Homogeneous dihydroxylation of olefins catalyzed by OsO4 2- immobilized on a dendritic backbone with a tertiary nitrogen at its core position

Article abstract of DOI:10.1248/cpb.c12-00682

OsO₄^2- immobilized on a poly(benzyl ether) dendrimer with a tertiary nitrogen at its core position efficiently catalyzed the homogeneous dihydroxylation of olefins with a low level of osmium leaching. The dendritic osmium catalyst could be applied to the wide range of olefins. Furthermore, the dendritic osmium catalyst was recovered by reprecipitation and then reused up to five times.

Full text of DOI:10.1248/cpb.c12-00682

1594
Note
Chem. Pharm. Bull. 60(12) 1594–1598 (2012)
Vol. 60, No. 12
Homogeneous Dihydroxylation of Olefins Catalyzed by OsO4 ꢀ
Immobilized on a Dendritic Backbone with a Tertiary Nitrogen at Its
Core Position
2
,
a
b
b
a
Ken-ichi Fujita,* Kensuke Inoue, Teruhisa Tsuchimoto, and Hiroyuki Yasuda
a
National Institute of Advanced Industrial Science and Technology (AIST); AIST Tsukuba Central 5, 1–1–1 Higashi,
b
Tsukuba, Ibaraki 305–8565, Japan: and Department of Applied Chemistry, School of Science and Technology, Meiji
University; Higashimita, Tama-ku, Kawasaki, Kanagawa 214–8571, Japan.
Received August 1, 2012; accepted September 25, 2012
OsO4 ꢀ immobilized on a poly(benzyl ether) dendrimer with a tertiary nitrogen at its core position
efficiently catalyzed the homogeneous dihydroxylation of olefins with a low level of osmium leaching. The
dendritic osmium catalyst could be applied to the wide range of olefins. Furthermore, the dendritic osmium
catalyst was recovered by reprecipitation and then reused up to five times.
2
Key words dihydroxylation; dendrimer; osmium-catalyst
The osmium-catalyzed dihydroxylation of olefins is one of Results and Discussion
1)
the most efficient methods for the synthesis of vicinal diols.
Novel bis(ammonium bromide) core dendrimers 3 were
Although these reactions have had widespread application readily synthesized as follows (Chart 1). After the addition of
in organic synthesis, there are several obstacles that stand in an amine compound 2 to an N,N-dimethylformamide (DMF)
the way of their large-scale application to the drug and fine solution of the third-generation poly(benzyl ether) dendritic
11)
chemical industries: high cost, hazardous toxicity, volatility, bromide G3–Br, the reaction mixture was stirred at 70°C for
and the possibility of contamination with toxic osmium in 15h under an argon atmosphere. In all cases, the correspond-
2)
the final product. One of the most promising solutions to ing bis(ammonium bromide) core dendrimers 3 were obtained
these problems is the immobilization of catalytic osmium on in fair chemical yields.
2
−
an insoluble support, which could be recovered by filtration
of the reaction mixture.
Next, novel OsO4 core dendrimers 4 were prepared by an
3
–5)
However, the lower activity of the ion-exchange procedure, as follows (Table 1). 3 and K OsO
2
4
insoluble immobilized catalyst remains a major problem.
Metallodendrimers, with catalytic sites immobilized on
the dendrimer, are particularly useful as synthetic catalysts
by virtue not only of their good solubility and fair catalytic
6
,7)
activity but also of their recyclability by reprecipitation.
2−
Recently, we prepared OsO4 core dendrimer having the
third-generation poly(benzyl ether) dendron 1 (Fig. 1), which
efficiently catalyzed the homogeneous dihydroxylation of
olefins and was recovered by reprecipitation after dihydrox-
8
–10)
ylation.
In this paper, we report a new type of a dendritic
osmium catalyst by the modification of the core unit. By the
introduction of a tertiary nitrogen at the core of the dendrimer
support, the leaching of osmium off the dendritic backbone
was suppressed during dihydroxylation. Furthermore, we re-
port the high recyclability of the dendritic osmium catalyst
with good chemical yields.
2
-
Fig. 1. Dendritic OsO4 Core Catalyst 1
Chart 1. Synthesis of Dendrimers 3
The authors declare no conflict of interest.
*
To whom correspondence should be addressed. e-mail: k.fujita@aist.go.jp
© 2012 The Pharmaceutical Society of Japan

December 2012
Table 1. Preparation of OsO4 Core Dendrimers 4
1595
2
−
a)
of the bis(quaternary ammonium salt) catalyst. However, the
leaching level of osmium during dihydroxylation did not de-
8)
pend on the length between two nitrogens.
