Imidazolium ion tethered TsDPENs as efficient ligands for Iridium catalyzed asymmetric transfer hydrogenation of α-keto phosphonates in water

Article abstract of DOI:10.1016/j.jorganchem.2016.03.010

For the first time, an efficient method has been developed by the use of imidazolium ion tethered TsDPENs as efficient ligands for Iridium-catalyzed asymmetric transfer hydrogenation (ATH) of α-ketophosphonates in water. The reaction provided the desired

Full text of DOI:10.1016/j.jorganchem.2016.03.010

Journal of Organometallic Chemistry 810 (2016) 12e14
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Communication
Imidazolium ion tethered TsDPENs as efficient ligands for Iridium
catalyzed asymmetric transfer hydrogenation of
in water
a-keto phosphonates
,
*
Mengxia Sun a, Joann Campbell a, Guowei Kang a, Huigang Wang b, Bukuo Ni a
a Department of Chemistry, Texas A&M University-Commerce, Commerce, TX 75429-3011, USA
b Department of Chemistry, Zhejiang Sci-Tech University, 310018, China
a r t i c l e i n f o
a b s t r a c t
Article history:
For the first time, an efficient method has been developed by the use of imidazolium ion tethered
TsDPENs as efficient ligands for Iridium-catalyzed asymmetric transfer hydrogenation (ATH) of -keto-
phosphonates in water. The reaction provided the desired product -hydroxyphosphonates in moderate
to good yields (44e78%) and good to excellent enantioselectivities (up to >99% ee) under mild reaction
conditions without adding any surfactants. The enantiomeric excess was determined by 13P NMR by
using (ꢀ)-cinchonidine as chiral solvating agent, which is a much more convenient method than chiral
HPLC.
Received 15 February 2016
Received in revised form
7 March 2016
Accepted 8 March 2016
Available online 11 March 2016
a
a
Keywords:
Asymmetric transfer hydrogenation
Iridium
© 2016 Elsevier B.V. All rights reserved.
a
-Ketophosphonates
Water
1. Introduction
Recently, asymmetric transfer hydrogenation (ATH) of ketones
has proven to be one of the most versatile and powerful approaches
Optically active
a
-hydroxy phosphonates are an important class
for the synthesis of chiral hydroxyl compounds due to its safety and
easy operation [8]. Over the past two decades, the ATH of ketones
with catalysts of transition metals Ru, Rh, and Ir complexes of chiral
ligand TsDPEN (p-toluenesulfonyldiphenylethylenediamine) and
their modifications has been studied extensively and achieved
great success [8]. Surprisingly, little progress has been achieved for
of biologically active compounds, which can be further used as
versatile chiral building blocks for a variety of key structural ele-
ments in pharmaceuticals and natural products [1]. Thus, it is not
surprising that the development of efficient asymmetric catalytic
methods for the synthesis of these invaluable chiral
a-hydroxy
phosphonates have received much attention in recent years [2,3].
Among the numerous methods developed, the asymmetric
hydrophosphonylation of carbonyl compounds with dia-
lkylphosphite is well established [4]. Another efficient and conve-
ATH of
of -keto phosphonates in the presence of some transition metal
complexes [10]. So far, only one example has been reported by
Johnson and co-worker, in which the Ru-catalyzed ATH of -keto
phosphonates was described by the use of HCO2H/Et3N as a hydride
source and DMSO as a solvent, giving the desired products -hy-
a-keto phosphonates [9]. This is probably due to the lability
a
a
nient route to chiral
a
-hydroxy phosphonates is the asymmetric
-keto phosphonates, such as asym-
reduction of easily available
a
a
metric reduction with borane using chiral auxiliaries [5] or with
catecholborane in the presence of chiral oxazaborolydine catalysts
[6] and the asymmetric hydrogenation [7]; however, most of these
methods require relatively high catalyst loadings and/or result in
low enantioselectivity. Therefore, it is still highly desirable to
droxy phosphonates with high enantioselectivity [9]. Recently, ATH
performed in water has received growing interest due to its po-
tential benefits in terms of being economic, environmentally
benign and hazardless in handling compared to organic solvents.
Unfortunately, to the best of our knowledge, no ATH of
a-keto
develop an efficient catalytic system for the synthesis of chiral
hydroxy phosphonates with high enantioselectivity.
a
-
phosphonates performed in water solvent has been reported. One
aspect of our research is aimed at the development of effective and
water-compatible catalysts for asymmetric chemical trans-
formations in aqueous media [11]. We recently reported imidazo-
lium ion tethered TsDPENs as efficient water-compatible ligands for
* Corresponding author.
E-mail address: bukuo.ni@tamuc.edu (B. Ni).
http://dx.doi.org/10.1016/j.jorganchem.2016.03.010
0022-328X/© 2016 Elsevier B.V. All rights reserved.

