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Investigations on rhodium-catalyzed asymmetrichydroformylationCitation for published version (APA):Zijp, E. J. (2007). Investigations on rhodium-catalyzed asymmetric hydroformylation. Eindhoven: TechnischeUniversiteit Eindhoven. https://doi.org/10.6100/IR627570

DOI:10.6100/IR627570

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Investigations on Rhodium-Catalyzed Asymmetric Hydroformylation

PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Technische Universiteit Eindhoven, op gezag van de Rector Magnificus, prof.dr.ir. C.J. van Duijn, voor een commissie aangewezen door het College voor Promoties in het openbaar te verdedigen op dinsdag 3 juli 2007 om 16.00 uur door Eric Jurriën Zijp geboren te Sleeuwijk

Dit proefschrift is goedgekeurd door de promotor: prof.dr. D. Vogt Copromotor: dr. H.C.L. Abbenhuis

Investigations on Rhodium-Catalyzed Asymmetric Hydroformylation / by Eric Jurriën Zijp

Eindhoven : Eindhoven University of Technology, 2007

A catalogue record is available from the Eindhoven University of Technology Library

ISBN: 978-90-386-1055-9

Omslag: Oranje Vormgevers Eindhoven, naar een idee van Henrike Klein Ikkink

Druk: Universiteitsdrukkerij, Technische Universiteit Eindhoven

Copyright © 2007 Eric J. Zijp

Table of Contents

Table of Contents

1

19

51

69

87

103

105

107

111

Chapter 1 Introduction and Scope

Chapter 2 Synthesis of Bisaminophosphine Ligands and Their

Coordination Behavior

Chapter 3 DFT Study into Models of Bisaminophosphine

Ligands

Application of Bisaminophosphine Ligands in

Rh-Catalyzed Asymmetric Hydrogenation

Chapter 4 Application of Bisaminophosphine Ligands in Rh-

Catalyzed Asymmetric Hydroformylation

Chapter 5 Phosphonite-Phospholane Ligands Applied in Rh-

Catalyzed Asymmetric Hydroformylation

Summary

Samenvatting

Dankwoord

Curriculum Vitae

Chapter 1

Introduction and Scope

Asymmetric hydroformylation is considered as a

transformation of high potential for the fine chemical industry

since decades. This is due to the role aldehydes and derived

building blocks play in organic synthesis. However, few ligand

systems meet the requirements for industrial applications in

terms of selectivity and activity, though significant progress has

been made in recent years. New classes of ligands and deeper

understanding of the stereoselective step obtained by

spectroscopic studies and theoretical investigations have

brought this reaction close to the edge of real application. More

theoretical insight is necessary to be able to make the final step.


1.1 Introduction

Since the discovery by Roelen in 1938[1] regioselective hydroformylation (Eq. 1) has

developed into an important industrial process for the production of linear aldehydes

(softeners for plastics and detergent industry). An industrial application of the

asymmetric hydroformylation reaction, leading to the branched aldehyde, however still

does not exist. The expected potential of the reaction can be illustrated by the interest

shown by academia as well as industry, resulting in many publications including

reviews[2-5] and an excellent book by van Leeuwen and Claver[6] on the matter.

R R

CHO

RCHO+

branched linear

CO/H2

cat. *

(1)

Here we emphasize on the possible applications of asymmetric hydroformylation, a

historic overview on the catalyst-systems and ligands used for the reaction and the

knowledge of the important factors determining the ability of a ligand to induce

stereoselection in this transformation.

1.2 Application

Asymmetric hydroformylation potentially could be an important reaction for the

synthesis of chiral aldehydes as intermediates in drug synthesis. A recent review

illustrates that several substrate classes can be selectively hydroformylated to the

branched product.[7] Either the tendency of substrates to chelate to the catalyst (e.g.

vinyl acetate) or the electronic preference for branched aldehyde formation (e.g.

vinylarenes) can be exploited by the synthetic chemist. The branched selective

hydroformylation of unfunctionalized alkenes remains a challenge, as well as the regio-

control within internal alkenes to form one branched aldehyde over the other branched

product.

Other emerging technologies in industry are the combination of biocatalysis and

hydroformylation (e.g. biocatalysts provide access to chiral substrates for

hydroformylation)[8] or the combination of chemocatalytic reactions (e.g. tandem

2


hydroformylation / reductive amination and asymmetric allylic alkylation providing

chiral alkenes for hydroformylation).[9,10]

1.3 Platinum/Tin Catalyzed Asymmetric Hydroformylation

The first studies applying platinum/tin as the catalyst in asymmetric hydroformylation

appeared not long after the introduction of the rhodium catalyzed analogue.[11-13]

Mainly diphosphines were applied (Figure 1). The use of DIOP (1) in asymmetric

hydroformylation of styrene gave mainly linear aldehyde (b/l = 0.3) and a maximum ee

of 22%.[14] Modification of the ligand to BDP-DIOP (2) gave somewhat better

selectivity to the branched aldehyde and higher ee's up to 65%.[15]

The disadvantages of the platinum/tin based systems are

• The low selectivity to the branched product

• The need of an excess of (poisonous) SnCl2 with respect to platinum

• Racemization of the product aldehydes caused by the Lewis acid SnCl2

• High amount of alkene hydrogenation

• Undesired alkene isomerization

• Low activity compared to rhodium-based catalysts

O

O

PPh2

PPh2

O

O

P

P

NH

PPh2PPh2

PPh2 PPh2

1 2 3

4 5

PPh2

PPh2

Figure 1 Chiral diphosphine ligands used in the Pt/Sn-catalyzed asymmetric hydroformylation. DIOP

(1), BDP-DIOP (2), PPM (3), BDPP (4), BINAP (5).

3


The racemization of the product aldehydes could be suppressed by trapping the chiral

aldehydes as the acetal by using triethyl orthoformate as the co-solvent. Although the

speed of reaction was much lower than in benzene, the enantioselectivity induced by

PPM (3) as ligand improved from 70% to >96%.[16-17] Meessen et al and Van Duren et

al. showed that the excess of tin(II)chloride could be omitted while retaining a

sufficient activity by the use of large biteangle ligands. The preformation of the catalyst

proved also to be effective with only one equivalent of the tin-source.[18]

Other ligands were developed to gain more insight in the mechanism governing the

enantioselectivity. Kollár et al. showed for the first time that the direction of

enantioselectivity can change sign with increasing temperature in a study with BDPP

(4) as the chiral ligand employed.[19] This was explained by a conformational change of

the six-membered chelate ring. The concept of enantio-inversion was later studied in

more detail with BINAP (5). Using dynamic NMR studies it was shown that this effect

was caused by changes in the conformation of the ligand.[20] At higher temperature

these changes altered the geometry around the platinum atom, which in turn caused the

insertion of the substrate (styrene) to take place from the other enantioface.

Casey et al. studied this phenomenon by performing deuterioformylation.[21] The

enantioselectivity turned out not to be fully determined until the final hydrogenolysis of

the platinum acyl intermediate.

1.4 Rhodium catalyzed asymmetric hydroformylation[7]

The bidentate ligands used in asymmetric hydroformylation were traditionally the

diphosphines developed for asymmetric hydrogenation, i.e. ligands for square planar

complexes. The enantiomeric excesses obtained for rhodium catalysts with these

ligands remained below 60%.

4


Rh

H

COL

LR

Rh

H

CO

LL

Rh

H

COL

LCO

L

Rh

H

CO

LCO

CHO

R

R

L

Rh

H

CO

L

Rh

COL

LCO

R

Rh

COL

LCO

R

Rh

CO

LL

O R

L

Rh

O R

LCO H

H

R

CHO

towards linear aldehyde

branchedaldehyde

Scheme 1 Catalytic cycle for the branched selective hydroformylation of a terminal linear alkene.

Rhodium catalyzed hydroformylation however requires trigonal bipyramidal

complexes, as is shown in the proposed catalytic cycle for the rhodium-catalyzed

hydroformylation of a linear alkene (Scheme 1) and in more detail for a bidentate

ligand in Scheme 2.

Rh CO

H

CO

P

P PP

Rh CO

HOC

ee ea Scheme 2 Equatorial/equatorial ee and equatorial/axial ea coordination modes in trigonal bipyramidal

Rh-complexes.

The equilibrium between the ee and ea coordinated bidentate ligand to the rhodium

center is an important factor in the capacity of a ligand to induce stereodifferentiation.

This will be shown for different successful classes of ligands (vide §1.5). This resting

state of the catalyst is usually detected using in situ spectroscopic techniques and is

therefore often the target in molecular modelling studies. For 1-alkenes the rate limiting

step could be the hydrogenolysis of the rhodium acyl intermediate.[6]

5


One of the CO molecules is released from this trigonal bipyramidal complex. Then

alkene coordination followed by insertion in the Rh-H bond gives either a linear or

branched rhodium alkyl species. CO coordination followed by migratory insertion gives

either the branched or the linear rhodium-acyl species. These complexes undergo

hydrogenolysis to release aldehydes and regenerate the Rh-H catalyst. All the steps in

the rhodium-catalyzed hydroformylation can be reversible, with the exception of the

final hydrogenolysis.

The steric constraints of the ligands employed in hydroformylation are different

because of this altered geometry for the Pt/Sn and Rh catalysts. If the alkene

coordinates in the equatorial plane (in the rhodium catalyst), the interaction of the

substrate with the ligand is weaker than in a square planar intermediate (platinum),

certainly if the bidentate phosphine is also coordinated in the equatorial plane.

1.5 Ligands

In the 1990’s three new types of ligands have led to high ee’s in the asymmetric

hydroformylation of styrene, namely diphosphites, the mixed phosphine-phosphite

ligand BINAPHOS and the modular AMPP ligands. In the 2000’s the understanding of

the enantioselective step in the reaction rose through a theoretical investigation of the

latter ligand type applying QM/MM methods. The world-record holder concerning ee

for styrene is a hybrid phosphine-phosphoramidite ligand adapted from BINAPHOS

and was just developed in 2006. Bis-phosphacyclic ligands originally designed for

asymmetric hydrogenation proved also to induce high enantioselectivities in the

asymmetric hydroformylation of several substrates, albeit with rather low activities.

These ligand systems will be discussed in more detail (vide infra).

1.5.1 Diphosphites

Babin and Whiteker at Union Carbide reported the asymmetric hydroformylation of

various alkenes with ee’s up to 90% using bulky diphosphites (6) derived from

(2R,4R)-pentane-2,4-diol (figure 2).[22]

6


OP

O

O

tBu

tBu

R

R

OP

O

O

tBu

tBu

R

R6

Figure 2 Chiral diphosphite (6) from Union Carbide.

Investigations on the bridge-lengths of other diphosphites based on commercially

available chiral diols showed some distinct features: when the bridging backbone

consists of two carbon atoms the ligands adopt the e-a coordination and low ee’s are

obtained. Ligands having four carbon atoms in the bridge lead to the anticipated e-e

configuration, but also here the ee’s are low. Only when ligands with three carbon

atoms between the phosphite moieties are applied the bidentate ligand sits in the

trigonal plane of the complex and is rigid and bulky enough to lead to high ee’s.[23,24]

Also ligands based on sugar backbones give good ee’s if a three-carbon bridge is

involved.[25]

When the bisphenol groups of the diphosphites were replaced by bisnaphthols a

matched and a mismatched combination was found. By increasing the steric bulk on the

3- and 3’-positions of the bisnaphthol the ee’s increased, with an optimum reached for

SiMe3 groups.[26]

OO

PO

tBu

tBu

OOP

O

tBu

tBu

7

Figure 3 Kelliphite (7).

Although (S,S)-Kelliphite (7) (Figure 3) has 4 carbons between the phosphite moieties

it forms the best performing diphosphite ligand concerning regioselectivity in the

asymmetric hydroformylation of vinyl acetate. Using a beautiful example of a

multisubstrate screening Whiteker and coworkers[27] tested several phosphite-based

7


ligands on their performance with the benchmark substrates. An unprecedented b/l of

125 was reached along with an excellent ee of 88 % (at 25 °C).

1.5.2 BINAPHOS[28-32]

The benchmark ligand system for years has been the mixed phosphine-phosphite

BINAPHOS (8) (see figure 4). Where C1 symmetric ligands were generally avoided in

favor of C2 symmetric ligands (e.g. the diphosphites, vide supra), in this case the

dissymmetric substitution pattern proved to be very efficient. Most research on ligands

for the asymmetric hydroformylation reaction after this discovery was aimed on the

development of new C1 symmetric catalyst modifiers.

O

O

PO

PPh2

8

Figure 4 Takaya’s (R,S)-BINAPHOS (8).

The shown configuration (R for the bisnaphthyl unit, S for the bisnaphthol unit) was the

most efficient ligand in a larger series. The absolute configuration of the bisnaphthyl

determines the absolute configuration of the product, in the matched pair the used

bisnaphthol in the phosphite moiety has the opposite configuration. At 60 °C both

groups work together and 94% ee is obtained for styrene, when the mismatched pair is

used only 25% ee is reached. The rationalization of this phenomenon lies in the fact the

(R,S)-ligand has the tendency to bring the phosphorus donor atoms in closer proximity,

likewise in the free ligand.

HP-NMR measurements show that the RhH(CO)2(R,S-BINAPHOS(8)) is a single

species in toluene-d8 under CO atmosphere. The more σ-donor phosphine P atom sits in

the plane with the CO ligands whereas the more π-accepting phosphite P atom sits

apical to the hydride. No apical-equatorial interchange is observed at any temperature.

8


This unique dissymmetric environment in a single catalytically active species seems to

be an important factor in the high enantioselectivity obtained.

1.5.3 AMPP

Aminophosphane phosphinite (AMPP) ligands were developed in the 1980’s and used

for enantioselective hydrogenation.[33] In 2000 a new class of AMPP ligands (9),

bearing a stereogenic P atom of the aminophosphane moiety, was synthesized by Vogt

and coworkers (see figure 5). High enantioselectivities were reached when they were

applied in the asymmetric hydroformylation of vinylarenes.[34] O

MeN

Ar2PPh

Me

PPh

R9

Figure 5 Modular class of AMPP ligands (9) with stereogenic phosphorus atom.

The stereogenic P atom seemed to be essential for obtaining good ee’s. But also here

the coordination of the ligands in the catalytic resting state was important. The ligands

which give high ee all coordinate in a stable equatorial/axial manner, with the

aminophosphane moiety in the axial position. This could be concluded from combined

HP-IR and HP-NMR studies.

The origin of stereoinduction of the AMPP ligands was investigated by combining DFT

and QM/MM calculations.[35] Alkene insertion into the rhodium-hydride bond was the

selectivity-determining step, and not the alkene coordination. Different weak non-

bonding interactions of styrene with the substituents of the stereogenic phosphorus

atom in an axial position are responsible for stereodifferentiation.

1.5.4 Phosphine-phosphoramidite[36]

Zhang and coworkers just recently synthesized the mixed phosphine-phosphoramidite

ligand 10 (R,S)-Yanphos (figure 6) from the chiral synthon NOBIN (2-amino-2’-

hydroxy-1,1’-binaphthyl) and compared the space-filling and stick models (based on

CAChe MM2 calculations) of the active intermediates in hydroformylation reactions

with the ones applying BINAPHOS. Due to the crowded N-substituent the

RhH(CO)2(10) complex provides a deeper and more closed chiral pocket than the

9


corresponding RhH(CO)2(BINAPHOS) complex. Besides this the complex is

conformationally more rigid. The envision was this could lead to higher asymmetric

induction.

O

ON

PPh2

P

10 Figure 6 Zhang’s hybrid phosphine-phosphoramidite ligand 10.

Ligand 10 proved indeed to give a better performance in terms of ee and conversion

under mild conditions than BINAPHOS for a large number of vinylarenes and vinyl

acetate as the substrates. It has to be noted that not all applied conditions were similar

to the optimized conditions for BINAPHOS. For vinyl acetate the results matched the

previous best result using diazaphospholane ligand (11).[37]

A big advantage of the applied ligand systems seems to be the absence of racemization

of the produced aldehydes which does occur when BINAPHOS is applied, even before

full conversion.

Future developments are aimed at structural variation of the N-substituent of the

phosphine-phosphoramidite ligand for application in asymmetric hydroformylation as

well as other homogeneously metal-catalyzed transformations.

1.5.5 Bis-phosphacycles[38]

Bis-phosphacycles (figure 7), which were known to act as successful ligands in

asymmetric hydrogenation reactions, proved also to be efficient in inducing high

enantioselectivities in asymmetric hydroformylation of several substrates. The

assumption that good hydrogenation ligands are not efficient hydroformylation ligands

is therefore not true. The application of TangPhos (13) in the hydroformylation of

norbornylene was in fact already shown in 2005.[39]

10


P

H

tBu

PH

tBu

PP

Ph

PhPh

Ph

N

N

O

O

P

O

O

NH

HN

Ph

Ph

N

N

O

O

P

O

O

NH

NH

Ph

Ph

P

tBuH

P

tBuH

11 12

13 14 Figure 7 Bis-phosphacyclic ligands. Diazaphospholane (11), (S)-Binapine (12), (S,S,R,R)-Tangphos (13),

(R,R)-Ph-BPE (14).

Diazaphospholane (11) is the most efficient ligand for the hydroformylation of vinyl

acetate (96% ee) whereas (S)-Binapine (12) induced the highest ee ever reported (94%)

for allyl cyanide. The optimal working conditions should be carefully determined for

individual ligands and substrates. For instance Tangphos (13) should not be used in

excess with respect to rhodium. The non-coordinating anion (acac)- in the formed

[Rh(Tangphos)2]+[acac]- proved to racemize the chiral products, whereas Ph-BPE (14)

did not show the same behavior and is best used in a 2-fold excess. The activities and

regioselectivities were generally low compared to the hybrid ligands Yanphos and

BINAPHOS. The introduction of electronwithdrawing substituents in close proximity

of the phosphorus atoms may overcome this disadvantage. The common elements in

this class of ligands are the phosphacyclic motif and the two-carbon bridging group

between the phosphorus atoms. Wills’ successful bis-diazaphospholidine ligand

ESPHOS (15, see figure 8), which is only suitable for vinyl acetate (ee = 90%, b/l =

16:1) also belongs to this selection[40]

PP

N

NN

N

Ph

Ph

15 Figure 8 Bis-diazaphospholidine ligand ESPHOS (15).

11


1.5.6 Monodentate phosphorus-based ligands

Due to the low enantioselectivities and despite the good regioselectivities obtained in

the 1970's [41] the use of monodentate chiral phosphorus-based ligands was virtually

abandoned in favor of the more efficient bidentate ligands.[42]

Some literature examples employing monodentate chiral phosphorus-based ligands (see

Figure 9) other than phosphines are the TADDOL-based phosphonite ligand (16) of

Seebach et al. [43] and the diazaphospholidine (17) of Wills and coworkers.[40] The

phosphonite of Seebach induces in the asymmetric hydroformylation of styrene very

good b/l ratios of about 20 and an ee of 20% where the diazaphospholidine shows a

limited b/l ratio and virtually no ee. The bisnaphthyldiamine based diazaphospholidine

(18) of Reetz and coworkers gave the highest ee for styrene (up to 37%).[44]

O

O

O

O

Ph Ph

Ph Ph

P

MeO

PN

N

Ph

N

N

O

O

P

O

O

NH

NH

Ph

Ph

O

OP N

Ph

Ph

N

NP X

R

R

O

OP O

R

R

16 17 18

19 20 21

Figure 9 Monodentate chiral ligands 16-21 employed in Rh-catalyzed asymmetric hydroformylation.

Monodentate phosphoramidites were successfully applied in asymmetric hydrogenation

of various substrates owing to their modular nature and ease of preparation allowing for

the construction of large libraries of ligands to be used in fast identification of new and

efficient catalysts. This prompted a feasibility study of these versatile compounds as

chiral ligands in the rhodium-catalyzed asymmetric hydroformylation of the benchmark

12


substrates styrene and vinyl acetate. Good activities, chemoselectivities and

regioselectivities were generally achieved. The best ee however reached only a

moderate value of 27% when ligand 19 was used.[45] The highest activities were found

when the phosphites of Whiteker and coworkers (20) were applied[46] and very high

regioselectivities (b:l = 39) were obtained with the phosphacyclic ligand (21) developed

by Clark et al.[37]

22.1 - 5% 22.2 - 14% 22.3 - 68%

O

OP N O

OP N

O

OP N

tBu

tBu

Figure 10 Phosphoramidite ligand series 22.1-22.3 with obtained ee when employed in asymmetric

hydroformylation of allyl cyanide at 60 ºC (L:Rh = 3:1) in benzene.

Best results in terms of enantioselectivity for allyl cyanide as the substrate were

obtained with the phosphoramidites 22 by Ojima and coworkers (see Figure 10).[47] In

the ligand series 22.1-22.3 the importance of the 3- and 3'-positions was once more

confirmed. Upon lowering the temperature to 25 ºC 80% ee was obtained in toluene,

although complete conversion was only reached after 74h. A solvent screening

confirmed that toluene was the best solvent among those tested (THF, dichloromethane

and MeOH).

The authors performed a molecular modelling study (Spartan; MM2/PM3) to try to

understand the dramatic effect by using the bulkiest ligand 22.3. It was shown that due

to the steric repulsion the two ligands should coordinate in the equatorial-equatorial

positions of the trigonal-bipyramidal Rh-complex.

13


1.6 Conclusions

Asymmetric hydroformylation has become a more competitive transformation for fine-

chemical industry. The development of more selective and active ligand systems,

applicable for more than a single substrate has taken a high flight. Commercially

available ligands for asymmetric hydrogenation proved to form efficient

hydroformylation catalysts under the right conditions determined by using HTE

techniques.

1.7 Perspective

There is a lot to gain by spectroscopic analysis of hydroformylation catalysts under

working conditions, which is only occasionally done so far. A better understanding of

the stereoselective step could be acquired by theoretical investigations on sufficient

high level of modelsystems of the most successful systems. Comparison of different

catalyst-systems is often difficult since experimental conditions are critical and hardly

ever identical; a comprehensive database with all available data on the asymmetric

hydroformylation reaction would prove invaluable in seeing through all quantitative

structure performance relationships.

14


1.8 Aim and Scope of Thesis

In this thesis the development of new hydroformylation catalysts is presented. Newly

synthesized ligands and their transition metal complexes were analyzed carefully via

spectroscopic means, X-ray analyses and DFT calculations. Application in asymmetric

hydrogenation and hydroformylation reactions showed the potential in catalysis. The

catalysts were monitored under working conditions to determine the coordination-

modes. The obtained data can be used for a better understanding of the reaction and the

development of new generations of catalysts.

In Chapter 2 the successful synthesis of a series of symmetrically and non-

symmetrically substituted chiral bisaminophosphine ligands following two modular

routes applying easy purification procedures is shown. X-ray analyses of both free

ligands and mononuclear cis-coordinated transition metal complexes thereof indicated

the trigonal planar geometry of the nitrogen atoms, as well as a P-N bond with double

bond character.

Chapter 3 contains DFT calculations performed on model compounds for

bisaminophosphine ligands to analyze the geometries and charge distributions. The

computed structure of a simplified cis-Pd complex of a bidentate bisaminophosphine

ligand gives valuable information on the coordination behavior. Catalysts generated in

situ from [Rh(cod)2]BF4 and bisaminophosphine ligands were used in the asymmetric

hydrogenation of methyl Z-acetylaminocinnamate with ee’s up to 91%.

The application of C2-symmetric bisaminophosphine ligands in the Rh-catalyzed

asymmetric hydroformylation of prochiral alkenes is described in Chapter 4. HP-NMR

studies indicated that equatorial - equatorial is the preferred coordination mode, which

could be confirmed by HP-IR spectroscopy.

In Chapter 5 hybrid Me-BINOLane ligands are described which form active catalysts

in the Rh-catalyzed asymmetric hydroformylation of styrene. Branched/linear ratio’s

higher than 20 were obtained. The found ee’s depend mostly on the atropisomeric

element in the phosphonite part of the ligand and reach values just over 50%.

15


1.9 References

[1] O. Roelen (to Ruhrchemie AG) German patent 849548, 1938. [2] F. Agbossou, J. -F. Carpentier, A. Mortreux, Chem. Rev. 1995, 95, 2485. [3] S. Gladiali, J. C. Bayón, C. Claver, Tetrahedron Asymmetry, 1995, 6, 1453. [4] B. Breit, W. Seiche, Synthesis, 2001, 1. [5] C. Claver, M. Diéguez, O. Pàmies, S. Castillón, Top. Organomet. Chem. 2006, 18, 35. [6] C. Claver, P. W. N. M. van Leeuwen, Rhodium Catalyzed Hydroformylation (Eds. C. Claver, P.

