Chiral ferrocenyl P,S-ligands for highly efficient copper-catalyzed asymmetric [3+2] cycloaddition of azomethine ylides

Article abstract of DOI:10.1016/j.tet.2015.01.003

A series of chiral ferrocenyl P,S-ligands based on benzimidazole and imidazole backbones have been prepared from Ugi's amine through a three-step transformation. These ligands were successfully employed in the Cu-catalyzed asymmetric [3+2] cycloaddition o

Full text of DOI:10.1016/j.tet.2015.01.003

Tetrahedron xxx (2015) 1e7
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Chiral ferrocenyl P,S-ligands for highly efficient copper-catalyzed
asymmetric [3þ2] cycloaddition of azomethine ylides
,
,
*
Fu-Zhong Han a b, Sai-Bo Yu b, Cheng Zhang b, Xiang-Ping Hu b
a College of Chemistry and Chemical Engineering, Qiqihar University, Qiqihar 161006, China
b Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of chiral ferrocenyl P,S-ligands based on benzimidazole and imidazole backbones have been
prepared from Ugi’s amine through a three-step transformation. These ligands were successfully
employed in the Cu-catalyzed asymmetric [3þ2] cycloaddition of azomethine ylides with various
electron-deficient olefins, giving the corresponding cycloadducts in high endo-selectivities and excellent
enantioselectivities (up to 99% ee).
Received 6 November 2014
Received in revised form 24 December 2014
Accepted 4 January 2015
Available online xxx
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Asymmetric catalysis
Chiral P,S-ligand
[3þ2]-Cycloaddition
Copper
Azomethine ylide
1. Introduction
called ImiFerroS), which were readily prepared from Ugi’s amine.4
These ligands proved to be highly effective for the Cu-catalyzed
The development of ferrocence-based chiral ligands for asym-
metric catalysis has made great success over the past decades due
to the rigidity, stability and readily structural modification of the
ferrocene backbone.1 Within this context, Ugi’s amine (N,N-di-
methyl-1-ferrocenylethylamine) derivatives constitute the largest
family of chiral ferrocence ligands, which are synthesized mostly
based on two significant features of Ugi’s amine: 1) the highly
stereoselective o-lithiation; and 2) the stereospecific substitution at
asymmetric [3þ2] cycloaddition of azomethine ylides with cyclic
a
-enones, predominately giving endo-cycloadducts in high enan-
tioselectivities of up to >99% ee. As a continuation of this work,
herein we report our results in details on the synthesis of ImiFerroS
ligands and the investigation of their reactivity in the Cu-catalyzed
asymmetric [3þ2] cycloaddition of azomethine ylides with various
electron-deficient olefins.
the
configuration.2 Recently, a strategy for the development of new
ligands by the introduction of a heterocyclic framework into the
a-ferrocenylmethyl position with full retention of the absolute
2. Results and discussion
a
-
2.1. Synthesis of ImiFerroS ligands
ferrocenylmethyl position has attracted tremendous interest. The
presence of a heterocyclic scaffold could significantly change the
nature of the chiral ferrocene backbone, therefore resulting in new
ligands for the use in those catalytic reactions that are less suc-
cessful with conventional ligands. Indeed, many chiral ferrocenyl
P,P-, P,N-, and P,S-ligands bearing a heterocyclic framework have
been developed and found to be highly efficient in a variety of
asymmetric catalysis such as hydrogenation, allylic alkylation,
hydroboration, cycloaddition, and so on.3 In 2010, we reported
a new class of ferrocene/benzimidazole-based P,S-ligands (we
ImiferroS ligands 1 can be readily prepared from Ugi’s amine by
a three-step transformation. A representative synthesis of (Rc,SFc)-
ImiFerroS 1a is shown in Scheme 1 as reported by us previously.4
Initially, Ugi’s amine 2 was subjected to highly diastereoselective
ortho-lithiation with n-BuLi, and then trapping with ClPPh2 to give
(R)-1-[(S)-2-(diphenylphosphino)ferr-ocenyl]ethylamine [(Rc,SFc)-
3] in 67% yield.5 Displacement of the amino group by a benzimid-
azole in HOAc afforded (Rc,SFc)-4 with the retentive configuration.
Subsequent lithiation of the 2-position of benzimidazole ring with
n-BuLi, followed by trapping with diphenyl disulfide generated the
target ferrocenyl P,S-ligand (Rc,SFc)-1a in good yields. With the
similar procedure, a variety of ImiferroS ligands 1be1e4 with
* Corresponding author. Tel.: þ86 411 84379276; fax: þ86 411 84684746; e-mail
addresses: xiangping@dicp.ac.cn, xiangping1974@163.com (X.-P. Hu).
http://dx.doi.org/10.1016/j.tet.2015.01.003
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.
