Swift C‒C Bond Insertion by a 12-Electron Palladium(0) Surrogate

The selective activation of C-C bonds holds vast promise for catalysis. So far, research has been primarily directed at rhodium and nickel under harsh reaction conditions. Herein, we report C-C insertion reactions of a 12-electron palladium(0) surrogate stabilized by a cyclic(alkyl)(amino) carbene (CAAC) ligand. Benzonitrile (1), biphenylene (2), benzocyclobutenone (3), and naphtho[b]cyclopropene (4) were studied. These substrates allow elucidation of the effect of ring strain as well as hybridization encompassing sp3, sp2 and sp hybridized carbon atoms. All reactions proceed quantitatively at or below room temperature. This work therefore outlines perspectives for mild C-C bond functionalization catalysis.


1
H and 13 C NMR spectra were recorded on a Bruker Avance III 400 or a Bruker Avance III 300 instrument operating at 400.13 and 300.13 MHz for 1 H and at 100.62 and 75.47 MHz for 13 C, respectively, or a JEOL ECX 400 or a JEOL ECX 270 instrument operating at 400.18 and 269.71MHz for 1 H and at 100.62 and 67.82 MHz for 13 C, respectively, at a probe temperature of 23 °C.The chemical shifts δ are calculated in ppm; the solvent residual signals of incomplete deuterated solvent molecules were used as internal reference for the 1 H NMR spectra and the carbon solvent signals for 13 C NMR spectral data.NMR multiplicities are abbreviated as follows: s = singlet, d = doublet, t = triplet, q = quartet, spt = septet, m = multiplet, br = broad signal.Coupling constants J are given in Hz.Melting points were determined using an Electrothermal IA9200 Programmable Digital Melting Point Apparatus.UV-VIS spectra were recorded on a J&M Analytik AG TIDAS 100 spectrometer and Schlenk cuvettes with a path length of 1 cm as solutions in THF.Solvents were purified using a two-column solid-state purification system (MBraun SPS 5/7 or Glass Contour System, Irvine, CA) and transferred to the glovebox without exposure to air.Pentane, hexanes and benzene were stored over a mirror of potassium, whereas all other solvents were stored over activated molecular sieves.NMR solvents were obtained dry and packaged under argon and stored over activated molecular sieves or a mirror of potassium (C6D6).The palladium(0) complex CAAC imine -Pd(0) (1) 1 was synthesized as reported in the literature.Naphtho[b]cyclopropene was gratefully provided from Peter Chen's lab, where it was synthesized as reported in the literature. 2 All other reagents were obtained from commercial sources and used as is without further purification.

Synthesis and Crystallization of Metal Complexes (CAAC imine )Pd(CN)(Ph) 2
CAAC imine -Pd(0) (1 eq., 25 mg, 40 µmol) was dissolved in benzene to give a dark-red solution.Benzonitrile (1.2 eq./5.0 µl/48 µmol) was added, and the solution turned orange-yellow within 4 hours, whereby a yellow precipitate forms.Quantitative precipitation was induced by adding npentane.The product 2 was washed with n-pentane and dried in vacuo to give it as a yellowish solid in quantitative yield.Single crystals suitable for X-ray crystallography were obtained by slow evaporation of a concentrated pyridine solution.
Note: In pyridine, quantitative conversion requires 4 days at room temperature.

Figure S7
. 1 H-NMR reaction monitoring in benzene-d6 of the formation of 2 tentatively suggests the formation of an intermediate π-complex according to comparison with related NMR spectra in the literature. 1 Note that the starting material gives broad signals in benzene-d6, and that precipitate is already present after 15 min reaction time.

(CAAC imine )Pd(benzocyclobutenone) 3
CAAC imine -Pd(0) (1.0 eq., 10 mg, 14 µmol) was dissolved in benzene to give a red solution.Benzocyclopropenone (1.2 eq., 2 mg, 17 µmol) was added and the solution instantaneously turned yellow.Yellow crystals formed over the course of 3 h.The crystalline material was collected, washed with pentane and dried in vacuo to give the product as yellow solid in quantitative yield.Crystals formed this way were suitable for X-ray crystallography.