W. N. M. van Leeuwen), Kluwer-CMC, Dordrecht, 2000, pp 107. [7] M. L. Clarke, Curr. Org. Chem. 2005, 9, 701. [8] E. D. Daugs, W.-J. Peng, C. L. Rand (to DOW Technologies Inc.) World patent WO

2005110986 A1, 2004. [9] J. R. Briggs, J. Klosin, G. T. Whiteker, Org. Lett. 2005, 7, 4795. [10] M. C. J. Harris, M. Jackson, I. C. Lennon, J. A. Ramsden, H. Samuel, Tetrahedron Lett. 2000,

41, 3187. [11] G. Consiglio, P. Pino, Helv. Chim. Acta, 1976, 59, 642. [12] Y. Kawabata, T. M. Suzuki, I. Ogata, Chem. Lett. 1978, 4, 361. [13] P. Haelg, G. Consiglio, P. Pino, J. Organomet. Chem. 1985, 296, 281. [14] C. U. Pittmann, Y. Kawabata, L. I. Flowers, J. Chem. Soc., Chem. Commun. 1982, 473. [15] G. Parinello, R. Deschenaux, J. K. Stille, J. Org. Chem. 1986, 51, 4189. [16] G. Parinello, J. K. Stille, J. Am. Chem. Soc. 1987, 109, 7122. [17] J. K. Stille, G. Parinello (to Colorado State University Research Foundation), World Pat.

88/08835, 1988. [18] a) P. Meessen, D. Vogt, W. Keim, Organometallics, 1998, 551, 165. b) R. van Duren, Platinum

Catalyzed Hydroformylation, PhD thesis, University of Eindhoven, 2004. c) R. van Duren, L. L.

J. M. Cornelissen, J. I. van der Vlugt, J. P. J. Huijbers, A. M. Mills, A. L. Spek, C. Müller, D.

Vogt, Helv. Chim. Acta, 2006, 89, 1547. [19] L. Kollár, J. Bakos, I. Tóth, B. Heil, J. Organomet. Chem. 1988, 350, 277. [20] L. Kollár, P. Sándor, G. Szalontai, J. Mol. Cat. 1991, 67, 191. [21] C. P. Casey, S. C. Martins, M. A. Fagan, J. Am. Chem. Soc. 2004, 126, 5585. [22] J. E. Babin, G. T. Whiteker (to UCC) World Pat. 93/03839, 1993. [23] G. J. H. Buisman, E. J. Vos, P. C. J. Kamer, P. W. N. M. van Leeuwen, J. Chem. Soc. Dalton

Trans. 1995, 409. [24] G. J. H. Buisman, P. C. J. Kamer, P. W. N. M. van Leeuwen, Tetrahedron Asymmetry, 1993, 4,

1625. [25] see for example a) M. Diéguez, O. Pàmies, A. Ruiz, S. Castillón, C. Claver, Chem. Eur. J. 2003,

7, 3086; b) M. Diéguez, A. Ruiz, C. Claver, Dalton Trans. 2003, 2957. [26] G. J. H. Buisman, L. A. van der Veen, A. Klootwijk, W. G. J. de Lange, P. C. J. Kamer, P. W.

N. M. van Leeuwen, D. Vogt, Organometallics, 1997, 16, 2929. [27] C. J. Cobley, J. Klosin, C. Qin, G. T. Whiteker, Org. Lett. 2004, 6, 3277.

16

Chapter 1 Introduction and Scope [28] N. Sakai, S. Mano, K. Nozaki, H. Takaya, J. Am. Chem. Soc. 1993, 115, 7033. [29] N. Sakai, K. Nozaki, H. Takaya, J. Chem. Soc. Chem. Comm. 1994, 395. [30] T. Higashijima, N. Sakai, K. Nozaki, H. Takaya, Tetrahedron Lett. 1994, 35, 2033. [31] T. Horiuchi, T. Ohta, K. Nozaki, H.Takaya, Chem. Comm. 1996, 155. [32] T. Horiuchi, T. Ohta, E. Shirakawa, K. Nozaki, H.Takaya, J. Org. Chem. 1997, 62, 4285. [33] a) M. Petit, A. Mortreux, F. Petit, G. Buono, G. Pfeiffer, New. J. Chem. 1983, 7, 583. b) E.

Cesarotti, A. Chiesa, G. D’Alfonso, Tetrahedron Lett. 1982, 23, 2995. c) G. Pracejus, H.

Pracejus, J. Mol. Catal. 1984, 24, 227. [34] R. Ewalds, E. B. Eggeling, C. H. Alison, P. C. J. Kamer, P. W. N. M. van Leeuwen, D. Vogt,

Chem. Eur. J. 2000, 6, 1496. [35] J. J. Carbó. A Lledós, D. Vogt, C. Bo, Chem. Eur. J. 2006, 12, 1457. [36] Y. Yan, X. Zhang, J. Am. Chem. Soc. 2006, 128, 7198. [37] T. P. Clark, C. R. Landis, S. L. Freed, J. Klosin, K. A. Abboud, J. Am. Chem. Soc. 2005, 127,

5040. [38] A. T. Axtell, J. Klosin, K. A. Abboud, Organometallics, 2006, 25, 5003. [39] J. Huang, E. Bunel, A. Allgeier, J. Tedrow, T. Storz, J. Preston, T. Correll, D. Manley, T.

Soukup, R. Jensen, R. Syed, G. Moniz, R. Larsen, M. Martinelli P. J. Reider [40] S. Breeden, D. J. Cole-Hamilton, D. F. Foster, G. J. Schwarz, M. Wills, Angew. Chem. Int. Ed.

2000, 39, 4106. [41] a) I. Ogata, Y. Ikeda, Chem. Lett. 1972, 487. b) M. Tanaka, Y. Watanabe, T.-A. Mitsudo, K.

Yamamoto, Y. Takegami, Chem. Lett. 1972, 483. [42] F. Lagasse, H. B. Kagan, Chem. Pharm. Bull. 2000, 48, 315. [43] J. -I. Sakaki, W. B. Schweizer, D. Seebach, Helv. Chim. Acta, 1993, 76, 2644. [44] M. T. Reetz, H. Oka, R. Goddard, Synthesis, 2003, 1809. [44] L. Panella, Phosphoramidite Ligands and Artificial Metalloenzymes in Enantioselective

Rhodium-Catalysis, PhD thesis, Rijksuniversiteit Groningen, 2006. [46] A. T. Axtell, C. J. Cobley, J. Klosin, G. T. Whiteker, A. Zanotti-Gerosa, K. A. Abboud, Angew.

Chem. Int. Ed. 2005, 44, 5834. [47] Z. Hua, V. C. Vassar, H. Choi, I. Ojima, Proc. Natl. Acad. Sci. USA, 2004, 101, 5411.

17

Chapter 2

Synthesis of Bisaminophosphine Ligands and

Their Coordination Behavior

The versatile modular synthesis of novel symmetrically and

non-symmetrically substituted bisaminophosphine ligands is

described. Investigation of the molecular structures showed the

trigonal planar geometry of the nitrogen atoms and a

significant contribution of π-bonding to the P-N bond.

Upon complexation to late transition metals mononuclear cis-

coordination was mainly found.

Chapter 2 Synthesis of Bisaminophosphine Ligands and Their Coordination Behavior

2.1 Introduction

The coordination chemistry of diphosphine ligands with a variety of transition metals

is widely studied and several types of coordination modes have been established over

the years.[1] Numerous families of novel (chiral) ligands have been synthesized,[2] with

emphasis on cis-chelating properties to form monomeric metal complexes. Besides

ligand design based on desired behavior towards transition metal complexes and the

catalytic activity of such systems, the approach of modular design and availability of

cheap resources has gained significant importance.

Especially in asymmetric catalysis such a modular approach is highly desirable, since

full understanding of the factors governing the enantioselectivity during the catalytic

cycle is often lacking and the availability of tunable ligand families would greatly

enhance the generation of data leading to new insights. We have therefore set out to

explore new chiral diamines as chiral auxiliaries, since they form a class of hitherto

neglected ligand backbones.

N

NPPh2

PPh2

N

N

H

H

PPh2

PPh2

N PN

o-An

Ph

P

P

N

N

N

N

PhPh

i

ii

iii iv

Figure 1 Aminophosphine ligand systems based on substituted heteroatoms: Piperazine (i) and 1,2-

diaminobenzene (ii), developed by the group of Woollins3 and the ligands SEMI-ESPHOS (iii) and

ESPHOS (iv) reported by Wills et al.10

The synthesis and limited use of heteroatom substituted phosphines (Figure 1) and

their transition metal complexes has received quite some attention lately,[3-5] due to

the search for new structural diversity and catalytic activities. However, little has

appeared on the use of chiral diamines as backbone structures for phosphorus ligands,

although some reports described their application in the asymmetric hydrogenation of

20


various substrates.[6-9] Wills et al. have described the synthesis and application of the

so-called ESPHOS ligand system iv (Figure 1) in the rhodium-catalyzed asymmetric

hydroformylation of vinylacetate, with high enantioselectivities, although commercial

availability of the chiral diamine used is limited.[10] Generally chiral amines are

widely available nowadays due to heavy industrial investments in commercially

viable synthetic intermediates and specialty chemicals. Therefore the application of

chiral amines to build up the chiral backbone could be a viable approach.

In this chapter we report on the synthesis of novel chiral bidentate aminophosphine

ligands modularly constructed from chiral amines, both symmetrically and non-

symmetrically substituted, together with a study of their coordination chemistry

towards the transition metals palladium, platinum and rhodium.

2.2 Results

2.2.1 Symmetrically Substituted Bisaminophosphines

ClPPh2

OO

BrBr

NH

R1

R2NH

R1

R2PPh2PPh2

R1

R2N

R1

R2N

A

B

4 equiv chiral amine

2 equiv KOH (aq)

2 equiv chiral amine

2 equiv LiAlH4

NEt3

Scheme 1 Generic synthesis routes A and B to bisaminophosphine ligands.

The authors from references 6-9 chose condensation on diethyloxalate followed by

reduction of the corresponding diamide to synthesize their class of ligands. However,

in this protocol the reduction of the amide bonds is often not trivial. This method

required a case by case optimization making this route unsuitable for a parallel

approach.

We prepared the chiral bidentate aminophosphine ligands L1-L9 following two other

synthetic methodologies (scheme 1). This enables a modular construction of the

ligands in the way that there might be an alternative route if the first would fail.

21


Procedure A follows the two-step approach where the chiral amine moieties are

introduced in the backbone of the ligand by a nucleophilic SN2 substitution on a

dihaloalkane, generally dibromoethane, to form two secondary amines with a two-

carbon bridge spacer obtained as their hydrohalides. After treatment with a strong

base the diamine is purified by distillation. These intermediate diamines may be used

as ligands in e.g. asymmetric hydrosilylation of prochiral ketones.[11] By reaction of

the diamine with ClPPh2 in the presence of NEt3 to scavenge the liberated

hydrochloric acid, the corresponding diphosphines were obtained in good overall

yields. During the first step of this synthetic route an excess of chiral amine is used (4

equiv) but no solvent. Recovery of the precious chiral amine is possible during the

distillative workup, which is most efficiently achieved when the synthesis is

performed at larger scale (min. 50 mmol). Variation of the number of carbons in the

bridge can be achieved (Cn with n >1).

On a smaller scale, if the desired amount of ligand is lower or the chiral amine

building block is more expensive or less available, procedure B may be appropriate.

Here condensation of glyoxal with two equivalents of the appropriate chiral amine

gave the corresponding diimine in high yield. Reduction of the diimine with LiAlH4

and subsequent reaction of the amino-functionalities with ClPPh2 in the presence of

NEt3 afforded the bisaminophosphines in good yield. Washing with acetonitrile

afforded the pure compound without the need for further purification. We have to

stress that the intermediate diimines can be used as ligands themselves if applied to

e.g. semihydrogenation of alkynes.[12] A disadvantage of this second route may be the

limitation to ligands with a 2 carbon bridge. Note that both routes should enable the

introduction of other chlorophosphine compounds without much alteration.

22


Table 1 List of the prepared bisaminophosphines L1 – L9, the followed methodology for each ligand

and few remarks on the synthesis.

Ligand code

Ligand Structure

Procedure A / B

Remarks

L1 C2-spea-PPh2 NN

PPh2 PPh2 A

L2 C2-rpea-PPh2 NN

PPh2 PPh2 A

L3 C2-paea-PPh2 NN

PPh2 PPh2OMeMeO

A introduction phosphorus low yield

L4 C2-ppa-PPh2 NN

PPh2 PPh2 A

L5 C2-1nea-PPh2 NN

PPh2 PPh2

A diamine not purified by distillation

L6 C2-Cyea-PPh2 NN

PPh2 PPh2 B intermediate diamine very mobile oil

L7 C2-thna-PPh2 NNPPh2PPh2

B intermediate diimine not isolated

L8 C3-rpea-PPh2 N N

PPh2PPh2

A use of dibromopropane

L9 C3-ppa-PPh2 N N

PPh2PPh2

A use of dibromopropane

To expand the family of bisaminophosphine ligands to a smaller bridge size the

heteroatom bridge N-Si-N was considered, since a large variety of commercially

available dichlorosilane compounds exists, which can be converted into the

corresponding diaminosilane intermediates by a simple condensation step. The

condensation of the N-Si-N compounds with ClPPh2 imposed an unforeseen problem

due to the labile character of the Si-N bond in acidic environment. During the

attempts to synthesize N,N'-bis[(R)-(α)-methylbenzylamine)-N,N'-bis-

(diphenylphosphino)diaminodimethylsilane 2, unwanted diphosphazane 3 was

obtained in high yield with respect to ClPPh2 (scheme 2).

Workers in the group of Woollins did succeed in the synthesis of the PNSiNP

sequence, following the synthetic approach where aminophosphine units are

deprotonated and coupled to the dichlorosilane compound. Their coordination

behavior to transition metals was studied, where even exploitation of the labile N-Si-

N linkage was envisioned.[13]

23


NHNH

Si

NN

Si

PPh2 PPh2

NPPh2

PPh2

ClPPh2

NEt3

ClPPh2

NEt31

2

3

Scheme 2 Attempted synthesis of PNSiNP sequence 2 and obtained diazaphosphane 3.

The structures of the prepared ligands including the determination of the absolute

configuration of the stereogenic carbon atom could be confirmed by the molecular

structures of two ligands for which crystals suitable for X-ray analyses could be

grown.

Figures 2 and 3 show the structures of L6 and L7 respectively and tables 2 and 3

contain selected bond lengths, distances and angles of the ligands. Both ligands

possess C2 symmetry, the geometry around the nitrogen atoms is trigonal planar with

the sum of angles around N close to 360º and P-N distances around 1.68 Å indicating

considerable double-bond character (via a π-interaction) between the P and N atom.

P1

N1

C1

C2

N2

C4P2

Figure 2 ORTEP representation of ligand L6. Displacement ellipsoids are drawn at 50% probability

level. Hydrogen atoms are omitted for clarity.

24


Table 2 Selected bond lengths, distances and angles for ligand L6.

Bond lengths (Å) P1-N1 1.6793(16) P2-N2 1.6835(16) P1-P2 (dist) 6.379 N1-N2 (dist) 3.815

Angles (º) P1-N1-C1 122.97(13) P1-N1-C3 116.40(13) C1-N1-C3 120.17(15) P2-N2-C2 124.20(12) P2-N2-C4 118.66(13) C2-N2-C4 116.58(15) Sum angles N1 359.5 sum angles N2 359.4

C3P1

C1C2 N2N1

P2C13

Figure 3 ORTEP representation of ligand L7. Displacement ellipsoids are drawn at 50% probability

level. Hydrogen atoms are omitted for clarity.

Table 3 Selected bond lengths, distances and angles for ligand L7.

Bond lengths (Å) P1-N1 1.6887(21) P2-N2 1.6874(18) P1-P2 (dist) 6.407 N1-N2 (dist) 3.450

Angles (º) P1-N1-C1 123.32(14) P1-N1-C13 122.41(16) C1-N1-C13 113.41(19) P2-N2-C2 124.16(14) P2-N2-C3 119.87(14) C2-N2-C3 115.94(16) Sum angles N1 359.1 sum angles N2 360.0

Bisaminophosphine L4 was oxidized by 30% aqueous H2O2 to check if the

phenomena of a virtually flat geometry around N and a P-N bond with double bond

character would also occur after oxidation. X-ray analysis revealed the unambiguous

molecular structure of the ligand (Figure 4), and showed the slightly distorted trigonal

planar geometry of the nitrogen atoms and a more pronounced P-N double bond (1.66

Å), presumably due to the greater donation of the N lone pair to the more electron

poor phosphorus atom (an upfield shift of 12.1 ppm in 31P NMR was observed upon

25


oxidation compared to the non-oxidized ligand). Detailed information on bond

lengths, distances and angles for ligand oxide 4, is listed in Table 4.

P2C12

N1 O2O1 C2N2C1

P1C3

Figure 4 ORTEP representation of ligand L4 oxide 4. Displacement ellipsoids are drawn at 50%

probability level. Hydrogen atoms are omitted for clarity.

Table 4 Selected bond lengths, distances and angles for ligand L4 oxide 4.

Bond lengths (Å) P1-N1 1.661(3) P2-N2 1.652(3) P1-O1 1.477(3) P2-O2 1.477(3) P1-P2 (dist) 6.472 N1-N2 (dist) 3.787

Angles (º) O1-P1-N1 113.03(16) O2-P2-N2 111.10(17) P1-N1-C1 120.5(2) P1-N1-C12 123.0(3) C1-N1-C12 114.4(3) P2-N2-C2 121.7(2) P2-N2-C3 116.3(3) C2-N2-C3 118.6(3) sum angles N1 357.9 sum angles N2 356.6

Besides investigation of molecular structures and therewith structural features of the

prepared ligands, their electronic parameters were studied. A simple and efficient

method to evaluate the σ-donor character and hence the basicity of a phosphine

moiety is to measure the magnitude of the coupling constant 1JSe-P in the 31P NMR

spectrum of the 77Se isotopomer of the corresponding diphenylphosphine

selenide.[14,15] An increase in the coupling constant is indicative of increasing s-

character of the phosphorus lone-pair and hence of lower basicity. Ligands L1 and L9

were reacted with elemental selenium for 30 minutes in toluene at 70 °C. In the 31P

NMR spectrum of the corresponding selenides 5 and 6 in CH2Cl2, a singlet was found

at δ 70.3 ppm and 69.1 ppm, respectively. Both signals were flanked by two 77Se-

satellites, and the coupling constants JSe-P were 752 Hz and 750 Hz, respectively. This

shows that both ligands are essentially identical in their electronic character of the

26


phosphorus moieties. These values are in agreement with the few available literature

data on aminophosphines.[3a,4] The JSe-P values are higher than for corresponding

diarylphosphines, which implies lower basicity of the phosphine moiety, due to higher

electronegativity of the adjacent nitrogen atom.[16]

2.2.2 Non-Symmetrically Substituted Bisaminophosphines

Besides the extension of the set of modular bisaminophosphines and a study into their

coordination behavior we were curious if we could study the influence of an

individual aminophosphine moiety on the properties of the ligand. Hence we were

aiming at a versatile synthetic route which would enable the preparation of non-

symmetrically substituted chiral bisamines, which could be converted into the

corresponding bisaminophosphines by the application of a similar condensation with

chlorodiphenylphosphine as mentioned in paragraph 2.2.1.

First attempts consisted of a combination of a nucleophilic substitution and a

condensation, performed with two amines of choice on the same backbone (scheme

3).

i

ii

ClO

O

OBr

RNH2

RNH2

O

ONHR deprotection

Scheme 3 Attempted syntheses towards non-symmetrically substituted chiral diamines.

Reaction i) did not yield any identifiable products, the observed black color probably

indicating the formation of polymeric materials. Nucleophilic substitution on the

commercially available bromoalkane (ii), leaving the 1,3-dioxalane protected

aldehyde intact, nicely afforded the desired compounds applying different chiral

amines, but subsequent deprotection of the aldehyde did not occur under normally

successful mildly acidic conditions.

2-Chloroethanol however could serve as the basis of the synthesis of non-

symmetrically substituted chiral diamines (scheme 4).

27


NCl

H HClN

OH

HClOH

NH2

SOCl2KOH

N NR

H H

RNH2

KOH

ClPPh2

NEt3

N

PPh2

N

PPh2

R

L10 R =

L12 R =

L11 R =

7

8

9

Scheme 4 Synthetic procedure for non-symmetrically substituted bisaminophosphine ligands L10-L12.

A nucleophilic substitution in neat (R)-α-methylbenzylamine gave after KOH

treatment and recovery of the excess amine the chiral aminoalcohol 7. Conversion of

the alcohol function into the chloride leaving group by a reaction with thionylchloride,

meanwhile leaving the amine function protected as the hydrochloride, yields a

versatile building block which is stable in air for months. The introduction of the

second amine is again performed with a small excess of amine at a high temperature

to ensure homogeneity and the chiral, non-symmetrically substituted diamine can be

obtained 9. Conversion into the corresponding bisaminophosphine is done without

laborious purification of the diamine (only basic workup and removal of amine in

vacuo is required), by the reaction with chlorodiphenylphosphine in the presence of

triethylamine.

In the above described manner 3 ligands were synthesized, all based on the

intermediate aminoalcohol created from (R)-α-methylbenzylamine. The C1-symmetric

ligands L10 and L11 were obtained by respectively using achiral benzylamine and

(R)-α-ethylbenzylamine as the second amine. Curiosity driven the Cs-symmetric

ligand L12 was made by applying (S)-α-methylbenzylamine to obtain a ligand

possessing a mirror plane thus being a meso compound.

Theoretically this route would enable the synthesis of a large family of ligands, with

different steric and electronic properties on both aminophosphine moieties and

tunable stereogenic information.

28


2.2.3 Coordination Chemistry

The coordination behavior of the above described symmetrically substituted chiral

amine-based diphosphine ligands was studied with the representative ligand 1 towards

palladium, platinum and rhodium precursors.

Preparation of palladium(II) complexes C1 and C2.

Reaction of [PdCl2(cod)] with L1 for 2 hours in CH2Cl2 at room temperature resulted

in a yellow solid complex C1 (figure 5 (M = Pd, X = Cl)), for which the 31P NMR

spectrum showed a singlet at δ 87.3 ppm. Little structural information can be deduced

from this chemical shift however. The ligand backbone skeleton (viz. size, flexibility)

is analogous to the well studied ligand dppb, for which only the cis-isomer is

reported.[17]

NN

PPh2PPh2

MCl X

Figure 5 Prepared and studied complexes of ligand L1, C1 (M = Pd, X = Cl), C2 (M = Pd, X = Me)

and C3 (M = Pt, X = Cl).

To further elucidate the structure of complex C1, ligand L1 was reacted with

[PdCl(CH3)(cod)] to give complex C2 as a micro-crystalline yellow solid, (figure 5

(M = Pd, X = Me)), Characterization of this species in solution by 31P NMR

spectroscopy showed an AB system with two doublets at δ 91.3 ppm and 81.0 ppm

with coupling constants JP-P of 28 Hz, while in the 1H NMR spectrum a doublet of

doublets was present at δ 0.47 ppm for the methyl ligand at palladium. Both

observations clearly indicate the sole formation of cis-[PdCl(CH3)(L1)],[18] with the

downfield doublet at δ 91.3 ppm corresponding to the phosphine trans to chloride and

the upfield doublet at δ 81.0 ppm to the phosphine trans to the methyl ligand.

Furthermore, in the 1H NMR spectrum two triplets at δ 4.26 ppm and 4.41 ppm were

found for the inequivalent CH2-groups in the backbone. Both complexes C1 and C2

were surprisingly very soluble in acetonitrile, but we could obtain single crystals by

29


slow diffusion of hexanes into a CH2Cl2 solution of complex C1. The molecular

structure of this compound was unequivocally determined by X-ray crystallography.

Figure 6 shows the structure of C1. Table 5 contains data on selected bond lengths

and angles. The asymmetric unit cell contained two independent molecules that

differed mainly in the orientation of the phenyl rings on the phosphorus atoms. For

clarity only one residue molecule is shown.

C1 C4C2C3

N2N1

P2P1

Pd1

Cl2Cl1

Figure 6 ORTEP representation of the first of two independent molecules of complex C1, cis-

[PdCl2(L1)]. Displacement ellipsoids are drawn at 50% probability level. Hydrogen atoms are omitted

for clarity.

Table 5 Selected bond lengths, distances and angles for complex C1, cis-[PdCl2(L1)].

Bond lengths (Å) Pd1-P1 2.2681(6) Pd1-P2 2.2549(5) Pd1-Cl1 2.3507(5) Pd1-Cl2 2.3489(6) P1-N1 1.6811(18) P2-N2 1.6591(19) P1-P2 (dist) 3.381 N1-N2 (dist) 3.089

Angles (º) P1-Pd1-P2 96.74(2) Cl1-Pd1-Cl2 90.19(2) Cl1-Pd1-P1 83.36(2) Cl1-Pd1-P2 173.66(2) Cl2-Pd1-P1 173.41(2) Cl2-Pd1-P2 89.52(2) P1-N1-C1 116.56(14) P1-N1-C3 125.83(14) C1-N1-C3 113.91(17) P2-N2-C2 119.39(14) P2-N2-C4 123.21(14) C2-N1-C4 116.04(17) sum angles N1 356.3 sum angles N2 358.6

The geometry around the palladium atom in complex C1, cis-[PdCl2(L1)], is slightly

distorted square planar, with the aminophosphine moieties coordinated in a mutual

cis-fashion, in agreement with the spectroscopic data. The distortion is evident from

the bite angle P1-Pd1-P2 of 97°, which led to P1-Pd1-Cl1 and P1-Pd1-Cl2 angles of 83°

and 173°, respectively. The seven-membered chelate ring has a boat or open-envelope

conformation. Values found for the Pd-P, Pd-Cl and P-N bond lengths were within

30


the ranges reported for similar aminophosphine complexes.[3,19-21] The two P-N bond

lengths were 1.659 Å for P2-N2 and 1.681 Å for P1-N1. This is again a clear indication

of considerable double-bond character (via a π-interaction) between the P and N

atoms. The ethane backbone is severely twisted with a torsion angle N1-C1-C2-N2 of -

66°. Notably, the geometry around the nitrogen atoms N1 and N2 is trigonal planar,

with bond angles of between 116.0° and 125.8°. The intramolecular P1-P2 distance

was 3.38 Å while the N1-N2 distance was 3.09 Å.

