Asymmetric transfer hydrogenation catalysed by hydrophobic dendritic DACH-rhodium complex in water

Article abstract of DOI:10.1039/b608386b

Hydrophobic Frechet-type dendritic chiral 1,2-diaminocyclohexane- Rh(iii) complexes have been applied in the asymmetric transfer hydrogenation of ketones in water using HCOONa as hydrogen source. The catalysts were found to be finely dissolved in the liquid substrates in the aqueous mixture and exhibited high catalytic activity and enantioselectivity (52-97% ee). The catalytic loading could be decreased to 0.01 mol% and good conversion was still obtained with excellent enantioselectivity. Moreover, the catalyst could be easily precipitated from the mixture by adding hexane and reused several times without affecting the high enantioselectivity. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b608386b

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Asymmetric transfer hydrogenation catalysed by hydrophobic dendritic
DACH–rhodium complex in water
Lin Jiang,a Tong-Fei Wu,b Ying-Chun Chen,*a Jin Zhub and Jin-Gen Deng*b
Received 13th June 2006, Accepted 7th July 2006
First published as an Advance Article on the web 28th July 2006
DOI: 10.1039/b608386b
Hydrophobic Fre´chet-type dendritic chiral 1,2-diaminocyclohexane–Rh(III) complexes have been
applied in the asymmetric transfer hydrogenation of ketones in water using HCOONa as hydrogen
source. The catalysts were found to be finely dissolved in the liquid substrates in the aqueous mixture
and exhibited high catalytic activity and enantioselectivity (52–97% ee). The catalytic loading could be
decreased to 0.01 mol% and good conversion was still obtained with excellent enantioselectivity.
Moreover, the catalyst could be easily precipitated from the mixture by adding hexane and reused
several times without affecting the high enantioselectivity.
sults in asymmetric transfer hydrogenation reactions in organic
Introduction
solvents.9,10 It is intriguing to consider that the chiral DACH-
Water has triggered ongoing interest as an alternative solvent
metal complexes immobilised on highly hydrophobic Fre´chet-type
in organic synthesis due to its low cost, toxicity and environ-
dendrons could be utilised as recyclable transfer hydrogenation
mental impact.1 Since more and more metal-catalysed reactions
catalysts in water. Here, we would like to report our studies on this
are able to be conducted smoothly in aqueous solution,2 the
recycling of such catalysts is also a task of great environmental
importance, especially when expensive and toxic heavy metal
subject.
Results and discussion
complexes are employed. Water-soluble ligands are commonly
applied to give hydrophilic metal-catalysts that will be retained
in the aqueous phase,3 however, sometimes reduced catalytic
activity is encountered due to the biphasic characteristics of the
hydrophilic catalysts and the organic reactants. On the other hand,
catalysts immobilised on hydrophobic macromolecules have been
rarely investigated in aqueous reactions. This strategy might be
applicable in that the hydrophobic complex could be dissolved in
the liquid substrate to promote the reaction in a homogeneous
fashion, and high catalytic activity would be expected owing to
the high catalyst concentration in the substrate solution. Then the
catalysts could be recycled by adding inert solvent.
Recently the ruthenium or rhodium complexes of N-sulfonated
chiral diamines4,5 have been found to be more active cat-
alysts in the asymmetric transfer hydrogenation of ketones6
and imines7 in aqueous solution, in comparison with those
in organic solvents. In addition, recyclable N-sulfonated 1,2-
diphenylethylenediamine (DPEN)–ruthenium catalysts by em-
ploying water-soluble ligands6b,g or immobilisation on silica gel6f
have been successfully applied in water. However, the development
of recyclable catalysts based on chiral 1,2-diaminocyclohexane
(DACH)–metal complexes,8 especially for the rhodium complexes,
has not been well studied yet. Recently we reported the synthesis
of dendritic DPEN–ruthenium catalysts and achieved good re-
The core-functionalised dendritic ligands based on chiral 1,2-
diaminocyclohexane (DACH) were smoothly prepared in a similar
way as reported early.9a,c As illustrated in Scheme 1, the amino-
functionalised intermediate (R,R)-4, which was synthesised in
three steps from (R,R)-DACH, was condensed with Fre´chet’s
polyether dendrons, using (PhO)3P as the coupling reagent.
Then the dendritic ligands 1a–1d were obtained through the
deprotection of the Boc group. The dendritic structures could
be established through MS techniques (ESI HRMS or MALDI-
TOF MS). All of the MS spectra displayed a very prominent
peak corresponding to the dendrimers complexed with proton or
potassium cation. MALDI-TOF MS was applied for the analysis
of 1d (Table 1).
With the desired chiral dendritic ligands 1a–1d in hand, the
catalytic activity and enantioselectivity of their ruthenium or
rhodium complexes were studied via the transfer hydrogenation
of acetophenone 7a, and also compared with the monomeric
TsDACH 6–metal complex. We have conducted the transfer
hydrogenation reactions in three different conditions for detailed
comparison of the dendritic catalysis at 1 mol% catalyst loading:
(A) [RuCl2(cymene)]2 as the metal precursor in DCM solution,
Table 1 MS data of dendritic ligands
Compound
MW (calcd.)
