Organoruthenium Complexes Containing Phosphinodicarboxamide Ligands

: Ruthenium complexes of phosphinocarboxamide ligands, and their use to form metallacycles using halide abstraction/deprotonation reactions are reported. Thus, [Ru( p -cym){PPh 2 C(=O)NHR}Cl 2 ; R = i Pr ( 1 ), Ph ( 2 ), p -tol ( 3 )] and [Ru( p -cym){PPh 2 C(=O)N(R)C(=O)N( H )R}Cl 2 ; R = Ph ( 4 ), p -tol ( 5 )] were synthesized from [( p -cym)RuCl 2 ] 2 ( p -cym = para -cymene) and phosphinocarboxamides or phosphinodi-carboxamides, respectively. Single-crystal X-ray diffraction measurements on 1 – 5 reveal coordination to ruthenium through the phosphorus donor, with an intramolecular hydrogen bond between the amine-bound proton and a metal-bound chloride. Six-membered metallacycles formed by halide abstraction/deprotonation of complexes 4 and 5 afforded [Ru( p -cym){ κ 2 - P,N -PPh 2 C(=O)N(R)C(=O)NR}Cl] [R = Ph ( 6 ), p -tol ( 7 )]. These species exist as a mixture of two rotational isomers in solution, as demonstrated by NMR spectroscopy.


Results and Discussion
synthesis of M4L6 cage complexes, facilitated by hydrogen bonding interactions between the PCA moiety and the halide ion [13].

Synthesis and Characterization of [Ru(p-cym){κ 2 -P,N-PPh2C(=O)N(R)C(=O)NR}Cl] ([R = Ph (6), p-tol (7)]
With the intention to synthesize six-membered metallacycles via intramolecular cyclization, compounds 4 and 5 were reacted with K2CO3 and AgPF6 in CD2Cl2 at room temperature (Scheme 2A), affording 6 and 7, respectively (Figures S16-S22).In contrast, compound 2 showed no reaction under the same conditions.It is likely that the formation of the four-membered metallacycle is prohibited due to the higher ring strain resulting from the shorter PCA backbone.

