Supramolecular chiral dendritic monophosphites assembled by hydrogen bonding and their use in the Rh-catalyzed asymmetric hydrogenation

Article abstract of DOI:10.1039/b823047a

A new type of supramolecular chiral dendritic monophosphite ligands has been prepared via a hydrogen-bonding assembly. The Rh complexes of these supramolecular ligands have been successfully applied in the asymmetric hydrogenation of enamides and dehydroa

Full text of DOI:10.1039/b823047a

View Article Online / Journal Homepage / Table of Contents for this issue
PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Supramolecular chiral dendritic monophosphites assembled by hydrogen
bonding and their use in the Rh-catalyzed asymmetric hydrogenation†
Yong Li, Yan-Mei He, Zhi-Wei Li, Feng Zhang and Qing-Hua Fan*
Received 5th January 2009, Accepted 11th February 2009
First published as an Advance Article on the web 19th March 2009
DOI: 10.1039/b823047a
A new type of supramolecular chiral dendritic monophosphite ligands has been prepared via a
hydrogen-bonding assembly. The Rh complexes of these supramolecular ligands have been successfully
applied in the asymmetric hydrogenation of enamides and dehydroamino acid derivatives with good
enantioselectivities, which are comparable to those obtained from the free monophosphite ligands. The
supramolecular catalyst could be easily recycled via solvent precipitation.
here we report the synthesis and application of a new kind of
supramolecular chiral dendritic monophosphites assembled by
Metallodendrimers have been emerging as a promising class of
hydrogen bonding.
Introduction
catalysts as demonstrated in the pioneering work by van Koten in
1994 due to their well-defined and tunable molecular architectures
as well as nano-order size.1 To date, a number of organometallic
Results and discussion
dendrimers with catalytic sites at the core or at the periphery have
been reported.2 Most of these reported catalysts were prepared
by covalent attachment of the chiral centers onto the dendritic
supports. Such a covalent approach, however, often suffered from
time-consuming synthesis as well as difficult recycling of the often
expensive dendritic support in the case of catalyst deactivation.
An interesting alternative approach has recently been developed,
which relies on the noncovalent anchoring of catalyst to the
soluble support using well-defined binding sites.3 This reversible
noncovalent method not only facilitates the immobilization of
catalyst, but also enables the easy reuse of the dendritic support.
Although many supramolecular dendrimers based on noncovalent
interactions have been intensively studied, however, few of them
have been employed in catalysis.4,5 To the best of our knowledge,
there is no report on the synthesis of supramolecular chiral
dendritic catalysts and their applications in asymmetric catalysis.
Monodentate chiral phosphorus ligands have recently attracted
considerable attention because of their excellent performance,
relatively simple synthesis from readily available building materials
and good stability.6 Recently, we reported two kinds of chiral
dendritic monodentate phosphoramide ligands, in which the chiral
monodentate phosphoramide units were attached onto the focal
point of the dendritic wedges via chemical bond approach.7 It
was found that the dendritic wedges played important role on the
enantioselectivity and reactivity in the Rh-catalyzed asymmetric
hydrogenation of functionalized olefins, such as a-dehydroamino
acid derivatives and enamides. Higher enantioselectivity was
achieved as the dendritic wedges on the N-atom of the phospho-
ramidite ligand became bigger.7b As an extension of our research,7,8
To achieve the formation of stable hydrogen-bonding assembly,
a suitable combination of multiple hydrogen bonds is necessary.
In this regard, we employ the well-established Hamilton receptor
for our study, which can form six hydrogen bonds with barbituric
acid derivatives in apolar solvent.9 Both supramolecular building
blocks are readily available and can be easily modified by attaching
functional groups. To exemplify our new immobilization strategy,
series of dendritic Hamilton receptors and barbiturates bearing a
chiral monophosphite were designed and synthesized. Thus, the
chiral monophosphite could be easily anchored onto the focal
point of the dendritic support by way of complementary hydrogen-
bonding interactions (Fig. 1).
For the synthesis of the dendritic Hamilton receptors, Fre´chet-
type dendrimer was chosen as the support due to its inertness
to reaction. The O-alkylation of dimethyl 5-hydroxyisophthalate
with dendrons 1 afforded the dendritic diesters 3 (3a–3c). Subse-
quent treatment of compound 3 with excess 2,6-diaminopyridine
in the presence of n-BuLi, followed by the acylation with acetic
anhydride, led to the dendritic receptors DGn (DG1–DG3) in 60–
88% yields (Scheme 1).
