Synthesis of dendritic catalysts and application in asymmetric transfer hydrogenation

Article abstract of DOI:10.1021/jo048317v

(Chemical Equation Presented) Frechet-type core-functionalized chiral diamine-based dendritic ligands and hybrid dendritic ligands condensed from polyether wedge and Newkome-type poly(ether-amide) supported multiple ligands were designed and synthesized.

Full text of DOI:10.1021/jo048317v

Synthesis of Dendritic Catalysts and Application in Asymmetric
Transfer Hydrogenation
Ying-Chun Chen,*,† Tong-Fei Wu,‡ Lin Jiang,† Jin-Gen Deng,*,‡ Hui Liu,‡ Jin Zhu,‡ and
Yao-Zhong Jiang‡
Key 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, and West China School of Pharmacy, Sichuan University,
Chengdu 610041, China
jgdeng@cioc.ac.cn
Received September 22, 2004
Fre´chet-type core-functionalized chiral diamine-based dendritic ligands and hybrid dendritic ligands
condensed from polyether wedge and Newkome-type poly(ether-amide) supported multiple ligands
were designed and synthesized. The solubility of hybrid dendrimers was found to be finely controlled
by the polyether dendron. The catalytic efficiency and recovery use of dendritic ruthenium complexes
were compared in the transfer hydrogenation of acetophenone. The core-functionalized dendritic
catalysts demonstrated much better recyclability, which verified the stabilizing effects of the bulky
polyether wedge on the catalytically active complex. Moreover, the dendritic catalysts were applied
in the asymmetric transfer hydrogenation of ketones, enones, imine, and activated olefin, and
moderate to excellent enantioselectivitiy was achieved comparable to that of monomeric catalysts.
Introduction
unhindered active sites and may be analyzed with routine
spectroscopic techniques.3 Moreover, the globular shapes
of higher generation dendritic catalysts are suitable for
membrane filtration4 or selective precipitation under
specific conditions.5 The catalytic efficiency and recycl-
ability of the dendritic system largely depend on the
dendritic architecture that is used, and in general two
Homogeneous asymmetric catalysis is one of the most
important developments in chemistry. However, only a
few examples have been applied in industrial processes
due to the problems of separation and recycling of the
expensive and sometimes toxic catalysts.1 Recently sig-
nificant advances in the development of supported ho-
mogeneous asymmetric catalysts have been achieved for
the requirement of green chemistry. Some systems
depending on the use of insoluble resin beads allow the
facile recovery by filtration, but many of the potential
active catalyst sites may be inaccessible if the resin is
not compatible with the required solvent, and it may also
be difficult to accurately assess the level of catalyst
loading on resin beads.2
(3) For recent reviews on dendritic catalysts, see: (a) Oosterom, G.
E.; Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Angew.
Chem., Int. Ed. 2001, 40, 1828. (b) Astruc, D.; Chardac, F. Chem. Rev.
2001, 101, 2991. (c) Crooks, R. M.; Zhao, M.; Sun, L.; Chechik, V.;
Yueng, L. K. Acc. Chem. Res. 2001, 34, 181. (d) Reek, J. N. H.; de Groot,
D.; Oosterom, G. E.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Rev.
Mol. Biotechnol. 2002, 90, 159. (e) Twyman, L. J.; King, A. S. H.;
Martin, I. K. Chem. Soc. Rev. 2002, 31, 69. (f) van Heerbeek, R.; Kamer,
P. C. J.; van Leeuwen, P. W. N. M.; Reek, J. N. H. Chem. Rev. 2002,
102, 3717. (g) Fan, Q.-H.; Li, Y.-M.; Chan, A. S. C. Chem. Rev. 2002,
102, 3385. (h) Caminade, A.-M.; Maraval, V.; Laurent, R.; Majoral, J.-
P. Curr. Org. Chem. 2002, 6, 739.
Dendrimers are well-defined macromolecules with
controllable structures. Their applications in catalysis
have triggered increasing attention since the dendritic
catalysts have the advantages of total solubility and
(4) For an excellent review on the nanofiltration technique in
dendritic catalyst recycling, see: Dijkstra, H. P.; van Klink, G. P. M.;
van Koten, G. Acc. Chem. Res. 2002, 35, 798.