Preparation of dichloroplatinum(II) complexes C3-C5.

Reaction of [PtCl2(cod)] with ligand L1 resulted in the straightforward formation of a

white solid, complex C3, (figure 5 (M = Pt, X = Cl)). Characterization of the species

present in solution by 31P NMR spectroscopy showed a single peak at δ 62.1 ppm,

flanked by 195Pt satellites and a coupling constant JPt-P of 4151 Hz. This latter value is

a clear indication of cis-coordination of the diphosphine to the platinum center,

yielding cis-[PtCl2(L1)].[22] The chemical shift is remarkably high for a diphosphine-

based cis-platinum complex and reflects the electronic influence of the amino-groups.

It is virtually similar to a silsesquioxane-based diphosphinite Pt-complex developed

previously in our group.[23] When the same reaction was performed with the more

flexible ligand L9 an off-white solid was obtained, C4, for which the 31P NMR

spectrum showed a singlet at 60.5 ppm, together with 195Pt satellites and a coupling

constant JPt-P of 4285 Hz, suggesting formation of cis-[PtCl2(L9)]. The clear

preference of these ligands to coordinate in the cis-geometry is also visible for most

crowded ligand L5, after its reaction with the metal precursor complex C5 was

obtained, the signals in the 31P NMR spectrum (δ 60.4, JPt-P = 4120 Hz) indicating that

the obtained material was indeed cis-[PtCl2(L5)].

Preparation of chlorocarbonylrhodium(I) complex C6.

Grimblot et al. have previously reported X-ray photoelectron and IR spectroscopy

studies on RhCl(CO)-complexes with various phosphine ligands, including

aminophosphines, and their correlation with the results obtained in rhodium-catalyzed

hydroformylation of 1-hexene.[24] Their initial studies on the influence of the

(amino)phosphine ligand on the CO stretching frequency in the corresponding Rh-

31


complex led to the conclusion that all tested ligands led to trans-complexes except for

dppe (bis(diphenylphosphino)ethane) as applied ligand.

Upon addition of ligand L1 to a CH2Cl2-solution of [RhCl(CO)2]2, the solution

immediately turned yellow. After two hours of reaction at room temperature, removal

of volatiles left a clear yellow microcrystalline solid, complex C6.

The 31P NMR spectrum for this complex showed a mixture of the cis and trans-

isomers in a ratio of 34:66 in favor of the trans-isomer. This trans-complex was

characterized by a doublet at δ 81.0 ppm, and a coupling constant of JRh-P 133 Hz,

which is a typical value for diphenylphosphine ligands. The cis-complex appeared as

a set of two doublets of doublets at δ 99.6 ppm and δ 75.3 ppm. The respective

coupling constants JRh-P were 180 Hz for the P trans to the Cl ligand and 133 Hz for

the P trans to the CO ligand, while the JP-P was 33 Hz. The related FT-IR-spectrum

showed an absorption band in the carbonyl region at νCO 1968 cm-1, which is in the

range found for complexes with σ-donor ligands at the Rh center.[25-27]

2.3 Conclusions

We showed the successful synthesis of a series of symmetrically substituted chiral

bisaminophosphine ligands following two modular routes applying easy purification

procedures. X-ray analyses indicated the trigonal planar geometry of the nitrogen

atoms, as well as a P-N bond with double bond character. A generally applicable

reaction scheme was designed and used for the construction of non-symmetrically

substituted chiral bisaminophosphine ligands. Coordination towards palladium,

platinum and rhodium precursors showed a preference for mononuclear cis-

coordination.

2.4 Perspective

More commercially available chiral amines could be incorporated in the

bisaminophosphine ligands, both the symmetrically as non-symmetrically substituted.

To increase rigidity the backbone could be derived from 1,2-dibromocyclohexane and

32


the sequential direct amination of 1,2-dibromobenzene with several amines would

open up a whole new class of fine-tunable ligands after condensation with

chlorophosphines (figure 7).

N

N

PPh2

PPh2

N

NPPh2

PPh2

Figure 7 Envisioned more rigid bisaminophosphine ligand classes.

2.5 Acknowledgements

Part of this work has been published, Eric J. Zijp, Jarl Ivar van der Vlugt, Duncan M.

Tooke, Anthony L. Spek and Dieter Vogt, Dalton Transactions, 2005, 512-517.

Avantium Technologies, National Research School Combination for Catalysis and the

Netherlands Organization for Scientific Research (NWO) are kindly acknowledged

for financial support. BASF A.G. is thanked for a kind gift of chiral amines and

Umicor Co. for a loan of precious metals. Bart van As and Roser Bartra Vallverdu

(Erasmus Exchange Program) supported the experimental work in this chapter during

their graduation work and research stage respectively, for which we are indebted.

2.6 Experimental Section

All manipulations were carried out under argon using standard Schlenk techniques.

Chemicals were purchased from Acros, Aldrich, Lancaster or VWR and used as

received or distilled from CaH2 before use. (R)-α-ethylbenzylamine, (R)-1-(4-

methoxyphenyl)ethylamine and (S)-(1-(1-naphthyl))-ethylamine were received as a

kind gift from BASF AG. Solvents were either taken HPLC-grade from an argon-

flushed column, packed with aluminum oxide, or distilled under argon prior to use

over an appropriate drying agent. NMR spectra were recorded at room temperature on

a Varian Mercury 400 MHz spectrometer. Chemical shifts are given in ppm and

spectra are referenced to CDCl3 (1H, 13C{1H}) or 85% H3PO4 (31P{1H}). FT-IR

33


34

spectra were taken on an AVATAR E.S.P. 360 FTIR spectrometer. PdCl2(cod),[28]

PdCl(CH3)(cod),[29] and PtCl2(cod)[30] were prepared according to literature

procedures.

N,N'-bis[(S)-α-methylbenzyl]-N,N'-bis-(diphenylphosphino)-ethane-1,2-diamine (L1):

N,N

N,N'-bis[(R)-α-methylbenzyl]-N,N'-bis-(diphenylphosphino)-ethane-1,2-diamine (L2):

,2-

diamine

'-bis[(S)-α-methylbenzyl]-ethane-1,2-diamine was

prepared by following a procedure by Mimoun et

al.[31] To a flask containing 4 equivalents of (S)-α-

methylbenzylamine (46.7 g, 385 mmol) at 130 °C was added dropwise 1,2-

dibromoethane (17.0 g, 91 mmol). After 1 h at elevated temperature the mixture was

cooled to 80 °C and a 4M aqueous solution of KOH (28.4 g, 506 mmol) was added.

After extraction of the mixture with ethylacetate and concentration, the mixture was

fractionally distilled at 2.5 mbar and N,N'-bis[(S)-α-methylbenzyl]-ethane-1,2-

diamine (18.3 g, 68 mmol) was obtained at 155 °C as a colorless oil in 75% yield.

Spectral properties were similar as described in literature.

L1 was prepared by adding N,N'-bis[(S)-α-methylbenzyl]-ethane-1,2-diamine (2.51 g,

9.45 mmol) dropwise to a mixture of triethylamine (2.5 g, 25 mmol) and

chlorodiphenylphosphine (4.22 g, 19.1 mmol) in diethylether. The produced

ammoniumsalts are removed from the suspension by filtration and the mixture is

concentrated, forming a white solid. After stripping with hexanes and recrystallization

from hot acetonitrile the analytically pure compound L1 (4.21 g, 6.61 mmol) was

obtained as a white semi-crystalline solid in 70% yield. Spectral properties were

similar as described in literature.[6c]

N,N'-bis[(R)-α-methylbenzyl]-ethane-1 was prepared by following the procedure

described for L1. Starting from R-α-

methylbenzylamine (43.2 g, 356 mmol) and 1,2-dibromoethane (16.7 g, 89 mmol)

N,N'-bis[(R)-α-methylbenzyl]-ethane-1,2-diamine (18.9 g, 70 mmol) was obtained at

155 °C as a colorless oil in 79% yield. Spectral properties were similar as described in

literature.

NN

PPh2 PPh2

NN

PPh2 PPh2


35

Compound L2 was prepared by following the procedure described for L1 starting

from N,N'-bis[(R)-α-methylbenzyl]-ethane-1,2-diamine (2.72 g, 10.1 mmol),

triethylamine (2.5 g, 25 mmol) and chlorodiphenylphosphine (4.47 g, 20.3 mmol). L2

(4.78 g, 7.51 mmol) was obtained as a white semi-crystalline solid in 74% yield.

Spectral properties were similar as described in literature.[7]

N,N'-bis[(R)-1-(4-methoxyphenyl)-ethylamine]-N,N'-bis-(diphenylphosphino)-ethane-

1,2-diamine (L3):

Following the procedure described for L1,

starting from (R)-1-(4-methoxy

phenyl)ethylamine (55.1 g, 364 mmol) and

1,2-dibromoethane (16.91 g, 90 mmol)

N,N'-bis[(R)-1-(4-methoxyphenyl)-ethyl]-ethane-1,2-diamine (28.14 g, 86 mmol) was

obtained in 95% yield after removal of all volatiles.

Starting from N,N'-bis[(R)-1-(4-methoxyphenyl)-ethyl]-ethane-1,2-diamine (3.14 g,

9.6 mmol), chlorodiphenylphosphine (4.29 g, 19.4 mmol) and triethylamine (2.5 g, 25

mmol), L3 (1.14 g, 1.67 mmol) was obtained as a white solid in 17% yield with

similar spectral properties as described elsewhere.[32]

N,N'-bis[(R)-α-ethylbenzyl]-N,N'-bis-(diphenylphosphino)-ethane-1,2-diamine (L4):

arting

ompound L4 was prepared by following the procedure described for L1 starting

Following the procedure described for L1, st

from (R)-α-ethylbenzylamine (53.49 g, 441 mmol)

and 1,2-dibromoethane (18.97 g, 101 mmol).

Distillation at 1.6 mbar at 174 °C afforded N,N'-bis[(R)-α-ethylbenzyl]-ethane-1,2-

diamine (19.31 g, 71.9 mmol) in 71% yield.

C

from N,N'-bis[(R)-α-ethylbenzyl]-ethane-1,2-diamine (2.91 g, 10.8 mmol),



NN

PPh2 PPh2

NN

PPh2 PPh2OMeMeO


36

NN

PPh2 PPh2

1H NMR (CDCl3) δ 6.8-7.4 (m, 30H, Ph), 3.43 (dt, 2H, CHCH2CH3, 3JP-H = 16.8 Hz,

, Ph), 140.5, 139.3 (2d, Ph, 1JP-C = 67 Hz), 132.3, 131.5

,N'-bis[(S)-(1-(1-naphthyl)-ethyl)]-N,N'-bis-(diphenylphosphino)-ethane-1,2-diamine

N'-bis[(S)-(1-(1-naphthyl)-ethyl)]-ethane-1,2-

dia

the diamine was obtained in 95% y

(CDCl3) δ 8.15 (m, 2H, Ph), 7.84 (m, 2H, Ph), 7.78 (d, 2H, 3JH-H = 8.1 Hz),

MR (CDCl3) δ 141.5, 134.0, 131.6, 129.2, 127.4, 126.0, 125.9, 125.6, 124.0,

ollowing the (modified) procedure for L1, starting from N,N'-bis[(S)-(1-(1-

3JH-H = 7.3 Hz), 2.63 (m, 4H, CH2N), 1.94 (m, 4H, CHCH2CH3), 0.73 (t, 6H,

CHCH2CH3, 3JH-H = 7.3 Hz). 13C NMR (CDCl3) δ 143.6 (s

(2d, Ph, 2JP-C = 21 Hz), 128.2, 128.1, 128.0, 128.0, 127.8, 127.7, 126.8 (7s, Ph), 67.1

(d, CHCH2CH3, 2JP-C = 24 Hz), 50.3 (d, CH2N, 2JP-C = 8 Hz), 28.5 (d, CHCH2CH3, 2JP-C = 18 Hz), 12.0 (CHCH2CH3). 31P NMR (CDCl3) δ 45.6.

N

(L5):

N,

mine was prepared following the procedure for

L1, starting from (S)-(1-(1-naphthyl))-ethylamine

(15.1 g, 88 mmol) and 1,2-dibromoethane (8.3 g,

44 mmol). After removal of the access of amine

ield as a brownish syrup (15.47 g, 42 mmol) which

solidified upon standing.

1H NMR

7.67 (d, 2H, Ph, 3JH-H = 7.5 Hz), 7.45-7.55 (m, 8H, Ph), 4.53 (q, 2H, CHCH3, 3JH-H =

6.6 Hz), 2.68 (s, 4H, CH2CH2), 2.02 (bs, 2H, NH), 1.53 (d, 6H, CHCH3, 3JH-H = 6.6

Hz). 13C N

123.2 (10s, Ph), 53.9 (CHCH3), 47.7 (CH2NH), 24.0 (CHCH3).

F

naphthyl)ethyl)]-ethane-1,2-diamine (1.95 g, 5.3 mmol) in 20 mL toluene,

chlorodiphenylphosphine (2.38 g, 10.8 mmol) and 2 mL triethylamine (1.45 g, 14.3

mmol) in 30 mL toluene and a reaction overnight at 80 °C, L5 was obtained as a

white powder (2.33 g, 3.2 mmol) in 60% yield.


37

1H NMR (CDCl3) δ 7.85 (m, 4H, Ph), 7.65 (m, 2H, Ph), 7.47 (m, 2H, Ph), 7.36 (m,

2H, Ph), 7.08-7.30 (m, 20 H, Ph), 6.96 (m, 4H, Ph), 4.72 (dq, 2H, CHCH3, 3JP-H = 13

Hz; 3JH-H = 6.6 Hz), 2.69 (s, 4H, CH2CH2), 1.42 (d, 6H, CHCH3, 3JH-H = 6.6 Hz). 13C NMR (CDCl3) δ 140.4 (s, Ph), 140.4, 139.6 (dd, Ph, 1JP-C = 85 Hz), 134.1, 132.4

(dd, Ph, 1JP-C = 85 Hz), 132.4 (d, Ph, 2JP-C = 40 Hz), 131.6, 128.9, 128.4 (3s, Ph),

128.1, 128.0 (2d, Ph, 3JP-C = 6 Hz), 127.8, 125.8, 125.5, 125.3, 124.6, 56.6 (d,

CHCH3, 2JP-C = 31 Hz), 49.9 (d, CH2N, 2JP-C = 9 Hz), 21.0 (d, CHCH3, 3JP-C = 10 Hz). 31P NMR (CDCl3) δ 55.9.

N,N'-bis[(S)-(1-cyclohexylethyl)]-N,N ine (L6): 4] a

o a solution of the diimine (1.79 g, 6.5 mmol) in 25 mL diethylether was added in

(CDCl3) δ 2.83 (dq, 2H, CHCH3, 3JH-H = 5.4 Hz), 2.64 (m, 2H, CH2NH),

3), 47.1 (CH2NH), 42.8, 29.9, 28.2, 26.8, 26.6, 26.5

re described for L1 starting from N,N'-bis[(S)-(1-

'-bis-(diphenylphosphino)-ethane-1,2-diam

Following a procedure of Weber et al. [3

solution of (S)-(1-cyclohexyl)ethylamine (12.1 g,

95 mmol) in 50 mL hexanes was added to a 40

wt% aqueous solution of glyoxal (47 mmol). After 30 minutes of reaction the phases

were separated and the water layer was extracted with hexanes. After drying over

MgSO4, concentration in vacuo afforded the corresponding diimine as a white powder

(12.3 g, 44 mmol, 95%) with similar spectral properties as described in literature and

which was used without any purification.

T

portions LiAlH4 (1.05 g, 27.7 mmol). After one hour the excess of LiAlH4 was

neutralized by carefully adding water. After drying over MgSO4, extraction with

diethylether and concentration the corresponding diamine was obtained in quantitative

yield as a colorless mobile oil (1.82 g, 6.5 mmol).

1H NMR

2.46 (m, 2H, CH2NH), 2.04 (bs, 2H, NH), 1.73 (m, 10H, Cy), 1.20 (m, 12H, Cy), 1.06

(d, 6H, CHCH3, 3JH-H = 5.4 Hz). 13C NMR (CDCl3) δ 58.0 (CHCH

(6s, Cy), 16.9 (CHCH3).

Following the procedu

cyclohexylethyl)]-ethane-1,2-diamine (1.03 g, 3.67 mmol), chlorodiphenylphosphine

(1.65 g, 7.48 mmol) and triethylamine (1.5 mL, 10.7 mmol) the analytically pure

NN

PPh2 PPh2


38

compound L6 (1.98 g, 3.05 mmol) was obtained as a white semi-crystalline solid in

83% yield.

1H NMR (CDCl3) δ 7.12-7.22 (10H, PPh2), 2.64 (dm, 4H, CH2N, 3JP-H = 36.2 Hz),

.0 (2d, Ph, 2JP-C

2: C, 77.75; H, 8.39; N, 4.32. Found: C, 77.53; H, 8.53; N,

,N'-bis[(R)-(1,2,3,4-tetrahydro-1-naphthylamine)]-N,N'-bis-(diphenylphosphino)-

ed procedure described for L6

fi

(CDCl3) δ 7.3-7.2 (m, 28H, Ph), 4.04 (m, 2H, CH), 2.81 (m, 4H), 2.64 (m,

NNPPh2PPh2

2.23 (m, 2H, CHCH3), 1.89 (m, 2H, Cy), 1.68 (m, 8H, Cy), 1.50 (m, 2H, Cy), 1.17

(m, 6H, Cy), 1.06 (d, 6H, CHCH3, 3JH-H = 6.3 Hz), 0.75 (m, 4H, Cy). 13C NMR (CDCl3) δ 140.7, 140.5 (2d, Ph, 1JP-C = 48 Hz), 132.4, 132

= 21 Hz), 128.0 (d, Ph, 4JP-C = 4 Hz), 127.9 (d, Ph, 3JP-C = 6 Hz), 61.8 (d, CHCH3, 2JP-

C = 26 Hz), 49.3 (d, CH2N, 2JP-C = 26 Hz), 42.8 (d, CHCHCH3, 3JP-C = 10 Hz), 31.2,

30.0, 26.4, 26.2, 26.0 (5s, Cy), 19.2 (d, CHCH3, 3JP-C = 11 Hz). 31P NMR (CDCl3) δ 46.0.

Anal. Calcd. for C42H54N2P

4.24.

N

ethane-1,2-diamine (7)

Following the modifi

compound L7 was prepared starting from (R)-1,2,3,4-

tetrahydro-1-naphthylamine (9.1 g, 62 mmol), aqueous

40% glyoxal (3.5 mL, 31 mmol) the intermediate

ltration and washing as an off-white solid in 87% yield

(8.5 g, 27 mmol) which was used without purification. Lithiumaluminiumhydride (2.2

g, 58 mmol) was added in portions to a solution of diimine (8.2 g, 26 mmol) in

diethylether. After neutralization with water and extraction with diethylether the

intermediate crude diamine was obtained. Chlorodiphenylphosphine (2.3 mL, 12.8

mmol) was added to a solution of the diamine (2.02 g, 6.3 mmol) in diethylether

containing triethylamine (2 mL, 14.3 mmol). Usual workup afforded L7 in 78% yield

(3.38 g, 4.9 mmol). Clear rectangular crystals suitable for X-ray analysis were

prepared by crystallization from dichloromethane/hexanes (1/3).

diimine was obtained after

1H NMR

4H) 1.76 (m, 4H), 1.56 (m, 4H).


13C NMR (CDCl3) δ 140.2, 139.9, 139.3, 137.9, 132.1 (d, Ph, 3JP-H = 10 Hz), 128.7,

128.2, 127.9 (d, Ph, 4JP-H = 5.7 Hz), 126.3, 125.3, 60.5 (d, CHN, 2JP-C = 21 Hz), 49.2

(d, CH2N, 2JP-C = 8 Hz), 30.3, 29.5, 21.6. 31P NMR (CDCl3) δ 55.6.

N,N'-bis[(R)-α-methylbenzyl]-N,N'-bis-(diphenylphosphino)-propane-1,3-diamine (L8)

N,N'-bis[(R)-α-methylbenzyl]-propane-1,3-

diamine was prepared by following the

procedure described for L1. Starting from R-

α-methylbenzylamine (57.14 g, 423 mmol) and 1,3-dibromopropane (18.17 g, 97

mmol) N,N'-bis[(R)-α-methylbenzyl]-propane-1,3-diamine (19.06 g, 64 mmol) was

obtained at 151 °C (2.2 mbar) as a colorless oil in 66% yield.[33]

N N

PPh2PPh2

1H NMR (CDCl3) δ 7.3-7.2 (m, 10H, Ph), 3.72 (q, 2H, CHCH3, 3JH-H = 6.6 Hz), 2.51

(m, 4H, CH2CH2CH2), 1.61 (m, 2H, CH2CH2CH2), 1.54 (bs, 2H. NH), 1.34 (d, 6H,

CHCH3, 3JH-H = 6.6 Hz). 13C NMR (CDCl3) δ 146.1, 128.6, 127.0, 126.8 (4s, Ph), 58.7 (CHCH3), 47.7

(CH2NH), 30.6 (CH2CH2CH2) 24.0 (CHCH3).

Compound L8 was prepared by following the procedure described for L1 starting

from N,N'-bis[(R)-α-methylbenzyl]-propane-1,3-diamine (2.53 g, 8.96 mmol),



1H NMR (CDCl3) δ 7.3-7.2 (m, 16H, Ph), 7.04 (m, 4H, Ph), 3.93 (dq, 2H, CH), 2.41

(m, 4H, CH2CH2CH2), 1.51 (m, 6H, CHCH3), 0.82 (m, 2H, CH2CH2CH2).

13C NMR (CDCl3) δ 144.8, 140.0 (dd, Ph, 2JP-C = 14 Hz), 132.5 (dd, Ph, 2JP-C = 20

Hz), 128.2, 128.1, 127.9, 127.8, 127.8, 127.4 (d, Ph, 3JP-C = 2 Hz), 126.8, 59.1 (d,

CHCH3, 2JP-C = 26 Hz), 47.1 (d, CH2N, 2JP-C = 8 Hz), 29.2 (CH2CH2CH2), 21.8 (d,

CH2N, 2JP-C = 18 Hz, CHCH3). 31P NMR (CDCl3) δ 48.0.

39


N,N'-bis[(R)-α-ethylbenzyl]-N,N'-bis-(diphenylphosphino)-propane-1,3-diamine (L9):

Following the procedure described for L1,

starting from (R)-α-ethylbenzylamine (49.07

g, 363 mmol) and 1,3-dibromopropane (17.35

g, 86 mmol). Distillation at 1.5 mbar at 165

°C afforded N,N'-bis[(R)-α-ethylbenzyl]-propane-1,3-diamine (16.33 g, 53 mmol) in

61% yield.[31]

N N

PPh2PPh2

1H NMR (CDCl3) δ 7.2-7.4 (10H, Ph), 3.43 (t, 2H, CHCH2CH3, 3JH-H = 6.2 Hz), 2.49

(m, 4H, CH2NH), 1.55-1.80 (m, 8H, CH2CH2CH2; CHCH2CH3; NH), 0.79 (t, 6H,

CHCH2CH3, 3JH-H = 7.3 Hz). 13C NMR (CDCl3) δ 144.4, 128.5, 127.5, 127.1 (4s, Ph), 65.5 (CHCH2CH3), 46.8

(CH2NH), 31.2 (CHCH2CH3), 30.4 (CH2CH2NH), 11.1 (CHCH2CH3).

Starting from N,N'-bis[(R)-α-ethylbenzyl]-propane-1,3-diamine (2.64 g, 8.5 mmol),

chlorodiphenylphosphine (3.83 g, 17.4 mmol) and triethylamine (2.4 g, 24 mmol),

compound L9 (5.14 g, 7.57 mmol) was obtained as a white solid in 89% yield.

1H NMR (CDCl3) δ 7.40-7.34 (m, 10H, Ph), 7.28-7.14 (m, 16H, Ph), 6.91-6.85 (m,

4H, Ph), 3.43 (dt, 2H, CHCH2CH3, 3JP-H = 16.1 Hz, 3JH-H = 6.2 Hz), 2.40 (m, 4H,

CH2N), 2.20 (m, 4H, CHCH2CH3), 0.81 (t, 6H, CHCH2CH3, 3JH-H = 7.7 Hz), 0.72 (m,

2H, CH2CH2CH2). 13C NMR (CDCl3) δ 143.4 (s, Ph), 140.1, 139.9 (2d, Ph, 1JP-C = 67 Hz), 132.6, 131.5

(2d, Ph, 2JP-C = 21 Hz), 128.3, 128.0, 128.0, 127.7, 127.6, 127.5, 126.8 (7s, Ph), 66.3

(d, CHCH2CH3, 2JP-C = 26 Hz), 47.2 (d, CH2N, 2JP-C = 11 Hz), 28.5 (CHCH2CH3),

28.2 (CH2CH2CH2), 11.8 (CHCH2CH3). 31P NMR (CDCl3) δ 45.8.

