Facile synthesis of chiral diphosphine-containing multiple dendrimeric catalysts for enantioselective hydrogenation

Article abstract of DOI:10.1002/cjoc.201200648

A new kind of chiral diphosphine PyrPhos-functionalized codendrimers have been synthesized via a liquid-phase strategy in high yields. The resulting dendrimeric PyrPhos ligands were purified by a simple solvent precipitation without the need for chromatographic separation, and well characterized by ¹H, ¹³C and ³¹P NMR, MALDI-TOF mass spectroscopy as well as elemental analysis. Their rhodium complexes were applied to the asymmetric hydrogenation of α-acetamido cinnamic acids. Excellent enantioselectivities were achieved, which are comparable to those with the corresponding small molecular catalysts. In addition, these codendrimeric catalysts showed better catalytic performance than the dendrimeric catalysts with Rh(PyrPhos) sites located in the focal point of poly(aryl ether) dendrons or in the periphery of poly(propyleneimine) dendrimers.

Full text of DOI:10.1002/cjoc.201200648

FULL PAPER
DOI: 10.1002/cjoc. 201200648
Facile Synthesis of Chiral Diphosphine-Containing Multiple
Dendrimeric Catalysts for Enantioselective Hydrogenation†
Zhao, Liwen(赵立文)
He, Yanmei(何艳梅)
Liu, Ji(刘继)
Feng, Yu*(冯宇)
Fan, Qinghua*(范青华)
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function,
Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, China
A new kind of chiral diphosphine PyrPhos-functionalized codendrimers have been synthesized via a liq-
uid-phase strategy in high yields. The resulting dendrimeric PyrPhos ligands were purified by a simple solvent pre-
1
cipitation without the need for chromatographic separation, and well characterized by H, 13C and 31P NMR,
MALDI-TOF mass spectroscopy as well as elemental analysis. Their rhodium complexes were applied to the
asymmetric hydrogenation of α-acetamido cinnamic acids. Excellent enantioselectivities were achieved, which are
comparable to those with the corresponding small molecular catalysts. In addition, these codendrimeric catalysts
showed better catalytic performance than the dendrimeric catalysts with Rh(PyrPhos) sites located in the focal point
of poly(aryl ether) dendrons or in the periphery of poly(propyleneimine) dendrimers.
Keywords asymmetric catalysis, codendrimer, chiral diphosphine, hydrogenation, amino acid
Introduction
synthesis.[6] Using this facile method, all the target
products were efficiently obtained in high yield and pu-
rity without the use of chromatographic separation.
Most recently, we extended this method to the synthesis
of another codendrimers consisting of Fréchet-type
dendrons and Tomalia-type PAMAM dendrons.[7] These
dendrimers were also employed in the synthesis of
codendrimeric achiral phosphines and their use in the
Pd-catalyzed Suzuki coupling reactions. Based on this
success and as a part of our continuing efforts in the
synthesis of novel chiral dendrimeric catalysts for
asymmetric catalysis,[2c,3b,8] we here report a new kind
of easily available chiral dendrimeric diphosphines
(Figure 1) for the Rh-catalyzed asymmetric hydrogena-
tion. The molecular design was made on the basis of the
following considerations. (1) The easily available
(R,R)-3,4-bis(diphenylphosphino)-pyrrolidine (PyrPhos)
contains a functional amino group, to which organic or
inorganic supports may be directly attached.[9] Its rho-
dium complexes have proven to be very effective in the
asymmetric hydrogenation of prochiral olefins. (2) The
Fréchet's poly(aryl ether) dendrons are inert to catalytic
reaction, and can be easily prepared on large amount
scale from commercially available starting materials.[8,10]
(3) The codendrimeric ligands consist of two different
dendrimeric wedges.[11,12] One segment can be used as
the soluble support,[5] and other one for the attachment
of PyrPhos ligands. Thus, the attachment of PyrPhos
The use of metallodendrimers in homogeneous ca-
talysis is an important frontier of fundamental research
over the past decade.[1] Due to their well-defined and
unique three-dimension molecular architectures, it is
possible to fine tune their catalytic properties by sys-
tematically adjusting their structure, shape, size, and
solubility. In a favorable case, better catalytic perform-
ance can be achieved as compared to the parent small
molecular system. Among these organometallic den-
drimeric catalysts reported to date, transition metal
complexes of dendrimeric phosphorus ligands have at-
tracted much attention.[2] Despite great progress made in
this field, the synthesis of the dendrimer, particular a
higher generation dendrimer, is still difficult and
time-consuming processes. In addition, successful ex-
amples of chiral dendrimeric catalysts for asymmetric
catalysis are rare.[2b,2c,3,4] Therefore, it is desirable to
develop new type of chiral diphosphine-containing den-
drimeric catalysts which are highly effective and can be
easily synthesized from readily available materials.
