Immobilization of a modified tethered rhodium(III)-p-toluenesulfonyl-1,2- diphenylethylenediamine catalyst on soluble and solid polymeric supports and successful application to asymmetric transfer hydrogenation of ketones

Article abstract of DOI:10.1002/adsc.201000340

Catalyst immobilization through covalent attachment onto a support is one strategy to provide recyclable systems. Here, soluble and surface-functionalized solid polymers were used as supports for a modified tethered rhodium(III)-p-toluenesulfonyl-1,2-diphenylethylenediamine [Rh(III)-TsDPEN] complex. The supported catalysts were applied to the asymmetric transfer hydrogenation of phenyl ketones in aqueous solution of sodium formate. High ee values (up to 99%) and good activities were achieved. It was discovered that the solid polymer-supported catalyst could be recycled at least four times without a significant decrease of the activity when a mixture of sodium formate and formic acid was used as the hydrogen source. This catalytic system provides a promising approach towards an ecologically and economically rational production of enantioenriched building blocks.

Full text of DOI:10.1002/adsc.201000340

FULL PAPERS
DOI: 10.1002/adsc.201000340
Immobilization of a Modified Tethered Rhodium(III)-p-Toluene-
G
sulfonyl-1,2-diphenylethylenediamine Catalyst on Soluble and
Solid Polymeric Supports and Successful Application to
Asymmetric Transfer Hydrogenation of Ketones
Jonas Dimroth,a,b,d Juliane Keilitz,c,d Uwe Schedler,b Reinhard Schomꢀcker,a,*
and Rainer Haagc,*
a
Technische Universitꢀt Berlin, Department of Chemistry, Straße des 17. Juni 124, 10623 Berlin, Germany
Fax : (+49)-30-314-79552; e-mail: schomaecker@tu-berlin.de
PolyAn GmbH, Rudolf-Baschant-Str. 2, 13086 Berlin, Germany
b
Fax : (+49)-30-91207811
c
Freie Universitꢀt Berlin, Institute of Chemistry and Biochemistry, Takustraße 3, 14195 Berlin, Germany
Fax : (+49)-30-838-53357; e-mail: haag@chemie.fu-berlin.de
These authors contributed equally to this work.
d
Received: May 2, 2010; Revised: July 29, 2010; Published online: September 15, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000340.
Abstract: Catalyst immobilization through covalent supported catalyst could be recycled at least four
attachment onto a support is one strategy to provide times without a significant decrease of the activity
recyclable systems. Here, soluble and surface-func- when a mixture of sodium formate and formic acid
tionalized solid polymers were used as supports for a was used as the hydrogen source. This catalytic
modified tethered rhodium
1,2-diphenylethylenediamine
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
complex. The supported catalysts were applied to the enantioenriched building blocks.
asymmetric transfer hydrogenation of phenyl ke-
tones in aqueous solution of sodium formate. High Keywords: asymmetric catalysis; asymmetric transfer
ee values (up to 99%) and good activities were hydrogenation; immobilization; recycling; rhodium;
achieved. It was discovered that the solid polymer- supported catalysts
Introduction
Hydrogen transfer reactions have been known for
more than a century but only became prominent in
Asymmetric transfer hydrogenation (ATH) is a pow- 1925 when the specific conversion of aldehydes into
erful method for the preparation of enantioenriched alcohols in the presence of aluminum alkoxides and
secondary alcohols and other compounds, which are 2-propanol was reported.[4–7] However, asymmetric
important chiral building blocks in pharmaceuticals transfer hydrogenation mediated by organometallic
and agro chemicals production. Among the catalytic catalysts remained inferior until the early 1990s when
approaches based on chiral complexes, such as asym- essential progress in catalyst design was achieved.[8,9]
metric hydrogenation or asymmetric hydrosilylation, In 1995, Noyori and co-workers introduced the p-tol-
ATH is somewhat favourable in terms of operational uenesulfonyl-1,2-diphenylethylenediamine (TsDPEN)
safety and ecological aspects.[1] The use of hydrogen ligand in conjunction with Ru-h6-arene. This system
sources such as 2-propanol or formates and mild reac- proved to be a highly efficient catalyst for ATH using
tion conditions allow for simple and safe processes 2-propanol or formic acid and even aqueous solutions
since toxic reagents and the sophisticated equipment of formates as hydrogen donors.[10–13] Several modifi-
associated with the use of hydrogen gas at high pres- cations of the ligand structure, e.g., use of monotosy-
sure can be avoided.[2,3]
lated 1,2-diaminocyclohexane (TsDAC), and the ap-
plication of Ir-cp* and Rh-cp* in addition to Ru-
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Jonas Dimroth et al.