Anal. Calcd. for C45H48N2P2: C, 79.62; H, 7.13; N, 4.13. Found: C, 79.30; H, 7.09; N,

4.03.

40


41

N,N'-bis[(R)-(α)-methylbenzylamine)-diaminodimethylsilane (1)

(R)-α-methylbenzylamine (18.8 g, 155 mmol) was

added to a solution of dichlorodimethylsilane (9.43

mL, 78 mmol) and triethylamine (21.5 mL, 155

mmol) in diethylether. After removal of the ammoniumsalts by filtration,

concentration and distillation at 180°C and 1.5 mbar 1 was obtained as a clear liquid

in 89 % yield (20.6 g, 69 mmol).

1H NMR (CDCl3) δ 7.16-7.30 (m, 10H, Ph), 4.08 (m, 2H, CHCH3, 3JH-H = 6.6 Hz),

1.35 (d, 6H, CHCH3, 3JH-H = 6.6 Hz), 0.96 (bm, 2H, NH), -0.08 (s, 6H, (Si(CH3)2), 1JSi-H = 3.3 Hz). 13C NMR (CDCl3) δ 149.6, 128.3, 126.3, 126.0 (4s, Ph), 51.0 (CHCH3), 28.1

(CHCH3), -0.4 (Si(CH3)2).

Attempted synthesis of N,N'-bis[(R)-(α)-methylbenzylamine)-N,N'-bis-

(diphenylphosphino)diaminodimethylsilane (2)

Following the procedure of L1 starting from N,N'-

zylamine)-diaminodimethylsilane

1 (1.77 g, 5.9 mmol), chlorodiphenylphosphine (2.65,

12.0 mmol) and triethylamine (2.5 mL, 18.0 mmol) in

diethylether (25 mL). No immediate reaction occurred, after 48 h at reflux

temperature ammoniumsalts were filtered off and crude 31P NMR showed full

conversion of the chlorodiphenylphosphine. After workup and recrystallization from

boiling acetonitrile diazaphosphane N,N-bis-(diphenylphosphino)-(R)-(α)-

methylbenzylamine 3 was obtained in 39% yield (calculated from N,N'-bis[(R)-(α)-

methylbenzylamine)-diaminodimethylsilane 1) as a white crystalline powder (1.13 g,

2.31 mmol) with similar spectral properties as described in literature.[33]

bis[(R)-(α)-methylben

,N'-bis[(R)-α-ethylbenzyl]-N,N'-bis-(diphenylphosphino)-ethane-1,2-diamine oxide (4): N

L4 (100 mg, 151 μmol) was dissolved in 5 mL THF

and an excess of 30% H2O2 (aq) was added. The

mixture was vigorously stirred for 16 h at room

temperature. After removal of the THF in vacuo the

NN

PPh2 PPh2O O

NHNH

Si

NN

Si

PPh2 PPh2


42

aqueous mixture was extracted with CH2Cl2 and after drying over MgSO4 4 was

obtained as a white solid. Yield: 89% (94.1 mg, 134 μmol).

31P NMR (CDCl3) δ 33.5.

,N'-bis[(S)-α-methylbenzyl]-N,N'-bis-(diphenylphosphino)-ethane-1,2-diamine

L1 (85.9 mg, 135 μmol) was dissolved in 5 mL

).

.33; P, 3.53. Found: C, 63.55; H, 5.41;

,N'-bis[(R)-α-ethylbenzyl]-N,N'-bis-(diphenylphosphino)-propane-1,3-diamine selenide

Following the same procedure as for compound

P NMR (CH2Cl2) δ 69.1 (s, JSe-P = 750 Hz).

.78; P, 3.35. Found: C, 64.74; H, 5.82;

-((R)-α-methylbenzyl)-2-aminoethanol (7)

g, 81 mmol) was added dropwise to

c

NOH

H

N

selenide (5):

toluene and excess black selenium was added. The

reaction mixture was stirred for 30 minutes at 70 °C.

Filtration to remove unreacted selenium by cannula

the filtrate to dryness, leaving 5 as a white solid.

Yield: 95% (101.8 mg, 128.2 μmol). 31P NMR (CH2Cl2) δ 70.3 (s, JSe-P = 752 Hz

was followed by evaporation of

Anal. Calcd. for C42H42N2P2Se2: C, 63.48; H, 5

P, 3.58.

N

(6):

5, ligand L9 (92.1 mg, 136 μmol) was converted

to selenide 6 in a yield of 98% (111.3 mg, 133.0

μmol).

31

Anal. Calcd. for C45H48N2P2Se2: C, 64.59; H, 5

P, 3.38.

N

2-Chloroethanol (6.5

(R)-α-methylbenzylamine (24.6 g, 203 mmol) at 100°C.

After cooling to 80°C aqueous 4M KOH was added and the

ted with CH2Cl2. After washing with water the excess (R)-α-organic phase was extra

NN

PPh2 PPh2Se Se

N N

PPh2PPh2Se Se


43

methylbenzylamine could be recovered by distillation and 7 was obtained as an clear

oil in 76% yield (10.16 g, 61 mmol).

1H NMR (CDCl3) δ 7.2-7.4 (m, 5H, Ph), 3.77 (q, 1H, CHCH3, 3JH-H = 6.6 Hz), 3.58

l3) δ 145.3, 128.5, 127.0, 126.5 (4s, Ph), 61.2 (CH2OH), 58.1

-(2-chloroethyl)-(R)-α-methylbenzylamine hydrochloride (8)

ol 7 (3.3 g, 20 mmol) in

precipitated, after filtrat

(D2O) δ 7.37 (m, 5H, Ph), 4.37 (q, 1H, CHCH3, 3JH-H = 6.9 Hz), 3.66 (m, 3

CH3),

-(benzyl)-N’-((R)-α-methylbenzyl)-N,N'-bis-(diphenylphosphino)-ethane-1,2-diamine

To N-(2-chloroethyl)-α-methylbenzylamine hydro

ents benzylamine (3 mL, 27 mmol) and the

nt

1 starting from crude N-(benzyl)-N’-(R)-α-

ethylbenzyl-ethane-1,2-diamine (0.76 g, 2.99 mmol), chlorodiphenylphosphine

(m, 2H, CH2OH) 2.62 (m, 2H, CH2N), 2.28 (bs, 2H, NH / OH), 1.37 (d, 3H, CHCH3, 3JH-H = 6.6 Hz). 13C NMR (CDC

(CHCH3), 49.0 (NHCH2), 24.1 (CHCH3).

N

N-((R)-1-methylbenzyl)-2-aminoethan

50 mL chloroform was reacted with 3 equivalents thionyl

chloride (7.5 g, 63 mmol) and the mixture was refluxed for 2

h. After cooling to room temperature a white solid

ion and washing with diethylether 8 was obtained as a white

solid in 85% yield (3.7 g, 17 mmol). 1H NMR

2H, CH2Cl), 3.00-3.15 (m, 2H, NHCH2), 1.57 (d, 3H, CHCH3, JH-H = 6.9 Hz). 13C NMR (D2O) δ 137.7, 132.2, 131.8, 130.0 (4s, Ph), 61.0 (NHCH2), 49.3 (CH

41.5 (CH2Cl), 20.6 (CHCH3).

N

(L10)

chloride 8 (1.80 g, 8.2 mmol) was added 3

equival

mixture was heated to 175 °C u il it became homogeneous. After treatment with

aqueous 45% KOH and removal of the excess of benzylamine in vacuo the crude

diamine was obtained in 68% yield (1.42 g, 5.6 mmol) which was used as such.

Following the procedure for L

m

NCl

H HCl

N

PPh2

N

PPh2


44

(1.41 g, 6.39 mmol) and triethylamine (1 mL, 7.5 mmol) L10 was obtained as a white

solid in 89% yield (1.66 g, 2.66 mmol).

1H NMR (CDCl3) δ 6.95-7.4 (m, 30H, Ph), 4.01 (dq, 1H, CHCH3, 3JH-H = 7.0 Hz),

.90 (dd, 2H, PhCH2N, 3JP-H = 7.7 Hz, 2JH-H = 1.9 Hz), 2.6-2.9 (m, 4H, CH2CH2), 1.57

lphosphino)-ethane-

,2-diamine (L11)

l-

benzylamine hydrochloride 8 (1.2 g, 5.5 mmol) in

6

and additional (R)-α-ethylbenzyl

4.3 mmol), chlorodiphenylphosphine

), 3.48 (dq, 1H, CHCH3, 3JH-H = 7.0 Hz), 3.35

t, 1H, CHCH2CH3, 3JH-H = 7.3 Hz), 2.4-2.8 (m, 4H, CH2CH2), 1.95 (m, 2H,

o)-ethane-

-

chloroethyl)-(R)-α-methylbenzylamine hydrochloride

N

PPh2PPh2

3

(d, 3H, CHCH3, 3JH-H = 7.0 Hz). 31P NMR (CDCl3) δ 64.6 (benzyl), 48.9 ((R)-α-methylbenzyl)

N-((R)-α-ethylbenzyl)-N’-((R)-α-methylbenzyl)-N,N'-bis-(dipheny

1

To a solution of N-(2-chloroethyl)-(R)-α-methy

N

20 mL DME at 80 °C was added 3 equivalents (R)-

mmol). The precipitated white solid was filtered off

amine (4 mL, 26 mmol) was added. After treatment

with aqueous 45% KOH, extraction with dichloromethane and removal of the excess

of (R)-α-ethylbenzylamine in vacuo the crude diamine was obtained in 79% yield

(1.22 g, 4.3 mmol) which was used as such.[35]

Following the procedure for L1 starting from crude N-((R)-α-methylbenzyl)-N’-(R)-

α-methylbenzyl-ethane-1,2-diamine (1.22 g,

α-ethylbenzylamine (1.84 g, 13.

(1.89 g, 8.6 mmol) and triethylamine (1 mL, 7.5 mmol) L11 was obtained as a white

solid in 69% yield (1.93 g, 2.97 mmol).

1H NMR (CDCl3) δ 6.8-7.4 (m, 30H, Ph

(d

CHCH2CH3), 1.35 (d, 3H, CHCH3, 3JH-H = 7.0 Hz), 0.70 (t, 3H, CHCH2CH3, 3JH-H =

7.3 Hz). 31P NMR (CDCl3) δ 47.8 ((R)-α-methylbenzyl), 45.1 ((R)-α-ethylbenzyl)

N-((R)-α-methylbenzyl)-N’-((S)-α-methylbenzyl)-N,N'-bis-(diphenylphosphin

1,2-diamine (L12)

Following the procedure for L10, starting from N-(2NN

PPh2PPh2


45

(1.59 g, 7.30 mmol) and (S)-α

reaction of the crude intermediate diam

chlorodiphenylphosphine (1.58

PdCl2(cod) (32.9 mg, 115.2 μmol) and L1 (73.4 mg,

115.3 μmol) were dissolved in 5 mL CH2Cl2 and

ours at ambient temperature.

w

to leave complex C1 as a pure

Layering with CH2Cl2/CH3CN un

7.55 (t, 1H, Ph, 3JH-H = 6.8 Hz), 7.49 (d, 1H, Ph,

H-H = 5.6 Hz), 7.41 (t, 6H, Ph, 3JH-H = 7.2 Hz), 7.30 (d, 6H, Ph, 3JH-H = 7.6 Hz), 6.99

Following the same procedure as for complex C1,

but starting from PdCl(CH3)(cod) (10.5 mg, 39.6

μmol) and L1 (27.2 mg, 42.7 μmol), complex C2

NN

PPh2PPh2

PdCl Cl

-methylbenzylamine (3.80 g, 31.3 mmol) gave after

ine (0.97 g, 3.59 mmol) with

g, 7.20 mmol) in the presence of triethylamine (1.82

g, 17.9 mmol) L12 as a white solid in 67% yield (1.53 g, 2.41 mmol) with the same

spectral properties as the intermediate diamine for L1.

cis-[PdCl2(L1)] C1

stirred for 12 h

Solvents were then evaporated in vacuo. After that

ere removed by stripping 2 times with 5 mL CH2Cl2

yellow solid in 96% yield (90.1 mg, 110.6 μmol).

der slight argon flow gave yellow rectangular single

crystals, suitable for X-ray analysis.

1H NMR (CDCl3) δ 7.99 (pq, 2H, Ph, 4JH-H = 4.0 Hz, 3JH-H = 11.2 Hz), 7.70 (pq, 2H,

Ph, 4JH-H = 4.0 Hz, 3JH-H = 11.2 Hz),

the remaining traces of solvent

3J

(t, 4H, Ph, 3JH-H = 7.2 Hz), 6.90 (dd, 4H, Ph, 3JH-H = 7.6 Hz, 4JH-H = 1.2 Hz), 4.27 (m,

2H, CH), 3.59 (pq, 2H, CH2, 3JH-H = 6.8 Hz, 3JH-H = 11.2 Hz), 3.05 (pq, 2H, CH2, 4JH-

H = 4.0 Hz, 3JH-H = 11.2 Hz), 0.82 (d, 6H, CH3, 3JH-H = 6.8 Hz). 31P NMR (CDCl3) δ 87.3 (s).

Anal. Calcd. for C42H42Cl2N2P2Pd: C, 61.97; H, 5.20; N, 3.44. Found: C, 62.03; H,

5.24; N, 3.48.

cis-[PdCl(CH3)(L1)] C2

was obtained as a pure yellow solid. Yield: 94%

(29.6 mg, 37.2 μmol).

NN

PdCl Me

PPh2PPh2


46

1H NMR (CDCl3) δ 7.87 (dt, 2H, Ph, 3JH-H = 8.8 Hz, 4JH-H = 1.6 Hz), 7.83 (m, 2H,

h), 7.63 (ddd, 2H, Ph, 3JH-H = 11.2 Hz, 4JH-H = 1.2 Hz), 7.54 (ddd, 2H, Ph, 3JH-H =

3

PtCl2(cod) (36.3 mg, 97.0 μmol) and L1 (66.3

ere dissolved in 5 mL CH2Cl2

n

as a white powder. Yield: 92% (80.6

(dd, 4H, 3JH-H = 8.0 Hz), 7.49

, 4H), 7.40 (m, 6H), 7.42 (t, 8H, 3JH-H = 6.8 Hz), 7.32 (t, 6H, 3JH-H = 6.8 Hz), 6.90

(L9) C4

Following the same procedure as for complex

and L9 (75.0 mg, 110.5 μmol)

NN

PPh2PPh2

PtCl Cl

P

11.2 Hz, 4JH-H = 1.2 Hz), 7.45 (d, 5H, Ph, 4JH-H = 2.0 Hz), 7.35 (d, 5H, Ph, J1 = 7.6

Hz), 7.32 (m, 2H, Ph), 7.28 (m, 2H, Ph), 7.22 (dd, 4H, Ph, 3JH-H = 9.2 Hz, 4JH-H = 2.0

Hz), 7.16 (dd, 2H, Ph, 3JH-H = 7.2 Hz, 4JH-H = 2.8 Hz), 6.73 (dd, 2H, Ph, 3JH-H = 8.0

Hz, 4JH-H = 1.6 Hz), 4.41 (t, 2H, CH2), 4.26 (t, 2H, CH2), 3.35 (m, 2H, CH), 1.01 (d,

3H, CH3, 3JH-H = 7.6 Hz), 0.73 (d, 3H, CH3, 3JH-H = 6.8 Hz), 0.47 (dd, 3H, Pd(CH3), 3JH-H = 7.6 Hz, 3JH-H = 4.4 Hz). 31P NMR (CDCl3) δ 91.3 (d, JP-P = 28 Hz, P trans to Cl), 81.0 (d, JP-P = 28 Hz, P

trans to CH3).

cis-[PtCl2(L1)] C

mg, 104.1 μmol) w

and stirred for 2 hours at r.t. Then the solvent was

removed in vacuo. After that the remaining traces

g 2 times with 5 mL hexanes to leave complex C3

mg, 89.3 μmol).

1H NMR (CDCl3) δ 7.99 (dd, 4H, 3JH-H = 8.0 Hz), 7.73

of solvent were removed by strippi

(m

(dd, 4H, 3JH-H = 7.6 Hz, 4JH-H = 1.2 Hz), 4.29 (t, 2H, CH, 3JH-H = 7.2 Hz), 3.60 (dt, 4H,

CH2, 3JH-H = 14.4 Hz, 4JH-H = 2.8 Hz), 3.01 (t, 4H, CH2, 4JH-H = 13.6 Hz), 0.80 (d, 6H,

CH3, 3JH-H = 6.8 Hz). 31P NMR (CDCl3) δ 62.1 (s, JPt-P = 4151 Hz).

cis-PtCl2

C3, but using lig

and PtCl2(cod) (35.3 mg, 94.3 μmol) complex

C4 was obtained in a yield of 95% (84.7 mg,

89.6 μmol).

NN

PPh2PPh2

PtCl Cl


47

1H NMR (CDCl3) δ 8.24 (pq, 4H, 4JH-H = 4.4 Hz, 3JH-H = 6.8 Hz), 7.96 (pq, 4H, 4JH-H

4.4 Hz, 3JH-H = 6.8 Hz), 7.51 (t, 14H, 3JH-H = 7.2 Hz), 7.26 (t, 4H, 3JH-H = 2.4 Hz),

Following the same procedure as for complex C3,

d L5 (17 mg, 23 μmol) and

[Rh(μ-Cl)(CO)2]2 (56.9 mg,

146.3 μmol) and L1 (186.4 mg,

6

microcrystalline solid.

.6 (dd, cis, P trans to Cl, JRh-P = 180 Hz, JP-P = 33 Hz), 81.0 (d,

ans, JRh-P = 133 Hz), 75.3 (dd, cis, P trans to CO, JRh-P = 133 Hz, JP-P = 33 Hz)

3; H,

NN

PPh2PPh2

PtCl Cl

=

6.99 (t, 4H, 3JH-H = 3.6 Hz), 3.83 (t, 2H, NCH, 3JH-H = 8.4 Hz), 3.00 (m, NCH2), 2.67

(m, 2H, NCH2), 1.76 (m, 2H, CH2CH2CH2), 1.35 (m, 4H, CH2CH3), 0.30 (t, 6H, CH3, 3JH-H = 7.6 Hz). 31P NMR (CDCl3) δ 60.5 (s, JPt-P = 4285 Hz).

cis-PtCl2(L5) C5

but using ligan

PtCl2(cod) (8 mg, 21 μmol) complex C5 was

obtained as a white solid.

= 4120 Hz).

31P NMR (CDCl3) δ 60.4 (s, JPt-P

[Rh(Cl)(CO)(L1)] C6

292.7 μmol) were stirred in 10

mL of CH2Cl2 for 16 hours,

giving a light yellow solution.

was obtained as a bright-yellow

31P NMR (CDCl3) δ 99

After removal of the solvent in vacuo, complex C

tr

FTIR (ATR mode, solid, cm-1): ν 1967.5 (Rh(CO)).

Anal. Calcd. for C43H42ClN2OP2Rh: C, 64.31; H, 5.27; P, 3.49. Found: C, 64.1

5.37; P, 3.55.

NN

PPh2PPh2

RhCl CO

RhP CO

PCl


Crystal structure determinations

Intensity data for the molecular structures L6, L7, 5 and C1 were collected using

graphite-monochromated Mo-Kα radiation, on a Nonius Kappa CCD diffractometer

(see Table 6 for experimental details). An semi-empirical absorption correction based

on multiple measurements was applied using SADABS.[37a] The structure was solved

by automated Patterson methods using DIRDIF,[37b] and refined on F2 using

SHELXL97.[37c] Structure validation and molecular graphics preparation were

performed with the PLATON package.[38]

Table 6: Selected crystallographic data for molecular structures L6, L7, 5 and C1.

L6 L7 5 C1 formula C42H54N2P2 C46H46N2P2 C44H46N2O2P2 C42H42Cl2N2P2Pd FW (g mol-1) 648.81 688.79 696.77 814.04 crystal system triclinic monoclinic triclinic monoclinic space group P1 (no. 1) P21 (no. 4) P1 (no. 2) P21 (no. 4) a (Å) 8.6982(3) 15.2158(14) 11.5759(9) 11.3330(10) b (Å) 10.0730(6) 8.1986(4) 12.0731(10) 26.0777(10) c (Å) 11.6643(7) 15.7910(13) 16.6081(11) 12.6339(10) α (º) 69.066(4) 90 93.340(7) 90 β (º) 79.067(3) 103.775(7) 109.111(7) 92.7710(10) γ (º) 74.770(5) 90 117.831(6) 90 V (Å3) 915.79 1913.2 1876.6(3) 3729.4(5) Z 1 1 2 4 dcalc (g cm-3) 1.176 1.196 1.233 1.450 μ (Mo-Kα) (mm-1) 0.150 0.148 0.155 0.760 F(000) 350 732 740 1672 crystal size (mm) 0.20x0.2x0.3 0.24x0.30x0.48 - - T (K) 150 150 150 150 total reflections 23754 54708 - - unique reflections 7213 8737 - - R(nt) 0.029 0.029 - - wR2 (F2) 0.0782 0.1202 - - λ (Å) 0.71073 0.71073 0.71073 0.71073 R1 (F) 0.0317 0.0456 - -

48


2.7 References [1] C. A. Bessel, P. Aggarwal, A. C. Marschilok, K. J. Takeuchi, Chem. Rev. 2001, 101, 1031. [2] For a recent review on chiral phosphorus ligands, see: W. Tang, X. Zhang, Chem. Rev. 2003,

103, 3029. [3] a) M. Rodriguez i Zubiri, M. L. Clarke, D. F. Foster, D. J. Cole-Hamilton, A. M. Z. Slawin, J.

Woollins, J. Chem. Soc., Dalton Trans. 2001, 969; b) A. M. Z. Slawin, M. Wainwright, J. D.

Woollins, J. Chem. Soc., Dalton Trans. 2002, 513. [4] a) M. S. Balakrishna, V. Sreenivasa Reddy, S. S. Krishnamurthy, J. F. Nixon, J. C. T. R.

Burckett St. Laurent, Coord. Chem. Rev. 1994, 129, 1 and references therein; b) M. S.

Balakrishna, M. G. Walawalker, J. Organomet. Chem. 2001, 628, 76. [5] M. P. Magee, H.-Q. Li, O. Morgan, W. H. Hersh, Dalton Trans. 2003, 387. [6] a) M. Fiorini, G. M. Giongo, F. Marcati, W. Marconi, J. Mol. Cat. 1976, 1, 451; b) M. Fiorini,

F. Marcati, G. M. Giongo, J. Mol. Cat. 1977/78, 3, 385; c) M. Fiorini, F. Marcati, G. M.

Giongo, J. Mol. Cat. 1978, 4, 125; d) M. Fiorini, G. M. Giongo, J. Mol. Cat. 1979, 5, 303. [7] G. Pracejus, H. Pracejus, Tetrahedron Lett. 1977, 39, 3497. [8] K. Kashiwabara, K. Hanaki, J. Fujita, Bull. Chem. Soc. Jpn. 1980, 53, 2275. [9] R. Guo, X. Li, J. Wu, W. H. Kwok, J. Chen. M. C .K. Choi, A. S. C. Chan, Tetrahedron Lett.

2002, 43, 6803. [10] a) S. Breeden, M. Wills, J. Org. Chem. 1999, 64, 9735; b) S. Breeden, D. J. Cole-Hamilton, D.

F. Foster, G. J. Schwarz, M. Wills, Angew. Chem. Int. Ed. 2000, 39, 4106; c) J. Ansell, M.

Wills, Chem. Soc. Rev. 2002, 31, 259. [11] V. M. Mastrano, L. Quintero, C. A. de Parrodi, E. Juaristi, P. J. Walsh, Tetrahedron, 2004, 60,

1781. [12] M. W. van Laren, C. J. Elsevier, Angew. Chem. Int. Ed. 1999, 38, 3715. [13] a) M. L. Clarke, A. M. Z. Slawin, J. D. Woollins, Phosphorus, Sulfur and Silicon, 2001, 169,

5; b) S. M. Aucott, M. L. Clarke, A. M. Z. Slawin, J. D. Woollins, J. Chem. Soc., Dalton

Trans. 2001, 972. [14] P. W. Dyer, J. Fawcett, M. J. Hanton, R. D. W. Kemmitt, R. Padda, N. Singh, Dalton Trans.