Recently, we reported the first example of function-
alized codendrimers prepared via liquid-phase organic
synthesis (LPOS) by using the well-defined Fréchet-
type poly(aryl ether) dendron as the soluble support.[5]
This new method combines the advantages of both
conventional solution phase chemistry and solid-phase
*
E-mail: fanqh@iccas.ac.cn; Tel.: 0086-010-62554472
Received June 29, 2012; accepted August 24, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201200648 or from the author.
Dedicated to the 80th Anniversary of Chinese Chemical Society.
†
Chin. J. Chem. 2012, 30, 2009—2015
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2009

Zhao et al.
FULL PAPER
can be realized via LPOS strategy. (4) Unlike our pre-
vious reported dendrimers bearing PyrPhos at the focal
point (Figure 1A),[8b] the multiple catalytic sites are lo-
cated in the periphery of the dendrimer, which are easily
accessible to the substrate. Therefore, it is expected that
this type of dendrimeric diphosphine ligands bearing
from 2 to 8 PyrPhos units would be more effective than
dendrimeric Gn-PyrPhos in the Rh-catalyzed asymmet-
ric hydrogenation of prochiral olefins.
All solvents were dried using standard, published
methods and were distilled under a nitrogen atmosphere
before use. All other chemicals were used as received
from Aldrich, Alfa or Acros without further purification.
PyrPhos was prepared according to the reported proce-
dures.[13]
General procedure for the synthesis of chiral den-
drimeric PyrPhos ligands G2Gn-PyrPhos
In an ice-bath cooled (0 ℃) 10 mL round-bottomed
flask was charged with G2Gn-COOH, (3R,4R)-PyrPhos
hydrochloride (1.05 equiv. per COOH), EDCI (1.25
equiv. per COOH), HOBt (1.25 equiv. per COOH),
triethylamine (2.0 equiv.) and degassed DMF. After the
mixture was stirred for 40 min, the resulting mixture
was warmed to room temperature where it was stirred
for 48 h under nitrogen atmosphere. Then, the mixture
was poured into 20 mL H2O under vigorous stirring, the
precipitate was isolated by filtration, and washed with
0.2 equiv. KOH (5 mL), 0.2 equiv. HCl (5 mL) and wa-
ter (5 mL). The resulting precipitate was redissolved in
THF (3 mL), and precipitated into methanol, after filtra-
tion, giving the desired chiral dendrimeric ligands
G2Gn-PyrPhos as an off-white powder.
Experimental
Unless otherwise noted, all experiments were carried
out under an inert atmosphere of dry nitrogen by using
standard Schlenk-type techniques, or performed in a
1
nitrogen-filled glovebox. H NMR, 31P NMR and 13C
NMR spectra were recorded on a Bruker Model Ad-
vance DMX 300 Spectrometer (1H 300 MHz, 31P 121
MHz and 13C 75 MHz respectively). MALDI-TOF mass
spectra were obtained on a BIFLEX Ⅲ instrument
with α-cyano-4-hydroxycinnamic acid (CCA) as the
matrix. Elemental analyses were performed on a Flash
EA 1112 Elemental Analyzer. All enantiomeric excess
values were obtained from chiral GC analysis.
