Highly enantioselective reduction of ketones in air catalyzed by Rh-based macrocycles

Article abstract of DOI:10.1016/j.catcom.2018.10.030

The asymmetric transfer hydrogenation (ATH) of ketones catalyzed by Rh-based macrocycles proceeded smoothly in the presence of air with high catalytic activity and enantioselectivity. Even though the S/C ratio (substrate to catalyst molar ratio) was incre

Full text of DOI:10.1016/j.catcom.2018.10.030

Accepted Manuscript
Highly enantioselective reduction of ketones in air catalyzed by
Rh-based macrocycles
Wen-Jing Zhang, Sun-Hong Ruan, Wei-Yi Shen, Zhe Wang,
Dong-Li An, Yan-Yun Li, Jing-Xing Gao
PII:
DOI:
Reference:
S1566-7367(18)30561-2
doi:10.1016/j.catcom.2018.10.030
CATCOM 5541
To appear in:
Catalysis Communications
Received date:
Revised date:
Accepted date:
22 June 2018
27 October 2018
29 October 2018
Please cite this article as: Wen-Jing Zhang, Sun-Hong Ruan, Wei-Yi Shen, Zhe Wang,
Dong-Li An, Yan-Yun Li, Jing-Xing Gao , Highly enantioselective reduction of ketones
in air catalyzed by Rh-based macrocycles. Catcom (2018), doi:10.1016/
j.catcom.2018.10.030
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ACCEPTED MANUSCRIPT
Highly Enantioselective Reduction of Ketones in Air
Catalyzed by Rh-Based Macrocycles
Wen-Jing Zhang, Sun-Hong Ruan, Wei-Yi Shen, Zhe Wang,
Dong-Li An, Yan-Yun Li* yanyunli@xmu.edu.cn, Jing-Xing Gao
Department of Chemistry, College of Chemistry and Chemical
Engineering, and National Engineering Laboratory for Green Chemical
Production of Alcohols-Ethers-Esters, Xiamen University, Xiamen
361005, China
*Corresponding author.
Abstract
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The asymmetric transfer hydrogenation (ATH) of ketones catalyzed by
Rh-based macrocycles proceeded smoothly in the presence of air with
high catalytic activity and enantioselectivity. Even though the S/C ratio
(substrate to catalyst molar ratio) was increased up to 2000:1, the ATH of
ketone still afforded 92% isolated yield with 92% ee. Notably, the
Rh-based macrocycles could be successfully used to catalyze the ATH of
ketones without any need of inert atmosphere, which further highlighted
its advantage over those generally air-sensitive transition catalysts. The
addition of NH4I greatly improved both the catalytic activity and
enantioselectivity. On the basis of NMR evidence, we postulate that the
NH4I significantly enhanced the coordination between chiral macrocyclic
ligands and rhodium center.
Keywords
Asymmetric transfer hydrogenation; Ketones; Rhodium complex; Chiral
macrocyclic ligands; Air-stable chiral catalyst
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1. Introduction
Enantioselective reduction of prochiral ketones is a powerful method to
obtain chiral alcohols, which are important intermediate in
pharmaceuticals, agricultural chemicals, and other fine chemical
industries [1-19]. Among the enantioselective reduction of ketones,
asymmetric hydrogenation (AH) catalyzed by transition metal is an atom
economic process. However, it was generally conducted under
high-pressure hydrogen gas, which would cause safety problems.
Compared with AH, asymmetric transfer hydrogenation (ATH) uses
reducing agents, such as iPrOH, and HCOONa instead of hydrogen gas as
a source of hydrogen [20-22]. In the past few decades, ATH has been
developed as an alternative to AH processes because of its simple and
safe operation as well as easy availability of hydrogen sources.
Most ATH reactions require an inert atmosphere because those
transition metal catalysts are sensitive to the air and/or the moisture.
Therefore, the ATH conducting in air will deliver a convenient and green
procedure [23,24]. Herein, we demonstrated the ATH of ketones
catalyzed by Rh-based macrocycles catalysts, which could be
conveniently employed in air with high catalytic activity and
enantioselectivity.
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* *
* *
N
N
NH HN
PPh
PhP
PPh
PhP
N
N
NH HN
* *
* *
1
2
Figure 1. Chiral macrocyclic ligands 1 and 2.
2. Experimental
Typical procedure for ATH of ketones. Chiral macrocycles 1 and 2
were synthesized using the same procedure we previously reported [25].