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F.-Z. Han et al. / Tetrahedron xxx (2015) 1e7
Scheme 1. Synthesis of chiral ferrocenyl P,S-Ligands 1aeh bearing benzimidazole/imidazole ring.
various steric and electronic environments at the thioether moiety,
as well as ImiferroS ligands 1fe1h bearing an imidazole ring, were
synthesized in moderate to good yields. These ImiferroS ligands are
air and moisture-stable, and can be held at ambient temperature
for several weeks even in open air. The structure of (Rc,SFc)-Imi-
FerroS 1a was unambiguously confirmed by X-ray analysis.4
outstanding chiral metal catalysts and organocatalysts,6 which
stimulated us to investigate the efficiency of our newly developed
ferrocenyl P,S-ligands in this reaction. Our initial efforts focused on
the optimization of Cu-catalyzed enantioselective 1,3-dipolar cy-
cloaddition of azomethine ylides with electron-deficient olefins.
The cycloaddition of N-(4-chlorobenzylidene)glycine methyl ester
(5a) with dimethyl maleate (6) was chosen as a model reaction. The
reaction was performed in the presence of a catalyst loading of
1 mol % prepared in situ from copper salts and 1.1 equiv of ferro-
cenyl P,S-ligands, and some representative results are summarized
in Table 1. Copper salts showed a significant effect in the reaction,
and Cu(CH3CN)4ClO4 displayed the best result in terms of the yield,
2.2. Cu-catalyzed asymmetric [3D2] cycloaddition of azome-
thine ylides with dimethyl maleate
In the past decade, catalytic asymmetric [3þ2] cycloaddition
has achieved significant progress with the development of many
Table 1
Reaction condition screeninga
Entry
Ligand
[Cu]
Base
Solvent
T (ꢀC)
Yield %b
endo:exoc
ee %d
1
2
3
4
5
6
7
8
1a
1a
1a
1b
1c
1d
1e
1f
1g
1h
1e
1e
1e
1e
1e
1e
Cu(OAc)2
Cu(OTf)2
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
i-Pr2NEt
K2CO3
Et3N
Et3N
Et3N
Et3N
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
0
37
72
80
80
77
78
80
80
87
82
88
90
89
45
94
95
76/24
82/18
>95/5
>95/5
>95/5
>95/5
>95/5
>95/5
>95/5
>95/5
50/50
80/20
95/5
44
56
80
88
60
33
92
60
85
85
90
92
60
<10
96
98
Cu(CH3CN)4ClO4
Cu(CH3CN)4ClO4
Cu(CH3CN)4ClO4
Cu(CH3CN)4ClO4
Cu(CH3CN)4ClO4
Cu(CH3CN)4ClO4
Cu(CH3CN)4ClO4
Cu(CH3CN)4ClO4
Cu(CH3CN)4ClO4
Cu(CH3CN)4ClO4
Cu(CH3CN)4ClO4
Cu(CH3CN)4ClO4
Cu(CH3CN)4ClO4
Cu(CH3CN)4ClO4
9
10
11
12
13
14
15
16
Et2O
Toluene
Toluene
78/22
>95/5
>95/5
a
The reaction conditions: [Cu] (1 mol %), L* (1.1 mol %), 5a (0.5 mmol), 6 (0.6 mmol), solvent (3 mL), base (10 mol %), 12 h.
Isolated yields of a mixture of endo- and exo-7a.
b
c
Determined by 1H NMR analysis.
d
Determined for endo-cycloadduct by chiral HPLC (Chiralpak AS-H column, i-PrOH/n-hexane 50/50, 205 nm, 0.8 mL/min).
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F.-Z. Han et al. / Tetrahedron xxx (2015) 1e7
3
diastereo- and enantioselectivities (entries 1e3). The results in-
dicated that the ligand structure had less influence on the reactivity
and diastereoselectivity. In all cases, excellent endo-selectivities
(endo/exo >95/5) were observed (entries 3e10). However, the li-
gand structure dramatically affected the enantioselectivity. Thus,
ligand 1d bearing a methylthio group only gave an ee-value of 33%
(entry 6), while the corresponding 1e bearing an iso-propylthio
group provided 92% ee (entry 7). The introduction of an imidazole
ring instead of the benzimidazole framework improved the re-
activity and enantioselectivity in most cases (entries 8e10). For
example, ligand 1d gave the cycloadduct in 78% yield and with 33%
ee (entry 6), in contrast, the corresponding 1f with the imidazole
backbone led to the cycloadduct 7a in 80% yield and with 60% ee
(entry 8). However, the best result was obtained with (Rc,SFc)-
ImiferroS 1e bearing a benzimidazole framework and iso-pro-
pylthio group (entry 7). The reaction proved to be highly sensitive
to the base additives. Thus, the use of i-Pr2NEt and K2CO3 resulted
in dramatically decreased diastereoselectivities, but maintained
good yields and high enantioselectivities (entries 11 and 12). The
nature of the solvent showed a great impact on the reactivity,
diastereoselectivity, and enantioselectivity (entries 13e15). The
results suggested that toluene was the best choice, in which endo-
cycloadduct 7a was obtained as the only product in 94% yield
and with 96% ee (entry 15). The reaction temperature had slight
influence on the reactivity and enantioselectivity. Lowering the
reaction temperature to 0 ꢀC could further increase the enantio-
selectivity to 98% ee (entry 16).