Beijing National Laboratory for Molecular Sciences, CAS Key Labo-
ratory of Molecular Recognition and Function, Institute of Chemistry,
Chinese Academy of Sciences, Beijing, 100190, P. R. China. E-mail:
fanqh@iccas.ac.cn
† Electronic supplementary information (ESI) available: Characterization
of dendritic supports, chiral monophosphite ligands and supramolecular
ligand. See DOI: 10.1039/b823047a
Scheme 1
1890 | Org. Biomol. Chem., 2009, 7, 1890–1895
This journal is
The Royal Society of Chemistry 2009
©

View Article Online
Fig. 1 Supramolecular chiral dendritic monophosphite ligands assembled by hydrogen bonding.
To investigate the potential effect of the dendritic support on
the catalytic performance, two barbiturate-based chiral phosphite
ligands L1 and L2 containing an oligoglycol linker of different
length between the barbiturate group and the phosphite moiety
were designed. As shown in Scheme 2, an EDC coupling of the
barbiturate-functionalized carboxyl acid 410 with ethylene glycol
or triethylene glycol gave the barbiturate-containing alcohols 5
in moderate yields. Then, 5 reacted with chlorophosphite 611
to furnish the barbiturate-based ligands L1 and L2 in good
yields, respectively. All these dendritic Hamilton receptors and
group and the phosphite moiety. For example, the proton NMR
spectrum of a 1 : 1 (molar ratio) mixture of DG3 and L1 showed
large downfield shift for the NH protons relative to the free
components (Fig. 2). After complexation, the amide protons of
dendritic receptor shifted downfield from 7.89 and 8.33 ppm
to 9.13 and 9.61 ppm, respectively, and the imide protons of
the barbiturate-based ligand also shifted greatly downfield from
8.20 ppm to 12.73 ppm. The phosphorus NMR study further
confirmed the formation of the supramolecular dendritic ligands.
Due to the partial self-association of the barbiturate moiety, 31P
NMR spectrum of the free ligand L1 in CDCl3 showed two peaks
at 139.3 and 140.9 ppm. In contrast, for the mixture of DG3 and
L1, only one peak at 140.7 ppm was observed without appearing
the signals of the free ligand L1, indicative of the formation of the
third-generation supramolecular monophosphite ligand DG3L1.
Similarly, complexation of L2 with DG3 was also demonstrated by
1H and 31P NMR spectra (Fig. 2).
In order to investigate the asymmetric induction of these
supramolecular chiral monophosphites, the Rh-catalyzed asym-
metric hydrogenation of a-phenylenamide (7a) in CH2Cl2 was
chosen as a standard reaction. The catalysts were prepared
in situ by reacting 2 equiv. of the preformed supramolecular
ligands with [Rh(COD)2]BF4 in CH2Cl2 at room temperature.
As shown in Table 1, hydrogenation proceeded smoothly in the
presence of 2.0 mol% Rh/DG3L1 catalyst under atmosphere
hydrogen pressure, providing the reduced product with complete
1
monophosphite ligands were well characterized by H, 13C and
31P NMR spectroscopy as well as MALDI-TOF or HRMS
mass spectrometry. The obtained results are consistent with the
compounds synthesized.
With these complementary components in hand, supramolec-
ular dendritic monophosphite ligands assembled by hydrogen
bonding were prepared by mixing one equivalent of the cor-
responding dendritic receptor DGn with one equivalent of the
barbiturate-based ligands (L1 or L2) in dry CDCl3. The thus-
1
formed supramolecular dendrimers were studied by H and 31P
NMR spectra. Generally, the first-generation receptor DG1 only
partially participated in the formation of the supramolecular
dendritic assembly because of its poor solubility in CDCl3. To
our delight, the second- and third-generation receptor DG2 and
DG3 could complex the barbiturate-based ligands effectively in
CDCl3 irrespective of the linkage length between the barbiturate
Scheme 2
This journal is
The Royal Society of Chemistry 2009
Org. Biomol. Chem., 2009, 7, 1890–1895 | 1891
©

View Article Online
Fig. 2 Partial 1H NMR spectra (CDCl3, 300 MHz, 295 K, 8.0 mM) of L, DG3L and DG3.
Table 1 Condition optimization for the Rh-catalyzed asymmetric hydro-
genation of a-phenylenamide (7a)a
Table 2 Asymmetric hydrogenation of enamides catalyzed by
supramolecular dendritic Rh/DGnL1 catalystsa
Entry
Ligand
H2/atm
Conv. (%)b
Ee (%)b
Entry
Ligands
Ar
Ee (%)b
1
2
3
4d
5
6
7
8
9
DG3L1
DG3L1
DG3L1
DG3L1
DG1L1
DG2L1
DG1L2
DG2L2
DG3L2
1
20
60
60
20
20
60
60
60
100
100
100
100
100
100
100
37
82
1
2
3
4
5
6
7
DG3L1
DG2L1
DG3L1
DG2L1
DG3L1
DG2L1
DG3L1
C6H5 (7a)
87
83
86 (85)c
87
4-Cl-C6H5 (7b)
4-Cl-C6H5 (7b)
4-Br-C6H5 (7c)
4-Br-C6H5 (7c)
4-Me-C6H5 (7d)
4-Me-C6H5 (7d)
87(87)c
85
89
80
82
30
88(86)c
89
90(89)c
37
88
64 (93)e
a Reaction conditions: 0.1 mmol substrate, 2 mol% [Rh(COD)2]BF4,
Rh/DGnL1 = 1 : 2.2 (mol/mol), 60 atm H2, 1.5 mL DCM, 20 ◦C, 20 h;
b Based on chiral GC analysis; c Data in parentheses were obtained with
catalyst Rh/L1.
