A highly efficient synthesis of optically active ferrocenylethylamines via hydride reduction of chiral ferrocenylketimines

Article abstract of DOI:10.1002/cjoc.201300211

Due to using (R)- or (S)-α-methylbenzylamine as a chiral auxiliary, and low-temperature regime for reduction of the intermediate ferrocenyl-mono- or 1,1′-bis-ketimines, the corresponding secondary mono- or 1,1′-bis-amines were prepared with high diastereoselectivity. Removal of the α-methylbenzyl group afforded the optically active primary mono- and bis-ferrocenylethylamines in high yields. The absolute configuration of (R,R)-3a and (S,S)-3b was determined by X-ray single crystal diffraction. We have developed an efficient and highly stereoselective synthesis of the chiral mono- and bis-ferrocenylamines via sodium borohydride reduction, followed by reductive cleavage of the α-methylbenzyl moiety using 5% Pd/C and HCOONH ₄. The selectivity was up to 99% de. Copyright

Full text of DOI:10.1002/cjoc.201300211

FULL PAPER
DOI: 10.1002/cjoc.201300211
A Highly Efficient Synthesis of Optically Active
Ferrocenylethylamines via Hydride Reduction of Chiral
Ferrocenylketimines
Hengyu Qian,a,b Shihai Yan,c Xiuling Cui,*,a Chao Pi,a Cheng Liu,a and Yangjie Wu*,a
a Henan Key Laboratory of Chemical Biology and Organic Chemistry, Key Laboratory of Applied Chemistry of
Henan Universities, Department of Chemistry, Zhengzhou University, Zhengzhou, Henan 450052, China
b Henan Key Laboratory of Surface & Interface Science, School of Material & Chemical Engineering, Zhengzhou
University of Light Industry, Zhengzhou, Henan 450002, China
c Lab of Biofuel, Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shan-
dong 266101, China
Due to using (R)- or (S)-α-methylbenzylamine as a chiral auxiliary, and low-temperature regime for reduction of
the intermediate ferrocenyl-mono- or 1,1'-bis-ketimines, the corresponding secondary mono- or 1,1'-bis-amines
were prepared with high diastereoselectivity. Removal of the α-methylbenzyl group afforded the optically active
primary mono- and bis-ferrocenylethylamines in high yields. The absolute configuration of (R,R)-3a and (S,S)-3b
was determined by X-ray single crystal diffraction.
Keywords chiral, reduction, ferrocenylketimine, diastereoselectivity, ferrocenylethylamine
Introduction
was improved by condensation of the corresponding
ketones and (R)- or (S)-α-methylbenzylamine in dry
toluene in the presence of active Al2O3, and reduction of
the ketimines to provide the corresponding amine with
complete enantiopurity.
Chiral ferrocene derivatives are the most useful
ligands in asymmetric synthesis,[1] among which the
ferrocene ligands with planar chirality have increased
exponentially due to their excellent catalytic results.[2]
The tertiary α-ferrocenylalkylamines were usually used
as a precursor for the synthesis of ferrocenes displaying
planar chirality.[2b,3] Diastereoselective addition of or-
ganolithium reagent to the C＝N bond of chiral ferro-
cenylimines derivatives, followed by cleavage of the
chiral auxiliary portion, provided a useful method.[4]
Such methodology is less tolerable to functional groups.
Moreover, the protection of inert gas and low tempera-
ture are required since the organolithium reagent is
highly active and sensitive to the moisture and O2 in air.
In contrast, sodium borohydride is an inexpensive, easy
to handle and environmentally friendly reducing reagent
for chemoselective reduction of ketimines.[5] Herein, we
report a convenient route to synthesize the optically ac-
tive mono- and bis-ferrocenylethylamines via highly
diastereoselective reduction of ketimine with sodium
borohydride and the subsequent cleavage of α-methyl-
benzyl group by Pd/C and ammonium formate as H2
resources. This methodology was based on the previ-
ously described research[5a] devoted to diastereoselec-
tive hydride reduction of the ferrocenylketimine, which
Experimental
General
Melting points were measured on an X4-1 micro-
scopic apparatus and were uncorrected. Elemental
analyses were determined with a Carlo Erba 1160 ele-
1
mental analyzer. H and 13C NMR spectra were re-
corded on a Bruker DPX 400 spectrometer, using
CDCl3 as solvent and TMS as an internal reference
standard. IR spectra were recorded on a Bruker-Vector
22 spectrophotometer. Optical rotations were deter-
mined at 589 nm on a Perkin-Elmer 341 polarimeter at
20 ℃. All solvents were dried according to the standard
methods. (R)-, (S)- α-methylbenzylamine (ee 99.5%)
and sodium borohydride were purchased from ACROS
and used without purification.
