Dynamic NMR Studies

With regard to a stereoselection in catalysis, the dynamics in solution are relevant. To this end, the temperature dependent dynamics of ^MeO1-py, ^Et1-py and ^Ar1-py have been reported previously. In all cases only one dynamic process – indicated by an inequivalence of the aryl substituents at low temperatures – has been observed and assigned to the ring-inversion without further evidence.^21,25,28 In order to shed light on the timescale of the relevant molecular motions various temperature dependent NMR studies (-90 °C to 130 °C) were conducted with the free ligands ^X(P^O)H, the corresponding salts ^X(P^O)M and the methyl complexes ^X1.

For the protonated ligand ^MeO(P^O)H no change in the spectrum is observed at temperatures down to -90 °C implying that still all molecular motions are fast. For the sodium salt ^MeO(P^O)Na the anisyl moieties are inequivalent at -90 °C (Figure 5-8), but only one diastereomer is detected as the compound exhibits only one ³¹P NMR resonance. Here, it is assumed that the interconversion between two enantiomers is slow rendering the aryl moieties inequivalent and that either only a single exo₃/exo₂ conformation is populated or rather unlikely that the interconversion between these conformations is still fast. The similar shift of the anisyl ortho protons H_12a and H_12b (6.64/6.32 ppm, Figure 5-8, Table 5-1), which is a measure for the exo₂ content, indicates that probably only the exo₃ configuration is populated, as it was also observed for PAr₂Ar’ phosphines.^150,151 This can be confirmed by a

1H, ¹H ROESY spectrum at -80 °C showing NOE-correlations between the sulfonic acid ortho proton H₃ to both the anisyl ortho protons H_12a and H_12b (Figure 5-9), and is also in line with the solid state structure of ^MeO(P^O)HNEt3.¹⁴⁹

Figure 5-8. Variable temperature ¹H NMR spectra (400 MHz, CD3OD) of ^MeO(P^O)Na and ^MeO1.

Figure 5-9. ¹H,¹H ROESY spectra (CD3OD, -80 °C) of ^MeO(P^O)Na (left) and ^MeO1 (right) for conformational analysis, evidencing an exo3 (left), respectively an exo2 (right) configuration.

For the Pd complex ^MeO1 similarly only the aryl moieties are rendered inequivalent at -90 °C. In this case the anisyl ortho protons H₁₂ exhibit a strong shift difference at -90 °C (8.60/6.87, Figure 5-8, Table 5-1) indicating the population of a single exo₂ configuration, which is in line with the solid state structure for ^MeO1-lut.⁴⁵ Accordingly, there is only a NOE-correlation between H₃ and H_12b but not between H₃ and H_12a visible in the ¹H, ¹H ROESY spectrum at -80 °C (Figure 5-9). The observed downfield shift to 8.60 ppm for the ortho H_12a resonance assigned to the aryl moiety with the MeO-group in the endo position can be explained due to paramagnetic anisotropy. Because H12a is directed exo and thus forced into close proximity to the palladium dz2 orbital.^152,153 Considering further aryl resonances, it can be observed that the protons in meta position of the anisyl ring (H11, H9), which resonate at 7.0 ppm, split up in separated signals with a moderate shift difference at -90 °C (7.17, 6.94 ppm). By contrast, the resonance of the para anisyl protons (H10) remains rather unchanged (Figure 5-8).

Table 5-1. Configuration of the aryl moieties at phosphorus.

entry compound

For the other symmetric substituted compounds, rather similar processes are observed by NMR spectroscopy (Table 5-1). ^CF3(P^O)Li adopts an exo₃ arrangement, whereas the corresponding complex is arranged in an exo₂ fashion as evidenced by the variable temperature ¹H NMR shifts. For the very bulky 2,6-(OMe)₂C₆H₃-moeity an exo₃ arrangement for ^Ar(P^O)H is evidenced by a ¹H ¹H ROESY spectrum at -20 °C. Whereas for the corresponding complex ^Ar1 an NMR analysis of the configuration is not possible at -90 °C, due to broad resonances, solid state structures show that exo3 as well as exo2 are possible arrangements (Table 5-1).²⁴

For symmetric substitution patterns at phosphorus (^MeO1, ^CF31, ^Ar1) freezing of a molecular motions at low temperature results in the inequivalence of the aryl substituents only. This indicates that a single conformation (one pair of enantiomers) must be adopted (Figure 5-8, Table 5-1). Similarly to this, Rieger et al. reported that for a bulky (P^O)H ligand exhibiting 1-methoxynapthalene substituents a restriction of the molecular motion is evidenced by inequality of the two 1-methoxynapthalene substituents in the ¹H NMR spectra at room temperature. For the corresponding palladium complexes also a single diastereomer exhibiting two inequivalent aryl moieties was observed.³¹ In contrast, Claverie et al. observed that for very bulky naphthyl and phenanthryl substituted (P^O)-ligands two stable diastereomers exist in solution. Here, DFT calculations implied that the exo3 and one of the exo₂ isomers coexist because of sterically hindered rotation. Consequences upon coordination to palladium could not be clarified completely due to complexity of the spectra.²⁸

Figure 5-10. Variable temperature ¹H NMR spectra (400 MHz, CD3OD) of ^Ar/(MeO)2(P^O)Na and ^Ar/(MeO)21.

The asymmetric compounds ^Ar/(MeO)2(P^O)Na and ^Ar/(MeO)21 form a pair of diastereomers at low temperature, which results not only in the inequivalence of the aryl substituents but in a complete second set of ¹H NMR resonances (Figure 5-10). The formation of diastereomers can be related to the combination of the permanent asymmetric center at

phosphorus with the stereocenter derived at low temperature due to a fixed conformation. For the sodium salt as well as for the Pd complex, a 2:3 ratio of the diastereomers is observed.