a Reaction conditions: 0.1 mmol substrate, 2 mol% [Rh(COD)2]BF4,
Rh/ligand = 1 : 2.2 (mol/mol), 1.5 mL DCM, 20 ◦C, 20 h; b Based on
chiral GC analysis; c Data in parentheses was obtained with catalyst
Rh/L1; d Hydrogenation was carried out at -5 ◦C; e Data in parentheses
was obtained with catalyst Rh/L2.
Table 3 Asymmetric hydrogenation of a-dehydroamino acid esters cat-
alyzed by supramolecular dendritic Rh/DGnL1 catalystsa
conversion and good enantioselectivity (entry 1). It was found
that higher hydrogen pressure provided better enantioselectivity
(entries 1–3). Slightly higher enantioselectivity was observed
when the reaction was carried out under lower temperature
(entry 4). Interestingly, the enantioselectivity increased obviously
with increasing dendrimer generation (entries 2, 5 and 6). It was
also noted that the third-generation catalyst afforded comparable
enantioselectivity to that obtained from the catalyst bearing the
free ligand L1 (entry 2, 86% vs. 85% ee).
Then, we investigated the effect of the linkage length between
the barbiturate group and the phosphite moiety on the catalyst
performance (Table 1). In sharp contrast to Rh/DGnL1, catalysts
Rh/DGnL2 with a short linkage showed much lower enantiose-
lectivity and reactivity (entries 7–9). Higher generation dendrimer
catalyst gave much better enantioselectivity which, however, was
significantly lower than that obtained from the catalyst bearing the
free ligand L2 (entry 9, 64% vs. 93% ee). The negative dendrimer
effect was probably due to the steric effect of the bulk dendritic
wedges.
Entry
Ligands
Ar
Ee (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
DG2L1
DG3L1
DG2L1
DG3L1
DG2L1
DG3L1
DG2L1
DG3L1
DG2L1
DG3L1
DG2L1
DG3L1
DG2L1
DG3L1
C6H5 (9a)
83
C6H5 (9a)
87(88)c
83
4-Cl-C6H5 (9b)
4-Cl-C6H5 (9b)
4-Br-C6H5 (9c)
4-Br-C6H5 (9c)
4-F-C6H5 (9d)
4-F-C6H5 (9d)
4-MeO-C6H5 (9e)
4-MeO-C6H5 (9e)
3-Cl-C6H5 (9f)
3-Cl-C6H5 (9f)
H (9g)
85(88)c
86
86(88)c
83
86(87)c
87
87(91)c
81
83(87)c
90
H (9g)
90(91)c
a Reaction conditions: 0.1 mmol substrate, 2 mol% [Rh(COD)2]BF4,
Rh/DGnL1 = 1 : 2.2 (mol/mol), 1.5 mL DCM, 20 ◦C, 20 h; b Based on
chiral GC analysis; c Data in parentheses were obtained with catalyst
Rh/L1.
To further demonstrate the efficiency of these supramolecular
dendritic catalysts, other enamides (Table 2) and a-dehydroamino
acid esters (Table 3) were hydrogenated by using the second- and
1892 | Org. Biomol. Chem., 2009, 7, 1890–1895
This journal is
The Royal Society of Chemistry 2009
©

View Article Online
Table 4 Catalyst recycling in the asymmetric hydrogenation of 7a cat-
alyzed by dendritic Rh/DG3L1 catalysta
General procedure for the preparation of Fre´chet-type dendritic
diester 3a ~ 3c
3a (Gn = G1)12a
. To a solution of dendritic benzyl bromide
Cycle
Run 1
Run 2
Run 3
Run 4
Run 5
Run 6
1 (1.5 g, 3.9 mmol) in acetone (50 mL) was added dimethyl
5-hydroxyisophthalate (0.87 g, 4.1 mmol), K2CO3 (0.7 g,
4.7 mmol), KI, and a catalytic amount of 18-crown-6. The
resulting mixture was refluxed overnight. After removing the
solvent, the residue was extracted with CH2Cl2 (50 mL ¥ 2).
