Asymmetric transfer hydrogenation of ketones catalyzed by nickel complex with new PNO-type ligands

Article abstract of DOI:10.1016/j.cclet.2012.02.005

The new polydentate mixed-N, P, O chiral ligands have been synthesized by the condensation of bis(o-formylphenyl)-phenylphosphane and R-phenylglycinol in CHCl₃, and fully characterized by IR, NMR and EIMS spectra. These ligands were employed with a simple Ni complex Ni(PPh_s) ₂Cl₂ in situ as catalytic systems for asymmetric transfer hydrogenation of ketones, and the corresponding optical alcohols were obtained with up to 84% ee under mild conditions.

Full text of DOI:10.1016/j.cclet.2012.02.005

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 533–536
www.elsevier.com/locate/cclet
Asymmetric transfer hydrogenation of ketones catalyzed by
nickel complex with new PNO-type ligands
a
a
Zhen Rong Dong a, , Yan Yun Li , Shen Luan Yu ,
*
Guo Song Sun b, Jing Xing Gao a,
*
a State Key Laboratory for Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering,
Xiamen University, Xiamen 361005, China
b Guangxi Research Institute of Chemical Industry, Nanning 530001, China
Received 5 December 2011
Available online 30 March 2012
Abstract
The new polydentate mixed-N, P, O chiral ligands have been synthesized by the condensation of bis(o-formylphenyl)-
phenylphosphane and R-phenylglycinol in CHCl3, and fully characterized by IR, NMR and EIMS spectra. These ligands were
employed with a simple Ni complex Ni(PPhs)2Cl2 in situ as catalytic systems for asymmetric transfer hydrogenation of ketones, and
the corresponding optical alcohols were obtained with up to 84% ee under mild conditions.
# 2012 Zhen Rong Dong. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Nickel complex; NPO-type ligand; Asymmetric transfer hydrogenation; Ketones
Among the most spectacular recent developments in catalytic asymmetric synthesis, asymmetric transfer
hydrogenation (ATH) is an attractive method for the preparation of optically active alcohols [1,2] because of its
operational simplicity and wide substrate scope. In this reaction, generally, chiral ligands are responsible for obtaining
high enantioselectivity. Therefore, the design and synthesis of new chiral ligands are always a challenge for
researchers. In the past decades, numerous different PP, NN, NO, NPN and PNNP-type ligands have been applied for
this reaction [3], these mixed type ligands have attracted more and more attention because of their better ability to
stabilize metal center and special chiral coordination environments surrounding the metal center. In previous studies of
asymmetric transfer hydrogenation of ketones, however, most of research was focused on the expensive noble
platinum metal-based complexes, such as Ru [4], Rh [5], and Ir [6] complexes. Compared with these precious metals,
the first-row transition metals, which are more abundant and benign, attract more and more research interest because
they are cost-effective and ‘‘green’’ catalysts. We reported the first example of iron catalyst used in the ATH reaction of
ketones in 2004 [7], from then on, Morris and co-workers developed very excellent iron catalysts for the reaction in the
recent years [8].
Although there have been some successful examples of iron complexes, as catalysts for ATH of ketones, other first-
row transition metals, such as Ni or Co complexes, are still rarely reported [9].
* Corresponding authors.
E-mail addresses: zrdong@xmu.edu.cn (Z.R. Dong), jxgao@xmu.edu.cn (J.X. Gao).
1001-8417/$ – see front matter # 2012 Zhen Rong Dong. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2012.02.005

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Z.R. Dong et al. / Chinese Chemical Letters 23 (2012) 533–536
Ph
Ph
*
*
NH
PPh
NH
O
OH
OH
N
OH
OH
Ph
a
b
*
PPh
+
PPh
OH
H N
2
O
N
1
*
*
Ph
Ph
2
3
Scheme 1. Synthesis of the NPO-type ligands. Reagent and conditions: (a) CHCl3, anhydrous Na2SO4, reflux, 26 h; (b) NaBH4, C2H5OH, reflux, 2
days.
Recently, we synthesized the new PNO-type chiral ligands, which have been fully characterized by IR, NMR and
EIMS spectra [10], and found that these chiral ligands coupled with a simple Ni complex Ni(PPh3)Cl2 in situ exhibited
good catalytic activity and enantioselectivity as catalysts for asymmetric transfer hydrogenation of a series of aromatic
ketones.
The Ni complex Ni(PPh3)Cl2 was synthesized according to literature [11].
The NPO-type chiral ligands are synthesized as Scheme 1.
The condensation of bis(o-formylphenyl)phenylphosphane 1 [12] with R-phenylglycinol in CHCl3 was refluxed for
26 h in the presence of anhydrous Na2SO4 under a nitrogen atmosphere. After cooling down to room temperature, the
mixture was filtrated and the solvent was removed in vacuo to afford a light yellow solid 2 in 80% yield, featuring the
1
MS signals at 557.2 (M+1). The H NMR spectrum of 2 presented two doublets at d 8.61 and d 8.55 for the imino
protons. The 31P NMR spectrum exhibited a singlet at d À10.83.
A suspension of 2 and NaBH4 in absoluteethanol was refluxed with stirring for 2 days. The solutionwas then cooled to
room temperature and H2O was introduced to destroy the excess NaBH4. The mixture was extracted with CH2Cl2 and
washed successively with saturated NH4Cl solution and H2O. The organic fraction was dried over anhydrous Na2SO4,
followedbyfiltering, concentratingtoaffordthecorrespondingNPO-typeligand3asawhitesolidin60% yield, featuring
the MSsignalsat 561.3(M+1). Thedisappearanceof the peaksatd 8.61 andd 8.55 inthe1H NMRspectrum of3 indicated
that the two imino groups were reduced to the corresponding amino groups, and a broad peak (4H) at d 2.68 for the –NH–
and –OH protons was also observed. The 31P NMR spectrum exhibited a singlet at d À26.07.
To examine the catalytic activity of the Ni-based system, several catalytic systems, which was generated in situ
from the new NPO-type ligands 2, 3 and our earlier PNNP ligand 4 [13a] with Ni(PPh3)2Cl2 respectively, have been
investigated for the ATH of propiophenone. The typical results were listed in Table 1.
Table 1
Asymmetric transfer hydrogenation of propiophenone catalyzed by Ni-NPO system.a
* *
NH HN
O
OH
*
Ni(PPh3)2Cl2,Chiral Ligands
2-Propanol,KOH
Ph2P
PPh2
ligand 4: (S,S)-PNNP
Entry
Ligand
Time (h)
Temp. (8C)
Yieldb (%)
Eeb (%)
1
2
3
4
3
3
22
21
20
20
26
70
70
70
70
25
5
93
16
81
–
–
84
67.5
66
–
2
3
4c
5
a
Unless otherwise stated, the reaction was carried out with S/C/OHÀ = 100/1/6.
Yields and enantiomeric excesses were determined by GC analysis using a CP-Chirasil-Dex column.
S/C/OHÀ = 100/1/4.
b
c