substituted substrates (5aec) gave nearly same performance
(entries 1e3). The electronic property of the substituent slightly
affected the enantioselectivity (entries 4e10), and the substrate 5i
bearing a strong electron-withdrawing substituent led to a slightly
decreased enantioselectivity to 95% ee (entry 9). 2-Naphthyl-
substituted substrate 5k also worked well, giving endo-cycloadduct
7k as the only product in 90% yield and with 98% ee (entry 11).
However, heteroaromatic substrate 5l turned out to be an inferior
reaction partner, providing the cycloadduct 7l in 83% yield, 91%
endo-selectivity and with 79% ee for endo-cycloadduct (entry 12).
Unfortunately, the present catalyst system didn’t tolerate non-
aromatic substrates. Thus, low conversion was observed when N-
(cyclohexylmethylene)glycine methyl ester 5m was subjected to
this reaction (entry 13).
The present catalytic system proved to be remarkably tolerant
and remain high reactivity for azomethine ylides derived from
amino acid esters other than glycinate. Thus, under the optimal
reaction conditions, the azomethine ylide 5n derived from alanine
smoothly reacted with dimethyl maleate 6 to predominately give
endo-cycloadduct 7n (93/7 dr) in 82% yield and with 98% ee
(Scheme 2).
Under the optimal reaction conditions, the scope of azomethine
ylides for this 1.3-dipolar cycloaddition was investigated, and the
results are shown in Table 2. The results demonstrated that the
present catalytic system was highly efficient to promote the
asymmetric [3þ2] cycloaddition of aromatic azomethine ylides
with dimethyl maleate. A variety of imino esters derived from
substituted benzaldehydes reacted with dimethyl maleate to give
the corresponding endo-cycloadducts in high yields and with ex-
cellent enantioselectivities (95e99% ee) (entries 1e10). The sub-
stitution pattern on the phenyl ring had little effect on the reactivity,
diastereoselectivity and enantioselectivity. Thus, all 2-, 3-, and 4-Cl
Scheme 2. Cu-catalyzed asymmetric [3þ2] cycloaddition of N-(4-chlorobenzylidene)
alanine methyl ester 5n with 6.
High stereoselectivity observed in the cycloaddition can be ra-
tionalized by using the proposed transition state as shown in Fig. 1.
The in situ-formed azomethine ylide is oriented in a specific way as
shown in Fig. 1 after the coordination to Cu-metal center, due to the
steric repulsion between the phenyl group in the ylide and the
phenyl group on the phosphorus atom of the chiral ligand. The
possible coordination of the carbonyl group of dimethyl maleate to
the Cu center resulted in the cycloadduct with predominant endo-
selectivity. Furthermore, the steric congestion imposed by the fer-
rocene backbone effectively blocks the approach of dimethyl mal-
eate from the Si (C]N) face of the ylide. A Re face attack leads to the
formation of (2S,3R,4S,5R)-7d, which is compatible with the ex-
perimental result.
Table 2
Cu-catalyzed asymmetric [3þ2] cycloaddition: scope of azomethine ylidesa
Entry
Substrate (R)
Product
Yield (%)b
endo/exoc
ee (%)d
1
2
3
4
5
6
7
8
5a: R¼4-ClC6H4
5b: R¼2-ClC6H4
5c: R¼3-ClC6H4
5d: R¼C6H5
7a
7b
7c
7d
7e
7f
7g
7h
7i
95
96
95
89
87
92
93
91
96
97
90
83
d
>95/5
>95/5
>95/5
>95/5
95/5
>95/5
>95/5
>95/5
>95/5
>95/5
>95/5
91/9
98
98
99
99
98
99
97
97
95
98
98
79
de
5e: R¼4-FC6H4
5f: R¼4-BrC6H4
5g: R¼4-MeC6H4
5h: R¼4-MeOC6H4
5i: R¼4-NO2C6H4
5j: R¼4-CF3C6H4
5k: R¼2-naphthyl
5l: R¼2-thienyl
5m: R¼cyclohexanyl
Fig. 1. Proposed model for enantioinduction.