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arene resulted in a broad range of new complexes coupling procedures. In order to avoid unwanted in-
which are among the most efficient and versatile cata- teractions between catalyst and support, sufficient dis-
lysts in ATH today.[14–17] A further improvement of tance between the polymeric support and the catalytic
enantioface discrimination and complex stability was center had to be assured. Therefore, a six-carbon-
achieved through the tethering of the phenyl or cyclo- atom spacer was introduced at the tosyl group using a
pentadienyl groups, respectively, to the chiral diamine straightforward synthesis strategy.
ligand by Wills and co-workers.[18] These catalysts
showed high rates and excellent enantioselectivities in
the triethylamine/formic acid system as well as in Ligand Synthesis
aqueous solutions of sodium formate.[19,20]
With respect to operational and environmental as- Enantiopure (1R,2R)-(+)- and (1S,2S)-(À)-1,2-di-
pects, a major drawback of homogeneously dissolved phenyl-1,2-ethylenediamine (2) was obtained in multi-
catalysts is the elaborate separation from reactants gram quantities according to a procedure by Corey
and products after the reaction has finished. In order and co-workers,[37] and conversion to 3 has also been
to overcome this problem and to permit catalyst recy- described.[38] The work presented here was exclusively
cling, a multitude of methods for the immobilization performed with the (S,S)-enantiomer of 3. The
of catalysts has been developed.[21,22]
methyl-protected linker was introduced by reaction
Catalysts based on TsDPEN have been the focus of with methyl adipoyl chloride leading to Boc-protected
various immobilization approaches. For instance, (S,S)-4. Subsequent deprotection to (S,S)-5 and reduc-
Lemaire and co-workers prepared copolymers made tive amination with 2-(2,3,4,5-tetramethylcyclopenta-
of styrene-p-sulfonyl-DPEN and styrene/divinylben- dienyl)-benzaldehyde (6)[19] led to the protected
zene which were used with different metal precur- ligand (S,S)-7 which can be either deprotected to
sors.[23] Although first recycling results were poor, this (S,S)-8 or subjected to rhodium insertion yielding the
approach was successfully followed by other monomeric catalyst (S,S)-9 (Scheme 1).
groups.[24–26] Solid organic and inorganic supports, to
which TsDPEN or derivatives were covalently bound,
have also widely been used,[27–32] and some attempts Supports and Coupling
have been made to use soluble supported[33,34] as well
as micellar-embedded TsDPEN-based catalysts.[35,36]
There are two possible routes to obtain supported
Here we report the modification and covalent bind- complexes (S,S)-10. Either ligand (S,S)-8 can be cou-
ing of a tethered Rh(III)-TsDPEN complex to both pled to one of the amine-functionalized supports 11
AHCTUNGTRENNUNG
soluble hyperbranched polymers and solid polymeric before rhodium is inserted (Path A) or the order can
chips as supports. The immobilized catalysts were be reversed, by first inserting rhodium to obtain (S,S)-
used in the asymmetric transfer hydrogenation of ke- 12 and then coupling it to the support 11 (Path B,
tones. A major focus of this work was the optimiza- Scheme 2). Path B has the advantage that only one
tion of the system with regard to economical and en- reaction step has to be performed on the polymeric
vironmental aspects. Thus, besides using water as a support.
harmless, safe, and easily available solvent, the focus
lay on facile catalyst separation and recycling.
As already described by Wills and co-workers,[19]
the H NMR spectra of compounds (S,S)-7 and (S,S)-
1
8 are very complex due to the mixture of isomers of
the cyclopentadiene moiety. However, for the methyl-
Results and Discussion
protected RhACHTGUNTERNNU(G III) complex (S,S)-9 a well-defined
1H NMR spectrum was obtained (see Supporting In-
1
In order to support the tethered catalyst 1, developed formation). Surprisingly, the H NMR spectrum of the
by Wills and co-workers (Figure 1),[19] we decided to deprotected Rh
ACTHNUTRGNEU(GN III) complex (S,S)-12 was found to be
utilize a linker that could be connected to amine-func- very complex, but the substance was proven to be the
tionalized soluble and solid supports via simple amide desired compound by HR-MS and FT-IR analysis
(see Supporting Information).
Hyperbranched polymers are promising soluble
supports because they show similar properties like
dendrimers, e.g., low viscosity and high density of
functional groups, but can be easily synthesized in a
one-step procedure.[39] Hyperbranched polyglycerol 15
(hPG) is especially featured by its good solubility in a
wide variety of solvents, its high chemical stability,
and weak coordinating properties to metals. hPG 15
has a very high loading with hydroxy groups (Mn =
Figure 1. Tethered (R,R)-TsDPEN-Rh
A
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Immobilization of a Modified Tethered RhodiumACTHNUGRTENUNG(III)-p-Toluenesulfonyl-1,2-diphenylethylenediamine
Scheme 1. Synthesis of carboxylic ligand (S,S)-8 and monomeric RhACTHUNRTGNEUNG(III) complex (S,S)-9.