Synthesis and Characterization of [Ru
With the intention to synthesize six-membered metallacycles via intramolecular cyclization, compounds 4 and 5 were reacted with K 2 CO 3 and AgPF 6 in CD 2 Cl 2 at room temperature (Scheme 2A), affording 6 and 7, respectively (Figures S16-S22).In contrast, compound 2 showed no reaction under the same conditions.It is likely that the formation of the four-membered metallacycle is prohibited due to the higher ring strain resulting from the shorter PCA backbone.Scheme 2. (A) Formation of six-membered metallacycles (6 and 7).Reaction conditions: 1 eq. 4 or 5, 3 eq.K2CO3 and 1.3 eq.AgPF6, room temperature.(B) Ligand replacement reaction upon exposure to CO. Reaction conditions: 1 eq. of 4 or 5, excess CO, room temperature.
The 31 P NMR spectroscopic resonances for the cyclized products 6 and 7 are shifted downfield with respect to the corresponding monodenate complexes 4 and 5 (Table 1).This is in line with previously reported six-membered N,P-metallacycles, such as [Ru-κ 3 -NNP-{HCl(CO)}]; and S19 and S24) [27][28][29].Our NMR spectroscopic studies support the structure described in Scheme 2 (Figures S17, S18, S21-S23 and S26-S28); and we propose that upon initial coordination (6-7), reaction with K2CO3 can deprotonate the PDCA amide.However, it is not until one of the coordinated halides is removed by AgPF6, that formal cyclization takes place.This assertion has been corroborated by deprotonation experiments, in the absence of AgPF6.Further halide replacement by [PF6] − has been ruled out by means of NMR spectroscopy and MS analyses (ion trap).Although one resonance is observed in the 31 P NMR spectra (Table 1), both 6 and 7 are observed to exist as a mixture of two distinct isomers (6a-7a/6b-7b), as determined by 1 H NMR spectroscopy (Figures S16-S24 and Table S1).Additionally, 1 H-1 H COSY NMR spectra of the cyclized products (6-7), allowed for the deconvolution of the signals associated with the individual products, with distinctive correlations between the individual i Pr fragments (Figures S18 and  S22).Integration of the 1 H NMR signals from the p-cymene ring indicate an isomer ratio of 60:40 for 6 and 87:13 for 7.In both cases, the major product shows a complete loss of symmetry (as observed by 1 H and 13   S1), allowed for the calculation of the hydrodynamic radii.These values are in good agreement with the values obtained from the crystal structures of 2 and 5, and the geometry optimized structures of 7 (vide infra).An increase in the hydrodynamic radius is observed between 2 and 5 due to the increased length of the ligand, with only a small change in hydrodynamic radius observed upon cyclization (7).Similar to compounds 1-5, scalar spin-spin coupling is observed in the 13 C{ 1 H} NMR spectra of 6 and 7 between the p-cymene and the phosphorus of the PDCA ligand [ 13 C{ 1 H} NMR] (Figure S22) [31].With the signals for the non-quaternary aromatic carbons, in the p-cymene fragment, as four distinctive doublets ( 2 JCP = 3-6 Hz) (Figure S22).
The existence of two rotational isomers for compounds 6 and 7 can be explained by the restricted rotation of the p-cymene ring.DFT calculations demonstrate the existence of two rotamers, with either the i Pr (6a′/7a′) or Me (6b′/7b′) of the p-cymene ring lying above the Cl ligand (Figures 2 and S26-S28).These rotamers are computed to be close in energy (ΔG = −0.4kcal mol −1 in 6 and −0.2 kcal mol −1 in 7), suggesting minimal thermodynamic preference for either isomer.We propose, therefore, that the product distribution is determined by kinetic control.The strong preference for one isomer in 7 is likely due to a strong conformational preference for complex 5 in solution, which gets "locked in" when the complex cyclises on treatment with a halide abstractor and base.High-temperature NMR measurements on 6 and 7 were hindered as the complexes display poor solubility in CD3C6D5 and decompose in CDCl3 and CD3CN.Variable temperature NMR studies ( 1 H and 31 P NMR spectroscopy) in CD2Cl2 (268-298 K) showed no coalescence, indicating higher temperatures are required for interconversion.
The 31 P NMR spectroscopic resonances for the cyclized products 6 and 7 are shifted downfield with respect to the corresponding monodenate complexes 4 and 5 (Table 1).This is in line with previously reported six-membered N,P-metallacycles, such as [Ruκ 3 -NNP-{HCl(CO)}]; and S19 and S24) [27][28][29].Our NMR spectroscopic studies support the structure described in Scheme 2 (Figures S17, S18, S21-S23 and S26-S28); and we propose that upon initial coordination (6-7), reaction with K 2 CO 3 can deprotonate the PDCA amide.However, it is not until one of the coordinated halides is removed by AgPF 6 , that formal cyclization takes place.This assertion has been corroborated by deprotonation experiments, in the absence of AgPF 6 .Further halide replacement by [PF 6 ] − has been ruled out by means of NMR spectroscopy and MS analyses (ion trap).Although one resonance is observed in the 31 P NMR spectra (Table 1), both 6 and 7 are observed to exist as a mixture of two distinct isomers (6a-7a/6b-7b), as determined by 1 H NMR spectroscopy (Figures S16-S24 and Table S1).Additionally, 1 H-1 H COSY NMR spectra of the cyclized products (6-7), allowed for the deconvolution of the signals associated with the individual products, with distinctive correlations between the individual i Pr fragments (Figures S18 and S22).Integration of the 1 H NMR signals from the p-cymene ring indicate an isomer ratio of 60:40 for 6 and 87:13 for 7.In both cases, the major product shows a complete loss of symmetry (as observed by 1 H and 13 C{ 1 H} NMR spectra) on the p-cymene fragment (Figures S18 and S22), with the minor product remaining bilaterally symmetrical (6a-7a (symmetric) and 6b-7b (asymmetric)).The diffusion coefficients (D) of 2, 5 and 7, determined by DOSY NMR experiments (Table S1), allowed for the calculation of the hydrodynamic radii.These values are in good agreement with the values obtained from the crystal structures of 2 and 5, and the geometry optimized structures of 7 (vide infra).An increase in the hydrodynamic radius is observed between 2 and 5 due to the increased length of the ligand, with only a small change in hydrodynamic radius observed upon cyclization (7).Similar to compounds 1-5, scalar spin-spin coupling is observed in the 13 C{ 1 H} NMR spectra of 6 and 7 between the p-cymene and the phosphorus of the PDCA ligand [ 13 C{ 1 H} NMR] (Figure S22) [31].With the signals for the non-quaternary aromatic carbons, in the p-cymene fragment, as four distinctive doublets ( 2 J CP = 3-6 Hz) (Figure S22).
The existence of two rotational isomers for compounds 6 and 7 can be explained by the restricted rotation of the p-cymene ring.DFT calculations demonstrate the existence of two rotamers, with either the i Pr (6a /7a ) or Me (6b /7b ) of the p-cymene ring lying above the Cl ligand (Figure 2 and Figures S26-S28).These rotamers are computed to be close in energy (∆G = −0.4kcal mol −1 in 6 and −0.2 kcal mol −1 in 7), suggesting minimal thermodynamic preference for either isomer.We propose, therefore, that the product distribution is determined by kinetic control.The strong preference for one isomer in 7 is likely due to a strong conformational preference for complex 5 in solution, which gets "locked in" when the complex cyclises on treatment with a halide abstractor and base.Hightemperature NMR measurements on 6 and 7 were hindered as the complexes display poor solubility in CD 3 C 6 D 5 and decompose in CDCl 3 and CD 3 CN.Variable temperature NMR studies ( 1 H and 31 P NMR spectroscopy) in CD 2 Cl 2 (268-298 K) showed no coalescence, indicating higher temperatures are required for interconversion.