(5) For selected reports on dendritic catalyst recycling by precipita-
tion, see: (a) Reetz, M. T.; Lohmer, G.; Schwickardi, R. Angew. Chem.,
Int. Ed. 1997, 36, 1526. (b) Petrucci-Samija, M.; Guillemette, V.;
Dasgupta, M.; Kakkar, A. K. J. Am. Chem. Soc. 1999, 121, 1968. (c)
Hu, Q.-S.; Pugh, V.; Sabat, M.; Pu, L. J. Org. Chem. 1999, 64, 7528.
(d) Fan, Q.-H.; Chen, Y.-M.; Chen, X.-M.; Jiang, D.-Z.; Xi, F.; Chan, A.
S. C. Chem. Commun. 2000, 789. (e) Maraval, V.; Caminade, A.-M.;
Majoral, J.-P. Organometallics 2000, 19, 4025.
† Sichuan University.
‡ Chinese Academy of Sciences.
(1) Kragl, U.; Dwars, T. Trends Biotechnol. 2001, 19, 442.
(2) For reviews on recoverable catalysts, see the following special
issue: Chem. Rev. 2002, 102 (10).
10.1021/jo048317v CCC: $30.25 © 2005 American Chemical Society
Published on Web 01/13/2005
1006
J. Org. Chem. 2005, 70, 1006-1010

Synthesis of Dendritic Catalysts
SCHEME 1. Synthesis of Core-Functionlized
Dendritic Ligandsa
a Reagents: (i) (PhO)3P, Py; (ii) TFA/DCM or HCl/EtOAc.
dendritic catalysts (Figure 1, type d) through the coupling
of higher generation Fre´chet’s polyether dendrons8 with
Newkome-type poly(ether amide) supported multiple
ligands.7b Thus the hybrid dendrimer9 not only will be of
the physical character of the Fre´chet’s polyether den-
drons and reactivity of the periphery dendritic catalysts,
but also can be easily synthesized and recovered through
solvent precipitation. Moreover, the efficiency of polyether
dendritic wedges can be improved.
FIGURE 1. Different dendritic catalysts.
basic strategies evolved: one (or more) catalyst(s) in the
core of dendrimer (Figure 1, type a), the other multiple
active sites at the periphery of the dendrimer (type b).
Recently, insoluble polymer supported periphery-func-
tionalized dendritic catalysts were also developed (type
c).6
Results and Discussion
Recently we reported the synthesis of core-function-
alized dendritic ligands based on Noyori-Ikariya’s TsD-
PEN ligand and the application of their Ru(II) com-
plexes in the asymmetric transfer hydrogenation of
acetophenone.7a High catalytic activity and completely
maintained enantioselectivity were observed, and the
higher generation catalysts could be recovered through
solvent precipitation and reused several times without
apparent loss of activity. Nevertheless, it still has the
traditional disadvantages of core-functionalized dendritic
catalysts: the efficiency of the dendritic wedge is very
low. We also reported the synthesis of other types of
dendrimers with up to 12 chiral diamine based ligands
at the periphery of Newkome-type poly(ether amide).7b
Their Ru(II) complexes demonstrated high catalytic
activity and enantioselectivity in the asymmetric transfer
hydrogenation of ketones and imines. However, we
cannot easily realize their recycling use. To keep the
advantages and get over disadvantages of these two types
of catalysts, get to know more about the stabilizing effects
of the bulky dendrons, we first synthesized the hybrid
Ligand Synthesis. The core-functionalized dendritic
ligands were smoothly prepared by condensation of
amino-derived chiral DPEN (S,S)-1 with Fre´chet’s poly-
ether dendrons8 in pyridine, using (PhO)3P10 as the
coupling reagent, and subsequent deprotection of the Boc-
group (Scheme 1).7a The dendritic ligands were soluble
in nonpolar solvents (DCM, chloroform, toluene, THF,
etc.) but almost completely insoluble in alcoholic solvents.
