Chapter 2: Synthesis of tri-aryl ligands and their application in the rhodium-catalysed hydroformylation reaction

2.1 Introduction

Phosphine ligands have shown great application in various catalysed reactions including hydroformylation and other carbonylation reactions.1a,b,c These ligands are usually easy to synthesise and also to be modified to enhance the catalytic activity of metals such as rhodium and palladium.2a,b The most commonly used ligand is triphenyl phosphine, mainly because it has shown to provide fairly high yields in a wide range of catalysed reactions generally affording the desired products with high selectivity.3 Although a lot of research has been done on the effects of ligands on catalysed reactions, there are still some questions that need to be answered. One of these includes the steric and electronic effects of monodentate phosphine ligands on the outcome of the hydroformylation reaction.4 Thus, within this study, a range of monodentate phosphine ligands was synthesised with different stereoelectronic properties and their influence on the Rh-catalysed hydroformylation reaction was investigated.

Phosphines are considered to be both σ-donors and π-acceptors as they can donate electron density to the metal via the phosphorus lone pair as well as accept electron density (π-back donation) within the free d-orbitals that are situated on the phosphorus atom. It is therefore the interplay between these two characteristics that determines the electronic effect of the ligand on the catalyst. If an electron-withdrawing group is situated on the phosphine it will remove electron density from the phosphorus atom, which in turn hampers σ-donation but enhances π-back donation. As a result electron density is removed from the metal and the bond between the metal and other ligands lengthens, enhancing the labilisation of the ligands on the metal (CO in the case of the hydroformylation reaction). With electron-donating

41 groups the opposite effect is observed: enhancing the basicity of the phosphine ligand will strengthen the metal-ligand bonds.

Steric effects are mostly defined in terms of the Tolman Cone Angle,5 which is depicted in Figure 2.1. This is generally defined as the angle swept by a virtual cone with an apex centered at the metal atom, which touches all the peripheral atoms of the substituents situated on the phosphorus atom. The larger this angle becomes the more steric hindrance the ligand causes around the metal centre. This in turn could assist in the labilisation of a ligand to afford a vacant co-ordination site much faster for the (for example) alkene to co-ordinate on the metal centre, which in turn could improve the rate of the reaction.

On the other hand, steric bulk in one ligand may also cause a shift in the relative positions of the ligands on the metal. Usually, with small ligands on the Rh-catalyst (which usually co- ordinates ligands in a trigonal bipyrimidal fashion), an equatorial-equatorial arrangement is obtained. But, when increasing their size, the ligands will at some point become so large that they shift to an equatorial-axial arrangement. In the hydroformylation reaction, this rearrangement results in less hindrance for the incoming alkene and as a result would favour branched aldehydes in comparison with linear aldehydes.

 2.28 Å

Figure 2.1

42 The remainder of this chapter shall describe and discuss efforts to prepare a logical series of ligands with which to systematically probe the stereo-electronic effects thereof on the outcome of the Rh-catalysed hydroformylation reaction of 1-octene.

2.2 Synthesis of tri-aryl using the Grignard method

The general synthesis for the monodentate phosphine ligands included the preparation of an aryl-containing Grignard reagent, followed by a nucleophilic attack of the Grignard reagent on a phosphorus chloride reagent. In general, there are two methods to prepare Grignard reagents: (i) reactions between organic halides and solid magnesium, and (ii) halogen- magnesium exchange reactions. The first was the reaction of choice in this study and was developed by Stuebe et al.6 In general, 1.2 equivalents of the desired aryl halide were added to a THF mixture containing solid magnesium (1 equivalent) and a few iodine crystals. The mixture was then heated under reflux to produce the desired Grignard reagent (Scheme 2.1).

I2 crystal Mg + ArX ArMgX THF reflux

X = halide Ar = Aryl

Scheme 2.1

This preparation of the Grignard reagent worked best with aryl bromides, proceeding to completion within a few hours at most. In cases where aryl chlorides were used the reaction tended to be slow. Several attempts to improve the situation were made. These included changes to the ratios of added reagents, activation of the magnesium turnings with hydrochloric acid, and ultrasonication of the reaction mixture. These modifications were rewarded with some improvements, but in many cases the preparation of the Grignard reagent required more than twenty four hours’ reaction time, compared with the several hours required for the corresponding bromides. 43 Another attempt was made by changing the solvent from THF to diethyl ether, as this solvent has been shown to be an useful system for this reaction.7 However, this move failed to solve the problem and consequently the aryl bromides were preferred as substrates.

The next step then was to use the Grignard reagent and react it with a specific phosphorus chloride reagent, including , dichlorophenylphosphine and trichlorophosphine (Scheme 2.2).

Ph2PCl Ph2PAr

PhPCl2 ArMgX + PhPAr2 + XMgCl

PCl3 PAr3 (THF, -40 °C) Ar = Aryl

Scheme 2.2

Initially attempts were made to synthesise triphenylphosphine, as it is a common phosphine produced by this process. The first few reactions of the Grignard reagent (phenylmagnesium bromide) with chlorodiphenylphosphine failed to yield the desired product. Instead, 31P NMR spectroscopy revealed that several oxidised forms of phosphine were obtained, showing respective signals at around 29.9 ppm and 37.0 ppm. These signals correspond with those of the structures given in Figure 2.2.

What can be inferred from the structures of these products is that there was some source of oxygen that oxidised some of the starting material as well as the desired product and that there also appeared to have been water present in the reaction mixture.

44 O O P P OH

29.9 ppm 37.0 ppm

Figure 2.2

In order to try and solve this problem the first attempt was to see if there was any difference in adding the Grignard reagent to the chlorodiphenylphosphine in comparison to adding the reagents the other way around. It was found that matters improved slightly when adding the Grignard reagent to a THF mixture of the chlorodiphenylphosphine at -40 °C, but the yield of the desired phosphine (33%) was still unacceptably low.

The 31P NMR spectrum of the isolated product revealed a signal with a chemical shift at -5.06 ppm, in accordance with that anticipated for triphenylphosphine. The 1H NMR spectrum gave two broad peaks at 7.36 and 7.35 ppm which revealed the presence of the phenyl rings, while 13C NMR spectroscopy readily revealed the ipso carbon, meta carbons, para carbon and ortho carbons corresponding to the chemical shifts 137.9 ppm (d, 3C, C1, C1’ and C1’’, J = 10.9 Hz), 133.7 ppm (d, 6C, C3, C3’, C3’’, C5, C5’ and C5’’, J = 19.6 Hz), 128.6 ppm (s, 3C, C4, C4’ and C4’’) and 128.4 ppm (d, 6C, C2, C2’, C2’’, C6, C6’ and C6’’, J = 6.9 Hz), respectively.

Satisfied that the Grignard method could be used to afford the desired products, it was decided to further optimise it. This was primarily achieved by scaling up the reaction as well as by increasing the amount of the Grignard reagent used in comparison with the chlorophosphine. These changes gave rise to much higher reaction yields, such that the product could be obtained in yields as high as 95% (by 31P NMR spectroscopy).

45 During the work-up and isolation of the product, a small amount of the product was oxidised, as the peak at 37.0 ppm was still observed. This peak was more pronounced than before work-up, which was a clear indication that the product was being oxidised during the work- up procedure, despite the fact that triphenylphosphine is usually considered to be quite stable. This problem of oxidation could not be totally circumvented despite numerous efforts. Nonetheless satisfying yields of the requisite products could be obtained with which to perform further studies making use of these ligands, as is clear from Table 2.1.

In this way, a range of phosphines could be synthesised that were substituted at one, two or all three of the phenyl rings and variously in the ortho or para positions thereof with methyl or ethyl groups. This approach, while conceptually fairly simple, was technically not trivial to carry through, but, once performed, provided a series of ligands of systematically changing stereo-electronic effects with which to combine with Rh to perform hydroformylation studies. It will be immediately noted from the table that only the mono-mesitylene derivative (ligand 5) was prepared. Despite numerous efforts and varying reaction conditions, the di- and trimesitylene-based phosphines could not be prepared, presumably because of steric reasons.