The combined organic layer was washed with brine, dried over
anhydrous Na2SO4, purified by flash column chromatography to
Conv (%)
Ee (%)
100
85
100
86
100
85
100
85
100
85
88
84
a Reaction conditions: 0.1 mmol substrate, 2 mol% [Rh(COD)2]BF4,
Rh/DG3L1 = 1 : 2.2 (mol/mol), 60 atm H2,1.5 mL DCM, 20 ◦C, 20 h.
third-generation dendritic ligands DG2L1 and DG3L1. Generally,
complete conversions and good enantioselectivities (83–90% ee)
were obtained in all cases. Notably, in comparison with DG2L1,
the third-generation supramolecular dendritic ligand DG3L1
gave better enantioselectivities, which were comparable to those
obtained from the free ligand L1.
Another important feature of dendrimer catalysts is the
easy and reliable separation of the chiral catalysts.2c To ex-
plore the recyclability of the supramolecular dendritic catalyst,
the Rh/DG3L1-catalyzed asymmetric hydrogenation of methyl
2-acetamido cinnamate was chosen as the standard reaction. Upon
the completion of the reaction, the catalyst was quantitatively
precipitated by the addition of hexane and reused at least five times
with similar reactivities and enantioselectivities (Table 4).
1
give 3a (1.8 g, 90% yield) as a white solid. H NMR (300 MHz,
CDCl3) d: 3.93 (s, 6H), 5.04 (s, 4H), 5.06 (s, 2H), 6.59 (d, J =
2.1 Hz, 1H), 6.68 (d, J = 1.97 Hz, 2H), 7.30–7.43 (m, 10H), 7.81
(s, 2H), 8.29 (d, J = 0.92 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d: 52.4, 70.2, 70.3, 101.9, 106.4, 120.2, 123.3, 127.5, 128.0, 128.6,
131.9, 136.8, 138.5, 158.7, 160.3, 166.1.
3b (Gn = G2)12b
.
Following the procedure for 3a. 87% yield; 1H
NMR (300 MHz, CDCl3) d: 3.92 (s, 6H), 5.00 (s, 4H), 5.03 (s, 8H),
5.07 (s, 2H), 6.56–7.68 (m, 9H), 7.25–7.42 (m, 20H), 7.82 (s, 2H),
8.29(d, J =0.66Hz, 1H);13CNMR(75MHz, CDCl3)d:51.4, 69.0,
69.1, 69.3, 100.6, 100.8, 105.3, 105.4, 119.1, 122.3, 126.5, 127.0,
127.2, 127.6, 130.8, 135.8, 137.4, 138.1, 157.7, 159.1, 159.2, 165.0.
3c (Gn = G3)12. Following the procedure for 3a. Yield 90%; 1H
NMR (300 MHz, CDCl3) d: 3.89 (s, 6H), 4.95 (s, 12H), 5.00 (s,
16H), 5.03 (s, 2H), 6.53–6.56 (m, 7H), 6.65–6.67 (m, 14H), 7.29–
7.41 (m, 40H), 7.80 (d, J = 1.4 Hz, 2H), 8.28 (d, J = 1.4 Hz, 1H).
13C NMR (75 MHz, CDCl3) d: 52.5, 70.1, 70.2, 70.3, 101.7, 101.9,
106.5, 120.2, 123.4, 127.3, 127.6, 127.7, 128.1, 128.4, 128.5, 128.7,
132.0, 136.9, 138.7, 139.3, 139.4, 158.8, 160.2, 160.3, 166.1. MS
(MALDI-TOF): m/z for C115H100O19 Calcd 1785.7. found 1808.3
[M + Na]+, 1824.3 [M + K]+.
Conclusions
In summary, we have developed a new type of supramolecular
chiral dendritic monophosphite ligands through the hydrogen-
bonding assembly for the first time. These supramolecular ligands
were successfully applied in the Rh-catalyzed asymmetric hydro-
genation of enamides and a-dehydroamino acid derivatives with
good enantioselectivities, which are comparable to those obtained
from the free chiral monophosphite ligands. The supramolecular
catalyst could be recycled and reused readily at least 5 times
without obvious loss of enantioselectivity and reactivity. These
supramolecular ligands are modular, and further applications to
other asymmetric reactions are underway in our laboratory.
General procedure for the preparation of the dendritic Hamilton
receptor DG1–DG3
DG1. To a solution of 2,6-diaminopyridine (recrystallized
from hot ethyl acetate) (0.24 g, 1.56 mmol) in THF at -78 ◦C was
added dropwise a solution of n-BuLi in hexane (2.5 M, 1.6 mL),
and stirred at -78 ◦C for a further 30 min. A solution of compound
3a (0.2 g, 0.39 mmol) in 10 mL THF was then added. The reaction
mixture was stirred at -78 ◦C for 4 h, then gradually warmed
to room temperature and stirred overnight. The reaction was
then quenched with a saturated aqueous solution of NH4Cl, and
extracted with CH2Cl2. The organic layer was washed with water
and brine, dried over Na2SO4 and concentrated in vacuo. After
the residue was resolved in THF, Ac2O and Et3N were added.