In this work, by employing a dendritic osmium catalyst
having an ethereal oxygen at the center of the core 4a, the
dihydroxylation proceeded smoothly and the leaching level of
osmium was almost the same as that in the case of 1 (Table
2
, entry 2). On the other hand, by employing a dendritic os-
mium catalyst having a tertiary nitrogen at the core 4b, the
chemical yield was almost the same as those in the cases of
1 and 4a and the leaching level of osmium decreased (Table
b)
Os content of 4 (mmol/g)
Entry
Catalyst
c)
Found
Calcd
2
, entry 3). Although we have no definitive explanation at the
1
2
3
4a
4b
4c
0.14
0.091
0.11
0.43
0.42
0.41
moment for the suppression of the osmium leaching, the coor-
dination of the introduced tertiary nitrogen with the osmium
center could be responsible. However, 4c, which had two
tertiary nitrogens at the core of the dendritic backbone, could
a) Reaction conditions: 3, an equimolar amount of K OsO , carried out in water
and dichloromethane at room temperature for 5h. b) Determined by XRF. c) Os
2
4
content of an ideal catalytic composition containing a bis(ammonium cation) and an not catalyze the dihydroxylation reaction completely (Table 2,
osmate ion in 1:1 molar ratio, as shown in 4.
entry 4). Based on this unexpected result, we then performed
the cis-dihydroxylation reaction of trans-β-methylstyrene by
were vigorously stirred in water and dichloromethane as a use of 1mol% of 1 in the presence of 1mol% of N,N,N′,N′-
two-phase condition, followed by extraction. The Os content tetramethylethylenediamine. As a result, the dihydroxylation
12)
of 4 was determined by X-ray fluorescence analysis (XRF). In reaction did not proceed at all. From these results, it is
2−
all cases, the ion-exchange for OsO4 was incomplete.
assumed that the introduction of one tertiary nitrogen at the
We then examined the utility of dendrimers 4 as osmium dendrimer core is desirable for the suppression of the leaching
catalysts by performing the cis-dihydroxylation of an olefin level of osmium during dihydroxylation.
(
Table 2). By employing 1mol% of the dendritic osmium
We subsequently performed the cis-dihydroxylation of
catalysts 4, the cis-dihydroxylation reactions of trans-β- various olefins by employing 1mol% of the dendritic osmium
methylstyrene were carried out by the use of N-methylmor- catalyst having a tertiary nitrogen 4b according to Table 3. In
pholine N-oxide (NMO) as a re-oxidant in CH CN–H O (4:1 all cases, the dihydroxylation reactions proceeded, and almost
3
2
(v/v)) at room temperature. After the disappearance of trans- all olefins were converted to the corresponding diols for a few
β-methylstyrene, which was monitored by thin-layer chroma- hours, except for methyl trans-cinnamate, which is an elec-
tography (TLC), the reaction mixture was evaporated. The tron-deficient olefin, and (E)-5-decene, which is an internal
residue was dissolved in a small amount of acetone, and the olefin (Table 3, entries 5 and 11). Especially, when substituted
acetone solution was poured into water. After the precipitated styrene derivatives were used, the dihydroxylations were com-
dendritic osmium catalysts were separated from the aqueous pleted within 1h (Table 3, entries 1–4). The dihydroxylations
mixture, the chemical yields were determined by integrat- catalyzed by the dendritic osmium catalyst 4b were more
1
ing H-NMR absorptions referring to an internal standard, rapid than those reported for the immobilized osmium cata-
3
–5)
which was added to the aqueous mixture, and the leaching of lysts,
due to the homogeneity of 4b.
The reusability of the dendritic osmium catalyst 4b was
osmium off the dendritic backbone was determined by the in-
ductively coupled plasma-atomic emission spectroscopy (ICP- examined using trans-β-methylstyrene (Table 4). This catalyst,
AES) measurement of the aqueous mixture. which was recovered by reprecipitation after the dihydrox-
We previously performed the cis-dihydroxylation of an ylation, catalyzed the subsequent dihydroxylation reactions.
olefin by employing a dendritic osmium catalyst 1 and its As a result, it was efficiently recycled up to six times, and
analogues, which differed in the length between two nitrogens the corresponding diols were consistently obtained in good
a)
Table 2. Dihydroxylation of trans-β-Methylstyrene Catalyzed by 4
b)
c)
Entry
Catalyst
n
X
Time (h)
Yield (%)
Os leaching (%)
d)
1
1
0
1
1
2
—
O
0.5
0.5
0.5
24
93
92
92
0
2.2
2.4
1.4
—
2
3
4
4a
4b
4c
NCH3
NCH3
a) Reaction conditions: 1 or 4 (1mol%), olefin (1eq), NMO (1.3eq), CH CN–H O (4:1, v/v 0.25M based on olefin), carried out at room temperature for indicated time. b)
3
2
1
Determined by integration of H-NMR absorptions referring to an internal standard. c) Determined by ICP-AES. d) Quoted from ref. 8.