Via a similar strategy, the previously reported periph-
ery-functionalized dendron (R,R)-67b was condensed with
higher generation Fre´chet’s polyether dendritic wedges,
and the following deprotection of the Boc-group readily
gave the hybrid dendritic chiral ligands (R,R)-7b and
(R,R)-8b (Scheme 2). Their physical character is the same
as that of the polyether wedges, and the dendritic ligands
are insoluble in methanol and isopropyl alcohol, but can
be easily dissolved in THF or DCM.
1
In H NMR of core dendrimers 2a-5a, the resonance
signal at δ 4.9-5.3 ppm from benzylic protons and the
signal at δ 1.3-1.5 ppm of the Boc group indicated the
coupling of dendron wedges with the ligand. However,
(6) (a) Bourque, S. C.; Maltais, F.; Xiao, W.-J.; Tardif, O.; Alper, H.;
Arya, P.; Manzer, L. E. J. Am. Chem. Soc. 1999, 121, 3035. (b) Arya,
P.; Rao, N. V.; Singkhonrat, J.; Alper, H.; Bourque, S. C.; Manzer, L.
E. J. Org. Chem. 2000, 65, 1881. (c) Bourque, S. C.; Alper, H.; Manzer,
L. E.; Arya, P. J. Am. Chem. Soc. 2000, 122, 956. (d) Arya, P.; Panda,
G.; Rao, N. V.; Alper, H.; Bourque, S. C.; Manzer, L. E. J. Am. Chem.
Soc. 2001, 123, 2889. (e) Antebi, S.; Arya, P.; Manzer, L. E.; Alper, H.
J. Org. Chem. 2002, 67, 6623. (f) Dahan, A.; Portnoy, M. Chem.
Commun. 2002, 2700. (g) Dahan, A.; Portnoy, M. Org. Lett. 2003, 5,
1197. (h) Lu, S.-M.; Alper, H. J. Am. Chem. Soc. 2003, 125, 13126.
(7) (a) Chen, Y.-C.; Wu, T.-F.; Deng, J.-G.; Liu, H.; Jiang, Y.-Z.; Choi,
M. C. K.; Chan, A. S. C. Chem. Commun. 2001, 1488. (b) Chen, Y.-C.;
Wu, T.-F.; Deng, J.-G.; Liu, H.; Cui, X.; Zhu, J.; Jiang, Y.-Z.; Choi, M.
C. K.; Chan, A. S. C. J. Org. Chem. 2002, 67, 5301.
(8) Hawker, C. J.; Fre´chet, J. M. J. J. Am. Chem. Soc. 1990, 112,
7638.
(9) For some recent examples of hybrid dendrimers, see: (a) Gray-
son, S. M.; Fre´chet, J. M. J. J. Am. Chem. Soc. 2000, 122, 10335. (b)
Nierengarten, J.-F.; Eckert, J.-F.; Rio, Y.; Carreon, M. del P.; Gallani,
J.-L.; Guillon, D. J. Am. Chem. Soc. 2001, 123, 9743. (c) Grayson, S.
M.; Fre´chet, J. M. J. Org. Lett. 2002, 4, 3171. (d) Sivanandan, K.;
Vutukuri, D.; Thayumanavan, S. Org. Lett. 2002, 4, 3751. (e) Zhang,
S.; Rio, Y.; Cardinali, F.; Bourgogne, C.; Gallani, J.-L.; Nierengarten,
J.-F. J. Org. Chem. 2003, 68, 9787. (f) Cho, B.-K.; Jain, A.; Mahajan,
S.; Ow, H.; Gruner, S. M.; Wiesner, U. J. Am. Chem. Soc. 2004, 126,
4070.
