Synthesis and Structure of (Nitronyl Nitroxide-2-ido)( tert -butyldiphenylphosphine)gold(I) and -(Di( tert -butyl)phenylphosphine)gold(I) Derivatives; Their Comparative Study in the Cross-Coupling Reaction

: We synthesized two new organogold derivatives of a nitronyl nitroxide (NN) with phosphine ligands, namely NN-Au-P t BuPh 2 and NN-Au-P t Bu 2 Ph. They were characterized by X-ray di ﬀ raction analysis, cyclic voltammetry, and ESR, IR, and UV / Vis spectroscopy. The X-ray structural analysis revealed a tendency of the NN moiety to form a large number of short intermolecular contacts. This phenomenon is related to the anionic nature of the paramagnetic group NN, as evidenced by a signiﬁcantly lower oxidation potential in comparison with purely organic derivatives of NN radicals. The cross-coupling reaction of NN-Au-PPh 3 , NN-Au-P t BuPh 2 , or NN-Au-P t Bu 2 Ph with an activated bromoarene, namely, p -BrC 6 H 4 NO 2 , was investigated. It was shown that regardless of the presence of the bulky tert -butyl substituent, all gold derivatives have similar activities in the cross-coupling reaction and give a cross-coupling product, NN-C 6 H 4 NO 2 , with comparable yields.


Introduction
(Nitronyl nitroxide-2-ido)-Au, i.e., (NN-2-ido)-Au, organometallic derivatives with a phosphine ligand developed by K. Okada et al., are interesting types of paramagnetic compounds in terms of their unique structure and electronic and electrochemical properties [1] (Figure 1). The advantage of these organogold derivatives is that they have high stability in solid and dissolved states in contrast to the NN-2-ide radical anion (τ < 30 min at room temperature [2]). Therefore, these metal-radical species are expected to be applicable to various fields of science. A triphenylphosphine gold derivative of an NN called NN-Au-PPh3 is known to enter into a Pd(0)-catalyzed cross-coupling reaction with aryl iodides and bromides, with the former reacting smoothly in most cases and the latter being less active and interacting only in the presence of electron acceptor substituents [1]. On the other hand, there are no reports on how variation of the phosphine ligand influences the Pd(0)-mediated cross-coupling process. One would expect two types of such an influence: via electronic effects and via steric effects. Here, we concentrated on the latter by performing the synthesis of two paramagnetic derivatives, NN-Au-P t BuPh2 (1) and NN-Au-P t Bu2Ph (2) (Figure 2), containing one and two bulky tert-butyl substituents, respectively. Both paramagnetic compounds were completely characterized (including X-ray diffraction [XRD] analysis) and then were studied together with a structurally related compound, NN-Au-PPh3, in a cross-coupling reaction with an activated bromoarene, namely p-BrC6H4NO2.