Scheme 2. Synthesis of supported RhACTHUNTGRNEUNG(III) complexes (S,S)-10.
10,000 gmolÀ1; 13.5 mmolgÀ1), which can be easily duced by the catalytic units, proceeds between the
converted to amine groups through a mesylation/azi- polymers. Synthesis pathway A proved to be suitable
dation/reduction procedure yielding hPG-amine and because solubilizing building blocks also had to
11a.[40]
be introduced to make the final catalyst water-soluble,
During the synthesis of hPG-supported RhACHUTGNTERNN(NUG III) cat- long amphiphilic chains, composed of a C18-alkyl
alyst 10a, it became apparent that the approach de- chain and a monomethylated poly(ethylene glycol)
scribed as path B (Scheme 2) was not applicable for chain (mPEG750, Mn =750 gmolÀ1), were attached via
hPG-amine 11a. As soon as the polymer 11a was amide coupling. These amphiphilic chains had already
added to the activated RhACTHUNTGRNEUNG(III) complex (S,S)-12, a been used by our group to construct core-multishell
flocculent precipitate was formed that could not be architectures for the transport of drugs and dyes as
solubilized in any solvent and therefore could not be well as for the stabilization and catalytic application
characterized. It is assumed that cross-linking, in- of metal nanoparticles.[41–44] The resulting dendritic
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polymers were surrounded by a hydrophilic PEG
shell, which made them soluble in a wide variety of
solvents from water to toluene.
In order to obtain the water-soluble immobilized
ligand (S,S)-10a, a one-pot protocol was developed
starting with the activation of the carboxylic acid of
(S,S)-8, followed by addition of hPG-amine 11a and
coupling of the activated amphiphilic building block
14 to the residual amine groups. Subsequent insertion
of RhCl3 hydrate and purification via ultrafiltration
delivered hPG-supported RhACTHNUGRTNEUNG(III) complex (S,S)-10a
with a metal loading of 0.417 mmolgÀ1 as determined
by ICP-MS (inductively coupled plasma mass spec-
trometry).
As solid supports, we used two different types of
commercially available surface-functionalized poly-
meric chips (PCs): membranes 11b (base material
polypropylene) and sinter chips 11c (base material
polyethylene) (Figure 2).[45] These reactive surface
PCs were delivered with Boc-protected amines which
Figure 2. Solid polymeric support materials: amine-function-
alized membranes 11b (a) and sinter chips 11c (b). After
were easily deprotected before the linker-containing coupling of TsDPEN-Rh
ACHTUNGTRENNUNG
complex (S,S)-12 was coupled. Amine loading was in
the range of 0.8 to 2.5 mmol/cm2 (geometric surface).
For the immobilization on solid supports 11b and
11c, synthesis pathway B (Scheme 2) was chosen to
keep the number of synthetic steps on the solid phase termined via ICP-MS and found to be four times
as small as possible and to avoid unspecific binding of lower than the specified amine loading.
rhodium onto the surface. According to standard
amide coupling procedures, the carboxylic linker of
RhACHTUNGTRENNUNG(III) complex (S,S)-12 was activated with TBTU in Catalytic Testing
DMF at room temperature. The solution was added
to PCs after they had been prepared via acidic cleav- With the soluble supported RhACTHNUTRGNE(UNG III) complex (S,S)-10a
age of the Boc protecting groups. DMF solution and at hand, we started to investigate its catalytic activity
supports were then shaken for 20 h, washed with or- and selectivity with acetophenone (16a) as model sub-
ganic solvents, and dried under reduced pressure.
The successful coupling was indicated by the bright tested: 2-propanol, HCOOH/Et3N, and HCOONa/
orange color of the supports after the procedure was water. The results obtained with hPG-Rh(III) com-
strate. Three different hydrogen donor systems were
AHCTUNGTRENNUNG
finished (see Figure 2). FT-IR analysis showed clear plex (S,S)-10a in comparison to those obtained with
phenyl and sulfonamide signals at 1495/1590 cmÀ1 and the monomeric analogue (S,S)-9 and the unmodified
1155 cmÀ1, respectively. The rhodium loading was de- complex (S,S)-1 are shown in Table 1.
