3.5 Diphosphines with a Hetero-substituted Backbone
3.5.1 Synthesis of Si-Diphosphines and Transformation into their Pd(II) Complexes
Silane bridged diphosphines with varying alkylsilane backbone were synthesized and transformed into the corresponding Pd(II) complexes for investigations of the catalytic isomerization reaction.
Following the synthetic route[86] outlined in Scheme 50, the methylation of chlorophosphines 105 and 106 proceeds nearly quantitatively. Subsequent lithiation with tert-BuLi in heptane at 100°C affords the corresponding lithium salts 109 and 110, which precipitated as white solids. Addition of 0.5 equiv. of di-alkyl-dichloro-silanes 111 and 112 at low temperatures led to the formation of the desired silane-diphosphines 113-116 in moderate to good yields, either as oils or colorless crystals.
Scheme 50. Synthetic route to silane diphosphines 113-116.
As shown in Scheme 51, the diphosphines 113-116 were readily converted to the corresponding dichloro complexes (117 to 120) by treating ligands 113-120 with one equiv. of palladium precursor (COD)PdCl2 at room temperature. After filtration of insoluble parts, the filtrate was evaporated in vacuo. The solid dichloro complexes 117-120 were dissolved in methylene chloride and treated with two equiv. of silver triflate. After the generated silver chloride was filtered off, the yellow filtrate was evaporated yielding the desired triflate complexes (121-(OTf)2-124-(OTf)2) as pale yellow solids. After recrystallization from methylene chloride and pentane the complexes could be isolated in pure form.
Scheme 51. Transformation of ligands 113-116 into the corresponding Pd(II) ditriflate complexes 121-(OTf)2-124-(OTf)2.
3.5.2 Catalytic Methoxycarbonylation of Methyl Oleate
The results outlined in Table 14 demonstrate that all silane diphosphine catalyzed reactions showed no significant conversion of methyl oleate. With regard to their observed lack of catalytic activity firstly the formation of the catalytically active species was investigated in more detail. 1H and
31P{H} NMR spectra of 121-(OTf)2-124-(OTf)2 in a mixture of CD2Cl2/MeOH were recorded.
Complex 123-(OTf)2 with tert-butyl groups gave defined hydride species upon addition of methanol. Addition of MeOH/CD2Cl2 (2:3, v/v) to complex 121-(OTf)2 resulted immediately in
formation of Pd black and double protonated diphosphine ligand, the corresponding hydride complex appeared as minor species. Complexes 122-(OTf)2 and 124-(OTf)2 produced the corresponding hydride complexes less efficiently. In detail, for complex 124-(OTf)2 traces of hydride species were formed, for complex 122-(OTf)2 no signals indicating the formation of the hydride complex spectra could be observed as is evident from NMR measurements. These findings underline the importance of the nature of the diphosphine ligands in stabilizing the hydride species [(P^P)Pd(H)(MeOH)]+. Less bulky complexes (iso-propyl groups attached to phosphorus in 122-(OTf)2 and 124-(OTf)2) in combination with the rather flexible C-Si-C backbone, have rarely the ability to stabilize the active hydride species.
Table 14. Methoxycarbonylation of methyl oleate with complexes 121-(OTf)2-124-(OTf)2.
Entry
Pd(II) complex Conversion of MOa) Amount of 1,19-diester1) 0.048 mmol of catalyst precursor in 10 mL of methanol. Technical grade high oleic sunflower oil methyl ester (92.5% methyl oleate) was used as substrate. Conversions are calculated from GC data.b) Results after 90 h reaction time
Actually, the poor conversion of methyl oleate indicate that hydride species somehow enter into the catalytic cycle, although not observed directly in the NMR spectra. If the hydride species, generated from complexes 121-(OTf)2 and 123-(OTf)2, are stabilized by addition of 2.3 equiv. of PPh3, full conversion is observed and unique signals for the hydride species are recorded in the NMR spectra. Although defined hydride signals for complexes 122-(OTf)2 and 124-(OTf)2 are obtained, the conversion to the hydride is not enhanced, the starting triflate complexes remains untouched up to 90 % (Table 15).
Table 15. Hydride complex formation of complexes 121-(OTf)2 and 123-(OTf)2 with 2.3 equiv. of methoxycarbonylation reaction is not only the ability to generate the hydride species, but also the ability to isomerize the internal double bond of methyl oleate to the terminal chain end. In order to investigate the isomerization ability of complexes 121-(OTf)2-124-(OTf)2, in-situ NMR experiments were conducted at room temperature with complexes 121-(OTf)2 and 123-(OTf)2 in the presence of 20 equiv. of methyl oleate. In the thermodynamical equilibrium of the isomerization mixture, the double bond is distributed all over the aliphatic C-19 chain according the following:
Internal (94.3 %), conjugated (5.5 %) and terminal (< 0.2 %) as is illustrated in Scheme 52.[85]
Scheme 52. 1H NMR spectra of olefinic region of a solution of methyl oleate in a solution CD2Cl2/MeOH (3:2, v/v) and Pd(II) catalyst 123-(OTf)2 at room temperature.