(A)
O
O
O
O
O
PPh2
C N
PPh2
O
n
O
Gn-PyrPhos
—
(n = 0
3)
(B)
PPh2
PPh2
PPh2
O
O
N
C
O
O
O
O
N
N
O
C
PPh2
PPh2
CH2O
O
C
N
O
O
n-1
PPh2
C
O
PPh2
PPh2
O
G2Gn-PyrPhos
—
(n = 1 3)
Figure 1 Molecular structures of PyrPhos-functionalized dendrimers: (A) PyrPhos located at the focal point of the dendrimer (See ref-
erence [8b]), and (B) PyrPhos-containing codendrimers (This work).
2010
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Chiral Diphosphine-Containing Multiple Dendrimeric Catalysts for Enantioselective Hydrogenation
G2G1-PyrPhos: From G2G1-COOH (200.7 mg, 0.22
mmol), (3R,4R)-PyrPhos hydrochloride (221.8 mg, 0.51
mmol), EDCI (105.8 mg, 0.55 mmol), HOBt (74.6 mg,
0.55 mmol), triethylamine (90.1 mg, 129 µL, 0.89 mmol)
and 10 mL degassed DMF to yield G2G1-PyrPhos
(352.0 mg, 91%) as an off-white powder. 1H NMR (300
MHz, CDCl3) δ: 2.80—2.96 (br m, CHPPh2, 4H), 3.22
(t, J＝11.5 Hz, CH2CHPPh2, 2H), 3.69 (t, J＝12.9 Hz,
CH2CHPPh2, 2H), 3.92—3.98 (m, CH2CHPPh2, 2H),
4.11 —4.23 (m, CH2CHPPh2, 2H), 4.82—5.02 (m,
ArCH2O, 14H), 6.57—6.70 (m, ArH, 9H), 7.03—7.60
(m, ArH＋PhH, 63H); 13C NMR (75 MHz, CDCl3) δ:
168.7, 160.2, 160.2, 158.6, 139.2, 138.4, 136.8, 133.9,
133.7, 133.6, 133.5, 133.2, 129.5, 129.2, 128.8, 128.8,
128.7, 128.6, 128.0, 127.6, 117.6, 114.9, 106.5, 106.4,
101.8, 101.7, 70.3, 70.1, 70.1, 51.3, 51.2, 48.8, 48.6,
39.5, 37.6, 37.4; 31P NMR (121 MHz, CDCl3) δ: －13.5,
－13.6. MS (MALDI-TOF) m/z: Calcd for C113H98N2-
O9P4: 1751.9, found: 1749.3. Anal. calcd for C113H98N2-
O9P4: C 77.47, H 5.64, N 1.60; found C 77.04, H 5.91,
N 1.98.
G2G2-PyrPhos: From G2G2-COOH (199.2 mg, 0.16
mmol), (3R,4R)-PyrPhos hydrochloride (328.7 mg, 0.69
mmol), EDCI (157.9 mg, 0.82 mmol), HOBt (111.3 mg,
0.82 mmol), triethylamine (123.4 mg, 191 µL, 1.32
mmol) and 10 mL degassed DMF to yield
G2G2-PyrPhos (424.4 mg, 89%) as an off-white powder.
1H NMR (300 MHz, CDCl3) δ: 2.73—2.90 (br m,
CHPPh2, 8H), 3.16 (t, J＝11.8 Hz, CH2CHPPh2, 4H),
3.62 (t, J＝13.1 Hz, CH2CHPPh2, 4H), 3.84—3.95 (m,
CH2CHPPh2, 4H), 4.02—4.16 (m, CH2CHPPh2, 4H),
4.78—4.96 (m, ArCH2O, 18H), 6.48—6.59 (m, ArH,
9H), 6.98—7.32 (m, ArH＋PhH, 109H); 13C NMR (75
MHz, CDCl3) δ: 168.6, 160.2, 159.4, 158.6, 139.2,
138.4, 136.8, 133.8, 133.7, 133.6, 133.4, 133.2, 129.5,
129.2, 129.1, 128.8, 128.7, 128.6, 128.6, 128.0, 127.6,
117.7, 114.8, 113.7, 106.4, 101.7, 70.1, 70.0, 51.2, 48.7,
39.4, 37.5; 31P NMR (121 MHz, CDCl3) δ: －13.5,
－13.6. MS (MALDI-TOF) m/z: Calcd for C185H160N4-
O13P8: 2895.1, found: 2893.3 [M]＋, 2909.2 [M＋O]＋
(oxidation occurred in matrix), 2916.2 [M＋Na]＋. Anal.