Table 1. Comparison of hydrogen donor systems for the asymmetric transfer hydrogenation of acetophenone (16a) using
hPG-supported RhACHTUNGTRENNUNG
(III) complex (S,S)-10a, monomeric analogue (S,S)-9, and Wills catalyst (S,S)-1.[a]
Hydrogen donor system
hPG-Rh
(III) complex (S,S)-10a
Monomeric analogue (S,S)-9
Wills catalyst (S,S)-1
Conv. [%]b)
ee [%]b,c)
Conv. [%]b)
ee [%]b,c)
Conv. [%]b)
ee [%]b,c)
2-propanol
HCOOH/Et3N (5/2)
HCOONa (5 equiv.)/water
4
53
100
92
97
98
85
87
100
94
97
98
81
100
100
94
96
97
[a]
Reaction conditions: substrate/catalyst (S/C) 100/1, 0.43 mmol acetophenone (16a), 1 mL solvent, 408C, 6 h.
Determined by gas chromatography.
The (S)-enantiomer was formed in excess.
[b]
[c]
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Immobilization of a Modified Tethered RhodiumACTHNUGRTENUNG(III)-p-Toluenesulfonyl-1,2-diphenylethylenediamine
Table 2. Substrate scope of the asymmetric transfer hydroge-
nation of various ketones 16 with hPG-supported Rh(III)
catalyst (S,S)-10a in HCOONa/water.[a]
The hPG-supported catalyst (S,S)-10a as well as its
monomeric analogue (S,S)-9 show the best perfor-
mance in the aqueous hydrogen donor system, achiev-
ing full conversion after 6 h, and the highest ee value
(98%). In both cases emulsions of catalyst and aceto-
phenone (16a) in the aqueous phase were formed
after addition of the substrate, although (S,S)-10a was
initially solubilized in the HCOONa/water system.
This led to a significantly higher local concentration
of substrate and catalyst in the droplets and therefore
to higher reaction rates. The trend towards higher
enantioselectivity in the HCOONa/water system has
been observed for all catalysts, and by comparing the
monomeric analogue (S,S)-9 and Wills catalyst (S,S)-
1, one can see that the modification at the tosyl
moiety did not have a significant influence on the cat-
alytic performance. Nevertheless, immobilization on
the soluble support is unfavourable when 2-propanol
or HCOOH/Et3N is used as hydrogen donor system.
Since the formation of an emulsion was observed in
the aqueous system, we tested different mixtures of
water with methanol as cosolvent (1:1, 2:1, and 1:2).
In all cases, full conversion and an ee of 98% was
achieved after 6 h. However, the water/MeOH mix-
tures of 2:1 and 1:1 were not sufficient to avoid the
formation of an emulsion and the 1:2 mixture could
not completely solubilize sodium formate, which re-
sulted in a gel-like mixture that could not be stirred
anymore.
ACHTUNGTRENNUNG
Substrate
R1
Time [h] Conv. [%]b) ee [%]b,c)
R2
16a
16b 4’-NO2
16c 4’-Cl
16d 4’-OMe
16e
16f 4’-F
16g 4’-Me
16h 4’-OH
H
H
H
H
H
Me
H
H
H
6
6
6
6
18
6
14
48
100
68
98
89
95
96
99
97
99
79
100
100
100
100
100
91
H
16i 2-acetonaphthone 10
100
> 99
[a]
Reaction conditions: S/C 100/1, 0.43 mmol ketone 16,
2.15 mmol HCOONa, 1 mL water, 408C.
Determined by gas chromatography.
[b]
[c]
The (S)-enantiomer was formed in excess.
In order to test the versatility of the catalyst, differ-
ent substrates were subjected to asymmetric transfer
hydrogenation with hPG-RhACTHNUTRGENUGN(III) catalyst (S,S)-10a in
the HCOONa/water system (Table 2). In comparison
to data presented in the literature for Wills catalyst 1
in the HCOOH/Et3N hydrogen donor system, similar
enantioselectivities were observed.[19] For Ru catalysts
in aqueous systems with HCOONa, similar enantiose-
lectivities and varying activities are found.[25,46,47] It is
remarkable that due to the high catalyst robustness
all experiments could be performed under non-inert
conditions. Thus, no protective gas or degassed sol-
vents were necessary.
Figure 3. Recycling of hPG-supported RhACTHUNRTGNEUNG(III)-complex
(S,S)-10a in the asymmetric transfer hydrogenation of aceto-
phenone (16a). Reaction conditions: S/C 100/1, 1.29 mmol
16a, 6.45 mmol HCOONa, 3 mL water, 408C, 6 h.