2003, 104. [15] S. Jeulin, S. Duprat de Paule, V. Ratovelomanana-Vidal, J. P. Genêt, N. Champion, P. Dellis,

Angew. Chem. Int. Ed. 2004, 43, 320 and references therein. [16] R. P. Pinnell, C. A. Megerle, S. L. Manatt, P. A. Kroon, J. Am. Chem. Soc. 1973, 95, 977. [17] V. D. Makhaev, Z. M. Dzhabieva, S. V. Konovalikhin, O. A. D’Yachenko, G. P. Belov,

Koord. Khim. 1996, 22, 598. [18] a) G. P. C. M. Dekker, C. J. Elsevier, K. Vrieze, P. W. N. M. van Leeuwen, Organometallics

1992, 11, 1937; b) M. A. Zuideveld, B. H. G. Swennenhuis, M. D. K. Boele, Y. Guari, G. P.

F. van Strijdonck, J. N. H. Reek, P. C. J. Kamer, K. Goubitz, J. Fraanje, M. Lutz, A. L. Spek,

P. W. N. M. van Leeuwen, J. Chem. Soc. Dalton Trans. 2002, 2308. [19] A. D. Burrows, M. F. Mahon, M. T. Palmer, J. Chem. Soc., Dalton Trans. 2000, 1669.

49

Chapter 2 Synthesis of Bisaminophosphine Ligands and Their Coordination Behavior [20] A. M. Z. Slawin, J. D. Woollins, Q. Zhang, Inorg. Chem. Commun. 1999, 2, 386. [21] J. Bravo, C. Cativiela, J. E. Chaves, R. Navarro, E. P. Urriolabeitia, Inorg. Chem. 2003, 42,

1006. [22] C. J. Cobley, P. G. Pringle, Inorg. Chim. Acta 1997, 265, 107. [23] J. I. van der Vlugt, M. Fioroni, J. Ackerstaff, R. W. J. M. Hanssen, A. M. Mills, A. L. Spek,

A. Meetsma, H. C. L. Abbenhuis, D. Vogt, Organometallics, 2003, 22, 5697. [24] a) J. Grimblot, J. P. Bonnelle, A. Mortreux, F. Petit, Inorg. Chim. Acta 1979, 34, 29; b) J.

Grimblot, J. P. Bonnelle, C. Vaccher, A. Mortreux, F. Petit, G. Pfeiffer, J. Mol. Cat. 1980, 9,

357. [25] P. Suomalainen, S. Jääskeläinen, M. Haukka, R. H. Laitinen, J. Pursiainen, T. A. Pakkanen,

Eur. J. Inorg. Chem. 2000, 2607. [26] M. J. Atherton, K. S. Coleman, J. Fawcett, J. H. Holloway, E. G. Hope, A. Karaçar, L. A.

Peck, G. C. Saunders, J. Chem. Soc., Dalton Trans. 1995, 4029. [27] K. G. Moloy, J. L. Petersen, J. Am. Chem. Soc. 1995, 117, 7696. [28] D. R. Drew, J. R. Doyle, Inorg. Synth. 1990, 28, 346. [29] F. T. Ladipo, G. K. Anderson, Organometallics, 1994, 13, 303. [30] H. C. Clark, L. E. Manzer, J. Organomet. Chem. 1973, 59, 411. [31] H. Mimoun, J. Y. de Saint Laumer, L. Giannini, R. Scopelliti, C. Floriani, J. Am. Chem. Soc.

1999, 121, 6158. [32] L. Xueliang, Z. Suizhi, G. Hefu, Huaxue Shiji, 1994, 16, 132. [33] O. Equey, A. Alexakis, Tetrahedron Asymmetry, 2004, 15, 1069. [34] L. Weber, A. Rausch, H. B. Wartig, H. -G. Stammler, B. Neumann, Eur. J. Inorg. Chem.

2002, 2438. [35] R. P. Kamalesh Babu, S. S. Krishnamurthy, M. Nethaji, Tetrahedron Asymmetry, 1995, 6,

427. [36] S. M. Ludeman, D. L. Bartlett, G. Zon, J. Am. Chem. Soc. 1979, 44, 1163. [37] a) SADABS, Bruker AXS, Karlsruhe, Germany, 2003; b) P. T. Beurskens, G. Admiraal, G.

Beurskens, W. P. Bosman, S. García-Granda, R. O. Gould, J. M. M. Smits, C. Smykalla,

DIRDIF99 program system; University of Nijmegen, The Netherlands, 1999; c) G. M.

Sheldrick, SHELXL97; University of Göttingen, Germany, 1997. [38] A. L. Spek, J. Appl. Cryst. 2003, 36, 7.

50

Chapter 3

DFT Study into Models of

Bisaminophosphine Ligands


Rh-Catalyzed Asymmetric Hydrogenation

DFT calculations were performed on model compounds for

bisaminophosphine ligands to analyze the geometries and

charge distributions. The computed structure of a simplified

cis-Pd complex of a bidentate bisaminophosphine ligand gives

valuable information on the coordination behavior.

Catalysts generated in situ from [Rh(cod)2]BF4 and

bisaminophosphine ligands perform efficiently in the

asymmetric hydrogenation of (Z)-N-acetylaminocinnamate with

ee’s up to 91%. The individual contributions of

aminophosphine moieties are recognized.

Chapter 3 DFT Study into Models of Bisaminophosphine Ligands

52

MeO

AcO

COOH

NHAc

COOMe

NHAc

[Rh(cod)(DiPamp)]BF4 / H2

deprotection

HO

HO

COOH

NH2

iv v

3.1 Introduction

The demand for enantiomerically pure compounds especially for pharmaceuticals and

agrochemicals paved the way for asymmetric hydrogenation to become one of the most

studied and efficient methods to produce chiral compounds.[1] The breakthrough in this

field was initiated by Knowles and ultimately led to the discovery of the C2-symmetric

chelating compound DiPAMP (Figure 1) as a very efficient ligand the Rh-catalyzed

asymmetric hydrogenation of dehydroamino acids.[2]

PP

MeO

OMe

i ii iii

O

O

PPh2

PPh2

P

P

Figure 1 Breakthrough ligands for asymmetric hydrogenation: DiPamp (i), DIOP (ii) and DuPhos (iii).

The industrial production of L-DOPA (Parkinson’s Disease) by Monsanto emphasized

the possibility of a practical synthesis employing the developed technology (Figure

2).[3] For this work Knowles was awarded the Nobel Prize in 2001.[4] Other important

ligands in this reaction over the years are DIOP (Kagan)[5] and DuPhos (Burk).[6]

(Figure 1)

Figure 2 Monsanto’s L-DOPA (iv) process and a model substrate (v) for the asymmetric transformation.

Especially the fine chemicals industry has a strong interest in the development of new

generic classes of chiral ligands. Also in academia there is a continuing interest in this

subject aiming at deeper insight. This is reflected by the large number of publications

appearing every year. The two dedicated issues in Advanced Synthesis & Catalysis in

2003 on the subject of catalytic hydrogenation underlines this.[7]

Recently the focus shifted towards the application of monodentate ligands, mainly

phosphoramidites and phosphites (Figure 3) with a strong interest from industry due to

Chapter 3 Application of Bisaminophosphine Ligands in Rh-Catalyzed Asymmetric Hydrogenation

a simple synthesis.[8] Here high-throughput experimentation techniques come into play,

especially since coworkers from DSM together with the group of Feringa and the

research group of Reetz independently discovered that combinations of chiral ligands or

even the application of chiral and an additional achiral ligand could increase the

performance of individual systems significantly.[9] The number of experiments to be

performed raises exponentionally with all variables, surely if one takes into account that

each substrate has its own optimal catalytic system (ligand, metal-(precursor) and

physical conditions). A rational approach is therefore highly desirable.

O

OP O

O

OP NMe2

vi vii Figure 3 Parent monodentate BINOL-based phosphoramidite (vi) and phosphite (vii) ligands for

asymmetric hydrogenation.

Many attempts are made to quantify ligand properties and their performance in

catalysis. Two of the earliest and most famous are the quantifications of electronic

effects and steric effects by the introduction of the respective Tolman factors χ and

θ.[10] These parameters were applied to monodentate phosphorus ligands. For bidentate

phosphorus ligands the natural bite angle βn was introduced by Casey et al.[11] and

further developed by Van Leeuwen who correlated βn of series of ligands to their

performance in various homogeneously catalyzed transformations.[12] Nowadays still

high demands in computational power are required to assess ligand properties in order

to ultimately come to de novo design of ligands for a specific reaction, substrate and

regio- and stereospecifity, which still remains an elusive goal.[13]

In the late 1970’s symmetrically substituted bisaminophosphine ligands were developed

and used in the Rh-catalyzed asymmetric hydrogenation of functionalized alkenes.[14-17]

53


N

PEt2

N

PEt2

N N

PPh2PPh2

N NMe Me

PPh2 PPh2

MeN N

PPh2

Me

PPh2

Ph Ph

viii ix

x xi

Figure 4 PNNP ligands for Rh-catalyzed asymmetric hydrogenation.

Figure 4 shows some of the reported PNNP ligands; viii and ix would form 7-

membered rings with the stereogenic carbons outside the ring when complexed to Rh

while x and xi have the stereogenic information within this chelate ring.

Ligands viii-xi all performed distinctly different in catalysis and in order to come to a

better understanding of the catalytic system the expansion of this applied set of ligands

is desired. When the individual contributions of the two aminophosphine moieties in

the ligands could be investigated by an independent variation of the two chiral amines

used this would be a powerful additional tool. A fine attempt was made by Roucoux et

al.[18], however they only used commercially available non-symmetric diamines for

their purpose and were therefore limited in the number of variations.

In this chapter we present DFT calculations on model compounds mimicking the

studied bisaminophosphine ligands, to come to a better understanding of the relevant

electronic and geometric parameters of our system. The bisaminophosphine ligands

described in Chapter 2, both symmetrically as non-symmetrically substituted, were

applied in the asymmetric hydrogenation of methyl Z-acetylaminocinnamate.

54


3.2 Results

3.2.1 DFT Calculations on model compounds.

Models. Phosphines substituted with aryl and alkyl groups typically show mainly σ-

donor character. In order to compare the electronic properties of the bisaminophosphine

ligands from Chapter 2 with ordinary phosphines, we calculated the electron densities

on the phosphorus atoms of the four model compounds PPh3 (I), CH3PPh2 (II),

Ph2PN(CH3)2 (III) and Ph2P(pyrrole) (IV), depicted in Figure 5, by using DFT

methods. For computational purposes monodentate analogues were considered. This

allowed us to avoid oversimplification by the commonly used PH2-group, which has

very little relevance to the actual systems and is normally chosen for obvious

restrictions by computation time, and to use the more realistic PPh2-group instead.

Using the bidentate equivalent of III, model compound V, depicted in Figure 6, we also

investigated the corresponding complex (VI), cis-[PdCl2(V)]. Here methyl groups were

introduced on the phosphorus moieties instead of phenyl groups as a compromise

arising from computational limitations.

PPh3 CH3PPh2N

CH3 CH3

PPh2N

PPh2

I II III IV Figure 5 Model compounds I to IV as used in the DFT calculations.

NN

PMe2Me2P

CH3CH3NN

PMe2Me2P

CH3CH3

PdCl Cl

V VI

Figure 6 Illustration of model compounds V and VI (cis-[PdCl2(V)]), and the optimized structure for VI,

calculated by DFT.

Geometries. Selected geometric parameters (bond lengths and angles) obtained for the

optimized geometries of model compounds I-IV are listed in Table 1. The P-Cα,Ph

distance was constant for the complete series at 1.85 Å, while significant differences

were found for the P-N distance. In case of the aminophosphine III this bond length

55


was 1.73 Å, which is in good agreement with the values found for such bonds in

compounds 6 and 7 (1.68 Å, vide Chapter 2) while in the pyrrolyl-based compound IV

this bond length was calculated to be 1.76 Å. This is in close agreement with the

experimental data provided by Atwood et al.[19], being 1.71 Å. The only angle

comparable between the aforementioned models is the Cα,Ph-P-Cα,Ph’, which shows a

nearly constant value. Little differences exist between the internal angles Cα,Ph-P-CCH3

for compound II and Cα,Ph-P-N for compound III, which is due to the different

orientation of the two phenyl groups. These are reciprocally in trans position, towards

the methyl and N(CH3)2 group.

Table 1 Selected bond lengths and angles for the optimized geometries of model compounds I to IV and

Pd-complex VI.a

PPh3 (I)

CH3PPh2 (II)

(CH3)2NPPh2 (III)

Ph2P(pyr) (IV)

cis-PdCl2(V) (VI)

Bond lengths (Å) -Cα, Ph 1.85 P-Cα, Ph 1.85 P-Cα, Ph 1.85 P-Cα, Ph 1.85 Pd-Cl 2.40

P-CCH3 1.86 P-N 1.73 P-N 1.76 Pd-P 2.35

N-CCH3 1.46 P-N 1.72

P-CCH3 1.84

N-CCH3 1.47

P-P 3.85 Bond Angles (°)a

Cα,Ph-P-Cα, Ph Cα, Ph-P-Cα, Ph 101.7 Cα, Ph-P-Cα, Ph 102.0 Cα, Ph-P-Cα, Ph 102.6 Cl1-Pd-Cl2 87.5 102.6 Cα, Ph-P-CCH3

102.5 Cα, Ph-P-N 101.5 Cα, Ph-P-N 100.7 Cl1-Pd-P1 81.5 Cα, Ph-P-CCH3 99.9 Cα, Ph-P-N 105.8 Cα, Ph-P-N 102.4 Cl2-Pd-P2 81.5 N-P-CCH3 115.6 Cl1-Pd-P2 168.9 Cl2-Pd-P1 168.9 Pd- P1-N1 121.2 Pd- P1-N2 121.2 P1-Pd-P2 109.5

a Repeated entries are referred to the angles estimated on the two different Ph or methyl groups.

Also listed in Table 1 are the geometric parameters of the corresponding palladium

complex VI of model compound V. It is striking that the computed values for the bond

lengths for Pd-complex VI are slightly higher than found in complex C1 (Chapter 2).

This might originate from the applied basis set 6-31G and B3LYP but could also be an

effect of the obvious different substituents on the phosphorus atom, i.e. methyl-units

instead of phenyl groups. As for the correlation between the calculated and

experimentally determined geometry of complex C1, the overall general features are

comparable, especially with regard to the intramolecular P-P distance (3.85 Å vs. 3.83

56


Å) and some of the angles (e.g. Pd-P1-N1). The angles found for the optimized

calculated geometry of VI deviate from experimentally determined values, with an

overestimation of the bite angle P1-Pd-P2 (Δ = ~12°) and consequently the Cl1-Pd-P2

angle falls short in the computed complex. This might well be related to the simplified

model structure used, neglecting also the chiral substituents on the nitrogen atoms.

Charges. The electron distributions in the model compounds were analyzed through an

electrostatic charges analysis. Although atomic charges are not an observable in

quantum mechanics, they are appropriate to get an idea on the electron distribution.

Different schemes and algorithms can be employed. In this study the Mulliken

population analysis was considered.[20] This method assigns charges by partitioning the

orbital overlap evenly between the two atoms that are involved. In Table 2, the

Mulliken atomic charges are reported for the four model compounds I-IV and Pd-

complex VI.

Table 2 Selected Mulliken Atomic Charges for model compounds I to IV and complex VI.a,b

PPh3 (I)

CH3PPh2 (II)

(CH3)2NPPh2 (III)

Ph2P(pyr) (IV)

cis-[PdCl2(V)] (VI)

Atomic Charges

P-Cα, Ph +0.186 P-Cα, Ph +0.352 P-Cα, Ph +0.491 P-Cα, Ph +0.562 Pd -0.967

P-N -0.421 P-N -0.321 P1-N1 +1.09

P1-N1 -0.304

P2-N2 +1.095

P2-N2 -0.304

Cl1 -0.258

Cl2 -0.258

a Electron Units (charge of electron is equal to -1) b Atoms considered in the Mulliken Population

analysis are in italics.

The charge on the phosphorus atoms is lowest in case of PPh3 (I), and the value

increases going along compounds II, III to IV. Therefore the introduction of a nitrogen

atom unequivocally raises the positive charge on the P atom, with a stronger effect

when the π-acidic pyrrole moiety is incorporated rather than a tertiary amine.

57


With respect to the palladium-complex VI there is strong indication of a nearly net -1

charge on the metal, with the P atoms bringing a +1 charge. Compound III bears

closest resemblance to the model ligand V used in compound VI. Comparing the net

charges on the free ligand with those present in the metal complex, the P atom

undergoes a dramatic change increasing the net positive charge of 0.5, while the charge

on the nitrogen atom decreases to a negative charge of -0.2. This can be interpreted as a

strong backdonation of the P atoms towards the Pd atom, especially if a net charge of -

0.2 is present on a chlorine atom.

3.2.2 Rh-catalyzed asymmetric hydrogenation of methyl Z-acetylaminocinnamate

The bisaminophosphine compounds described in Chapter 2 were employed as ligands

in the asymmetric hydrogenation of methyl (Z)-N-acetylaminocinnamate, one of the

benchmark substrates to assess the performance of a given chiral modifier in this

reaction (Eq. 1). The standard metal precursor [Rh(cod)2]BF4 was used, which during

catalysis is converted in-situ to [Rh(cod)L]BF4 while one of the cod (cyclooctadiene)

groups is lost and hydrogenated.

COOCH3

NHAc

H2

[Rh(cod)L]BF4

COOCH3

NHAc

*(1)

First the optimal solvent for our system was determined from a small set of commonly

used solvents in hydrogenation reactions, namely methanol, ethyl acetate and

dichloromethane. The novel ligand L7 (figure 7) was the ligand of choice for the

screening. Besides, for one entry an excess of ligand to metal (2.2 equiv) was used to

check if the performance would be significantly different. The obtained results under

typical conditions are summarized in Table 3.

58


Table 3 Initial solvent and stoichiometry screening for asymmetric hydrogenation of methyl (Z)-N-

acetylaminocinnamate results with [Rh(cod)L]BF4a

entry solvent equiv L TOF (mol mol-1 h-1)b conv (%)c ee (%)d 1 MeOH 1.1 73 100 40 (S) 2 CH2Cl2 1.1 37 100 66 (S) 3 EtOAc 1.1 31 100 85 (S) 4 EtOAc 2.2 34 100 85 (S)

a Reaction conditions: 0.011 mmol L7 (R) ; 0.01 mmol [Rh(cod)2]BF4 ; 5 mL solvent ; H2 atmosphere

1.1 bar ; T = 25 ºC; 1 mmol (Z)-N-acetylaminocinnamate. b Turn Over Frequency, average conversion of (Z)-N-acetylaminocinnamate over first hour. c Percent conversion of (Z)-N-acetylaminocinnamate after 18 h. d Enantiomeric excess determined by chiral GC, absolute configurations given in parentheses.

NNPPh2PPh2

NN

PPh2 PPh2

NN

PPh2 PPh2

NN

PPh2 PPh2OMeMeO

NN

PPh2 PPh2

NN

PPh2 PPh2

NN

PPh2 PPh2

L1 L2

L3 L4

L5 L6

NN

PPh2 PPh2

NN

PPh2 PPh2

NN

PPh2 PPh2

L7 L10

L11 L12

Figure 7 Bisaminophosphine ligands L1-L7 and L10-L12 used in asymmetric hydrogenation.

Obviously the performance of our catalytic system is greatly influenced by the solvent

used. The initial TOF is highest for MeOH, but in this solvent the ee was lowest. This

may be caused by a degree of degradation of the ligand by the protic solvent, which is

59


partially described by Pracejus et al.,[15] although with another Rh-precursor ([Rh(μ-Cl)

(C2H4)2]2) methanol outperforms benzene as the solvent in both stereospecifity as

activity in that study. Entries 2 and 3 show equal TOF’s for dichloromethane and ethyl

acetate but for ethyl acetate the highest ee was obtained (85%), which might be caused

by a beneficial participation of the carboxylic function of this ester. A similar run with

double the amount of ligand (entry 4) showed comparable activity and selectivity.

Independent of the solvent the major product obtained has the S configuration.

The ligands shown in figure 7 were now applied in the reaction using ethyl acetate, the

solvent in which the highest ee was obtained for ligand L7. The results are summarized

in Table 4.

Table 4 Asymmetric hydrogenation of (Z)-N-acetylaminocinnamate results with [Rh(cod)L]BF4

a

Entry Ligand L TOF (mol mol-1 h-1)b conv (%)c ee (%)d 1 L1 50 >99 85 (R) 2 L2 43 >99 85 (S) 3 L3 65 >99 85 (S) 4 L4 32 91 79 (S) 5 L5 85 >99 91 (R) 6 L6 93 >99 16 (R) 7 L7 31 >99 85 (S)

non symmetrically substituted ligands 8 L10 58 >99 35 (S) 9 L11 39 >99 84 (S) 10 L12 48 >99 0

a Reaction conditions: 0.011 mmol ligand ; 0.01 mmol [Rh(cod)2]BF4 ; 5 mL EtOAc ; H2 atmosphere 1.1

bar ; T = 25 ºC; 1 mmol (Z)-N-acetylaminocinnamate. b Turn Over Frequency, average conversion of (Z)-N-acetylaminocinnamate over first hour. c Percent conversion of (Z)-N-acetylaminocinnamate after 18 h. d Enantiomeric excess determined by chiral GC, absolute configurations given in parentheses.

The first striking observation is that all ligands but L6 perform equally well when ee is

concerned. In a small range of ee’s on average 85% ee is obtained, in any case the

major product being the enantiomer with the sign of rotation opposite of the sign of

rotation of the amine used in the synthesis of the ligand. The exception L6 gives only a

low ee of 16% (entry 5) but remarkably it is also the fastest ligand in the series with an

initial TOF of 93 on average over the first hour. Best ligand overall is L5 based on the

60


most crowded 1-naphthylethyl moiety, which gives a good TOF and the highest ee of

91% (entry 4).

L6 is the only ligand which does not possess an aromatic ring in the stereogenic amine

part, possibly making the phosphorus atoms less crowded and subsequently the Rh

center more open for the incoming substrate. Possibly the absence of π-π interactions

between ligand and substrate also plays a role. These differences may be the cause for

the observed highest activity for L6, although activities do not reach industrially viable

values (>500 mol mol-1 h-1) but it should be noted that the applied pressure is only 1.1

bar while in commercial processes the use of higher pressures is common practice.

C2-rpea-ppa-PPh2 (L11) is a pseudo C2-symmetric ligand and gives the highest ee for

the three non symmetrically substituted ligands. The ligand with one achiral element

(L10) fails to block one specific quadrant which you could identify in the quadrant

diagram model.[2] This model occupied and vacant quadrants indicate areas of

maximum and minimum repulsive interactions between parts of the catalyst and the

prochiral substrate. Therefore is is not surprising the ligand L10 generated limited

chiral induction.

Figure 8 31P{1H} spectra of in-situ generated [Rh(cod)(bisaminophosphine)]BF4 complexes of ligand L5

(top) and ligand L10 (bottom).

A means to investigate the electronic properties of the bisaminophosphine ligands is to

measure the NMR-spectra of the corresponding complexes to assess the chemical shifts

61


(δ 31P{1H} (ppm)) and the coupling constant of the Rh-P bond (1JRh-P (Hz)). This has

been done for the various ligands, including the non symmetrical ligands; the selected

data from the obtained spectra are summarized in Table 5. For illustration purposes

NMR-spectra of one symmetrical (L5) and one non-symmetrical ligand (L10) are

shown in Figure 8.

It was confirmed that the complexes derived by in-situ mixing the ligand and the metal

precursor [Rh(cod)2]BF4 in CDCl3 are the same as a complex synthesized on a larger

scale, isolated by precipitation and purified by crystallization (entry 0 vs. entry 1).

All complexes show comparable values, chemical shifts δ 31P around 84 ppm, and

coupling constants around 164 Hz. Both values are in the expected ranges for a cationic

Rh(I) complex bearing a diene and an electron-poor diphosphorus ligand. No

quantitative relationship can be deduced from these numbers.

Table 5 NMR study [Rh(cod)(bisaminophosphine)]BF4 complexes.

Entry Ligand L δ 31P{1H} (ppm) 1JRh-P (Hz) JP-P (Hz) 0 L1 a 83.7 163.6 - 1 L1 83.8 162.4 - 2 L2 83.7 163.6 - 3 L3 85.7 163.6 - 4 L4 85.6 166.0 - 5 L5 84.0 161.1 - 6 L6 81.1 161.1 - 7 L7 82.9 163.6 -

non symmetrical ligands -

8 L10 89.6 , 77.5 159.9 , 164.7 24.4 9 L11 85.0 , 84.0 163.6 , 163.6 22.7 10 L12 84.9 162.5 -

a preformed and isolated complex

For the non symmetrically substituted ligands (entries 8-10) the picture changes, since

the phosphorus atoms are not equivalent anymore and coupling between the phosphorus

atoms occurs. For L10 the difference is significant (upfield shift of ca. 12 ppm for the

benzylaminophosphine moiety compared to the phenylethylaminephosphine group

(entry 8)). This proves the possibility of a new concept in designing and synthesizing

62


bisaminophosphine ligands with different electronic and steric properties for the two

donating groups.

3.3 Conclusions

From the DFT calculations the role of the nitrogen in P-N bond containing compounds

becomes more clear; the nitrogen increases the positive charge on the phosphorus atom,

which is indicative for a degree of π-bonding in the P-N bond. Upon complexation with

palladium the charge on P increases significantly.

