Synthesis, Characterisation and Reactivity of Copper(I) Amide Complexes and Studies on Their Role in the Modified Ullmann Amination Reaction

A series of copper(I) alkylamide complexes have been synthesised; copper(I) dicyclohexylamide (1), copper(I) 2,2,6,6-tetramethylpiperidide (2), copper(I) pyrrolidide (3), copper(I) piperidide (4), and copper(I) benzylamide (5). Their solid-state structures and structures in [D6]benzene solution are characterised, with the aggregation state in solution determined by a combination of DOSY NMR spectroscopy and DFT calculations. Complexes 1, 2 and 4 are shown to exist as tetramers in the solid state by X-ray crystallography. In [D6]benzene solution, complexes 1, 2 and 5 were found by using 1H DOSY NMR to exist in rapid equilibrium between aggregates with average aggregation numbers of 2.5, 2.4 and 3.3, respectively, at 0.05 m concentration. Conversely, distinct trimeric, tetrameric and pentameric forms of 3 and 4 were distinguishable by one-dimensional 1H and 1H DOSY NMR spectroscopy. Complexes 3–5 are found to react stoichiometrically with iodobenzene, in the presence or absence of 1,10-phenanthroline as an ancillary ligand, to give arylamine products indicative of their role as potential intermediates in the modified Ullmann reaction. The role of phenanthroline has also been explored both in the stoichiometric reaction and in the catalytic Ullmann protocol.


Experimental
General information: All manipulations were carried out under a nitrogen atmosphere in a glovebox or using standard Schlenk techniques. Glassware was dried at a minimum temperature of 120 °C for at least 12 h prior to use. Toluene and n-hexane were dried and degassed over activated alumina using an Innovative Technologies PureSolv solvent purification system. Tetrahydrofuran was freshly distilled over sodium and benzophenone under a nitrogen atmosphere prior to use. Potassium carbonate was dried under vacuum at 180 °C for 48 h and 1,10-phenanthroline was dried under vacuum at 85 °C for 36 h.
Copper(I) mesityl was prepared according to a reported procedure by Tsuda et al. [1] Dimethyl sulfoxide and [D 6 ]DMSO were distilled over calcium hydride under vacuum and stored over 4 Å molecular sieves under a nitrogen atmosphere. All amines used were distilled over calcium hydride or sodium and then stored over 4 Å molecular sieves under a nitrogen atmosphere. All other chemicals were used as received from their respective suppliers. All products, other reagents and deuterated NMR solvents were stored in a nitrogen-filled glovebox, where liquid reagents were stored over 4 Å molecular sieves. 1 H and 13 C NMR spectroscopy data were obtained at room temperature using Bruker AV-400 spectrometers except for 1 H DOSY and 1 H-1 H ROESY NMR which were recorded on a Bruker AV-500. Elemental analyses were performed at the London Metropolitan University.
The yields reported for the syntheses of the copper(I) amide complexes were calculated from the amount isolated after purification. The quantities of each compound present after the catalytic and stoichiometric reactions were calculated by NMR through the use of mesitylene as an internal standard and are reported as a mean of at least two independent runs. 1 H and 13 C NMR data were analysed using MESTRELAB MestReNova; 1 H-1 H ROESY NMR data were analysed using Bruker TopSpin; and 1 H DOSY NMR data were processed and analysed using Bruker Dynamics Centre and TopSpin respectively.

Preparation of 1 H DOSY NMR solutions of the copper(I) amide complexes with internal
standards: Copper(I) amide complex (0.04 mmol, 0.05 M) and 1,2,3,4tetraphenylnaphthalene (15 mg, 0.04 mmol, 0.05 M) were added to a glass vial and then dissolved in [D 6 ]benzene (668 μL). 1-phenylnaphthalene (13 μL, 0.07 mmol, 0.10 M) and tetramethylsilane (19 μL, 0.14 mmol, 0.20 M) were then added. Finally, the solution was transferred to a J. Youngs tap NMR tube for analysis. (Amount of copper(I) amide complex was adjusted for the desired concentration). an internal standard, iodobenzene (111 μL, 1.00 mmol) and then piperidine (10 μL, 0.10 mmol) in a nitrogen-filled glovebox. The vial was capped tightly and then taken out of the glovebox. The mixtures were then stirred at 80 °C using an oil bath for 18 h. The contents of the vial were then passed through a syringe filter to remove any solid in a glovebox or nitrogen-filled glove bag into a NMR tube. The filtered solution was then analysed by 1 H NMR spectroscopy to calculate the quantity of 1-phenylpiperidine product formed.

NMR spectra of complexes
The following NMR spectra were obtained using Bruker AV-400 spectrometers at 400 MHz between 21 and 24 °C.

DFT optimised structures
Grey = carbon; orange = copper; blue = N; green-grey = Si; hydrogen atoms are not shown for clarity. The methods used to calculate the energy minimised structures and the radii, r calc , can be found in the full-text.

1 H DOSY NMR data of 3 and 4 in the presence of 1,10-phenanthroline and internal standards
The following 1 H DOSY NMR spectra were obtained using a Bruker AV-500 spectrometer at 500 MHz and 25°C.