General Procedures
4,4,5,5-Tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl [3] and (NN-2ide)(triphenylphosphine)gold [4] were synthesized as reported earlier. Other chemicals were of the highest purity commercially available and were used as received. All the solvents were of reagent quality. The reactions were monitored by thin-layer chromatography on silica gel 60 F254 aluminum sheets from Merck. The chromatography was carried out using silica gel (0.050-0.160 mm) for column chromatography. Infrared (IR) spectra were obtained from KBr pellets by means of a Bruker VECTOR 22 infrared spectrometer. Continuous-wave ESR spectra were acquired on a Bruker ER200D X-band spectrometer at MW power 2 mW with modulation 0.01 mT/100 kHz. Cyclic voltammetry measurements were performed in a CH2Cl2 solution with a computer-controlled P-8nano potentiostat/galvanostat (Elins, Russia) in combination with a three-electrode cell (Gamry, Warminster, PA, USA); 0.1 M tetrabutylammonium hexafluorophosphate was used as a supporting electrolyte. Pt, a Pt wire, and Ag/AgCl served as working, counter, and reference electrodes, respectively. The cell was calibrated by measurement of the redox potential of ferrocene as an internal standard. A triphenylphosphine gold derivative of an NN called NN-Au-PPh 3 is known to enter into a Pd(0)-catalyzed cross-coupling reaction with aryl iodides and bromides, with the former reacting smoothly in most cases and the latter being less active and interacting only in the presence of electron acceptor substituents [1]. On the other hand, there are no reports on how variation of the phosphine ligand influences the Pd(0)-mediated cross-coupling process. One would expect two types of such an influence: via electronic effects and via steric effects. Here, we concentrated on the latter by performing the synthesis of two paramagnetic derivatives, NN-Au-P t BuPh 2 (1) and NN-Au-P t Bu 2 Ph (2) (Figure 2), containing one and two bulky tert-butyl substituents, respectively. Both paramagnetic compounds were completely characterized (including X-ray diffraction [XRD] analysis) and then were studied together with a structurally related compound, NN-Au-PPh 3 , in a cross-coupling reaction with an activated bromoarene, namely p-BrC 6 H 4 NO 2 .
Crystals 2020, 10, x FOR PEER REVIEW 2 of 12 A triphenylphosphine gold derivative of an NN called NN-Au-PPh3 is known to enter into a Pd(0)-catalyzed cross-coupling reaction with aryl iodides and bromides, with the former reacting smoothly in most cases and the latter being less active and interacting only in the presence of electron acceptor substituents [1]. On the other hand, there are no reports on how variation of the phosphine ligand influences the Pd(0)-mediated cross-coupling process. One would expect two types of such an influence: via electronic effects and via steric effects. Here, we concentrated on the latter by performing the synthesis of two paramagnetic derivatives, NN-Au-P t BuPh2 (1) and NN-Au-P t Bu2Ph (2) (Figure 2), containing one and two bulky tert-butyl substituents, respectively. Both paramagnetic compounds were completely characterized (including X-ray diffraction [XRD] analysis) and then were studied together with a structurally related compound, NN-Au-PPh3, in a cross-coupling reaction with an activated bromoarene, namely p-BrC6H4NO2.

General Procedures
4,4,5,5-Tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl [3] and (NN-2ide)(triphenylphosphine)gold [4] were synthesized as reported earlier. Other chemicals were of the highest purity commercially available and were used as received. All the solvents were of reagent quality. The reactions were monitored by thin-layer chromatography on silica gel 60 F254 aluminum sheets from Merck. The chromatography was carried out using silica gel (0.050-0.160 mm) for column chromatography. Infrared (IR) spectra were obtained from KBr pellets by means of a Bruker VECTOR 22 infrared spectrometer. Continuous-wave ESR spectra were acquired on a Bruker ER200D X-band spectrometer at MW power 2 mW with modulation 0.01 mT/100 kHz. Cyclic voltammetry measurements were performed in a CH2Cl2 solution with a computer-controlled P-8nano potentiostat/galvanostat (Elins, Russia) in combination with a three-electrode cell (Gamry, Warminster, PA, USA); 0.1 M tetrabutylammonium hexafluorophosphate was used as a supporting electrolyte. Pt, a Pt wire, and Ag/AgCl served as working, counter, and reference electrodes, respectively. The cell was calibrated by measurement of the redox potential of ferrocene as an internal standard.

General Procedures
4,4,5,5-Tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl [3] and (NN-2-ide) (triphenylphosphine)gold [4] were synthesized as reported earlier. Other chemicals were of the highest purity commercially available and were used as received. All the solvents were of reagent quality. The reactions were monitored by thin-layer chromatography on silica gel 60 F 254 aluminum sheets from Merck. The chromatography was carried out using silica gel (0.050-0.160 mm) for column chromatography. Infrared (IR) spectra were obtained from KBr pellets by means of a Bruker VECTOR 22 infrared spectrometer. Continuous-wave ESR spectra were acquired on a Bruker ER200D X-band spectrometer at MW power 2 mW with modulation 0.01 mT/100 kHz. Cyclic voltammetry measurements were performed in a CH 2 Cl 2 solution with a computer-controlled P-8nano potentiostat/galvanostat (Elins, Russia) in combination with a three-electrode cell (Gamry, Warminster, PA, USA); 0.1 M tetrabutylammonium hexafluorophosphate was used as a supporting electrolyte. Pt, a Pt wire, and Ag/AgCl served as working, counter, and reference electrodes, respectively. The cell was calibrated by measurement of the redox potential of ferrocene as an internal standard.