(10) Rabilloud, G.; Sillion, B. J. Heterocycl. Chem. 1980, 17, 1065.
J. Org. Chem, Vol. 70, No. 3, 2005 1007

Chen et al.
TABLE 2. Comparison of Dendritic and Monomeric
SCHEME 2. Synthesis of Hybrid Dendritic
Ligandsa
Catalysts in Asymmetric Transfer Hydrogenation of
Acetophenonea
c
entry
ligand
conv (%)b
TOF (h-1
)
ee (%)d
17b
27a
3
9
>99
>99
96
13.2
11.0
9.7
97.1
96.5e
96.2
97.1
4b
7b
8b
4
97
8.2
a Reactions were conducted in DCM solution at 28 °C for 20 h,
S/C ) 100. b Conversions were determined by GC. c The average
TOFs were calculated over the 5 h reaction time. d Determined
by GC with a Chrompack CP Chirasil-dex column (25 m × 0.25
mm). e (S)-Alcohol was obtained.
TABLE 3. Solvent Effects on Dendritic Catalysts in
Asymmetric Transfer Hydrogenation of Acetophenonea
a Reagents: (i) EDCI/HOBt, DIPEA; (ii) TFA, DCM, then NH3.
TABLE 1. MS Data of Dendrimers
dendrimer
MW (calcd)
MW (found)
2a
3a
2b
3b
4b
5b
7b
8b
806.2878
1230
806.2828a,e
c
entry
ligand
solvent
conv (%)b
TOF (h-1
)
ee (%)d
1230b,e
684.2429a,d
1108.4179a,d
1956.7929a,d
3676.03c,e
3224.7c,e
1
2
4b
4b
4b
4b
4b
4b
7b
8b
7b
8b
DCM
THF
>99
98
96
70
68
98
97
94
99
98
11.0
8.0
96.5
95.1
95.8
93.4
94.7
96.0
96.7f
96.7f
98.2f
97.8f
684.2532
1108.4207
1956.7556
3675.41
3224.2
3
Toluene
DMF
7.4
4
7.2
5
CH3CN
6.2
e
4926c,e
6
-
6.2
4921
e
7
-
6.0
a ESI HRMS. b FAB MS. c MALDI-TOF MS. d (M + H). e (M +
Na).
e
8
-
3.8
9
THF
THF
15.0
10.4
10
a Reactions were conducted at 28 °C for 20 h, S/C ) 100.
b Conversions were determined by GC. c The average TOFs were
calculated over the 5 h reaction time. d Determined by GC with a
Chrompack CP Chirasil-dex column (25 m × 0.25 mm). e In neat
HCOOH-NEt3 azeotrope for 28 h. f (R)-Alcohol was obtained.
the usually poor 13C NMR spectrum was observed due
to the dominant ratio of dendron wedges in the core
dendrimers, especially for higher generation ones. For
the hybrid dendrimers 7 and 8, the structures were
similarly resolved and better 13C NMR was obtained.
Indeed, the confirmation of the dendritic structures
could be more smoothly obtained through MS techniques
(ESI, FAB, or MALDI-TOF MS). All of the MS spectra
displayed a very prominent peak corresponding to the
dendrimers complexed with proton or sodium cation
except for the Boc-protected higher generation den-
drimers 4a, 5a, 7a, and 8a, whose elemental analyses
were well obtained. MALDI-TOF MS was applied for the
analysis of 5b and hybrid dendritic ligands 7b and 8b
(Table 1).
Asymmetric Transfer Hydrogenation Reaction.
