Does the metal protect the ancillary ligands ? C – H strengthening and deactivation in amines and phosphines upon metal-binding † Ainara Nova

Chelating amines, phosphines and other Nand P-donor ligands are widely used as ancillary ligands in homogenous catalysts based on late transition metals. These ligands stabilize the metal centre and provide the chemical environment required for transforming reactants into products. In addition, the stability of these ligands, which is based on the low reactivity of their aliphatic backbones, plays a key role in catalyst robustness. Nonetheless, under the harsh conditions required for some catalysts, e.g. an air atmosphere, strong oxidants and/or high temperatures, these ligands can undergo degradative transformations leading to catalyst deactivation. In particular, the C–H bonds adjacent to the N and P lone pairs (LP) may undergo homolytic cleavage. In this work, DFT(M06) and CCSD(T) calculations show that these C–H bonds are strengthened and deactivated upon metal-binding. This conclusion is in consonance with the experiments recently reported by Bietti et al. showing the C–H deactivation of amines by acids and metal salts. The relative stability of several chelating ligands (L = en, dmpe, dppea, DuPHOS, mcp, dien, tacn, bpym) bound to late transition metals (M = Fe, Ru, Co, Ir, Pd, Pt) in complexes 1–8 (Fig. 1) was explored by means of DFT(M06) calculations. The strength of the C–H bonds in the a position with respect to N and P in the free ligand, L(C–H), was determined relative to the metal-bound ligand, ML(C–H), by computing the radical stabilization energy (RSE; eqn (1)), which is defined as the DH0K of the isodesmic reaction given in eqn (2).

Chelating amines, phosphines and other N-and P-donor ligands are widely used as ancillary ligands in homogenous catalysts based on late transition metals. 1 These ligands stabilize the metal centre and provide the chemical environment required for transforming reactants into products.3][4][5][6][7][8][9] Nonetheless, under the harsh conditions required for some catalysts, e.g. an air atmosphere, strong oxidants and/or high temperatures, these ligands can undergo degradative transformations [10][11][12][13][14][15] leading to catalyst deactivation.7][18][19] In this work, DFT(M06) and CCSD(T) calculations show that these C-H bonds are strengthened and deactivated upon metal-binding.This conclusion is in consonance with the experiments recently reported by Bietti et al. showing the C-H deactivation of amines by acids 20 and metal salts. 21he relative stability of several chelating ligands (L = en, dmpe, dppea, DuPHOS, mcp, dien, tacn, bpym) bound to late transition metals (M = Fe, Ru, Co, Ir, Pd, Pt) in complexes 1-8 (Fig. 1) was explored by means of DFT(M06) calculations.The strength of the C-H bonds in the a position with respect to N and P in the free ligand, L(C-H), was determined relative to the metal-bound ligand, ML(C-H), by computing the radical stabilization energy (RSE; eqn (1)), which is defined as the DH 0K of the isodesmic reaction given in eqn (2).
RSE is a relative quantity, which has been traditionally used to explore substituent effects on the stability of the methyl radical, by using CH 4 /CH 3 as a reference. 22In this study, L(C-H)/L(C ) is used as a reference to assess the influence of metal coordination on the stability of the C radical in the ligand.In this framework, the RSE equals the difference between the C-H bond dissociation energies (BDE) in ML(C-H) and L(C-H) (eqn (1)).Remarkably, all RSE computed for the chelating ligands in complexes 1-8 have negative values (Table 1), i.e. these C-H bonds are strengthened when the ligand coordinates to the metal.For the en ligand in complex 1 (Fig. 1), RSE has a value of À9.4 kcal mol À1 (Table 1), i.e. the C-H BDE of this amine ligand is 9.4 kcal mol À1 higher when it chelates the PdCl 2 moiety.RSE was also computed for a phosphorus analogue of the en ligand, dmpe, bound to Pt (2).In this species, the RSE calculated for the methylene position was À4.5 kcal mol À1 .The comparison of these two RSE values suggests that, upon coordination of the ligand to the metal, C-H bonds attached to N are more strengthened than those attached to P. This is clearly the case for the dppea ligand in complex 3.The CH 2 (NH 2 ) unit of this N,P-donor ligand yields RSE = À6.4 kcal mol À1 , whereas the CH 2 (PPh 2 ) unit yields RSE = À1.7 kcal mol À1 .In 4, the tertiary C-H of the DuPHOS ligand has a fairly negative RSE of À3.3 kcal mol À1 .Complexes 5-8 have a wide range of RSE between the minimum and The strengthening of the C-H bonds in complexes 1-8 can also have a significant impact on their kinetic reactivity.This issue was explored by defining and computing DDG ‡ (eqn (3)), which measures the influence of the metal on the energy barrier for H abstraction from the ligand by the methoxy radical (eqn (4) and ( 5)).DDG ‡ was then used to calculate the ratio between the rate constants for the free and metal-bound ligand at 298 K, k L /k ML (eqn ( 6)).