MW (found)
aKey Laboratory of Drug-Targeting of Education Ministry and Depart-
ment of Medicinal Chemistry, West China School of Pharmacy, Sichuan
University, Chengdu, 610041, China. E-mail: ycchenhuaxi@yahoo.com.cn;
Fax: +86 28 85502609; Tel: +86 28 85502609
1a
1b
1c
1d
585.2297
1009.3972
1857.7321
3554
586.2351a,b
1010.4095a,b
1858.7390a,b
3593c,d
bKey Laboratory of Asymmetric Synthesis & Chirotechnology of Sichuan
Province and Union Laboratory of Asymmetric Synthesis, Chengdu Institute
of Organic Chemistry, Chinese Academy of Sciences, Chengdu, 610041,
China. E-mail: jgdeng@cioc.ac.cn
a ESI HRMS. b (M + H)+. c MALDI-TOF MS. d (M + K)+.
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Scheme 1 Synthesis of dendritic DACH ligands.
the azeotrope of HCOOH–NEt3 as the hydrogen source at 28 ◦C;
(B) [RuCl2(cymene)]2 as the metal precursor in aqueous solution,
HCOONa as the hydrogen source at 35 ◦C; (C) [RhCp*Cl2]2
as the metal precursor in aqueous solution, HCOONa as the
hydrogen source at 40 ◦C. The average turnover frequency (TOFs,
in relation to per Ru– or Rh–complex) and enantioselectivity were
summarised in Table 2.
Table 2 Comparison of the catalytic efficiency of dendritic catalysts
in different conditions in the asymmetric transfer hydrogenation of
acetophenonea
Although quite different results were obtained under three
reaction conditions, in general, good retention of high enantiose-
lectivity was observed for all dendritic catalysts as compared to the
monomeric metal complex of 6. Much slower catalytic activity was
detected for the fourth generation dendritic 1d–Ru(II) or Rh (III)
complex due to its bulky structure, especially in the organic solvent
(Table 2, entries 5, 10 and 15).11 On the other hand, we were pleased
to find that all hydrophobic dendritic DACH–Ru(II) or Rh(III)
complexes could be finely dissolved in organic acetophenone and
maintained the high catalytic activity in water (conditions B,
entries 7–10, and conditions C, entries 12–15). Therefore, the
asymmetric reactions in the aqueous mixture promoted by the
hydrophobic dendritic catalysts still proceeded in a homogeneous
way. In addition, much better results were obtained by employing
[RhCp*Cl2]2 as the metal precursor (conditions C).6d Moreover,
the catalytic loading could be further decreased under conditions
C. The reduction of acetophenone took place smoothly at
0.1 mol% of 1b–Rh(III), furnishing a >99% conversion with 94%
ee in 4 h (entry 16). The reaction was also feasible with S/C ratio
up to 10000, though moderate conversion was obtained and a
prolonged reaction time was necessary (entry 17).
Having demonstrated that the dendritic DACH–Rh(III) cata-
lysts have high catalytic efficacy in water, we then tested the
recyclability of these dendritic catalysts via the solvent precip-
itation method. We employed the second generation dendritic
1b–Rh(III) complex at 1 mol% loading as the example. After a
specific reaction time, hexane was added to precipitate the 1b–
Rh catalyst, and then the organic phase containing the product
was removed. Before the next reaction could be conducted, 1 equiv.
HCOOH was added to adjust the pH value to about 7. As shown in
Table 3, the recycling use of dendritic 1b–Rh(III) catalyst was
Entry
Ligand
Conditions
TOF/h−1
Conv. (%)
Eeb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16c
17d
6
A
A
A
A
A
B
B
B
B
B
C
C
C
C
C
C
C
3.6
3.5
3.3
3.8
0.3
41
37
36
37
20
384
344
364
324
236
>99
>99
>99
>99
80
>99
>99
>99
>99
95
>99
>99
>99
>99
99
>99
61
94
93
94
93
93
88
88
88
87
85
95
96
96
96
95
94
95
1a
1b
1c
1d
6
1a
1b
1c
1d
6
1a
1b
1c
1d
1b
1b
a Conditions A: [RuCl2(cymene)]2 (0.002 mmol), diamine ligand
(0.0044 mmol), acetophenone (0.4 mmol) and HCOOH–NEt3 (0.2 mL)
were stirred in DCM (0.5 mL) at 28 ◦C. The average TOFs were calculated
over 5 h reaction time. Conversions were determined by GC analysis
after 30 h; Conditions B: [RuCl2(cymene)]2 (0.002 mmol), diamine ligand
(0.0044 mmol), acetophenone (0.4 mmol) and HCOONa (2.4 mmol) were
stirred in water (1 mL) at 35 ◦C. The average TOFs were calculated over
2 h reaction time. Conversions were determined by GC analysis after 4 h;
Conditions C: [RhCp*Cl2]2 (0.002 mmol), diamine ligand (0.0044 mmol),
acetophenone (0.4 mmol) and HCOONa (2.4 mmol) were stirred in
water (1 mL) at 40 ◦C. The average TOFs were calculated over 15 min
reaction time. Conversions were determined by GC analysis after 40 min.
b Determined by GC analysis on a Chrompack CP Chirasil-dex column.
