Methodologies in Asymmetric Catalysis - American Chemical Society

Chapter 11

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Phosphite Ligands in Asymmetric Hydrogenation Montserrat Diéguez, Oscar Pàmies, Aurora Ruiz, and Carmen Claver* Departament de Química Física i Inorgànica, Universitat Rovira i Virgili, Pl. Imperial Tàrraco,1,43005Tarragona,Spain

Phosphites are extremely attractive ligands for transition metal catalysts. Their available synthesis allows the modification of electronic and steric properties providing the synthesis of series of chiral ligands that can lead to a successful ligand optimization. This chapter describe the use of phoshite ligands in the metal-catalyzed asymmetric hydrogenation of C=C and C=N, which are two of the major homogeneous processes in asymmetric synthesis.

The asymmetric hydrogénation of prochiral compounds catalyzed by chiral transition-metal complexes has been widely used in stereoselective organic synthesis and some processes have found industrial applications (1,2,3). For many years, the scope of this reaction has been gradually extended in both reactant structure and catalyst efficiency. A large number of chiral ligands, mainly P- and N-containing ligands with either C2- or CI-symmetry, have been successfully applied (1,2,3). Diphosphines have played a dominant role among the P-ligands, but recently a group of less electron-rich phosphorus compounds —phosphite ligands—has received much attention. Phosphite ligands have © 2004 American Chemical Society In Methodologies in Asymmetric Catalysis; Malhotra, S.; ACS Symposium Series; American Chemical Society: Washington, DC, 2004.

161


162

been successfully applied in many other transition-metal-catalysed reactions such as hydroformylation (4,5,6,7,8,9), hydrocyanation (10) and allylic alkylation (11,12,13,14). These ligands are extremely attractive for catalysis because they are easy to prepare from readily available alcohols. The availability of many alcohols makes simple ligand tuning possible, allowing the synthesis of many series of chiral ligands that can be screened in the search for high activity and selectivity. Another advantage of phosphite ligands is that they are less sensitive to air and other oxidizing agents than phosphines. On the other hand, phosphites are more prone to side reactions like hydrolysis, alcoholysis, and the Arbuzov reaction. These side reactions are minimized, however, when bulky aryl phosphites are used. In this chapter, we report the opportunities that these ligands provide for improving the performance of asymmetric hydrogénation.

Ligand Synthesis In general, phosphite ligands are synthesized very efficiently in two steps from the corresponding alcohols (Scheme 1). The first step is the formation of the corresponding phosphorochloridite, usually by reaction of a diol with PC1 and a base. This phosphorochloridite then reacts with a new alcohol in basic media to form the desired monophosphite or diphosphite ligand. 3

R20H

ι

W

fr

Rl

VoR

2

PCI

0» OH

R

2

Scheme 1. Typical synthesis of (a) monophosphite and (b) diphosphite ligands.

Hydrogénation of carbon-carbon double bonds The hydrogénation of carbon-carbon double bonds is widely used for the preparation of high value compounds that can be used as interesting building blocks for asymmetric synthesis. For instance, the hydrogénation of a-

In Methodologies in Asymmetric Catalysis; Malhotra, S.; ACS Symposium Series; American Chemical Society: Washington, DC, 2004.

163 dehydroaminoacid derivatives and enamides provides access to unnatural aminoacids and amines that are useful intermediates for the pharmaceutical and agrochemical industries (1-3). The hydrogénation of a-dehydroaminoacid derivatives is also a typical reaction for testing the efficiency of new chiral ligands. In this section we describe the results published for the asymmetric hdrogenation of C=C bonds with di- and mono-phosphite ligands.


Diphosphite ligands The first reports on the use of diphosphite ligands in asymmetric hydrogénation were introduced by Brunner (15), Wink (16) and Kolich (17). Brunner and Wink used diphosphite ligands based on carbohydrate and tartaric acid derivatives in the Rh-catalyzed hydrogénation of enamides and obtained low enantioselectivies (1-34 % ee) (Figure 1). Kolich used chiral diphosphites based on optically active binapthol in the Ru-catalyzed hydrogénation of 2-(4isobutyl-phenyl)aciylic acid and also obtained low ee's (7-34 %) (figure 1).

η

(RO) P-0 2

|-0-P(OR)

2

(RO) P 2

ee'supto34%

15

PiORh P(OR*)

2

ee's upto10%16

Figure 1. Structure of the first phosphite ligands used in the asymmetric hydrogénation reaction

In 1998, Selke et al. also reported the use of diphosphite ligands with glucopyranoside backbone in the rhodium-catalyzed hydrogénation of methyl (Z)-2-N-aœtamidocinnamate and showed rather low enantioselectivities (ee's up to 13%) (Figure 2) (18).

(RO) P'° 2

°-p(OR)

ee'suptom

2

18

Figure 2. Structure of the diphosphite ligands used by Selke


164


An important breakthrough in the use of phosphite ligands for asymmetric hydrogénation came with the work of Reetz and coworkers (19). These authors developed a series of C2 derivative ligands derived from mannitol with different phosphite substituents (a-e) (Figure 3).