calcd for C185H160N4O13P8: C 76.75, H 5.57, N 1.94;
found C 76.37, H 5.64, N 1.89.
39.5, 37.8, 37.6, 37.4;. 31P NMR (121 MHz, CDCl3) δ:
－13.3, －13.4. MS (MALDI-TOF) m/z: Calcd for
C329H284N8O21P16: 5181.4 found: 5173.5 [M]＋. Anal.
calcd for C329H284N8O21P16: C 76.26, H 5.52, N 2.16;
found C 76.09, H 5.66, N 1.86.
General procedure for hydrogenation reaction using
Rh(G2Gn-PyrPhos) as catalyst
In-situ catalyst preparation: G2Gn-PyrPhos and
[Rh(COD)2 ]＋BF－ (1.0 equiv. per PyrPhos) were
4
stirred at room temperature for 30 min in CH2Cl2 (10
mL) under nitrogen atmosphere. Solvent was removed
under reduced pressure to yield an orange-yellow solid.
The resulting catalyst was dissolved in toluene, which
was directly used in the following catalytic reaction
without further purification.
Asymmetric hydrogenation: In a 10 mL glass-lined
stainless steel reactor with a magnetic stirring bar was
charged with substrate (1.0 equiv.), the above prepared
catalyst Rh(G2Gn-PyrPhos) (0.005 equiv.) and metha-
nol/toluene (V/V＝2∶1, 3 mL). The autoclave was
closed and pressurized with H2 to 60 atm. The mixture
was stirred with magnetic stirring bar under the H2
pressure at 20 ℃ for 2 h. After carefully venting of
hydrogen, most of the reaction solvent was removed
under reduced pressure. The conversion and enantiose-
lectivity of the reduced product were obtained by chiral
GC with a 25 m×0.25 mm Chrompack Chirasil-L-Val
column.
Results and Discussion
Synthesis and characterization of the carboxylic
acid-functionalized codendrimers
According to our previous reported liquid-phase
synthesis method,[5] the synthetic route to these new
codendrimers was outlined in Scheme 1. The second-
generation poly(aryl ether) dendron (G2CH2OH), which
was readily synthesized via the reported convergent
method,[11] was chosen as the soluble supports, and
commercially available dimethyl 5-hydroxyisophthalate
1 as the growth unit. Reaction of G2CH2OH with 1 un-
der the Mitsunobu reaction conditions gave G2G1-
COOMe in high yield. The resulting dendrimeric ester
was then reduced by LiAlH4 to provide the dendritic
alcohol (G2G1-CH2OH). Repetitive Mitsunobu coupling
and an ester reduction sequence lead to the formation of
second- and third-generation codendrimeric esters
(G2G2-COOMe and G2G3-COOMe). The target carbox-
ylic acid-functionalized codendrimers were obtained by
hydrolyzing the corresponding ester dendrimers. Nota-
bly, all the resulting dendrimeric intermediates and the
target codendrimers were efficiently obtained in high
yield by a simple solvent precipitation. Their structures
G2G3-PyrPhos: From G2G3-COOH (201.5 mg, 0.11
mmol), (3R,4R)-PyrPhos hydrochloride (445.0 mg, 0.94
mmol), EDCI (213.4 mg, 1.11 mmol), HOBt (150.5 mg,
1.11 mmol), triethylamine (180.2 mg, 258 µL, 1.78
mmol) and 10 mL degassed DMF to afford G2G3-
1
PyrPhos (490.4 mg, 85%) as an off-white powder. H
NMR (300 MHz, CDCl3) δ: 2.79—2.95 (br m, CHPPh2,
16H), 3.23 (t, J＝10.7 Hz, CH2CHPPh2, 8H), 3.69 (t,
J＝12.5 Hz, CH2CHPPh2, 8H), 3.92—3.97 (m, 8H),
4.11—4.18 (m, 8H), 4.88—5.06 (m, 26H), 6.54—6.65
(m, 9H), 7.05—7.68 (m, 201H); 13C NMR (75 MHz,
CDCl3) δ: 170.4, 168.7, 160.2, 160.1, 159.5, 158.7,
138.5, 136.9, 135.9, 133.9, 133.8, 133.7, 133.5, 133.3,
129.6, 129.3, 129.3, 128.9, 128.8, 128.8, 128.7, 128.1,
127.7, 114.9, 113.7, 106.8, 106.5, 101.8, 70.2, 51.2, 48.6,
1
were confirmed by H NMR, 13C NMR, and MALDI-
TOF mass spectroscopy. (For details, see the Supporting
Information).