The absolute configuration was R. c Under conditions C at 4 mmol scale,
S/C = 1000, 4 h. d Under conditions C at 40 mmol scale, S/C = 10000,
72 h.
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Table 3 Recycling use of dendritic 1b–Rh in the asymmetric transfer
Table 4 Asymmetric transfer hydrogenation of ketones catalysed by
dendritic 1b–Rh in H2O–HCOONaa
hydrogenation of acetophenone in watera
Entry
Substrate
t/h
Conv.b (%)
Eec (%)
1
2
3
4
5
6
7
8
9
7a
7b
7c
7d
7e
7f
7g
7h
7i
0.7
0.5
0.8
1
1.5
0.8
0.5
5
>99
99
97
95
>99
99
96
93
92
94
81
97
96
91e
57
72e
52e
Run
t/min
Conv.b (%)
Eec (%)
1
2
3
4
5
6
40
40
40
60
60
90
>99
>99
98
99
85
96
95
94
95
95
95
98
70d
69d
97d
94d
9
4
1.3
10
11
7j
7k
97
a Conditions: [RhCp*Cl2)]2 (0.002 mmol), ligand 1b (0.0044 mmol), ketone
7 (0.4 mmol) and HCOONa (2.4 mmol) were stirred in water (1 mL) at
40 ◦C. b Determined by GC analysis. c Determined by GC analysis on
a Chrompack CP Chirasil-dex column. d Isolated yield. e Determined by
HPLC analysis on OD or AS column.
a Conditions: [RhCp*Cl2)]2 (0.01 mmol), ligand 1b (0.022 mmol), ace-
tophenone (2.0 mmol) and HCOONa (12 mmol) were stirred in water
(5 mL) at 40 ◦C. b Determined by GC analysis. c Determined by GC analysis
on a Chrompack CP Chirasil-dex column.
quite successful (Table 3, runs 1–6). Excellent conversion (97%)
and enantioselectivity (95%) were obtained even in the sixth run
with some extension of the reaction time. On the other hand,
it should be noted that, in contrast to the previously reported
dendritic DPEN–Ru(II) catalysts,9 the dendritic DACH–Rh(III)
or Ru(II) complexes exhibited very limited recyclability in organic
solution.12
addition, a,b-unsaturated ketone 7k was chemoselectively reduced
to the corresponding allylic alcohol in high yield, while the ee was
not satisfying (entry 11).9c
Conclusions
In conclusion, dendritic chiral monosulfonylated DACH ligands
supported on the core of Fre´chet-type dendrons have been
synthesised. Their ruthenium(II) and rhodium(III) complexes have
been tested in the transfer hydrogenation of ketones in organic
or aqueous solution, and much better catalytic efficacy has been
noted in an aqueous system using HCOONa as the hydrogen
source. The highly hydrophobic dendritic rhodium(III) complexes
were found to be finely dissolved in the liquid substrates in
the reaction mixture and exhibited high catalytic activity and
enantioselectivity for a range of ketones. The catalytic loading
could be decreased to 0.01 mol% and good conversion was
still obtained with excellent enantioselectivity. Moreover, the
catalyst could be easily precipitated from the mixture by adding
hexane and reused several times without affecting the high
enantioselectivity. We believe that the application of other immo-
bilised hydrophobic catalysts in aqueous catalysis could be also
desirable.
Subsequently, we extended this protocol to a range of aromatic,
heteroaromatic and functionalised ketones (Fig. 1), aiming to
determine the potential applicability of the dendritic catalytic
system in the asymmetric transfer hydrogenation in water. The
results are summarised in Table 4. In the case of acetophenone
derivatives, excellent conversions and high ees could be obtained
irrespective of the substitution on the aryl ring (Table 4, entries 1–
5), however, a lower ee was observed for the ortho-substituted
ketone 7e (entry 5). 1-Tetralone 7f was completely converted
to the corresponding alcohol with excellent ee (entry 6). The
heteroaromatic ketones were also tested. 2-Acetylthiophene 7g
was successfully reduced in 98% conversion and 96% ee in 0.5 h
(entry 7). On the other hand, the transfer hydrogenation of
pyridyl ketones 7h and 7i in homogenous DCM–HCOOH–NEt3
conditions seemed unfeasible, in sharp contrast, both substrates
were smoothly reduced in the H2O–HCOONa system, affording
good isolated yields, while much higher reactivity and ee were
obtained for 2-acetylpyridine 7h than those of 3-acetylpyridine
7i (entry 8 vs. entry 9).13 a-Ketoester 7j could be smoothly
transfer hydrogenated in moderate enantioselectivity (entry 10). In
Experimental
General methods
Melting points were determined in open capillaries and are
uncorrected. TLC was performed on glass-backed silica plates.