The reaction mixture was allowed to stir overnight. After the
solvent was removed, the residue was purified by flash column
chromatography to provide the compound DG1 (0.18 g, 60% yield
Experimental
General
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 nitrogen-filled glovebox. H
1
NMR, 13C NMR and 31P NMR spectra were recorded on a Bruker
Model Advance DMX 300 or 400 Spectrometer (1H 300 MHz,
13C 75 MHz and 31P 162 MHz, respectively). Chemical shifts (d)
are given in ppm and are referenced to residual solvent peaks
(1H and 13C NMR) or to an external standard (85% H3PO4, 31P
NMR). MALDI-TOF mass spectra were obtained on a BIFLEX
III instrument with a-cyano-4-hydroxycinnamic acid (CCA) as the
matrix. All enantiomeric excess values were obtained from GC
analysis with a Chrompack CHIR-L-VAL column. 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 or Acros without further
purification.
1
for two steps) as a white powder. H NMR (300 MHz, DMSO-
d6) d: 2.11 (s, 6H), 5.10 (s, 4H), 5.23 (s, 2H), 6.66–6.76 (m, 3H),
7.32–7.46 (m, 10H), 7.79–7.84 (m, 8H), 8.14 (s, 1H), 10.15 (s, 2H),
10.48 (s, 2H). 13C NMR (75 MHz, DMSO-d6) d: 23.9, 69.4, 69.5,
101.2, 106.4, 109.4, 110.5, 117.6, 120.0, 127.7, 127.8, 128.4, 135.6,
136.9, 139.0, 140.0, 150.0, 150.6, 158.3, 159.6, 164.9, 169.3. MS
(MALDI-TOF): m/z for C43H38N6O7: calcd. 750.3, found 751.0
[M + H]+, 773.0 [M + Na]+, 789.0 [M + K]+.
This journal is
The Royal Society of Chemistry 2009
Org. Biomol. Chem., 2009, 7, 1890–1895 | 1893
©

View Article Online
DG2. Following the procedure for DG1. 70% yield; 1H NMR
(300 MHz, CDCl3) d: 2.14 (s, 6H), 4.95 (s, 4H), 4.99 (s, 8H), 5.02
(s, 2H), 6.55–6.66 (m, 9H), 7.28–7.40 (m, 20H), 7.62–7.71 (m, 4H),
7.91–7.99 (m, 7H), 8.41 (br. 2H). 13C NMR (300 MHz, CDCl3) d:
24.5, 70.0, 70.1, 70.2, 101.6, 101.8, 106.3, 106.4, 109.8, 110.2, 117.5,
117.9, 127.5, 128.0, 128.6, 135.9, 136.7, 138.2, 139.1, 140.7, 149.3,
149.8, 159.2, 160.1, 160.2, 164.4, 169.0. MS (MALDI-TOF): m/z
for C71H62N6O11: calcd. 1174.4, found 1175.0 [M + H]+, 1197.0
[M + Na]+, 1213.0 [M + K]+.
(m, 8H), 8.06–8.19 (m, 4H), 11.50 (s, 2H). 13C NMR (75 MHz,
DMSO-d6) d: 8.3, 25.1, 31.7, 52.1, 64.1, 64.4, 68.0, 69.7, 69.7, 69.8,
121.7, 121.9, 123.3, 125.1, 125.3, 125.8, 126.0, 126.6, 126.7, 128.6,
128.7, 130.3, 130.7, 130.8, 131.1, 131.7, 132.0, 146.9, 147.9, 147.9,
150.1, 170.9, 172.7. 31P NMR (162 MHz, DMSO-d6) d: 146.4;
HRMS (SIMS) for C34H33N2O10P, [M + H]+: calcd. 661.1946,
found 661.1943; [M + Na]+: 683.1759.