The application of bisaminophosphine ligands in the Rh-catalyzed asymmetric

hydrogenation of (Z)-N-acetylaminocinnamate gives ee’s up to 91% and full conversion

under ambient conditions in the donating solvent ethyl acetate.

3.4 Perspective

The increase in computational power will enable the modeling of more realistic

compounds without concessions due to complexity. Or alternatively one may choose

higher level calculations to yet a better understanding of electronic interactions in

ligand, their transition metal complexes or even essential transformations during a

catalytic cycle.

The commercial availability of a wide range of chiral amines opens up extra

possibilities to find ligands with extraordinary effects in catalysis. The applied types of

bisaminophosphines may be used, and are being used, for various other homogeneously

catalyzed transformations; an example is the nickel-catalyzed alkylation of allylic

acetates.[21] Rhodium in combination with this type of bisaminophosphine ligands is

also effective in the asymmetric hydrogenation of activated ketones[18] The new

symmetrical and non symmetrical substituted bisaminophosphines reported here can

contribute to a better insight into and performance of these reactions, since their

modular and easy construction allows for ligand fine tuning in an automated synthesis

and testing setup.

63



Avantium Technologies is kindly acknowledged for financial support, Umicor Co is

thanked for the generous loan of precious metals. All DFT calculations were performed

by Marco Fioroni. We are indebted to Ton Staring for valuable technical assistance.


General



received or distilled from CaH2 before use. Solvents were either taken HPLC-grade

from an argon-flushed column, packed with aluminum oxide, or distilled under argon

prior to use over an appropriate drying agent. NMR spectra were recorded at room

temperature on a Varian Mercury 400 MHz spectrometer. Chemical shifts are given in

ppm and spectra are referenced to CDCl3 (1H) or 85% H3PO4 (31P{1H}). All described

ligands were prepared following procedures described in Chapter two. (Z)-N-

acetylaminocinnamate was kindly synthesized by Gabriela Ionescu.[22] [Rh(cod)2]BF4

was synthesized following literature procedures[23] and kept under Ar.

Hydrogenation of (Z)-N-acetylaminocinnamate

A Schlenk tube was charged with 1 mmol substrate ((Z)-N-acetylaminocinnamate),

0.01 mmol catalyst precursor [Rh(cod)2]BF4 and ligand (0.011mmol) in 5 mL of the

appropriate solvent. After three H2 purges the reaction mixture was stirred at 298 K

under a constant H2 atmosphere (1.1 bar). Samples were taken under an outflow of H2

gas. The conversion was determined on a 50 m PONA (HP) column (carrier gas 150

kPa He, FID detector). For the ee measurement an L-Chiralsil Val column (carrier gas

120 kPa He, FID detector) was used.

NMR studies on [Rh(cod)(bisaminophosphine)]BF4 complexes

[Rh(cod)2]BF4 (4.0 mg, 9.9 µmol) and 1.0 equiv of the appropriate ligand were stirred

in 0.6 mL of CDCl3 at room temperature for 30 min. The solution was transferred to an

NMR tube and the locked 31P NMR spectrum was recorded.

64


Computational Methods

For all the presented calculations, the Gaussian98 series of computer programs have

been used.[24]

Density Functional Methods

Standard computational methods based on the Density Functional Theory (DFT) have

been employed.[25] The used functional is the three-parameter exchange functional of

Becke[26] together with the correlation functional of Lee, Yang and Parr (B3LYP).[27]

For the P, C, Cl and H atoms the basis set used is the Pople style basis set 6-31G[28]

with diffuse (+) s- and p- functions added on the heavy atoms[29] and polarization

function[30] (d, p), adding one d function on the heavy atoms and one p function on the

hydrogens [6-31+G(d, p)]. For the transition metal palladium, the LanL2DZ Hay-Wadt

relativistic small-core effective core potential (ECP) and the corresponding basis set,

split valence double-ζ, were used.

The geometries of all the model compounds have been fully optimized using analytical

gradients technique at the B3LYP level of theory previously cited. No symmetry

constraints have been introduced. The optimized stationary points have been confirmed

through an harmonic vibrational analysis (B3LYP level), using analytical or numerical

differentiation of the obtained analytical energy first derivative. Energy calculations

were performed at the same level of the geometry optimization, including the zero-

point vibrational energy correction, applying the harmonic oscillator approximation.

65


3.7 References

[1] W. Tang, X. Zhang, Chem. Rev. 2003, 103, 3029 and references therein. [2] a) B. D. Vineyard, W. S. Knowles, M. J. Sabacky, G. L. Bachman, O. J. Weinkauff. J. Am.

Chem. Soc. 1977, 99, 5946. b) W. S. Knowles, Acc. Chem. Res. 1983, 16, 106. [3] W. S. Knowles, J. Chem. Educ. 1986, 63, 222. [4] W. S. Knowles, Angew. Chem. Int. Ed. 2002, 41, 1998. [5] H. B. Kagan, Chem. Commun. 1971, 481. [6] W. A. Nugent, T. V. RajanBabu, M. J. Burk, Science, 1993, 259, 479. [7] various authors, Adv. Synth. Catal. 2003, issues 1-2. [8] see for example a) M. v. d. Berg, A. J. Minnaard, R. M. Haak, M. Leeman, E. P. Schudde, A.

Meetsma, B. L. Feringa, A. H. M. de Vries, C. E. P. Maljaars, C. E. Willans, D. Hyett, J. A. F.

Boogers, H. J. W. Hendrickx, J. G. van de Vries, Adv. Synth. Catal. 2003, 345, 308. b) M. T.

Reetz, J.-A. Ma, R. Goddard, Angew. Chem. Int. Ed. 2005, 44, 2962. [9] a) D. Peña, A. J. Minnaard, J. A. F. Boogers, A. H. M. de Vries, J. G. de Vries, B. L. Feringa,

Org. Biomol. Chem. 2003, 1, 1087. b) M. T. Reetz, T. Sell, A. Meiswinkel, G. Mehler, Angew.

Chem. Int. Ed. 2003, 42, 790. [10] a) C. A. Tolman, J. Am. Chem. Soc. 1970, 92, 2953; b) C. A. Tolman, J. Am. Chem. Soc. 1970,

92, 2956 ; c) C. A. Tolman, Chem. Rev. 1977, 77, 313. [11] C. P. Casey, G. T. Whiteker, Israel J. Chem. 1990, 30, 299. [12] P. W. N. M. van Leeuwen, P. C. J. Kamer, J. N. H. Reek, P. Dierkes, Chem. Rev. 2000, 100,

2741 and references therein. [13] MM/SEQM: K. D. Cooney, T. R. Cundari, N. W. Hoffman, K. A. Pittard, M. D. Temple, Y.

Zhao, J. Am. Chem. Soc. 2003, 125, 4318; AMS model: K. Angermund, W. Baumann, E.

Dinjus, R. Fornika, H. Görls, M. Kessler, C. Krüger, W. Leitner, F. Lutz, Chem. Eur. J. 1997, 3,

755; DFT: S. A. Decker, Organometallics, 2001, 20, 2827 and F. Delbecq, V. Guiral, P. Sautet,

Eur. J. Org. Chem. 2003, 2092. [14] a) M. Fiorini, G. M. Giongo, F. Marcati, W. Marconi, J. Mol. Cat. 1976, 1, 451; b) M. Fiorini,

F. Marcati, G. M. Giongo, J. Mol. Cat. 1978, 3, 385; c) M. Fiorini, F. Marcati, G. M. Giongo, J.

Mol. Cat. 1978, 4, 125; d) M. Fiorini, G. M. Giongo, J. Mol. Cat. 1979, 5, 303. [15] G. Pracejus, H. Pracejus, Tetrahedron Lett. 1977, 39, 3497. [16] K. Kashiwabara, K. Hanaki, J. Fujita, Bull. Chem. Soc. Jpn. 1980, 53, 2275. [17] R. Guo, X. Li, J. Wu, W. H. Kwok, J. Chen. M. C. K. Choi, A. S. C. Chan, Tetrahedron Lett.

2002, 43, 6803. [18] A. Roucoux, I. Suisse, M. Devocelle, J.-F. Carpentier, F. Agbossou, A. Mortreux, Tetrahedron:

Asymmetry, 1996, 7, 379. [19] J. L. Atwood, A. H. Cowley, W. E. Hunter, S. K. Mehrotra, Inorg. Chem. 1982, 21, 1354. [20] R. S. Mulliken, J. Chem. Phys. 1955, 23, 1833. [21] H. Bricout, J.-F. Carpentier, A. Mortreux, Tetrahedron Lett. 1996, 37, 6105. [22] S. Gladiali, L. Pinna, Tetrahedron Asymmetry, 1991, 2, 623.

66

Chapter 3 Application of Bisaminophosphine Ligands in Rh-Catalyzed Asymmetric Hydrogenation [23] T. G. Schenck, J. M. Downes, C. R. C. Milne, P. B. Mackenzie, H. Boucher, J. Whelan, B.

Bosnich, Inorg. Chem. 1985, 24, 2334. [24] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, V. G.

Zakrzewski, J. A. Montgomery Jr., R. E. Stratmann, J. C. Burant, S. Dapprich, J. M. Millam, A.

D. Daniels, K. N. Kudin, M. C. Strain, O. Farkas, J. Tomasi, V. Barone, M. Cossi, R. Cammi, B.

Mennucci, C. Pomelli, C. Adamo, S. Clifford, J. Ochterski, G. A. Petersson, P. Y. Ayala, Q.

Cui, K. Morokuma, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J.

Cioslowski, J. V. Ortiz, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.

Gomperts, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, C.

Gonzalez, M. Challacombe, P. M. W. Gill, B. G. Johnson, W. Chen, M. W. Wong, J. L. Andres,

M. Head-Gordon, E. S. Replogle, J. A. Pople, Gaussian 98, Revision A.3 (by Gaussian, Inc.),

1998, Pittsburgh. [25] R. G. Parr, W. Yang, in Density Functional Theory of Atoms and Molecules, R. G. Parr, and W.

Yang, (Eds.): Oxford Science Publications, 1989, Oxford. [26] A. D. Becke, J. Chem. Phys. 1993, 95, 5648. [27] C. Lee, W. Yang, R. G. Parr, Phys. Rev. B, 1988, 37, 785. [28] W. J. Hehre, R. Ditchfield, J. A. Pople, J. Chem. Phys. 1972, 56, 2257. [29] M. J. Frisch, J. A. Pople, J. S. Binkley, J. Chem. Phys. 1984, 80, 3265. [30] R. Krishnan, J. S. Binkley, R. Seeger, J. A. Pople, J. Chem. Phys. 1980, 72, 650.

67

Chapter 4


Rh-Catalyzed Asymmetric Hydroformylation

C2-symmetric bisaminophosphine ligands were applied in the

Rh-catalyzed asymmetric hydroformylation of prochiral

alkenes. For styrene the branched/linear ratio reached 12, the

ee remained limited to 12%. Vinyl acetate was hydroformylated

more efficiently: the desired branched product was observed in

high selectivity with a branched/linear ratio up to 50. The ee’s

were medium with a maximum of 51%. HP-NMR studies

indicated that equatorial - equatorial is the preferred

coordination mode, which could be confirmed by HP-IR

spectroscopy.

Chapter 4 Application of Bisaminophosphine Ligands in Rh-Catalyzed Asymmetric Hydroformylation

70

R R

CHO

RCHO+

branched linear

CO/H2

cat. *

4.1 Introduction

Hydroformylation or oxo-synthesis is the atom-efficient process in which an aldehyde

is produced from an alkene via the catalyzed addition of carbon monoxide and

dihydrogen (Eq. 1).

(1)

Propene is the most important substrate in industrial applications, since annually bulk

amounts of n-butanal are converted among others to plasticizer alcohols for the

polymer industry.[1-3] The regioselectivity is here a very important parameter; the linear

aldehyde being the desired product.[4]

The branched product is desired in the asymmetric hydroformylation of prochiral

substrates, here the carbon skeleton of an alkene is extended by one carbon atom and a

stereocenter is created. The thus formed optically active aldehydes are of high synthetic

utility in organic synthesis.[5] These chiral molecules, in enantiomerically pure form, are

valuable precursors for drugs, agrochemicals and food additives.[4] An example lies in

the asymmetric hydroformylation of allyl cyanide described by De Vries et al.[6] The

product 2-methyl-3-cyanopropanal can be converted by a hydrogenation step to 3-

methyl-4-aminobutanol which is used as a building block for a new Tachykinin NK1

receptor antagonist[7]

A real breakthrough occurred in this field with the discovery of the Rh/BINAPHOS (i)

catalyst systems by Takaya et al.[8] Since then, new active chiral ligands such as

aminophosphine phosphinites (ii)[9] and diphosphites (iii)[10,11] have been developed,

see figure 1. Also Pt/Sn-based systems were considered and successfully applied.[12]

However, hydroformylation has yet not been used in organic synthesis on a frequent

basis. Simultaneous control of regio- and enantioselectivity, while maintaining

sufficient activity is the big challenge to be addressed.


O

O

PO

PPh2

O

MeN

Ar2PPh

Me

PPh

R

i ii

OOPP

O

O

tBu

tBu

O

O

tBu

tBu

R

R

R

R

P

O

O

tBu

tBu

R

R

OO

OP

O

O

tBu

tBu

R

R

O

iii iv Figure 1 Ligands for asymmetric hydroformylation: BINAPHOS (i), AMPP (ii), diphosphites (iii, iv).

Recently progress has been made in the field with the development of new chiral

AMPP (aminophosphine phosphonite) ii ligands in the group of Vogt.[9] Although the

BINAPHOS system remains the benchmark catalyst in asymmetric hydroformylation,

the AMPP ligand family provides enormous potential for variation and ligand fine-

tuning. A very recent theoretical investigation by Carbó et al. gave more insight in

these systems and will potentially lead to more successful ligands in due time.[13] Sugar

based diphosphites (e.g. iv) give a tremendous number of successful ligands from the

chiral pool.[11]

All ligands which provide high enantioselectivities have one common characteristic:

the ligands coordinate in the hydrido rhodium complexes in a specific mode. Either in

the equatorial/equatorial (ee) manner (diphosphites) or the equatorial/axial (ea) manner

(BINAPHOS/AMPP) in the trigonal bipyramidal.[14] In the latter cases the stronger π-

acceptor phosphorus atom occupies the axial position, trans to the hydride, while the

equatorial position of the complex is occupied by the stronger σ-donor phosphorus

atom.

71


Rh CO

H

CO

P

P PP

Rh CO

HOC

ee ea

Rh RhCO

PPP

P

OC

CO

CO

Scheme 1 Equatorial/equatorial ee and equatorial/axial ea coordination modes in trigonal bipyramidal

Rh-complexes. Righthand side: catalytically inactive bridged dinuclear species.

In our view a neglected ligand type in asymmetric hydroformylation may be found in

the bisaminophosphine ligands. These ligands, easily constructed from commercially

available chiral amines and chlorophosphines (see Chapter 2), provide the desired

modularity and therefore could be fine-tuned for different enantioselective

transformations. Especially the possibility of independent variation of the two amine

groups, and thereby the two aminophosphine moieties, allows to tune electronic and

steric properties. This is in contrast with the BINAPHOS ligand (i) in Figure 1 which

suffers from a tedious multi-step synthetic route.

v

PP

N

NN

N

Ph

Ph

Figure 2 ESPHOS ligand (v) for asymmetric hydroformylation of vinyl acetate.

A successful ligand based on chiral diamines, although in the form of a bis-

diazaphospolidine, was developed by Breeden et al.[15] This ESPHOS ligand (v) (figure

2) was applied in the asymmetric hydroformylation of vinyl acetate, with high

enantioselectivities, however with styrene as the substrate the product was virtually

racemic. The limited commercial availability of the used chiral diamine and the not

straightforward synthesis of the 1,2 substitution pattern on the phenyl backbone makes

the synthesis less suited for modular approaches.

Here we present the first application of bisaminophosphine ligands, synthesized in

Chapter 2 in the asymmetric hydroformylation of alkenes. The coordination of the

ligand to the rhodium center in the resting state of the catalyst under syngas conditions

was investigated using in-situ HP-NMR and HP-IR spectroscopy techniques.

72


4.2 Results

4.2.1 Catalysis

Styrene, being a generally accepted and widely used benchmark substrate for the

asymmetric hydroformylation reaction, was selected as the first substrate see Eq. 2.

CO/H2

Rh/L

CHO

CHO

+*

(2)

The catalysts were prepared for the screening by in situ mixing the ligands with the

metalprecursor Rh(acac)(CO)2 in a ratio 2:1 and heating in an autoclave under typical

reaction conditions (60°C, 20 bar syngas (1:1 CO/H2)). Subsequently the substrate with

internal standard was injected under pressure and the mixture was allowed to react for

15 h. After workup and derivatization to the trifluoro acetic ester the products were

analyzed by (chiral) GC. The results are presented in Table 1.

Table 1 Selected results of asymmetric hydroformylation of styrene performed by bisaminophosphine /

Rh(acac)(CO)2 catalyst systems.a

Entry Ligand conv (%) b b/l c ee (%) d

1 L1 57 3.6 -2 2 L2 66 3.6 2 3 L3 e 20 2.4 2 4 L4 22 7.2 9 5 L5 34 11.5 -1 6 L6 92 4.2 -12 7 L7 61 4.6 5

a Reaction conditions: T = 60°C; p = 20 bar (1:1 CO/H2); solvent: toluene, [Rh] = 0.46 mM; Rh:S =

1300; L:Rh = 2; preformation t = 1h; t = 15h. b Percent conversion of styrene after 15h. c Branched /

linear ratio. d Enantiomeric excess determined by chiral GC. e T = 40°C.

All ligands give active catalysts in this enantioselective conversion and the desired

branched product is in any case the dominant regioisomer. Only the ligand based on 1-

naphthylethylamine L5, however, induces the excellent branched/linear ratio which is

generally expected for styrene and similar vinylarenes (entry 5).[16] The steric crowding

around the Rh center is expected to be highest for this catalyst complex. The highest

conversion and simultaneously the highest enantioselectivity was found for ligand L6,

based on the cyclohexyl moiety, but the overall performance is still far from good.

73


O

O

Me

CO/H2

Rh/L O

CHOO

Me OCHO

O

Me+

* (3)

The second substrate for the asymmetric hydroformylation is vinyl acetate, see Eq. 3.

The branched product of this conversion is 2-acetoxypropanal which is a precursor for

the synthesis of hydroxy-amino acid threonine in the Strecker synthesis. The product

can also be converted to 2-hydroxypropanal, a useful intermediate in the synthesis of

steroids, pheromones, antibiotics and peptides.[17] Here the reaction mixture can be

analyzed directly by GC after workup without an additional derivatization step. Results

are given in Table 2.

Table 2 Selected results of asymmetric hydroformylation of vinyl acetate performed by

bisaminophosphine / Rh(acac)(CO)2 catalyst systems.a

Entry Ligand conv (%)b b/l c ee (%)d

1 L1 70 3.2 4 2 L2 77 3.6 -5 3 L3 nd nd nd 4 L4 71 >50 12 5 L5 82 17 32 6 L5e 65 20 51 7 L6 68 4.2 18 8 L7 64 2.4 20

a Reaction conditions: T = 60°C; p = 20 bar (1:1 CO/H2); solvent: benzene, [Rh] = 0.54 mM; Rh:S =

1400; L:Rh = 2; preformation t = 1h; t = 20h. b Percent conversion of vinyl acetate after 20h. c Branched /

linear ratio. d Enantiomeric excess determined by chiral GC. e T = 40°C. f nd = not determined.

The use of bisaminophosphine ligands for the asymmetric hydroformylation of vinyl

acetate proves to be an efficient one. All applied ligands give more than 60%

conversion and the desired branched product is in some cases the only product

observed. The ethyl substituents on the α-positions with respect to the nitrogen atoms

in the case of L4 seems to be steering the regioselectivity to a great extend providing an

excellent regioselectivity of >50. The enantioselectivity is highest for the ligand with

the biggest aryl substituent 1-naphthyl (L5) used in entries 5 and 6. Lowering the

reaction temperature to 40 °C raises the ee above 50 % which remains only a fair result.

74


For both substrates styrene and vinyl acetate the chirality-inducing elements seem to be

too far of the metal center, or the backbones are too flexible to force the incoming

alkene in one specific geometry allowing the formation of both enantiomers of the

product. It has to be stressed that only a small excess of bidentate ligand to rhodium is

used (2:1) for both substrates. In order to obtain higher enantiomeric excesses it might

be essential to apply a larger excess of ligand (4 equiv with respect to rhodium). Also at

lower ligand to metal ratios [HRh(CO)4] can be formed.

In order to evaluate and quantify the differences in performance of the

bisaminophosphine ligands in the asymmetric hydroformylation of styrene and vinyl

acetate, HP-NMR and HP-IR could be valuable. These tools give insight into the

coordination mode of the used ligands under (pseudo-)reaction conditions. The

postulation that only one specific coordination mode may be present in the catalyst to

give an efficient enantioselective catalyst can be checked.

4.2.2 HP-NMR

NNPPh2PPh2

NN

PPh2 PPh2

NN

PPh2 PPh2OMeMeO

NN

PPh2 PPh2

NN

PPh2 PPh2

NN

PPh2 PPh2

L1 L2

L3 L4

L5 L6

N

PPh2

N

PPh2

L7 L8

NN

PPh2 PPh2

Figure 3 Bisaminophosphine ligands L1-L8 applied in HP-NMR studies.

75


The ligands shown in figure 3 were reacted with one equivalent of the metal precursor

Rh(acac)(CO)2 in toluene-d8. After stirring for 5 minutes the clear yellow solution was

transferred to a 10 mm sapphire NMR tube where it was subjected to 20 bar 1:1 CO:H2

syngas pressure. The tube was subsequently heated to 60°C for 1 h. After this

preformation the pressure was carefully released and the solution was quickly

transferred to a routine 5 mm NMR tube for spectra to be recorded at room

temperature. Selected parameters are presented in Table 3.

Table 3 Selected NMR data on bisaminophosphine / Rh(acac)(CO)2 catalyst system preformed with

CO/H2.

Ligand δ 31P{1H} (ppm) δ 1H (ppm) 1JRh-P (Hz) 1J Rh-H (Hz) 2J P-H (Hz)

L1 / L2 88.6 -9.18 144.0 9.1 13.7 L3 88.1 -9.15 142.8 6.7 15.6 L4 88.8 -9.30 142.8 6.7 13.7 L5 89.3 -9.11 147.7 5.5 6.8 L6 87.4 -9.24 144.0 6.1 11.9 L7 88.0 -8.90 140.4 6.7 16.8 L8 100.1 -9.27 152.6 4.0 -

The 31P{1H} spectra show a doublet at around 88 ppm with a 1JRh-P (Hz) coupling of

around 145 Hz. This seems to indicate that the two phosphorus atoms are magnetically

equivalent and therefore coordinate predominantly in the equatorial - equatorial

coordination mode, although the complexes are dynamic. Figure 4 shows the 31P{1H}-

NMR spectrum of the representative catalyst system based on ligand L7.

ppm

Figure 4 31P{1H}-NMR spectrum of the representative catalyst system based on ligand L7.

76


In the hydride region a clear doublet of triplets was visible around –9 ppm for all

ligands with a C2 bridge but L5, vide infra. Figure 5 shows the 1H-NMR spectrum in

the hydride region of the representative ligand L7.

ppm

Figure 5 1H-NMR spectrum of the hydride region of the representative catalyst system based on ligand

L7.

The values of 1J Rh-H range from 5.5 to 9.1 Hz and the 2J P-H coupling constants vary

between 11.9 and 16.8 Hz. These numbers do not give a clear indication weather the

seemingly obvious equatorial - equatorial coordination mode is the major or the only

species in solution, since it is known that the species may interchange on the NMR

timescale giving rise to average coupling constants.

Ligand L5 based on 1-naphthyl has a distinctly different appearance in 1H NMR. From

NMR simulation it could be deduced that the 1J Rh-H and the 2J P-H differ that little in

magnitude (5.5 Hz vs. 6.8 Hz) in this catalyst system that the signal appears as a pseudo

quartet. Also from these coupling constants it is obvious that L5 coordinates

predominantly in the equatorial - equatorial mode. An equatorial - axial relationship

would lead to larger values for the found coupling constants as found for related

diphosphite systems.[18] No indication is found that bridged species (Scheme 1) exist

under these (concentrated) conditions and therefore are also thought to be absent during

the hydroformylation experiments.[19]

77


The only measured ligand with a C3 bridge, L8, surprisingly only shows a doublet in

the hydride region, which could imply fast exchange of the phosphorus atoms. The 31P{1H}-NMR spectrum gives a doublet more downfield than for the other ligands in

this series and the 1JRh-P coupling is significantly larger. This could indeed indicate a

larger contribution of ea coordinated species in solution.

To validate the assumption that after releasing pressure the obtained complexes in

solution are stable enough to be measured in the way described above the 1H-NMR

spectrum of the ligand L5 were also measured in the 10 mm sapphire NMR tube after

the same preformation on a Bruker 200 MHz under pressure. Figure 6 shows the

obtained spectrum (hydride region).

-8.4 -8.8 -9.2 -9.6 ppm

Figure 6 1H-NMR spectrum of L5 / Rh(acac)(CO)2 catalyst system under syngas conditions (hydride

region).

