Mild sp2Carbon–Oxygen Bond Activation by an Isolable Ruthenium(II) Bis(dinitrogen) Complex: Experiment and Theory

The isolable ruthenium(II) bis(dinitrogen) complex [Ru(H)2(N2)2(PCy3)2] (1) reacts with aryl ethers (Ar–OR, R = Me and Ar) containing a ketone directing group to effect sp2C–O bond activation at temperatures below 40 °C. DFT studies support a low-energy Ru(II)/Ru(IV) pathway for C–O bond activation: oxidative addition of the C–O bond to Ru(II) occurs in an asynchronous manner with Ru–C bond formation preceding C–O bond breaking. Alternative pathways based on a Ru(0)/Ru(II) couple are competitive but less accessible due to the high energy of the Ru(0) precursors. Both experimentally and by DFT calculations, sp2C–H bond activation is shown to be more facile than sp2C–O bond activation. The kinetic preference for C–H bond activation over C–O activation is attributed to unfavorable approach of the C–O bond toward the metal in the selectivity determining step of the reaction pathway.


General Experimentation
All manipulations were carried out under standard Schlenk-line and glovebox techniques under an inert atmosphere of argon or dinitrogen. An MBraun Labmaster glovebox was employed operating at <0.1ppm O 2 and <0.1ppm H 2 O. Solvents were dried over activated alumina from an SPS (solvent purification system) based upon the Grubbs design and degassed before use.
Glassware was dried for 12 hours at 120°C prior to use. d 6 -Benzene and d 8 -toluene were freezepump-thaw degassed and stored over molecular sieves prior to use.
NMR spectra were obtained on BRUKER 400 or 500 MHz machines, all peaks are references against residual solvent peak or internal standard peak with values quoted in ppm. Data were processed in Topspin or MestReNova. Infrared spectra were recorded on a Perkin Elmer FT-IR Paragon 1000 spectrometer with the solid sample impregnated into KBr disk.

Materials
1,5-Cyclooctadiene was freeze-pump-thaw degassed and stored over molecular sieves prior to use. Ethanol was dried over magnesium, distilled and stored over molecule sieve prior to use.
Chemicals purchased from Sigma Aldrich, Alfa Aesar and Fluorochem and used without further purification unless stated.
In situ NMR data for 1 same as above.
In situ NMR data for 1-    In situ NMR data for 4a same as above.

For C-O Bond Activation of 2,6-bis-p-tolyloxy(phenyl)acetophenone with 1
In order to identify the major by-product during C-O bond activation of 2,6-bis-p-tolyloxy(phenyl)acetophenone with 1, reactions were carried out with both 4-methylphenol and 4-tert-butylphenol. The latter was used as a surrogate for the former in order to facilitate product separation and purification by crystallization. A combination of NMR spectroscopy and single x-ray crystallography was used to determine the structures of the products from both the reaction of 1 with 4-methylphenol and 4-tert-butyl phenol. In situ NMR data for 3a-H 2 same as above. In situ NMR data for 4a same as above.

Complexation
In situ NMR data for 5-N 2 same as above.

Xray Data
The X-ray crystal structure of 1 The two Ru-H hydrogen atoms in the structure of 1 were located from ΔF maps and refined freely.

The X-ray crystal structure of 4a
The Ru-H hydrogen atom in the structure of 4a was located from a ΔF map and refined freely. The included toluene solvent molecule was found to be disordered across a centre of symmetry, and two unique orientations of ca. 29 and 21% occupancy were identified (with the action of the inversion centre generating two further orientations of the same occupancies). The geometries of both orientations were optimised, the thermal parameters of adjacent atoms were restrained to be similar, and all of the atoms were refined isotropically.

The X-ray crystal structure of 4b
The Ru-H hydrogen atom in the structure of 4b was located from a ΔF map and refined freely.

The X-ray crystal structure of 4c
The Ru-H hydrogen atom in the structure of 4c was located from a ΔF map and refined freely. The complex lists across a mirror plane that passes through Ru1, H1, C1 to C7, O7, C8, C10, N11 and N12. When refined using AFIX 137, the methyl hydrogen atoms on C10 would not settle, and so the AFIX 33 command was used instead. The included benzene solvent molecule was found to be disordered across a mirror plane, and this was modelled using one complete 50% occupancy molecule (with the action of the mirror plane generating a second 50% occupancy orientation). The geometry of the unique orientation was optimised, and all of the nonhydrogen atoms were refined anisotropically.

The X-ray crystal structure of 6b
The Ru-H hydrogen atom in the structure of 6b was located from a ΔF map and refined freely. The included solvent was found to be highly disordered, and the best approach to handling this diffuse electron density was found to be the SQUEEZE routine of PLATON. [X1] This suggested a total of 73 electrons per unit cell, equivalent to 36.5 electrons per asymmetric unit. Before the use of SQUEEZE the solvent clearly resembled a straight chain disordered across a centre of symmetry, but the length of the chain was uncertain. Pentane (C 5 H 12 , 42 electrons) was chosen as it was the most recently used crystallisation solvent. 0.85 pentane molecules corresponds to 35.7 electrons, so this was used as the solvent present. As a result, the atom list for the asymmetric unit is low by 0.85(C 5 H 12 ) = C 4.25 H 10.2 (and that for the unit cell low by C 8.5 H 20.4 ) compared to what is actually presumed to be present.