9
10
11
12
13
7j
7k
7l
2.3. Cu-catalyzed asymmetric [3D2] cycloaddition of
N-(4-chlorobenzylidene)glycine methyl ester with various
electron-deficient olefins
7m
d
a
Reaction conditions: Cu(CH3CN)4ClO4 (1 mol %), (Rc,SFc)-ImiferroS 1e (1.1 mol %),
imino ester 5 (0.5 mmol), 6 (0.6 mmol), Et3N (10 mol %), toluene (3 mL), 0 ꢀC for 12 h.
b
Isolated yields of a mixture of endo- and exo-7.
To further extend the scope of the present catalytic system, the
1,3-dipolar cycloaddition of N-(4-chlorobenzylidene)glycine methyl
ester 5a with other electron-deficient olefins was then performed,
c
Determined by 1H NMR.
d
Determined for endo-cycloadduct by chiral HPLC.
Not determined because of low conversion.
e
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4
F.-Z. Han et al. / Tetrahedron xxx (2015) 1e7
Fig. 2. Cycloadducts of the reaction of N-(4-chlorobenzylidene)glycine methyl ester 5a with various electron-deficient olefins.
and the results are listed in Fig. 2. With dimethyl fumarate and
N-phenylmaleimide, high endo-selectivities and good enantiose-
lectivities were achieved. However, for tert-butyl acrylate, the
present catalytic system proved to be less efficient, displaying only
moderate enantioselectivity (67% ee). As we have demonstrated
previously, the present catalytic system was highly effective for
4.2. Synthesis of 1-{(R)-1-[(S)-2-diphenylphosphinoferro-
cenyl]ethyl}benzimidazole (4)
A solution of 4.41 g (10 mmol) of (Rc,SFc)-3 together with 5.8 g
(50 mmol) of benzimidazole in 50 mL of degassed acetic acid was
warmed to 80 ꢀC and stirred at this temperature for 8 h. The reaction
mixture was then concentrated in vacuum and neutralized with
50 mL of saturated NaHCO3. The mixture was extracted three times
with CH2Cl2, washed with brine, and dried over Na2SO4. The solvent
wasremovedunder reduced pressureandthe residuewaspurifiedby
cyclic
cycloadduct 11 in excellent enantioselectivity (99% ee). However, for
acyclic -enones, high enantioselectivities but moderate diaster-
a-enones, such as 2-cyclopentenone, giving the sole endo-
a
eoselectivities were observed.
recrystallization with ethanol to afford the pure product as a brown
25
solid (7.78 g, 93% yield). Mp:198e199 ꢀC;[
a]
D
¼ꢁ300.7 (c1.0, CHCl3);
3. Conclusion
1H NMR (400 MHz, CDCl3):
d 7.65 (s,1H), 7.37e7.45 (m, 4H), 7.32e7.34
(m, 3H), 7.01e7.04 (m, 2H), 7.08e7.14 (m, 2H), 6.84 (m,1H), 6.64e6.68
(m, 2H), 6.47e6.51 (m, 2H), 5.96 (m,1H), 4.82 (s,1H), 4.36 (s,1H), 4.17
(s, 5H), 3.85 (s,1H),1.93 (d, J¼6.8 Hz, 3H); 31P NMR (162 MHz, CDCl3):
In conclusion, we have developed a series of ferrocenyl P,S-
ligands with a benzimidazole or an imidazole framework. These
ligands can be easily prepared from Ugi’s amine through a three-
step transformation, and showed high air- and moisture-stability.
These ligands proved to be highly efficient in the Cu-catalyzed
asymmetric [3þ2] cycloaddition of azomethine ylides with vari-
ous electron-deficient olefins, giving the cycloadducts in high endo-
selectivities (up to >95/5 dr) and good to excellent enantiose-
lectivities (up to 99% ee). Further applications of these ferrocenyl
P,S-ligands in other type of asymmetric reactions are currently in
progress.
d
ꢁ25.3; 13C NMR (100 MHz, CDCl3):
d 143.3,141.0,136.4,136.4,136.2,
136.1, 134.9, 134.7, 131.9, 131.6, 131.4, 129.2, 128.2, 128.1, 127.8, 127.4,
127.3, 122.1, 121.4, 119.9, 110.4, 91.9, 91.7, 72.7 (d, J¼4 Hz), 70.8, 70.2.
4.3. General procedure for the synthesis of (Rc,SFc)-ImiFerroS
1aeh
To a suspension of (Rc,SFc)-4 (514 mg, 1 mmol) in 10 mL of dried
diethyl ether was added a solution of n-BuLi (0.6 mL, 2.5 M) in
hexane at ꢁ30 ꢀC. After the addition was completed, the reaction
mixture was warmed to room temperature and stirred for 4 h. A
solution of disulfide (1.1 mmol) in 10 mL of dried diethyl ether was
added at 0 ꢀC, and the solution was stirred at room temperature
overnight. The reaction mixture was quenched with 10 mL of sat-
urated NaHCO3, and then was extracted three times with 10 mL of
CH2Cl2. The combined organic phase was washed with brine and
dried over Na2SO4. The solvent was removed under reduced pres-
sure and the crude product was purified by flash chromatography
(ethyl acetate/petroleum ether¼1/20) to afford a pure product.
