New route to biaryl phosphanes with axial chirality as ligands for enantioselective hydrogenations

Article abstract of DOI:10.1002/adsc.200404034

We have found a modular route for the synthesis of Cl-MeOBIPHEP ligands via the corresponding biphenol that allows us to introduce several substituents without the necessity to separate the enantiomers of each derivative. These new diphosphanes were used

Full text of DOI:10.1002/adsc.200404034

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New Route to Biaryl Phosphanes with Axial Chirality as Ligands
for Enantioselective Hydrogenations
Birgit Drie˚en-Hˆlscher,a,* Joachim Kralik,a Friederike Agel,a Christian Steffens,a
Chunhua Hub
a
Institute of Technical Chemistry and Macromolecular Chemistry, RWTH Aachen and University of Paderborn,
Faculty of Sciences, Technical Chemistry, Warburger Str. 100, 33098 Paderborn, Germany
Fax: (þ49)-5251-603244, phone: (þ49)-5251-603616; e-mail: bdh@tc.upb.de
b
Institute of Inorganic Chemistry, RWTH Aachen, Templergraben 55, 52056 Aachen, Germany
Received: February 4, 2004; Accepted: May 25, 2004
Dedicated to Professor Joachim Bargon on the occasion of his 65th birthday.
Supporting Information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: We have found a modular route for the syn- Keywords: asymmetric hydrogenation; atropisomeric
thesis of Cl-MeOBIPHEP ligands via the correspond- diaryl-core diphosphanes; crystal structure determina-
ing biphenol that allows us to introduce several sub- tion; dimethyl itaconate; homogeneous catalysis;
stituents without the necessity to separate the enan- P ligands; ruthenium
tiomers of each derivative. These new diphosphanes
were used in the ruthenium-catalyzed enantioselec- Abbreviations: Tf2O: trifluoromethanesulfonic acid
tive hydrogenation of dimethyl itaconate with ee val- anhydride; DEIPA: diethylisopropylamine; DPPP:
ues up to 97%.
1,2-bis(diphenylphosphino)propane; cod: 1,5-cyclooc-
tadiene; dba: dibenzylideneacetone
Introduction
rivative. We were interested in modifying these ligands
by varying the electronic and steric properties of the
The use of chiral transition metal complex catalyzed re- phosphorus donors.
actions is well established and highly attractive for the
The new derivatives 1b e were synthesized by react-
synthesis of optically active products.[1] Atropisomeric ing the readily available 4-chloro-3-methoxyphenol (2)
diaryl-core diphosphanes like BINAP and MeOBI- with diiodomethane to form 3, followed by the oxidative
PHEP are attracting increasing interest because of their coupling of 3 to 4 (Scheme 1). The acetal 4 is cleaved in
exceptional ability to induce asymmetry in numerous re- acidic media and yields the biphenol 5.
actions.[2] Consequently, there also exists a large interest
in expanding the library of axially chiral diphosphanes,[3]
and the quest for new efficient ligand systems is still a
major challenge in catalysis research.
Results and Discussion
Here we introduce new derivatives of bidentate chiral li-
gands 1b e which contain the 5,5’-dichloro-6,6’-dime-
thoxybiphenyl backbone (Figure 1). The ligand 1a with
phenyl groups at the phosphorus donors, called Cl-