A comparison of the dynamics for the free ligands and the complexes with coordinated ligands reveals that regularly rather similar processes for the corresponding ligand/complex couple are observed (Figure 5-8, Figure 5-9). The resonances of the non-chelating aryl substituents in the ¹H NMR split upon freezing of the molecular motion. These new resonances provide further insights into the aforementioned process. In general, it is found here, that the pair of corresponding ortho-aryl protons experiences the largest shift difference, whereas the para proton resonances remain nearly unchanged (Figure 5-8). This is in line with an aryl rotation process, where the para-protons are within the axis of rotation. By contrast, a ring flip should have a more pronounced influence on these para-protons. Since the complexes and the corresponding free ligands show a similar, single motional process and the shift of the ¹H NMR resonances of the aryl protons upon freezing of the motions is in line with an aryl rotation, it can be concluded that a ring flip process is not observed within the accessible temperature range.

In order to gain insights into the exact energetic barriers of the observed processes dynamic NMR studies of the ligands ^X(P^O)H, the corresponding salts ^X(P^O)M, and the corresponding complexes were performed. Rate constants at variable temperatures were determined by a full line shape analysis, and an Eyring plot yielded ∆H^≠ and ∆S^≠, respectively (Table 5-2). For comparison, ∆G^≠_Tc (at the coalescence temperature T_c) was calculated from

∆H^≠ and ∆S^≠, and also derived independently from the distance of the resonances in the slow exchange region (∆ν) according to the equations:¹⁵⁴ analysis was not applicable, as was the case for most of the ^X(P^O)H compounds. The ∆G^≠Tc

values obtained by the two different approaches agree well and the comparison of ∆G^≠Tc for

MeO1 (∆G^≠Tc = 43 kJ/mol, Tc = -50 °C, Table 5-2) determined for the MeO-groups nicely fits with the value determined by Jordan et al. for ^MeO1-py (∆G^≠Tc = 44 kJ/mol, Tc = -50 °C).²⁵

A comparison of the different ligands reveals that for the protonated ligands ^X(P^O)H the rotational barrier increases with the steric bulk: MeO < CF3 ~ Ar. Here, CF3 appears much smaller than 2,6-(MeO)2C6H3, but for steric interaction the steric bulk directly attached at the

The barriers for the salts ^X(P^O)M (M = Na, Li) are in general significantly higher than for the protonated species (e.g. ∆G^≠Tc-CF3(P^O)H = 59 kJ/mol vs. ∆G^≠Tc-CF3(P^O)Li = 68 kJ/mol) and in some cases even in the same order as for the complexes. It might be assumed that bulkiness of the sulfonate group is increased by coordination of M (note that in

X(P^O)H the proton is attached to the phosphorus atom) and that the rotational barriers consequently increase. Additionally, ionic interactions of e.g. the MeO-substituents with the counter ion might further contribute to the rotational barrier.

The rotational barriers for complexes ^X1 are always at least 10 kJ/mol higher than for the free ligands ^X(P^O)H. The highest barriers were found for ^CF31 for which even at 130 °C no fast interconversion was observed (∆G^≠Tc > 76 kJ/mol). Since for ^Et1 in comparison to

MeO1 also a higher barrier was observed (∆G^≠Tc = 64 kJ/mol vs. ∆G^≠Tc = 44 kJ/mol for

MeO1)²⁵, it appears that small changes in the β-position of the ortho substituents (OMe, vs.

CH2Me, vs. CF3) can have a significant impact on the rotational barriers, as also observed for the free ligands (vide supra). The increase of the rotational barriers of around 10-20 kJ/mol upon coordination of the free ligands to a Pd-center agrees with previous observations on arylphosphine complexes. Here, it was reported that for P(o-Tol)3 ∆G^≠ increases steadily from the free phosphine (∆G^≠<<30 kJ/mol, not observable),^151,155 to a single phosphine coordinated complexes ((CO)xM-P(o-Tol)3, ∆G^≠ = 36-45 kJ/mol),^156,157 to a bis-trans coordinated,

(P^O)Na and ^Ar/(MeO)21 with a higher barrier for the complex (∆G^≠Tc-Ar/(MeO)2(P^O)Na = 39 kJ/mol vs. ∆G^≠Tc-Ar/(MeO)21 = 59 kJ/mol). However, for the protonated ligand

Ar/(MeO)2

(P^O)H no formation of diastereomers can be observed down to -90 °C (∆G^≠Tc-Ar/(MeO)2(P^O)H < 35 kJ/mol), but a rather high barrier of 52 kJ/mol is found for an isolated process only affecting the rotation of the (MeO)₂C₆H₃ group.

In conclusion, of the two motional processes affecting stereoselectivity the aryl rotation possesses the significantly higher barriers in the range of 40-60 kJ/mol, whereas the ring flip process could not be observed in the accessible temperature range and must exhibit barriers always below ca. 35 kJ/mol. The observed barriers and corresponding coalescence temperatures are low in comparison to the temperatures required for an effective insertion, 60-90 °C. Only ^CF31 is an exception. Thus, in general the ligand framework must be regarded as conformationally fluxional.

Table 5-2. Results of line shape analysis and derived energy barriers for ^X(P^O)H, ^X(P^O)M, and ^X1. observed up to 130 °C; ^fno formation of diastereomers observed, only rotation of 2,6-(OMe)2C6H3- is hindered, different process then for entry 2-9 to 2-10 occurs; ^gformation of diastereomers observed.