As can be seen in the Table 2.1 these phosphines were obtained in acceptable to good yields. Only a few cases gave relatively poor (< 50%) yields. It is also clear that there is a relationship between the degree and position of the alkyl substitution and the chemical shift of the signal in the 31P NMR spectrum of the relevant compound. Thus as one moves from triphenylphosphine (54) to para-tolyldiphenylphosphine (55) to ortho- tolyldiphenylphosphine (56) the chemical shift changes from -5.06 ppm to -5.90 ppm and - 13.39 ppm, respectively. This shift gave an indication that changes in the electron density on the phosphorus atom occured with the position of substitution, which will be shown to be the case at a later stage in this discussion.

46 Table 2.1 Phosphine ligands and their 31P NMR signals.

ligand Structure % isolated yield 31P NMR ppm

54 PPh3 85 -5.1

55 Ph2P 75 -5.9

56 78 -13.4 Ph2P

57 90 -14.8 Ph2P

58 Ph2P 78 -15.9

59 PhP 39 -6.2 2

60 PhP 50 -20.4 2

61 PhP 43 -24.2 2

62 P 42 -7.5 3

63 P 60 -29.2 3

64 P 72 -34.0 3

In order to characterise these ligands NMR spectroscopy, GCMS, EIMS and IR spectroscopy were performed. In NMR spectroscopy the chemical shifts of the signals of the various 47 phosphines were similar as the only differences amongst them were the position and the number of methyl or ethyl substituents on the phenyl rings. The unsubstituted phenyl rings in the ligands, if any, provided signals that were similar to those of triphenylphosphine. In contrast extra signals were observed in the aromatic region on both the 1H and 13C NMR spectra for the substituted rings, clearly demonstrating their lack of symmetry.

For the 1H NMR spectrum of tri-para-tolylphosphine (62) the signals included a triplet at δ 7.03 ppm (t, 6H, H2, H2’, H2’’, H6, H6’ and H6’’, J = 7.7 Hz) and a doublet at 6.96 ppm (d, 6H, H3, H3’, H3’’, H5, H5’ and H5’’, J = 7.5 Hz) representing the ortho and the meta hydrogen atoms, respectively. The triplet signal is generated by H-H and H-P coupling.

Another signal was observed at 2.17 ppm (s, 9H, CH3), which indicated the presence of the methyl groups. In the 13C NMR spectrum signals were observed at 138.4 ppm (s, 3C, C4, C4’ and C4’’), 134.1 ppm (d, 3C, C1, C1’ and C1’’, J = 9.4 Hz), 133.6 ppm (d, 6C, C3, C3’, C3’’, C5, C5’ and C5’’, J = 19.8 Hz) and 129.2 ppm (d, 6C, C2, C2’, C2’’, C6, C6’ and C6’’, J = 7.2 Hz) assigned to the para carbons, the ipso carbons, meta carbons and ortho carbons, respectively. A signal was also observed at 21.3 ppm (s, 3C, CH3), which corresponded to the methyl groups present on the rings. In the 13P NMR spectrum a single peak at -7.49 ppm (s, 1P) was observed. GCMS and HRMS both confirmed the anticipated molecular ion peak at m/z 304. The remainder of the ligands were similarly characterised.

Single crystal X-ray diffractometry was performed on the crystal obtained for ligand 55 and the structure that were obtained is given in Figure 2.3. As can be seen from the figure the ligand has a methyl group on one of the aryl rings para with respect to the phosphorus atom. The crystallographic information is given as an appendix in the back of the thesis.

48 Figure 2.3

2.3 Determination of the stereo-electronic properties of the synthesised tri-aryl phosphine ligands

One of the greatest challenges in quantifying the stereo-electronic properties of phosphine ligands involves the separation of the steric and the electronic properties of these ligands, as they are closely related. Several methods have been developed through the years in order to evaluate each of these properties. To quantify the electronic properties of phosphine ligands

methods such as NMR measurements of first order Pt–P, P–BH3 or Rh–P coupling constants,8,9,10 or CO stretching frequency measurements of Vaska-type and other complexes,11,12 became useful. Computational methods using Density Functional Theory (DFT) and semi-empirical Hamiltonians have also shown to provide a means of evaluating the electronic properties of phosphine ligands.13,14

Another method includes the use of the first order phosphorus-selenium coupling constant, 1 JP-Se, with which the basicity (s-character) of a phosphine ligand can be measured. In this

method phosphine selenide compounds, R3P=Se, are prepared and analysed using NMR spectroscopy.15 It is well established that the coupling constant between two directly linked

49 atoms is primarily governed by the Fermi-contact interactions between the respective s- orbitals.16 Electron-withdrawing substituents on the phosphine ligands result in an increase in the s-character of the phosphorous lone pair while electron-donating substituents result in a decrease in s-character according to Bent’s rule.17 In turn the more basic the phosphine ligand becomes (thus having a less s-character), the smaller the coupling constant becomes.

In this study the phosphine selenide compounds and Vaska-type compounds were used to probe the stereoelectronic properties of the synthesised phosphine ligands. As depicted in Scheme 2.3, the phosphine ligands (1 equivalent) were oxidised with selenium (4 equivalents) by heating them in under reflux for 5 hours. The resulting product was then analysed by 31P NMR spectroscopy from which three signals were observed. These included a tall signal which corresponded to the Se-oxidised phosphine (with the non spin- active isotope of Se), and two small signals on either side of the long signal, which corresponded to the spin coupling of the selenium with the phosphorus atom. From these signals the P=Se coupling constant was determined for each ligand, the results of which are given in Table 2.2.

CHCl3 60 °C Se PAr + Se 3 (s) 5 h PAr3

Scheme 2.3

Vaska designed a square planar complex involving an iridium metal centre with a CO ligand, one halide ligand and two other variable ligands of the same type.11 It has been demonstrated that these complexes are useful for determining the σ-donor characteristics of ligands such as phosphines using the CO vibrational frequency observed by infrared spectroscopy. Furthermore work performed by Roodt et al.12 showed that metals such as Rh can also form Vaska-type complexes, which behave in a similar way as the original Vaska complexes. In the present study it was decided to prepare Vaska-type complexes with Rh, in which each of the ligands (4 equivalents) was stirred with di-carbonyl-tetra-chloro di-rhodium(I) (1 equivalent) in acetone for 2 hours at room temperature (Scheme 2.4). The resulting products

50 were analysed by infrared spectroscopy, where the vibrational frequency of the CO stretch on the complex was determined. These results are given in Table 2.2.

PAr r.t. 3 + PAr3 [Rh-µ-Cl(CO)2]2 2 h Cl Rh CO PAr3

Scheme 2.4

In Table 2.2 it can be seen that there is a good correlation between the chemical shift observed on the 31P NMR spectrum for each ligand and the values of the the P=Se coupling constants and CO vibrational frequencies. As was mentioned before, according to Bent’s rule as the s-character on the phosphorus atom increases (as a result of a decrease in the basicity of the phosphine ligand) the P=Se coupling constant increases.

Likewise, as the electron density on the phosphorus atom increases the CO vibrational frequency shifts to a lower value. An electron-rich ligand donates more electron density onto the Rh metal, which in turn causes more π-back donation onto the CO ligand weakening the C=O bond. As a result, the CO vibrational frequency lowers to a smaller value.

This increase in electron density is due to the inductive electron-donating properties of alkyl groups on aromatic rings. It can be seen that this electron donation was more pronounced as the chain length of the alkyl group increased, as the presence of the ethyl group on the ortho position of the ring gave rise to a more electron-rich phosphine than in the case where the methyl group is in the ortho position.