Chloro(tert-butyldiphenylphosphine)gold
Chloroauric acid trihydrate (0.1 g, 0.254 mmol) was dissolved in EtOH (2 mL) under argon followed by the addition of phosphine (0.123 g, 0.508 mmol). The reaction mixture was stirred for 24 h at room temperature. A white precipitate formed, and the solution became colorless. The resulting mixture was evaporated under reduced pressure, and the residue was recrystallized from CH 2 Cl 2 -hexane (1:1) to prepare the title product with yield 0.080 g (67%). The spectral characteristics were identical to those reported before [5].

The General Protocol for the Palladium-Catalyzed Cross-Coupling Reactions
An aryl halide (1.0 eq.), an Au complex (1.0 eq.), and Pd(PPh 3 ) 4 (10 mol%) were dissolved in toluene under argon. The mixture was heated at 70 • C until total consumption of the Au complex. Next, the solvent was removed by rotary evaporation. The residue was purified by column chromatography (SiO 2 , CH 2 Cl 2 -hexane [2:1] as the eluent) to obtain 2-(4-nitrophenyl)NN. Analytical characteristics of the product were identical to those published earlier [4].

Single-Crystal XRD Analysis
X-ray crystallographic analysis of the crystals was carried out at 296(2) K on a Bruker Kappa Apex II CCD diffractometer using ϕ,ω-scans of narrow (0.5 • ) frames with Mo Kα radiation (λ = 0.71073 Å) and a graphite monochromator. The structures were solved by direct methods using the SHELX-97 software [7] and refined by the full-matrix least-squares method against all F 2 in anisotropic approximation in the SHELXL-2014/7 software [8]. Absorption corrections were applied via the empirical multiscan method in the SADABS 2008/1 software [9]. The hydrogen atoms' positions were calculated with the riding model. Solvating molecules of CH 2 Cl 2 were observed in the crystal packing of 1. Crystals of 2 contain two crystallographically independent molecules. Crystal data and structure refinement details are listed in Table 1.