Recycling of catalyst (S,S)-10a was performed three
times with acetophenone (16a) as substrate. After six
hours reaction time, full conversion was achieved. flask with magnetic stirrer in air. Compared to tests
Methanol was added, the catalyst was separated by ul- with the soluble catalyst the reaction volume was ex-
trafiltration, and subjected to the next run. Stable tended in order to guarantee complete wetting of the
enantioselectivities of 98% were obtained, and the support. A catalyst-bearing polymeric chip was simply
conversion dropped from the first to the second run added to a mixture of ketone and HCOONa/water. In
to 65%, but then remained stable (Figure 3). During the case of acetophenone (16a), membrane-supported
ultrafiltration after the third run, accumulation of the catalyst (S,S)-10b and sinter-supported catalyst (S,S)-
catalyst on the ultrafiltration membrane was observed 10c showed a similar performance. In Figure 4, con-
that could not be solubilized again. This seems to version of acetophenone using (S,S)-10b is plotted
result from cross-linking between the polymers, in- against time; (S,S)-10c was favoured for further tests,
duced by the catalytic units (see above).
because the support was mechanically more stable.
Tests to elucidate the substrate scope of the solid
The catalytic performance of (S,S)-10b/c was also
tested in an ordinary reaction set-up using a standard catalyst showed similar results in terms of ee values
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Table 4. Comparison of catalytic performance in the ATH of
acetophenone (16a) using hPG-supported RhCAHTUNGTRENNNUG
(S,S)-10a, sinter-supported Rh
ACHTUNGTRENNUNG
monomeric analogue (S,S)-9.[a]
Catalyst
Time [h]
Conv. [%][b]
ee [%][b,c]
A
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
4
4
4
18
57
37
98
99
98
[a]
Reaction conditions: S/C ~430/1, 1 mmol 16a, 5 mmol
HCOONa, 10 mL water, 408C.
Determined by gas chromatography.
[b]
[c]
The (S)-enantiomer was formed in excess.
the non-immobilized catalyst (S,S)-9. This could be as-
cribed to the amphiphilic properties of the functional
matrix of the support material which affords a high
local concentration of substrate and hydrogen donor
in the microenvironment of the catalyst.[25]
Figure 4. Asymmetric transfer hydrogenation of acetophe-
none (16a). Reaction conditions: S/C ~450/1, 1 mmol 16a,
10 mmol HCOONa, 40 mL water, 508C; conversion was de-
termined by gas chromatography.
Catalyst recycling was performed either with or
compared to those obtained with the soluble analogue without washing the supports with methanol after
(cf. Table 2 and Table 3). each run. A high decrease of activity was observed
Due to the different catalyst loading and reaction within the first three cycles when the supports were
conditions, the activity of the soluble and solid cata- repeatedly used in the standard water/HCOONa
lysts could not be reliably compared. Hence, we system [model substrate acetophenone (16a)] without
tested the catalytic performances of hPG-supported washing or further treatment (see Table 5). This de-
Rh
(S,S)-9 under the same reaction conditions as (S,S)- was determined via ICP-MS analysis. A leaching of
10c within the kinetically controlled range (Table 4). 56 ppm (rhodium per total amount of substrate)
ACHTUNGTRENNUNG(III) complex (S,S)-10a and monomeric catalyst crease is not fully explained by metal leaching which
High ee values of 98–99% were obtained in all which corresponds to approximately 2% of the initial
cases but significant differences were found in terms rhodium content was observed after the first run.
of conversion. Notably, the sinter-supported catalyst After two runs, approximately 4% of the rhodium
(S,S)-10c showed a superior performance compared had leached into the product, but the conversion had
to both the soluble-supported catalyst (S,S)-10a and dropped by 50% in the third run (cf. entry 1 and 3).
In further runs, the amount of rhodium loss was sig-
nificantly lower. Thus, unspecifically bound complex
(S,S)-12 or rhodium is assumed to have washed out
during the first run. The ee values were determined to
Table 3. Substrate scope of the asymmetric transfer hydroge-
nation of various ketones 16 with sinter-supported Rh
ACHTUNGTNER(NUNG III)
catalyst (S,S)-10c in HCOONa/water.[a]
Table 5. Recycling of sinter-supported RhACTHNUTRGNEUNG(III) catalyst (S,S)-
10c in the ATH of acetophenone (16a) in HCOONa/water
without intermediate washing.[a]
Run Time [h] Conv. [%][b] ee [%][b,c] Leaching [ppm][d]
Substrate
R1
Time [h] Conv. [%][b] ee [%][b,c]
1
2
3
4
5
6
8
16
8
16
8
16
100
100
53
68
55
98
98
98
98
98
98
56
35
14
n.d.
n.d.
12
R2
16a
H
H
H
H
H
6
6
6
6
6
97
36
71
79
58
98
87
95
97
98
16b 4’-NO2
16c 4’-Cl
16d 4’-OMe
59
16e
H
Me
[a]
Reaction conditions: S/C ~430/1, 1 mmol 16a, 5 mmol
HCOONa, 10 mL water, 408C.