Synthesis of compounds (R,R)-3a and (S,S)-3b
Acetylferrocene (2.28 g, 10 mmol) and (R)- or (S)-
α-methylbenzylamine (1.452 g, 12 mmol) were dis-
*
E-mail: wyj@zzu.edu.cn, cuixl@zzu.edu.cn; Tel.: 0086-0371-67767753; Fax: 0086-0371-67767753
Received March 17, 2013; accepted June 5, 2013; published online July 5, 2013.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201300211 or from the author.
992
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Chin. J. Chem. 2013, 31, 992—996

A Highly Efficient Synthesis of Optically Active Ferrocenylethylamines
solved in dry toluene in the presence of active Al2O3,
then refluxed for 20 h. The mixture was filtered and the
filtrate was evaporated under reduced pressure. The un-
stable crude ferrocenylketimines 2 were obtained and
reduced with sodium borohydride (1.85 g, 50 mmol),
which was added over 2 h at −15 ℃ in methanol. The
mixture was stirred for 8 h, then evaporated to dryness,
extracted with ether and dried over Na2SO4. The residue
was isolated by flash chromatography over silica gel
(chloroform/ethyl acetate, V∶V＝5∶1). (R,R)-3a: 2.74
g (82%), orange solid, m.p. 65－66 ℃, [α]2D0 −43.7 (c
α-methylbenzylamine (2.90 g, 24 mmol) were dissolved
in dry toluene in the presence of active Al2O3, then re-
fluxed for 20 h. The mixture was filtered and the filtrate
was evaporated under reduced pressure. The crude
ferrocenylketimines 8a, 8b were obtained and reduced
with sodium borohydride (3.7 g, 100 mmol) without
isolation. Sodium borohydride was added in portion
over 2 h at −15 ℃ in methanol. The mixture was
stirred for 8 h, then evaporated to dryness, extracted
with ether and dried over Na2SO4. The residue was pu-
rified by flash chromatography over silica gel (chloro-
form/ethyl acetate, V∶V＝4∶1). (R,R,R,R)-9a: 3.98 g
1
1.2, benzene); H NMR (CDCl3, 400 MHz) δ: 1.23 (d,
1
J＝6.5 Hz, 3H), 1.40 (d, J＝6.6 Hz, 3H), 3.33 (q, J＝
6.6 Hz, 1H), 3.82 (q, J＝6.7 Hz, 1H), 4.07 (s, 5H), 4.02,
4.11, 4.12, 4.16 (each s, 4H), 7.26－7.36 (m, 5H); 13C
NMR (CDCl3, 100 MHz) δ: 22.7, 25.5, 49.2, 55.1, 64.8,
66.9, 67.4, 68.1, 68.4, 93.3, 126.7, 126.7, 128.4, 146.2;
IR (KBr) v: 3020, 1108, 1020, 875, 500 cm−1. Anal.
calcd for C20H23FeN: C 72.07, H 6.91, N 4.20; found C
72.10, H 6.91, N 4.21. (S,S)-3b: 2.83 g (85%), orange
solid, m.p. 65－66 ℃, [α]2D0 ＋43.2 (c 1.2, benzene);
1H NMR (CDCl3, 400 MHz) δ: 1.24 (d, J＝6.8 Hz, 3H),
1.39 (d, J＝6.8 Hz, 3H), 3.33 (q, J＝6.7 Hz, 1H), 3.81
(q, J＝6.6 Hz, 1H), 4.06 (s, 5H), 4.02, 4.11, 4.13, 4.16
(s, 4H), 7.24－7.36 (m, 5H); 13C NMR (CDCl3, 100
MHz) δ: 22.8, 25.5, 49.3, 55.2, 64.9, 66.9, 67.5, 68.2,
68.4, 93.4, 126.7, 126.7, 128.4, 146.3; IR (KBr) v: 3021,
1100, 1020, 870, 510 cm−1. Anal. calcd for C20H23FeN:
C 72.07, H 6.91, N 4.20; found C 72.11, H 6.92, N 4.20.