Addition of methyl oleate (20 equiv.) to a solution of 121-(OTf)2 in methanol showed no isomerization behavior, even after 12 hours reaction time (at 90 °C only little isomerization has been achieved). With complex 123-(OTf)2 slow and incomplete isomerization of methyl oleate was observed after stirring for 15 minutes at room temperature. Even after 12 hours the equilibrium mixture was not detected. Heating up to 90 °C for 1 hour does not change the isomer ratio further significantly (Scheme 52).
To further probe the behavior of complexes 121-(OTf)2 and 123-(OTf)2 under reactor conditions (20 bar CO) isomerization experiments were performed with 6 equiv. of CO.
Scheme 53. 31P{1H} NMR spectrum of the reaction of complex 123-(OTf)2 in methanol-d4 with 6 equiv. of CO at 25 °C. Insert: 13C NMR -CO resonance.
Addition of CO to a solution of complex 118-(OTf)2 in MeOH-d4 or alternatively in MeOH/CD2Cl2
in the ratio of 2:3 immediately resulted in a mixture of the doubly protonated/deuterated diphosphine 125 and bridged hydrido/deuterido-carbonyl 123-(-H/D)(-CO). The bridging CO ligand appears as quintet in the 13C{1H} NMR spectrum. Key resonances for the deuterated complex are showen in Scheme 53. The mixture was completely converted within 12 h to the doubly deuterated/protonated ligand 125 via reductive elimination. If 20 equiv. of MO and 6 equiv.
CO were added to the solution of complex 123-(OTf)2 in MeOH/CD2Cl2 (2:3, v/v) the isomerization proceeds incompletely due to the reaction to the protonated/deuterated ligand.
In contrast to 123-(OTf)2, complex 124-(OTf)2 did not show any isomerization activity in the presence of CO at room temperature (95 % of complex 124-(OTf)2 was still unchanged as was shown by 31P NMR measurements).
These results demonstrate that the crucial step is defined by the generation of the catalytically active hydride species to enter the catalytic cycle. Stable and well defined hydride species are almost exclusively obtained for the more bulky diphosphines 121-(OTf)2 and 123-(OTf)2, respectively. However, the isomerization ability is not limited to more bulky diphosphines (121-(OTf)2 and 123-(OTf)2), also less steric demanding diphosphine derived Pd hydride complexes promote isomerization of methyl oleate.
Comparing the complex [(dtbpp)Pd(OTf)2] with the silane complexes (121-(OTf)2-124-(OTf)2), the substitution of the backbone’s centered carbon atom for an organosilicon group has a negative influence on the hydride species formation and thus, on the catalyst productivity. Once the hydride species are formed, these complexes are less stable in methanol solution and fast decomposition occurs to doubly protonated ligand and Pd black.
4 Summary and Outlook
The isomerizing alkoxycarbonylation of fatty acid esters is a very unusual reaction in that it converts the double bond deep in the fatty acid chain to a terminal ester group selectively. This is achieved by Pd(II) catalysts with the specific diphosphine 1,2-Bis[(di-tert-butylphosphino)methyl]
benzene (dtbpx). To date, this particular diphosphine stood solitude in promoting this reaction. This thesis aimed at probing the solitude nature of dtbpx, and to possibly find more easily accessible or even more selective catalysts.
The bulky diphosphines 29-34 and 38 with o-tolyl backbones were generated in moderate to good yields starting from o-bromo-benzylbromide 10 and the corresponding dialkylphosphines (Scheme 54). These ligands were transformed into the corresponding diphosphine Pd(II) ditriflate complexes 51 to 57-(OTf)2. X-ray structure determinations were performed for all complexes. The bite angles of all complexes as inferred from the solid state structures are all in the range of 89.4°
to 94.7° and similar to the prototypical symmetrical ligand dtbpx (99.3°) in 58-(OTf)2. The size of the catalytic pocket of the novel Pd(II) complexes is reflected by the half cone angles , which decrease in the range of 56-(OTf)2 > 52-(OTf)2 > 53-(OTf)2 > 55-(OTf)2 > 54-(OTf)2 > 51-(OTf)2, with 51-(OTf)2 as most sterically demanding complex.