51 Table 2.2 Ligands and their selected analytical data.

Ligand structure 31P NMR P=Se 31P NMR Vaska complex Coupling (Hz) (CO shift) (cm-1)

54 PPh3 -5.06 729.4 1979

55 -5.90 725.6 1977 Ph2P

56 -13.39 723.3 1975 Ph2P

57 -14.80 722.2 1972 Ph2P

58 Ph2P -15.93 723.6 1970

59 PhP -6.21 721.7 1976 2

60 PhP -20.35 711.4 1971 2

61 PhP -24.24 709.1 1966 2

62 P -7.49 718.0 1975 3

63 P -29.20 703.9 1966 3

64 P -33.95 700.7 1960 3

The position of the alkyl group also played a role, as a phosphine ligand that had a methyl group on the para position of the ring was shown to be less electron-rich than a phosphine ligand having a methyl group on the ortho position of the ring. Also as the number of methyl

52 groups substituted on the rings of the tri-aryl phosphine ligands increased, the electron density on the phosphorus atom also increased. This point shall be touched upon again later.

Another observation to note is that there was no linear correlation between the P=Se coupling constants and the CO vibrational frequencies, albeit that a general trend is followed. This was expected since the values of CO vibrational frequencies are mainly influenced by the electronic properties of the phosphorus atom, while the P=Se coupling constants are sensitive to both the electronic and the steric properties of the phosphine ligands. Thus with the phosphine ligands that have varied steric bulk around the phosphorus centre, the P-Se coupling constant magnitudes changed slightly in relation to that characteristic.

The value for the CO stretching frequency of triphenylphosphine with the Rh-based Vaska- type complex was found to be 1979 cm-1. Some literature articles report a discrepancy, -1 namely that a CO stretching frequency of 1965 cm has been noted for the PPh3 Rh Vaska complex,18a,b which is a significant difference from the 1979 cm-1 reported here. One of the reasons reported is that this difference is found to be the consequence of the production of cis (high frequency) and trans (low frequency) isomers, where in a certain environment the one prefers to form above the other.19 In this case it seems that preparing the Vaska-type complexes in acetone resulted in the formation of the cis isomer.

Tolman introduced the concept of a cone angle, Θ, to describe the steric properties of phosphine ligands.5 It is regarded (as mentioned before) to be the apex angle of a cylindrical cone, which is centred at a distance of 2.28 Å from the centre of the phosphorus atom and which touches the van der Waals radii of the outermost atoms of the phosphine ligand. In order to describe the steric properties of the 1st generation of tri-aryl phosphine ligands prepared here, it was decided to calculate the cone angle of each of these ligands.

Dias et al.20 as well as Andersen et al.15 reported the Tolman cone angles for some of the ligands that were synthesised as part of the present study, and the values are given in Table 2.3 and are marked with an asterisk. The remainder of the cone angles had to be calculated from crystallographic data. According to Tolman, for unsymmetrical phosphine ligands 53 (PR1R2R3), the cone angle can be calculated using the following equation: Θ = 2/3 Σ Θi/2, where the angle Θi is defined as shown in Figure 2.4 to be the angle obtained from the corresponding symmetric P(Ri)3 phosphine ligand.

P

 3 /2  /2 1 2.28 Å

 2 /2

Figure 2.4

From Table 2.3 (overleaf) it is clear that the Tolman cone angle, as would be reasonably anticipated, varied with the number, position of attachment and nature of the aryl substituents.

54 Table 2.3 Ligands and their calculated Tolman cone angles.

ligand structure Tolman Cone Angle ( degrees)

54 PPh3 145 *

55 Ph2P 145 *

56 161* Ph2P

57 190 Ph2P

58 Ph2P -

59 PhP 145 2

60 PhP 177 * 2

61 PhP 187 2

62 P 145 * 3

63 P 194 * 3

64 P 218 3 *Tolman cone angle values from the literature

55 2.4 The effects of the stereo-electronic properties of tri-aryl phosphine ligands on the Rh-catalysed hydroformylation reaction

The hydroformylation reaction is a homogeneous catalytic process in which alkenes are converted into aldehydes.21 Because of its great importance in industrial applications for the synthesis of a wide range of chemicals, it has become a key factor to understand the mechanism by which it produces the desired aldehydes and how it can be manipulated to give the best performance possible.

Originally the catalysts designed for this process included a hydrido-tetracarbonylcobalt, but later on it was discovered that rhodium could also be used as a catalyst.22 Although rhodium is more expensive than cobalt, it has been shown through numerous studies that it tends to give better yields and higher selectivity under milder conditions.23

In this study the role that phosphine ligands play on the efficiency of the Rh-catalyst was investigated. The general reaction that was performed is given in Scheme 2.5. Here, acetylacetonatodicarbonylrhodium(I) (0.0091mol%) was added together with the ligand (Rh:P = 1:10) under study and 1-octene into a high pressure autoclave reactor containing toluene (where the ratio of 1-octene to toluene was 1:1). The resulting mixture was

pressurised with 25 atm of syngas (H2/CO 1:1, constant pressure) after which the reactors were heated at 100 °C for exactly 2 hours.

H Rh(CO)2(acac), PAr3 Toluene O H2/CO (1:1), 25 atm + 100 °C

O H

Scheme 2.5

56 Analysis of the resulting mixture was performed using GC-FID, making use of a GC column which separated the compounds based on their boiling points. The boiling points for 1-octene and its isomers are in the region of 122-126 °C, while those for nonanal and its isomer is 191 °C and 185 °C, respectively. This is in good correlation with the peaks observed on the GC- FID chromatogram, which are summarised in Table 2.4.

To accurately calculate the amount of conversion of the octene to the nonanal, the response factors for both 1-octene and nonanal were determined. This was done by preparing a range of standards starting from 0.2 to 3.2 mmol/mL for 1-octene, and 0.18 to 2.91 mmol/mL for nonanal in toluene. These standards were then analysed on the GC-FID, after which the peak area of the peaks observed on the GC chromatogram was determined. The peak areas were then plotted against the corresponding concentration values of the standards, the graph of which is given in Figure 2.5.

Table 2.4 Components of hydroformylation mixture ( ZB 1.30 m column).

Compound Boiling point (°C) Retention time (min)

Toluene 111 3.2

3-octene 122 3.7

4-octene 122 3.9

1-octene 123 4.0

2-octene 126 4.1

2-methyloctanal 185 9.0

1-nonanal 191 9.7

57 Figure 2.5

From the graph it can be seen that both sets of standards gave linear curves with R2 values of 0.999 and 0.995, respectively. From these curves the gradients show that both compounds seem to have a similar response factor as a ratio of 1.05:1 was obtained. The peaks observed on the GC chromatogram could therefore be directly compared to determine the yields of the aldehydes obtained from the hydroformylation reactions. This was calculated by taking the sum of both peaks corresponding to the nonanal isomers and dividing it by the sum of the peaks corresponding to both the octene mixture (isomers) and the nonanal isomers. The results of the Rh-catalysed hydroformylation reactions are summarised in Table 2.5 (other analytical data are provided for ease of reference and comparison).

It took some time to optimise this hydroformylation reaction as it is sensitive to a number of variables, including temperature, pressure, surface area to volume ratio of solvent or liquid media, ratios and order of the different reagents added, amount of catalyst and stirring speed. Originally low yields were obtained and therefore several attempts were made to optimise the reaction conditions with triphenylphosphine. This included applying a constant pressure of 25 atm of syngas instead of simply pressurising the reaction once off and using only the amount 58 of gas present in the reactor. This made a significant difference to the outcome as the yields increased to satisfying levels. Other variations involved changes in the ratio of ligand to Rh catalyst, the amount of catalyst being used, the temperature and the amount of toluene and octene used. The latter changed the surface area to volume ratio of the solvent and in turn affects the gas mass transfer rate.