Under air atmosphere, the complex RhH(CO)(PPh3)3 (9.2 mg, 0.01
mmol), (R, R, R’, R’)-2 (8.0 mg, 0.01 mmol), and NH4I (22.0 mg, 0.15
mmol) were placed in a tube equipped with a Teflon-coated magnetic
o
stirring bar. Then, iPrOH was added and the mixture was stirred at 65 C
for 30 min. Next, an appropriate amount of KOH/iPrOH solution was
added, and the mixture was continually stirred for another 10 min. Later,
ketone was introduced, and the mixture was stirred at the desired
temperature for the required reaction time. At the end of experiment, the
reaction products were determined by GC using a chiral CP-Chiralsil-Dex
CB column.
Synthesis of Rh-based macrocycle 3. The reaction was conducted in air.
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A solution of RhH(CO)(PPh3)3 (92.0 mg, 0.1 mmol), (S,S,S’,S’)-2 (80.0
mg, 0.1 mmol), and NH4I (218.0 mg, 1.5 mmol) in iPrOH (35 mL) was
o
stirred at 65 C for 30 min. The resulting brown solution was cooled to
room temperature. Removal of the solvent under reduced pressure
afforded a brown solid. The brown solid was dissolved in CH2Cl2 and
washed thrice with H2O. The organic layers were dried over anhydrous
Na2SO4. After filtration and removing the solvent in vacuum, the crude
product was recrystallized from CH2Cl2/n-hexane solution to give brown
solid, Rh-based macrocycle 3.
3. Results and Discussion
Using iPrOH as hydrogen source and solvent, we chose propiophenone
as the model substrate for ATH. With the catalyst formed in situ from
rhodium complexes and chiral macrocycles 1 or 2, the enantioselective
reduction of propiophenone was conducted in the presence of air (Table
1). Among the tested catalyst systems, the catalyst generated in situ from
RhH(CO)(PPh3)3 and
chiral macrocycle
2
afforded
good
enantioselectivity (70% ee, Table 1, entry 6). The activity difference
between macrocycle 1 and 2 was attributed to the promoting effect of NH
functions in the ligand 2, which was similar to our previous results [25].
Notably, the reaction proceeded in open air without any need of inert
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atmosphere, leading to more convenient operations.
Table 1 ATH of propiophenone catalyzed by Rh-based macrocycles in air [a]
O
OH
Rh complex / chiral macrocycle
*
KOH/iPrOH
Conv.
(%)[b]
Ee
[b]
Entry
Catalyst
Config.
(%)[b]
35
33
11
51
6
1
RhCl3·3H2O/(R, R, R’, R’)-1
RhCl3·3H2O/(R, R, R’, R’)-2
RhCl(PPh3)3/(R, R, R’, R’)-1
RhCl(PPh3)3/(R, R, R’, R’)-2
RhH(CO)(PPh3)3/(R, R, R’, R’)-1
RhH(CO)(PPh3)3/(R, R, R’, R’)-2
[Rh(COD)Cl]2/(R, R, R’, R’)-1
[Rh(COD)Cl]2/(R, R, R’, R’)-2
[Cp*RhCl2]2/(R, R, R’, R’)-1
[RhCl2Cp*]2/(R, R, R’, R’)-2
(C2H4)4Rh2Cl2/(R, R, R’, R’)-1
(C2H4)4Rh2Cl2/(R, R, R’, R’)-2
15
17
26
22
7
S
S
S
S
S
S
S
S
S
S
S
S
2
3
4
5
6
24
13
18
21
16
15
20
70
19
27
57
37
5
7
8
9
10
11
12
23
[a] Propiophenone (1 mmol) with ketone/Rh/macrocycles/KOH = 100:1:1:8 (molar
ratio), iPrOH (10 mL), 65 °C, 4 h. [b] Conversion and enantiomeric excesses (ee)
were determined by GC analysis using a chiral CP-Chiralsil-Dex CB column. The
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absolute configuration was determined by comparison of the retention times with the
literature data.