(Rc,SFc)-ImiFerroS 1a was obtained as a yellow solid in 86% yield.
4. Experimental section
4.1. General remarks
All reactions were carried out under a nitrogen atmosphere. All
solvents were purified by standard procedure, and commercially
obtained reagents were used without further purification. 1H NMR
spectra were recorded on a Bruker 400 MHz spectrometer in
chloroform-d.3 Chemical shifts are reported in ppm with the in-
ternal TMS signal at 0.0 ppm as a standard. 13C NMR spectra were
recorded on a Bruker 100 MHz spectrometer in chloroform-d3.
Chemical shifts are reported in ppm with the internal chloroform
signal at 77.0 ppm as a standard. 31P NMR spectra were recorded on
a Bruker 162 MHz spectrometer in chloroform-d3, chemical shifts
are reported in ppm with the external 85% H3PO4 signal at 0.0 ppm
as a standard. All reactions were monitored by TLC with silica gel-
coated plates. Enantiomeric ratios were determined by chiral HPLC
using a chiralpak AS-H column or a chiralcel OD-H with n-hexane
and i-PrOH as solvents. Optical rotations were recorded on a Jasco
P-1020 polarimeter. The absolute configuration of the known
products were determined by comparing optical rotation with the
reported data.
Mp: 165e167 ꢀC; [
CDCl3):
a
]
25: ꢁ239.2 (c 1.0, CHCl3); 1H NMR (400 MHz,
D
d
7.40e7.47 (m, 4H), 7.26e7.32 (m, 9H), 7.00e7.02 (m, 2H),
6.85 (m, 1H), 6.58 (m, 2H), 6.47e6.50 (m, 3H), 4.89 (s, 1H), 4.42 (d,
J¼2.0 Hz, 1H), 4.16 (s, 5H), 3.77 (s, 1H), 1.67 (s, 3H); 31P NMR
(162 MHz, CDCl3):
135.9, 135.0, 134.8, 131.5, 131.3, 130.9, 129.3, 129.2, 129.0, 128.1,
128.0, 127.7, 127.5, 127.3, 122.1, 121.5, 119.8, 111.6; HRMS calcd for
d
ꢁ25.2; 13C NMR (100 MHz, CDCl3):
d 146.1,
C
37H31FeN2PS [MþH]: 623.1317, found 623.1389.
(Rc,SFc)-ImiFerroS 1b was obtained as a yellow solid in 67% yield.
25
Mp: 151e152 ꢀC; [
CDCl3):
a
]
¼ꢁ220.8 (c 1.0, CH2Cl2); 1H NMR (400 MHz,
D
d 7.41e7.44 (m, 2H), 7.31e7.36 (m, 5H), 7.24e7.29 (m, 4H),
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F.-Z. Han et al. / Tetrahedron xxx (2015) 1e7
5
7.01 (m, 2H), 6.81e6.85 (m, 1H), 6.55e6.57 (m, 2H), 6.44e6.48 (m,
1H), 6.59 (s, 1H), 5.81e5.83 (m, 1H), 4.66 (s, 1H), 4.41 (s, 1H), 4.09 (s,
5H), 3.84 (s,1H), 3.45e3.50 (m,1H),1.76 (d, J¼6.8 Hz, 3H),1.22e1.25
3H), 4.91 (s, 1H), 4.42 (s, 1H), 4.15 (s, 5H), 3.78 (s, 1H), 1.73 (d,
J¼10.4 Hz, 3H); 31P NMR (162 MHz, CDCl3):
d
ꢁ24.9; 13C NMR
(m, 6H); 31P NMR (162 MHz, CDCl3):
d
ꢁ24.5; 13C NMR (100 MHz,
(100 MHz, CDCl3):
d
145.8, 143.5, 136.8, 136.2, 136.1, 135.1, 134.9,
CDCl3):
d
22.2, 23.3, 23.9, 50.6 (d, J¼9 Hz), 69.3, 69.6, 69.9, 70.1, 70.7,
133.6, 132.1, 131.4, 131.2, 129.4, 129.1, 128.2, 128.1, 127.1, 127.3, 127.3,
122.2,121.5,119.8,111.7, 90.8 (d, J¼24.0 Hz), 77.7 (d, J¼10.4 Hz), 73.1,
70.9, 70.3, 69.1, 51.8, 18.8; HRMS calcd for C37H30ClFeN2PS [MþH]:
657.0984, found 657.0975.