1596
Vol. 60, No. 12
a)
Table 3. Dihydroxylation of Various Olefins Catalyzed by 4b
b)
Entry
1
Olefin
Product
Time (h)
0.5
Yield (%)
91
2
3
0.5
1
92
95
4
5
6
1
8
1
84
86
96
7
8
9
1
2
3
3
95
85
92
97
1
1
0
1
7
88
1
1
2
3
1
1
87
85
a) The reaction conditions were the same as in Table 2. b) Isolated yield.
a)
Table 4. Catalyst Recycling in Dihydroxylations by Use of 4b
First
Second
Third
Fourth
Fifth
Sixth
b)
Yield (%)
92
98
99
1
96
2
93
3
99
4
Time (h)
0.5
1.4
0.5
1.3
c)
Os leaching (%)
0.9
0.7
0.7
0.4
1
a) The reaction conditions were the same as in Table 2. b) Determined by integration of H-NMR absorptions referring to an internal standard. c) Determined by ICP-AES.

December 2012
1597
chemical yields within 0.5–4h in all rounds. Furthermore, the (KBr) 3387, 2940, 1597, 1500, 1458, 1323, 1206, 1155, 1051,
−1
1
leaching level of osmium progressively decreased with each 833 cm ; H-NMR (400MHz; CDCl ) δ: 6.84 (d, J=2.0Hz,
3
successive reuse of 4b. Especially, the leaching level was less 4H, ArH), 6.67 (d, J=2.4Hz, 8H, ArH), 6.65–6.61 (m, 2H,
than 1% in each of experiments three through six.
ArH), 6.54 (d, J=2.0Hz, 16H, ArH), 6.51 (t, J=2.4Hz, 4H,
ArH), 6.37 (t, J=2.2Hz, 8H, ArH), 4.99 (s, 8H, OCH Ar), 4.95
2
+
Conclusion
(s, 16H, OCH Ar), 4.75 (s, 4H, N CH Ar), 3.89−3.85 (m, 4H,
2
2
+
The osmium core dendrimer catalyzed the homogeneous CH CH N ), 3.74 (s, 48H, OCH ), 3.12 (s, 3H, NCH ), 3.09
2
2
3
3
+
13
dihydroxylation reactions of olefins. The leaching level of (s, 12H, N CH ), 2.43 (s, 4H, CH N); C-NMR (100MHz;
3
2
osmium during dihydroxylation was suppressed by the in- CDCl ) δ: 160.9, 160.0, 159.8, 139.1, 138.8, 128.9, 112.2, 106.5,
3
troduction of a tertiary nitrogen at the core of the dendritic 105.2, 104.4, 101.7, 99.8, 70.05, 69.96, 67.8, 62.0, 55.3, 50.7,
backbone. Also, in the case of the recycling of the dendritic 50.2, 43.0; Anal. Calcd for C123H Br N O ·H O: C, 64.59;
141
2
3
28
2
osmium catalyst, the dihydroxylations proceeded smoothly H, 6.30; N, 1.84; Br, 6.99%. Found: C, 64.50; H, 6.20; N, 1.74;
with low levels of osmium leaching.
Br, 6.97%.
2
,2′-{Ethane-1,2-diylbis(methylazanediyl)}bis(N-[3,5-bis-
Experimental
{3,5-bis(3,5-dimethoxybenzyloxy) benzyloxy}benzyloxy]-N,N-
General Kieselgel 60 F254 (Merck) was used for TLC, dimethylethanaminium) Dibromide (3c): White powder; mp
and Wakogel C-300 (Wako) was used for silica gel column 67–69°C; IR (KBr) 3420, 2939, 1597, 1456, 1323, 1206, 1155,
−
1
1
chromatography. G3–Br was prepared by the method in the 1051, 833cm ; H-NMR (400MHz; CDCl ) δ: 6.85 (d, J=
3
11)
literature. Degassed solvent, which was bubbled by argon 2.0Hz, 4H, ArH), 6.68 (d, J=2.0Hz, 8H, ArH), 6.64–6.61 (m,
for more than 1h, was used in the preparation of 4. Other re- 2H, ArH), 6.55 (d, J=2.0Hz, 16H, ArH), 6.52 (t, J=2.2Hz,
agents and dry solvents were commercially available and were 4H, ArH), 6.38 (t, J=2.4Hz, 8H, ArH), 4.99 (s, 8H, OCH Ar),
2
+
used as received.
