Rh(II)-Cp-TsDPEN catalyzed aqueous asymmetric transfer hydrogenation of chromenones into saturated alcohol: C=C and C=O reduction in one step

Article abstract of DOI:10.1016/j.tetlet.2012.04.050

As an efficient catalyst for asymmetric transfer hydrogenation reaction (ATH reaction) of α,β-unsaturated ketones, Rh-Cp-TsDPEN (Cp = 1,2,3,4,5-pentamethylcyclopenta-1,3-diene, TsDPEN = N-(p-toluenesulfonyl)-1,2- diphenyl- ethylenediamine) shows high chemoselectivity on C=O and C=C reduction. In our method, both C=O and C=C bonds in a variety of chromenone derivatives were reduced efficiently in aqueous media, resulting in at least 98% ee and up to 99% yields in a convenient way without further purification. The product was a useful intermediate for deriving chiral chroman-4-amine, which was reported as an effective agent against hypotension and inflammatory pain by inhibiting human bradykinin B1 receptor.

Full text of DOI:10.1016/j.tetlet.2012.04.050

Tetrahedron Letters 53 (2012) 3828–3830
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
⁄
Rh(II)-Cp –TsDPEN catalyzed aqueous asymmetric transfer hydrogenation
of chromenones into saturated alcohol: C@C and C@O reduction in one step
Lei Tang a,c, Zechao Lin , Qiwei Wang , Xiaobei Wang , Linfeng Cun , Weicheng Yuan , Jin Zhu ,
Jingen Deng
a
a,c
a
a,b
a
a
a
a,b,c,
⇑
Key Laboratory for Asymmetric Synthesis & Chirotechnology of Sichuan Province, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China
Key Laboratory of Drug-Targeting of Education Ministry and Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
Graduate School of Chinese Academy of Sciences, Beijing 100049, China
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
As an efficient catalyst for asymmetric transfer hydrogenation reaction (ATH reaction) of a,b-unsaturated
Received 3 March 2012
Revised 4 April 2012
Accepted 12 April 2012
Available online 20 April 2012
⁄
⁄
ketones, Rh-Cp –TsDPEN (Cp = 1,2,3,4,5-pentamethylcyclopenta-1,3-diene, TsDPEN = N-(p-toluenesulfo-
nyl)-1,2-diphenyl- ethylenediamine) shows high chemoselectivity on C@O and C@C reduction. In our
method, both C@O and C@C bonds in a variety of chromenone derivatives were reduced efficiently in
aqueous media, resulting in at least 98% ee and up to 99% yields in a convenient way without further puri-
fication. The product was a useful intermediate for deriving chiral chroman-4-amine, which was reported
as an effective agent against hypotension and inflammatory pain by inhibiting human bradykinin B1
receptor.
Keywords:
Transfer hydrogenation
Asymmetric catalysis
⁄
Ó 2012 Published by Elsevier Ltd.
Rh-Cp –TsDPEN
Chromenone
⁄
Noyori type catalyst, such as Rh-Cp –TsDPEN complex
be reduced directly, it would be more convenient to synthesize chi-
ral chroman-4-ol (3). Thus, we proposed that as a special type of
⁄
(
(
Cp = 1,2,3,4,5-pentamethylcyclo-penta-1,3-diene, TsDPEN = N-
p-toluenesulfonyl)-1,2-diphenyl-ethylenediamine), is of crucial
a
,b-unsaturated ketones, chromenone (1) could be reduced to chi-
⁄
importance on ketones’ ATH reaction (asymmetric transfer hydro-
genation reaction). It has shown powerful reactivity as well as
excellent stereo-control in many fields.1 Moreover, it exhibits
highly chemoselectivity for the C@O functional group in ATH reac-
tion of
ral chroman-4-ol (3) in water directly catalyzed by Rh-Cp Cl–
TsDPEN.
We selected chromenone (1a) to be the template substrate, as
outlined in Table 1. For the composition of hydrogen source was
proved to be of crucial effect on the activity of ATH reaction in
9
,b-unsaturated ketones in the organic phase.2 However,
,3
a
4
c,10
the chemoselectivity of those types of catalyst would be switched
water,
the change of composition was initially tested at 30 °C
from C@O to C@C bonds in the transfer hydrogenation if the solu-
tion was replaced with water. In that case, as shown in our earlier
study, saturated alcohol with high ee value was detected when the
substrate was chalcone, which means both C@C and C@O double
bonds have been reduced together.4a When the substrate was ben-
zylidene acetone, which reacted with excessive HCOONa as a
(entries 1–4). It was clearly suggested that HCOONa with a small
amount of HCOOH led to a better result (entry 2) than without
HCOOH addition (entry 1). Nevertheless, the reaction with pure
4
hydrogen source, similar chemoselectivity was observed. Besides,
O
⁄
[
Rh-Cp Cl
2
]
2
was proved to be the most efficient metal source to
4
b,c
prepare such saturated alcohol, which affords 81% conversion.
R
OH
NH
2
On the other hand, it was reported that compounds with the
structure of chroman-4-amines (4) were effectively against hypo-
tension and inflammatory pain as a selective antagonist of brady-
O
2
*
*
R
R
O
O
O
5
kinin B1 receptors. The chroman-4-amines (4) could be easily
3
4
prepared from chiral chroman-4-ol (3)5 by CBS, AH, or ATH
,6a
5,6
7
1b,8
R
reaction (Fig. 1). Obviously, if easy-obtained chromenone (1) could
O
1
⇑
Corresponding author. Fax: +86 2885238597.
E-mail address: jgdeng@cioc.ac.cn (J. Deng).
Figure 1. Preparation of chroman-4-amines (4) from chroman-4-ones (2) or
chromenone (1).
0
040-4039/$ - see front matter Ó 2012 Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.tetlet.2012.04.050