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Zhao et al.
FULL PAPER
Scheme 1 Liquid-phase synthesis of the carboxylic acid-functionalized codendrimers
O
COOCH3
HO
O
O
COOCH3
COOCH3
1
COOCH3
CH2OH
O
a
G2
O
O
G2-CH2OH
G2G1-COOMe
O
b
OH
G2
G2G1-CH2OH
1, a
COOCH3
COOCH3
O
G2G2-COOMe
COOCH3
b
O
O
O
COOCH3
COOCH3
1, a
O
G2G2-CH2OH
G2
O
COOCH3
COOCH3
G2G3-COOMe
O
COOCH3
COOH
COOMe
O
O
O
c
COOH
COOH
COOMe
COOMe
O
O
G2
G2
O
n-1
n-1
COOH
COOMe
G2Gn-COOH
(n = 1, 2, 3)
G2Gn-COOMe
(n =1, 2, 3)
Reagents and conditions: (a) DIAD, PPh3, THF, r.t., 24—48 h. (b) LiAlH4, THF, 80 ℃, 1 h. (c) KOH aq., THF/CH3OH, 2—8 h, 100 ℃
Synthesis and characterization of the chiral Pyr-
Phos-functionalized codendrimers
ethyl-N,N-dimethylcarbodiimide (EDCI) and 1-hydroxy-
benzotriazole (1-HOBT) as coupling Reagents. Using
this method, the chiral diphosphine-functionalized
codendrimers bearing 2 to 8 PyrPhos units at their pe-
riphery were obtained in excellent yields (Scheme 2).
The highly effective and easily fixation of the chiral
PyrPhos ligands at the periphery of the above coden-
drimers were achieved via LPOS strategy by using
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Chiral Diphosphine-Containing Multiple Dendrimeric Catalysts for Enantioselective Hydrogenation
Scheme 2 Liquid-phase synthesis of chiral codendrimeric PyrPhos ligands G2Gn-PyrPhos (n＝1, 2, 3) and the molecular structure of
G2G3-PyrPhos
PPh2
PPh2
O
N
C
COOH
PPh2
Ph2P
Ph2P
O
O
O
O
NH HCl
C
C
N
N
PPh2
PPh2
O
COOH
COOH
O
O
O
G2
G2
EDCI, HOBt, Et3N, DMF,
r.t., 24 - 60 h
n-1
PPh2
n-1
G2G1-PyrPhos (n = 1);
G2G2-PyrPhos (n = 2);
G2G3-PyrPhos (n = 3)
COOH
C
N
PPh2
PPh2
G2Gn-COOH
(n =1, 2, 3)
O
Ph2P
N
PPh2
PPh2
PPh2
C
O
N
PPh2
PPh2
C
O
O
O
N
C
O
O
O
O
PPh2
C
N
O
O
O
O
O
PPh2
PPh2
CH2O
O
N
C
PPh2
PPh2
O
G2G3-PyrPhos
O
C N
O
O
O
PPh2
C
N
PPh2
PPh2
C
O
N
PPh2
Ph2P
Synthesis of multiple dendrimeric catalysts and ap-
plication in the asymmetric hydrogenation of
α-acetamido cinnamic acids
Unlike the conventional dendrimer synthesis, the
resulting codendrimeric ligands were easily purified by
a simple solvent precipitation without the use of chro-
matography separation at the end of reaction. This is
based on the difference in solubility between the mac-
romolecular dendrimers and the small molecular by-
products as well as excess reagents. The structures of all
these codendrimeric ligands were confirmed by using
1H, 13C and 31P NMR and MALDI-TOF mass spec-
trometry as well as elemental analysis (For details, see
Supporting Information). All results are consistent with
the compounds synthesized.