4.95 (s, 16H, OCH Ar), 4.83 (s, 4H, N CH Ar), 3.91–3.84 (m,
Microanalyses were performed with a CE Instruments 4H, CH CH N ), 3.76 (s, 48H, OCH ), 3.15 (s, 12H, N CH ),
2
2
+
+
2
2
3
3
+
EA1110 elemental analyzer. IR spectra were recorded on a 3.06–2.96 (m, 4H, NCH CH N ), 2.71 (s, 4H, NCH CH N),
2
2
2
2
1
13
Shimadzu IR Prestige-21 FT-IR spectrophotometer. H- and 2.30 (s, 6H, NCH3); C-NMR (100MHz; CDCl ) δ: 160.9,
C-NMR spectra were measured with a Bruker Avance III 160.0, 159.8, 139.1, 138.8, 129.0, 112.2, 106.5, 105.2, 104.3,
00 spectrometer ( H: 400MHz, C: 100MHz). Chemical 101.7, 99.8, 70.1, 70.0, 68.1, 61.8, 55.3, 54.4, 51.1, 50.1, 42.9;
3
13
1
13
4
shifts were reported as ppm downfield from TMS as an in- Anal. Calcd for C126H148Br N O ·H O: C, 64.55; H, 6.45; N,
2
4
28
2
ternal standard in δ units. Coupling constants (J) are given in 2.39; Br, 6.82%. Found: C, 64.40; H, 6.37; N, 2.27; Br, 7.01%.
hertz (Hz). Melting points were determined on a Yanaco MP- Preparation of a Dendritic Osmium Catalyst 4: Typical
00D melting point apparatus, and were uncorrected. XRF Procedure To a dichloromethane solution (degassed; 24mL)
was recorded on a Shimadzu EDX-800HS analyzer. ICP-AES of 3b (1.203g, 0.530mmol), an aqueous solution (degassed;
was recorded on a Shimadzu ICPS-8100 analyzer. 12mL) of K OsO ·2H O (191.3mg, 0.519mmol) was added at
5
2
4
2
Synthesis of Dendritic Quaternary Ammonium Bro- room temperature under an argon atmosphere. The resulting
mide 3: Typical Procedure A dry DMF solution (5mL) two-phase mixture was vigorously stirred for 5h. The reaction
of N,N,N′,N,″N″-pentamethyldiethylenetriamine (196.3mg, mixture was extracted with dichloromethane (30mL×3). After
1
.132mmol) and 3,5-bis{3,5-bis(3,5-dimethoxybenzyloxy)- removal of the solvent under reduced pressure, 4b was ob-
benzyloxy}benzyl bromide (2.494g, 2.380mmol) was stirred tained as a black powder (1.224g). The Os content of 4b was
at 70°C for 15h under an argon atmosphere. The reaction mix- determined by XRF with the use of DMF–H O solution of 4b.
2
ture was evaporated to dryness, and the residue was purified
Compound 4a: Black powder; mp 76–78°C; Os content:
with silica gel column chromatography (ethyl acetate–metha- 0.14mmol/g; IR (KBr) 3422, 2938, 2837, 1597, 1456, 1431,
−1
nol=3:1 as an eluent) to obtain 3b (1.960g, 0.864mmol) in a 1323, 1206, 1155, 1053, 833cm ; Anal. Found: C, 62.57; H,
76% yield.
6.02; N, 1.14.
2
,2′-Oxybis(N-[3,5-bis{3,5-bis(3,5-dimethoxybenzyloxy)-
Compound 4b: Black powder; mp 69.5–71.5°C, Os content:
benzyloxy}benzyloxy]-N,N-dimethylethanaminium)
Dibro- 0.091mmol/g; IR (KBr) 3418, 2938, 1597, 1458, 1323, 1206,
−1
mide (3a): White powder; mp 68–70°C; IR (KBr) 3420, 1155, 1053, 835cm ; Anal. Found: C, 63.61; H, 6.17; N, 1.74.