Column chromatography was performed using silica gel (200–
300 mesh) eluting with ethyl acetate and petroleum ether. NMR
was recorded on Bruker 300 or 400 MHz spectrometers. Chemical
shifts are reported in ppm down field from tetramethylsilane
with the solvent resonance as the internal standard. Enantiomeric
excess was determined by GC analysis on a CP CHIPASIL-DEX
column and HPLC analysis on Chiralpak OD or AS column.
DCM was distilled from CaH2. All other reagents were used
without purification as commercially available.
Fig. 1 Structures of the various ketones.
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(R,R)–N-(4ꢀ-Nitrophenylsulfonyl)-1,2-diaminocyclohexane (2).
To a solution of (R,R)-1,2-diaminocyclohexane (0.9 g, 16.7 mmol)
and NEt3 (3 mL, 21 mmol) in DCM (40 mL) was added a solution
of 4-nitrobenzenesulfonyl chloride (3.7 g, 16.7 mmol) in DCM
(10 mL) in an ice bath. The mixture was stirred overnight at room
temperature and concentrated under reduced pressure. The residue
was acidified with dilute HCl and extracted with EtOAc–ether (1 :
20 v/v, 20 mL). Then the aqueous phase was neutralised with
ammonia. The solid was collected, washed with water, and air
dried. Yield 3.6 g (72%), mp = 177.5–178 ◦C. [a]D23 +32.1 (c = 0.49,
C2H5OH). 1H NMR (CDCl3, 300 MHz) d 1.05–2.06 (m, 8H), 2.40–
2.48 (m, 1H), 2.70–2.92 (m, 3H), 8.11 (d, J = 8.7 Hz, 2H), 8.37
(d, J = 8.7 Hz, 2H) ppm. 13C NMR (CDCl3 + DMSO, 75 MHz)
d 19.1, 19.6, 27.2, 28.4, 49.0, 54.9, 118.9, 122.9, 142.8, 144.3 ppm.
IR (KBr) m (cm−1): 3429, 3297, 1529, 1354, 1165, 1090. ESI MS
m/z: 300.1 [M + H]+ (100).
chromatography on silica gel gave the Boc-protected dendrimers
5a–5d.
(R,R)-5a. Yield 86%, mp = 185–187 ◦C. [a]D23 +30.6 (c = 0.35,
THF). 1H NMR (CDCl3, 300 MHz) d 1.08–2.05 (m, 8H), 1.46 (s,
9H), 2.82–2.86 (m, 1H), 3.30–3.33 (m, 1H), 4.45–4.47 (m, 1H),
5.10 (s, 4H), 5.72 (s, 1H), 6.81 (s, 1H), 7.10 (s, 2H), 7.34–7.43
(m, 10H), 7.76 (d, J = 7.8 Hz, 2H), 7.83 (d, J = 7.8 Hz, 2H),
8.04 (s, 1H) ppm. 13C NMR (DMSO + CDCl3, 75 MHz) d 23.5,
24.6, 28.5, 32.3, 32.9, 53.6, 57.0, 70.0, 105.2, 107.2, 120.0, 127.4,
127.8, 128.1, 128.4, 128.6, 136.7, 142.7, 156.2, 159.7, 165.7 ppm.
IR (KBr) m (cm−1): 3409, 3361, 1680, 1592, 1524, 1318, 1159. ESI
HRMS calcd. for C38H43N3O7S + Na 708.2720, found 708.2697.
◦
(R,R)-5b. Yield 88%, mp 173–174 C. [a]2D3 +17.6 (c = 0.49,
THF). 1H NMR (CDCl3, 300 MHz) d 1.08–2.00 (m, 8H), 1.46 (s,
9H), 2.75–2.87 (m, 1H), 3.20–3.35 (m, 1H), 5.04, 5.10 (s × 2, 12H),
6.59–6.69 (m, 7H), 7.06 (s, 2H), 7.30–7.43 (m, 20H), 7.75–7.95 (m,
4H) ppm. Partial 13C NMR (CDCl3, 75 MHz) d 24.9, 25.0, 28.3,
38.0, 39.5, 54.8, 59.5, 66.0, 70.1, 80.2, 101.5, 106.3, 106.4, 119.9,
127.5, 128.0, 128.5, 136.4, 136.6, 138.7, 160.0, 160.1, 165.7 ppm.
IR (KBr) m (cm−1): 3409, 3362, 1683, 1593, 1320, 1159, 1049. ESI
MS m/z: 1131.8 [M + Na]+. Calcd. for C66H67N3O11S C 71.39, H
6.08, N 3.78, S 2.89, found C 71.02, H 6.13, N 3.68, S 2.89%.
(R,R)–N -Boc-Nꢀ -(4ꢀ -nitrophenylsulfonyl)-1,2-diaminocyclo-
hexane (3). Compound 2 (2.0 g, 6.7 mmol), (Boc)2O (1.7 g,
7.8 mmol) and DIPEA (1.5 mL, 8.6 mmol) were stirred in
DCM (30 mL) at room temperature for 20 hours. The solution
was washed successively with 0.5 mol L−1 citric acid, water,
saturated sodium bicarbonate and brine, and dried over Na2SO4.