Table 2.5 Hydroformylation results with various ligands

P=Se 31P Vaska %yield 31P ligand Structure l:b NMR complex (CO nonanal NMR coupling (Hz) shift) (cm-1)

54 PPh3 48 2.5 -5.1 729.4 1979

55 Ph2P 44 2.4 -5.9 725.6 1977

56 40 2.4 -13.4 723.3 1975 Ph2P

57 37 2.1 -14.8 722.2 1972 Ph2P

58 Ph2P 30 2.2 -15.9 723.6 1970

59 PhP 40 2.4 -6.2 721.7 1976 2

60 PhP 32 2.4 -20.4 711.4 1971 2

61 PhP 26 2.2 -24.2 709.1 1966 2

62 P 37 2.6 -7.5 718.0 1975 3

63 P 19 2.6 -29.2 703.9 1966 3

64 P 14 2.7 -34.0 700.7 1960 3

59 Eventually it was discovered that, with a catalytic loading of 0.02 mol% under the conditions mentioned above, the yield of nonanal obtained in the Rh-catalysed hydroformylation reaction was as high as 95% when using triphenylphosphine as a ligand. However, because the main interest in this study was to determine the effects of the phosphine ligands on the outcome of the hydroformylation reaction, it was decided to manipulate the reaction conditions such that the reaction would provide only around 50% yield of the nonanal with triphenylphosphine as the ligand, which was the reference point for this study. The idea behind this move was to employ a set of reaction conditions under which ligand influences would be clearly detectable, which would not necessarily be the case for a reaction yielding 95% of the desired product. This was achieved by reducing the catalytic loading to 0.0091 mol% under otherwise the same conditions mentioned above, which gave a yield of 48% of the nonanal after 2 hours. All the reactions given in Table 2.5 were performed under these conditions.

As was mentioned in the previous section it was observed that the series of ligands shown in Table 2.5 do have different stereoelectronic properties. The electronic properties of these ligands have a significant effect on the Rh-catalysed hydroformylation reaction as the yields of nonanal obtained from these reactions in general decreased as the electron-rich character of the phosphine ligand increased, as would be anticipated from the literature.24

If one goes through the series of the mono-aryldiphenylphosphines the yield decreased from triphenylphosphine (48%) to para-tolyldiphenylphosphine (44%) to ortho- tolyldiphenylphosphine (40%). Replacing the methyl group on the ortho position with an ethyl group further increased the electron density at the phosphorus atom resulting in an even lower yield of nonanal (37%) in the hydroformylation reaction. Replacing the aryl group with a mesityl group provided an even more electron rich phosphine and also gave a lower yield of nonanal (30%). These results are illustrated in Figure 2.6 to show the relationship between the varying electron characteristics of the ligands and the yields of nonanal obtained in the hydroformylation reaction. The same trend was observed when moving to the di- arylphenylphosphines and the tri-arylphosphines, but as expected the influence was even more pronounced than for the mono-arylphosphines.

60 PPh3 Ph2P Ph2P Ph2P Ph2P

Figure 2.6

Also looking at the series of mono- to di- to tri-arylphosphines (for the same type and position of substituents), the same trend was observed. For example when going from the mono-o-tolyldiphenylphosphine to the di-o-tolylphenylphosphine to the tri-o-tolylphosphine the yields of nonanal obtained from these reactions were 40%, 32% and 19%, respectively (Figure 2.7). The same trend was observed with the p-tolyl phosphine series and the o- ethylphenyl phosphine series. Thus the incorporation of additional methyl or ethyl groups increased the electron density on the phosphorus atom which in turn caused a decrease in the yield of nonanal obtained in the hydroformylation reaction.

61 PPh3 Ph2P PhP P 2 3 Figure 2.7

This behaviour can be explained in terms of the first few steps of the mechanism elucidated for the Rh-catalysed hydroformylation reaction,25 part of which is given in Figure 2.8. In order for the alkene (in this case 1-octene) to co-ordinate on the Rh metal centre a CO ligand co-ordinated on the Rh first needs to be labilised creating a vacant co-ordination site for the incoming alkene. The rate at which the alkene co-ordinates to the metal centre is thus determined by the extent of the CO labilisation and the rate of its departure from the metal centre. This is in turn dependent on the strength of the Rh-CO bond, which can be manipulated by changing the environment around the Rh-catalyst.

62 R

H CO H H PR3 PR3 OC Rh R3P Rh PR3 R3P Rh PR3 CO CO CO

R Figure 2.8

When a phosphine ligand co-ordinates to the Rh metal, it changes the electron density on the metal centre. If one uses an electron-rich phosphine, it causes more σ-donation onto the metal centre via the phosphorus electron pair, while π-back donation is limited. As a result the electron density on the Rh metal increases and the metal then donates its electron density to the other ligands including CO. This then shortens the bond between Rh and CO, thus creating a stronger bond. Labilisation of the CO ligand is therefore diminished and in turn lowers the rate at which the alkene can co-ordinate to the Rh metal centre. This slows down the whole hydroformylation reaction giving lower production of the aldehyde within a certain time. This statement is valid when one keeps in mind that a link exist between the yields obtained and the rate of the reaction when all other variables remain constant. It was accepted that all other variables did remain constant when performing the hydroformylation reactions. Conversely, the co-ordination of an electron-poor phosphine would enhance π-back donation to that ligand and inhibit σ-donation, and as a result would enhance CO labilisation and cause an increase in the rate at which the hydroformylation reaction takes place.

The steric properties of the phosphine ligands are expected to influence the outcome of the linear to branched isomer ratio (l:b) of the nonanal products.26 However, as can be noted in Table 2.5, there seems to be no significant difference in the n:i ratios of the nonanal products obtained for each ligand, as most of them are in the region of 2.4:1. With the tri-aryl phosphine ligands containing a methyl or ethyl group on one of the ortho positions on each ring, the n:i ratio seems to vary only slightly, but not so much to say that there is a significant steric effect involved. Thus it seems that groups like methyl and ethyl are too small to show a determinative steric effect regardless of the fact that the Tolman cone angle increases from

63 145° to 218° for the series. The implication of this observation is that, while there is a small measure of sensitivity of the regioselectivity of the reaction to the Tolman cone angle within this series, most probably cone angles of greater than 218° would be required for more substantial effects to be noted.

2.5 The synthesis of fluoro-substituted tri-aryl phosphine ligands and their stereo-electronic properties

As was shown in the previous section, it is clear that the incorporation of an alkyl group (methyl, ethyl) influenced the electronic properties of a tri-aryl phosphine ligand. From this it was decided to investigate further manipulation of the electronic character of the phosphine ligands by the substitution of a fluorine atom onto the aromatic ring of systems already containing a methyl group on the ortho or para position of the phenyl rings. Generally the halogen atoms exhibit weakly electron-withdrawing inductive effects when substituted on aromatic rings. Fluorine atoms, being the most electron-negative of the halides, are expected to manifest the most electron-withdrawing characteristics of the halogens. Thus as a result one expected that it would remove electron density from the phosphorus atom, leading to a more electron-poor phosphine and faster Rh-catalysed hydroformylation reaction in the presence of such ligands as a consequence.

The general synthesis of these compounds once again involved the preparation of the aryl- containing Grignard reagent followed by the addition thereof to a THF solution of either chlorodiphenylphosphine, dichlorophenylphosphine or trichlorophosphine under the same conditions as depicted in Schemes 2.1 and 2.2, to give the corresponding mono-, di- and tri- (fluoro-substituted) tri-aryl phosphine ligands. These phosphine ligands were obtained in acceptable yields along with small amounts of the oxidised products. Data relating to these ligands are given in Table 2.6 (yields, 31P NMR spectroscopic signals, P=Se coupling constants and CO stretching frequencies).