R = R = f-Bu

C

1

2

Figure 3. D-Mannite diphosphite ligands developed by Reetz et al. These ligands were efficiently applied in the Rh-catalyzed hydrogénation of dimethyl itaconate (Table 1) and methyl JV-acetamidoaciylate.

Table 1. Rh-catalyzed hydrogénation of dimethyl itaconate using phophite ligands 1/

JLl

MeOfcC^C'^M©

" •

x! 3

2

Rh /1

"2

MeOfcC^C^Me ^2

%ee Entry T(°C) HConv Ligand 38.9 (S) 1 la 20 74 2 >99 96.8 (R) 20 lb 3 5.2 (R) 20 24 lc 4 87.8 (S) 20 >99 Id 94.5 (Λ) 5 20 >99 le 6 98.2 (R) -10 >99 lb 7 >99 96.2 (R) le -10 "General conditions: substrate/catalyst= 1000/1; t= 20 h; ligand/rhodium= 1/1; solvent= CH C1 . Substrate/catalyst^ 250/1. b

b

2

2

The results indicated that the sense of enantiodiscrimination is predominantly controlled by the configuration of the binaphthyl moiety (entries


165


4 and S). Moreover, they observed a cooperative effect between the stereogenic centers of the ligand backbone and the stereogenic binaphthyl phosphite moieties (entries 4 and 5). This resulted in a matched combination for ligand l e (entry 5 and 7). They also found that ligand l b with conformational flexibility in readily epimerizing biphenyl moieties proved superior to those with fixed binaphthyl chirality (entry 2 vs 4 and 5). The results obtained in the asymmetric hydrogénation of methyl iVacetamidoacrylate followed the same trend as those for dimethyl itaconate, but the enantioselectivities were somewhat lower (up to 88.7% ee). The group of Claver and coworkers have recently developed a series of highly modular Cl-diphosphite ligands with furanoside backbone derived from D-xylose and D-glucose (Figure 4) (20,21,22). The modular construction of these ligands allows sufficient flexibility to fine-tune (a) the different configurations of the carbohydrate backbone and (b) the steric and electronic properties of the diphosphite substituents. Both excellent enantioselectivities (ee up to >99%) and activities were achieved in the Rh-catalyzed hydrogénation of dimethyl itaconate (Table 2). Systematic variation of stereocenters C-3 and C-5 at the ligand backbone revealed that enantiomeric excesses depended strongly on the absolute configuration of C-3 and slightly on that of the stereocenter carbon C-5. Therefore, enantioselectivities were best with ligands 4 with R configuration on both C-3 and C-5 stereocenters. Variation in chirality at the axial chiral binaphthyl substituents in ligands 4 indicates that the sense of the enantiodiscrimination is predominantly controlled by the configuration of the biaryls at the phosphite moieties (entries 6 and 7). The presence of bulky substituents at the crrto-positions of the biaryl diphosphite moieties has a positive effect on enantioselectivity. The highest enantiomeric excess was found for allofuranoside ligand 4g, which has otrimethylsilyl substituents in the biphenyl moieties (entries 5 and 13). It was also found that the presence of a methyl substituent on the carbon C-5 significantly increased the activity (entries 3-12 vs 1 and 2). This set of ligands was also applied in the Rh-catalyzed hydrogénation of other benchmark dehydroamino acid derivatives. The results followed the same trend as those for dimethyl itaconate, but the activities were somewhat higher (21). Monophosphite ligands In the last few decades it was generally accepted that enantioselective hydrogénation was more effective in the presence of bidentate ligands. Recently, however, some monophosphorous ligands have been found to be very efficient for the Rh-catalyzed asymmetric hydrogénation (23,24,25). In the last



166

2R,

3S, 4/?, 5tf)

a c f g

(11?, 2*, 3R 4K, 5S)

R R R R

1

1

1

1

=R =H = R = f-Bu = f-Bu; R =OMe = SfWe ;R = H 2

2

2

3

2

2R 3S, 4K, SS)

d (S)»;R =H e R βH h (S) *; R = SiMe i (Rf \ R SiMe 1

1

8

x

1

1 s

3

3

Figure 4. Diphosphite ligands 2-7 with fîiranoside backbone.