Ligand Displacement Studies
To test the stability of the Ru-P bond, solutions of 4 and 5 in CD2Cl2 were exposed to an atmosphere of dry CO (Scheme 2B).NMR analysis indicated loss of the PDCA ligands and formation of [{p-cymene}RuCl2(CO)] [32] (Figure S25).Similar behaviour has been observed in [Rh(η 3 -TMPP)2][BF4]2 [TMPP = tris(2,4,6-trimethoxyphenyl)phosphine] that when exposed to an atmosphere of CO, can reversibly coordinate, a useful feature that has been used for chemosensing applications [33,34].In contrast, no reaction was observed on treating the metallacycle 6 with CO, suggesting that the chelate complex is more robust to ligand substitution.

Materials and Methods
For full details on experimental procedures, see the Supporting Information.Note: We observed that although compounds 1-3 display some stability, under aerobic conditions, decomposing over the course of a few weeks; samples of 4-7 are susceptible to spontaneous decomposition in solution/solid-state in the glovebox.
L-1-L-5 were prepared according to our previously reported methodologies [9].Crystals suitable for single-crystal X-ray diffraction for 1-5 were grown from concentrated toluene (layered with hexane) or C6D6 extracts at room temperature, respectively.

Ligand Displacement Studies
To test the stability of the Ru-P bond, solutions of 4 and 5 in CD 2 Cl 2 were exposed to an atmosphere of dry CO (Scheme 2B).NMR analysis indicated loss of the PDCA ligands and formation of [{p-cymene}RuCl 2 (CO)] [32] (Figure S25).Similar behaviour has been observed in [Rh(η 3 -TMPP) 2 ][BF 4 ] 2 [TMPP = tris(2,4,6-trimethoxyphenyl)phosphine] that when exposed to an atmosphere of CO, can reversibly coordinate, a useful feature that has been used for chemosensing applications [33,34].In contrast, no reaction was observed on treating the metallacycle 6 with CO, suggesting that the chelate complex is more robust to ligand substitution.

Materials and Methods
For full details on experimental procedures, see the Supporting Information.Note: We observed that although compounds 1-3 display some stability, under aerobic conditions, decomposing over the course of a few weeks; samples of 4-7 are susceptible to spontaneous decomposition in solution/solid-state in the glovebox.
L-1-L-5 were prepared according to our previously reported methodologies [9].Crystals suitable for single-crystal X-ray diffraction for 1-5 were grown from concentrated toluene (layered with hexane) or C 6 D 6 extracts at room temperature, respectively.
Volatiles were removed under vacuum, affording the target compounds 1-5.In the particular case of 2, the reaction was successfully scaled up, employing 50 mg (0.08 mmol) of [Ru(p-cymene)Cl 2 ] 2 , with full characterization described below.Figure 3 shows the general numbering scheme used for the the p-cymene ligand in compounds 1-5.

Figure 2 .
Figure 2. Illustrations for the geometry-optimized structures for 6a and 6b .

Figure 4 .
Figure 4. General numbering scheme for cyclization compounds 6a and b (R = Ph) and 7a and b (R= p-tol).* indicate multiplets in the NMR spectrum.

Figure 4 .
Figure 4. General numbering scheme for cyclization compounds 6a and b (R = Ph) and 7a and b (R= p-tol).* indicate multiplets in the NMR spectrum.

Table 1 .
Selected NMR spectroscopic data δ (ppm) for the free PCA/PDCAs L

-1-L-5, and complexes 1-7. Compound 31 P Free PCA/PDCA Ligand a 31 P PCA/PDCA Complex b 13 C{ 1 H} C=O PCA/PDCA Complex b 1 H NH PCA/PDCA Complex b
Chemical shifts reported in ppm in C 6 D 6 .b Chemical shifts reported in ppm in CD 2 Cl 2 .c Chemical shifts for Ph 2 P (C=O) and N (C=O) in ppm.
a d Signal not observed.