64 Characterisation of these ligands was performed using NMR spectroscopy, IR, GCMS and EIMS. From the NMR spectroscopy the unsubstituted phenyl rings gave similar signals to those of triphenylphosphine (1). More complex signals reflecting the lack of symmetry were observed in the aromatic region on both the 1H NMR and 13C NMR spectra for the substituted phenyl rings. Methods such as H-H decoupling, P-C decoupling, and HETCOR were also performed in order to allocate the signals to their corresponding atoms.

For the series of ligands 65-67, where the fluoride was substituted para to the phosphorus atom and the methyl ortho to the phosphorus atom, three different signals were observed in the aromatic region in the 1H NMR spectrum. For ligand 67 signals were observed at

chemical shifts δ 6.98 ppm (dt, 3H, H3, H3’ and H3’’, JH-P = 9.6 Hz, JH-H,H-F = 3.6 Hz), 6.81

ppm (td, 3H, H5, H5’ and H5’’, JH-P,H-H = 8.7 Hz, JH-H = 2.4 Hz), and 6.69 ppm (m, 3H, H6, H6’ and H6’’). The allocation of these signals was assigned by means of 10 dB H-H decoupling experiments. A decoupling on the 6.98 ppm signal resulted in the simplification of the triplet of doublets at 6.81 ppm to a triplet, implying that a fine H-H coupling existed between the two hydrogen atoms corresponding to these signals (H3 and H5). A decoupling on the 6.81 ppm signal resulted in the simplification of the doublet of triplets at 6.98 ppm to a doublet of doublets, confirming the deduction made above. Signal simplification was also observed in the multiplet at 6.69 ppm, which indicated H-H coupling between H5 and H6, which was confirmed by decoupling of the 6.69 ppm signal and the observation of

simplification of the 6.81 ppm signal. A signal at 2.39 ppm (s, 9H, CH3) indicated the presence of the methyl group.

65 Table 2.6 2nd generation ligands and their selected analytical data.

P=Se % Isolated 31P NMR Vaska complex Ligand Structure 31P NMR yield (ppm) (CO shift) (cm-1) Coupling (Hz)

54 PPh3 - -5.06 729.4 1979

65 85 -14.5 727 1977 Ph2P F

66 PhP F 40 -23.7 720 1976 2

67 P F 30 -33.2 708 1971 3 F 68 80 -12.8 730 1977 Ph2P

F 69 43 -20.8 726 1973 PhP 2 F 70 30 -29.4 724 1968 P 3 F 71 81 -5.5 740 1980 Ph2P

F

72 PhP 66 -6.0 740 1982 2

F 73 32 -6.6 745 1984 P 3

In the relevant 13C NMR spectra an interesting observation was made for all of these phosphine ligands, namely that the ipso-F carbon gave a very large coupling constant (above 240 Hz) and that its signal was observed far downfield of the spectrum (in the region of 160 ppm). For ligand 67, for example, the signal for the ipso-F carbon was observed at δ 163.4

66 ppm (d, 3C, C4, C4’ and C4’’, J = 248.5 Hz). A HETCOR analysis on this ligand showed that the three signals on the 1H NMR spectrum, namely 6.98 ppm, 6.81 ppm and 6.69 ppm corresponded with the three signals at 134.7 ppm (d, 3C, C6, C6’ and C6’’, J = 8.0 Hz), 117.3

ppm (dd, 3C, C3, C3’ and C3’’, JC-P = 20.7 Hz, JC-F = 5.2 Hz) and 113.3 ppm (d, 3C, C5, C5’ and C5’’, J = 20.3 Hz), respectively on the 13C NMR spectrum thereof. The ipso-P carbon and

ipso-CH3 carbon atoms corresponded with signals at 145.2 ppm (dd, 3C, C1, C1’ and C1’’, JC-

P = 28.7 Hz and JC-F = 7.8 Hz) and at 129.5 ppm (dd, 3C, C2, C2’ and C2’’, JC-P = 10.6 Hz and JC-F = 3.2 Hz), respectively, while the signal allocated to the methyl group was observed 31 at δ = 21.1 ppm (dd, 3C, CH3, JC-P = 21.7 Hz and JC-F = 1.4 Hz). On the P NMR spectrum a doublet was observed for ligand 67 at δ -33.2 ppm (d, 1P, J = 3.2 Hz), while on the 19F NMR spectrum a doublet was observed at -118.0 ppm (d, 3F, J = 9.3 Hz). Similar experiments were employed for the other ligands.

For some of the ligands crystals were obtained and analysed by single crystal X-ray diffraction. In Table 2.7 crystallographic representations of ligands 66 and 67 are given, from which it can be seen that the fluorine atoms are para to the phosphorus atom and the methyl groups are ortho with respect to the phosphorus atom. The complete X-ray analysed, from crystal mounting to data collection to data refinement, all, were performed by the author.

Selenium oxidation and Vaska complex formation were performed on these ligands, once again to probe the stereo-electronic characteristics of the phosphine ligands. This was done using the same methodology shown in Schemes 2.3 and 2.4 and discussed earlier in this chapter. These results are summarised in Table 2.6.

67 Table 2.7 crystal structures of fluoro-substituted phosphine ligands

Ligand Structure Lattice type

Monoclinic, 66 P 21/c

67 Triclinic, P ī

As was stated in the previous section, a decrease in the value of the P=Se coupling constant implies that the s-character on the phosphorus atom has decreased, which in turn implies that the basicity of the corresponding phosphine ligand has increased. Likewise, as the value of the vibrational frequency of the CO on the Vaska complex decreases, a concomitant increase in the electron density on the phosphorus atom is inferred. With the electron-withdrawing properties of the fluorine atom, one expects additional fluorine atoms on the ligand to cause the formation of a more electron-poor phosphine ligand. Thus as a result the values of the both the P=Se coupling constant and the vibrational frequency of the CO on the Vaska

68 complex should increase in that series and also with respect to the values of triphenylphosphine.

Comparing the values observed for the phosphine ligands containing a methyl group either in the ortho or para postion (given in Table 2.2) with those of the corresponding fluoro- substituted phosphine ligands in Table 2.6, this anticipated effect was clearly established. For example, a comparison of the analytical values obtained for the o-tolyldiphenylphosphine ligand 56 with those of ligands 65 and 68 showed that the values of the P-Se coupling constant had changed from 723 Hz to 727 Hz and 730 Hz, respectively. Likewise the vibrational frequencies of the CO have changed from 1975 cm-1 to 1977 cm-1 in both cases. Thus, the addition of the fluorine atom on both the para and meta positions of the ring rendered the phosphorus atom of the ligands slightly less electron-rich.

This effect was even more pronounced when the fluorine atom was positioned in the ortho position of the aryl rings. A comparison of the tri-p-tolylphosphine ligand 62 with ligand 73 showed that the value of the P-Se coupling constant increased from 718 Hz to 745 Hz, which is a significant difference. The vibrational frequency of the CO stretch has also increased significantly from 1975 to 1984 cm-1. Thus, ligand 73 is even more electron-poor than triphenylphosphine compared to its para-substituted counterpart.

The remainder of the ligands all revealed the same effect, and thus fluoride was deemed to be efficient in changing the electronic character of a tri-aryl phosphine ligand when substituted on any of the positions on the phenyl rings.

What was astonishing, however, was the fact that F-containing ligand 65 manifested similar P=Se coupling constants and CO vibrational frequencies to those of triphenylphosphine, indicating that the fluorine atom failed to fully mitigate and counteract the inductive effects of the methyl group. Even more surprising was the apparent electron-rich nature of the di- and tri-fluoride containing phosphine ligands 66 and 67 which manifested characteristics of ligands that were more electron-rich than triphenylphosphine. This situation was mirrored by the meta-fluoride containing phosphine ligands 68, 69 and 70 in which those ligands similarly 69 possessed ortho-methyl substitution. However, ligands 71, 72 and 73 (ortho-fluoride-para- methyl substitution) provided analytical data that were intuitively anticipated.