L2. Following the procedure for L1, 5b (300 mg, 1.16 mmol),
Et3N (0.23 mL, 1.74 mmol) and (S)-[1,1¢-binaphthyl-2,2¢-
diyl]chlorophosphite 6 (407 mg, 1.16 mmol) yielded L2 (570 mg,
86% yield) as a whitefoam. 1HNMR(300 MHz, DMSO-d6) d: 0.85
(t, J = 7.41 Hz, 3H), 1.74 (q, J = 8.46 Hz, 2H), 3.10 (s, 2H), 3.96–
4.16 (m, 4H), 7.19–7.69 (m, 8H), 8.06–8.20 (m, 4H), 11.54 (s, 2H);
13C NMR (75 MHz, DMSO-d6) d: 8.4, 31.7, 52.2, 62.8, 64.5, 121.6,
121.7, 123.3, 125.2, 125.4, 125.9, 126.0, 26.7, 126.8, 128.6, 128.7,
130.5, 130.7, 130.9, 131.2, 131.7, 132.0, 146.8, 147.9, 150.1, 171.1,
172.7; 31P NMR (162 MHz, DMSO-d6) d: 146.3; HRMS (SIMS)
for C30H25N2O8P, [M + H]+: calcd. 571.1246, found 571.1293.
DG3. Following the procedure for DG1. 88% yield; 1H NMR
(300 MHz, CDCl3) d: 2.08 (s, 6H), 4.91 (s, 8H), 4.94 (s, 4H),
4.97 (s, 16H), 5.01 (s, 2H), 6.52–6.64 (m, 21H), 7.25–7.38 (m,
40H), 7.58–7.70 (m, 6H), 7.89–8.00 (m, 5H), 8.33 (br., 2H). 13C
NMR (300 MHz, CDCl3) d: 24.5, 70.0, 70.1, 70.2, 101.6, 102.0,
106.4, 109.7, 110.0, 117.4, 117.9, 127.1, 127.5, 127.8, 128.0, 128.3,
128.3, 128.6, 129.9, 136.0, 136.7, 138.2, 139.2, 140.8, 149.3, 149.7,
159.2, 160.1, 160.1, 164.2, 168.8. MS (MALDI-TOF): m/z for
C127H110N6O19: calcd. 2022.8, found 2023.3 [M + H]+, 2045.4 [M +
Na]+, 2061.4 [M + K]+.
General procedure for the asymmetric hydrogenation of enamides
General procedure for the preparation of barbiturate-containing
alcohols 5a and 5b
The dendritic supramolecular monophosphite (9 ¥ 10-3 mmol),
generated by mixing one equivalent of the corresponding dendritic
receptor and one equivalent of the barbitaric-based monophos-
phite in dichloromethane (1 mL), and Rh(COD)2BF4 (4 ¥
10-3 mmol) in CH2Cl2 (1 mL) were stirred at room temperature for
10 min under nitrogen atmosphere. Then, in a 50 mL glass-lined
stainless steel reactor with a magnetic stirring bar was charged with
phenylenamide (16.1 mg, 0.1 mmol), the above in situ prepared
catalyst (1 mL, 2 ¥ 10-3 mmol). The autoclave was closed and
pressurized with hydrogen to 60 atm. The mixture was stirred at
ambient temperature for 20 h. After carefully venting of hydrogen,
conversion and enantioselectivity of the reduced product were
determined by chiral GC with a 25 m Chir-l-val capillary column.
5a. To a solution of barbituric acid derivative 4 (0.50 g,
2.34 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide
hydrochloride (EDCI, 0.49 g, 2.55 mmol) in THF (50 mL) at 0 ◦C
was added triethylene glycol (1.40 g, 9.33 mmol). The resulting
mixture was allowed to stand overnight at room temperature. After
the solvent was removed under reduced pressure, the residue was
purified by flash column chromatography to give 5a (0.56 g, 70%
yield) as a colorless oil. 1H NMR (300 MHz, DMSO-d6) d: 0.82 (t,
J = 7.53 Hz, 3H), 1.78 (q, J = 7.55 Hz, 2H), 3.02 (s, 2H), 3.42–3.57
(m, 10H), 4.09(t, J = 4.35 Hz, 2H), 4.56 (t, J = 5.4 Hz, 1H), 11.47
(s, 2H). 13C NMR (75 MHz, DMSO-d6) d: 8.3, 31.7, 52.2, 60.2,
64.2, 68.0, 69.6, 69.8, 72.3, 79.1, 150.0, 170.9, 172.6. HRMS (ESI)
for C14H22N2O8, [M + H]+: calcd. 347.1449, found 347.1453.
Acknowledgements
5b. Following the procedure for 5a, 4 (1.30 g, 6.07 mmol),
EDCI (1.40 g, 7.29 mmol) and ethylene glycol (2.90 g, 46.78 mmol)
yielded 5b (1.0 g, 66% yield) as a white solid. 1H NMR (300 MHz,
acetone-d6) d: 0.96 (t, J = 7.53 Hz, 3H), 1.89 (q, J = 7.50 Hz, 2H),
3.10 (s, 2H), 3.66–3.72 (m, 2H), 3.88 (t, J = 5.73 Hz, 1H), 4.10
(t, J = 4.80 Hz, 2H), 10.22 (s, 2H). 13C NMR (75 MHz, acetone-
d6) d: 8.9, 33.0, 60.4, 67.6, 150.2, 172.1, 173.3. HRMS (ESI) for
C10H14N2O6, [M + H]+: calcd. 259.0925, found 259.0924.