The measured chemical shifts and coupling constants were identical to the values

obtained for the system after releasing pressure. We believe that analogously the other

catalyst systems would show equal behavior and therefore that the comparison of

spectral parameters is justified.

The preformation of the catalyst complex is also followed over time at room

temperature under 20 bar syngas (1:1 CO/H2) pressure, see figure 7. The first spectrum

is taken after 21 minutes. After 7h the doublet of triplets pattern is already visible.

Every 7 hours another spectrum is recorded and it shows that after 42 hours the

preformation is complete. Compared to the preformation at 60°C no spectral

differences exist, only the rate of the reaction (full conversion in less than one hour) is

as expected slower. Note that the preformation conditions in the latter experiments are

equal to the conditions applied during the hydroformylation experiments, besides the

higher concentrations for the sake of sensitivity of the spectrometer. This confirms that

78


the 1 hour preformation time during regular hydroformylation experiments is likely to

be sufficient for a full transformation to the catalytic resting state.

56 h 49 h 42 h 35 h 28 h 21 h 14 h 7 h 21 min

δ (ppm)

Figure 7 HP-NMR of the L5 / Rh(acac)(CO)2 catalyst system followed over time, hydride region.

4.2.3 HP-IR

For additional information on the coordination behavior close to reaction conditions,

with regard to catalyst concentration and pressure, HP-IR is used. The ligand is

dissolved in cyclohexane and stirred with one equivalent of Rh(acac)(CO)2. The

solution is transferred to an autoclave equipped with IR-transparent windows (ZnS) and

a dedicated FT-IR machine where it is pressurized to 20 bar syngas (1:1 H2/CO) at 60

°C. The observed signals in the carbonyl stretching region are listed in Table 4. It is

apparent that for the measured C2 bridged ligands L2 and L5 there is only one complex

present in solution with equatorial – equatorial coordinated ligand since two bands

with equal intensities are found. This is similar to the findings of van der Vlugt et al.[20]

with sterically constrained diphosphonites, while with Xantphos type ligands mixtures

of ee and ea coordinated species are obtained which are in fast equilibrium, which is

reported by van der Veen et al. [21]

79


Table 4 Selected HP-IR data of the νCO on preformed Rh(acac)(CO)2 catalyst systems

Ligand ν1 (cm-1) ν2 (cm-1)

L2 1953 1984 L5 1941 1955 L8 1963 , 1954 , 1942 1983

The C3 bridged ligand L8 shows more bands with different intensities in the IR-

spectrum. This indicates that more than one species are present. This is consistent with

the findings in the HP-NMR experiments. The position of the bands in the spectrum are

indicative for the electron density on the Rh atom in the catalyst complex. The lower

wavenumbers obtained for the ligand L5 would indicate more donation from the

phosphorus atoms to the Rh center than ligand L2.

4.3 Conclusions

The tested bisaminophosphine ligands give active catalysts in the asymmetric

hydroformylation of styrene and vinyl acetate when combined with Rh(acac)(CO)2 as

the metal precursor. Where branched/linear ratio reach excellent values, namely up to

12 for styrene and >50 for vinyl acetate, the enantioselectivities remained low with a

maximum of 51 % for vinyl acetate. HP-NMR experiments show that all ligands

coordinate predominantly in the equatorial-equatorial coordination mode in the trigonal

bipyrimidal resting state of the catalyst. For the 1-naphthyl derived bisaminophosphine

ligand L5 HP-IR proves this is the only coordination mode. However, the ability to

differentiate between stereoisomers apparently remains low.

4.4 Perspective

Considering the requirements for efficient stereocontrol, the obtained low ee makes

sense. First one specific coordination mode of the ligand in the active catalyst has to be

selected, which is equatorial-equatorial in this case applying the bisaminophosphine

ligands. The precondition of coordination mode is now met. Then interactions of the

substituents of the chiral ligand with the substrate (during coordination in the transition

state) have to control the stereoselectivity.

80


Due to the fact there is a lot of space in the plane of an ee-coordinated species, the

ligand has to bear very bulky groups for efficient interaction. This is reflected by the

fact that all successful systems relying on an ee-coordinated ligand, reported so far, are

very bulky ligands like the diphosphites described by Babin and Van Leeuwen.[10] As a

consequence, the rigidity and the bulk of the bisaminophosphine ligands should be

increased, preferably based on more structural information on the systems derived from

molecular structures obtained by X-ray diffraction and or computer modeling studies.

For instance the data presented in Chapters 2 and 3 could prove to be valuable.

With the demonstrated ability to control the coordination mode effectively, the

bisaminophosphine ligands have a high potential to reach higher ee’s in asymmetric

hydroformylation, especially with view on their modular construction.


Part of this work has been published (Eric J. Zijp, Jarl Ivar van der Vlugt, Duncan M.

Tooke, Anthony L. Spek and Dieter Vogt, Dalton Transactions, 2005, 512-517).

Avantium Technologies is kindly acknowledged for financial support, Umicor Co. is

thanked for the generous loan of precious metals. Brahim Mezzari is gratefully

acknowledged for technical assistance during the HP-NMR experiments and Pieter

Magusin for discussions on this part of the research. Ruben van Duren is thanked for

the aid on the HP-IR experiments.


General


Syngas (1:1 CO/H2) was bought from Hoekloos. Solvents were either taken HPLC-

grade from an argon-flushed column, packed with aluminum oxide, or distilled under

argon prior to use over an appropriate drying agent. NMR spectra were recorded at

room temperature on a Varian Mercury 400 MHz spectrometer, the HP-NMR spectra

were recorded on a Bruker 200 MHz spectrometer. Chemical shifts are given in ppm

and spectra are referenced to CDCl3 (1H) or 85% H3PO4 (31P{1H}). High-pressure

infrared measurements were performed on a Shimadzu Fourier Transform Infrared

81


Spectrophotometer FT-IR 8300 with a Michelson interferometer. The spectra were

processed with Hyper-IR software provided by Shimadzu Corp. An in-house build

autoclave after design by Van Leeuwen et al.22 made from stainless steel (SS 316) with

a volume of 50 mL, equipped with a temperature controller and a pressure transducer

was placed in the spectrophotometer. The infrared beam was led through ZnS windows

(transparent up to 700 cm-1, 10 mm internal diameter) and an effective path length of

0.4 mm. Stirring was performed with a mechanical stirrer equipped with a Rushton-

type stirrer. Gas chromatographic analyses were done on a Shimadzu 17A or a Carlo

Erba (Vega Serie 2) apparatus. The reaction mixtures obtained from the asymmetric

hydroformylation of styrene were analyzed on a 25 m Ultra 2 column (carrier gas 100

kPa N2, FID detector) and for vinyl acetate on a 50 m PONA column (carrier gas 150

kPa He, FID detector). The enantiomeric excess for 2-phenylpropanal was determined

after reduction of the aldehyde and subsequent esterification to the corresponding

trifluoro acetate on a 25 m Lipodex E capillary column (carrier gas 50 kPa H2, FID

detector), 2-acetoxypropanal was analyzed without derivatization on a 50 m FS-

Cyclodex β I/P column (carrier gas 140 kPa He, FID detector).

Hydroformylation experiments

Caution! The hydroformylation experiments are performed with syngas (1:1 = CO/H2)

which is extremely poisonous. Accidents may be lethal. When working with carbon

monoxide a sensitive personal detector should be carried and all experiments are to be

performed in a well ventilated fumehood equipped with a detector, maintaining the CO

concentration in the fumehood below the MAC-value.

Hydroformylation of styrene

Hydroformylation experiments were carried out in home made 75 mL stainless steel

autoclaves, equipped with a glass inner beaker and a magnetic stirrer. The temperature

was controlled by an internal thermocouple. In a typical hydroformylation experiment

the autoclave was heated up to 60 °C and dried under vacuum for 1 h. After cooling the

catalyst precursor (13.1 μmol in 5 mL toluene) is introduced by syringe, rinsing the

Schlenk tube with an additional 5 mL solvent. Likewise the appropriate ligand (26.2

μmol) is added after which the autoclave is purged with syngas, pressurized to 20 bar

and heated to the reaction temperature for the duration of the preformation time (1 h).

82


Then a freshly prepared stock solution of styrene ((2.0 mL, 17.4 mmol) filtered over

neutral, activated alumina), internal standard n-decane (1.0 mL, 5.1 mmol) and 5 mL

toluene was added under pressure. The total mixture was allowed to react for 15 h. The

autoclave was then cooled, depressurized and vented with argon. The reaction mixture

was transferred and distilled quantitatively to remove catalyst and excess of ligand. A

sample was analyzed for conversion and regioselectivity. For the ee determination a

part of the mixture was dropped into a suspension of LiAlH4 in Et2O and after 1 h

quenched with water. The mixture was extracted and dried over NaSO4 and evaporated

to dryness under reduced pressure. The residue was dissolved in CH2Cl2 and treated

with 2 equiv of trifluoro acetic acid anhydride. After evaporation to dryness under

reduced pressure a sample of the resulting trifluoro acetate (20 μL) was dissolved in

CH2Cl2 and analyzed by chiral GC.

Hydroformylation of vinyl acetate

A similar procedure as for the hydroformylation of styrene was used. Vinyl acetate (1.5

mL, 16.3 mmol), internal standard ethyl propionate (0.5 g, 4.9 mmol) and benzene as

solvent were applied. After the catalytic experiment the reaction mixture was distilled

under vacuum in order to remove catalyst and excess of ligand. The composition of the

mixture was measured directly by GC without further workup.

HP-NMR experiments

A 10mm outer diameter sapphire NMR tube was filled with a solution of

Rh(acac)(CO)2 (5.0 mg, 19.4 mmol), 1.1 equiv ligand ((21.3 mmol) small excess for

referencing to free ligand) and toluene-d8 (1.5 mL). The tube was purged three times

with syngas and pressurized to 20 bar. The tube was then brought to the desired

temperature and spectra were recorded over time.

HP-IR experiments

The autoclave was flushed with argon for at least an hour. Then a solution of

Rh(acac)(CO)2 (4.9 mg, 19 mmol) and ligand (20 mmol) in 15 mL cyclohexane were

introduced under argon outflow. The equipment was flushed three times with syngas

and afterwards brought to the desired temperature and syngas pressure. Spectra were

recorded after 1 hour preformation.

83


4.7 References

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Compounds, Vol 1, Wiley-VCH, Weinhein, 1996, 3. [3] W. A. Herrmann, B. Cornils, Angew. Chem, 1997, 109, 1074. [4] a) B. Cornils, W. A. Herrmann, Ed., Applied Homogeneous Catalysis with Organometallic

Compounds, Vol 1, Wiley-VCH, Weinhein, 2002, 31; b) P. W. N. M. van Leeuwen, C. Claver,

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1997, 16, 2929. [11] M. Diéguez, O. Pàmies, A. Ruiz, S. Castillón, C. Claver, Chem. Eur. J. 2003, 7, 3086. [12] a) J. K. Stille, H. Su, P. Brechot, G. Parinello, L. S. Hegedus, Organometallics, 1991, 10, 1183;

b) R. van Duren, Platinum Catalyzed Hydroformylation, PhD thesis, Eindhoven University of

Technology, 2004. [13] J. J. Carbó, A. Lledós, D. Vogt, C. Bo, Chem. Eur. J. 2006, 12, 1457. [14] R. Ewalds, Asymmetrische Hydroformylierung mit Phosphor-chiralen Aminophosphin

phosphinit-Liganden, PhD thesis, RWTH Aachen, 1997. [15] a) S. Breeden, M. Wills, J. Org. Chem. 1999, 64, 9735; b) S. Breeden, D. J. Cole-Hamilton, D.

F. Foster, G. J. Schwarz, M. Wills, Angew. Chem. Int. Ed. 2000, 39, 4106; c) J. Ansell, M.

Wills, Chem. Soc. Rev. 2002, 31, 259. [16] T. J. Kwok, D. J. Wink, Organometallics, 1993, 12, 1954. [17] C. F. Hobbs, W. S. Knowles, J. Org. Chem. 1981, 46, 4422. [18] a) C. B. Dieleman, P. C. J. Kamer, J. N. H. Reek, P. W. N. M. van Leeuwen, Helv. Chim. Acta,

2001, 84, 3269; b) G. J. H. Buisman, L. A. van der Veen, P. C. J. Kamer, P. W. N. M. van

Leeuwen, Organometallics, 1997, 16, 5681. [19] A. Castellanos-Páez, S. Castillón, C. Claver, P. W. N. M. van Leeuwen, W. G. J. de Lange,

Organometallics, 1998, 17, 2543. [20] J. I. van der Vlugt, R. Sablong, P. C. M. M. Magusin, A. M. Mills, A. L. Spek, D. Vogt,

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84


[21] L. A. van der Veen, P. H. Keeven, G. C. Schoenmaker, J. N. H. Reek, P. C. J. Kamer, P. W. N.

M. van Leeuwen, M. Lutz, A. L. Spek, Organometallics, 2000, 19, 872. [22] A. van Rooy, Rhodium Catalysed Hydroformylation with Bulky Phosphites as Modifying

Ligands, PhD thesis, Universiteit van Amsterdam, 1995.

85

Chapter 5

Phosphonite-Phospholane Ligands Applied in

Rh-Catalyzed Asymmetric Hydroformylation

Mixed phosphonite-phospholane ligands are effective when

applied in Rh-catalyzed asymmetric hydroformylation of

styrene. Branched/linear ratio’s higher than 20 were obtained

while the ee reached a moderate 55%. The dependence of the

ligand performance on pressure, temperature, and ligand

concentration was studied. NMR studies did not reveal the

coordination mode of the ligands in the trigonal bipyramidal

resting state of the catalytic cycle.

Chapter 5 Phosphonite-Phospholane Ligands Applied in Rh-Catalyzed Asymmetric Hydroformylation

5.1 Introduction

The discovery and development of new successful ligands for asymmetric

homogeneous catalysts is usually a very tedious process most of the time only governed

by rules of thumb and accompanied by a lot of trial and error. However, a huge variety

of chiral ligands has been developed for certain reactions, e.g. for hydrogenation or

allylic substitution, that have never been tested for other catalytic transformations. The

potential of this existing pool of chiral ligands should not be underestimated although

results might come as a surprise, valuable new insight might be generated. Interesting

results on asymmetric hydroformylation were reported very recently by Abboud et al.

applying phosphacyclic ligands that were developed for asymmetric hydrogenations.[1]

A similar approach was followed in this study, applying phosphonite-phospholane

ligands in the Rh-catalyzed asymmetric hydroformylation of styrene.

In a joint effort of CIBA SC and A. Salzer at RWTH Aachen, a flexible approach to the

synthesis of different families of bidentate phosphorus ligands was followed for

application in asymmetric catalysis. The asymmetric hydrogenation of dehydration acid

derivatives, enamides, and itaconates proceeded with ee values of up to 98.7 %.[2]

Evaluating the structure of the mixed phosphonite-phospholanes (see Figure 1) in that

study revealed attractive features which often proved to be valuable if applied in

asymmetric hydroformylation of alkenes: The ligands consist of a rigid ligand scaffold

with mixed phosphorus functionalities expected to allow for a predominant ea

configuration of the ligand in the trigonal bipyramidal resting state of the catalyst.

Besides this the stereogenic information is close to the phosphorus for the phospholane

part[3] and the generally very effective atropisomeric bisnaphthol[4] is included in the

phosphonite moiety of the ligand.

Those observations prompted us to apply the ligands in the asymmetric

hydroformylation of styrene. Chapter 1 of this thesis contains an introduction to the

field of asymmetric hydroformylation, including description of the successful ligands,

studies into the mechanism of stereoselection and possible applications in real-life

chemistry.

88


89

O

OP

S

P

O

OP

S

P

I II Figure 1 Applied BINOLane ligands I and II.

Here we present the successful application of the BINOLane ligands in the asymmetric

hydroformylation of styrene. Investigations of the coordination mode of the ligands in

the trigonal bipyramidal resting state of the catalyst were undertaken.

5.2 Results

5.2.1 Catalysis

Styrene, being a generally accepted and widely used benchmark substrate for the

asymmetric hydroformylation reaction, was selected as the substrate (see Eq. 1).

CO/H2

Rh/L2

CHO

CHO

+*

(1)

The catalysts were prepared for this thorough screening by in situ mixing the ligands

with the metal precursor Rh(acac)(CO)2 in a ratio 2:1 and heating in a AMTEC SPR16

reactor under typical reaction conditions (60°C, 20 bar (1:1 CO/H2)) for 1 hour.

Subsequently the substrate with internal standard was injected and the mixture was

allowed to react under the indicated reaction conditions while measuring the gas

uptake. After workup the product distribution was analyzed by (chiral) GC directly or,

alternatively, after derivatization to the trifluoro acetic ester. Both methods gave

identical values for the ee. The results of the first screening are presented below (Table

1).


Table 1 Selected results of initial ligand screening under standard conditions.a

Ligand Conversion b b/l c ee (%) d I 100 21 31 (S) II 27 21 37 (R)

a Reaction conditions: T = 60 °C; p = 20 bar (1:1 CO/H2); solvent: 4 mL toluene; 2 mL styrene, 1 mL

decane internal standard; 14.3 μmol Rh(acac)(CO)2; L:Rh = 2; preformation t = 1h; reaction t = 24h. b

Percent conversion of styrene after 24h c Branched / linear ratio. d Enantiomeric excess determined by

chiral GC.

The catalyst based on BINOLane I, with the (R) enantiomer of BINOL in the

phosphonite moiety, gives full conversion of styrene in the applied time. The

branched/linear ratio is excellent with 21 and a reasonable ee of 31% is reached. With

BINOLane II, with an opposite configuration of the BINOL part of the ligand, the

conversion after 24 hours is still low and the branched/linear ratio is also 21. The

obtained branched/linear ratios can compete with the numbers obtained for settled

hybrid ligands like AMPP (20-40) [5] and BINAPHOS (7-12).[4a] The ee values of the

styrene hydroformylation products induced by the BINOLane ligands however, are

moderate compared to the renowned ligands AMPP (46%-75%)and BINAPHOS (85%-

94%).

It seems that the absolute configuration of the BINOL moiety determines the absolute

configuration of the major product. The stereogenic centers of the phospholane ring

form an inefficient matched or miss-matched pair in terms of enantioselectivity.

To determine the stability of the catalyst we followed the reaction over time by taking

samples on predetermined times, while measuring the gas uptake. The samples were

analyzed on b/l ratio and enantioselectivity (see Table 2 for details and Figure 2 for a

graphic representation).

90


91

0 5 10 15

0

50

100

150

200

250

Gas

upt

ake

(mL)

0

10

30

40

20

Gas uptake ee (R) b/l

Table 2 b/l ratio’s and ee’s followed over time for the respective ligands (R,R)-Me-BINOLane (I) and

(S,R)-Me-BINOLane (II).a

time (h) b/l (I) b ee (S) (I) (%) c b/l (II) b ee (R) (II) (%) c 0,37 22,8 32 19,2 38 0,71 23,5 32 19,6 36 1,04 23,9 32 19,6 35 1,87 24,6 31 20,4 36 3,21 24,8 33 20,2 37 5,21 24,3 33 20,9 36 9,55 23,0 33 21,5 37 15,3 22,6 33 21,8 38

a Reaction conditions: T = 60 °C; p = 20 bar (1:1 CO/H2); solvent: 4 mL toluene; 2 mL styrene, 1 mL

decane internal standard; 14.3 μmol Rh(acac)(CO)2; L:Rh = 2; preformation t = 1h; reaction t = 16h; 100

μL samples taken over time b Branched / linear ratio c Enantiomeric excess determined by chiral GC.

Figure 2a) upper and 2b) lower. Gas uptake, b/l ratio and ee followed over time for the respective

ligands (R,R)-Me-BINOLane (I) and (S,R)-Me-BINOLane (II).

0 5 10 150

100

200

300

400

500

600

700 Gas uptake ee (S) b/l

Time (h)

Gas

upt

ake

(mL)

0

25

50

75

100


For both ligands I and II the ee’s are virtually constant. The b/l ratio’s seem to increase

slowly over time, maybe dropping marginally when the conversion is full (at extended

reaction times for ligand I). This indicates that the catalyst is stable over time, but the

preformation time could be extended (or the reaction conditions during preformation

intensified) to ensure full conversion to the catalyst resting state prior to substrate

injection.

To assess the dependencies of the performance of the system on applied pressure,

temperature, and stoichiometry these parameters were systematically varied.

Firstly the applied pressure was varied from 10-40 bar syngas (1:1 CO/H2). The

obtained data are gathered in Table 3 and 4.

Table 3 b/l ratio and ee obtained for different applied pressures by using ligand (R,R)-Me-BINOLane (I).a

bar conversion (%) b b/l c ee (S) d 10 100 18 26 20 100 19 30 30 99 24 33 40 99 25 32

a Reaction conditions: T = 60 °C; p = x bar (1:1 CO/H2); solvent: 4 mL toluene; 2 mL styrene, 1 mL

decane internal standard; 14.3 μmol Rh(acac)(CO)2; I:Rh = 2; preformation t = 1h; reaction t = 24h; b

Percent conversion of styrene after 24h c Branched / linear ratio d Enantiomeric excess determined by

chiral GC. Table 4 b/l ratio and ee obtained for different applied pressures by using ligand (S,R)-Me-BINOLane (II).a

bar conversion (%) b b/l c ee (R) d 10 13 18 36 20 27 21 36 30 32 22 36 40 36 22 37

a Reaction conditions: T = 60 °C; p = x bar (1:1 CO/H2); solvent: 4 mL toluene; 2 mL styrene, 1 mL

decane internal standard; 14.3 μmol Rh(acac)(CO)2; II:Rh = 2; preformation t = 1h; reaction t = 24h; b

Percent conversion of styrene after 24h c Branched / linear ratio d Enantiomeric excess determined by

chiral GC.

92


93

0 5 10 15 200

100

200

300

400

500

10 bar 20 bar 30 bar 40 bar

Time (h)

Gas

Upt

ake

(mL)

0

10

20

30

Conversion (%

)

Figure 3 Gas uptake followed over time for different applied pressures by using ligand (II).

For increasing syngas pressure the conversion, the ee, and the b/l ratio all seem to go

up, albeit with small numbers. This is in contrast with the AMPP ligands where a

negative influence of the pressure on the enantioselectivity was observed.[5] Coworkers

of DOW Pharma found for a range of ligands applied for styrene, allyl cyanide and

vinyl acetate that all enantioselectivities were unaffected by changing pressure. The

regioselectivity for the styrene increased with increasing pressure, where the vinyl

acetate products were obtained with a lower regioselectivity.[6]

The second investigated parameter was the reaction temperature which was varied from

25-120 ºC. Tables 5 and 6 show the selected results. During these investigations the

applied temperature during the 1h catalyst preformation was constant with 60 ºC but the

reaction times varied.


Table 5 b/l ratio and ee obtained for different reaction temperatures applying ligand (R,R)-Me-

BINOLane (I). a

Temperature (°C) b/l b ee (S) (%) c 25 32 32 40 32 31 60 21 31 80 12 21 100 5 3 120 3 0

a 14.3 μmol Rh(acac)(CO)2, 2 equiv I, 4 mL toluene, 2 ml styrene, 1 mL decane, p = 20 bar CO:H2 (1:1),

1h preformation b Branched / linear ratio c Enantiomeric excess determined by chiral GC.

Table 6 b/l ratio and ee obtained for different reaction temperatures applying ligand (S,R)-Me-

BINOLane (II). a

Temperature (°C) b/l b ee (R) (%) c 25 29 55 40 28 52 60 21 37 80 14 28 100 6 8 120 4 2

a 14.3 μmol Rh(acac)(CO)2, 2 equiv II, 4 mL toluene, 2 ml styrene, 1 mL decane, p = 20 bar CO:H2 (1:1),

1h preformation b Branched / linear ratio c Enantiomeric excess determined by chiral GC.

At lower temperature the selectivity of the reaction, both in terms of b/l ratio as ee were

maximum, reaching 97% selectivity of the branched product for ligand I and more than

50% enantiomeric excess for ligand II. Logically the rate of reaction is lowest in these

cases. At higher reaction temperature the undesired polymerization of styrene plays a

significant role, besides a higher degree of degradation of the catalyst under these harsh

conditions.

The last parameter that was varied was the Rh/L(I) ratio. Table 7 gives the relevant

numbers and a graphic representation is shown in Figure 4.

94


95

Table 7 Conversion, b/l ratio and ee obtained for several stoichiometries of ligand (R,R)-Me-BINOLane

(I) to Rh. a

x equiv ligand (I) Conversion (%) b/l ee (S) (%) 0 100 2 0 1 100 8 12 2 31 20 22 3 12 22 29 4 0 - - 5 0 - -

a 14.3 μmol Rh(acac)(CO)2, x equiv (I), 4 mL toluene, 2 ml styrene, 1 mL decane, T = 60 °C, p = 20 bar

CO:H2 (1:1), 1h preformation, 23h reaction. b Percent conversion of styrene after 23h c Branched / linear

ratio c Enantiomeric excess determined by chiral GC.