(83%), orange oil, [α]2D0 −72.1 (c 1.0, benzene); H
NMR (CDCl3, 400 MHz) δ: 1.19 (d, J＝6.4 Hz, 3H),
1.33 (d, J＝6.4 Hz, 3H), 3.28 (q, J＝6.6 Hz, 1H), 3.76
(q, J＝6.5 Hz, 1H), 3.90－4.10 (m, 4H), 7.23－7.32 (m,
5H); 13C NMR (CDCl3, 100 MHz) δ: 22.7, 25.4, 49.2,
55.2, 65.4, 67.8, 68.3, 68.7, 72.9, 126.6, 126.7, 128.4,
128.5; IR (KBr) v: 3025, 2964, 1629, 1452, 1368, 762,
702 cm−1. Anal. calcd for C30H36FeN2: C 75.00, H 7.50,
N 5.83; found C 75.32, H 7.61, N 5.98. (S,S,S,S)-9b:
4.03 g (84%), orange oil, [α]2D0 ＋71.5 (c 1.0, benzene);
1H NMR (CDCl3, 400 MHz) δ: 1.20 (d, J＝5.4 Hz, 3H),
1.32 (d, J＝6.5 Hz, 3H), 3.28 (q, J＝6.5 Hz, 1H), 3.78
(q, J＝6.4 Hz, 1H), 3.91－4.08 (m, 4H), 7.22－7.32 (m,
5H); 13C NMR (CDCl3, 100 MHz) δ: 22.7, 25.4, 49.3,
55.2, 65.5, 67.8, 68.3, 68.7, 72.8, 126.6, 126.7, 126.8,
128.4; IR (KBr) v: 3040, 2950, 1635, 1451, 1360, 768,
690 cm−1. Anal. calcd for C30H36FeN2: C 75.00, H 7.50,
N 5.83; found C 75.45, H 7.59, N 5.95.
Synthesis of compounds (R)-4a and (S)-4b
Synthesis of compounds 10a, 10b
Ammonium formate (252 mg, 4 mmol) and 5% Pd/C
(20 mg) were added to the solution of compounds
(R,R)-3a or (S,S)-3b (333 mg, 1 mmol) in dry methanol,
respectively. After stirred for 3 h at 65 ℃, the mixture
was filtered and concentrated in vacuum. The crude
products (R)-4a and (S)-4b were separated by chroma-
tography on silica gel (chloroform/ethyl acetate, V∶V
＝4∶1). (R)-4a: 206 mg (90%), orange oil, [α]D20
−26.8 (c 1.04, benzene); 1H NMR (CDCl3, 400 MHz) δ:
1.34 (d, J＝6.6 Hz, 3H), 1.77 (br, 2H), 3.80 (q, J＝6.5
Hz, 1H), 4.11－4.15 (m, 4H), 4.15 (s, 5H); 13C NMR
(CDCl3, 100 MHz) δ: 24.7, 45.9, 65.6, 65.7, 67.3, 67.4,
68.3, 96.3; IR (KBr) v: 3445, 3060, 2970, 1560, 1108,
1010, 805 cm−1. Anal. calcd for C12H15FeN: C 62.88, H
6.55, N 6.11; found C 62.52, H 6.81, N 6.21. (S)-4b:
211 mg (92%), orange oil, [α]2D0 ＋26.2 (c 1.04,
Ammonium formate (504 mg, 8 mmol) and 5% Pd/C
(40 mg) were added to the solution of compounds 9a,
9b (480 mg, 1 mmol) in dry methanol. After stirred for
3 h at 65 ℃, the mixture was filtered and concentrated
in vacuum. The crude products 10a, 10b were purified
by chromatography on silica gel (chloroform/ethyl ace-
tate, V∶V＝4∶1). (R,R)-10a: 207 mg (76%), orange
oil, [α]2D0 −32.1 (c 0.01, CHCl3) [lit.[6] [α]2D0 −33.3 (c
1
0.01, CHCl3)]; H NMR (CDCl3, 400 MHz) δ: 2.18 (d,
J＝6.5 Hz, 3H), 3.11 (q, J＝6.8 Hz, 1H), 4.24－4.81 (m,
4H); 13C NMR (CDCl3, 100 MHz) δ: 30.9, 45.2, 70.0,
70.3, 70.5, 73.3; IR (KBr) v: 3354, 3020, 2970, 1580,