Remarkably, as for the RSE, DDG ‡ has negative values for all complexes 1-8 (Table 1); i.e.DG L ‡ o DG ML ‡ , showing that these C-H bonds, in addition to being strengthened, are also deactivated when the ligand coordinates to the metal.C-H strengthening and deactivation have been already correlated experimentally. 23This relationship is intuitive and may seem obvious but, in other chemical systems, the strongest chemical bonds are preferentially cleaved 24,25 when no radicals are involved.
In the phosphines, the alternative oxidation of P by the methoxy radical was not explored. 26,27he C-H bonds of the en ligand in complex 1 (Fig. 1), which are strengthened by 9.4 kcal mol À1 , are significantly deactivated as shown by the negative value of DDG ‡ , À6.9 kcal mol À1 (Table 1); i.e. radical H abstraction is five orders of magnitude faster in the free en ligand than in 1, k L /k ML = 1.2 Â 10 5 .In the phosphine ligands, which showed softer C-H strengthening when compared to the amines, this deactivation effect is somewhat reduced.The rate constants for H abstraction from dmpe and DuPHOS decrease by four and two orders of magnitude when these ligands are bound to Pt in complexes 2 and 4, respectively.Moreover, in complex 3, the higher strengthening of the C-H bonds attached to N (RSE = À6.4 kcal mol À1 ), when compared to those attached to P (RSE = À1.7 kcal mol À1 ), involves a stronger deactivation of the former positions, as shown by the values of DDG ‡ , À8.5 kcal mol À1 (k L /k ML = 1.6 Â 10 6 ) and À2.7 kcal mol À1 (k L /k ML = 9.8 Â 10 1 ), respectively.In complexes 5, 6 and 7, C-H deactivation upon coordination to the metal can also be rather significant, with k L /k ML ranging from one to ten orders of magnitude.In complex 8, the position of the abstracted H relative to the metal has a strong influence on the extent of C-H deactivation.For the b position, which showed the highest C-H strengthening (RSE = À8.1 kcal mol À1 ), DDG ‡ equals À12.1 kcal mol À1 (k L /k ML = 7.5 Â 10 8 ), whereas for the d position, which showed the lowest C-H strengthening (RSE = À2.8 kcal mol À1 ), DDG ‡ equals À1.4 kcal mol À1 (k L /k ML = 1.1 Â 10 1 ).The wide range of values found for RSE and DDG ‡ suggests that both quantities are very sensitive to the chemical environment of the C-H bond, including the nature of the donor atom, the metal and the coordination geometry.In line with this, the plot of DDG ‡ (y) vs. RSE (x) shows a moderate correlation (Fig. S1, ESI †), with the linear regression yielding y = 0.92x À 0.86 kcal mol À1 (r 2 = 0.80).This r 2 value seems satisfactory considering the diverse nature of complexes 1-8.Furthermore, for non-equivalent positions within the same complex (3, 5, 8), the apparent trend is that the stronger the C-H bond, the less reactive it is.
To gain further insight into the origin of the C-H strengthening, the electronic structures of the species used to compute the RSE (eqn (1)) were explored in detail for the [Ir(tacn)(Cl) 3 ] complex (7), which showed the largest effect (Table 1).The spin density (r) of the free tacn radical (r 1 in Fig. 2) shows that the unpaired electron is delocalized over C and N; the local spin densities on these atoms are r C = 0.79 and r N = 0.16, respectively.This species is thus stabilized by a 3e/2c interaction between the donor (N LP) and acceptor (C radical), 28 which is reinforced by the parallel alignment of the orbitals.The local spin densities in the metal-bound system (r 2 ), [Ir(tacn )(Cl) 3 ], r C = 0.95 and r N = À0.03,show that this interaction is suppressed when the N LP coordinates to the metal centre.The higher stabilization of the C radical in the free tacn ligand than in the metal-bound contributes to the negative value of the RSE found for this system, À15.0 kcal mol À1 (Table 1).

