Synthesis, Crystal Structure of Chiral Ferrocenyl Amino Alcohols, and Its Use for Asymmetric Transfer Hydrogenation

Article abstract of DOI:10.1134/S1070328418110106

Abstract: Two chiral ferrocenyl amino alcohols (IIIa and IIIb) have been synthesized for the iridium catalyzed asymmetric transfer hydrogenation of aromatic ketones. The structures of two chiral ferrocenyl amino alcohols have been determined by single crystal X-ray diffraction (CIF files CCDC nos. 1056737 (IIIa) and 1056734 (IIIb)). The results show that the activity and enantioselectivity of the chiral iridium catalyst are very sensitive to the substrate structure. Ir(I)-catalyzed asymmetric transfer hydrogenation of acetophenone resulted in moderate to good yield and lower enantioselectivity; asymmetric transfer hydrogenation of proopiophenone and 2-benzoylpyridine resulted in lower yield and lower enantioselectivity; as for 4-benzoylpyridine, good results have been achieved.

Full text of DOI:10.1134/S1070328418110106

ISSN 1070-3284, Russian Journal of Coordination Chemistry, 2018, Vol. 44, No. 11, pp. 688–692. © Pleiades Publishing, Ltd., 2018.
Synthesis, Crystal Structure of Chiral Ferrocenyl Amino Alcohols,
1
and Its Use for Asymmetric Transfer Hydrogenation
a,
a
a
Y. M. Zhang *, P. Q. Li , and P. Liu
a
College of Sciences, Hebei University of Science & Technology, Shijiazhuang, 050018 P.R. China
e-mail: ailym@126.com
Received December 1, 2017
*
Abstract—Two chiral ferrocenyl amino alcohols (IIIa and IIIb) have been synthesized for the iridium cata-
lyzed asymmetric transfer hydrogenation of aromatic ketones. The structures of two chiral ferrocenyl amino
alcohols have been determined by single crystal X-ray diffraction (CIF files CCDC nos. 1056737 (IIIa) and
1
056734 (IIIb)). The results show that the activity and enantioselectivity of the chiral iridium catalyst are very
sensitive to the substrate structure. Ir(I)-catalyzed asymmetric transfer hydrogenation of acetophenone
resulted in moderate to good yield and lower enantioselectivity; asymmetric transfer hydrogenation of proop-
iophenone and 2-benzoylpyridine resulted in lower yield and lower enantioselectivity; as for 4-benzoylpyri-
dine, good results have been achieved.
Keywords: synthesis, crystal structure, chiral ferrocenyl amino alcohol, asymmetric transfer hydrogenation,
chiral iridium complex
DOI: 10.1134/S1070328418110106
INTRODUCTION
nation of prochiral ketones to optically active alcohols
using chiral catalysts has become one of the most
attractive research fields, because it has those advan-
tages, such as high chemical yields, experimental sim-
plicity, and no necessary requirment for the use of
molecule hydrogen and high-pressure equipment [6].
We are interested in the preparation of this kind of
optically active catalysts and in using them to achieve
enantioselective reduction. In this paper, we are
Enantiomerically pure ferrocenyl amino alcohol
compounds have been found for widespread use as
chiral ligands in several reactions [1–4]. Considerable
efforts have been focused on the design of ferrocenyl
amino alcohols with potential applications in drug
delivery and biomedical engineering. These com-
pounds are very effective catalysts for a wide range of
reactions because of the ligands of nitrogen atom and
oxygen atom with many metals [5]. In addition, the reporting the synthetic and structural investigation of
steric effect of the specific microenvironment created two chiral ferrocenyl amino alcohol compounds
by the ferrocene skeletone structure could modulate (S,R)-IIIa and (S,R)-IIIb (Scheme 1), applied in the
the catalytic behaviors of the chiral ferrocenyl amino iridium catalyzed asymmetric transfer hydrogenation
alcohols. In particular, asymmetric transfer hydroge- of acetophenone.
H C H R
H
3
O
C
R
CH OH
2
CH3
N
H
(1) 4 Å mol. sieve benzene
(2) NaBH4, EtOH
+
Fe
Fe
H N
2
CH OH
2
I
II
III
IIIa: R =
IIIb: R =
Scheme 1.
1
The article is published in the original.
688