It has been demonstrated that the addition of salt could improve the
catalytic activity and enantioselectivity in some degree for some ATH
reaction [26]. Therefore, we investigated the effect of additives on ATH
of propiophenone with the catalyst formed in situ from RhH(CO)(PPh3)3
and chiral macrocycle 2 (Table 2). It was observed that both the catalytic
activity and enantioselectivity increased by the addition of salts. It was
very interesting to note that ammonium salts are more favorable to high
activity and enantioselectivity. For example, for the potassium salts and
ammonium salts with the same anions, higher activity and
enantioselectivity were obtained when ammonium salts were used as
additives (Table 2, entry 2 versus 6 and entry 3 versus 8). More
interestingly, for the ammonium salts with different anions as additives,
both yields and ees increased gradually from F-, Cl-, and Br- to I- (Table 2,
entries 5-8). When 10 eq. (related to catalyst) of NH4I were added, the
ATH of propiophenone catalyzed by Rh-based macrocycles proceeded
smoothly with excellent yield and enantioselectivity in 4 h (99% yield
and 95% ee, Table 2, entry 8).
Table 2 Effect of additive onATH of propiophenone catalyzed by
RhH(CO)(PPh3)3/(R, R, R’, R’)-2[a]
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Conv.
Entry
Additive
S/M/L/A/OH-
Ee (%)[b]
(%)[b]
1
2
3
4
5
6
7
8
9
None
100:1:1:0:8
24
37
39
46
71
82
99
99
67
70
72
72
79
86
91
93
95
79
KCl
100:1:1:10:8
100:1:1:10:8
100:1:1:10:18
100:1:1:10:18
100:1:1:10:18
100:1:1:10:18
100:1:1:10:18
100:1:1:10:18
KI
NH4Ac
NH4F
NH4Cl
NH4Br
NH4I
(CH3)4NBr
[a] Propiophenone (1 mmol), S/M/L/A/OH- = ketone/RhH(CO)(PPh3)3/(R,R,R’,
R’)-2/additive/KOH (molar ratio), iPrOH (10 mL), 65 °C, 4 h. [b] Conversion and ee
were determined by GC analysis using a chiral CP-Chiralsil-Dex CB column.
Encouraged by the results, we expanded the ATH catalyzed by
Rh-based macrocycles under air atmosphere to a wide range of ketones.
The catalyst systems prepared in situ from RhH(CO)(PPh3)3, chiral
macrocycle 2, and NH4I in iPrOH can efficiently catalyze
enantioselective reduction of ketones in the presence of base, giving the
corresponding secondary alcohols with high yields and excellent ees
(Table 3). It is worth noting that the reaction rates and enantioselectivities
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were mildly affected by the steric property of the substrates in alkyl
moiety. Acetophenone was reduced smoothly with 77% ee (Table 3, entry
1). While the methyl group was replaced with ethyl, propyl, n-butyl, and
isopropyl, high yield and up to 99% ee were obtained (Table 3, entries
2-5). Even the reduction of the more hindered cyclohexyl phenyl ketone
proceeded with 94% isolated yield and 99% ee (Table 3, entry 6). The
rate and enantioselectivity of the reduction were also influenced by
electronic properties of the substituents on the ketones. For example,
ketone with an electron-donating substituent such as the methyl group to
meta position was reduced smoothly with a moderate enantioselectivity
(73% ee, Table 3, entry 7). The introduction of an electron-withdrawing
substituent, as 3’-chloroacetophenone, tends to lower enantioselectivity
but higher yield (91% yield and 73% ee, Table 3, entry 8). Furthermore,
the heteroaromatic ketones, such as 1-(thiophen-2-yl)propan-1-one and
1-(thiophen-2-yl)butan-1-one,
were
also
reduced
with
high
enantioselectivity under mild conditions, furnishing 96-97% ee at 45 °C
in 24 h (Table 3, entries 9 and 10). With higher S/C ratios (substrate to
catalyst molar ratio), the present Rh-based macrocycle catalyst still
exhibited high enantioselectivity. For instance, the reduction of
cyclohexyl phenyl ketone with an S/C of 2000 afforded 92% isolated
yield with 92% ee (Table 3, entry 12). Compared with the rhodium
catalyst containing open-chain chiral diaminodiphosphine ligands [27],
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the Rh-based macrocycles exhibited high catalytic activity and
enantioselectivity. Notably, the reaction can be conducted without the
need for inert atmosphere, which further highlighted its advantage over
those air-sensitive transition catalysts.
Table 3 ATH of ketones catalyzed by RhH(CO)(PPh3)3/macrocycle 2[a]
O
OH
R'
RhH(CO)(PPh3)3/macrocycle 2
NH4I, KOH/iPrOH
R'
R
R
*
Temp. Time Isolated Yield
Ee
[b]
Entry
Substrate
Config.