The codendrimeric Rh-catalysts were prepared in
situ by mixing G2Gn-PyrPhos with [Rh(COD)2]BF4 (1.0
equiv. per PyrPhos unit) in dichloromethane at room
temperature for 30 min under nitrogen atmosphere.
Solvent was then removed under reduced pressure to
yield orange powders. Then, 31P NMR spectroscopies of
the rhodium complexes Rh(G2Gn-PyrPhos) were exam-
ined, respectively. It was found that the chemical shifts
of these three catalysts were very similar (for details,
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Zhao et al.
FULL PAPER
see the Supporting Information), indicating that the
density of PyrPhos units in the periphery could not in-
fluence the coordination of rhodium with the phospho-
rus atoms on the surface of the dendrimer. In addition,
the complete metallation of the codendrimeric di-
phosphine ligands was also confirmed by the 31P NMR
spectroscopy. For example, in the case of codendrimeric
ligand containing 8 PyrPhos units, the signals of the
unreacted PyrPhos units (δ＝－13.3 and －13.4) were
found to be shifted to lower field due to the metal com-
plexation (Figure 2).
Table 1 Asymmetric hydrogenation of α-acetamido cinnamic
acids catalyzed by the dendrimeric Rh-catalystsa
COOH
[Rh(COD)2]BF4
COOH
*
G2Gn-PyrPhos
NHCOCH3
NHCOCH3
R
H2
R
—
2a 2h
—
3a 3h
Entry
Ligand
Substrate (R) Conv.b/%
eec/%
1
2
3
4
5
6
7
8
9
G2G1-PyrPhos
G2G2-PyrPhos
G2G3-PyrPhos
G2G1-PyrPhos
G2G2-PyrPhos
G2G3-PyrPhos
G2G1-PyrPhos
G2G2-PyrPhos
G2G3-PyrPhos
2a (H)
＞99
96 (94.5)d
2a (H)
＞99 (60)e
＞99 (52)e
＞99
96
2a (H)
95
2b (o-Cl)
2b (o-Cl)
2b (o-Cl)
2c (m-Cl)
2c (m-Cl)
2c (m-Cl)
2d (p-Cl)
2d (p-Cl)
2d (p-Cl)
2e (o-Me)
2e (o-Me)
2e (o-Me)
2e (m-Me)
2e (m-Me)
2e (m-Me)
2e (p-Me)
2e (p-Me)
2e (p-Me)
94
＞99
93
＞99
94
＞99
95
＞99
96
＞99
96
10 G2G1-PyrPhos
11 G2G2-PyrPhos
12 G2G3-PyrPhos
13 G2G1-PyrPhos
14 G2G2-PyrPhos
15 G2G3-PyrPhos
16 G2G1-PyrPhos
17 G2G2-PyrPhos
18 G2G3-PyrPhos
19 G2G1-PyrPhos
20 G2G2-PyrPhos
21 G2G3-PyrPhos
22 G2G1-PyrPhos
23 G2G2-PyrPhos
24 G2G3-PyrPhos
＞99
95
＞99
95
＞99
95
＞99
92
＞99
91
＞99
92
＞99
96
＞99
96
＞99
96
＞99
94
Figure 2 31P NMR spectra of (a) G2G3-PyrPhos ligand and (b)
its Rh-complex.