SYNTHESIS, CRYSTAL STRUCTURE
689
EXPERIMENTAL
20
(
S,R)-IIIb: 65%, m.p. = 65–67°C; [α] = –23.6.
D
1
Materials and methods. Reagents and solutions. (c 0.88, EtOH); H NMR (CDCl ; δ, ppm): 0.92–
3
Organic solvents were analytical pure grade and 0.94 (d., J = 7.2 Hz, 3H, CH ), 0.96–0.98 (d., J =
3
obtained from Sinopharm Chemical Reagent Co. Ltd.
Benzene was dried by Na and distilled under vacuum.
S)-amino alcohols IIa, IIb were obtained from
7
.2 Hz, 3H, CH ), 1.42–1.44 (d., J = 7.1 Hz, 3H,
3
CH ), 1.63 (b., 2H, NH, OH), 1.75–1.82 (m., 1H,
3
(
(
CH )2CH), 2.50–2.55 (m., 1H, CHCH OH), 3.35–
3
2
Daruichemistry company. Acetylferrene I was pre-
pared by literature methods [7]. All reactions were car-
ried out under argon and monitored by thin-layer
chromatograph (TLC). Melting point (uncorrected)
was measured with a XT4 melting point apparatus.
3
.63 (m., 2H, CH OH), 3.53–3.63 (q., J = 6.4 Hz,
2
1
H, FcCH), 4.12–4.20 (m., 9H, C H , C H ); IR
5
5
5
4
–1
(
(
KBr; ν, cm ): 3372 (OH, NH ); 1103.9 and 996.6
2
the unsubstituted cyclopentadienyl ring), 1022.0–
1
1147.6 (single substituted cyclopentadienyl), 486.1 and
H NMR spectra were recorded on a Mercuryplus
5
09.9 (ν
).
Fe–C
instrument at 500 Hz, using CDCl as solvent and
3
TMS as the internal standard. IR spectra were deter-
mined on a Nicolet 6700 spectrophotometer using
For C H NOFe
17 25
KBr pellets. Optical rotations were measured on a Anal. calcd., % C, 64.77
WZZ-2s polarimeter.
H, 7.99
H, 7.83
N, 4.44
N, 4.28
Found, %
C, 64.70
Synthesis of compound IIIа. Acetylferrene (I)
1.18 g, 5.0 mmol) and L-phenylalaninol (IIa) (0.83 g,
.5 mmol) were dissolved in 20 mL benzene and added
(
5
Slow evaporation of the compounds IIIa and IIIb
in petroleum ether and ethylacetate yielded single
crystals suitable for X-ray analysis.
drop wise glacial acetic acid (0.25 mL), and the mix-
ture was heated under reflux. After the reaction was
completed, the resulting solution was washed with sat-
urated aqueous sodium chloride (2 × 10 mL), dried
over anhydrous sodium sulfate. Then the solvent was
removed under reduced pressure. The residue was
resolved in ethanol (15 mL) and the mixture was
X-ray structure determination. Single-crystal X-ray
diffraction data for III were collected on a Bruker
Apex II CCD diffractometer with MoK radiation
α
(
1
λ = 0.71073 Å) by using φ/ω scan technique at
13(2) K (IIIa) and 298(2) K (IIIb). The structure was
solved by direct methods with SHELXS-97 [8]. The
hydrogen atoms were assigned with common isotropic
displacement factors and included in the final refine-
ment by use of geometrical restrains. A full-matrix
cooled to 0°C. To the mixture was added NaBH
0.19 g, 5.0 mmol) in portions, then stirred at room
4
(
temperature until the reaction was over (checked by
TLC). The reaction was quenched by addition of
water, and the mixture was extracted with benzene.
The combined extracts were dried over anhydrous
sodium sulfate. After removal of the solvent by distil-
lation, the residue was purified by column chromatog-
raphy (silica gel, eluent: petroleum ether–AcOEt
2
least-squares refinement on F was carried out
using SHELXL-97 [9]. The empirical absorption cor-
rections were applied by the SADABS program. The
H-atoms of carbon were assigned with common iso-
tropic displacement factors and included in the final
refinement by the use of geometrical restraints. The
crystallographic data for complex III are listed in
Table 1. Hydrogen-bonding geometry are listed in
Table 2. The molecular structure and packing arrange-
ment in the unit cell of the title compounds are shown
in Figs. 1 and 2, respectively.
(
v : v = 3 : 1) to give yellow crystals IIIa.
2
0
(
S,R)-IIIa: 70.1%, m.p. = 100–102°C; [α]
=
D
1
‒
1
24.8 (c 0.83, EtOH); H NMR (CDCl ; δ, ppm):
3
.25–1.27 (d., J = 6.8 Hz, 3H, CH ), 1.57 (b., 1H,
3
OH), 2.78–2.80 (d., J = 6.8 Hz, 2H PhCH ), 3.09–
2
The atomic coordinates and other parameters of
the complexes have been deposited with the Cam-
bridge Crystallographic Data Center (CCDC
nos. 1056737 (IIIa) and 1056734 (IIIb); deposit@
ccdc.cam.ac.uk).
3
.12 (m., 1H, CHCH OH), 3.29–3.33 (m., 1H,
2
CHHOH), 3.56–3.60 (m., 2H, CHHOH, FcCH),
.03 (s., 5H, C H ), 4.06–4.11 (m., 4H, C H ), 4.20
4
(
5
5
5
4
s, 1HNH), 7.21–7.34 (m., 5H, ArH); IR (KBr; ν,
–
1
cm ): 3314, 3171 (OH, NH ); 1100.9 and 997.6 (the
2
The catalyst was generated in situ by refluxing
unsubstituted cyclopentadienyl ring), 1022.0–1147.6
ligands IIIa and IIIb (1.0 mmol %) with [Ir(COD)Cl]
(
single substituted cyclopentadienyl), 486.1, 509.9
2
(
4
1.0 mmol %) in 2-propanol at 50°С under argon for
ν(Fe–C); 748, 698 (single substituted phenyl).
h. After being cooled down to room temperature,
acetophenone (2.0 mmol) was added, followed by
KOH (1.5 mg, 0.03 mmol) under argon. The transfer
hydrogenation was conducted at desired temperature
under argon for a given time. The resulting solution
was purified by flash chromatography on a silica gel
For C H NOFe
21
25
Anal. calcd., % C, 69.43
Found, % C, 69.12
H, 6.94
H, 6.99
N, 3.86
N, 3.79
Compound IIIb was similarly prepared from L-leu- column eluted by petroleum ether/ethyl acetate (9/1)
cinol (IIb). and the product was analyzed by HPLC.
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 44 No. 11 2018