Having the core and hybrid dendritic ligands in hand,
the catalytic activity and enantioselectivity of their Ru-
(II) complexes were studied via the transfer hydrogena-
tion of acetophenone, and also compared with the
monomeric Ru(II) complex of (R,R)-N-(4-acetylaminophe-
nylsulfonyl)-1,2-diphenylethylenediamine (9).7b Initial
experiments were conducted in homogeneous DCM solu-
tion with formic acid-triethylamine azeotrope as the
hydrogen source. The average turnover frequency (TOFs,
in relation to the per-Ru(II) complex) and enantioselect-
ivity are summarized in Table 2.
retention of high enantioselectivity was observed in all
dendritic catalysts (only 4b was selected as an example
for core dendritic ligands).7a
On the other hand, the solubility of crowded dendritic
catalysts in solvents may affect the conformation of
dendrimers in solution,11 so the accessibility of substrate
to the active site may also be different. We investigated
the transfer hydrogenation of core dendritic ligand 4b
and hybrid ligands 7b and 8b in various solvents. The
results were summarized in Table 3. For core dendritic
catalyst 4b-Ru(II), DCM demonstrated the best solvent
effect, and comparable results could be obtained when
THF was used (Table 3, entry 2). However, poor conver-
sion was observed in polar DMF or acetonitrile solution
although the enantioselectivity was still high (entries 4
and 5). Interestingly, it was found that the highly
hydrophobic catalyst 4b-Ru(II) could be well dissolved
in neat HCOOH-NEt3 azeotrope. Good conversion and
enantioselectivity were obtained in the transfer hydro-
genation of acetophenone, while its TOF value was less
than what was obtained in nonpolar solvent (entry 6).
Hybrid dendrimers showed similar catalytic activity
It was found that the macromolecular catalysts showed
only a slight difference as compared to monomeric
catalyst 9-Ru(II) in regard to catalytic activity, and good
(11) De Backer, S.; Prinzie, Y.; Verheijen, W.; Smet, M.; Desmedt,
K.; Dehaen, W.; De Schryver, F. C. J. Phys. Chem. A 1998, 102, 5451.
1008 J. Org. Chem., Vol. 70, No. 3, 2005

Synthesis of Dendritic Catalysts
TABLE 4. Recycling Use of Dendritic Catalysts in
Asymmetric Transfer Hydrogenation of Acetophenonea
TABLE 5. Asymmetric Transfer Hydrogenation of
Unsaturated Compoundsa
entry
ligand
t (h)
conv (%)b
ee (%)c
17a
27a
37a
47a
57a
67a
7
5b (first)
20
20
25
30
40
40
20
24
25
20
24
98
92
87
85
73
52
96
70
31
97
72
96.5
96.6
96.8
96.7
96.3
87.0
96.2d
97.6d
97.4d
97.1d
97.2d
5b (second)
5b (third)
5b (fourth)
5b (fifth)
5b (sixth)
7b (first)
entry
substrate
ligand
t (h)
yieldb (%)
eec (%)
8
7b (second)
7b (third)
8b (first)
9
10
11
1
2
10a
10a
10a
10b
10b
10b
10c
10d
10d
10e
10e
10f
10f
11
4b
7b
8b
2b
4b
7b
7b
13
4b
13
4b
13
4b
4b
13
4b
24
24
24
24
24
24
24
28
28
45
45
72
72
10
2
90
85
83
85
80
86
75
87
85
86
91
61
54
90
94
98
90.1
91.4d
92.7d
95.1
8b (second)
3
4
a Reactions were conducted at 28 °C in DCM solution, S/C )
100. b Conversions were determined by GC. c Determined by GC
with a Chrompack CP Chirasil-dex column (25 m × 0.25 mm).
d (R)-Alcohol was obtained.
5
94.1
6
92.8d
93.9e
39.0e
37.3e
76.4e
74.9e
68.9e
67.5e
95.5e
60.6e
55.7e
7
8
9
10
11
12
13
14
15f
16f
under the same conditions (entries 7 and 8). However,
the best results (especially in regard to the TOF value)
were gained when THF was used as solvent, which
indicated the importance of the solubility of the dendrim-
ers in the solution for high catalytic efficiency (Table 2,
entries 9 and 10 vs entries 7 and 8).