M. Sun et al. / Journal of Organometallic Chemistry 810 (2016) 12e14
13
rhodium catalyzed ATH of aromatic ketones in water with high
enantioselectivity [12]. This result inspired us to extend the method
to a-keto phosphonates in pure water. Herein, we wish to report
enantioselectivity. In order to further optimize the reaction con-
ditions, the imidazolium tether ligands L2-L3 were examined (en-
tries 4e5). We found that both L2 and L3 showed comparable
reactivity; however, the ligand L2 gave slightly higher enantiose-
lectivity with 77% ee. These results indicate that ligand L2 with the
introduction of imidazolium ion into TsDPEN, greatly increased the
reactivity and slightly enhanced the enantioselectivity in compar-
ison with the original ligand TsDPEN L1. In the next set of experi-
ments, temperature and reaction time effects were studied. When
the reaction was carried out at 4 ꢁC, the same enantioselectivity and
chemical yield were obtained (entry 6). Comparable chemical
yields were observed, although the reaction time was prolonged to
8 and 16 h, respectively (entries 7e8). The influence of hydride
donor HCO2Na loading was also investigated. Interestingly, when
the amount of HCO2Na was reduced to 2.0 equiv., the enantiose-
lectivity increased to 84% ee (entry 9). Increasing the amount of
hydride donor HCO2Na to 8 equiv. was also not beneficial to the
selectivity and chemical yield (entry 10). The absolute stereo-
our preliminary results.
2. Results and discussion
The imidazolium ion tethered TsDPENs L2-L3 (Fig. 1) were
synthesized according to the procedures that we reported previ-
ously by our research group [12].
To examine the performance of ligands L2 and L3, the ATH of
diethyl benzoylphosphonate 1a was selected as a model reaction
for screening the metal catalysts and the amount of hydride donor
HCO2Na and the results are summarized in Table 1. As shown in
Table 1, when the reaction was performed in water with 1 mol% of
[IrCl2Cp*]2 as catalyst, 2 mol% of original TsDPEN L1 as ligand, and
5 equiv. of HCO2Na as hydride donor, the reaction proceeded
smoothly at room temperature for 24 h affording the desired
product diethyl (hydroxyl(phenyl)methylphosphonate 2a in 58%
yield with good enantioselectivity (71% ee) (entry 1); however, the
metal salt [RhCl2Cp*]2 with the ligand L1 was used as catalyst, the
reaction suffered from reduced enantioselectivity with only 7% ee
and lower reactivity (entry 2). When [RuCl2(p-cymene)]2 with L1
was used as catalyst, the reaction also resulted in lower reactivity
and enantioselectivity in comparison to the catalyst [IrCl2Cp*]2
(entry 3). These results demonstrate that the metal salt [IrCl2Cp*]2
showed the best performance in terms of chemical yield and
chemistry of product 2a was determined to be the (R) configuration
25
([
a]
¼ þ23.7 (c ¼ 0.9, CHCl3) at 84% ee), in comparison with the
D
optical rotation data that reported by literature [7b].
On the basis of the results summarized in Table 1, the reaction
conditions of entry 9 (Table 1) were chosen as standard reaction
conditions to study the substrate scope of a-keto phosphonates for
theATHandtheresultsaresummarizedinTable 2. Fromtheseresults,
it is obvious that the ester functional group had an important influ-
ence on the enantioselectivity. When the series of dialkyl benzoyl-
phosphonates, dimethyl ester 2b, diethyl ester 2a, and diisopropyl
ester 2c, were examined under standard reaction conditions, the
results indicated that the introduction of a more bulkier diisopropyl
ester 2c resulted in an appreciably higher reactivity and selectivity
than diethyl ester 1b and dimethyl ester 1a (entry 3 vs entries 1e2).
Next, a variety of diisopropyl
jected to ATH reactions and afforded the corresponding diisopropyl
-hydroxyphosphonates3d-linmoderatetogoodyieldswithhighto
a-keto phosphonates 2d-l were sub-
a
excellent enantioselectivities (entries 4e12). The nature of the sub-
stitutes on aromatic ring slightly influenced the reactivity and
enantioselectivity (entries 4e10). For diisopropyl benzoylphospho-
nates 1d-g bearing electron-donating and electron-withdrawing
groups at 4-substituted positions gave the corresponding products
Fig. 1. TsDPEN and imidazolium ion tethered TsDPENs.
Table 1
Optimization of reaction conditions for the ATH of diethyl benzoylphosphonate 1aa.
Entry
Catalyst
Ligand
HCO2Na (equiv.)
T (h)
Yield (%)b
ee (%)c
1
2
3
4
[IrCl2Cp*]2
L1
L1
L1
L2
L3
L2
L2
L2
L2
L2
5
5
5
5
5
5
5
5
2
8
24
24
24
4
4
4
8
16
4
58
43
39
70
72
70
69
67
70
69
71
7
[RhCl2Cp*]2
[RuCl2(p- cymene)]2
[IrCl2Cp*]2
[IrCl2Cp*]2
[IrCl2Cp*]2
[IrCl2Cp*]2
[IrCl2Cp*]2
[IrCl2Cp*]2
[IrCl2Cp*]2
57
77
71
77
78
78
84
76
5
6d
7
8
9
10
4
a
ATH was carried out with 0.5 mmol of substrate and 1.0 mol% of [IrCl2Cp*]2 and 2.0 mol% of ligands in 1 mL water.
Isolated yields.
b
c
The enantiomeric excesses were determined by13P NMR by using (ꢀ)-cinchonicdine as chiral solvating agent [13].
d
The reaction was performed at 4 ꢁC.