Communication ChemComm
This journal is © The Royal Society of Chemistry 2014 The origin of the C-H deactivation effect was also explored by analysing the spin densities of the H abstraction transition states (r 3 and r 4 ) used to compute DDG ‡ (eqn (3)) for complex 7.In the metal-free system, the spin density is delocalized over the O atom of the radical abstractor and the C and N atoms of the ligand, whereas, in the metal-bound system, is only significant for C and O.These data show that the incipient C radical of the H abstraction transition state is stabilized by the N LP only in the metal-free system, thus contributing to the negative value of DDG ‡ found for this system, À14.2 kcal mol À1 (Table 1).The hyperconjugation of the N LP with the parallel antibonding s*(C-H) orbital was explored by means of NBO analysis (version 5.9).The NLMO (Natural Localized Molecular Orbital) of the s*(C-H) orbital, where this interaction is most apparent, shows that the contribution of the N LP is lower when the tacn ligand coordinates to Ir (see Fig. S2 in the ESI †), yielding a lower stabilization energy for the N LPs*(C-H) interaction; 10.1 kcal mol À1 (free tacn), 4.4 kcal mol À1 ([Ir(tacn)(Cl) 3 ]).In line with these data, the C-H bond distance shortens from 1.113 Å in free tacn to 1.100 Å in [Ir(tacn)(Cl) 3 ].The reduced hyperconjugation of the N LP with the s*(C-H) orbital in the metal-bound system thus also contributes to the strengthening and deactivation of the C-H bonds a to N. 28 The lower Lewis basicity of the P LP compared to N provides a rational basis for the softer effects found for the C-H bonds a to P, when compared to those a to N (Table 1).
Highly accurate CCSD(T) calculations were also performed for system 1.The RSE value computed at this level of theory, À9.9 kcal mol À1 , is in excellent agreement with that computed at the DFT(M06) level, À9.4 kcal mol À1 (Table 1).The CCSD(T) value of DDG ‡ is also negative, À4.4 kcal mol À1 , and does not deviate much from the DFT(M06) result, À6.9 kcal mol À1 .Furthermore, very similar results were obtained for complexes 2, 7 and 8 when other functionals were used (Table S1, ESI †).
This may not be a universally applicable proof of the C-H strengthening and deactivation effects observed in this study.Nonetheless, support comes from a recent experimental study, in which Bietti and co-workers reported similar results for organic bases undergoing H abstraction reactions with the cumyloxyl radical (PhC(CH 3 ) 2 O ). 21E.g., the rate constant for H abstraction from the secondary C-H bonds of triethylamine (TEA) was at least two orders of magnitude higher with free TEA (k) than in the presence of [Mg(ClO 4 ) 2 ] (k Mg ).The authors suggest that the coordination of Mg to the N LP of TEA is the origin of this effect.This hypothesis was explored by following the approach used for complexes 1-8 (eqn (1)-( 6)).The structures of the Mg-TEA complex (9) and the associated transition state for H abstraction by PhC(CH 3 ) 2 O are given in Fig. S3 (ESI †).The RSE and DDG ‡ values found for this system (Table 1) are negative, À5.1 kcal mol À1 and À6.4 kcal mol À1 , respectively.These data show that the secondary C-H bonds of TEA are strengthened and deactivated upon coordination of its lone pair to Mg.The value of DDG ‡ yields a theoretical k/k Mg = 5.3 Â 10 4 , in consonance with the kinetics experiments that yielded k/k Mg > 200. 21n summary, we have shown that N-and P-donor ancillary ligands become more robust upon coordination to a metal centre.This effect arises from the coordination of the N and P LPs and may also reduce the acidity of the C-H bond.Given the large changes found, this effect cannot be ignored in assessing and optimizing catalyst robustness.
A.N. and D.B. acknowledge O. Eisenstein and R.H. Crabtree for fruitful discussions, the Research Council of Norway for funding (Grant 179568/V30) and the Norwegian Supercomputing Program for computational resources (Grant nn4654k).