Syntheses and Structures of NN-Au-P t BuPh 2 and NN-Au-P t Bu 2 Ph in Comparison with NN-Au-PPh 3
Metalloid radicals NN-Au-P t BuPh 2 (1) and NN-Au-P t Bu 2 Ph (2) were successfully prepared by the addition of NaOH/MeOH to a CH 2 Cl 2 solution containing NN-H and corresponding Cl-Au-P t BuPhR (1:1 ratio) in a 96% (1) and 88% (2) yield. Radicals 1 and 2 were stable under aerated conditions and were studied both in solution and in a solid state. Bluish-purple single crystals of 1 and 2 used in the structure determination were grown by slow evaporation of CH 2 Cl 2 -Et 2 O-heptane solutions at −5 • C.
The crystal structures were analyzed for short contacts between nonbonded atoms using software packages PLATON-2003 [13,14] and MERCURY-2020.1 (Build 280197) [15]. The analysis revealed that the crystal packing in NN-Au-PPh3, 1, and 2 is secured by intermolecular short contacts predominantly with the participation of the atoms of the NN moiety. Moreover, the number of such contacts is unusually large and reaches five in the gold derivative NN-Au-PPh3 (Table 2). For comparison, in purely organic NNs, the paramagnetic moiety participates in the formation of a limited number of short contacts, one or two, very rarely three contacts. The tendency of radicals NN-Au-PPh3, 1, and 2 to form an increased number of short contacts in the solid state is due to the anionic nature of the NN part, which effectively attracts positively charged atoms of neighboring molecules. This situation leads to supramolecular assembly of the gold derivatives into complicated 3D structures. To simplify their analysis, it is reasonable to choose lower-dimensional substructures and then to connect them via the short contacts to build the final 3D structures of paramagnets.
In NN-Au-PPh3, as a suitable substructure, one can choose the centrosymmetric dimer in which the molecules are linked by van der Waals interactions of type CPh-H⋅⋅⋅O2 (contacts i, Figure 4a) leading to short distances CPh-H…N (ii) and CPh-H…C (iii). The binding of molecules into dimers also causes the formation of short contacts iv between the carbon atoms of the aromatic rings. The propagation of the dimers via two intermolecular CMe-H⋅⋅⋅O1 van der Waals interactions (contacts v and vi) and short contacts C-H⋅⋅⋅C vii generates infinite layers (Figure 4b). The layers are bonded to each other due to additional contacts CPh-H⋅⋅⋅O1 (viii) and CPh-H⋅⋅⋅O2 (x) formed with the participation of oxygen atoms of the paramagnetic centers (Figure 4c).
In the case of gold derivative 1, the dimer shown in Figure 5a can serve as a suitable substructure. In the dimer, the molecules are linked by two van der Waals interactions CPh-H⋅⋅⋅O2 (contacts i, Figure 5a); the binding of molecules leads to short contacts between H atoms (contact ii). Next, the binding of the dimeric structures into the 3D framework occurs both through direct contacts of type CPh-H⋅⋅⋅O2 (iii) and via short contacts with bridging solvation molecules (Figure 5b).
The presence of two independent molecules in the crystal structure of derivative 2 and the absence of solvate molecules result in an intricate and complex network of intermolecular contacts. To clearly show these contacts, it is reasonable to isolate in the structure a pair of dimers A and B consisting of independent molecules (Figure 6a). One of the dimers is formed by the binding of molecules via four van der Waals interactions of the CMe-H⋅⋅⋅O1′ type (contacts i and ii). Another dimer is also formed due to short contacts CMe-H⋅⋅⋅O1 (contacts iii) with the participation of the tertbutyl group. The oxygen atom engages in two more intermolecular contacts (iv and v) with the H atoms of the phenyl ring and the tert-butyl group, thereby causing the binding of the dimers into The crystal structures were analyzed for short contacts between nonbonded atoms using software packages PLATON-2003 [13,14] and MERCURY-2020.1 (Build 280197) [15]. The analysis revealed that the crystal packing in NN-Au-PPh 3 , 1, and 2 is secured by intermolecular short contacts predominantly with the participation of the atoms of the NN moiety. Moreover, the number of such contacts is unusually large and reaches five in the gold derivative NN-Au-PPh 3 ( Table 2). For comparison, in purely organic NNs, the paramagnetic moiety participates in the formation of a limited number of short contacts, one or two, very rarely three contacts. The tendency of radicals NN-Au-PPh 3 , 1, and 2 to form an increased number of short contacts in the solid state is due to the anionic nature of the NN part, which effectively attracts positively charged atoms of neighboring molecules. This situation leads to supramolecular assembly of the gold derivatives into complicated 3D structures. To simplify their analysis, it is reasonable to choose lower-dimensional substructures and then to connect them via the short contacts to build the final 3D structures of paramagnets.
In NN-Au-PPh 3 , as a suitable substructure, one can choose the centrosymmetric dimer in which the molecules are linked by van der Waals interactions of type C Ph -H···O2 (contacts i, Figure 4a) leading to short distances C Ph -H . . . N (ii) and C Ph -H . . . C (iii). The binding of molecules into dimers also causes the formation of short contacts iv between the carbon atoms of the aromatic rings. The propagation of the dimers via two intermolecular C Me -H···O1 van der Waals interactions (contacts v and vi) and short contacts C-H···C vii generates infinite layers (Figure 4b). The layers are bonded to each other due to additional contacts C Ph -H···O1 (viii) and C Ph -H···O2 (x) formed with the participation of oxygen atoms of the paramagnetic centers (Figure 4c).
In the case of gold derivative 1, the dimer shown in Figure 5a can serve as a suitable substructure. In the dimer, the molecules are linked by two van der Waals interactions C Ph -H···O2 (contacts i, Figure 5a); the binding of molecules leads to short contacts between H atoms (contact ii). Next, the binding of the dimeric structures into the 3D framework occurs both through direct contacts of type C Ph -H···O2 (iii) and via short contacts with bridging solvation molecules (Figure 5b). Table 2. The parameters of short contacts and interatomic distances for NN-Au-PPh 3 [4], NN-Au-P t BuPh 2 (1), and NN-Au-P t Bu 2 Ph (2). C corresponds to an analogous carbon atom in another independent structure of NN-Au-P t Bu 2 Ph.