12
12
5
a Reactions were conducted at 28 °C in DCM solution, S/C )
100. b Isolated yield. c Determined by GC with a Chrompack CP
Chirasil-dex column (25 m × 0.25 mm). d (R)-Alcohol was obtained.
e Determined by HPLC on a chiral column. f Reaction was carried
out in 0.5 M THF solutions at 30 °C.
A significant advantage of dendritic catalysts is that
they can be easily separated from substrates and prod-
ucts through membrane filtration or precipitation owing
to the globular macromolecular structures. Therefore the
recyclability of these large dendritic catalysts was tested
by the precipitation method. After a specific reaction
time, DCM was removed under reduced pressure and dry
methanol was added to precipitate the dendritic catalyst.
Then the solution was removed and the next reaction
could be conducted. Table 4 shows the results with 5b-
Ru(II), 7b-Ru(II), and 8b-Ru(II) as the catalysts, respec-
tively. It was noted that the higher generation core
dendritic catalyst 5b-Ru(II) completely maintained the
enantioselectivity in successive use. 1-Phenethanol was
provided after 30 h for the fourth use with 85% conver-
sion and 96.7% ee (entry 4), and high enantioseletivity
(96.3%ee) remained even for the fifth use (entry 5).7a
However, further addition of [RuCl2(cymene)]2 into 5b-
Ru(II) catalysis could not regain the reactivity and even
poorer selectivity was observed (entry 6). Nevertheless,
for hybrid dendrimers 7b and 8b, whose active sites are
far from the bulky polyether dendrons, much poorer
recycling results were obtained, and the activity has been
mostly lost after three uses though without a decrease
in enantioselectivity (entries 7-11). It was noteworthy
that a similar observation had been reported for the
heterogeneous polymer immobilized TsDPEN catalysts.12,13
Therefore, the “dendritic effect” from large polyether
dendron was quite important to stabilize the catalytically
active complex. Such site-isolation effect had also been
observed in bis(µ-oxo)dicopper species toward oxidative
self-decomposition.14
For exploring the scope and limitations of the reaction
catalyzed by dendritic catalysts, various prochiral ketones
10a-f, imine 11, and activated olefin 12 were applied in
the asymmetric transfer hydrogenation reaction with
HCOOH-NEt3 as the hydrogen source (Table 5). In
general, excellent enantioselectivity (>90% ee) was
achieved for aromatic ketones with good isolated yields
for both types of dendritic catalysts (entries 1-7). R,â-
Unsaturated ketones 10d-f were selectively reduced to
allylic alcohol with low to moderate enantioselectivity.15
A methyl substituent in the R-position could increase the
enantioselectivity dramatically, but slightly lower en-
antioselectivitiy was obtained when bulky dendritic
ligand 4b was used compared with (S,S)-TsDPEN 13
(entries 8-13). Imine 11 was transfer hydrogenated to
useful Sultam with excellent enantiomeric purity and
yield by using 4b as the ligand (entry 14).16 In addition,
the prochiral R,R-dicyanoolefin 12 could be reduced with
almost quantitative yield, but the bulky dendron exhibits
no beneficial effect on the enantioselectivity (entries 15
vs 16).17
(12) (a) ter Halle, R.; Schulz, E.; Lemaire, M. Synlett 1997, 1257.
(b) Bayston, D. J.; Travers, C. B.; Polywka, M. E. C. Tetrahedron:
Asymmetry 1998, 9, 2015.
(13) For recent reports on recyclable TsDPEN-Ru(II) catalysts,
see: (a) Liu, P. N.; Gu, P. M.; Wang, F.; Tu, Y. Q. Org. Lett. 2004, 6,
169. (b) Liu, P. N.; Deng, J. G.; Tu, Y. Q.; Wang, S. H. Chem. Commun.
2004, 2070. (c) Li, X.; Chen, W.; Hems, W.; King, F.; Xiao, J.
Tetrahedron Lett. 2004, 45, 951. (d) Li, X.; Wu, X.; Chen, W.; Hancock,
F. E.; King, F.; Xiao, J. Org. Lett. 2004, 6, 3321.
(14) Enomoto, M.; Aida, T. J. Am. Chem. Soc. 1999, 121, 874.
