Synthesis of enantiopure 1,2-diamine attached to cross-linked polystyrene and its application to an insoluble catalyst for asymmetric hydrogenation

Article abstract of DOI:10.1016/S0040-4039(03)00742-1

A novel enantiopure 1,2-diamine (5) having two phenolic hydroxy groups was attached into chloromethylated polystyrene through benzyl ether linkage, which was used as a chiral ligand of the catalyst in asymmetric hydrogenation of acetophenone.

Full text of DOI:10.1016/S0040-4039(03)00742-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 3825–3828
Synthesis of enantiopure 1,2-diamine attached to cross-linked
polystyrene and its application to an insoluble catalyst for
asymmetric hydrogenation
Shinichi Itsuno,* Atsushi Tsuji and Miyuki Takahashi
Department of Materials Science, Toyohashi University of Technology, Toyohashi 441-8580, Japan
Received 28 November 2002; revised 3 March 2003; accepted 14 March 2003
Abstract—A novel enantiopure 1,2-diamine (5) having two phenolic hydroxy groups was attached into chloromethylated
polystyrene through benzyl ether linkage, which was used as a chiral ligand of the catalyst in asymmetric hydrogenation of
acetophenone. © 2003 Elsevier Science Ltd. All rights reserved.
Enantiopure 1,2-diamines have recently been known as
an efficient chiral auxiliary in various kinds of chiral
catalysts and reagents. Although a variety of 1,2-
cleave its methyl ether linkage to yield dihydroxydi-
amine dihydrobromide (S,S)-3. Once the usual aqueous
alkaline treatment was undertaken for (S,S)-3, extrac-
tion of the desired chiral 1,2-diamine having phenol
groups resulted in failure due to its solubility problem.
1
diamine structures have been designed and synthesized,
no attention has been paid to preparation of the 1,2-
diamines possessing phenolic hydroxy groups such as 5.
The phenol groups would be a very useful functionality
to attach the chiral 1,2-diamine moiety into solid sup-
port materials. Supported catalysts have found increas-
ing use in synthesis since they have inherent operational
We found that the use of polymer-supported piperazine
7
4
as a scavenger resin was quite effective to remove
boron derivatives and neutralize the HBr salt to afford
S,S)-5 in quantitative yield (Scheme 1).
(
2
and economical advantages. Surprisingly, it appears
that there is no report up until now on the immobiliza-
3
tion of chiral 1,2-diamine. We now report the first
preparation of a polymer-supported chiral 1,2-diamine
5
P by means of the reaction between 5 and
chloromethylated polystyrene 6. We also demonstrate
the asymmetric hydrogenation of acetophenone as a
test reaction using 5P complexed with RuCl2 and
4
BINAP.
5
According to Corey’s method, racemic 1,2-diamine 1
was readily prepared from 4,4%-dimethoxybenzil as a
starting material. Optical resolution of racemic 1 was
6
successfully achieved with (
L
)-(+)-tartaric acid. Enan-
tiomeric purity of the obtained chiral 1,2-diamine
S,S)-1 was determined by HPLC analysis of its di(t-
(
butyloxycarbonyl) derivative (S,S)-2. After optical res-
olution (S,S)-1 was treated with BBr in CH Cl to
3
2
2
Keywords: 1,2-diamine; cross-linked polystyrene; asymmetric hydro-
genation.
*
Corresponding author. Tel.: +81-(0)532-44-6813; fax: +81-(0)532-
4-6813; e-mail: itsuno@tutms.tut.ac.jp
4
Scheme 1. Preparation of chiral 1,2-diamine 5.
0
040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00742-1