The X-ray crystal structure of 8a
The Ru-H hydrogen atom in the structure of 8a was located from a ΔF map and refined freely. The O-H hydrogen atoms of the O50-and O60-based included 4-methylphenol moieties S32 were also located from ΔF maps, and were refined freely subject to an O-H distance constraint of 0.90 Å. The included heptane solvent molecule was found to be disordered. Three orientations were identified of ca. 51, 28 and 21% occupancy, their geometries were optimised, the thermal parameters of adjacent atoms were restrained to be similar, and only the non-hydrogen atoms of the major occupancy orientation were refined anisotropically (those of the minor occupancy orientations were refined isotropically).
The X-ray crystal structure of S1 The presumed one terminal and three bridging Ru-H and Ru-H-Ru hydrogen atoms in the structure of S1 could not be located; their presence (which would give both ruthenium atoms an octahedral coordination geometry) was inferred by analogy with the closely related species dinitrogen-tris(μ 2 -hydrido)-hydrido-tetrakis(triphenylphosphine)-di-ruthenium (CCDC refcode BUGSIF10) which has triphenyl phosphine ligands where S1 has tricyclohexyl phsophines. 5 As a consequence the atom list is low by 4 hydrogen atoms. The included solvent was found to be highly disordered, and the best approach to handling this diffuse electron density was found to be the SQUEEZE routine of PLATON. 11,12 This suggested a total of 219 electrons per unit cell, equivalent to 109.5 electrons per asymmetric unit. Before the use of SQUEEZE the solvent clearly resembled heptane (C 7 H 16 , 58 electrons), and 2 heptane molecules corresponds to 116 electrons, so this was used as the solvent present. As a result, and taking into account the 4 "missing" hydrides, the atom list for the asymmetric unit is low by 2(C 7 H 16 ) + 4H = C 14 H 36 (and that for the unit cell low by C 28 H 72 ) compared to what is actually presumed to be present.

Figure. S22
The crystal structure of the C S -symmetric complex 4c (50% probability ellipsoids). The mirror plane passes through Ru1, H1, the N 2 unit, and all of the phenyl-tert-butyl ketone ligand with the exception of two of the t-Bu methyl groups.

Figure. S25
The crystal structure of S1.

Figure. S26b
Line drawing of S1 including the one terminal and three bridging Ru-H and Ru-H-Ru hydrogen atoms.

DFT Studies Computational Details
DFT calculations were run using Gaussian 09 (Revision D.01) 13 using the BP86 density functional. [14][15][16] Ru and P centres were described with Stuttgart RECPs and associated basis sets (ECP28MWB for Ru and ECP10MWB for P). [17][18][19] The P basis set was augmented with the addition of d-orbital polarisation (ζ = 0.387). 20 6-31+G* basis sets were used for N and O and 6-31G** basis sets were used for all other atoms. [21][22][23] Geometry optimisation calculations were performed without symmetry constraints. The Gaussian 09 default optimisation criteria were tightened to 10 -9 on the density matrix and 10 -7 on the energy matrix. The default numerical integration grid was also improved using a pruned grid with 99 radial shells and 590 angular points per shell. Frequency analyses for all stationary points were performed using the enhanced criteria to confirm the nature of the structures as either minima (no imaginary frequency) or transition states (only one imaginary frequency). Intrinsic reaction coordinate (IRC) calculations were used to connect transition states and minima located on the potential energy surface allowing a full energy profile (calculated at 298.15 K, 1 atm) of the reaction to be constructed. 24,25 Free energies reported within the main text are corrected for the effects of benzene solvent (ε=2.2706) using the using the integral equation formalism polarizable continuum model (IEFPCM). 26 In addition, single point dispersion corrections were applied to the BP86 optimised geometries employing Grimme's D3 parameter set with the Becke-Johnson (BJ) damping as implemented in Gaussian. 27 The graphical user interface used to visualise the various properties of the intermediates and transition states was GaussView 5.0.9. 28 Natural Bond Orbital analysis was carried out using NBO 5.9. 29,30 The topology of the electron density for selected systems within the QTAIM framework was carried out using the AIMALL software. [31][32][33] Weak interactions were identified using the Non Covalent Interaction (NCI) approach. 34 The analysis was carried out with the NCIplot software and visualized using the VMD interface. 35,36 S38 Figure S27. Mechanisms for the formation of Ru(0). A transition state structure was not identified for TS N2-diss . (0.0)

Assessment of DFT Functional Effects
A range of DFT exchange-correlation functionals were chosen to assess the influence of functional on key steps in the C-H and C-O bond activation pathways (Table S6 and S7). The functionals include GGA functionals (BP86 14-16 , PBE 39 ) and hybrid-GGA functionals (B3LYP 38,40 , PBE0 39,41 ); hybrid Minnesota functionals, M06L 42 and M11L, long range-corrected functional, ωB97X 43 , and Grimme's D2 dispersion corrected ωB97X-D 43 . The BP86optimized coordinates for each conformer were re-optimised using the new functional.