic activity.

Comproportionation of [Ni(cod)(2)] (cod = cyclooctadiene) and [Ni(PPh(3))(2)X(2)] (X = Br, Cl) in the presence of six-, seven- and eight-membered ring N-aryl-substituted heterocyclic carbenes (NHCs) provides a route to a series of isostructural three-coordinate Ni(I) complexes [Ni(NHC)(PPh(3))X] (X = Br, Cl; NHC = 6-Mes 1, 6-Anis 2, 6-AnisMes 3, 7-o-Tol 4, 8-Mes 5, 8-o-Tol 6, O-8-o-Tol 7). Continuous wave (CW) and pulsed EPR measurements on 1, 4, 5, 6 and 7 reveal that the spin Hamiltonian parameters are particularly sensitive to changes in NHC ring size, N substituents and halide. In combination with DFT calculations, a mixed SOMO of ∣3d z 2〉 and ∣3d x 2-y 2〉 character, which was found to be dependent on the complex geometry, was observed and this was compared to the experimental g values obtained from the EPR spectra. A pronounced (31)P superhyperfine coupling to the PPh(3) group was also identified, consistent with the large spin density on the phosphorus, along with partially resolved bromine couplings. The use of 1, 4, 5 and 6 as pre-catalysts for the Kumada coupling of aryl chlorides and fluorides with ArMgY (Ar = Ph, Mes) showed the highest activity for the smaller ring systems and/or smaller substituents (i.e., 1>4≈6≫5).

Activation of an Alkyl C−H Bond Geminal to an Agostic Interaction: An Unusual Mode of Base-Induced C−H Activation

Deuterium labeling studies indicate that base-induced intramolecular C-H activation in the agostic complex 2-D proceeds with exclusive removal of a proton from the methyl arm of an (i)Pr substituent on the N-heterocyclic carbene (NHC) ligand. Computational studies show that this alkyl C-H bond activation reaction involves deprotonation of one of the C-H bonds that is geminal to the agostic interaction, rather than the agostic C-H bond itself. The reaction is readily accessible at room temperature, and a computed activation barrier of DeltaE (double dagger)(calcd) = +11.8 kcal/mol is found when the NHC 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene is employed as the external base. Charge analysis reveals that the geminal hydrogens are in fact more acidic than the agostic proton, consistent with their more facile deprotonation.

Catalytic Hydrodefluorination of Pentafluorobenzene by [Ru(NHC)(PPh3)2(CO)H2]: A Nucleophilic Attack by a Metal-Bound Hydride Ligand Explains an Unusual ortho-Regioselectivity†

The selective synthesis of fluoroarene compounds is a subject of intense current interest, driven by the prominent role such species play in many pharmaceuticals, agrochemicals, and other industrially important products. One attractive route to selectively substituted fluoroarenes involves the activation and functionalization of aromatic C F bonds derived from readily available perfluoroarenes. The simplest example of such a process is the hydrodefluorination reaction (HDF), in which fluorine is substituted for hydrogen. Catalytic HDF of C6F6 and C6F5H has been reported by Milstein et al. [3] and Holland et al. using Rh and Fe catalysts. However, both these systems exhibit practical problems that limit the mechanistic understanding of the HDF cycle. For example the Rh system requires high pressures of H2 as well as a sacrificial amine to remove HF, while with Fe no C F activation is observed in the absence of a reductant. As a consequence, the development of more active Rh or Fe catalysts has not been forthcoming. We recently reported the HDF of C6F6 and C6F5H using the ruthenium N-heterocyclic carbene (NHC) dihydride complex 1 (NHC = IMes, SIMes, IPr, SIPr; see Scheme 1 a) in the presence of trialkylsilanes at 70 8C in THF. Isolation and characterization of 1 allowed detailed kinetic studies to be undertaken, and these supported a mechanism involving initial phosphine dissociation to form 2 followed by HDF of the substrate to give the Ru F species, 3. Isolation of this 16e complex allowed us to demonstrate its reaction with trialkylsilane in the presence of PPh3 to regenerate catalyst 1. The most unusual feature of this system was the high regioselectivity for the formation of 1,2,3,4-C6F4H2 upon HDF of C6F5H, in complete contrast to the Milstein and Holland systems where the 1,2,4,5-isomer dominated. To account for the unusual ortho-regioselectivity we postulated the involvement of a tetrafluorobenzyne intermediate (Scheme 1b). Such species have been reported previously and could be formed here from 2 by successive C H and ortho-C F activation of C6F5H. However, density functional theory (DFT) calculations (with NHC = IMes) have now shown that this species lies more than 200 kJmol 1 above the reactants, effectively ruling it out as a viable intermediate under the conditions used experimentally. Further calculations, however, have now allowed us to define a series of alternative pathways which are based on a novel nucleophilic attack mechanism whereby a hydride ligand reacts directly with C6F5H. [10] These processes produced significantly lower barriers and, moreover, the lowestenergy pathway was found to be consistent with the unusual ortho-regioselectivity observed experimentally. Our calculations have shown that, after initial phosphine loss from 1, nucleophilic attack of hydride at C6F5H can occur through two different pathways (Scheme 2). In the concerted pathway I, the hydride is transfered from the metal onto the arene ring and the displaced fluorine migrates directly onto the metal center. In the alternative stepwise pathway II, an harene adduct, 4, is formed prior to the hydride attack. In this case the different orientation of the arene precludes direct transfer of fluorine onto the metal. Instead an intermediate is formed, 5, from which HF can be lost to form a s-aryl species, 6. Protonolysis by HF with concomitant F transfer to metal then yields 1,2,3,4-C6F4H2 and the M F species 3. The lowest-energy reaction profile for the HDF of C6F5H by 1 to give 1,2,3,4-C6F4H2 is computed to proceed through pathway II, and full details are shown in Figure 1. Initial Scheme 1. a) Catalytic hydrodefluorination (HDF) of C6F5H to 1,2,3,4C6F4H2 by 1; b) postulated tetrafluorobenzyne intermediate.