0 5 10 15 200

250

500

750

1000 1 equiv 2 equiv 3 equiv 4 equiv

Time (h)

Gas

Upt

ake

(mL)

Figure 4 Gas uptake followed over time for selected stoichiometries of ligand (R,R)-Me-BINOLane (I)

to Rh.

It can be seen that the fastest reactions are observed with the smallest amounts of

ligand. The metal precursor Rh(acac)(CO)2 without additional ligand is under the

applied conditions active as hydroformylation catalyst, albeit with very low selectivity

towards the desired branched product. Also with one equivalent ligand the rate is high

but now the selectivity rises fast. With 2 equivalents of ligand the optimal amount is

reached. The full potential of the ligand in steering the reaction is used and at higher

ratio’s of ligand to rhodium the reaction becomes too slow.


PCO

Rh CO

HOC

P

Rh CO

H

CO

OC

OC

P^P

CO CO

a b c

PP

Rh CO

HOC

Figure 5 Complex equilibria dependent on ligand concentration.

The reasons for this are the equilibria between non-coordinated, semi-coordinated and

coordinated complexes (Figure 5). If a larger amount of available Rh is present as

complexes a or b the reaction would become less selective. A higher concentration of

ligand would shift the equilibria more to the most selective coordinated complex c. An

even larger amount of ligand could force the formation of (inactive) complexes with

more than one coordinated ligand, which is undesirable.

A higher ratio of ligand to rhodium not always affects the catalysis in a positive way.

For instance sugar-derived diphosphite ligands are normally employed in a 1:1 ratio

and an increase does not affect the catalysis much at all.[7]

5.2.2 NMR Studies

Two small tests were done to check the coordination of the ligand to Pd and Rh. When

equimolar amounts of (R,R)-Me-BINOLane (I) were reacted with either Pd(cod)Cl2 or

[Rh(cod)2]BF4 in CDCl3 instantaneous reactions were observed. Obtained NMR-data

can be found in Table 8.

Table 8 NMR-data of metal-complexes of (R,R)-Me-BINOLane (I).

Metal precursor δ (ppm) phospholane

δ (ppm) phosphonite

2J(P-P) (Hz) 1J(P-M)

Pd(cod)Cl2 80.8 140.8 16.7 - [Rh(cod)2]BF4 65.0 163.9 34.6 148.3 - 233.5

The obtained values suggest a mononuclear cis-coordination for both complexes, as is

found for a related cationic complex described by the coworkers of CIBA SC (Figure 6,

R = ethyl).[2a]

96


97

S

PR R

P

R

R

Figure 6 Bisphospholane ligand by CIBA.

In a comparable manner as described in Chapter 4 for the bisaminophosphine ligands

the coordination behavior of the here used Me-BINOLane ligands was investigated to

reveal the structure of the trigonal bipyramidal resting state of the hydroformylation

catalyst. Equimolar amounts of ligand and Rh(acac)(CO)2 were dissolved in deuterated

toluene in a 10mm sapphire NMR tube and pressurized to 20 bar of syngas. After 1

hour preformation time at elevated temperature 60°C the tube was cooled to room

temperature and measured on a Bruker 200 MHz NMR machine.

Under the applied conditions however, no signal in the hydride region was obtained.

Strategies to lengthen relaxation times, to widen the spectral width, to increase

concentrations and to prolong measuring times did not result in any information on the

coordination behavior. Maybe at room temperature the coalescence is reached for a

fluxional process in the complexes, thus resulting in a non-appearing signal. No

variation in temperature was attempted.

Comparing the structure of the ligands to a bisphospholane ligand based on the same

benzo[b]thiophene scaffold (figure 6, with R = ethyl) where a bite angle of 85° P-Rh-P

is found in a cationic Rh complex the expected coordination mode in the trigonal

bipyramidal resting state of the catalyst would be equatorial-axial. In this coordination

mode the ideal 90° angle is closely resembled. The different electronic properties of the

phospholane and the phosphonite part present in the ligand used in our study could

ensure a preferential coordination and thus the respectable enantioselectivities achieved

in this study.


5.3 Conclusions

The Me-BINOLane ligands form active catalysts for the Rh-catalyzed asymmetric

hydroformylation of styrene and the regioselectivity for the branched product is high

with b/l ratio’s over 20. The ee’s obtained depend mostly on the atropisomeric element

in the phosphonite part of the ligand and reach values just over 50%. Application of 2

equivalents of ligand with respect to rhodium is most efficient in a compromise

between activity and enantioselectivity.

5.4 Perspective

The ee’s obtained in this study for the asymmetric hydroformylation of styrene can not

compete with the numbers obtained with a variety of other ligands reported elsewhere.

Since the coordination mode of the ligands under reaction conditions was not disclosed

it remains speculation if preferential coordination is reached. The synthetic strategy

however allows for independent variation of the ligands in both the phospholane as the

phosphonite part. Substitution on the 2- and 2’-positions of the used bisnaphthol often

creates a more stereoselective ligand, as could be the use of ethyl- or propyl-

substituents on the phospholane ring. Other substrates like vinyl acetate or allyl cyanide

could be used to check the efficacy of the ligands in their enantioselective conversion.

The presence of the sulfur heteroatom may act as a possibility to electronically modify

the backbone (e.g. by coordination to early transition metals) or as a means to anchor

the ligands to a support, thus allowing for recycling of the ligand (or catalyst).


Avantium Technologies is kindly acknowledged for financial support, Umicor Co. is

thanked for the generous loan of precious metals. CIBA SC is thanked for putting a

sample of the used ligands to our disposal and we are especially grateful to Ulrich

Berens for detailed help on the synthetic procedures. Leandra Cornelissen is

acknowledged for the blood, sweat and tears shed during the syntheses of the ligands.

Ton Staring is gratefully acknowledged for his skillful technical assistance during the

98


99

chromatographic analyses. And finally Christian Müller is thanked for his kind help

during the AMTEC runs.


General



received or distilled from CaH2 before use. Syngas (CO:H2 (1:1)) was bought from

Hoekloos. Solvents were either taken HPLC-grade from an argon-flushed column,

packed with aluminum oxide, or distilled under argon prior to use over an appropriate

drying agent. The NMR spectra were recorded on a Bruker 200 MHz spectrometer. Gas

chromatographic analyses were done on a Shimadzu 17A or a Carlo Erba (Vega Serie

2) apparatus. The reaction mixtures obtained from the asymmetric hydroformylation of

styrene were analyzed on a 25 m Ultra 2 column (carrier gas 100 kPa N2, FID detector).

The enantiomeric excess in the product 2-phenylpropanal was determined after

reduction of the aldehyde and subsequent esterification to the corresponding trifluoro

acetate on a 25 m Lipodex E capillary column (carrier gas 50 kPa H2, FID detector), or

without derivatization on a Supelco Betadex column (carrier gas 60 kPa He, FID

detector).

Hydroformylation experiments

Caution! The hydroformylation experiments are performed with syngas (1:1 = CO/H2)

which is extremely poisonous. Accidents may be lethal. When working with carbon

monoxide a sensitive personal detector should be carried and all experiments are to be

performed in a well ventilated fume hood equipped with a detector, maintaining the CO

concentration in the fume hood below the MAC-value.

Hydroformylation of styrene

Hydroformylation experiments were carried out in an AMTEC SPR16 machine. Before

use the reactors were heated up to 60 °C and dried under vacuum for 1 h. After cooling

the catalyst is introduced by syringe after which the autoclaves are purged with syngas,

pressurized to 20 bar and heated to the reaction temperature for the duration of the


preformation time (1 h). After cooling and lowering the pressure a freshly prepared

stock solution of styrene ((2.0 mL, 17.4 mmol) and internal standard n-decane (1.0 mL,

5.1 mmol) was added. The mixture was then brought to the desired temperature and

pressure and it was allowed to react. The autoclaves were then cooled, depressurized

and vented with argon. From the contents a sample was analyzed for conversion and

regioselectivity on a Ultra column. For the ee determination 1 mL of the mixture was

dropped into a suspension of 150 mg LiAlH4 in Et2O and after 1 h quenched with

water. The mixture was extracted and dried over NaSO4 and evaporated to dryness

under reduced pressure. The residue was dissolved in CH2Cl2 and treated with 0.5 mL

of trifluoro acetic anhydride. After evaporation to dryness under reduced pressure a

sample of the resulting trifluoro acetate (20 μL) was dissolved in CH2Cl2 and analyzed

on a Lipodex column. Alternatively the ee could be determined directly on a Supelco

Betadex column.

NMR experiments

A 10mm outer diameter sapphire NMR tube was filled with a solution of

Rh(acac)(CO)2 (5.0 mg, 19.4 mmol), 1.1 equiv ligand (21.3 mmol, small excess for

referencing to free ligand) in toluene-d8 (1.5 mL). The tube was purged three times with

syngas and pressurized to 20 bar. The tube was then brought to the desired temperature.

After 1 hour the pressure was released and the contents were quickly transferred to a 5

mm NMR tube and directly measured or analyzed on a Bruker 200 MHz NMR machine

without prior release of pressure.

100


101

5.7 References

[1] A. T. Axtell, J. Klosin, K. A. Abboud, Organometallics, 2006, 25, 5003. [2] a) U. Berens, U. Englert, S. Gwyser, J. Runsink, A. Salzer, Eur. J. Org. Chem. 2006, 2100; b)

U. Berens to Solvias A.G., WO 03/031456 A2. [3] e.g. Me-DuPhos; M. J. Burk, J. E. Feaster, W. A. Nugent, R. L. Harlow, J. Am. Chem. Soc.

1993, 115, 10125.

[4] For successful applications of the bisnaphthol unit in asymmetric hydroformylation see e.g.

(R,S)-BINAPHOS a) N. Sakai, S. Mano, K. Nozaki, H. Takaya, J. Am. Chem. Soc. 1993, 115,

7033 or (R,S)-Yanphos; b) Y. Yan, X. Zhang, J. Am. Chem. Soc. 2006, 128, 7198. [5] R. Ewalds, E. B. Eggeling, C. H. Alison, P. C. J. Kamer, P. W. N. M. van Leeuwen, D. Vogt,

Chem. Eur. J. 2000, 6, 1496. [6] A. T. Axtell, C. J. Cobley, J. Klosin, G. T. Whiteker, A. Zanotti-Gerosa, K. A. Abboud, Angew.

Chem. Int. Ed. 2005, 44, 5834. [7] M. Diéguez, O. Pàmies, A. Ruiz, S. Castillón, C. Claver, Chem. Commun., 2000, 1607.

Summary

Summary

Investigations on Rhodium-Catalyzed Asymmetric Hydroformylation

In asymmetric metal catalysis it is of special value to have chiral ligand classes

available which allow for a straight forward and highly modular, maybe even

automated synthesis and variability of the molecular structure. From an academic point

of view this is important in order to study in detail the structure-performance relations

in order to generate basic understanding of stereoselection mechanisms and ultimately

derive at a rational design of new catalysts for a given synthetic problem. From an

industrial point of view readily available ligand libraries allow for a rapid sceening and

optimization of a catalyst for a given substrate, as especially in fine chemicals business

the given time for development is extremely short.

Theoretical insight, next to structure-performance relations, is obtained by studying the

coordination behavior of the ligands in catalytically active species by means of

structural analysis and in situ spectroscopic investigations. This can provide valuable

data for further theoretical studies on a high level.

Chapter one gives an introduction in asymmetric hydroformylation. Starting with a

historical overview and ending with the state-of-the-art ligand systems that give the

currently most active and selective catalysts. High-Throughput-Experimentation,

theoretical investigations, and spectroscopic studies are identified as the important

elements leading to success.

In Chapter two the versatile modular synthesis of novel symmetrically and non-

symmetrically substituted bisaminophosphine ligands is described. Molecular structures

of the ligands and complexes thereof revealed a trigonal planar geometry of the

nitrogen atoms bound to the phosphorus donor atom, resulting from a significant

contribution of π-bonding to the P-N bond.

103

Summary

DFT calculations were performed on model compounds for bisaminophosphine ligands

to analyze the geometries and charge distributions, which are discussed in Chapter

three. The computed structure of a simplified cis-Pd complex of a bidentate

bisaminophosphine ligand gives valuable information on the coordination behavior.

Application of catalysts generated in situ from [Rh(cod)2]BF4 and bisaminophosphines

in the asymmetric hydrogenation of methyl (Z)-N-acetylaminocinnamate gave ee’s of

up to 91%. The contributions to stereoselection of individual aminophosphine moieties

are recognized.

Chapter four shows that the bisaminophosphine ligands form effective catalysts in the

Rh-catalyzed asymmetric hydroformylation of prochiral alkenes. The regioselectivities

for styrene and vinyl acetate were very good, while the enantioselectivities however

stay low with 12% and 51% respectively. HP-NMR studies indicated that equatorial -

equatorial coordination mode in the catalytic resting state is preferred for these ligands,

as was confirmed by HP-IR spectroscopy.

Finally in Chapter five mixed phosphonite-phospholane ligands are presented. They

are effective when applied in the Rh-catalyzed asymmetric hydroformylation of

styrene. Branched/linear ratio’s higher than 20 were obtained and the ee reached a

moderate 55%. NMR studies did not reveal the coordination mode of the ligands in the

trigonal bipyrimidal resting state of the catalytic cycle. The dependency of the catalyst

performance on the parameters temperature, pressure and L/Rh ratio were determined.

104

Samenvatting

Samenvatting

Onderzoek in Rhodium-Gekatalyseerde Asymmetrische Hydroformylering

In asymmetrische homogene metaalkatalyse is het van extreem belang om klassen van

chirale liganden beschikbaar te hebben die eenvoudig en modulair opgebouwd zijn en

wellicht zelfs geautomatiseerd gesynthetiseerd kunnen worden. Voor de academische

wereld is dit belangrijk om gedetailleerd structuur-prestatie relaties te bestuderen om

kennis te vergaren over de mechanismen van stereoselectie om uiteindelijk uit te komen

bij het rationele ontwerp van nieuwe katalysatoren voor een bepaald synthetisch

probleem. Vanuit het oogpunt van de chemische industrie zullen beschikbare

databanken aan liganden bijdragen aan snelle screening en optimalisatie van

katalysatoren voor een gegeven substraat, wat belangrijk is aangezien vooral in de fijn-

chemische industrie de beschikbare tijd voor ontwikkeling erg kort is.

Theoretisch inzicht, naast structuur-prestatie relaties, wordt verkregen door het

coördinatie-gedrag van liganden in de katalytisch actieve deeltjes te bestuderen door

structuur analyses en in situ spectroscopische technieken. Dit kan belangrijke data

opleveren voor verdere theoretische studies op een hoog niveau.

Hoofdstuk één geeft een introductie over asymmetrische hydroformylering, startend

met een historisch overzicht en eindigend met de toonaangevende ligandsystemen die

op dit moment de meest actieve en selectieve katalysatoren vormen. High-Throughput-

Experimentation, theoretische beschouwingen en spectroscopische onderzoeken

worden genoemd als belangrijke factoren die hierbij tot succes kunnen leiden.

In Hoofdstuk twee is de modulaire synthese van nieuwe symmetrisch en niet-

symmetrisch gesubstitueerde bisaminofosfine liganden beschreven. Kristalstructuren

van liganden en complexen daarvan lieten de trigonaal planaire geometrie zien van de

stikstof atomen die gebonden zijn aan de fosfor donoratomen. Dit is het gevolg van een

substantiële bijdrage van een π-binding aan de P-N binding.

105

Samenvatting

Er zijn Density Functional Theory berekeningen op model verbindingen voor

bisaminofosfine liganden uitgevoerd om geometrieën en ladingverdelingen te

analyseren zijn uitgevoerd. Dezen worden in Hoofdstuk drie gepresenteerd. De

berekende structuur van een gesimplificeerd cis-Pd complex van een bidentate

bisaminofosfine ligand gaf belangrijke informatie over het coördinatiegedrag. De

toepassing van katalysatoren in-situ gegenereerd van [Rh(cod)2]BF4 en

bisaminophosphines in de asymmetrische hydrogenering van methyl (Z)-N-

acetylaminocinnamaat gaf ee’s tot 91%. De bijdragen van de individuele aminofosfine

delen aan de stereoselectie zijn onderkend.

Hoofdstuk vier laat zien dat bisaminofosfine liganden effectieve katalysatoren vormen

in de Rh-gekatalyseerde asymmetrische hydroformylering van prochirale alkenen. De

regioselectiviteiten van zowel styreen als vinyl acetaat waren erg goed, de ee’s bleven

echter laag met respectievelijk 12% en 51%. NMR studies onder verhoogde druk gaven

aan dat equatoriaal – equatoriaal de geprefereerde coördinatie vormt voor de liganden,

wat bevestigd werd door hoge druk IR-spectroscopie.

Tenslotte worden in Hoofdstuk vijf gemixte fosfoniet-fosfolaan liganden

gepresenteerd. Ze zijn effectief wanneer ze toegepast worden in de Rh-gekatalyseerde

asymmetrische hydroformylering van styreen. Iso/n ratio’s hoger dan 20 werden

behaald en de ee bereikte een matige 55%. NMR studies konden de coördinatie van de

liganden in de trigonaal bipyrimidale slapende toestand van de katalysator in de

katalytische cyclus niet verhelderen. De afhankelijkheid van de prestaties van het

systeem van de temperatuur, de druk en de ligand tot rhodium verhouding zijn bepaald.

106

Dankwoord

Dankwoord

Een proefschrift moet je in je eentje afronden, maar de inhoud ervan komt tot stand

dankzij de inbreng van velen. Hier is een goede gelegenheid om al die personen

nogmaals te bedanken.

Je moet niet starten met bouwen zonder een goed fundament. Dat is gelegd op de UvA

waar ik mijn studie Scheikunde heb afgesloten in de groep van Kees Elsevier. In die

onderzoeksgroep werd ik gegrepen door de sfeer; de sfeer van fundamentele

wetenschap en de sfeer tussen de aio’s onderling waar je moeiteloos in opgenomen

werd. Met name wil ik Jeroen en Boke noemen als personen waar ik veel van geleerd

heb.

Aangestoken door het virus begon ik als promovendus in de homogene katalyse in de

groep van Dieter Vogt. Beste Dieter, onze onderlinge communicatie is niet altijd

vlekkeloos verlopen. Maar ik denk dat ik voor beiden spreek als ik zeg dat we altijd het

beste met elkaar voor hadden en met het onderzoek wat moest leiden tot dit

proefschrift. Geduld is een schone zaak gebleken. Copromoter Erik, je bent een man

met een on-conventionele manier van begeleiden en aanpak. Dat is je grote kracht maar

laat het niet je valkuil vormen! Ook de overige leden van mijn promotiecommissie wil

ik hierbij danken voor hun input.

De sfeer in de groep was ongeëvenaard. Iedereen had zo zijn of haar unieke bijdrage

aan het geheel.

Jarl, senior aio, work-alholic 1e klas, altijd goed voor serieuze gesprekken en culturele

of sociale uitjes: zonder jou zou dit nooit gelukt zijn... Als ik één iemand ken die ik

succes gun in zijn carrière ben jij het, en het gaat je nog lukken ook!

Gaby, je klaagzang was meestal duidelijk hoorbaar, maar je hebt het ook niet

gemakkelijk gehad.

107

Dankwoord

Niek, mijn gewaardeerde kamergenoot, door schade en schande heb ik van je kunnen

leren. Concerten, films, borrels; we gingen echt overal heen. Ook na de TU blijf ik je

achtervolgen; je bent als collega niet weg te denken.

Ruben, mijn andere gewaardeerde kamergenoot, was altijd hoorbaar vrolijk aanwezig.

Je bent een man van staal en je organisatietalent en gastvrijheid kent geen weerga.

Oeteldonk is niet hetzelfde zonder jou!

Michiel, samen hebben we wel aan onze onderwijstaken voldaan, het was een

genoegen! Dankzij de gezamelijke sappel- en karnemelksessies bleven onze vitamine C

en calcium gehaltes goed op peil.

Mabel, ik vergeet ons tripje naar Venetië nooit meer en zonder jou had ik de Spaanse

filmcultuur nooit ontdekt.

Jos, man zonder compromissen, veel daden en weinig woorden: respect!

Gijs, je bent een persoon vol eigen-aardigheden, een lopend Handbook of Chemistry

and Physics. Zorg dat je dat boekje afschrijft...

Kathi en Laura, de knappe dames in STW 4.36; jullie hebben een speciaal plekje in

mijn hart veroverd, ik zal jullie voortgang op de voet blijven volgen en bewaken.

Ook van de oude Silly’s (Mark, Tessa en Rob), de overige jongere garde (Leandra,

Bart, Patrick en Michèle), delegaties aan Post-Docs (met name Sam, Rafaël, Marije,

Marco, Daniël en Vincent) en studenten (met name afstudeerder Bart, Erasmus-stagaire

Roser, Jeroen v. B., Jos en Saskia) kon ik veel leren of kon ik kennis aan overdragen.

Christian als goedlachse hardwerkende UD was tenslotte onmisbaar. Allen bedankt!

Daarnaast hebben vele andere SKA-ers de tijd onvergetelijk gemaakt bij lunches,

koffiepauzes, de borrel, de FORT, film, Tourpoul, Niok Soccer Cup, etc. Ik denk met

name aan Bouke, Chrétien, Joost, Sander, Thijs en Tiny. Ook overige OBP-ers (oa vele

secretaresses, good-old Ton Staring, vrolijke Wout(er) van Herpen en de mentale

ondersteuning van Wilma en vooral Annemieke) bleken vaak onmisbaar.

108

Dankwoord

Er was ook een leven naast de TU. Vele, vele uren heb ik doorgebracht bij Unicum, met

afstand de gezelligste tafeltennisvereniging van het land: veelal om te tafeltennissen (ik

bedank mijn teamleden Bert, Erik en Truus voor het rondcrossen met mij in de regio)

maar ook zeker voor de gezelligheid na vrij spelen, competitie of bij het 1e team, het

landskampioenschap van de jongens in Middelburg en vele feestavonden waren

onvergetelijk. Het was maar goed dat het op loopafstand van huis was!

Dat huis was mijn kamer op het Villapark, dat ik al die jaren trouw ben gebleven. Dat

kan ook niet anders met een hospita als mevrouw Vermulst. U gunde me alle privacy en

vrijheid gunt in uw huis en tuin, naast goede gesprekken met een kop koffie en altijd

een koek.

Ik begon over een fundament. Het echte fundament is uiteraard gelegd door mijn

ouders. Ook oma en grote broer Robin zijn als familie altijd dichtbij. Dankzij jullie

allen, door een goede opvoeding en onvoorwaardelijke steun denk ik een integer

persoon te zijn geworden, met een goede set normen en waarden. En is dat naast liefde

niet wat feitelijk het belangrijkste is in het leven?

Bij liefde denk ik meteen aan mijn lieve Henrike. Je hebt veel geduld moeten

opbrengen, maar uiteindelijk is er echt een einde aan gekomen. Nu kunnen we verder

bouwen aan onze toekomst. Zullen we samen proberen ervoor te zorgen dat de beren

weggaan?

Terugkijkend: ik heb nergens spijt van, maar sommige zaken zou ik nu anders (beter?)

aanpakken. Zou ik weer gaan promoveren? Jazeker!!

Eric

109

Curriculum Vitae

Curriculum Vitae

Eric Zijp werd op 24 november 1976 in Sleeuwijk geboren. Op

OSG de Meergronden te Almere behaalde hij in 1995 zijn VWO

diploma, waarna hij aan de Universiteit van Amsterdam begon

aan de studie Scheikunde. In de groep Anorganische Chemie van

Prof. dr. Kees Vrieze en Prof. dr. Kees Elsevier werden onder

supervisie van Dr. Jeroen Diederen palladium gekatalyseerde

ringsluitingen bestudeerd. In dezelfde groep werden tevens oxidatieve addities aan

Rh(I)-Terpy*-complexen onderzocht met als coach Dr. Boke de Pater. In 2000

behaalde hij zijn diploma en begon als promovendus in de groep Homogene Katalyse

en Coördinatie Chemie onder leiding van Prof. dr. Dieter Vogt aan de Technische

Universiteit Eindhoven, wat uiteindelijk resulteerde in dit proefschrift. Een jaar

werkte hij gedetacheerd vanuit Yacht op projectbasis bij DSM, afdeling LS-ASC&D.

Momenteel is hij werkzaam als Chemist bij ChemShop in Weert.

Eric Zijp was born on the 24th of November 1976 in Sleeuwijk, the Netherlands. He

graduated from OSG de Meergronden in Almere in 1995 and shortly after started his

chemistry studies at the University of Amsterdam. In the group Inorganic Chemistry

of Prof. dr. Kees Vrieze and Prof. dr. Kees Elsevier he studied under guidance of Dr.

Jeroen Diederen on palladium catalyzed ring-annulations. In the same group oxidative

additions to Rh(I)-Terpy*-complexes were investigated, herein coached by Dr. Boke

de Pater. In 2000 he received his diploma and started as PhD-student in the group

Homogeneous Catalysis and Coordination Chemistry of Prof. dr. Dieter Vogt at the

Eindhoven University of Technology ultimately resulting in this thesis. For one year

he worked for Yacht at DSM, LS-ASC&D department. Currently he is employed as

Chemist at ChemShop in Weert.

111

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