3
826
S. Itsuno et al. / Tetrahedron Letters 44 (2003) 3825–3828
1
0
Our previous study revealed that a phenolic function-
ality is quite suitable for immobilization reaction to
chloromethylated polystyrenes. Thus, the sodium
and DPEN for the same reaction, no example has
been reported on the use of polymeric 1,2-diamine. In
order to demonstrate the efficiency of the polymer-
supported chiral 1,2-diamine 5P, we performed the
asymmetric hydrogenation of acetophenone using the
polymer-supported Ru complex derived from (S)-
8
phenoxide derived from (S,S)-5 was allowed to react
with 1% cross-linked chloromethylated polystyrene to
give polymer-supported diamine (S,S)-5P, as shown in
Scheme 2. In this immobilization reaction, both
hydroxy groups of (S,S)-5 seem to react with the
chloromethyl groups of 6 based on the diamine load-
ing of 5P calculated by nitrogen analysis. Under the
same reaction conditions, 1,2-diphenylethylenediamine
BINAP, RuCl and (S,S)-5P. The results are summa-
rized in Table 1. In most cases 2-propanol is the
choice of solvent for the hydrogenation using this cat-
2
9
alyst system. Unfortunately, no reaction was achieved
by using the polymer-supported complex in pure 2-
propanol as a solvent (run 5). Styrene-based cross-
linked polymers show little swelling in an alcoholic
solvent which thus may prevent accessibility to the
catalyst site in the polymer network. Addition of
DMF as a co-solvent remarkably improved the reac-
tivity of the hydrogenation using the polymeric cata-
lyst. Acetophenone was smoothly hydrogenated with
the polymer-supported Ru complex derived from
(
DPEN) was not incorporated to the polymer, which
means that no nucleophilic substitution reaction
between the primary amino groups of 1,2-diamine and
the chloromethyl groups in 6 took place. In the cases
of higher content of the chloromethyl group (5Pg,
5
Ph) and a higher degree of crosslinking (5Pe), some
unreacted chloromethyl groups remained.
One of the most important asymmetric reactions using
enantiopure 1,2-diamine as a chiral ligand is hydro9-
genation of simple ketones developed by Noyori et al.
Although Noyori reported the use of a polymeric cata-
lyst prepared from polymer-supported BINAP, RuCl2
(S,S)-5P and (S)-BINAP–RuCl in a 1:1 2-propanol/
2
DMF mixture to give the R alcohol with 73% ee in
11
100% yield (run 7). This result strongly supported
that the active complex was formed in the polymer
1
2
since BINAP–RuCl alone gives no reaction. Pure
2
DMF retarded the reaction with the polymeric catalyst
(
run 10). In a 1:1 2-propanol/DMF mixture a homoge-
neous catalyst derived from DPEN yielded the same
alcohol with 81% ee in 92% yield (run 1). In DMF the
ee decreased to 72% (run 2). Instead of BINAP the
use of xylBINAP produced the same product in higher
enantioselectivity as expected from the asymmetric
1
3
hydrogenation data reported by Noyori (run 11).
The degree of crosslinking and loading influenced both
the reactivity and the enantioselectivity. A lower
degree of crosslinking gave better reactivity. Higher
ees and conversions were obtained when 5Pc was
used.
Isolation of the product by simple filtration was quite
easy when the polymer-supported chiral catalyst was
used. The recycling experiments were also readily per-
formed. After a reaction was completed and the poly-
mer-supported catalyst was allowed to settle, the
solution containing the product was removed through
a syringe. A further amount of acetophenone in 2-
propanol/DMF was injected and the reaction was
repeated. When (R,R)-5Pc–(R)-BINAP–RuCl2 was
employed, quantitative yields were obtained in the
four continuous recycling experiments and the ee val-
ues of the chiral product were 73, 73, 73, and 74% ee,
respectively.
In summary, we have shown an efficient preparative
route to the polymer-supported chiral 1,2-diamine 5P.
Asymmetric hydrogenation of acetophenone smoothly
occurred by using the 5P–BINAP–RuCl2 system in
2
-propanol/DMF. We have shown that the immobi-
lized catalyst can be reused at least four times without
loss of activity. Studies of other asymmetric reactions
using the polymeric chiral 1,2-diamine are currently
under way.
Scheme 2. Preparation of polymer-supported chiral 1,2-
diamine.