NMR data of 3 and 4 in the presence of 1,10-phenanthroline in [D 6 ]DMSO
The following 1 H and 13 C NMR spectra were obtained using Bruker AV-400 spectrometers at 400 MHz and 23 °C. 1 H-1 H ROESY NMR spectrum was obtained using a Bruker DRX400 or AV-500 spectrometer at 400 and 500 MHz respectively at 23 °C.    ) + (aP) 2 + bP. [b] The complex has crystallographic Ci symmetry. [c] There are two independent C2symmetric complexes. ) + (aP) 2 + bP. [b] There are two independent C2-symmetric complexes.
The absolute structure of 1 was determined by use of the Flack parameter [0.037(9)]. Figure S37 The crystal structure of 1 (50% probability ellipsoids).

The X-ray crystal structure of 2
The structure of 2 has crystallographic C i symmetry about an inversion centre at the middle of the Cu 4 N 4 ring. Figure S38 The crystal structure of the C i -symmetric complex 2 (50% probability ellipsoids).

The X-ray crystal structure of 4
The absolute structure of 4 was determined by use of the Flack parameter [0.07 (3)]. Figure S39 The crystal structure of 4 (50% probability ellipsoids).

The X-ray crystal structure of 6
The structure of 6 was found to contain two independent complexes (6-i and 6-ii), each with C 2 symmetry. However, the two independent complexes differ in that whilst the Cu(1)-based molecule has the C 2 axis along the Cu(1)···Cu(2) vector (the copper atoms not coordinated to the piperidine ligands, i.e. the short diagonal of the Cu 4 rhombus), the Cu(4)-based molecule has the C 2 axis along the Cu(4)···Cu(5) vector (the copper atoms coordinated to the piperidine ligands, i.e. the long diagonal of the Cu 4 rhombus). For this latter case, a direct consequence of the position of the C 2 axis is that both the N(31) and N(61)-based piperidine ligands are inherently disordered. In each case this disorder was modelled by using one complete, geometry optimised, 50% occupancy orientation, with a second 50% occupancy orientation generated by action of the C 2 axis; the non-hydrogen atoms of the unique orientations were refined anisotropically. The N-H hydrogen atoms of the piperidine ligands in both independent complexes could not be located from ΔF maps and so were added in idealised positions at an N-H distance of 0.90 Å. The absolute structure of 6 was determined by use of the Flack parameter [0.070(11)]. Figure S40 The structure of one (6-i) of the two crystallographically independent C 2symmetric complexes present in the crystal of 6 (50% probability ellipsoids). Figure S41 The structure of one (6-ii) of the two crystallographically independent C 2symmetric complexes present in the crystal of 6 (50% probability ellipsoids).

The X-ray crystal structure of 6b
The structure of 6b was found to contain two independent complexes (6b-i and 6b-ii), each with C2 symmetry. However, the two independent complexes differ in that whilst the Cu(1)based molecule has the C2 axis along the Cu(1)···Cu(2) vector (the copper atoms not coordinated to the piperidine ligands, i.e. the short diagonal of the Cu4 rhombus), the Cu(4)based molecule has the C2 axis along the Cu(4)···Cu(5) vector (the copper atoms coordinated to the piperidine ligands, i.e. the long diagonal of the Cu4 rhombus). For this latter case, a direct consequence of the position of the C2 axis is that both the N(31) and N(61)-based piperidine ligands are inherently disordered. In each case this disorder was modelled by using one complete, geometry optimised, 50% occupancy orientation, with a second 50% occupancy orientation generated by action of the C2 axis; the non-hydrogen atoms of the unique orientations were refined anisotropically. Additionally, the N(21)-based piperidine ligand in the Cu(1)-based complex was also found to be disordered. Two orientations were identified of ca. 57 and 43% occupancy, their geometries were optimised, the thermal parameters of adjacent atoms were restrained to be similar, and only the nonhydrogen atoms of the major occupancy orientation were refined anisotropically (those of the minor occupancy orientation were refined isotropically). The N-H hydrogen atoms of the piperidine ligands in both independent complexes could not be located from ΔF maps and so were added in idealised positions at an N-H distance of 0.90 Å.
Despite being a very different polymorph, the molecular structure of 6b is remarkably similar to that of 6. As with the chiral tetragonal species, the structure of the racemic monoclinic species 6b contains two independent C 2 -symmetric molecules (6b-i and 6b-ii) with one molecule having the C 2 axis along the short diagonal of the Cu 4 rhombus (the Cu(1)···Cu(2) vector) and the other having the C 2 axis along the long diagonal of the Cu 4 rhombus (the Cu (4) Figure S42 The structure of one (6b-i) of the two crystallographically independent C 2symmetric complexes present in the crystal of 6b Figure S43 The structure of one (6b-i) of the two crystallographically independent C 2symmetric complexes present in the crystal of 6b (50% probability ellipsoids). Figure S44 The structure of one (6b-ii) of the two crystallographically independent C 2symmetric complexes present in the crystal of 6b