−1
2
938, 1597, 1456, 1323, 1206, 1155, 1053, 835, 681cm ;
Compound 4c: Black powder; mp 72–74°C; Os content:
1
H-NMR (400MHz; CDCl ) δ: 6.84–6.81 (m, 4H, ArH), 0.11mmol/g; IR (KBr) 3418, 2940, 1591, 1456, 1323, 1206,
3
−1
6
(
(
1
.67 (d, J=2.0Hz, 8H, ArH), 6.62–6.59 (m, 2H, ArH), 6.53 1153, 1053, 835cm ; Anal. Found: C, 62.21; H, 6.26; N, 2.21.
d, J=2.0Hz, 16H, ArH), 6.51–6.48 (m, 4H, ArH), 6.35 Dihydroxylation Reaction To CH CN–H O (4:1,
t, J=2.2Hz, 8H, ArH), 4.97 (s, 8H, OCH Ar), 4.93 (s, v/v) solution (3.75mL) of 4 (0.01mmol) was added an olefin
a
3
2
2
+
6H, OCH Ar), 4.77 (s, 4H, N CH Ar), 4.15–4.07 (m, 4H, (1mmol) and NMO (1.3mmol) successively at room tempera-
CH CH N ), 3.73 (s, 48H, OCH ), 3.71–3.64 (m, 4H, OCH ), ture under an argon atmosphere. The reaction mixture was
.13 (s, 12H, N CH ); C-NMR (100MHz; CDCl ) δ: 160.9, stirred until the olefin disappeared (as monitored by TLC:
2
2
+
2
2
3
2
+
13
3
3
3
1
60.0, 159.8, 139.2, 138.9, 138.8, 128.9, 112.1, 106.5, 105.2, hexane as an eluent in case of hydrocarbon olefins). The reac-
04.5, 101.7, 99.8, 70.0, 69.9, 67.8, 64.6, 64.4, 55.3, 50.9; Anal. tion mixture was evaporated and the residue was dissolved
Calcd for C122H138Br N O ·H O: C, 64.43; H, 6.20; N, 1.23; in acetone. The acetone solution was poured into water to
1
2
2
29
2
Br, 7.03%. Found: C, 64.28; H, 6.13; N, 1.15; Br, 7.34%.
,2′-(Methylazanediyl)bis(N-[3,5-bis{3,5-bis(3,5-di- the aqueous solution was decanted. In Table 4, the recovered 4
methoxybenzyloxy)benzyloxy}benzyloxy]-N,N-dimethylethan- was reused for subsequent dihydroxylation reactions.
aminium) Dibromide (3b): White powder; mp 68–70°C; IR
In Tables 2 and 4, the chemical yields were determined
precipitate 4 as a grayish powder. After centrifugal separation,
2

1598
Vol. 60, No. 12
1
1
1229–11230 (1999).
by integrating H-NMR absorptions referring to an internal
standard (3-hydroxybenzyl alcohol (1.5mmol)), which was
added to the decanted aqueous solution. The leaching level
of osmium was determined by ICP-AES measurement of the
decanted aqueous solution.
6
7
)
)
“Dendrimers and Other Dendritic Polymers,” ed. by Fréchet J. M.
J., Tomalia D. A., John Wiley & Sons, New York, 2001.
Muraki T., Fujita K., Kujime M., J. Org. Chem., 72, 7863–7870
(2007).
8)
Fujita K., Yamazaki M., Ainoya T., Tsuchimoto T., Yasuda H., Tet-
rahedron, 66, 8536–8543 (2010).
Fujita K., Ainoya T., Tsuchimoto T., Yasuda H., Tetrahedron Lett.,
51, 808–810 (2010).
In Table 3, the decanted aqueous solution was concentrated
under reduced pressure, and was purified with silica gel col-
umn chromatography.
9)
The dihydroxylation products in Table 3 are known com- 10) However osmium core dendrimers have been reported before our
8
,9)
pounds, and their NMR spectra are in accordance with those
previous reports, their catalytic activity was as low as in the case
of heterogeneity: Tang W.-J., Yang N.-F., Yi B., Deng G.-J., Huang
Y.-Y., Fan Q.-H., Chem. Commun., 2004, 1378–1379 (2004).
13)
5)
reported in the literature (entries 1–6, entries 7 and 11,
14)
15)
16)
entry 8, entries 9, 12 and 13, entry 10 ).
1
1) Muraki T., Fujita K., Oishi A., Taguchi Y., Polym. J., 37, 847–853
(
2005).
Acknowledgment This work was supported by Japan
Society for the Promotion of Science (JSPS) KAKENHI
23550183).
1
2) In contrast, by performing the cis-dihydroxylation reaction of trans-
β-methylstyrene by use of 1mol% of 1 in the presence of 2mol% of
triethylamine, the dihydroxylation was completed within 0.5h (92%
yield).
(
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