MeOBIPHEP, is already known and was originally syn-
thesized via another route.[4]
Our aim was to find an easy route to diphenyldiphos-
phanes with several diarylphosphanyl substituents with-
out the necessity to separate the enantiomers of each de- Figure 1. Cl-MeOBIPHEP (R)-1.
Adv. Synth. Catal. 2004, 346, 979 982
DOI: 10.1002/adsc.200404034
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Birgit Drie˚en-Hˆlscher et al.
FULL PAPERS
Scheme 1. Synthesis of the biphenol 5 starting from 4-chloro-3-methoxyphenol 2. Reaction conditions: a) NaH, DMF, CH2I2,
rt, 92%; b) 1. n-BuLi, THF, 08C; 2. CuCl2, ꢀ408C, 77%; c) HCl, EtOH, reflux, 91%.
Table 1. Yields of isolated Cl-MeOBIPHEP ligands (R)-
1a e and NMR data.
Entry
Ligand
Yield [%]
31P NMR[a]
1H NMR[b]
1
2
3
4
5
1a
1b
1c
1d
1e
62
20
42
24
53
ꢀ14.2
ꢀ16.0
ꢀ13.7
ꢀ59.1
ꢀ10.6
3.17
3.31
3.27
3.30
3.22
[a]
Scheme 2. Synthesis of the diphosphanes (R)-1 starting from
(R)-5. reaction conditions: a) Tf2O, pyridine, toluene, 92%; b)
Pd2(dba)3 ¥CHCl3, DPPP, DMSO, DEIPA, R2PH, 1008C,
20 62%.
Recorded in CDCl3.
Chemical shift of the OCH3 proton resonances.
[b]
Compound (R)-5 was separated by crystallization
with N-benzylcinchonidinium chloride in a chemical
yield of 29% (ee¼98%) and was then isolated in
>99.9% ee after recrystallization from chloroform.
The other enantiomer (S)-5 could also be separated
from the mother liquor. In order to bind a low-valent
phosphorus centre to the aryl nucleus, (R)-5 was reacted
with trifluoroacetic anhydride to yield the biphenol di-
triflate (R)-6. The last step, the substitution of thetriflate
groups of (R)-6 with secondary phosphanes R2PH was
mediated by palladium(0) catalysts in the presence of
a base (Scheme 2).[5]
The yields of the enantiomerically pure products (R)-
1a e are moderate or low, but the palladium catalyzed
coupling has not yet been optimized. Table 1 lists the
1
yields, the 31P NMR and the H NMR chemical shifts
for the methoxy groups of (R)-1a e (see also Support-
ing Information).
We determined the optical purity at the stage of the bi-
phenol 5 by chiral HPLC. The absolute configuration of
1d was assigned as (R) from the crystal structure deter-
mination. Bond lengths and angles show the expected
values, and the two phenyl rings of the biaryl backbone
are twistedagainsteachother, thetwist angle being74.78
Figure 2. ORTEP illustration, with thermal ellipsoids drawn
at the 30% probability level, of (R)-1d in the crystal.
(Figure 2). We assume that the other derivatives have 1a e for asymmetric catalysis (Scheme 3). The number
the same configuration because all were synthesized us- of publications on ruthenium catalyzed hydrogenations
ing the enantiomerically pure (R)-5.
of dimethyl itaconate is rather small[6] and an excellent
In a first set of experiments, we used the ruthenium chiral catalyst to date is [Ru(BINAP)(CH3CN)
catalyzed hydrogenation of dimethyl itaconate (7) to (cod)]BF4 which leads to the formation of dimethyl suc-
study the potential of Cl-MeOBIPHEP ligands (R)- cinate (8) with an enantiomeric excess of 95%.[7]
980
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Adv. Synth. Catal. 2004, 346, 979 982