Compounds
Contacts and Distances d, Å d-VdW, Å Symm. Op. alternating ABAB chains. In turn, the chains are linked together into a 3D framework through short contacts viii-xii with the participation of oxygen atoms of the nitroxide groups ( Figure 6b).    The presence of two independent molecules in the crystal structure of derivative 2 and the absence of solvate molecules result in an intricate and complex network of intermolecular contacts. To clearly show these contacts, it is reasonable to isolate in the structure a pair of dimers A and B consisting of independent molecules (Figure 6a). One of the dimers is formed by the binding of molecules via four van der Waals interactions of the C Me -H···O1 type (contacts i and ii). Another dimer is also formed due to short contacts C Me -H···O1 (contacts iii) with the participation of the tert-butyl group. The oxygen atom engages in two more intermolecular contacts (iv and v) with the H atoms of the phenyl ring and the tert-butyl group, thereby causing the binding of the dimers into alternating ABAB chains. In turn, the chains are linked together into a 3D framework through short contacts viii-xii with the participation of oxygen atoms of the nitroxide groups (Figure 6b).   Table 2. The parameters of short contacts and interatomic distances for NN-Au-PPh3 [4], NN-Au-P t BuPh2 (1), and NN-Au-P t Bu2Ph (2). C′ corresponds to an analogous carbon atom in another independent structure of NN-Au-P t Bu2Ph.   Figure 7 shows experimental ESR spectra of NN-Au-P t BuPh 2 and NN-Au-P t BuPh 2 (recorded at room temperature in a dilute degassed toluene solution) and their modeling in Winsim v.0.96 [16] by the procedure described earlier [17]. Isotropic g values were determined using solid DPPH as the standard, and accuracy rates of determining the hyperfine coupling constants and g values are estimated as 0.005 mT and 0.0001, respectively. The spectra are very similar and feature dominant couplings with two equivalent nitrogen atoms and one phosphorus atom producing a pattern consisting of a quintet of doublets with g values somewhat higher than typical for purely organic R-NNs. The magnetic parameters for NN-Au-P t BuPh 2 are as follows: A(2N) = 0.795 mT, A(P) = 0.225 mT, and g iso = 2.0071; for NN-Au-P t Bu 2 Ph: A(2N) = 0.800 mT, A(P) = 0.215 mT, and g iso = 2.0068. No finer couplings could be resolved in the spectra probably because bulky substituents impeded radical rotation in solution, thus resulting in an incomplete average of interfering anisotropic interactions. As with previous works [1,4], no signs of couplings with gold were found in the spectra, although the only stable natural isotope, 197 Au, is magnetic, with I = 3/2, which indicates an identical zero s-character of SOMO in Au(I).

ESR Spectra of NN-Au-P t BuPh 2 and NN-Au-P t Bu 2 Ph
finer couplings could be resolved in the spectra probably because bulky substituents impeded radical rotation in solution, thus resulting in an incomplete average of interfering anisotropic interactions. As with previous works [1,4], no signs of couplings with gold were found in the spectra, although the only stable natural isotope, 197 Au, is magnetic, with I = 3/2, which indicates an identical zero scharacter of SOMO in Au(I).

Electrochemical Properties of NN-Au-P t BuPh2 and NN-Au-P t Bu2Ph
To obtain more information about the electronic properties of NN metalloorganic complexes NN-Au-P t BuPh2 and NN-Au-P t Bu2Ph, their electrochemical analysis was performed. Figure 8 depicts cyclic voltammograms of the compounds synthesized in a CH2Cl2 solution. The two compounds have similar values of oxidation potential: E1/2 ox = −0.03 V for NN-Au-P t BuPh2 and E1/2 ox = −0.06 V for NN-Au-P t Bu2Ph (vs. the Fc/Fc + redox couple), which is comparable to that of NN-Au-PPh3 (E1/2 ox = −0.07 V). Overall, the organogold paramagnets have low oxidation potential as compared, for example, to that of NN-H (+0.38 V) [18]. This specific feature of the NN gold derivatives, as shown above, drastically affects the crystal packing of radicals.