＞99
94
＞99
94
2e (p-OMe) ＞99
2e (p-OMe) ＞99
2e (p-OMe) ＞99
95
With these codendrimeric catalysts in hand, we chose
the Rh-catalyzed asymmetric hydrogenation of
α-acetamido cinnamic acids as the model reaction to
investigate the relationship between the generation and
its catalytic properties of G2Gn-PyrPhos. According to
our previous study, all hydrogenations with a substrate/
rhodium ratio of 200 were carried out in MeOH/toluene
(2∶1, V/V) under 60 bar hydrogen pressure at 20 ℃
for 2 h. All dendrimeric catalysts Rh(G2Gn-PyrPhos)
were tested, and the results are summarized in Table 1.
Generally, both excellent activities and enantioselectiv-
ities were obtained in all cases, which are comparable to
that obtained with small molecular catalyst (Table 1,
Entry 1).[9] Firstly, the effect of dendrimer generation on
the catalyst performance was investigated (Table 1, En-
tries 1—3). It was found that the catalytic activity
slightly decreased with increasing dendrimer generation
(Table 1, Entries 2 and 3). Upon prolonged reaction
time (2 h), complete conversions were obtained in all
cases. This results suggested higher accessibility of the
active sites in the periphery than that located in the focal
point, which showed a dramatic drop in catalytic activ-
ity on going from generation 3 to generation 4.[8b] In
addition, these codendrimeric catalysts exhibited better
95
94
a
Hydrogenations were carried out in 0.03 mol/L solution of sub-
strate 2 under the following reaction conditions: substrate/ cata-
lyst＝200 (mole ratio); solvent＝MeOH/toluene (2∶1, V/V, 3
mL); reaction temperature＝20 ℃; H2 pressure＝60 atm; reac-
tion time＝2 h. b Based on GC and 1H NMR analysis. c ee values
of 3 were determined by chiral GC with a 25 m×0.25 mm
d
Chrompack Chirasil-L-Val column. Data in the bracket was
obtained from the corresponding small molecular catalyst re-
ported in our previous study.[9] e Data in the bracket was obtained
when the reaction was carried out in 75 min under otherwise
identical conditions.
catalytic performance than the dendrimeric catalysts
with Rh(PyrPhos) attached in the periphery of poly
(propyleneimine), in which a decrease in both activity
and selectivity of the dendrimer catalysts was observed
on going to the higher generations.[4b]
Encouraged by these excellent results, we decided to
further investigate the applications of the codendrimeric
catalysts in the asymmetric hydrogenation of other sub-
stituted α-acetamido cinnamic acids. In general, all sub-
2014
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 2009—2015

Chiral Diphosphine-Containing Multiple Dendrimeric Catalysts for Enantioselective Hydrogenation
van Leeuwen, P. W. N. M. Angew. Chem., Int. Ed. 2001, 40, 1828; (b)
strates studied were smoothly hydrogenated in complete
conversions with excellent enantioselectivities (Table 1,
Entries 4—24). It was found that the reaction is rela-
tively insensitive to the electrical characteristic. Notably,
the steric hindrance effect of substrates slightly influ-
enced the enantioselectivity of the codendrimeric cata-
lysts, and ortho-substituted α-acetamido cinnamic acids
gave slightly low enantioselectivity (Table 1, Entries
4—6 and 13—15).
Astruc, D.; Chardac, F. Chem. Rev. 2001, 101, 2991; (c) van
Heerbeek, R.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Reek, J. N.
H. Chem. Rev. 2002, 102, 3717.
[2] For reviews, see: (a) Caminade, A. M.; Maraval, V.; Laurent, R.;
Majoral, J. P. Curr. Org. Chem. 2002, 6, 739; (b) Caminade, A. M.;
Servin, P.; Laurent, R.; Majoral, J. P. Chem. Soc. Rev. 2008, 37, 56;
(c) Ma, B. D.; Fan, Q. H. Scientia Sinica Chim. 2010, 40, 827.
[3] For reviews, see: (a) Kassube, J. K.; Gade, L. H. Top. Organomet.