Single Crystal Structure Elucidation and Refinement (SC-XRD)
X-ray Structure Determination: X-ray quality crystals were selected in Fomblin YR-1800 perfluoroether (Alfa Aesar) at ambient temperature.The samples were cooled to 100(2) K (compounds 2, 4, 6) or 150(2) K (compounds 3 and 5) during measurement.The data were collected on a Bruker Kappa IS Duo Photon II CPAD diffractometer (compounds 2 and 6) or Bruker APEX-II CCD diffractometer (3, 4, and 5) using monochromated MoKα (λ = 0.71073 Å) radiation.The structures were solved by intrinsic phasing (SHELXT) 3 and refined by full matrix least squares procedures (SHELXL) 4 within the OLEX2 5 platform.Semi-empirical absorption corrections (multiscan and additional spherical absorption correction) were applied to the recorded diffraction data using the SADABS application within the APEX2 or APEX3 platform. 6All nonhydrogen atoms were refined anisotropically, hydrogen atoms were included in the refinement at calculated positions using a riding model.The isotropic displacement parameters of all hydrogen atoms were tied to those of their corresponding carrier atoms by a factor of 1.2 or 1.5.All special refinement details (if required) for disordered structures as well as molecular structure representations are summarized down below.A summary on standard crystallographic parameters as well as the CSD entry numbers within the Cambridge Crystallographic Data Centre (CCDC) is subsequently provided in Tables S1 and S2.

Special Refinement Details:
Compound 2: The structure shows no signs of disordered atom positions and all atoms except hydrogen atoms were refined anisotropically with high precision.
Compound 3: One of the Dip groups was found to be disordered which is why a disorder model was described for tilting of the whole fragment containing C27, C28, C29, C27A, C28A and C29A.Two respective split positions have been refined according to the free variable 2 (FVAR2) which refined into occupancies of 0.82 and 0.18.To fix the refinement, soft DELU and ISOR restraints were embedded to the refinement reaching more reasonable displacement.
Compound 4: The compound crystallized with two independent halves of a pyridine solvent molecule, both of which were located on crystallographic twofold axes (Wyckoff position 4e).These solvent molecules were disordered with regard to the position of the pyridine's nitrogen atom.Accordingly, equal coordinate (EXYZ) and equal anisotropic displacement parameter (EADP) constraints were applied for the affected atoms.
Compound 5⋅2C6H6: The structure was solved based on comparably poor diffraction data, due to poor scattering behavior.Recrystallization from various solvents turned out to be unsuccessful.The best choice of single crystal was obtained from benzene solutions, which led to the incorporation of solvent molecules.The crystals were thin, colorless needles, which further complicated the data collection.We are aware of the high value of Rint and provided the only and hence best data where a structure solution was possible.The high Rint is caused by the poor scattering of the crystal as evident from checking the reciprocal space in all three directions of the unit cell.The reciprocal space revealed no twinning, modulation, or other ambiguity.The Pdcomplex is nicely ordered whereas the benzene molecules show slight rotational disorder, yet no description of a disorder model is necessary here.
Compound 6⋅C5H5N: The structure of the Pd-complex shows no signs of disordered atom positions and all atoms except hydrogen atoms were refined anisotropically with high precision.It is notable that the solvent molecule is slightly tilting, yet the description of a disorder model was not performed.
Molecular Structure Representations: All molecular structure representations in the ESI as well as the main article have been prepared with the Diamond software package 7 or OLEX2 5 in combination with POV-Ray 3.7. 8A mixed representation of ellipsoid plots as well as wires/sticks was chosen for clarity.All ellipsoids are represented at the 50% probability level.

Computational Details
All computations were carried out with ORCA 5.0.3. 9The structural parameters were optimized without constraints and tighter-than-default convergence settings (tightopt) using the r²SCAN-3c composite method. 10The optimized structural parameters were verified as true minima by the absence of negative eigenvalues in the harmonic vibrational frequency analysis.
Ring strains were computed as the reaction enthalpies of the following homodesmic equations: Scheme S1.Homodesmic equations for the computation of ring strains.
* Restraints used to fix disorder.** Please see special refinement details for further information (vide infra).

Table S6 .
Energies of computed compounds.

Table S7 .
Computed ring strains with comparison to literature values, if available.