Biaryl Phosphanes with Axial Chirality
FULL PAPERS
Our catalysts can be synthesized by reacting [(cod) Conclusions
Ru(h3-methallyl)2], the diphosphanes (R)-1a e (one
equivalent) and trifluoroacetic acid (two equivalents) To summarize, we have found a new route for the syn-
in methanol/dichloromethane as solvent mixture.[8] For- thesis of Cl-MeOBIPHEP ligands (R)-1a e and used
mation of the complexes {[(R)-1a e]Ru(OOCCF3)2} is these diphosphanes for the synthesis of chiral ruthenium
complete after 70 hours at room temperature. The iso- complexes. The complexes with the general formula
lated compounds are yellow or orange solids which {[(R)-1a e]Ru(OOCCF3)2} have been successfully
have been characterized by 31P NMR spectroscopy. All used in the enantioselective hydrogenation of dimethyl
Cl-MeOBIPHEP-containing ruthenium complexes cat- itaconate (ee values up to 97%). In conclusion, the high-
alyze the hydrogenation of dimethyl itaconate (7) with ly flexible synthesis of Cl-MeOBIPHEP ligands via the
high enantioselectivities and almost complete conver- biphenol opens a broad range of possible modifications
sion of the substrate after short reaction times (Table 2). for further optimization of this ligand family by elec-
The enantioselectivities of all five complexes (ranging tronic and steric variations. Most of the research results
from 91 to 97% ee) are in some aspects even better than reported here are encompassed by pending patent[9] ap-
that with the best hydrogenation catalyst known to date. plications. Further work will include investigations into
Electronic effects seem to be less important for asym- other enantioselective reactions using these ligands.
metric induction, as becomes evident by comparing en-
try 2 with entry 3. Steric effects seem to be more impor-
tant because the ligands with the smaller aryl groups
Experimental Section
phenyl and furyl (entries 6 and 9) give somewhat lower
ee values compared to the bulkier derivatives. The
ruthenium catalysts formed with the Cl-MeOBIPHEP
ligands not only show high asymmetric induction, but
also show a significant catalytic activity. Activities are
dependent on the ligand used: the electron-withdrawing
p-fluorophenyl-substituted ligand 1b shows lower activ-
ity (entry 2) than in the case of an electron-donating li-
gand (entry 3). At higher temperatures, the reaction is
faster and quantitative conversion could be reached af-
ter 30 minutes (entries 6 8). The total number of cata-
lytic turnovers is high. An initial turnover frequency of
around 200 hꢀ1was determined.
Typical Procedure for the Preparation of (R)-1
A solution of 79 mg (0.19 mmol) DPPP in 10 mL DMSO is
added to 0.220 g (0.19 mmol) [Pd(PPh3)4] under argon. To
the resulting suspension 0.99 g (5.3 mmol) diphenylphos-
phane, 0.85 g (6.6 mmol) DEIPA and a solution of 1.00 g
(1.7 mmol) ditriflate (R)-6 in 10 mL DMSO are added in this
order. The resulting clear yellow solution is heated to 1008C.
After the reaction is complete, the solvent is removed under
vacuum, and the residue dissolved in 10 mL methanol. Crystal-
lization at ꢀ258C afforded (R)-1 as a white, crystalline solid;
yield: 0.70 g (62%).
Catalyst Preparation
To a solution of 155 mg (0.484 mmol) [Ru(cod)(methallyl)2] in
5 mL CH2Cl2 are added 432 mg (0.484 mmol) (R)-1a under ar-
gon. After stirring for 1 h, 79 mL (1.025 mmol) trifluoroacetic
acid are added and the mixture is stirred for 72 h under the ex-
clusion of light. The solvent is removed under reduced pressure
to give complex {[(R)-1a e]Ru(OOCCF3)2} in quantitative
yield.
Scheme 3. Hydrogenation of dimethyl itaconate (7).
Table 2. Hydrogenation of dimethyl itaconate (7) with {[(R)-1a e]Ru(OOCCF3)2} as catalysts.[a]
Entry
Catalyst
Temperature [ 8C]
Conversion [%]
% ee
1
2
3
4
5
6
7
8
9
[(1a)Ru(OOCCF3)2]
[(1b)Ru(OOCCF3)2]
[(1c)Ru(OOCCF3)2]
[(1d)Ru(OOCCF3)2]
[(1e)Ru(OOCCF3)2]
[(1a)Ru(OOCCF3)2]
[(1b)Ru(OOCCF3)2]
[(1c)Ru(OOCCF3)2]
[(1d)Ru(OOCCF3)2]
22
22
22
22
22
50
50
50
50
100
70
100
0
100
100
100
100
17
92 (S)
95 (S)
95 (S)
92 (S)
92 (S)
96 (S)
97 (S)
93 (S)
[a]
Reaction conditions: 0.02 mmol Ru; 2.0 mmol 7; 5 mL MeOH, 1 bar H2; reaction time: 60 minutes for the experiments at
228C and 30 minutes for experiments at 508C; conversion and enantiomeric excesses were determined by GC.
Adv. Synth. Catal. 2004, 346, 979 982
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Birgit Drie˚en-Hˆlscher et al.
FULL PAPERS
[2] a) M. McCarthy, P. J. Guiry, Tetrahedron 2001, 57, 3809;
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Asymmetric Hydrogenation of Dimethyl Itaconate (7)
To a 60-mL glass autoclave with a magnetic stirrer are added
under argon dimethyl itaconate (7, 2.0 mmol), 0.100 g diglyme,
and catalyst (R)-1a (1 mol %) in 5 mL methanol. The autoclave
is sealed and pressurized to 1 bar with hydrogen. The reaction
mixture is stirred for 1 h at room temperature, the pressure
then released. Conversion was determined by GC of the crude
reaction mixture, while the enantiomeric excess was deter-
mined by chiral GC after distillation under reduced pressure.
Crystallographic data (excluding structure factors) for the
structure 1d reported in this paper have been deposited with
the Cambridge Crystallographic Data Centre as supplementa-
ry publication no. CCDC-156383. Copies of the data can be ob-
tained free of charge on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK [Fax: int. codeþ44(1223)336 033;
E-mail: deposit@ccdc.cam.ac.uk].
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Acknowledgements
We are very grateful to Bayer AG for financial support and the
good cooperation. We would like to thank Dr. H. Hugl, Dr. W.
Lange, Dr. T. Prinz, Dr. C. Dreisbach and Dr. H.-C. Militzer
(all Bayer AG) for helpful scientific discussions.
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982
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Adv. Synth. Catal. 2004, 346, 979 982