We are grateful to the financial support from the National Natural
Science Foundation of China (20532010 and 20772128) and
Chinese Academy of Sciences.
Notes and references
1 J. W. J. Knapen, A. W. van der Made, J. C. de Wilde, P. W. N. M. van
Leeuwen, P. Wijkens, D. M. Grove and G. van Koten, Nature, 1994,
372, 659.
General procedure for the preparation of barbiturate-based chiral
monophosphite ligands L1 and L2
2 (a) Selected reviews on dendritic organometallic catalysts, see: G. E.
Oosterom, J. N. H. Reek, P. C. J. Kamer and P. W. N. M. van Leeuwen,
Angew. Chem., Int. Ed., 2001, 40, 1828; (b) D. Astruc and F. Chardac,
Chem. Rev., 2001, 101, 2991; (c) R. van Heerbeek, P. C. J. Kamer,
P. W. N. M. van Leeuwen and J. N. H. Reek, Chem. Rev., 2002, 102,
3717; (d) L. J. Twyman, A. S. H. King and I. K. Martin, Chem. Soc.
Rev., 2002, 31, 69; (e) B. Helms and J. M. J. Fre´chet, Adv. Synth. Catal.,
2006, 348, 1125; (f) J. K. Kassube and L. H. Gade, Top. Organomet.
Chem., 2006, 20, 61; (g) Q. H. Fan, Y. M. Li and A. S. C. Chan, Chem.
Rev., 2002, 102, 3385; (h) Q. H. Fan, G. J. Deng, Y. Feng, and Y. M. He,
Handbook of Asymmetric Heterogeneous Catalysis, ed. K. Ding and Y.
Uozumi, Wiley-VCH, Weinheim, 2008, p. 131.
3 (a) For recent review, see: R. van de Coevering, R. J. M. K. Gebbink
and G. van Koten, Prog. Polym. Sci., 2005, 30, 474; (b) F. Ribaudo,
P. W. N. M. van Leeuwen and J. N. H. Reek, Top. Organomet. Chem.,
2006, 20, 39; (c) for selected examples, see: C. Bianchini, P. Barbaro,
V. D. Santo, R. Gobetto, A. Meli, W. Oberhauser, R. Psaro and
L1. To a solution of the corresponding barbituric acid ester
5a (500 mg, 1.45 mmol) and Et3N (0.31 mL, 2.17 mmol)
in THF (10 mL) at 0 ◦C was added dropwise a solution
of (S)-[1,1¢-binaphthyl-2,2¢-diyl]chlorophosphite 6 (510 mg,
1.45 mmol) in THF (10 mL). The resulting mixture was stirred at
room temperature for 16 h. The precipitate of Et3NHCl was filtered
over a pad of Celite. After the solvent was removed under reduced
pressure, the residue was purified by flash column chromatography
to give L1 (830 mg, 87%yield)as awhite foam. 1H NMR(300MHz,
DMSO-d6) d: 0.80 (t, J = 7.41 Hz, 3H), 1.74 (q, J = 8.46 Hz,
2H), 3.00 (s, 2H), 3.56–3.60 (m, 8H), 3.97–4.08 (m, 4H), 7.19–7.64
1894 | Org. Biomol. Chem., 2009, 7, 1890–1895
This journal is
The Royal Society of Chemistry 2009
©

View Article Online
F. Vizza, Adv. Synth. Catal., 2001, 343, 41; (d) L. Shi, X. W. Wang,
C. A. Sandoval, M. X. Li, Q. Y. Qi, Z. T. Li and K. L. Ding, Angew.
Chem., Int. Ed., 2006, 45, 4108; (e) H. Q. Yang, L. Zhang, L. Zhong,
Q. H. Yang and C. Li, Angew. Chem., Int. Ed., 2007, 46, 6861; (f) S. Z.
Luo, J. Y. Li, H. Xu, L. Zhang and J. P. Cheng, Org. Lett., 2007, 9,
3675; (g) L. Xing, J. H. Xie, Y. S. Chen, L. X. Wang and Q. L. Zhou,
Adv. Synth. Catal., 2008, 350, 1013.