S. Itsuno et al. / Tetrahedron Letters 44 (2003) 3825–3828
3827
a
Table 1. Asymmetric hydrogenation of acetophenone using the (S,S)-5P–(S)-BINAP–RuCl complex
2
Run
(S,S)-5P
Solvent (2-propanol:DMF)
1-Phenylethanol
Ee (%)c
Yield (%)b
Config.
d
d
1
2
3
4
5
6
7
8
9
(R,R)-DPEN
(R,R)-DPEN
(S,S)-5Pa
(S,S)-5Pb
(S,S)-5Pc
1:1
DMF
1:1
1:1
2-Propanol
2:1
1:1
1:1
1:2
DMF
1:1
92
100
87
86
0
81
72
73
74
–
71
73
73
70
75
93
73
68
69
67
63
S
S
R
R
–
R
R
S
R
R
R
R
R
R
R
R
(S,S)-5Pc
46
(S,S)-5Pc
(R,R)-5Pc
100
100
100
38
100
69
39
91
78
43
d
(S,S)-5Pc
(S,S)-5Pc
(S,S)-5Pc
10
11
12
13
14
15
16
e
(S,S)-5Pd
1:1
1:1
1:1
1:1
f
(S,S)-5Pe
(S,S)-5Pf
(S,S)-5Pg
(S,S)-5Ph
f
f
1:1
a
Reactions were conducted at 1 MPa of H and at room temperature for 1 h using acetophenone (5 mmol), t-BuOK (1 M t-BuOH soln. 100 mL),
2
1
,2-diamine (0.025 mmol) and BINAP–RuCl2 (0.025 mmol).
b
c
d
e
f
Determined by GC.
Determined by HPLC using Chiralcel OD.
(R)-BINAP was used.
(S)-xylBINAP (2,2%-bis(di-3,5-xylylphosphino)-1,1%-binaphthyl) was used.
Contains unreacted chloromethyl groups.
Acknowledgements
Acids; Wiley-VCH: Weinheim, 2000; Vol. 2, p. 945; (b)
Kirschning, A.; Monenschein, H.; Wittenberg, R. Angew.
Chem., Int. Ed. Engl. 2001, 40, 650.
This research was supported by a Grant-in-Aid for
Scientific Research from the Ministry of Education,
Science and Culture of Japan. Financial support from
Amano Institute of Technology and The Naito
Research Grant is also gratefully acknowledged.
3. Polymer-supported achiral 1,2-diamine has been prepared
and used for complexation with metal cation: Menger, F.
M.; Tsuno, T. J. Am. Chem. Soc. 1990, 112, 6723.
4. BINAP=2,2%-bis(diphenylphosphino)-1,1%-binaphthyl.
5. (a) Corey, E. J.; Pikul, S. Org. Synth. 1992, 71, 22; (b)
Corey, E. J.; Lee, D. H.; Sarshar, S. Tetrahedron: Asym-
metry 1995, 6, 3.
References
6. Pikul, S.; Corey, E. J. Org. Synth. 1992, 71, 22.
7. 2% cross-linked polystyrene supported piperazine (load-
1
. (a) Corey, E. J.; Imwinkelried, R.; Pikul, S.; Xiang, Y. B.
J. Am. Chem. Soc. 1989, 111, 5493; (b) Corey, E. J.;
Sarshar, S.; Bordner, J. J. Am. Chem. Soc. 1992, 114,
ing: 4.2 mmol piperazine/g).
8. (a) Itsuno, S.; Sakurai, Y.; Ito, K.; Maruyama, T.; Naka-
hama, S.; Fr e´ chet, J. M. J. J. Org. Chem. 1990, 55, 304;
(b) Itsuno, S.; Wakasugi, T.; Ito, K. Polym. Bull. 1988,
20, 435; (c) Itsuno, S.; Nakano, M.; Ito, K.; Hirao, A.;
Owa, M.; Kanda, N.; Nakahama, S. J. Chem. Soc.,
Perkin Trans. 1 1985, 2615.
9. Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40,
40.
10. Ohkuma, T.; Takeno, H.; Honda, Y.; Noyori, R. Adv.
Synth. Catal. 2001, 343, 369.
7
938; (c) Uemura, M.; Daimon, A.; Hayashi, Y. J. Chem.
Soc., Chem. Commun. 1995, 1943; (d) Ohkuma, T.; Ooka,
H.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J. Am. Chem.
Soc. 1995, 117, 2675; (e) Blake, A. J.; Cooke, P. A.;
Kendall, J. D.; Simpkins, N. S.; Westaway, S. M. J.
Chem. Soc., Perkin Trans. 1 2000, 147; (f) Ohtsuka, Y.;
Miyazaki, D.; Ikeno, T.; Yamada, T. Chem. Lett. 2002,
2
4; (g) Gibson, S. E.; Han, P.; Jefferson, G. R. Chem.
Commun. 1998, 123; (h) Trost, B. M.; Hildbrand, S.;
Dogra, K. J. Am. Soc. 1999, 121, 10416; (i) Alexakis, A.;
Sedrani, R.; Normant, J. F.; Mangeney, P. Tetrahedron:
Asymmetry 1990, 1, 283; (j) Watanabe, M.; Murata, K.;
Ikariya, T. J. Org. Chem. 2002, 67, 1712.
11. Representative procedure for asymmetric hydrogenation
of acetophenone: polymer-supported chiral 1,2-diamine
((S,S)-5Pc, 2.9 mg, 0.025 mmol) and (S)-
BINAP[RuCl ](dmf) (23 mg, 0.025 mmol) were added to
2
n
dry DMF (2 mL) in a dry, degassed 100-mL glass auto-
clave. To this suspension was added a degassed mixture
of acetophenone (0.58 mL, 5 mmol) and a 1.0 M 2-
2
. (a) Itsuno, S. In Lewis Acids in Organic Synthesis;
Yamamoto, H., Ed. Polymer-Supported Metal Lewis

3
828
S. Itsuno et al. / Tetrahedron Letters 44 (2003) 3825–3828
propanol solution of t-BuOK (100 mL, 0.1 mmol) in
-propanol (2 mL), and then, hydrogen was pressurized
12. After the complex formation of the polymer-supported
2
1,2-diamine with BINAP, some amount of free BINAP–
to 1 MPa. The suspension was stirred at room temper-
ature for 1 h. After the reaction, the mixture was
filtered and concentrated. The yield determined by GC
was 100%. The enantioselectivity was determined by
HPLC analysis using a Daicel Chiralcel OD column
RuCl was detected in the solution part by NMR analy-
sis. Based on the NMR analysis of the solution part, we
can estimate that at least 85% of the polymeric 1,2-
2
diamine forms the complex with BINAP–RuCl .
2
13. Ohkuma, T.; Koizumi, M.; Doucet, H.; Pham, T.;
Kozawa, M.; Murata, K.; Katayama, E.; Yokozawa, T.;
Ikariya, T.; Noyori, R. J. Am. Soc. 1998, 120, 13529.
(eluent, 1:20 2-propanol–hexane; flow rate, 0.4 mL/
min).