Determined by gas chromatography.
The (S)-enantiomer was formed in excess.
Determined by ICP-MS (n.d. not determined).
[a]
Reaction conditions: S/C ~430/1, 1 mmol ketone 16,
5 mmol HCOONa, 10 mL water, 408C.
Determined by gas chromatography.
[b]
[c]
[d]
[b]
[c]
The (S)-enantiomer was formed in excess.
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Immobilization of a Modified Tethered RhodiumACTHNUGRTENUNG(III)-p-Toluenesulfonyl-1,2-diphenylethylenediamine
be 98% in all runs, and thus proved to be independ-
ent of the conversion in the investigated range.
For both soluble- and insoluble-supported
TsDPEN-based catalysts good to excellent recyclabili-
A decrease of catalytic activity was also observed ty in ATH of acetophenone in water has been report-
in recycling experiments in water/HCOONa with in- ed by other groups. Soluble poly(ethylene glycol)-sup-
termediate washing and drying (Table 6). In a reac- ported Ru-TsDPEN catalysts were used by Xiao
tion that was run for four hours to a conversion of et al.[33] achieving more than ten runs without observ-
57% in the first run, a slight drop by 6% and 7% was able loss of activity and an ee of 93%, and by Li,
observed in the second and third runs, respectively. Chan and coworkers[48] achieving eight runs with ees
After a fourth run with almost identical conversion, of 95–97%. High enantioselectivity (up to 98% ee)
the fifth run was performed overnight achieving 79% was achieved by Itsuno et al.[25] in five consecutive
conversion within 16 h. The following sixth run only runs using hydrophilized polystyrene-supported cata-
achieved 27% conversion within four hours. Again, ee lysts, and silica materials were shown to be readily re-
values were stable throughout the experiment.
coverable supports, but lower ees were observed.[29,49]
The herein presented approach provides a promis-
ing example of a repeatedly reusable immobilized
ATH catalyst keeping the enantioselectivity constant-
ly high at 98% ee for at least seven runs (PC-support-
ed version). A straightforward comparison of litera-
ture data with our results is hardly possible due to the
different reaction conditions. Additionally, the report-
ed data are sometimes not sufficient to give evidence
for a stable catalyst activity since the given conver-
sions are often determined beyond the kinetically
controlled range.
Table 6. Recycling of sinter-supported RhACTHNUTRGNEUNG(III) catalyst (S,S)-
10c in the ATH of acetophenone (16a) in different systems
with intermediate washing.[a]
Run Time
[h]
HCOONa
HCOONa/HCOOH
1:1
Conv.
[%][b]
ee
Conv.
ee
[%][b,c]
[%][b]
[%][b,c]
1
2
3
4
5
6
7
4
4
4
4
16
4
4
57
51
44
43
79
27
23
99
98
99
99
99
98
98
82
85
84
81
100
61
59
98
98
98
98
99
98
98
Conclusions
In this contribution, we have described the immobili-
zation of a tethered TsDPEN-RhACTHUNTGRNEUNG(III) catalyst on vari-
[a]
Reaction conditions: S/C ~430/1, 1 mmol 16a, 10 mL
water, 408C, 5 mmol hydrogen source.
Determined by gas chromatography.
ous amine-functionalized supports. To the best of our
knowledge, this is the first report of an immobilized
version of this catalyst. Coupling was accomplished
onto a soluble as well as onto surface-functionalized
solid supports. Comparison of the catalytic perfor-
mance in the HCOONa/water system in air showed
[b]
[c]
The (S)-enantiomer was formed in excess.
When the experimental conditions were changed in that the enantioselectivity was as high as reported for
order to avoid increasing basicity during the reaction, the unmodified analogues in the literature, and in
we observed an enhancement of the reaction rate, terms of activity the solid polymer-supported catalyst
and recycling was successful for at least four times was found to be superior in the aqueous system even
without significant loss of activity. Thus, we per- in comparison to the monomeric analogue. Unfortu-
formed the same recycling experiment as described nately, recycling of the soluble-supported catalyst
before in a mixture of sodium formate and formic (S,S)-10a resulted in catalyst precipitation during ul-
acid in water (Table 6). The first four runs showed trafiltration after the third run. In case of the solid
conversions between 81% and 85% within four hours. polymer-supported catalyst (S,S)-10c, a successful re-
Only when the reaction was run for 16 h – which cycling was achieved, when a mixture of sodium for-
means that it was left without fresh substrate after mate and formic acid in water was used in order to
full conversion was achieved – was a decrease of cata- avoid a basic solution pH. Additionally, the use of the
lyst activity observed in the subsequent run (cf. cycles water/HCOONa/HCOOH hydrogen donor system re-
4 and 6). Also with this hydrogen donor system stable sulted in a considerable rate enhancement without de-
ee values between 98% and 99% were observed.