4 (a) J. M. J. Fre´chet, Proc. Natl. Acad. Sci. U. S. A., 2002, 99, 4782;
(b) D. K. Smith, A. R. Hirst, C. S. Love, J. G. Hardy, S. V. Brignell and
B. Huang, Prog. Polym. Sci., 2005, 30, 220.
5 (a) Selected examples of supramolecular dendrimer catalysts, see: D.
de Groot, B. F. M. de Waal, J. N. H. Reek, A. P. H. J. Schenning,
P. C. J. Kamer, E. W. Meijer and P. W. N. M. Leeuwen, J. Am. Chem.
Soc., 2001, 123, 8453; (b) M. Ooe, M. Murata, T. Mizugaki, K. Ebitani
and K. Kaneda, J. Am. Chem. Soc., 2004, 126, 1604; (c) R. van de
Coevering, A. P. Alfers, J. D. Meeldijk, E. Martinez-Viviente, P. S.
Pregosin, R. J. M. K. Gebbink and G. van Koten, J. Am. Chem. Soc.,
2006, 128, 12700; (d) L. Plault, A. Hauseler, S. Nlate, D. Astruc, J. Ruiz,
S. Gatard and R. Neumann, Angew. Chem., Int. Ed., 2004, 43, 2924.
6 (a) I. V. Komarov and A. Borner, Angew. Chem., Int. Ed., 2001, 40,
1197; (b) T. Jerphagnon, J. L. Renaud and C. Bruneau, Tetrahedron:
Asymmetry, 2004, 15, 2101; (c) J. G. de Vries and L. Lefort, Chem.–
Eur. J., 2006, 12, 4722; (d) M. T. Reetz, Angew. Chem., Int. Ed., 2008,
47, 2556; (e) L. Eberhardt, D. Armspach, J. Harrowfield and D. Matt,
Chem. Soc. Rev., 2008, 37, 839; (f) M. van den Berg, A. J. Minnard,
E. P. Schudde, J. van Esch, A. H. M. de Vries, J. G. de Vries and B. L.
Feringa, J. Am. Chem. Soc., 2000, 122, 11539; (g) M. van den 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. Henderickx and J. G. de Vries, Adv.
Synth. Catal., 2003, 345, 308; (h) A. G. Hu, Y. Fu, J. H. Xie, L. X. Wang
and Q. L. Zhou, Angew. Chem., Int. Ed., 2002, 41, 2348; (i) Y. Liu and
K. L. Ding, J. Am. Chem. Soc., 2005, 127, 10488.
7 (a) W. J. Tang, Y. Y. Huang, Y. M. He and Q. H. Fan, Tetrahedron:
Asymmetry, 2006, 17, 536; (b) F. Zhang, Y. Li, Z. W. Li, Y. M. He, S. F.
Zhu, Q. H. Fan and Q. L. Zhou, Chem. Commun., 2008, 6048.
8 (a) Q. H. Fan, Y. M. Chen, X. M. Chen, D. Z. Jiang, F. Xi and A. S. C.
Chan, Chem. Commun., 2000, 789; (b) G. J. Deng, Q. H. Fan, X. M.
Chen, D. S. Liu and A. S. C. Chan, Chem. Commun., 2002, 1570; (c) B.
Yi, Q. H. Fan, G. J. Deng, Y. M. Li, L. Q. Qiu and A. S. C. Chan, Org.
Lett., 2004, 6, 1361; (d) L. Wu, B. L. Li, Y. Y. Huang, H. F. Zhou, Y. M.
He and Q. H. Fan, Org. Lett., 2006, 8, 3605; (e) Z. J. Wang, G. J. Deng,
Y. Li, Y. M. He, W. J. Tang and Q. H. Fan, Org. Lett., 2007, 8, 1243.
9 (a) S. K. Chang and A. D. Hamilton, J. Am. Chem. Soc., 1988, 110, 1318;
(b) P. Tecilla, R. P. Dixon, G. Slobodkin, D. S. Alavi, D. H. Waldeck and
A. D. Hamilton, J. Am. Chem. Soc., 1990, 112, 9408; (c) P. Tecilla and
A. D. Hamilton, J. Chem. Soc., Chem. Commun., 1990, 1232; (d) S. J.
Geib, C. Vicent, E. Fan and A. D. Hamilton, Angew. Chem., Int. Ed.,
1993, 32, 119.
10 O. Felix, M. Crego-Calama, I. Luyten, P. Timmerman and D. N.
Reinboudt, Eur. J. Org. Chem., 2003, 1463.
11 A. Korostylev, I. Gridnev and J. M. Brown, J. Organomet. Chem., 2003,
680, 329.
12 (a) Y. Feng, Y. M. He, L. W. Zhao, Y. Y. Huang and Q. H. Fan, Org.
Lett., 2007, 9, 2261; (b) G. J. Deng, B. Yi, Y. Y. Huang, W. J. Tang,
Y. M. He and Q. H. Fan, Adv. Synth. Catal., 2004, 346, 1440.
This journal is
The Royal Society of Chemistry 2009
Org. Biomol. Chem., 2009, 7, 1890–1895 | 1895
©