L. Tang et al. / Tetrahedron Letters 53 (2012) 3828–3830
3829
Table 1
Optimizing conditions for (S, S)-Cp RhClTsDPEN catalyzed ATH reaction in water
Table 2
⁄
a
⁄
a
Substances scope for (S, S)-Cp RhClTsDPEN catalyzed ATH reaction in water
O
OH
O
OH
O
(
S,S)-Cp*RhClTsDPEN, S / C = 100
(S,S)-Cp*RhClTsDPEN, S / C = 100
HCOOH / HCOONa = 4 : 20
R
R
HCOOH / HCOONa (5 eq), H O
2
O
a
O
3a
O
H O, 60
°C, 3 h
3
1
2
1
Entry HCOOH:HCOONa Temp (°C) Time (h) Conversionb (%) ee (%)
c
Isolated yieldb (%)
eec (%)
99
Entry
1
Substance
1
2
3
4
5
6
7
8
9
0
1
0:1
30
30
30
30
40
40
40
60
60
60
60
3
3
3
3
3
3
3
1
1
1
1
13
27
9
99
99
99
—
99
99
99
99
99
99
99
O
3:20
5:20
1:0
3:20
4:20
5:20
2:20
3:20
4:20
5:20
99
ND
89
93
66
80
91
93
89
1
a
O
O
F
2
3
4
5
8
9
98
2311
92
99
99
99
99
99
98
99
99
99
—
1b
1c
O
1
1
O
F
a
⁄
The reaction was performed with 0.0016 mmol of Cp RhClTsDPEN, 0.16 mmol of
a and 0.8 mmol of HCOONa and several equivalents of HCOOH (as mentioned in
1
O
table above) in 1 ml of water under argon atmosphere.
O
b
Determined by 1H NMR.
c
Cl
Determined by HPLC in chiral AS column.
1d
O
O
HCOOH didnot work (entry 4). When the temperature was in-
creased to 40 °C, the conversion value elevated significantly
without any decrease in ee value (entries 5–7), and the most satis-
factory result was achieved by adding 1 equiv HCOOH, which yield
Br
99
1e
O
O
9
3% conversion. With the temperature increment, the reaction
51
activity was increased as well (entries 8–11). Therefore, the most
suitable condition should be stirring at 60 °C with the hydrogen
source composed of 5 equiv HCOONa and 0.8 equiv HCOOH. This
reaction condition will lead to 93% conversion and 99% ee in only
h, and the amount of chroman-4-ones was barely detectable.
With the best condition in hand, substrate scope was performed
subsequently, as shown in Table 2. Similar to template substrate
1a), chromenone derivatives with electron-withdrawing substitu-
ents in benzyl ring performed perfectly on both stereo selectivity
and reactivity. At least 92% isolated yield could be achieved except
for 1c. Although, chromenone derivatives with electron accepter
substituents also showed high ee value, the activity declined sub-
stantially. When the substituent was methyl group, only an inter-
mediate yield was obtained (entries 8 and 11). Furthermore, fewer
products were obtained when the stronger electron-donating
methoxy was introduced (entries 9 and 12). Only trace amount
of chroman-4-one (2) would be present in all the products men-
tioned above. Pure products could be obtained by extracting
the substrate-product mixture with alkaline to remove the sub-
strate directly. It was unexpected that substrates with methyl or
phenyl substitution in 2-position did not have any reactivity (en-
tries 13 and 14).
1f
O
O
O
O
28
1
1g
O
(
1
0
1
99
1
1
1
h
Cl
O
1
1
O
O
1
55
i
O
12
13
29
j
O
O
1
2
O
O
ND
1
l
O
In order to explore the potential of the current catalyst system,
amplification of this reaction was carried out. With 6.8 mmol of 1a
as the starting material, the reaction time was extended to 6 h in
the best condition, and there was no significant decline on the
reactivity and stereoselectivity (Scheme 1). After treated with alka-
line, the product could be acquired with 96% isolated yield and 99%
ee value.
1
4
ND
—
1m
O
Ph
a
⁄
The reaction was performed with 0.0016 mmol of Cp RhClTsDPEN, 0.16 mmol
of 1, 0.8 mmol of HCOONa and 0.16 mmol of HCOOH in 1 ml of water at 60 °C for 3 h
under argon atmosphere.
b
The crude product was treated by ice cooled 2 N KOH solution, stirred at 10 °C
In conclusion, a new method to prepare a series of chiral chro-
man-4-ol derivatives catalyzed by Rh-Cp –TsDPEN complex was
2 2
for 0.5 h, extracted with CH Cl and evaporated to afford the product.
c
⁄
Determined by HPLC in chiral AS or OD column.
discovered. The reaction was conducted at 60 °C with excessive
HCOONa and HCOOH as hydrogen source in water, and both C@C
and C@O double bonds of chromenone derivatives were com-
pletely reduced in one step with at least 98% ee and up to 99%
yield. In addition, the product could be obtained with a convenient
procedure by adding alkaline directly. At last, the reaction was