6
90
Table 1. Crystallographic data and structure refinement summary of IIIa and IIIb
Value
ZHANG et al.
Parameter
IIIa
IIIb
Formula weight
Temperature, K
363.27
113(2)
333.25
298(2)
Wavelength, MoK , Å
0.71073
0.71073
α
Crystal system
Space group
a, Å
b, Å
c, Å
β, deg
Volume, Å3
Z
Orthorhombic
P2 2 2
5.6467(11)
10.323(2)
29.563(6)
90
Monoclinic
P21
1
1 1
10.4849(9)
7.3600(5)
11.9561(11)
111.735(2)
857.04(12)
1723.2(6)
4
2
Crystal size
ρcalcd, mg/m–3
0.20 × 0.18 × 0.12
0.40 × 0.15 × 0.13
1.291
1.400
Absorption coefficient, mm–1
0.882
0.884
F(000)
768
14069/3953 (0.0338)
99.2
356
Reflections collected/unique (Rint)
Completeness to θ = 27.88° (25.01°), %
Data/restraints/parameters
Limiting indices
4279/2745 (0.0481)
98.8
3953/32/240
–6 ≤ h ≤ 7,
2745/1/194
–7 ≤ h ≤ 12,
–7 ≤ k ≤ 8,
–14 ≤ l ≤ 12
1.069
–
12 ≤ k ≤ 13,
38 ≤ l ≤ 37
.983
R = 0.0271, wR = 0.0570
–
Goodness of fit on F2
Final R indices (I > 2σ(I))
R indices (all data)
0
R = 0.0688, wR = 0.1578
1
2
1
2
R = 0.0332, wR = 0.0595
R = 0.0883, wR = 0.1727
1
1
2
2
Absolute structure parameter
Largest diff. peak and hole, e Å–3
–0.008(12)
.293 and –0.388
–0.03(4)
0.547 and –0.423
0
Table 2. Geometric parameters of hydrogen bond for IIIa and IIIb *
Distance, Å
D–H···A
Angle DHA, deg
D–H
H…A
D…A
IIIa
2.082(10)
IIIb
1.85(11)
1.92(10)
O(1)–H(1A)···N(1)
0.828(10)
0.82(11)
2.909(2)
179(2)
O(1)–H(1)···O(2)
2.672(8)
2.764(8)
176(10)
173(9)
O(2)–H(2C)···O(1)#1
O(2)–H(2D)···N(1)#2
0.85(10)
0.85(10)
2.10(10)
2.949(8)
174(9)
*
Symmetry transformations used to generate equivalent atoms: x – 1, y, z (IIIa); #1 –x, y + 1/2, –z + 1; #2 x, y + 1, z (IIIb).
RESULTS AND DISCUSSION
pounds IIIa and IIIb were characterized by X-ray
diffraction, their molecular structure is shown in
The title compounds, chiral ferrocenyl amino Fig. 1. Single crystal X-ray diffraction analysis
alcohols IIIa and IIIb were prepared from acetylfer- reveals that the configuration of chiral center
rene I and (S)-amino alcohols IIa and IIb. Com- formed in the reductive amination of acetylferrene
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY
Vol. 44
No. 11
2018