In ligands 65-67 and 71-73, the fluorine atom is conjugated to the phosphorus atom and one might reasonably anticipate a combination of and interplay between inductive and resonance effects, the former being negative and the latter positive with respect to electron density. The complete turnaround in the stereo-electronic data in moving from series 65-67 to 71-73 seems to point to the fact that ortho-group proximity to the phosphorus atom dominated the outcome of the conjugation/induction interplay. It appears as if the inductive effects of the ortho group dominate over those of the para group even if the para group is as electronegative as a fluorine atom (electronegativity = 4.0) and the ortho group as weakly inductively electron density donating as the methyl group. Furthermore, it is quite possible that the fluorine atom may donate electron density on demand via resonance effects, very much in the way it does so during electrophilic aromatic substitution reactions. Ligands 71-73, while allowing for resonance contributions, appear to be inductive-effect dominant (not resonance-dominant) and ortho-substituent dominant in electronic effects, being the only series (71-73) of the three (65-67 and 68-70) with increasingly electron-poor phosphorus atoms along the series.

The ortho-methyl-meta-fluoride substituted series of ligands, which, because of the relative positions of the substituents, should reflect only inductive effects (phosphorus and fluorine atoms not conjugated), also bear out the ortho-dominant substituent idea even (apparently) for instances of dramatically differing positive and negative inductive effects (methyl vs. fluoride). Once again, the ortho-group (methyl) dominates giving increasing electron density within the series.

These observations are in line with frontier molecular orbital theory,27 where it is stated that within halogenobenzenes (or then aromatic rings with substituted halogens) the halogen shows a mixture of the properties of electron-withdrawing groups and electron-donating groups. The halogen undergoes some overlapping with its lone pairs to gain some covalent bonding, but its high electronegativity causes it to hold tightly onto its electrons at the same time.

70 2.6 The application of fluorine-substituted tri-aryl phosphine ligands within the hydroformylation reaction

The hydroformylation reaction of 1-octene was performed with each of the fluoride- containing phosphine ligands using exactly the same conditions as shown in Scheme 2.5, and the resulting reaction mixture was analysed by GC-FID. The results obtained are given in Table 2.8 together with other analytical data for ease of reference.

From Table 2.8 it is evident that ortho-dominant effects are reflected by the hydroformylation reaction. It was observed that the phosphine ligand series 65-67 and 68-70 both revealed electron-rich characteristics in comparison with triphenylphosphine, firstly because the yields of aldehyde obtained in general were lower than that of triphenylphosphine, and secondly the yields along both series decreased. Ligands 65-67 gave yields of 32%, 23% and 13% for aldehyde products, respectively, as one moves from the mono- to the tri-fluoride substituted phosphine ligands as shown in Figure 2.9. Similarly ligands 68-70 gave yields of 38%, 25% and 18%, respectively (Figure 2.9). These results correlated well with the values of the P-Se coupling constants and the CO vibrational frequencies, where a decrease in either value revealed the presence of a more electron-rich phosphine ligand, which then in turn slowed down the rate of the hydroformylation reaction and as a consequence lower yields were obtained. Thus it was quite evident that the addition of a fluorine atom on the meta and para position of an aryl ring could not overcome the weakly donating effect of a methyl group on the ortho position of the aryl ring.

71 Table 2.8 Hydroformylation results of the 2nd generation ligands.

31P Vaska %yield P=Se 31P NMR Ligand Structure l:b NMR complex (CO nonanala Coupling (Hz) (ppm) shift) (cm-1)

54 PPh3 48 2.5 -5.1 729.4 1979

65 32 2.3 -14.5 727 1977 Ph2P F

66 PhP F 23 2.3 -23.7 720 1976 2

67 P F 13 2.5 -33.2 708 1971 3 F 68 38 2.8 -12.8 730 1977 Ph2P

F 25 2.4 -20.8 726 1973 69 PhP 2 F 70 18 2.5 -29.4 724 1968 P 3 F 71 50 2.7 -5.5 740 1980 Ph2P

F 56 2.6 -6.0 740 1982 72 PhP 2 F 73 58 2.7 -6.6 745 1984 P 3 a Average of four independent catalytic runs

72 Figure 2.9

Ligands 71-73 on the other hand, revealed electron-poor characteristics in comparison with triphenylphosphine, as the yields of aldehyde obtained in all cases were higher than that of triphenylphosphine. An increase was also observed in the yields as one moves along the series, namely 50%, 56% and 58%, respectively (Figure 2.9). This clearly gave an indication that the fluorine atom in the ortho position of the aryl ring brought about a dominant negative inductive effect, therefore withdrawing electrons from the phosphorus atom and counteracting the donating effect of the methyl group on the para position of the ring. This concomitantly gave rise to a more electron poor phosphine, which in turn increased the rate of the hydroformylation reaction and consequently provided the higher yields of the aldehydes observed.

73 2.7 The synthesis of trifluorobenzo-phosphine ligands, their stereo-electronic properties and their application in the hydroformylation reaction

It was decided to synthesise a third generation of phosphine ligands which contained a trifluoromethyl group. After having discovered that fluoride can undergo an interplay between inductive and resonance effects, it was decided to use a trifluoromethyl group in order to place the fluorine atoms one bond distance further from the aryl ring. This would be expected to remove the resonance effect of fluoride as was observed before and should purely reveal electron-withdrawing characteristics.

In his book Frontier Orbitals and Organic Chemical Reactions,27 Fleming explains how the HOMO energies monosubstituted , which are related to the ionization potentials of these compounds, can be calculated using photoelectron spectroscopy. As electron-donating groups are substituted onto the ring, the HOMO energy increases, while with electron-withdrawing groups the HOMO energy decreases. The HOMO energies for benzene, benzotrifluoride and fluorobenzene are -9.40 eV, -9.9 eV and -9.5 eV, respectively, which then indicates that both the trifluoromethyl group and the fluorine atom are electron- withdrawing groups. Furthermore it is stated that these energies parallel the reactivity of the arene in question towards electrophilic substitution, except in the case of halogenobenzenes as had been previously discovered. Thus it would be expected that the presence of the trifluoromethyl group on the aryl ring of a phosphine ligand should mainly withdraw the electrons from the phosphorus atom, rendering it more electron poor than triphenylphosphine.

The synthesis of these trifluorobenzo phosphine ligands was performed using the Grignard method under the same conditions shown in Schemes 2.1 and 2.2, which in turn provided the mono-, di- and tri-trifluoromethyl substituted tri-aryl phosphines in acceptable yields (42- 67%) along with small amounts of the oxidised products. The yields and selected analytical data of these ligands are given in Table 2.9.

These ligands were characterised using NMR spectroscopy, IR spectroscopy and EIMS. On the 1H NMR spectra signals were observed only in the aromatic area, as would be expected 74 since the structures only contain hydrogen atoms located on the phenyl rings. On 13C NMR spectra a characteristic signal were observed that indicated the presence of the tri- fluoromethyl groups, which included a widely spread quartet signal having a large coupling constant around 270 Hz. For ligand 80, for example, 1H NMR spectroscopy revealed signals

at 7.62 ppm (dd, 6H, H3, H3’, H3’’, H5, H5’, H5’’, JH-H = 7.8 Hz, JH-H = 0.6 Hz) and 7.40 ppm (t, 6H, H2, H2’, H2’’, H6, H6’, H6’’, J = 7.7 Hz), which correspond to the meta and ortho hydrogen atoms on the substituted phenyl rings, respectively. On the 13C NMR spectrum the

ipso-P carbon, ortho carbons, ipso-CF3 carbon and meta carbons were observed at 140.2 ppm (d, 3C, C1, C1’, C1’’, J = 14.0 Hz), 134.0 ppm (d, 6C, C2, C2’, C2’’, J = 20.1 Hz), 131.5 ppm (q, 3C, C4, C4’, C4’’, J = 32.8 Hz) and 125.7-125.6 ppm (m, 6C, C3, C3’, C3’’, C5, C5’, C5’’), respectively. The carbon of the trifluoromethyl group was observed at 123.8 ppm (q, 3C, - 31 19 CF3, J = 272.6 Hz). On the P NMR and F NMR spectra signals were observed at -5.6 ppm and -67.7 ppm, respectively. The remainder of the ligands were analysed in a similar way.