3
830
L. Tang et al. / Tetrahedron Letters 53 (2012) 3828–3830
O
O
OH
3. (a) Sandoval, C. A.; Ohkuma, T.; Muniz, K.; Noyori, R. J. Am. Chem. Soc. 2003, 125,
3490–13503; (b) Abdur-Rashid, K.; Clapham, S. E.; Hadzovic, A.; Harvey, J. N.;
1
(
S,S)-Cp*RhClTsDPEN, S / C = 100
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P.; Singer, S. W.; Powell, D. R.; Hayashi, R. K.; Kavana, M. J. Am. Chem. Soc. 2001,
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3a
1
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H O, 60 °C, 6 h
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1
a
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4
.
.
(a) Xue, D.; Chen, Y. C.; Cui, X.; Wang, Q. W.; Zhu, J.; Deng, J. G. J. Org. Chem.
1
g, 6.8 mmol
Isolated yield: 96%
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ee: 99%
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Scheme 1. The ATH reaction of 1a–3a on Gram-Scale.
5
amplified to gram-scale, which could be utilized in asymmetric
synthesis in the future.
6
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Acknowledgments
7
We are grateful for financial support from the National Natural
Science Foundation of China (No. 20972154), and the National Ba-
sic Research Program of China (973 Program, No. 2010CB833300).
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⁄
9
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2
.
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7
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