Concentrating the solvent gave 3 as a pale yellow solid. Yield 2.6 g
◦
(R,R)-5c. Yield 74%, mp 131–133 C. [a]2D3 +15.8 (c = 0.35,
◦
1
(99%), mp = 159–162 C. [a]2D3 +42.1 (c = 0.42, C2H5OH). H
NMR (CDCl3, 300 MHz) d 1.12–2.03 (m, 8 H), 1.45 (s, 9H), 2.93–
2.96 (m, 1H), 3.34–3.37 (m, 1H), 4.40 (d, J = 7.5 Hz, 1H), 6.23 (d,
J = 5.4 Hz, 1H), 8.06 (d, J = 7.8 Hz, 2H), 8.34 (d, J = 8.1 Hz, 2H)
ppm. 13C NMR (CDCl3, 75 MHz) d 24.3, 24.5, 28.2, 32.5, 33.6,
53.4, 59.8, 80.2, 124.1, 128.0, 147.4, 149.6, 157.0 ppm. IR (KBr) m
(cm−1): 3386, 3349, 1678. ESI MS m/z: 438.1 [M + K]+, 422.1 [M +
Na]+. Calcd. for C17H25N3O6S: C 51.10, H 6.31, N 10.52, S 8.03,
found C 51.30, H 6.36, N 10.57, S 7.79%.
THF). 1H NMR (CDCl3, 300 MHz) d 0.86–2.01 (m, 8H), 1.46 (s,
9H), 2.84–2.86 (m, 1H), 3.30–3.33 (m, 1H), 4.90–5.01 (m, 28H),
6.57–6.68 (m, 19H), 7.02 (s, 2H), 7.28–7.41 (m, 40H), 7.65–7.80
(m, 4H) ppm. Partial 13C NMR (CDCl3, 75 MHz) d 26.4, 26.9,
28.3, 34.9, 35.4, 53.8, 59.8, 69.9, 70.0, 80.3, 101.5, 101.6, 106.4,
119.7, 127.5, 127.9, 128.1, 128.2, 128.3, 128.5, 136.4, 136.7, 138.7,
139.1, 160.0, 160.1, 165.5 ppm. IR (KBr) m (cm−1): 3509, 3407,
3316, 1680, 1595, 1158, 1051. Calcd. for C122H115N3O19S C 74.79,
H 5.92, N 2.14, S 1.64, found C 74.76, H 5.94, N 2.09, S 1.26%.
(R,R)–N -Boc-Nꢀ -(4ꢀ -aminophenylsulfonyl)-1,2-diaminocyclo-
hexane (4). Compound 3 (2.5 g, 6.3 mmol), ammonium formate
(2 g, 32 mmol) and 10% Pd/C (400 mg) were stirred in methanol
(50 mL) for 20 min. The mixture was filtered through Celite. The
filtrate was concentrated and water (20 mL) was added, and then
the resultant precipitate was filtered, washed with water, and air
dried to give 4 as a white solid. Yield 2.3 g (95%), mp 176–177 ◦C.
(R,R)-5d. Yield 55%, mp 93–98 ◦C. [a]D23 +4.6 (c = 0.37, THF).
1H NMR (CDCl3, 300 MHz) d 0.89–1.95 (m, 8H), 1.46 (s, 9H),
2.82–2.86 (m, 1H), 3.31–3.32 (m, 1H), 4.75–4.98 (m, 60H), 6.55–
6.83 (m, 45H), 7.14–7.37 (m, 80H), 7.72–7.78 (m, 4H) ppm. IR
(KBr) m (cm−1): 3527, 3500, 3415, 3031, 1685, 1595, 1449, 1156,
1050. Calcd. for C242H211N3O35S C 76.85, H 5.82, N 1.15, S 0.88,
found C 76.56, H 5.77, N 1.14, S 0.54%.
1
[a]2D3 +69.6 (c = 0.39, C2H5OH). H NMR (CDCl3, 300 MHz) d
1.10–2.05 (m, 8 H), 1.46 (s, 9 H, CH3), 2.79–2.82 (m, 1H), 3.27–
3.31 (m, 1H, NCH), 3.94 (br s, 2H), 4.53 (d, J = 7.8 Hz, 1H), 5.43
(d, J = 5.7 Hz, 1H), 6.70 (d, J = 8.7 Hz, 2H), 7.63 (d, J = 8.1 Hz,
2H) ppm. 13C NMR (DMSO + CDCl3, 75 MHz) d 24.4, 24.6, 28.4,
32.4, 33.0, 53.9, 57.4, 78.7, 113.4, 127.6, 128.6, 151.7, 156.6 ppm.
IR (KBr) m (cm−1): 3477, 3381, 3295, 1689. ESI MS m/z: 392.2 [M +
Na]+. Calcd. for C17H27N3O4S: C 55.26, H 7.37, N 11.73, S 8.68,
found C 55.35, H 7.37, N 11.56, S 8.48%.
