As these Heck reactions have been established to proceed through a heterogeneous Pd(0) active species, two pathways have been proposed in the literature for the reduction of the Pd(II) precatalyst. In the first, proposed originally by Louie and Hartwig181 then revised by Sommer and colleagues (Scheme 6.3),199 a phosphorus-
donor group of the pincer ligand is displaced by the amine base used, giving a cyclometallated palladium-amine intermediate. This is able to undergo β-hydride elimination from an alkyl group of the coordinated amine, to form a palladium hydride complex. As the cyclometallated carbon and hydride occupy coordination sites that are mutually cis-coordinated, reductive elimination of the aryl backbone of the pincer should be facile, yielding a Pd(0) species.
Pd Cl Pd Cl Et2N R2P H H Pd Cl H R2P + Et2N reductive elimination R2P H R2 P PdCl NEt3 β-hydride elimination PR2 PR2 PR2 PR2 ligand exchange
Scheme 6.3 Decomposition pathway for PCP pincer complexes in the presence of an amine base.
A second route to the Pd(0) species was proposed by Beletskaya200 for cyclometal-
lated N-C chelates, but may also be applicable for the decomposition of PCP pincer complexes (Scheme 6.4). In this pathway a phosphorus donor group dissociates from the palladium and is replaced with the π-coordinated alkene. This is able to un- dergo insertion into the palladium-carbon bond of the pincer ligand, much like in the classical Heck mechanism (Figure 6.1). However, in this configuration β-hydride elimination is unable to occur, as the seven-membered ring formed in the insertion step prevents the β-hydrogen from interacting with the palladium. Dissociation of the second phosphorus donor allows free rotation that brings the hydrogen into the proximity of the palladium, rendering the insertion product susceptible to β-hydride
elimination and giving a styryl-substituted pincer ligand. The palladium-hydrido species generated is subsequently reduced to Pd(0) through hydride abstraction by the inorganic base, just as in the final step of the classical Heck reaction mechanism.
R2P PR2 Ph + PdHCl Pd Cl Pd Cl R2P Ph Ph Pd Cl PR2 R2P Ph Cl Pd H Ph R2P R2P H migratory insertion β-hydride elimination β-hydride elimination PR2 PR2 PR2 ligand exchange HCO3- [PdCl]- + H2CO3
Scheme 6.4 Alternate decomposition pathway for PCP pincer complexes in the Heck reaction.
As these decomposition pathways are able to yield molecular Pd(0) species, and it has already been mentioned that mercury may poison some molecular Pd(0) species, further evidence was needed to unambiguously state that the active catalyst is a col- loidal (rather than molecular) Pd(0) species. An observation in agreement with a nanoparticulate active catalyst is the behaviour of 30 at different catalyst loadings. This complex achieved a 25% conversion after 16 hours at a 0.002 mole % loading, but counterintuitively, the conversion decreased to 16% after 22 hours at double the catalyst loading (0.004 mole %). If a catalytic cycle involving a molecular catalyst species was operating, a greater yield of product would be expected at a greater catalyst loading. However, when nanoparticles are the active catalyst, the activity is extremely concentration dependent. Low concentrations of catalyst precursor of- ten demonstrate a disproportionately high activity due to the formation of smaller colloidal particles of palldium, which have a greater ratio of palladium at the surface (active) sites than larger particles, and hence are more active.185 Moreover, constant
reaction of the aryl bromide with the surface of the nanoparticles prevents aggrega- tion and Ostwald ripening; at a low palladium concentration more aryl bromide will be present per palladium atom, so this effect will be more pronounced.185 The rate
of decompostion to form the active Pd(0) catalyst will depend on the coordination environment of the metal and therefore be specific to each complex,201 explaining
why 30 was the only complex used that displayed a decrease in conversion moving from 0.002 to 0.005 mole % loading.
Since the three complexes evaluated all showed similar product ratios (roughly 1:2:20
gem:cis:trans) the same active catalyst is expected in all reactions. It is worth noting
that while 30 displayed an almost 1:1 cis:trans ratio after 22 hours, this is not seen as indicative of a molecular active catalyst. Increasing the steric bulk of the active catalyst is seen to increase the yield of the gem rather than cis product.202 In this
case, the predominance of the cis isomer was not seen in shorter reactions with 30, and so the increased amount present in the longest reactions is likely to be due to
cis/trans isomerisation in solution pending analysis.
From the decomposition pathways previously outlined (Scheme 6.3 and Scheme 6.4), a key step in the formation of the active catalyst species is the dissociation of one of the phosphorus donor atoms from the palladium. This allows for the formation of a complex with the correct cis-geometry for the reductive elimination or alkene inser- tion to occur. Dissociation of the remaining phosphorus donor group is then required for the formation of colloidal palladium. This requirement for Pd−P dissociation can help explain the different rates of reactivity seen between compounds 28, 29, and 30 in the Heck reaction. P−O bonds are notorious for undergoing facile hydrol- ysis;203,204 at millimole percent catalyst loadings it can be assumed that the amount
of adventitious water present is sufficient to facilitate this cleavage. Moreover, un- der these basic reaction conditions (DMF solvent, excess potassium carbonate) this reaction will be more facile, as hydroxide is a better nucleophile than water. Once a P−O bond is broken, the chelate effect can no longer provide additional stabilisation to the phosphine hydroxide ligand, allowing it to more readily dissociate from the complex. Once the dissociation has occurred, phosphinous acid/phosphine oxide tautomerism will reduce the availability of the phosphorus lone pair of electrons for ligand-metal bonding, making the coordination site cis to the P−C bond more readily available, facilitating precatalyst decomposition (Scheme 6.5). Similar P−O cleavage was observed in reactions between methyllithium the POCOP platinum complex 25 (Chapter 4), where PMe(C6F5)2 was observed as a minor product.