Facile intermolecular aromatic C–F bond activation reaction of [Ru(dmpe)2H2](dmpe = Me2PCH2CH2PMe2)

cis-[Ru(dmpe)2H2] reacts at –78 °C with hexafluorobenzene to generate the pentafluorophenyl hydride complex,trans-[Ru(dmpe)2(C6F5)H]; reaction also takes place with C6F5H, C6F5CF3, C6F5OCH3,1,2,3,4-C6F4H2 and 1,2,3-C6F3H3 to yield products from C–F insertion exclusively.

Ruthenium xantphos complexes in hydrogen transfer processes: reactivity and mechanistic studies.

The in situ combination of [Ru(PPh3)3(CO)H2] with xantphos is catalytically active for the alkylation of alcohols with the ketonitrile (t)BuC(O)CH2CN in a model oxidation-Knoevenagel-reduction process. The precursor complex [Ru(xantphos)(PPh3)(CO)H2] was isolated and reacted with stoichiometric amounts of PhCH2OH and PhCHO. Under these conditions, the alcohol is decarbonylated to afford [Ru(xantphos)(CO)2H2] and finally [Ru(xantphos)(CO)3], both of which prove to be less active for catalysis than the starting complex. The reactivity of the xantphos system contrasts with that of [Ru(dppp)(PPh3)(CO)H2], which is catalytically inactive for the Knoevenagel reaction and fails to show any stoichiometric reactivity with alcohols.

The influence of N-heterocyclic carbenes (NHC) on the reactivity of [Ru(NHC)4H]+ with H2, N2, CO and O2

The five-coordinate ruthenium N-heterocyclic carbene (NHC) hydrido complexes [Ru(IiPr(2)Me(2))(4)H][BAr(F) (4)] (1; IiPr(2)Me(2)=1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene; Ar(F)=3,5-(CF(3))(2)C(6)H(3)), [Ru(IEt(2)Me(2))(4)H][BAr(F) (4)] (2; IEt(2)Me(2)=1,3-diethyl-4,5-dimethylimidazol-2-ylidene) and [Ru(IMe(4))(4)H][BAr(F) (4)] (3; IMe(4)=1,3,4,5-tetramethylimidazol-2-ylidene) have been synthesised following reaction of [Ru(PPh(3))(3)HCl] with 4-8 equivalents of the free carbenes at ambient temperature. Complexes 1-3 have been structurally characterised and show square pyramidal geometries with apical hydride ligands. In both dichloromethane or pyridine solution, 1 and 2 display very low frequency hydride signals at about delta -41. The tetramethyl carbene complex 3 exhibits a similar chemical shift in toluene, but shows a higher frequency signal in acetonitrile arising from the solvent adduct [Ru(IMe(4))(4)(MeCN)H][BAr(F) (4)], 4. The reactivity of 1-3 towards H(2) and N(2) depends on the size of the N-substituent of the NHC ligand. Thus, 1 is unreactive towards both gases, 2 reacts with both H(2) and N(2) only at low temperature and incompletely, while 3 affords [Ru(IMe(4))(4)(eta(2)-H(2))H][BAr(F) (4)] (7) and [Ru(IMe(4))(4)(N(2))H][BAr(F) (4)] (8) in quantitative yield at room temperature. CO shows no selectivity, reacting with 1-3 to give [Ru(NHC)(4)(CO)H][BAr(F) (4)] (9-11). Addition of O(2) to solutions of 2 and 3 leads to rapid oxidation, from which the Ru(III) species [Ru(NHC)(4)(OH)(2)][BAr(F) (4)] and the Ru(IV) oxo chlorido complex [Ru(IEt(2)Me(2))(4)(O)Cl][BAr(F) (4)] were isolated. DFT calculations reproduce the greater ability of 3 to bind small molecules and show relative binding strengths that follow the trend CO >> O(2) > N(2) > H(2).