(oC)
(h)
(%)
(%)[b]
O
1
65
4
91
77
96
93
96
99
99
S
S
O
O
2
65
65
65
65
65
3
4
4
6
92
94
94
90
94
3[c]
4[c]
5
R
R
S
nPr
O
nBu
O
iPr
O
6[c]
4
R
10

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O
S
S
7
8
65
65
8
3
92
91
73
73
O
Cl
O
S
S
S
9
45
45
42
22
76
76
97
96
O
10[d]
S
O
11[e]
80
80
46
24
87
92
91
92
S
S
iPr
O
12[f]
[a] Substrate (1 mmol), S/M/L/A/B = substrate: RhH(CO)(PPh3)3: (R, R, R’, R’)-2:
NH4I: KOH = 200:1:1:15:23 (molar ratio), iPrOH (10 mL). [b] Determined by GC
analysis using a chiral CP-Chiralsil-Dex CB column. The absolute configuration was
determined by comparison of the retention times with the literature data. [c] (S, S, S’,
S’)-2 was used. [d] S/M/L/A/B = 100:1:1:15:23. [e] S/M/L/A/B = 1000:1:1:15:40. [f]
S/M/L/A/B = 2000:1:1:15:40.
Given the promoting effect of the additives, the mechanism
experiments were conducted to understand the active effect role of NH4I
on the above-described ATH. The NMR experiments provided evidence
for the effect of NH4I during the generation of precatalyst in the catalytic
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reaction. As shown in Figure 2, the 31P NMR spectrum of
31
RhH(CO)(PPh3)3 exhibited signal at δ 29.94 ppm while the P NMR
spectrum of macrocycle 2 exhibited signal at δ -27.51 ppm in iPrOH.
When they were mixed together and stirred for 30 min at 65 °C, a new
signal at δ -5.95 ppm appeared. This signal was regarded as free
triphenylphosphine (PPh3), indicating that the dissociation process of
PPh3 from RhH(CO)(PPh3)3 happened. However, the interaction between
metal precursor and macrocycle 2 was sluggish at this time. With the
addition of NH4I, the mixture of RhH(CO)(PPh3)3, macrocycle 2, and
31
NH4I was stirred for 30 min at 65 °C. The P NMR spectrum showed
another new signal at δ 35.45 ppm, accompanying the disappearance of
signal at δ -27.51 ppm and the increase of signal at δ -5.94 ppm. It
demonstrated that the phosphino groups of macrocycle 2 were
coordinated to the rhodium atom. The NMR results showed that the
addition of NH4I enhanced the generation of coordinated Rh-macrocycle
species, which is the key active catalytic intermediate for the catalytic
cycle.
Figure 2. 31P NMR spectrum of Rh-based macrocycle catalyst system in iPrOH.
Generally, a well-defined complex would be convincing evidence to
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understand the catalytic mechanism. Therefore, we synthesized the
precatalyst Rh-based macrocycle 3. As outlined in Scheme 1, the
air-stable compound 3 could be conveniently obtained by simple one-pot
31
method. The P NMR spectrum of Rh-based macrocycle 3 in CDCl3
exhibited single signal at δ 36.54 ppm (Figure 3), which means that all
the phosphino groups of compound 3 coordinating to the rhodium center
are in the same chemical environment. Infrared transmittance spectra
could give valuable information for the functional groups of catalyst,
particularly for the carbonyl groups (CO). The IR spectra of
RhH(CO)(PPh3)3 and Rh-based macrocycle 3 (please see SI) showed that
RhH(CO)(PPh3)3 exhibits characteristic bands at 1920 cm-1 ν(CO), which is
consistent with the literature [9]. In the IR spectra of Rh-based
macrocycle 3, the characteristic bands of carbonyl group disappeared,
suggesting that in this compound, the CO group was replaced by the
macrocycle ligand. The HRMS spectrum of Rh-based macrocycle 3 is
presented in SI. Combined with the above results of the 31P NMR
spectrum and IR spectrum, it can be confirmed that the signal at
1045.21746 corresponds to [Rh-2]·NH4I, whereas the signal at 945.29787
corresponds to 2·NH4I. Therefore, the interaction between NH4I and
macrocycle 2 most likely occurred through hydrogen bond.