72.4 (d, J¼4 Hz), 76.4 (d, J¼10 Hz), 93.3 (d, J¼25 Hz), 117.5, 127.7 (d,
J¼6 Hz), 127.8, 128.1 (d, J¼7 Hz), 128.7, 129.2, 131.7 (d, J¼18 Hz),
135.2 (d, J¼21 Hz), 137.1 (d, J¼8 Hz), 137.9 (d, J¼8 Hz), 139.2; HRMS
calcd for C30H31FeN2PS [MþH]: 539.1373, found 539.1391.
(Rc,SFc)-ImiFerroS 1c was obtained as a yellow solid in 62% yield.
25
Mp: 146e148 ꢀC; [
CDCl3):
a]
¼ꢁ311.9 (c 1.0, CH2Cl2); 1H NMR (400 MHz,
4.4. General procedure for catalytic asymmetric 1,3-dipolar
cycloaddition of azomethine ylides
D
d 7.39e7.44 (m, 4H), 7.28e7.34 (m, 6H), 7.26e7.27 (m, 3H),
6.97e6.99 (m, 2H), 6.86 (m, 1H), 6.53e6.60 (m, 2H), 6.49e6.51 (m,
2H), 5.98e6.00 (m, 1H), 4.88 (s, 1H), 4.39 (s, 1H), 4.13 (s, 5H), 3.75 (s,
Under nitrogen atmosphere, a solution of [Cu(CH3CN)4]ClO4
(0.005 mmol) and (Rc,SFc)-ImiFerroS 1e (0.0055 mmol) in 1 mL of
toluene was stirred at room temperature for 1 h. The reaction
mixture was cooled to 0 ꢀC, and then a solution of imino esters 5
(0.5 mmol) in 2 mL of toluene, Et3N (0.05 mmol) and dimethyl
dimelate 6 (0.6 mmol) were added successively. Once the material
consumed (monitored by TLC), the mixture was filtered through
Celite. The filtrate was concentrated in vacuum to give an endo/exo
ratio of the crude product (determined by 1H NMR). The residue
was purified by flash chromatography (petroleum/EtOAc, 2/1) to
afford the cycloadduct, which was then analyzed by chiral HPLC to
determine the enantiomeric excess.
1H), 1.70 (d, J¼6.6 Hz, 3H); 31P NMR (162 MHz, CDCl3):
d
ꢁ24.9; 13
C
NMR (100 MHz, CDCl3):
d 149.8, 137.1, 136.2, 136.1, 135.0, 134.8,
131.6, 131.4, 129.3, 129.0, 128.7, 128.1, 128.0, 127.7, 127.6, 127.2, 127.2,
121.0,120.9,118.2,111.0, 90.8 (d, J¼24.0 Hz), 77.8 (d, J¼10.8 Hz), 72.9
(d, J¼3.2 Hz), 71.0, 70.3, 68.8, 51.2, 38.1, 18.3; HRMS calcd for
C
38H33FeN2PS [MþH]: 637.1530, found 637.1516.
(Rc,SFc)-ImiFerroS 1d was obtained as a yellow solid in 75% yield.
25
Mp: 99e100 ꢀC; [
CDCl3):
a
]
¼ꢁ352.3 (c 1.0, CH2Cl2); 1H NMR (400 MHz,
D
d 7.41 (m, 2H), 7.31 (m, 3H), 7.23e7.25 (m, 2H), 6.86e6.99
(m, 3H), 6.49e6.59 (m, 4H), 5.95e5.97 (m, 1H), 4.92 (s, 1H), 4.40 (s,
1H), 4.17 (s, 5H), 3.74 (s, 1H), 2.65 (s, 3H), 1.84 (d, J¼6.6 Hz, 3H); 31
P
NMR (162 MHz, CDCl3):
d
ꢁ24.5; 13C NMR (100 MHz, CDCl3):
d
150.9, 136.7, 136.6, 135.9, 135.9, 134.9, 134.8, 131.3, 129.0, 128.1,
4.4.1. Trimethyl (2S,3R,4S,5R)-5-(4-chlorophenyl)pyrroli-dine-2,3,4-
tricarboxylate (endo-7a).3o White solid, 95% yield, endo/exo >95/5,
98% ee. Chiralpak AS-H column, 40 ꢀC, 205 nm, n-hexane/i-prop-
anol¼50/50, flow rate¼0.8 mL/min, tr¼7.67 and 10.1 min. 1H NMR
128.0,127.7,127.2,127.1,120.9,120.7,117.9,110.7, 90.5 (d, J¼24.0 Hz),
77.8 (d, J¼9.2 Hz), 73.1, 71.2, 70.3, 68.7, 51.0, 18.4, 15.3; HRMS calcd
for C32H29FeN2PS [MþH]: 561.1217, found 561.1198.
(Rc,SFc)-ImiFerroS 1e was obtained as a yellow solid in 63% yield.