760 cm−1. Anal. calcd for C14H20FeN2: C 61.76, H 7.35,
N 10.29; found C 61.38, H 7.51, N 10.18. (S,S)-10b:
212 mg (78%), orange oil, [α]2D0 ＋32.9 (c 0.01,
CHCl3); 1H NMR (CDCl3, 100 MHz) δ: 2.18 (d, J＝6.6
Hz, 3H), 3.12 (q, J＝6.9 Hz, 1H), 4.23－4.82 (m, 4H);
13C NMR (CDCl3, 400 MHz) δ: 30.9, 45.8, 70.2, 70.5,
70.6, 73.4; IR (KBr) v: 3360, 3010, 2950, 1585, 740
cm−1. Anal. calcd for C14H20FeN2: C 61.76, H 7.35, N
10.29; found C 61.32, H 7.58, N 10.07.
1
benzene) [lit.[3b] [α]2D0 ＋26.7 (c 1.04, benzene)]; H
NMR (CDCl3, 400 MHz) δ: 1.35 (d, J＝6.5 Hz, 3H),
1.79 (br, 2H), 3.80 (q, J＝6.5 Hz, 1H), 4.11－4.18 (m,
4H), 4.15 (s, 5H); 13C NMR (CDCl3, 100 MHz) δ: 24.6,
46.0, 65.6, 65.8, 67.3, 67.4, 68.2, 96.2; IR (KBr) v: 3450,
3050, 2970, 1560, 1105, 1010, 800 cm−1. Anal. calcd for
C12H15FeN: C 62.88, H 6.55, N 6.11; found C 62.49, H
6.63, N 6.19.
Results and Discussion
Synthesis of compounds 9a, 9b
As shown in Scheme 1, the condensation of ace-
Diacetylferrocene (2.70 g, 10 mmol) and (R)- or (S)-
tylferrocene 1 with (R)- and (S)-α-methylbenzylamine
Chin. J. Chem. 2013, 31, 992—996
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Qian et al.
FULL PAPER
afforded the chiral ketimines 2a, 2b.[5a] The ketimines
2a, 2b were used directly for the next step without puri-
fication. Subsequent reduction of the ketimines 2a, 2b
with sodium borohydride at −15 ℃ in dry methanol
gave the chiral secondary amines 3a, 3b in good yields
(3a: 82%; 3b: 85%) and with excellent diastereoselec-
tivities (de≥99%). And the absolute configuration of
optically active ferrocenylamines [(R,R)-3a; (S,S)-3b]
was determined by X-ray diffraction.[7]
Suitable single crystals of compounds (R,R)-3a and
(S,S)-3b were developed from n-hexane. The X-ray
crystal structure analysis of (R,R)-3a (Figure 1) and
(S,S)-3b (Figure 2) showed clearly that the absolute
configuration of the new stereogenic center was R in
(R,R)-3a and S in (S,S)-3b. These results suggested that
the prochiral ferrocenylketimines 2a, 2b were success-
fully transformed into chiral secondary amines with
high diastereoselectivity. Meanwhile, the substituted
cyclopentadienyl and benzene ring are in cis arrange-
ment, the value of torsion angle for C(11)-N(1)-C(13)-
C(14) is 56.3° [(R,R)-3a] and 55.3° [(S,S)-3b], respec-
tively. The two cyclopentadienyl rings are nearly paral-
lel, with a deviation from an ideal parallel conformation
giving the dihedral angles of 1.3° for (R,R)-3a and 1.7°
for (S,S)-3b.