The stereo-electronic properties of these ligands were also probed by preparing the Vaska complexes and the P=Se compounds from these ligands as is given in Schemes 2.3 and 2.4. The values of the P=Se coupling constants and CO vibrational frequencies for each ligand are summarised in Table 2.9.

As can be deduced from this table ligands 75-77 (where the trifluoromethyl group was in the meta position of the aryl rings) and ligands 78-80 (where the trifluoromethyl group was in the para position of the aryl rings) followed the expected trend as the values of the P=Se coupling constants (742-767 Hz) and the CO vibrational frequencies (1982-1989 cm-1) are much higher than the corresponding values determined for triphenylphosphine (729.4 Hz, 1979 cm-1) indicating that they were less electron-rich than triphenylphosphine. Also the values of these parameters along the series of ligands 75-77 and of ligands 78-80 indicated increased electron-deficiency at the phosphorus atom as more trifluoromethyl-substituted aryl rings were incorporated into the phosphine. Thus these phosphine ligands became more electron-poor along the series, revealing the efficiency of the trifluoromethyl group to withdraw electrons from the phosphorus atom when positioned on the meta and para sites of the aryl ring. This electron-withdrawing effect was also reflected in the 31P NMR

75 spectroscopic signals, as the signals were in general observed at a lower field on the spectrum than for that of triphenylphosphine.

Table 2.9 The 3rd generation ligands and their selected analytical data.

P=Se 31P Vaska % isolated 31P NMR Ligand Structure NMR complex (CO yield (ppm) Coupling (Hz) shift) (cm-1)

54 PPh3 - -5.1 729.4 1979

F3C 74 66 -9.8 755.8 1976 Ph2P

CF3 75 67 -4.9 741.7 1986 Ph2P

CF3 76 60 -4.7 750.0 1988 PhP 2 CF3 77 45 -4.6 766.8 1989 P 3

78 Ph2P CF3 67 -4.9 740.8 1982

79 PhP CF3 50 -5.2 752.4 1985 2

80 P CF3 42 -5.6 766.0 1989 3

However, a strange anomaly was revealed when studying ligand 74, where it was found that the value of the CO vibrational frequency of the Vaska complex thereof was lower than that of triphenylphosphine, and, together with the higher-field lying 31P NMR spectroscopic signal at -9.8 ppm (in comparison with the signal at -5.1 ppm for triphenylphosphine), revealed an apparently more electron-rich phosphine ligand than triphenylphosphine. In contrast the P=Se coupling constant gave a value of 755.8 Hz, which is much higher than that for triphenylphosphine (729.4 Hz) indicating changes to the s-character of the phosphorus atom of this ligand. It should be recalled at this stage that the P=Se coupling constant is

76 sensitive to both steric and electronic effects while the Vaska CO stretching frequencies are sensitive only to electronics. The ortho-trifluoromethyl group should, therefore, also exert a steric influence on the phosphorus atom.

These observations, however, correspond with research done by Suomalainen et al.28 where they reported that the 31P NMR spectroscopic signal for the same ligand 74 was observed at - 9.4 ppm, which correlates with the signal (-9.8 ppm) observed in the present study. Furthermore they also calculated the Tolman cone angles for their ligands and found that ligand 74 exhibits an angle of 174° in comparison with the cone angle of 149° for triphenylphosphine reported in their study, therefore implying a steric influence of the tri- fluoromethyl group on the phosphorus atom. The Vaska-type complex for ligand 74 in their study gave a CO vibrational frequency of 1977 cm-1, which was reflected by the value of 1976 cm-1 for ligand 74 in the present study.

The hydroformylation reaction was performed with the 3rd generation ligands using the same conditions used throughout this study, where the catalyst to ligand ratio was 1:10. The reaction time was also restricted to 2 hours in order to directly compare the results with those of the 1st and 2nd generation ligands. Analysis of the resulting products was performed using the GC-FID, the resulting data of which are given in Table 2.11 together with other analytical data for ease of reference.

77 Table 2.11 Hydroformylation results of the 3rd generation ligands.

31P P=Se 31P Vaska % yield Ligand Structure l:b NMR NMR complex (CO nonanala (ppm) Coupling (Hz) shift) (cm-1)

54 PPh3 48 2.5 -5.1 729.4 1979

F3C 74 31 2.2 -9.8 755.8 1976 Ph2P

CF3 75 52 2.6 -4.9 741.7 1986 Ph2P

CF3 76 56 2.3 -4.7 750.0 1988 PhP 2 CF3 77 62 2.5 -4.6 766.8 1989 P 3

78 Ph2P CF3 60 2.4 -4.9 740.8 1982

79 PhP CF3 60 2.5 -5.2 752.4 1985 2

80 P CF3 62 2.5 -5.6 766.0 1989 3 a Average of four independent catalytic runs

From Table 2.11 it can be seen that the electronic anomaly as discovered before is importantly reflected by the hydroformylation reaction for ligand 74, as the yield (31%) of the aldehyde that was obtained here is much lower than that for triphenylphosphine (54, 48%). This clearly substantiated the analytical data indicative of a more electron-rich phosphine ligand. This effect was once again reflected by the research done by Suomalainen et al.29 where they performed the hydroformylation reaction of 1-hexene and 1-propene using similar ligands. With ligand 74 they did not obtain any conversion at all for both reactions, whereas in the present study at least a small amount of conversion was observed. In either case the performance of the hydroformylation reaction using ligand 74 was less efficient than when triphenylphosphine was used, indicating that in all cases the ortho-trifluoromethyl- substituted phosphine ligand exhibits an electron-rich character. The only reason provided in

78 the article is that, as depicted in Figure 2.10, the ortho-trifluoromethyl group is close to the rhodium centre, therefore hindering the alkene to approach the metal centre.

Figure 2.10 Crystal structure of a rhodium complex of ligand 21

On the other hand ligands 75-80 all gave higher hydroformylation yields of the aldehyde in comparison with reactions using triphenylphosphine, as would normally be expected for ligands less electron-rich than triphenylphosphine. Along the series of ligands 75-77 (where the trifluoromethyl group was meta with respect to the phosphorus atom) the hydroformylation results were fairly discriminative as the yields obtained increased from 52% to 56% and 62%, respectively. This corresponded well with the values of the 31P NMR signals, the P=Se coupling constants and the CO vibrational frequencies. For ligands 78-80 the hydroformylation results were not as discriminative as the yields of aldehyde obtained were similar along the series (60%, 60% and 62% respectively), even though the values of the P-Se coupling constants and the CO vibrational frequencies were quite different and even similar to those of the meta- trifluoromethyl substituted phosphine ligands.