Table 2. Rh-catalyzed asymmetric hydrogénation of dimethyl itaconate using diphosphates 2-7."

il

MeOsC^X^Me H2

£#tfty

1 2 3 4 5 6 7 8 9 10 11 12 13

b

Ligand 2c 3c 4c 4f 4g 4d 4e 4h 4i 5c 6c 7c

f l 3

Ha Rh/2-7

MeOfi'^C^m H2

%Conv(t/h) 12(8) 28(8) 90(8) 82(8) 100 (6) 50(8) 46(8) 100(8) 100 (8) 100(8) 87(8) 73(8) 100(4)

Hee 22 (R) 64 (R) 90 (Λ) 85 (Λ) 97 (Λ) 50 (S) 52 (Λ) 90(5) 92 (R) 2(R) 67 (Λ) 29 (/?) >99(R)

4R [Rh(cod)2]BF4 = 0.01 mmol; ligand/Rh =1.1; substrate/Rh = 100; CH2CI2 = 6 mL; PH2 = 5 bar, Τ = 25 °C. T = 5°C;PH2 = 30bar 8

b



168 few years, therefore, the use of monophosphate ligands in this process has been widely studied. Research in this area was initiated by Reetz and coworkers (26). In connection with the previously described diphosphite ligands derived from mannitol 1, they found out that the related monophosphite ligands 8d and 8e provided similar enantioselectivities (Figure Sa), so they extended their study to other simple binol-based monophosphite ligands 9 (Figure 5b) and found excellent results when an appropriate phosphite substituent was choosen. The results (100% conversion and 98.8% ee) were therefore best with ligands 9p and 9q containing chiral 1-phenylethanol units. However, the additional stereogenic center appears to play a minor role since the results were the same for both ligands. (a)

CH q 3

P-OR

Ό

8d «0> " >8· (To * S (

Kno1

1 ο η Η

R

ee

CH

89.2%

3

k

CH(CH )

m

2-Br-C6H 2,6-CH -CgH 2.6-(C H )-C H

3

2

• η

ο Ρ

4

3

6

3

5

6

3

(/Q-CHCCHsXCeHs) (S)-CH(CH )(C HIJ) 3

6

97.6% 96.6% 89.8% 39.2% 28.6% 99.2% 982%

Figure S. Monophosphite ligands tested by Reetz and coworkers in the Rhcatalyzed hydrogénation of dimethyl itaconate.

This set of ligands was also applied in the Rh-catalyzed hydrogénation of methyl JV-acetamidoaciylate. The results followed the same trend as those for dimethyl itaconate, but the enantioselectivities were somewhat lower (ee's up to 95.5%). Reetz and coworkers have taken advantage of these highly modular ligands 9 to show that catalyst optimization for a given substrate is possible simply by varying the alcohol unit (R) incorporated to the binaphthol basic framework. Enantioselectivities were therefore excellent in the asymmetric hydrogénation of different enamides using these highly modular ligands (Figure 6) (27).


169 NHAc

0^ R*CH C(CH ) ee's up to 95.3%

9

2


NHAc

α

XT

3

NHAc

00^

R = (R)-CH(CH )(C H5) ee's up to 9 5 . 8 % 3

NHAc

3

6

R»CH (C6H5> R-if^HiCHsMCeHg) ee's up to 9 4 . 3 % ee's up to 9 7 % 2

Figure 6. Optimized enantioselectivities obtained in the Rh-catalyzed asymmetric hydrogénation of various enamides using ligands 9. Other groups have also explored the use of this type of ligand for the asymmetric hydrogénation of caibon-caibon double bonds (28, 29, 30). In particular, Dreisbach and coworkers have recently extended the study to enantiomerically pure biphenyl-based monophosphites (Figure 7). They studied the effect of the substitutents (R1-R4) of the biphenyl moiety in combination with the variation of the alcohol unit attached to the biphenol basic framework (R) and found excellent ligands for the rhodium-catalyzed asymmetric hydrogénation of dimethyl itaconate and methyl iV-acetamidoaciylate (ee's up to 99%) (30).

R

R

2

Figure 7. General structure of the biphenyl monophosphite ligands developed by Dreisbach and coworkers. Very recently, Reetz and coworkers have developed a new concept in combinatorial asymmetric catalysis (31). These authors discovered that certain


170 mixtures of different chiral monodentate ligands (in which two such ligands are bonded to rhodium) are much more active and enantioselective than either of the pure ligand systems (Scheme 2).


9j 76.6% 9n 32.4% ee 9j£n 84.6% ee

Scheme 2. Comparison of the traditional and the combinatorial approach in the Rh-catalyzed asymmetric hydrogénation.

Hydrogénation of carbon-nitrogen double bonds The enantioselective hydrogénation of caibon-nitrogen double bonds is a simple and convenient route to the synthesis of chiral amines. However, while many highly enantioselective chiral catalysts have been developed for the asymmetric hydrogénation of C=C and O O , only veryfeweffective catalysts are amiable for the enantioselective hydrogénation of O N (1-3). The most widely used catalyst systems for this process are the diphosphine-rhodium (I) and diphosphine-iridium (I) complexes. Little attention has been paid to the use of phosphite ligands for the asymmetric hydrogénation of O N . So far only two reports are known in the literature (32, 33). Thefirstof these reports used a binol-based diphosphite ligand 10 in the Ir-catalyzed asymmetric hydrogénation of unhindered imines and obtained low enantioselectivies (

Methodologies in Asymmetric Catalysis - American Chemical Society

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