Chem. 2006, 20, 61; (b) Fan, Q. H.; Ding, K. L. Top. Organomet.
Chem. 2011, 36, 207.
[4] For selected examples of periphery-functionalized chiral phosphorus
ligand-containing dendritic catalysts, see: (a) Köllner, C.; Pugin, B.;
Togni, A. J. Am. Chem. Soc. 1998, 120, 10274; (b) Engel, G. D.;
Gade, L. H. Chem. Eur. J. 2002, 8, 4319; (c) Rodriguez, L. I.;
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Organometallics 2006, 25, 1368; (d) Kasssube, J. K.; Wadepohl, H.;
Gade, L. H. Adv. Synth. Catal. 2009, 351, 607.
Conclusions
In summary, we have described the facile synthesis
of a new kind of multiple dendrimeric diphosphine
ligands bearing from 2 to 8 PyrPhos units in the periph-
ery of dendrimers. Their rhodium complexes were ap-
plied to the asymmetric hydrogenation of α-acetamido
cinnamic acids, giving complete conversions and excel-
lent enantioselectivities. Better catalytic performance of
these codendrimeric catalysts was observed as com-
pared to those obtained from the dendrimeric catalysts
with Rh(PyrPhos) sites located in the focal point of
poly(aryl ether) dendrons[8b] or in the periphery of
poly(propyleneimine) dendrimers.[4b] Extending the use
of these codendrimeric catalysts to other catalytic reac-
tions is being underwent in our laboratory.
[5] Feng, Y.; He, Y. M.; Zhao, L. W.; Huang, Y. Y.; Fan, Q. H. Org. Lett.
2007, 9, 2261.
[6] For selected reviews on LPOS, see: (a) Gravert, D. J.; Janda, K. D.
Chem. Rev. 1997, 97, 489; (b) Zhao, L. W.; Fan, Q. H.; He, Y. M.;
Zhou, H. F.; Chan, A. S. C. Prog. Chem. 2006, 18, 316.
[7] Liu, J.; Feng, Y.; He, Y. M.; Yang, N. F.; Fan, Q. H. New J. Chem.
2012, 36, 380.
[8] (a) Fan, Q. H.; Chen, Y. M.; Chen, X. M.; Jiang, D. Z.; Xi, F.; Chan,
A. S. C. Chem. Commun. 2000, 789; (b) Yi, B.; Fan, Q. H.; Deng, G.
J.; Li, Y. M.; Qiu, L. Q.; Chan, A. S. C. Org. Lett. 2004, 6, 1361; (c)
Wang, Z. J.; Deng, G. J.; Li, Y.; He, Y. M.; Tang, W. J.; Fan, Q. H.
Org. Lett. 2007, 9, 1243; (h) Zhang, F.; Li, Y.; Li, Z.; He, Y. M.; Zhu,
S.; Fan, Q. H.; Zhou, Q. L. Chem. Commun. 2008, 6048; (i) Deng, G.
J.; Fan, Q. H.; Chen, X. M. Chin. J. Chem. 2002, 20, 1139.
[9] Fan, Q. H.; Deng, G. J.; Lin, C. C.; Chan, A. S. C. Tetrahedron:
Asymmetry 2001, 12, 1241.
Acknowledgement
This work is supported by the National Basic
Research Program of China (973 Program, Nos.
2010CB833300 and 2011CB808600).
[10] Hawker, C. J.; Fréchet, J. M. J. J. Am. Chem. Soc. 1990, 112, 7638.
[11] Wooley, K. L.; Hawker, C. J.; Fréchet, J. M. J. J. Am. Chem. Soc.
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[12] Chen, Y. C.; Wu, T. F.; Jiang, L.; Deng, J. G.; Liu, H.; Zhu, J.; Jiang,
Y. Z. J. Org. Chem. 2005, 70, 1006.
[13] Nagel, U.; Kinzel, E.; Andrade, J.; Prescher, G. Chem. Ber. 1986,
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Chin. J. Chem. 2012, 30, 2009—2015
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
2015