General procedure for deprotection of Boc-group
Boc-protected dendrimer 5a–5d (0.42 mmol) was dissolved in
DCM (1 mL) and cooled in ice water. TFA (2 mL) was added and
the solution was stirred for 1 h (HCl–EtOAc solution was used to
deprotect Boc-group of dendrimer 5d). The solvent was removed
under vacuum. The mixture was neutralised with ammonia and
then extracted with EtOAc (20 mL). The organic layer was washed
with water, dried and concentrated to give the desired product 1a–
1d as a white solid.
General procedure for condensation of Freche´t-type acid with
(R,R)-4
◦
(R,R)-1a. Yield 92%, mp 212–214 C. [a]2D3 −8.0 (c = 0.34,
1
(R,R)-4 (150 mg, 0.41 mmol), dendritic acid (1.05 equiv.) and
triphenyl phosphate (370 mg, 1.1 mmol) were stirred in pyridine
(2 mL) at 95 ◦C for 24 h. The solution was poured into water
(30 mL) and extracted with EtOAc (40 mL). The organic layer
was washed successively with 0.5 mol L−1 citric acid, water, satu-
rated sodium bicarbonate and brine, and dried (Na2SO4). Flash
THF). H NMR (DMSO, 300 MHz) d 1.05–1.80 (m, 8H), 2.58–
2.75 (m, 2H), 5.18 (s, 4H), 6.94 (s, 1H), 7.22 (d, J = 2.1 Hz, 2H),
7.35–7.49 (m, 10H), 7.80 (d, J = 8.7 Hz, 2H), 7.97 (d, J = 8.7 Hz,
2H) ppm. 13C NMR (DMSO, 75 MHz) d 29.2, 29.6, 37.0, 38.3,
59.0, 64.6, 74.8, 110.3, 112.1, 125.2, 132.5, 132.6, 132.9, 133.1,
133.6, 141.6, 141.8, 147.6, 164.6, 170.5 ppm. IR (KBr) m (cm−1):
3322 | Org. Biomol. Chem., 2006, 4, 3319–3324
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3432, 3303, 1655, 1591, 1522, 1322, 1159, 1059. ESI HRMS calcd.
for C33H35N3O5S + H 586.2375, found 586.2351.
2 For reviews, see: (a) D. Sinou, Adv. Synth. Catal., 2002, 344, 221; (b)
C.-J. Li, Acc. Chem. Rev., 2002, 35, 533; (c) K. H. Shaughnessy and
R. B. DeVasher, Curr. Org. Chem., 2005, 9, 585; (d) N. E. Leadbeater,
Chem. Commun., 2005, 2881.
1
(R,R)-1b. Yield 91%. [a]2D3 +11.3 (c = 0.24, THF). H NMR
3 For reviews, see: (a) J. P. Geneˆt and M. Savignac, J. Organomet. Chem.,
(CDCl3, 300 MHz) d 0.87–2.14 (m, 8H), 2.75–2.87 (m, 1H),
3.20–3.35 (m, 1H), 4.89, 5.05 (s × 2, 12H), 6.49–6.74 (m, 9H),
7.28–7.45 (m, 20H), 7.89–8.04 (m, 4H) ppm. Partial 13C NMR
(CDCl3 + DMSO, 75 MHz) d 29.2, 29.7, 31.5, 36.8, 37.8, 59.1,
63.8, 74.6, 106.2, 110.2, 111.2, 111.8, 112.0, 125.0, 132.3, 132.7,
133.3, 140.9, 141.5, 143.8, 147.7, 164.4, 164.8, 170.8 ppm. IR (KBr)
m (cm−1): 3437, 1658, 1594, 1321, 1157, 1054. ESI HRMS calcd.
for C61H59N3O9S + H 1010.4050, found 1010.4095.
´
1999, 576, 305; (b) F. Joo´ and A Katho´, J. Mol. Catal. A: Chem., 1997,
116, 3; For recent examples, see: (c) S. H. Hong and R. H. Grubbs,
J. Am. Chem. Soc., 2006, 128, 3508 (d) J. P. Gallivan, J. P. Jordan and
R. H. Grubbs, Tetrahedron Lett., 2005, 46, 2577 (e) L. R. Moore and
K. H. Shaughnessy, Org. Lett., 2004, 6, 225.
4 For pioneering works of Noyori and Ikariya on this catalytic system,
see: (a) S. Hashiguchi, A. Fujii, J. Takehara, T. Ikariya and R. Noyori,
J. Am. Chem. Soc., 1995, 117, 7562; (b) A. Fujii, S. Inoue, S. Hishiguchi,
N. Uemastu, T. Ikariya and R. Noyori, J. Am. Chem. Soc., 1996, 118,
2521; (c) N. Uematsu, A. Fujii, S. Hashiguchi, T. Ikariya and R. Noyori,
J. Am. Chem. Soc., 1996, 118, 4916; (d) K. Matsumura, S. Hashiguchi,
T. Ikariya and R. Noyori, J. Am. Chem. Soc., 1997, 119, 8738; (e) S.
Hashiguchi, A. Fujii, K. J. Haack, K. Matsumura, T. Ikariya and R.