Scheme 1. Synthesis of precatalyst Rh-based macrocycle 3.
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Using Rh-based macrocycle complex 3 as catalyst, we investigated the
ATH of propiophenone in air. Without additional NH4I, the reaction
occurred smoothly with high catalytic activity and enantioselectivity
(ketone/3/KOH=100:1:18 (molar ratio), 99% yield, 96% ee, 65 °C, and 3
h). This result is as good as that obtained by in-situ catalyst (Table 2,
entry 8). On the basis of the spectroscopic evidence and catalytic
performance, the proposed promotion role of NH4I is favorable as, on the
+
one hand, ammonium ions (NH4 ) interacted with chiral macrocycle
through hydrogen bonds. This was confirmed from the previous catalytic
experiments (Table 2). For KI and NH4I, higher catalytic activity and
enantioselectivity were achieved when NH4I was used as the additives
(Table 2, entry 3 versus 8). This indicated that the interaction between
+
NH4 and chiral macrocyclic ligands could effectively promote the
catalytic activity and ees. On the other hand, I- was coordinated to the
rhodium center. This can also be further confirmed from the previous
catalytic experiments (Table 2, entries 5-8). With the increase in negative
ion coordination ability, the catalytic activity and enantioselectivity
increased correspondingly. Therefore, NH4I can significantly improve the
coordination between chiral macrocyclic ligands and rhodium center.
These results proved that the final Rh-based macrocyclic complex 3 is a
high catalytic active and enantioselective catalyst.
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Figure 3. 31P NMR spectrum of Rh-based macrocycle complex 3 in CDCl3.
4. Conclusions
In summary, the ATH of ketones catalyzed by Rh-based macrocycles
proceeded smoothly with highly catalytic activity and enantioselectivity.
The enantioselective reduction could be successfully conducted without
any need of inert atmosphere, which offers an easy, convenient, and
efficient method to achieve chiral alcohols with high enantioselectivity.
Addition of ammonium halide greatly improved the catalytic activity and
enantioselectivity. These findings may offer useful insight in the
development of novel chiral catalysts. Further investigations on the
reaction mechanism are currently ongoing in our laboratory.
Acknowledgments
We would like to thank the National Natural Science Foundation of
China (No. 21673190) for financial support.
Supplementarydata
AppendixA. Supplementarymaterial
Supplementary data to this article can be found online.
References
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[1] P. Dupau, in Organometallics as catalysts in the fine chemical industry, (Eds.: M.
Beller, H. U. Blaser), Springer-Verlag, Berlin, 2012.
[2] J. G. de Vries, C. J. Elsevier, The handbook of homogeneous hydrogenation,
Wiley-VCH, Weinheim, 2007.
[3] Y.-Y. Li, S.-L. Yu, W.-Y. Shen, J.-X. Gao, Iron-, cobalt-, and nickel-catalyzed
asymmetric transfer hydrogenation and asymmetric hydrogenation of ketones, Acc.
Chem. Res. 48 (2015) 2587–2598.
[4] R. H. Morris, Exploiting metal-ligand bifunctional reactions in the design of iron
asymmetric hydrogenation catalysts, Acc. Chem. Res. 48 (2015) 1494–1502.
[5] A. Bartoszewicz, N. Ahlsten, B. Martin-Matute, Enantioselective synthesis of
alcohols and amines by iridium-catalyzed hydrogenation, transfer hydrogenation, and
related processes, Chem.-Eur. J. 19 (2013) 7274–7302.
[6] H. U. Blaser, B. Pugin, F. Spindler, Asymmetric hydrogenation, Top. Organomet.
Chem. 42 (2012) 65–102.
[7] J. Magano, J. R. Dunetz, Large-scale carbonyl reductions in the pharmaceutical
industry, Org. Proc. Res. Dev. 16 (2012) 1156–1184.
[8] T. R. Ward, Artificial metalloenzymes based on the biotin-avidin technology:
Enantioselective catalysis and beyond, Acc. Chem. Res. 44 (2011) 47–57.
[9] R. Malacea, R. Poli, E. Manoury, Asymmetric hydrosilylation, transfer
hydrogenation and hydrogenation of ketones catalyzed by iridium complexes, Coord.
Chem. Rev. 254 (2010) 729–752.