79 2.8 Conclusions

The Grignard reagent was utilised to successfully synthesise a range of tri-aryl phosphine ligands with different alkyl and fluorine substituents at different positions from P-Cl derivatives. The phosphine ligands that were obtained each revealed systematically changing stereo-electronic properties. These stereo-electronic properties were probed by the preparation of Vaska complexes and phosphine selenide compounds from which the CO vibrational frequencies and the P-Se coupling constants were determined. In general, as the basicity of a phosphine ligand increased, the value of the P-Se coupling constant decreased. Likewise as the electron density on the phosphorus atom increased, the value of the CO vibrational frequency decreased. It was observed that the electronic properties of a phosphine ligand are dependent on the nature of the substituent such as an alkyl group or a fluorine atom, the number of substituents on the aryl rings of the phosphine ligand as well as the positions of the substituents on the aryl rings with respect to the phosphorus atom. The steric properties of the phosphine ligands were probed by calculating the Tolman Cone Angle. This angle varied with the number, position of attachment and nature of the aryl substituents.

Alkyl groups are electron-donating, and the longer the chain length the more electron donating the alkyl group becomes (to a limited extent). This was observed for the 1st generation of phosphine ligands, as the substitution of different alkyl groups (methyl, ethyl) at different positions in all cases caused an increase in the electron density of the phosphorus atom, giving rise to a series of electron-rich phosphine ligands in comparison with triphenylphosphine.

On the other hand the substitution of fluorine atoms on the aryl rings of a phosphine ligand revealed that fluorine atoms have both electron-donating and electron-withdrawing properties, as a possible interplay between resonance and inductive effects was observed. When fluorine atoms were substituted in the meta or para position and methyl groups in the ortho position of the aryl rings with respect the phosphorus atom, more electron-rich phosphine ligands were obtained. This indicated that the fluorine atoms possibly donated electron density onto the phosphorus atom by means of resonance. Conversely, substitution of fluorine atoms on the ortho position and methyl groups on the para position of the aryl rings with respect to the phosphorus atom, gave rise to less electron-rich phosphine ligands, 80 which indicated that the fluorine atoms withdrew electron density from the phosphorus atom. Being the most electro-negative atom it is expected that fluoride would withdraw electron density, but its lone pairs also allows orbital overlap leading to resonance with the aromatic system.

The substitution of a trifluoromethyl group on the aryl rings mainly gave rise to less electron- rich phosphine ligands, as this group generally withdraws electron density from the phosphorus atom. However, this was only observed when the trifluoromethyl group was substituted on the meta and the para position of the aryl rings of a phosphine ligand. With the substitution of the trifluoromethyl group on the ortho position of the aryl rings, more electron-rich phosphine ligands were obtained - an observation that cannot be explained.

The Rh-catalysed hydroformylation reaction was performed using the series of tri-aryl phosphine ligands that was synthesised. The conditions for this reaction were limited in such a way that a 50% conversion of 1-octene to the aldehyde was obtained when using triphenylphosphine as the ligand, which was the reference point for this study. It was observed that as one used a more electron-rich phosphine ligand within the hydroformylation reaction, lower conversion of the octene to the aldehyde within the limited time was achieved. This correlated well with the mechanism of the Rh-catalysed hydroformylation reaction, where the increasing basicity of a phosphine ligand lowers the rate of CO labilisation from the metal centre and in turn lowers the rate of alkene co-ordination. As a result accepting that all other variables remained constant, the rate of the hydroformylation reaction decreased and gave poorer yields of the aldehyde.

Little steric effects were observed in the hydroformylation reaction along the series of phosphine ligands, as the linear to branched ratios of the aldehydes were fairly constant throughout the series. Thus although the Tolman Cone Angle varied significantly along the series, it was not sufficient enough to induce a significant steric effect. What is clear from the results is that cone angles below 218° cause little effects on the l:b ratios of aldehydes and that larger cone angles are required to cause more substantial effects.

81 2.9 References

1. (a) Slaugh, L.H.; Mullineaux, R.D. Chem. Abstr. 1964, 64, 15745 and 1964, 64, 19420. (b) Sen, A.; Lai, T.W. J. Am. Chem. Soc. 1982, 104, 3520 (c) Drent, E. Pure Appl. Chem. 1990, 62, 661. 2. (a) Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.; Kumobayaashi, H.; Taketomi, T.; Akutagawa, S.; Noyori, R. J. Org. Chem. 1986, 51, 629. (b) Kwong, F.Y.; Chan, K.S. J. Chem. Soc., Chem. Commun. 2000, 1069. 3. Jardine, F.H.; Osborn, J.A.; Young, J.F.; Wilkinson, G. Chem. Ind. 1965, 560. 4. Riihimäki, H.; Kangas, T.; Suomalainen, P.; Reinius, H.K.; Jääskeläinen, S.; Haukka, M.; Krause, A.O.I.; Pakkanen, T.A.; Pursiainen, J.T. J. Mol. Catal. A: Chem. 2003, 200, 81. 5. Tolman, C.A. Chem Rev. 1977, 77, 313. 6. Stuebe, C; LeSuer, W.M.; Norman, G.R. J. Am. Chem. Soc. 1955, 77, 3526. 7. Richey, H.G. Grignard Reagents: New Developments, John Wiley and Sons, New York, 2000. 8. Allen, D.W.; Taylor, B.F. J. Chem. Soc., Dalton Trans. 1982, 51. 9. Cowley, A.H.; Damasco, M.C. J. Am. Chem. Soc. 1971, 93, 6815. 10. Roodt, A.; Steyn, G.J.J. Rec. Res. Dev. in Inorg. Chem., Transworld Research Network, Trivandrum, 2000, 2, 1. 11. Tolman, C.A. J. Am. Chem. Soc. 1970, 92, 2953. 12. Roodt, A.; Otto, S.; Steyl, G. Coord. Chem. Rev. 2003, 245, 121. 13. Perrin, L.; Clot, E.; Eisenstein, O.; Loch, J.; Crabtree, R.H. Inorg. Chem. 2001, 40, 5806. 14. Gillespie, A.M.; Pittard, K.A.; Cundari, T.R.; White, D.P. Internet Electrochem. J. Mol. Des. 2002, 1, 242. 15. Andersen, N.G.; Keay, B.A. Chem. Rev. 2001, 101, 997. 16. Nixon, J.F.; Pidcock, A. Annu. Rev. NMR Spectrosc. 1969, 2, 345. 17. Bent, H.A. Chem. Rev. 1961, 61, 275. 18. (a) Dunbar, K.R.; Haefner, S.C. Inorg. Chem. 1992, 31, 3676. 19. White, E. Organometallic Compounds of Cobalt, Rhodium, And Iridium, Chapman and Hall, London, 1985, 183.

82 20. Dias, P.B.; Minas de Piedade, M.E.; Martinho Simões, J.A. Coord. Chem. Rev. 1994, 135/136, 737. 21. Cornils, B.; Hermann, W.A.; Rasch, M. Angew. Chem. Int. Ed. 1994, 33, 2144. 22. Evans, D.; Osborn, J.A.; Wilkinson, G. J. Chem. Soc. (A) 1968, 3133. 23. van Leeuwen, P.W.N.M. Homogeneous Catalysis, Understanding the art, Kluwer Academic Publishers, Dordrecht, 2004. 24. Riihimäki, H.; Suomalainen, P.; Reinius, H.K.; Suutari, J.; Jääskeläinen, S.; Krause, A.O.I.; Pakkanen, T.A.; Pursiainen, J.T. J. Mol. Catal. A: Chem. 2003, 200, 69. 25. Heck, R.F. Acc. Chem. Res. 1969, 2, 10. 26. da Silva, A.C.; de Oliveira, K.C.B; Gusevskaya, E.V.; dos Santos, E.N. J. Mol. Catal. A: Chem. 2002, 179, 133. 27. Fleming, I. Frontier Orbitals and Organic Chemical Reactions, John Wiley and Sons, New York, 1976. 28. Suomalainen, P.; Reinius, H.K.; Riihimäki, H.; Laitinen, R.H.; Jääskeläinen, S.; Haukka, M.; Pursiainen, J.T.; Pakkanen, T.A.; Krause, A.O.I. J. Mol. Catal. A: Chem. 2001, 169, 67.

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