The ability for P−O bond hydrolysis to hasten complex degradation was demon- strated in the relative rates of active catalyst formation between 28 and 29; data suggested that the PCCCP-ligated precatalyst displayed a longer induction period than the POCOP-ligated species (Figure 6.3, bottom). However, because 29 un- derwent a less facile decomposition it proved to be the better catalyst precursor. A
Pd Cl Pd Cl PR2 OH H2O OH Pd Cl PR2 OH HO + PR2 O H PR2 O PR2 PR2 PR2
Scheme 6.5 P−O bond hydrolysis in a PCP pincer complex and subsequent tau- tomerism between phosphinous acid and phosphine oxide forms.
gradual deposition of colloidal palladium over time helps to prevent Ostwald ripen- ing and palladium black formation, ensuring a steady stream of active palladium nanoparticles are entering the reaction mixture. This ‘slow release’ of active palla- dium has been repeatedly invoked to explain why the tridentate pincer compounds are better precatalysts in the harsh conditions of the Heck reaction than analogous bidentate cyclometallated compounds.205
This effect was also observed when comparing compound 28 to its non-fluorinated analogues. While 28 achieved a TON of 18,000 for the cross-coupling of styrene with bromobenzene, replacing the electron-withdrawing pentafluorophenyl substituents on the phosphorus donor with electron-donating isopropyl groups gave a reported TON of 140,000 for the identical reaction. This dramatic difference in activities can be attributed to the electronic effects these substituents have on the phosphorus centres. Because they are more nucleophilic and better able to stabilise a nega- tive charge, phosphine ligands with electron-withdrawing substituents have been shown to be much more susceptible to hydrolysis under basic conditions than their more electron-rich counterparts.206,207This propensity for hydrolysis and subsequent
degradation shown by pentafluorophenyl-substituted PCP pincer complexes renders them less efficient at depositing catalytically active palladium nanoparticles than their non-fluorinated counterparts, making them poorer catalysts for the Heck re- action.
Counterintuitive to the notion that more stable precatalysts result in higher TONs was the observation that the complex with both phosphine and phosphinite func- tionalities, 30, was a poorer precatalyst for the Heck reaction than the phosphinite complex 28. The electronic effect that the ligands impart on the metal centre is responsible for this. As has been previously mentioned, tert-butyl phosphines are ex- ceedingly good σ-donors, while pentafluorophenyl phosphines and phosphinites are very poor σ-donors.37,38 This results in increased electron density on the palladium
from 2170 cm-1 in [(POCOP)Pd(CO)]+ (34) to 2140 cm-1 in [(POCCP)Pd(CO)]+
(36). Increasing the electron density on a metal centre has been shown to increase the energy barriers for alkene insertion and also reductive elimination.208,209 The
effect of replacing a poorly donating pentafluorophenyl group with a strongly do- nating tert-butyl group therefore should increase the energy requirement for the decomposition pathways shown in Scheme 6.3 and Scheme 6.4, making formation of the initial Pd(0) species less facile. Furthermore, the strong Pd−PtBu
2 bond
may hinder colloidal palladium formation, as the Pd(0) centres will not be able to aggregate and effectively form nanoparticles until the phosphine has dissociated. A similar phenomenon has previously been reported in the literature, whereby the presence of tert-butyl phosphine donors improve the stability of catalyst precursors, but at the cost of a lower activity.183
There is clearly a fine balance in the relationship between ligand electronic effects and precatalyst activity. Complexes containing either very strongly donating or very weakly donating ligands display surprisingly modest activities as Heck precatalysts; a feature that is exacerbated rather than moderated when both donor types are combined in the same ligand.
Evidently these are complicated reaction mixtures. A number of potential Pd(II) to Pd(0) decomposition pathways are available, and there are surely a number of different factors at work influencing palladium nanoparticle formation. Whilst this section has sought to explain the observed reactivities of compounds 28, 29 and 30, the factors determining the activity of PCP pincer complexes may not play a part in reactions catalysed by other ECE pincer species. Van Koten notes that for SCS pincer-porphyrin complexes, the more electron-rich the porphyrin, the faster the ac- tive catalyst formation and the higher the conversions obtained.201 Conversely, the
work reported herein, along with that of Eberhard183 suggests that for PCP pincer
complexes the presence of an electron-rich PtBu
2 groups slows down the formation
of Pd(0) species and results in poor catalyst activity. Therefore, the factors that influence palladium nanoparticle formation for one group of pincer complexes may not pertain to pincer complexes as a whole, and ligand electronic effects in each case must be balanced such that the desired ‘slow-release’ of the nanoparticulate active catalyst into solution is obtained.