creasing the enantioselectivity. Hence, an easily appli-
From these results we conclude that two factors de- cable and environmentally benign system for the
crease the catalytic activity and reduce the recyclabili- highly enantioselective synthesis of phenyl alcohols
ty of the catalyst in aqueous systems: (1) an increas- has been developed. Further investigations to eluci-
ing solution basicity and (2) a longer presence of the date the operating mode of this promising catalyst are
catalyst in solution after full conversion has been under way.
achieved.
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asc.wiley-vch.de
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FULL PAPERS
Experimental Section
Preparation of (S,S)-12
Compound (S,S)-8 (674 mg, 0.8 mmol) and RhCl3·H2O
(201 mg, 0.96 mmol) were dissolved in THF (50 mL). After
stirring for 20 h under reflux conditions, Et3N (4 mmol,
554 mL) was added. The mixture was stirred for further 3 h
and then concentrated under reduced pressure. Purification
via column chromatography (dichloromethane/methanol=
10/1) gave the product as a red solid; yield: 60%.
Preparation of (S,S)-4
This reaction was performed under dry conditions. The start-
ing material (S,S)-N-Boc-N-(4-aminophenylsulfonyl)-1,2-di-
phenylethylenediamine (3)[38] (7.95 g, 17.00 mmol, 1 equiv.)
and triethylamine (Et3N) (2.48 mL, 17.85 mmol, 1.05 equiv.)
were dissolved in dry tetrahydrofuran (THF; 400 mL) and
cooled to 08C. Methyl adipoyl chloride (2.78 mL, 3.19 g,
17.85 mmol, 1.05 equiv.) was added dropwise within 10 min,
and after stirring for further 10 min the ice bath was re-
moved. After one hour of stirring at room temperature, an-
other equivalent of Et3N was added, and the mixture was
stirred for 5 h. Precipitated Et3N·HCl salt was removed by
filtration, the solvent was removed under vacuum, and the
crude product was purified by flash column chromatography
(dichloromethane/methanol=100/1) to afford a colorless
solid; yield: 86%.
Preparation of (S,S)-13
In inert atmosphere, deprotected ligand (S,S)-8 (600 mg,
0.85 mmol, 0.3 equiv.) was dissolved in anhydrous dimethyl-
formamide (DMF; 30 mL), and N-hydroxysuccinimide
(103 mg, 0.89 mmol, 1.05 equiv.) and dicyclohexylcarbodi-
imide (177 mg, 0.86 mmol, 1.01 equiv.) were added. The mix-
ture was stirred at room temperature for 24 h. hPG-amine
11a (13.5 mmolgÀ1 amine groups, 210 mg, 2.83 mmol,
1.00 equiv.) in anhydrous DMF (5 mL) was added and
stirred for another 24 h at room temperature. Addition of
activated amphiphilic building block 14 (2.27 g, 1.98 mmol,
0.7 equiv.), followed by another 24 h at room temperature,
and subsequent ultrafiltration yielded hPG-supported ligand
(S,S)-13 as a yellow sticky solid; yield: 42%.
Preparation of (S,S)-5
The starting material (S,S)-4 (3.72 g, 6.10 mmol) was sus-
pended in dichloromethane (120 mL) and cooled to 08C.
Trifluoroacetic acid (TFA; 8 mL, ~2 mL per g of (S,S)-4)
was added, and the clear solution was stirred in the thawing
ice bath for 18 h. The mixture was neutralized with Et3N,
water was added, and the organic layer was washed with
water and brine and dried over anhydrous Na2SO4. The
crude product was purified via flash column chromatogra-
phy (dichloromethane/methanol=100/4) to give a colorless
solid; yield 87%.
Preparation of (S,S)-10a
(S,S)-13 (1.1 g, ~0.43 mmolgÀ1, 1 equiv.) and RhCl3 hydrate
AHCTUNGTRENNUNG
(117 mg, 0.56 mmol, 1.2 equiv.) were dissolved in methanol
(50 mL) and refluxed for 24 h. Ultrafiltration in methanol
gave (S,S)-10a in as a dark reddish brown sticky solid; yield:
97%.