(15) Hashiguchi, S.; Fujii, A.; Haack, K.-J.; Matsumura, K.; Ikariya,
T.; Noyori, R. Angew. Chem., Int. Ed. 1997, 36, 288.
(16) (a) Ahn, K. H.; Ham, C.; Kim, S.-K.; Cho, C.-W. J. Org. Chem.
1997, 62, 7047. (b) Mao, J. M.; Baker, D. C. Org. Lett. 1999, 1, 841.
J. Org. Chem, Vol. 70, No. 3, 2005 1009

Chen et al.
washed successively with 0.5 M citric acid, saturated sodium
bicarbonate, and brine and dried. Flash chromatography on
silica gel gave the Boc-protected hybrid dendrimers.
In conclusion, Fre´chet-type core dendritic DPEN ligands
and hybrid dendritic ligands based on Fre´chet’s polyether
dendron and Newkome’s poly(ether-amide) were designed
and synthesized. High catalytic activity and enantio-
selectivity, comparable to the monomeric catalyst, were
achieved in transfer hydrogenation of various unsatur-
ated compounds. Much better recyclability for higher
generation core-functionalized dendritic catalyst was
observed compared with that of the hybrid dendritic
catalysts. This finding supplied strong support for the
stabilizing effect of the bulky polyether dendron on the
catalytically active complex. In particular, to the best of
our knowledge, hybrid dendritic ligands and catalysts
have not been synthesized and used in asymmetric
synthesis.3,9 Future work to develop more efficient recy-
clable dendritic catalysts is in progress.
(R,R)-7a: 81% yield; [R]20 +21.5 (c 0.45, THF); 1H NMR
D
(CD3COCD3, 400 MHz) δ 1.32 (s, 27H), 2.47 (br s, 6H), 3.58-
3.78 (m, 12H), 4.12 (br s, 8H), 4.70-4.72 (m, 3H), 4.93-5.00
(m, 31H), 6.58-6.72 (m, 21H), 6.97-7.53 (m, 82H), 7.92 (br s,
3H), 9.72 (br s, 3H) ppm; partial 13C NMR (CD3COCD3,
50 MHz) δ 28.6, 37.0, 44.6, 60.7, 63.9, 68.2, 69.9, 70.5, 79.5,
102.1, 102.3, 107.3, 107.4, 119.6, 127.9, 128.2, 128.4, 128.6,
128.8, 129.2, 136.8, 138.1, 139.8, 140.3, 140.6, 140.7, 142.6,
142.7, 156.5, 160.7, 160.9, 161.0, 169.2, 173.2 ppm; IR (KBr)
3295, 1687, 1595, 1534, 1452, 1370 cm-1. Anal. Calcd for
C
201H204N14O37S3: C, 68.90; H, 5.87; N, 5.60; S, 2.75. Found:
C, 68.40; H, 5.81; N, 5.54; S, 2.50.
General Procedure for Deprotection of the Boc Group.
Boc-protected dendrimer (0.2 mmol) was dissolved in DCM (1
mL) and the solution was cooled with ice water. TFA (1 mL)
was added and the solution was stirred for 1 h. The solvent
was removed under vacuum and water (10 mL) was added.
The mixture was neutralized with ammonia and stirred at
room temperature for 2 h. The solid was collected, washed with
Experimental Section
General Methods. Melting points were determined in open
capillaries and were uncorrected. NMR spectra were recorded
with tetramethylsilane as the internal standard. Chiral 1,2-
diphenylethylene-diamine was produced in our laboratory
according to Corey’s procedure,18 [R]20D +106.7 (c 1.0, methanol,
R,R-isomer). All other reagents were used without purification
as commercially available.
water, and dried under vacuum.