Noyori, Angew. Chem., Int. Ed. Engl., 1997, 36, 288; (f) K. J. Haack,
S. Hashiguchi, A. Fujii, T. Ikariya and R. Noyori, Angew. Chem., Int.
Ed. Engl., 1997, 36, 285; (g) R. Noyori and S. Hashiguchi, Acc. Chem.
Res., 1997, 30, 97.
5 For recent developments, see: (a) D. S. Matharu, D. J. Morris, A. M.
Kawamoto, G. J. Clarkson and M. Wills, Org. Lett., 2005, 7, 5489;
(b) F. K. Cheung, A. M. Hayes, J. Hannedouche, A. S. Y. Yim and M.
Wills, J. Org. Chem., 2005, 70, 3188; (c) A. M. Hayes, D. J. Morris, G. J.
Clarkson and M. Wills, J. Am. Chem. Soc., 2005, 127, 7318; (d) R. W.
Guo, C. Elpelt, X. H. Chen, D. T. Song and R. H. Morris, Chem.
Commun., 2005, 3050; (e) W. Baratta, E. Herdtweck, K. Siega, M.
Toniutti and P. Rigo, Organometallics, 2005, 24, 1660; (f) J. B. Sortais,
V. Ritleng, A. Voelklin, A. Houluigue, H. Smail, L. Barloy, C. Sirlin,
G. K. M. Verzijl, J. A. F. Boogers, A. H. M. De Vries, J. G. De Vries and
M. Pfeffer, Org. Lett., 2005, 7, 1247; (g) J. Hannedouche, G. J. Clarkson
and M. Wills, J. Am. Chem. Soc., 2004, 126, 986; (h) A. Schlatter, M.
Kundu and W. D. Woggon, Angew. Chem., Int. Ed., 2004, 43, 6731;
(i) For a recent review, see: S. Gladiali and E. Alberico, Chem. Soc.
Rev., 2006, 35, 226.
1
(R,R)-1c. Yield 90%. [a]2D3 +3.4 (c = 0.30, THF). H NMR
(CDCl3, 300 MHz) d 0.89–1.72 (m, 8H), 2.94–2.99 (m, 1H), 3.32–
3.42 (m, 1H), 4.79–5.03 (m, 28H), 6.48–6.67 (m, 21H), 7.13–
7.38 (m, 40H), 7.75–7.90 (m, 4H) ppm. IR (KBr) m (cm−1):
3433, 3031, 1599, 1450, 1321, 1157, 1053. ESI HRMS calcd. for
C117H107N3O17S + H 1858.7395, found 1858.7390.
1
(R,R)-1d. Yield 85%. [a]2D3 +1.3 (c = 0.31, THF). H NMR
(CDCl3, 300 MHz) d 4.79–5.0 (m, 60H), 6.48–6.67 (m, 45H), 7.25–
7.38 (m, 84H) ppm. The signal of the DACH moiety is too small
to be detected. IR (KBr) m (cm−1): 3411, 3032, 1595, 1449, 1374,
1157, 1052. MALDI-TOF MS calcd. for C229H203N3O33S + K 3593,
found 3593.
General procedure for asymmetric transfer hydrogenation of
ketone compounds
[Cp*RhCl2]2 (1.3 mg, 0.002 mmol), dendritic ligand
1
6 (a) X. F. Wu, X. G. Li, W. Hems, F. King and J. L. Xiao, Org. Biomol.
Chem., 2004, 2, 1818; (b) X. G. Li, X. F. Wu, W. P. Chen, F. E. Hancock,
F. King and J. L. Xiao, Org. Lett., 2004, 6, 3321; (c) X. F. Wu, X. G.
Li, F. King and J. L. Xiao, Angew. Chem., Int. Ed., 2005, 44, 3407;
(d) X. Wu, D. Vinci, T. Ikariya and J. Xiao, Chem. Commun., 2005,
4447; (e) C. Letondor, N. Humbert and T. R. Ward, Proc. Natl. Acad.
Sci. U. S. A., 2005, 102, 4683; (f) P. N. Liu, J. G. Deng, Y. Q. Tu and
S. H. Wang, Chem. Commun., 2004, 2070; (g) Y. P. Ma, H. Liu, L.
Chen, X. Cui, J. Zhu and J. G. Deng, Org. Lett., 2003, 5, 2103; (h) F.
Wang, H. Liu, L. Cun, J. Zhu, J. Deng and Y. Jiang, J. Org. Chem.,
2005, 70, 9424; (i) Y. Himeda, N. Onozawa-Komatsuzaki, H. Sugihara,
H. Arakawa and K. Kasuga, J. Mol. Catal. A: Chem., 2003, 195, 95;
(j) H. Y. Rhyoo, H. J. Park, W. H. Suh and Y. K. Chung, Tetrahedron
Lett., 2002, 43, 269; (k) T. Thorpe, J. Blacker, S. M. Brown, C. Bubert, J.