Figure 1 Molecular structure of compound (R,R)-3a. Selected
bond lengths (Å) and angles (°): C(10)－C(11) 1.498(6), C(11)－
N(1) 1.464(6), N(1)－C(13) 1.445(5); C(10)-C(11)-N(1) 109.8(4),
C(11)-N(1)-C(13) 118.9(4), N(1)-C(13)-C(14) 115.1(4).
Removal of the chiral auxiliary is generally accom-
plished by hydrogenolysis with Pearlman’s catalyst to
give the corresponding amine.[5a] Normally, 20%
Pd(OH)2 on carbon and 344.75－379.22 kPa of hydro-
gen were required. The major drawback of this protocol
is the cost associated with the high palladium metal
loading and undergoing under hydrogen pressure. As an
economical and safe method, the compounds (R,R)-3a,
(R,R)-3b underwent cleavage of the α-methylbenzyl
moiety without loss of enantiomeric purity in the pres-
ence of ammonium formate as the hydrogen donor and
5% Pd/C as the catalyst, giving (R)-4a (90% yield,
≥99% ee) and (R)-4b (92% yield, ≥99% ee), respec-
tively (Scheme 1). This method took the advantages of
Figure 2 Molecular structure of compound (S,S)-3b. Selected
bond lengths (Å) and angles (°): C(10)－C(11) 1.481(7), C(11)－
N(1) 1.456(7), N(1)－C(13) 1.455(6); C(10)-C(11)-N(1) 110.7(4),
C(11)-N(1)-C(13) 118.6(4), N(1)-C(13)-C(14) 115.0(5).
Scheme 1
H
H
Ph
Ph
NH2
NH
N
5% Pd/C
NaBH4
MeOH, -15 oC
Fe
(R)-α-methylbenzylamine
Fe
H
H
HCO2NH4
Fe
Toluene, Al2O3
(R)-4a
(R,R)-3a
(R)-2a
Yield 90%, ee ≥ 99%
Yield 82%, de ≥ 99%
Fe
O
H
Ph
NH2
H
1
Ph
Toluene, Al2O3
NaBH4
MeOH, -15 oC
5% Pd/C
NH
H
Fe
H
N
HCO2NH4
(S)-α-methylbenzylamine
Fe
Fe
(S)-2a
(S)-4a
(S,S)-3a
Yield 85%, de ≥ 99%
Yield 92%, ee ≥ 99%
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Chin. J. Chem. 2013, 31, 992—996

A Highly Efficient Synthesis of Optically Active Ferrocenylethylamines
safety and mild reaction conditions.
corporation of the bulky alkyl group made the yield and
diastereoselectivity decreases.
Next we turned our attention to more prochiral
ferrocenylketimines, the results are presented in Table 1.
(R)-5a gave a mixture of ferrocenylamines (R,R)-6a and
(R,S)-6a in 85% yield with 68% de (Table 1, Entry 1),
This procedure was extended to the aryl- and het-
eroaryl ketimines, and afforded the chiral amines in
high yields with moderate to good stereoselectivity of
58%－80% de (Table 1, Entries 3－6). The best result
was obtained in the thienyl ketimine reduction [(R)-5f,
Table 1, Entry 6], providing the amine 6f in 90% yield
with 80% de.
1
which was determined by H NMR spectrum. There
were two well-separated signals of methine protons at
the new stereocenter position (R,R: δ 3.02; R,S: δ 3.14).
We failed to isolate these two diastereomers by silica
gel chromatography. Reduction of ferrocenylketimine
(R)-5b gave the mixture 6b in 56% yield with 74% de
(Table 1, Entry 2). These results suggested that the in-
1,1'-Bis-(α-aminoethyl)ferrocene was employed as
powerful synthetic precursors for the ferrocene deriva-
tives in asymmetric catalysis.[8] It was prepared by the
enantioselective reduction of the corresponding 1,1'-di-
acylferrocene (CBS reduction) using an excess of nu-
cleophile and oxazaborolidine as ligand in the litera-
ture.[2a,9] However, the optically active oxazaborolidine
is much more costly.[10] Herein, we were pleased to find
that the protocol mentioned above was applied to syn-
thesize the chiral 1,1'-bis-(α-aminoethyl)ferrocene
(Scheme 2). The 1,1'-diacylferrocene was reacted with
(R) and (S)-α-methylbenzylamine in toluene in the
presence of Al2O3, affording the ketimines 8a, 8b,
which were used for next step without purification. Re-
duction with sodium borohydride at －15 ℃ in dry
methanol provided the corresponding chiral secondary
amines 9a, 9b in good yields (9a, 83% and 9b, 84%)
and excellent stereoselectivity. For (R,R,R,R)-9a, the
diastereomeric excess was determined by 1H NMR
spectra (98% de). However, the diastereoselectivity de-
creased (82% de) at the higher reaction temperature (0
℃). Then cleavage of chiral auxiliary of 9a, 9b was
accomplished by 5% Pd/C in the presence of ammo-
nium formate to yield the chiral 1,1'-bis-(α-aminoethyl)-
ferrocene 10a and 10b.