Z.R. Dong et al. / Chinese Chemical Letters 23 (2012) 533–536
535
Table 2
Asymmetric transfer hydrogenation of various ketones catalyzed by Ni-NPO system.a
O
OH
O
Ni(PPh ) Cl / 3
3 2
2
R
2
R
2
g:
R
i
R
1
1
PrOH, KOH
Entry
Ketone
R1
Cat/OHÀ
Time (h)
Temp. (8C)
Yieldb (%)
eeb (%)
R2
1
2
3
4
5
6
7
8
H
CH3
CH2CH3
(CH2)2CH3
(CH2)3CH3
CH(CH3)2
CH3
1/4
1/6
1/8
1/8
1/6
1/6
1/6
1/4
20
21
56
21
56
48
53
24
70
70
70
70
70
70
70
70
81
93
66
84
60
80
76
75
60
10
H
H
51
H
90
H
72
m-CH3
p-CH3
98
CH3
96
g
>99
a
The reaction was carried out with S/C = 100.
b
Yields and enantiomeric excesses were determined by GC analysis using a CP-Chirasil-Dex column.
We found that the catalyst system generated from Ni(PPh3)Cl2 with ligand 3 efficiently catalyzed the reaction
(Table 1, entry 2) at 70 8C. The similar PNO ligand 2 was ineffective for the reduction of ketones, however, and the
enantioselectivity of chiral alcohol remarkably decreased (Table 1, entry 1). These results indicated that the structure
of the NH group was a crucial factor for ligand acceleration, and the NH functions in the ligand 3 and its structure are
responsible for the good enantioselectivity [13a]. In addition, our earlier ligand 4, which exhibited very excellent
catalytic results in ATH of aromatic ketones [13], was not so good together with Ni complex as with Ru or Ir
complexes (Table 1, entry 3). If the base was reduced, the ee value will slightly decrease (Table 1, entry 4). The
temperature was also important for the Ni-based catalytic system, the reaction will not proceed if the reaction
temperature is too low (Table 1, entry 5).
Encouraged by the results, the catalytic system Ni(PPh3)2Cl2/ligand 3 was then further investigated for the ATH of a
diverse range of ketones in 2-propanol (Table 2).
The catalytic system catalyzed asymmetric reduction of various ketones to the secondary alcohols with a satisfied
chemical yield and a moderate to good enantioselectivity, the best result is up to 84% ee. Generally, the enantioselectivity
was improved with increase of the bulkiness of the alkyl substituents (Table 2, entries 1–4), but n-butyrophonone is not a
good substrate for this catalytic system, the conversion of n-butyrophonone is only 51%. The introduction of a group to
the aromatic ring will make it more difficult to reduce the ketones (Table 2, entries 6 and 7). Notably, the catalyst can
promote the reduction of alkyl ketone smoothly (Table 2, entry 8), although the ee value is low.
In conclusion, we have disclosed a useful Ni-based catalyst system for the asymmetric transfer hydrogenation of
ketones, high conversions and good enantioselectivities were obtained. The further work will concentrate on
confirming the structure of the real catalyst and improving the enantioselectivity of the catalytic system.
Acknowledgments
The authors are grateful to the National Natural Science Foundation of China (No. 21173176) and the Natural
Science Foundation of Guangxi Province of China (No. 0991016) for the financial support of this work.
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20
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(q, 1H, J = 4 Hz), 3.64 (m, 1H), 3.71 (t, 2H, J = 9.75 Hz), 3.78 (q, 1H, J = 4 Hz), 3.93 (dd, 1H, J = 2.5 Hz and 12 Hz), 4.02 (d, 1H, J = 12.5 Hz),
6.91–6.95 (m, 2H), 7.18–7.37 (m, 21H); 13C NMR (100 MHz, CDCl3): d 144.2, 144.0, 140.5, 140.0, 136.6, 136.5, 136.0, 135.9, 135.8, 135.7,
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