Crosby, S. Fitzjohn, J. P. Muxworthy and J. M. J. Williams, Tetrahedron
Lett., 2001, 42, 4037; (l) J. Canivet, G. Labat, H. Stoeckli-Evans and
G. Su¨ss-Fink, Eur. J. Inorg. Chem., 2005, 4493.
(0.0044 mmol) and NEt3 (2 lL, 0.013 mmol) were stirred in
DCM at 40 ◦C for 1 h. After removal of DCM under reduced
pressure, ketone 7 (0.4 mmol), HCOONa (250 mg, 6 equiv.) and
water (1 mL) were added. After the reaction was completed
(monitored by TLC), the reaction mixture was extracted with
ether. The organic phase was dried over anhydrous Na2SO4 and
concentrated under reduced pressure. The product was directly
used for GC analysis. Products from 7h, 7j and 7k were purified
by flash chromatography on silica gel and the ees were determined
by HPLC analysis on OD or AS column.
General procedure for recycling of dendritic catalyst in asymmetric
transfer hydrogenation of acetophenone
7 J. Wu, F. Wang, Y. Ma, X. Cui, L. Cun, J. Zhu, J. Deng and B. Yu,
Chem. Commun., 2006, 1766.
[Cp*RhCl2]2 (6.5 mg, 0.01 mmol), dendritic ligand 1b
(0.022 mmol) and NEt3 (10 lL, 0.065 mmol) were stirred in DCM
at 40 ◦C for 1 h. After removal of DCM under reduced pressure,
acetophenone (0.24 mL, 2 mmol), HCOONa (1.25 g, 12 mmol)
and water (5 mL) were added. After a specific reaction time, n-
hexane (5 mL) was added to precipitate the dendritic catalyst,
and the organic phase containing the chiral alcohol was carefully
removed. Before the next reaction could be conducted, HCOOH
(80 lL, 2 mmol) was added to adjust the pH value of aqueous
solution to about 7. Then acetophenone (2 mmol) were added and
the mixture was stirred at 40 ◦C.
8 Ru–TsDACH catalysed ATH: (a) K. Puntener, L. Schwink and P.
Knochel, Tetrahedron Lett., 1996, 37, 8165; (b) H. Matsunaga, T.
Ishizuka and T. Kunieda, Tetrahedron Lett., 2005, 46, 3645; (c) G. J.
Kim, S. H. Kim, P. H. Chong and M. A. Kwon, Tetrahedron Lett.,
2002, 43, 8059; (d) C. M. Marson and I. Schwarz, Tetrahedron Lett.,
2000, 41, 8999; (e) Rh/Ir–TsDACH catalysed ATH: K. Murata, T.
Ikariya and R. Noyori, J. Org. Chem., 1999, 64, 2186; (f) ref. 6d
and 6l.
9 (a) Y.-C. Chen, T.-F. Wu, J.-G. Deng, H. Liu, Y.-Z. Jiang, M. C. K.
Choi and A. S. C. Chan, Chem. Commun., 2001, 1488; (b) Y.-C. Chen,
T.-F. Wu, J.-G. Deng, H. Liu, X. Cui, J. Zhu, Y.-Z. Jiang, M. C. K.
Choi and A. S. C. Chan, J. Org.Chem., 2002, 67, 5301; (c) Y.-C. Chen,
T.-F. Wu, L. Jiang, J.-G. Deng, H. Liu, J. Zhu and Y.-Z. Jiang, J. Org.
Chem., 2005, 70, 1006; (d) W. Liu, X. Cui, L. Cun, J. Zhu and J. Deng,
Tetrahedron: Asymmetry, 2005, 16, 2525.
10 For recent reviews on dendritic catalysts, see: (a) J. N. H. Reek, D. de
Groot, G. E. Oosterom, P. C. J. Kamer and P. W. N. M. van Leeuwen,
Rev. Mol. Biotechnol., 2002, 90, 159; (b) L. J. Twyman, A. S. H. King
and I. K. Martin, Chem. Soc. Rev., 2002, 31, 69; (c) Q.-H. Fan, Y.-M. Li
References
1 For a recent review, see: C.-J. Li and L. Chen, Chem. Soc. Rev., 2006,
35, 68.
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and A. S. C. Chan, Chem. Rev., 2002, 102, 3385; (d) A.-M. Caminade,
V. Maraval, R. Laurent and J.-P. Majoral, Curr. Org. Chem., 2002, 6,
739.
12 1–Rh or 6–Rh complex exhibited poor catalytic activity in the transfer
hydrogenation of acetophenone 7a in HCOOH–NEt3 system. 1c–Ru
complex showed good catalytic activity under conditions A, but the
recyclability was poor (1st use, 30 h, 99% conv., 93% ee; 2nd use, 30 h,
46% conv., 92% ee; 3rd use, 60 h, 7% conv., 65% ee).
11 For a similar structural effects on catalytic properties, see: B. Yi, Q.-H.
Fan, G.-J. Deng, Y.-M. Li, L.-Q. Qiu and A. S. C. Chan, Org. Lett.,
2004, 6, 1361.
13 K. Okano, K. Murata and T. Ikariya, Tetrahedron Lett., 2000, 41, 9277.
3324 | Org. Biomol. Chem., 2006, 4, 3319–3324
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