(400 MHz, CDCl3):
d
7.30 (s, 4H), 4.46 (d, J¼8.0 Hz, 1H), 4.16 (d,
23
Mp: 137e138 ꢀC; [
a]
D
¼ꢁ343.5 (c 1.0, CH2Cl2); 1H NMR (400 MHz,
J¼12.0 Hz,1H), 3.81 (s, 3H), 3.69e3.74 (m, 1H), 3.69 (s, 3H), 3.55e3.59
CDCl3):
d
7.41e7.44 (m, 2H), 7.30 (m, 3H), 7.23e7.25 (m, 1H), 7.21 (m,
(m, 1H), 3.28 (s, 3H), 3.23 (br, 1H).
1H), 6.90e6.91 (m, 2H), 6.81 (m, 1H), 6.48e6.54 (m, 4H), 6.01e6.03
(m, 1H), 4.90 (s,1H), 4.40 (s, 1H), 4.16 (s, 5H), 3.95e3.99 (m,1H), 3.75
(s, 1H), 1.82 (d, J¼6.6 Hz, 3H), 1.47 (d, J¼6.0 Hz, 3H), 1.40 (d, J¼6.6 Hz,
4.4.2. Trimethyl (2S,3R,4S,5R)-5-(2-chlorophenyl)pyrroli-dine-2,3,4-
tricarboxylate (endo-7b).3o White solid, 96% yield, endo/exo >95/5,
98% ee. Chiralpak AS-H column, 40 ꢀC, 205 nm, n-hexane/i-prop-
anol¼50/50, flow rate¼0.8 mL/min, tr¼7.38 and 20.1 min. 1H NMR
3H); 31P NMR (162 MHz, CDCl3):
d
ꢁ24.9; 13C NMR (100 MHz, CDCl3):
d
150.0,137.0,136.9,136.0,135.9,135.0,134.8,131.6,131.4,128.9,128.1,
128.0, 127.5, 127.1, 127.0, 120.8, 120.6, 118.1, 111.0, 90.9 (d, J¼26.4 Hz),
77.8 (d, J¼10.4 Hz), 73.0, 71.0, 70.2, 68.8, 51.0, 38.9, 23.9, 23.6, 18.4;
HRMS calcd for C34H33FeN2PS [MþH]: 589.1530, found 589.1545.
(400 MHz, CDCl3):
d
7.48e7.50 (d, J¼8.0 Hz,1H), 7.35e7.37 (d, J¼8.0 Hz,
1H), 7.20e7.29 (m, 2H), 4.78 (d, J¼8.0 Hz, 1H), 4.19 (d, J¼12.0 Hz, 1H),
3.84 (s, 3H), 3.79e3.88 (m, 2H), 3.67 (s, 3H), 3.25 (br, 1H), 3.19 (s, 3H).
(Rc,SFc)-ImiFerroS 1f was obtained as an orange needle in 71%
23
yield. Mp: 151e152 ꢀC; [
(400 MHz, CDCl3):
a
]
¼ꢁ240.3 (c 1.0, CH2Cl2); 1H NMR
4.4.3. Trimethyl (2S,3R,4S,5R)-5-(3-chlorophenyl)pyrroli-dine-2,3,4-
tricarboxylate (endo-7c).3o White solid, 95% yield, endo/exo >95/5,
99% ee. Chiralpak AS-H column, 40 ꢀC, 205 nm, n-hexane/i-prop-
anol¼50/50, flow rate¼0.8 mL/min, tr¼7.26 and 11.8 min. 1H NMR
D
d 7.49e7.53 (m, 2H), 7.35e7.36 (m, 3H),
7.08e7.12 (m, 1H), 6.99e7.05 (m, 2H), 6.73e6.76 (m, 2H), 6.63 (s,
1H), 6.57 (s, 1H), 5.71e5.77 (m, 1H), 4.67 (s, 1H), 4.40 (s, 1H), 4.12 (s,
5H), 3.81 (s, 1H), 2.33 (s, 3H), 1.76 (d, J¼6.8 Hz, 3H); 31P NMR
(400 MHz, CDCl3):
d
7.29 (s, 1H), 7.18 (s, 3H), 4.39 (d, J¼4.0 Hz, 1H),
(162 MHz, CDCl3):
d
ꢁ24.1; 13C NMR (100 MHz, CDCl3):
d
16.3, 21.9,
4.11 (d, J¼8.0 Hz, 1H), 3.74 (s, 3H), 3.64e3.69 (m, 1H), 3.62 (s, 3H),
50.5 (d, J¼9 Hz), 69.2, 69.5, 70.1, 71.6, 72.4, 76.3 (d, J¼10 Hz), 92.9 (d,
J¼25 Hz), 117.4, 127.7, 127.9, 128.1, 128.9, 129.2, 131.7, 135.2 (d,
J¼21 Hz), 136.8 (d, J¼9 Hz), 137.8, 140.5; HRMS calcd for
3.50e3.54 (m, 1H), 3.37 (s, 1H), 3.23 (s, 3H).