14
M. Sun et al. / Journal of Organometallic Chemistry 810 (2016) 12e14
Table 2
Na2SO4. Removal of the organic solvent gave the crude product,
which was purified by flash chromatography column on silica gel to
afford the product 2.
ATH of a
-keto phosphonatesa.
Acknowledgment
This research was supported National Science Foundation (CHE-
1213287), McNair Scholars Program (P217A090190-12), and the
Robert A. Welch Foundation (T-0014). The authors are also grateful
for the collaborative support from the National Natural Science
Foundation of China (21271155 and 21473161). We gratefully
acknowledge Prof. Allan D. Headley for his fruitful discussion for
this research work.
Entry Substrate R1
R2
T (h) Product Yield (%)b ee (%)c
1
2
3
4
5
6
7
8
1b
1a
1c
1d
1e
1f
1g
1h
1i
Ph
Ph
Ph
4-MeC6H4
Me
Et
i-Pr
i-Pr
6
4
4
6
6
4
6
4
4
4
6
8
2b
2a
2c
2d
2e
2f
2g
2h
2i
44
70
76
67
58
56
62
76
78
75
58
56
69
84
87
94
88
89
92
93
91
4-MeOC6H4 i-Pr
Appendix A. Supplementary data
4-FC6H4
4-ClC6H4
4-BrC6H4
2-BrC6H4
3-BrC6H4
PhCH2
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.jorganchem.2016.03.010.
9
10
11
12
1j
1k
1l
2j
2k
2l
84
>99
>99
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PhCH2CH2
a
ATH was carried out with 0.5 mmol of substrate, 1.0 mol% of [IrCl2Cp*]2, 2.0 mol
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3. Conclusion
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broad range of a-keto phosphonates in water, providing the desired
products 2a-l in moderate to good chemical yields with good to
excellent enantioselectivities (up to >99% ee). The reaction can be
conducted under mild conditions with low catalyst loading, and the
hydride donor loading can also be lowered to 2.0 equiv. of HCO2Na
without affecting the reactivity and enantioselectivity. Further
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4.1. General experimental procedure for asymmetric transfer
hydrogenation of a-keto phosphonates in water
The solution of [IrCl2Cp*]2 (1 mol%) and chiral ligand L2 (2 mol%)
in water (1 mL) was stirred at room temperature for 30 min. Sub-
sequently, dialkyl benzoylphosphonate 1 (0.4 mmol) and sodium
formate (0.8 mmol) was added to the reaction mixture. After re-
action mixture was stirred for the desired time, dichloromethane
was added to extract the product. The organic phase dried over