Electrochemical Properties of NN-Au-P t BuPh 2 and NN-Au-P t Bu 2 Ph
To obtain more information about the electronic properties of NN metalloorganic complexes NN-Au-P t BuPh 2 and NN-Au-P t Bu 2 Ph, their electrochemical analysis was performed. Figure 8 depicts cyclic voltammograms of the compounds synthesized in a CH 2 Cl 2 solution. The two compounds have similar values of oxidation potential: E 1/2 ox = −0.03 V for NN-Au-P t BuPh 2 and E 1/2 ox = −0.06 V for NN-Au-P t Bu 2 Ph (vs. the Fc/Fc + redox couple), which is comparable to that of NN-Au-PPh 3 (E 1/2 ox = −0.07 V). Overall, the organogold paramagnets have low oxidation potential as compared, for example, to that of NN-H (+0.38 V) [18]. This specific feature of the NN gold derivatives, as shown above, drastically affects the crystal packing of radicals.

Pd(0)-Mediated Cross-Coupling Reactions of NN-Au-P t Bu2Ph
To investigate the relation between the structure of the gold complexes of the phosphine ligand and their reactivity, we carried out the reaction of NN-Au-PPh3 with p-bromonitrobenzene. The following conditions were applied: p-BrC6H4NO2 (1.0 eq.), NN-Au-PPh3 (1.0 eq.), and Pd(PPh3)4 (0.1 eq.) were dissolved in toluene under argon, and the mixture was heated at 70 °C; the total conversion was achieved after 3 h, and the product yield was 88%. Next, the cross-coupling reactions of NN-Au-P t Bu2Ph and NN-Au-P t BuPh2 were conducted in a similar manner. As it turned out, the reaction times were almost the same (~3.5 h), and the cross-coupling products were obtained in similar yields (84-88%; Scheme 1). Therefore, the presence of tert-butyl substituents in the phosphine moiety of NN-Au-P t Bu2Ph does not influence the cross-coupling process.

Pd(0)-Mediated Cross-Coupling Reactions of NN-Au-P t Bu 2 Ph
To investigate the relation between the structure of the gold complexes of the phosphine ligand and their reactivity, we carried out the reaction of NN-Au-PPh 3 with p-bromonitrobenzene. The following conditions were applied: p-BrC 6 H 4 NO 2 (1.0 eq.), NN-Au-PPh 3 (1.0 eq.), and Pd(PPh 3 ) 4 (0.1 eq.) were dissolved in toluene under argon, and the mixture was heated at 70 • C; the total conversion was achieved after 3 h, and the product yield was 88%. Next, the cross-coupling reactions of NN-Au-P t Bu 2 Ph and NN-Au-P t BuPh 2 were conducted in a similar manner. As it turned out, the reaction times were almost the same (~3.5 h), and the cross-coupling products were obtained in similar yields (84-88%; Scheme 1). Therefore, the presence of tert-butyl substituents in the phosphine moiety of NN-Au-P t Bu 2 Ph does not influence the cross-coupling process.

Pd(0)-Mediated Cross-Coupling Reactions of NN-Au-P t Bu2Ph
To investigate the relation between the structure of the gold complexes of the phosphine ligand and their reactivity, we carried out the reaction of NN-Au-PPh3 with p-bromonitrobenzene. The following conditions were applied: p-BrC6H4NO2 (1.0 eq.), NN-Au-PPh3 (1.0 eq.), and Pd(PPh3)4 (0.1 eq.) were dissolved in toluene under argon, and the mixture was heated at 70 °C; the total conversion was achieved after 3 h, and the product yield was 88%. Next, the cross-coupling reactions of NN-Au-P t Bu2Ph and NN-Au-P t BuPh2 were conducted in a similar manner. As it turned out, the reaction times were almost the same (~3.5 h), and the cross-coupling products were obtained in similar yields (84-88%; Scheme 1). Therefore, the presence of tert-butyl substituents in the phosphine moiety of NN-Au-P t Bu2Ph does not influence the cross-coupling process.