Table 1 Hydride reduction of ketimines (R)-5
H
N
Ph
NaBH4
O
(R)-α-methylbenzylamine
R
R'
MeOH, -15 oC
Toluene, Al2O3
R
R'
(R)-5
H
H
+
HN
Ph
HN
Ph
R'
H
R
R
H
R'
(R,R)-6
(R,S)-6
a: R = ferrocenyl, R' = CH2CH3; b: R = ferrocenyl, R' = CH2CH2CH3;
c: R = 3-nitrophenyl, R' = CH3; d: R = 2-naphthyl, R' = CH3;
e: R = 2-furyl, R' = CH3; f: R = 2-thienyl, R'=CH3
Entry
R
R'
Product
de/%Yield/%
1
2
3
4
5
6
Ferrocenyl
CH2CH3 (R,R)-6a/(R,S)-6a 68
85
56
88
91
93
90
Ferrocenyl CH2CH2CH3 (R,R)-6b/(R,S)-6b 74
3-Nitrophenyl
2-Naphthyl
2-Furyl
CH3
CH3
CH3
CH3
(R,R)-6c/(R,S)-6c 64
(R,R)-6d/(R,S)-6d 58
(R,R)-6e/(R,S)-6e 62
(R,R)-6f/(R,S)-6f 80
Compared with the report in the literature,[5a] for
example, the reduction of (R)-2a at 25 ℃ gave the
2-Thienyl
Scheme 2
H
N
Ph
NaBH4
(R)-α-methylbenzylamine
N
H
H
N
Ph
Ph
NH2
NH2
5% Pd/C
Fe
MeOH, -15 oC
Fe
Fe
Toluene, Al2O3
HCO2NH4
Ph
N
O
H
(R,R,R,R)-9a
yield 83%, de 98%
(R,R)-10a
(R,R)-8a
yield 76%, de 98%
Fe
H
O
N
Ph
7
N
H
H
N
Ph
Ph
NH2
(S)-α-methylbenzylamine
NaBH4
5% Pd/C
Fe
Fe
Fe
MeOH, -15 oC
HCO2NH4
Toluene, Al2O3
NH2
Ph
N
(S,S,S,S)-9b
yield 84%, de 98%
(S,S)-10b
H
yield 78%, de 98%
(S,S)-8b
Chin. J. Chem. 2013, 31, 992—996
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995

Qian et al.
FULL PAPER
corresponding amine (R,R)-3a with 80% de, the en-
hancement in selectivity for NaBH4 in this paper may be
caused by the lower reactivity at low temperature. Un-
der the same reaction conditions, the reduction of ferro-
cenylketimine (R)-2a with sodium borohydride gave
higher stereoselectivity (99% de) than that of ferro-
cenylketimines (R)-5a (68% de) and (R)-5b (74% de),
respectively. This may be ascribed to the bulkier alkyl
substituent attached to the carbonyl group in (R)-5a and
(R)-5b than methyl group in (R)-2a, which could not
fulfil the BH−4 group under the plane, and reduce the
stereoselectivity. On the other hand, we also found that
(R)-5c－(R)-5f gave the corresponding amines in quan-
titative yield with moderate diastereoselectivity, where
the ferrocenyl moiety was replaced by the aryl or het-
eroaryl ring. These results suggest that different from
the ferrocenyl group, the aryl or hetaryl moiety could
not fulfill a spatial requirement to shield the π-plane
which consisted of the imine moiety and aryl or hetaryl
ring.