SYNTHESIS, CRYSTAL STRUCTURE
691
C(17)
C(15)
C(3)
C(1)
C(2)
C(4)
C(18)
C(17)
C(1)
O(1)
C(19)
C(5)
C(14)
C(3)
C(2)
C(4)
C(16)
C(15)
C(7)
C(14)
Fe(1)
C(8)
C(6)
C(5)
C(16)
N(1)
N(1)
C(13)
O(1)
C(10)
C(11)
C(20)
C(13)
C(21)
Fe(1)
C(9)
C(7)
C(8)
C(12)
C(6)
C(9)
O(2)
C(12)
IIIa
C(11)
C(10)
IIIb
Fig. 1. Molecule IIIa and IIIb with an atom numbering.
was assigned to be (R) (Fig. 1). The crystal structure by three pairs of the O(2)–H(2D)···N(1), O(2)–
of IIIa is associated by strong intermolecular hydro- H(2C)···O(1), O(1)–H(1)···O(2) hydrogen bonds
gen bonds O(1)–H(1A)···N(1). In the crystal pack- which involve axially coordinated water molecule
ing the molecules of IIIb are connected into a chain (Table 2).
O
OH
[Ir(COD)Cl]2/L*, iso-PrOH
KOH, reflux
Ph
R
Ph
R
N
a: R = CH b: R = CHCH c:
d:
N
3
2
3
Scheme 2.
The chiral ferrocenyl amino alcohols III were
applied to Ir-catalyzed asymmetric transfer hydroge-
nation of acetophenone using 2-propanol as a source
of hydrogen. The results of asymmetric transfer hydro-
genation of acetophenone by Ir(I)/IIIa and Ir(I)/IIIb
are listed in Table 3. The results show that Ir(I)-cata-
lyzed asymmetric transfer hydrogenation of acetophe-
none resulted in moderate yield and enantioselectivity
b
c
a
(
Table 3), preferring the S enantiomer. The absolute
configuration was assigned by comparing the literature
IIIa
[
10]. The catalytic activity of complex IIIa is better
than complex IIIb. We speculated that the difference
of the product’s enantiomer may be related to the ste-
ric effect created by the substituent rigid benzene ring
of the ferrocenyl amino alcohols ligands.
Fe
N
H
O
c
a
b
C
Asymmetric transfer hydrogenation of prochiral
ketones to provide chiral alcohols has received a great
deal of attention in the last decade or so. The chiral
ferrocenyl amino alcohols (IIIa and IIIb) were applied
to Ir-catalyzed asymmetric transfer hydrogenation of
various aromatic ketones (acetophenone, proopio-
phenone, 2-benzoylpridine, 4-benzoylpridine) using
2-propanol as a source of hydrogen.
IIIb
The results of asymmetric transfer hydrogenation
of ketones by Ir(I)/IIIa and Ir(I)/IIIb are listed in
Fig. 2. Three-dimensional molecular-packing diagram of
compounds IIIa and IIIb.
Table 3. It can be seen from Table 1 that the results
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 44 No. 11 2018

6
92
ZHANG et al.
Table 3. Asymmetric transfer hydrogenation of ketones in isopropanol catalyzed by chiral Ir(I) complexes
Entrya
Ketonesb
Yield, %c
ee, %d
Ligand
Time, h
Temperature, °C
1
2
3
4
IIIa
a
b
c
d
4
4
6
4
50
50
50
25
75.0
50.0
40.0
89.0
51.5
31.7
10.1
62.0
5
6
7
8
IIIb
a
b
c
d
6
6
6
4
50
50
50
25
63.0
54.0
35.0
80.0
54.0
30.8
4.0
81.9
a
b
c
d
L : M : KOH = 1 : 1 : 2 (L = ligand, M = metal) [Ir(COD)Cl2].
See the Scheme 2.
Yield was calculated as alcohol after chromatography.
ee values were determined by HPLC analysis of the isolated alcohol with Chiralcel OD columns.
obtained clearly demonstrate that the title compounds
have moderate catalytic activity and enantioselectivity
Ir(I) towards catalytic transfer hydrogenation. The
results show that the activity and enantioselectivity of
the chiral iridium catalyst are very sensitive to the sub-
strate structure. Ir(I)-catalyzed asymmetric transfer
hydrogenation of acetophenone resulted in moderate
yield and moderate enantioselectivity(entry 1 and 5,
Table 1, 63–75% yield, 51.4–54.0% ee); asymmetric
transfer hydrogenation of proopiophenone (entry 2
and 6, Table 3, 50.0–54.0% yield, 30.8–31.7% ee) and
ACKNOWLEDGMENTS
This work was supported by Natural Science Foun-
dation of Hebei Province (no. B2014208094).
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