1
(S,S)-2b: 91% yield; [R]20 +3.5 (c 0.15, CH2Cl2); H NMR
D
(CDCl3, 300 MHz) δ 4.39-4.41 (m, 1H) 4.60-4.61 (m, 1H), 5.08
(s, 4H), 6.79 (s, 1H), 7.48-7.03 (m, 22H), 7.61 (d, J ) 8.1 Hz,
2H), 7.67 (d, J ) 8.7 Hz, 2H) ppm; IR (KBr) 3430, 3195, 1676,
1591, 1323, 1158, 1056 cm-1; ESI HRMS calcd for C41H37N3O5S
+ H 684.2532, obsd 684.2429.
General Procedure for Condensation of Fre´chet-Type
Acid with (S,S)-1. (S,S)-N-Boc-N′-(4-aminophenylsulfonyl)-
1,2-dipheylethylenediamine (1) (467 mg, 1.0 mmol),7 Dendritic
acid (1.05 equiv), and triphenyl phosphite (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 phase was washed successively with 0.5 M
citric acid, sodium bicarbonate, and brine dried. Flash chro-
matography on silica gel gave the Boc-protected dendrimers
2a-5a.
Asymmetric Transfer Hydrogenation Reaction: Gen-
eral Procedure for Asymmetric Transfer Hydrogenation
of Unsaturated Compounds. [RuCl2(cymene)]2 (1.3 mg,
0.002 mmol), Dendritic ligand (1.1 equiv of Ru), and NEt3 (1.2
µL, 0.008 mmol) were stirred in DCM at room temperature
for 2 h. Then unsaturated compound (0.4 mmol) and formic
acid/triethylamine azeotrope (0.2 mL) were added in turn. The
solution was stirred at 28 °C and monitored by TLC. After
completion, the solution was diluted with 5 mL of ethyl acetate,
washed with brine, and dried (Na2SO4). Flash chromatography
gave the pure reduced product.
(S,S)-5a: 51% yield; mp 83-86 °C; [R]20 -2.57 (c 0.43,
D
acetone); 1H NMR (CDCl3, 300 MHz) δ 1.49 (s, 9H), 4.92, 4.98
(br s × 2, 60H), 6.55, 6.65 (br s × 2, 45H), 7.28-7.37 (m, 94H)
ppm, the two NCHs of DPEN are too small to be detected; IR
(KBr) 3415, 3031, 1687, 1449, 1373, 1157, 1051 cm-1; Anal.
Calcd for C242H213N3O35S: C, 77.40; H, 5.72; N, 1.12; S, 0.85.
Found: C, 77.80; H, 5.77; N, 1.12; S, 0.75.
For transfer hydrogenation of activated olefin 12, THF was
used as the solvent.
Acknowledgment. This work was financially sup-
ported by the National Natural Science Foundation of
China (Nos. 203900507 and 20025205). Y.-C.C. is grate-
ful for the financial support of Sichuan University.
General Procedure for the Synthesis of Boc-Protected
Hybrid Dendrimers. Branched ligand (R,R)-6 (192 mg, 0.1
mmol),7b Fre´chet-type acid (1.05 equiv), EDCI (25 mg, 0.13
mmol), and HOBt (14 mg, 0.1 mmol) were stirred in DCM (5
mL) and cooled in ice water. NEt3 (18 µL, 0.13 mmol) was
added and the solution was stirred overnight. The solution was
Supporting Information Available: Characterization
data for compounds 2a-4a, 8a, 3b-5b, 7b, and 8b; NMR and
GC or HPLC data for the reduction products; spectra of
dendritic ligands. This material is available free of charge via
the Internet at http://pubs.acs.org.
(17) Chen, Y.-C.; Xue, D.; Deng, J.-G.; Cui, X.; Zhu, J.; Jiang, Y.-Z.
Tetrahedron Lett. 2004, 45, 1555.
(18) Pikul, S.; Corey, E. J. Organic Syntheses; Wiley: New York;
Collect Vol. IX, p 387.
JO048317V
1010 J. Org. Chem., Vol. 70, No. 3, 2005