082300423201) for the financial support to this re-
search.
References
[1] (a) Togni, A.; Hayashi, T. Ferrocenes: Homogeneous Catalysis,
Organic Synthesis, Materials Science, VCH, Weinheim, 1995; (b)
Stepnicka, P. Ferrocenes: Ligands, Materials and Biomolecules,
John Wiley & Sons, Ltd, West Sussex, England, 2008.
[2] (a) Arrayas, P. G.; Adrio, J.; Carretero, J. C. Angew. Chem., Int. Ed.
2006, 45, 7674; (b) Atkinson, R. C. J.; Gibson, V. C.; Long, N. J.
Chem. Soc. Rev. 2004, 33, 313; (c) Dai, L. X.; Tu, T.; You, S. L.;
Deng, W. P.; Hou, X. L. Acc. Chem. Res. 2003, 36, 659; (d) Chiral
Ferrocenes in Asymmetric Catalysis, Eds.: Dai, L. X.; Hou, X. L.,
Wiley-VCH, Weinheim, 2010.
[3] Richards, C. J.; Locke, A. J. Tetrahedron: Asymmetry 1998, 9, 2377.
[4] (a) Fukuda, T.; Takehara, A.; Haniu, N.; Iwao, M. Tetrahedron:
Asymmetry 2000, 11, 4083; (b) Enders, D.; Lochtman, R.; Raabe, G.
Synlett 1996, 126; (c) Zhang, H. Q.; Zhou, Z. M.; Fang, M. Lett. Org.
Chem. 2006, 3, 802; (d) Matsumoto, Y.; Ohno, A.; Lu, S. J.;
Hayashi, T.; Oguni, N.; Hayashi, M. Tetrahedron: Asymmetry 1993,
4, 1763.
[5] (a) David, D. M.; Kane-Maguire, L. A. P.; Pyne, S. G. J. Chem. Soc.,
Chem. Commun. 1990, 888; (b) Glorian, G.; Maciejewski, L.; Bro-
card, J.; Agbossou, F. Tetrahedron: Asymmetry 1997, 8, 355; (c)
Bhattacharyya, S. Synth. Commun. 1994, 24, 2713; (d) Bhat-
tacharyya, S. Synlett 1994, 1029; (e) Periasamy, M.; Thirumalaiku-
mar, M. J. Organomet. Chem. 2000, 609, 137.
Conclusions
In summary, a simple and efficient method has been
developed for the synthesis of chiral mono- and bis-
ferrocenylamines via hydride addition to the ferro-
cenylketimines with high stereoselectivity, starting from
cheap and commercial available optical α-methylben-
zylamine. Meanwhile, cleavage of the α-methylbenzyl
moiety could be performed in high yield using a 5%
palladium/carbon catalyst in the presence of ammonium
formate as hydrogen donor.
[6] Kim, T. J.; Lee, H. Y.; Ryu, E. S.; Park, D. K.; Cho, C. S.; Shim, S.
C.; Jeong, J. H. J. Organomet. Chem. 2002, 649, 258.
[7] Details of the X-ray structure analyses of (R,R)-3a and (S,S)-3b were
made on a RAXIS-IV imagine plate area detector with a graphite
monochromated Mo Kα radiation (λ＝0.71073 Å). The structures
were solved by direct methods and expanded using Fourier tech-
niques and refined by full-matrix least-squares methods.
CCDC-293912 and CCDC-715334 contain the supplementary crys-
tallographic data for this paper.
[8] (a) Ballistreri, F. P.; Patti, A.; Pedotti, S.; Tomaselli, G. A.; Toscano,
R. M. Tetrahedron: Asymmetry 2007, 18, 2377; (b) Schwink, L.;
Knochel, P. Chem. Eur. J. 1998, 4, 950.
[9] Corey, E. J.; Helal, C. J. Angew. Chem., Int. Ed. 1998, 37, 1986.
[10] Schwink, L.; Knochel, P. Tetrahedron Lett. 1996, 37, 25.
Acknowledgement
We are grateful to the National Natural Science
Foundation of China (Nos. 20972139, 21102133) and
the Natural Science Foundation of Henan Province (No.
(Zhao, C.)
996
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