All complexes 51 to 57-(OTf)2 catalyze the isomerizing methoxycarbonylation of methyl oleate, to yield the linear 1,19-dimethyl nonadecanedioate 60 in moderate to good yield. The achieved results illustrate that the catalyst 58-(OTf)2 is not unique in transforming the internal double bond deep in the methyl oleate chain to the linear 1,19-diester 60 selectively. Furthermore, the catalytic results show a remarkable sensitivity to the ligand structure. The structure-productivity relationships were derived from crystallographic and catalytic data. Catalyst productivity increases with increasing steric bulk of the substituents of the phosphorus moiety in the following order 56-(OTf)2 < 52-(OTf)2 < 53-(OTf)2 < 55-(OTf)2 < 54-(OTf)2 < 51-(OTf)2 < 57-(OTf)2. The nature of the bulky substituents at the phosphorus appears to influence the productivity more distinctly than the selectivity. Remarkably, the selectivity for the linear 1,19-diester versus the branched by-products does not vary strongly for the different diphosphine ligands.
Scheme 54. Catalyst precursors with an o-tolyl backbone (Section 3.2).
Also for less bulky secondary alkyl substituents at phosphorus, a strong preference for the isomerizing methoxycarbonylation towards the linear product is observed.
Stoichiometric studies of hydride complex formation with coordinated MeOH reveal that for the less bulky substituted complexes (52-(OTf)2, 53-(OTf)2, 55-(OTf)2 and 56-(OTf)2) the formation of the active species is much less efficient as compared to the tert-butyl/adamantyl substituted diphosphine complexes (51-(OTf)2, 54-(OTf)2 and 57-(OTf)2). These results correlate with the observed minor productivities for less bulky Pd(II) complexes. The MeOH hydride species were stabilized by adding PPh3 as co-ligand. For the more stable hydride complexes 51-(OTf)2,
54-(OTf)2 and 55-(OTf)2 it was possible to isolate crystals suitable for X-ray diffraction. As a guideline for further improving the catalysis of the isomerizing methoxycarbonylation of methyl oleate, an efficient conversion of a given catalyst precursor to the active species and keeping the latter stabilized in the productive catalytic cycle appear decisive key issues.
In order to improve the selectivity towards the 1,19-diester compared to the state of the art dtbpx system the focus was on ligand backbone type I (Figure 4) containing especially the rigid adamantyl substituents. Keeping this in mind complex 76-(OTf)2 was synthesized and tested in the methoxycarbonylation of methyl oleate under various conditions. By using complex 76-(OTf)2 as a catalyst precursor the double bond of the fatty acid chain of methyl oleate could be converted to the terminal ester group with a selectivity of 96 %. Such an isomerization/functionalization selectivity is not only unprecedented,[6c,38,87] but also practically important in that it reduces the amount of undesired side products to half in comparison to the catalyst from 58-(OTf)2. It even matches successful approaches for the terminal functionalization of 2-olefins,[36a,87,88] though here the double bond is in direct vicinity to the targeted chain terminus.
The combined experimental and theoretical approach allow insights into the origin of the observed effect. By comparison to the established tert-butyl substituted catalyst from 58-(OTf)2, steric congestion at the metal center is not increased. Rather, the rigid nature of the adamantyl substituents results in a specific interaction with the methanol substrate relatively remote from the metal center, which destabilizes the transition states of unselective pathways. This is the reason for the observed higher selectivity towards the1,19-diester with complex 76-(OTf)2.
Figure 30. Origin of enhanced selectivity with adamantyl substituents (Section 3.3).
Note that this is also the first example of an understanding of the specific selectivities with adamantylphosphines in catalysis in general. The underlying principle of a specific interaction of the rather remote adamantyl framework with the substrate may be important for a rational development of other catalytic systems employing adamantyl substituted ligands.
In the further course of this work attempts to improve the catalytic productivity of complex 76-(OTf)2 -while keeping the selectivity constantly high- were undertaken. To this end, three new diphosphine ligands (rac/meso-90 and 100) with tert-butyl and adamantyl groups attached on the phosphorus atom were synthesized. The diastereomeric diphosphines rac/meso-90 could be separated successfully into the pure rac-90 and meso-90 compounds. After transformation into their corresponding Pd(II) complexes, the catalytic properties were investigated in the isomerizing alkoxycarbonylation reaction. The results demonstrate that with the structural combination it is at least possible to reach a trade-off with respect to productivity and selectivity. As compared to the tetra adamantyl complex 76-(OTf)2, for all three new complexes (rac-103-(OTf)2, meso-103-(OTf)2 and 104-(OTf)2) the productivity over time is improved while selectivity remains almost as high as for 76-(OTf)2. However, as compared to the benchmark system 58-(OTf)2 the new
complexes are less productive. For this reason, complexes 58-(OTf)2 and 76-(OTf)2 remain at the upper limit for selectivity and productivity, respectively. These results indicate that a putatively small change in the substitution pattern of the diphosphine influence both selectivity and productivity significantly.
productivity
selectivity
Figure 31. Effect of extremly bulky adamantyl versus tert-butyl substituents on catalytic activity and productivity (Section 3.4).
Further studies showed that an introduction of a SiR2-function in the center of an C3 backbone of the diphosphine resulted in less effiecient hydride species formation, a lower stability of the hydride complex and low productivity in catalysis.