[10] A. M. Palmer, A. Zanotti-Gerosa, Homogenous asymmetric hydrogenation:
Recent trends and industrial applications, Curr. Opin. Drug Discovery Dev. 13 (2010)
698−716.
[11] C. Wang, X. Wu, J. Xiao, Broader, greener, and more efficient: Recent advances
16

ACCEPTED MANUSCRIPT
in asymmetric transfer hydrogenation, Chem. Asian. J. 3 (2008) 1750–1770.
[12] L. A. Saudan, Hydrogenation processes in the synthesis of perfumery ingredients,
Acc. Chem. Res. 40 (2007) 1309–1319.
[13] T. Ikariya, A. J. Blacker, Asymmetric transfer hydrogenation of ketones with
bifunctional transition metal-based molecular catalysts, Acc. Chem. Res. 40 (2007)
1300–1308.
[14] F. D. Klingler, Asymmetric hydrogenation of prochiral amino ketones to amino
alcohols for pharmaceutical use, Acc. Chem. Res. 40 (2007) 1367–1376.
[15] W. C. Zhang, Y. X. Chi, X. M. Zhang, Developing chiral ligands for asymmetric
hydrogenation, Acc. Chem. Res. 40 (2007) 1278–1290.
[16] S. Gladiali, E. Alberico, Asymmetric transfer hydrogenation: Chiral ligands and
applications, Chem. Soc. Rev. 35 (2006) 226–236.
[17] T. Ikariya, K. Murata, R. Noyori, Bifunctional transition metal-based molecular
catalysts for asymmetric syntheses, Org. Biomol. Chem. 4 (2006) 393–406.
[18] R. Noyori, Asymmetric catalysis: Science and opportunities, Adv. Synth. Catal.
345 (2003) 15–32.
[19] R. Noyori, T. Ohkuma, Asymmetric catalysis by architectural and functional
molecular engineering: Practical chemo- and stereoselective hydrogenation of ketones,
Angew. Chem. Int. Ed. 40 (2001) 40–73.
[20] A. Matsunami, Y. Kayaki, Upgrading and expanding the scope of homogeneous
transfer hydrogenation, Tetrahedron Letters 59 (2018) 504–513.
[21] D. Wang, D. Astruc, The golden age of transfer hydrogenation, Chem. Rev. 115
(2015) 6621–6686.
[22]M. J. Palmer, M. Wills, Asymmetric transfer hydrogenation of C=O and C=N
bonds, Tetrahedron: Asymmetry 10 (1999) 2045–2061.
17

ACCEPTED MANUSCRIPT
[23]J.-S. Chen, Y.-Y. Li, Z.-R. Dong, B.-Z. Li, J.-X. Gao, Asymmetric transfer
hydrogenation of aromatic ketones catalyzed by the iridium hydride complex under
ambient conditions, Tetrahedron Letters 45 (2004) 8415–8418.
[24] O. Soltani, M. A. Ariger, E. M. Carreira, Transfer hydrogenation in water:
enantioselective, catalytic reduction of (E)-β,β-disubstituted nitroalkenes, Org. Lett.
11 (2009) 4196–4198.
[25] S.-L. Yu, W.-Y. Shen, Y.-Y. Li, Z.-R. Dong, Y.-Q. Xu, Q. Li, J.-N. Zhang, J.-X.
Gao, Iron-catalyzed highly enantioselective reduction of aromatic ketones with chiral
P2N4-type macrocycles, Adv. Synth. Catal. 354 (2012) 818–822.
[26] L. Zeng, F. Wu, Y.-Y. Li, Z.-R. Dong, J.-X. Gao, Synthesis and characterization
of novel chiral bidentate P,Ncontaining ligands and ruthenium(II) complex. The
application in asymmetric transfer hydrogenation of ketones, J. Organomet. Chem.
762 (2014) 34–39.
[27] J.-X. Gao, X.-D. Yi, P.-P. Xu, C.-L. Tang, H.-L. Wan, T. Ikariya, New chiral
cationic rhodium-aminophosphine complexes for asymmetric transfer hydrogenation
of aromatic ketones, J. Organomet. Chem. 592 (1999) 290–295.
Highlights
 Highly enantioselective asymmetric transfer hydrogenation of
ketones (up to 99% ee).
 The enantioselective reductions proceed smoothly without any
need of inert atmosphere.
 Addition of NH4I greatly improved the catalytic activity and
enantioselectivity.
18

Figure 1

Figure 2

Figure 3