Preparation of (S,S)-10b/10c
Preparation of (S,S)-7
a) Cleavage of protective groups: Surface-functionalized
support materials 11b/c were received with Boc-protected
amine groups. Cleavage was performed in a beaker; six PCs
(amine loading 1 mmol/cm2, 2ꢃ2 cm each) were added to
75 mL of a 6N solution of HCl in 2-propanol. After stirring
for 45 min, the PCs were accurately washed with methanol
and then dried under reduced pressure.
b) Amide coupling procedure: The dried polymeric chips
were added to a solution of N,N-diisopropylethylamine
(DIPEA; 25 mL, 145 mmol) in DMF (30 mL) in an argon at-
mosphere. Separately, compound (S,S)-12 (27 mg, 32 mmol)
This reaction was performed in an inert atmosphere accord-
ing to a procedure by Wills and co-workers.[19] Starting ma-
terials (S,S)-5 (3.43 g, 6.74 mmol, 1 equiv.) and 2-(2,3,4,5-tet-
ramethylcyclopentadienyl)-benzaldehyde
6.74 mmol, 1 equiv.) were dissolved in anhydrous methanol
(100 mL), and Na2SO4 was added. Then, NaBH(OAc)3
(6)[19]
(1.53 g,
AHCTUNGTRENNUNG
(2.86 g, 13.48 mmol, 2 equiv.) was added, and the mixture
was stirred for 16 h [in case of incomplete reduction another
equivalent of NaBHACTHNUTRGNEUNG(OAc)3 was added, and the mixture was
stirred for 5 additional hours]. After filtration through
Celiteꢂ, toluene and water were added, and the organic
layer was washed with water, brine and dried over anhy-
drous Na2SO4. The crude product was purified via flash
column chromatography (dichloromethane/methanol=400/
1) to give a yellow solid; yield: 69%.
and
O-(benzotriazol-1-yl)-N,N,N’,N’-tetramethyluronium
tetrafluoroborate (TBTU; 11.6 mg, 36 mmol) were dissolved
in DMF, and the solution was added to the PCs in DIPEA/
DMF. After shaking the flask for 20 h, PCs were removed
from the solution, washed with DMF and methanol and
dried under reduced pressure.
Preparation of (S,S)-8
General Procedure for Asymmetric Transfer
Hydrogenation of Ketones with Catalyst hPG-Rh
Complex 10a
Starting material (S,S)-7 (2.20 g, 3.06 mmol) was dissolved in
THF/water (3/1, 100 mL), and LiOH (366 mg, 15.3 mmol,
5 equiv.) was added. The mixture was stirred for 18 h, acidi-
fied with 2N HCl, and toluene was added. The organic layer
was washed with water, brine and dried over anhydrous
Na2SO4. After removal of the solvent, the crude product
was purified via flash column chromatography dichlorome-
thane/methanol=100/5) to give a yellow solid; yield 97%.
Ketone 16 (0.43 mmol) was added to a solution of 10a
(1 mol%) and HCOONa (146 mg, 2.15 mmol, 5 equiv.) in
water (1 mL), and the mixture was stirred at 408C for the
indicated time. Ethyl acetate was added and a sample was
taken and subjected to GC analysis.
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Adv. Synth. Catal. 2010, 352, 2497 – 2506

Immobilization of a Modified Tethered RhodiumACTHNUGRTENUNG(III)-p-Toluenesulfonyl-1,2-diphenylethylenediamine
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General Procedure for the Recycling of hPG-Rh
Complex 10a
After the reaction was finished, the reaction mixture was
transferred to the ultrafiltration cell, diluted with water/
methanol (1/1), and subjected to filtration. More and more
methanol was added, until in the last filtration approximate-
ly a water/methanol mixture of 1/10 was present. The sol-
vent was removed under vacuum and the catalyst was used
for the next reaction.
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General Procedure for Asymmetric Transfer
Hydrogenation of Ketones with Catalysts 10b and 10c
The standard experiment was performed in a 25-mL flask.
To a solution of 340 mg of sodium formate (5 mmol) and
ketone 16 (1 mmol) in 10 mL neat water at 408C, a PC-sup-
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General Procedure for the Recycling of Supported
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moved with a forceps and placed in a beaker with 10 mL of
methanol for 5 min. Then, the chip was rinsed with metha-
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Acknowledgements
The authors thank Cognis GmbH (Germany) for a donation
of octadecanedioic acid. We acknowledge Stephen Schrettl,
Cathleen Schlesener, and Marleen Selent for technical assis-
tance and Dr. Heike Matuschewski for providing functional-
ized test materials. This work is part of the Cluster of Excel-
lence “Unifying Concepts in Catalysis.” Financial support by
the Deutsche Forschungsgemeinschaft (DFG) (EXC 314) is
gratefully acknowledged. Furthermore, we are indebted to the
Berlin Senate Department of Science, Research, and Culture
for providing an Elsa-Neumann-Scholarship.
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