4.4.4. Trimethyl (2S,3R,4S,5R)-5-phenylpyrrolidine-2,3,4-tricarboxylate
(endo-7d).3o White solid, 89% yield, endo/exo >95/5, 99% ee. Chir-
alpak AS-H column, 40 ꢀC, 205 nm, n-hexane/i-propanol¼50/50, flow
rate¼0.8 mL/min, tr¼6.72 and 11.7 min. 1H NMR (400 MHz, CDCl3):
C
28H27FeN2PS [MþH]: 511.1060, found 511.1061.
(Rc,SFc)-ImiFerroS 1g was obtained as an orange needle in 51%
23
yield. Mp: 120e122 ꢀC; [
a
]
¼ꢁ116.8 (c 0.8, CH2Cl2); 1H NMR
D
(400 MHz, CDCl3):
d
7.48e7.49 (m, 2H), 7.34e7.35 (m, 3H),
d
7.19e7.29 (m, 5H), 4.42 (d, J¼8.0 Hz, 1H), 4.10 (d, J¼8.0 Hz, 1H), 3.74
7.12e7.20 (m, 6H), 7.01e7.05 (m, 2H), 6.75e6.79 (m, 2H), 6.69e6.71
(m, 2H), 6.03e6.06 (m, 1H), 4.63 (s, 1H), 4.39 (s, 1H), 4.09 (s, 5H),
3.81 (s, 1H), 1.54 (d, J¼6.8 Hz, 3H); 31P NMR (162 MHz, CDCl3):
(s, 3H), 3.64e3.68 (m, 1H), 3.62 (s, 3H), 3.50e3.53 (m, 1H), 3.16 (s, 3H).
4.4.5. Trimethyl (2S,3R,4S,5R)-5-(4-fluorophenyl)pyrroli-dine-2,3,4-
tricarboxylate (endo-7e).3o White solid, 87% yield, endo/exo¼95/5,
98% ee. Chiralpak AS-H column, 40 ꢀC, 205 nm, n-hexane/i-prop-
anol¼50/50, flow rate¼0.8 mL/min, tr¼7.19 and 9.99 min. 1H NMR
d
ꢁ24.9; 13C NMR (100 MHz, CDCl3):
d
22.1, 51.3 (d, J¼9 Hz), 69.1,
69.6, 70.1, 72.5 (d, J¼4 Hz), 93.0 (d, J¼25 Hz), 119.0, 126.4, 127.8,
127.9, 128.2 (d, J¼8 Hz), 128.7, 128.9, 129.2, 129.9, 131.8 (d, J¼19 Hz),
135.1 (d, J¼21 Hz), 135.4, 135.7, 136.8 (d, J¼9 Hz), 137.5; HRMS calcd
for C33H29FeN2PS [MþH]: 573.1217, found 573.1207.
(400 MHz, CDCl3):
d 7.22e7.26 (m, 2H), 6.89e6.93 (m, 2H), 4.38 (d,
J¼4.0 Hz, 1H), 4.05 (d, J¼8.0 Hz, 1H), 3.70 (s, 3H), 3.61e3.65 (m, 1H),
(Rc,SFc)-ImiFerroS 1h was obtained as an orange needle in 57%
3.59 (s, 3H), 3.46e3.50 (m, 1H), 3.16 (s, 3H), 2.83 (s, 1H).
23
yield. Mp: 149e150 ꢀC; [
(400 MHz, CDCl3):
a
]
¼ꢁ273.5 (c 1.0, CH2Cl2); 1H NMR
D
d
7.50e7.53 (m, 2H), 7.35e7.36 (m, 3H),
4.4.6. Trimethyl (2S,3R,4S,5R)-5-(4-bromophenyl)pyrroli-dine-2,3,4-
7.06e7.08 (m, 1H), 6.99e7.02 (m, 2H), 6.72e6.76 (m, 2H), 6.66 (s,
tricarboxylate (endo-7f).3o White solid, 92% yield, endo/exo >95/5,
Please cite this article in press as: Han, F.-Z.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.01.003

6
F.-Z. Han et al. / Tetrahedron xxx (2015) 1e7
99% ee. Chiralpak AS-H column, 40 ꢀC, 205 nm, n-hexane/i-prop-
(400 MHz, CDCl3):
d
7.22 (s, 4H), 4.57 (d, J¼8.0 Hz, 1H), 4.13 (d,
1
anol¼50/50, flow rate¼0.8 mL/min, tr¼7.99 and 10.8 min. H NMR
J¼8.0 Hz, 1H), 3.77 (s, 3H), 3.70 (s, 3H), 3.59e3.60 (m, 1H),
(400 MHz, CDCl3):
d 7.37e7.39 (m, 2H), 7.16e7.18 (m, 2H), 4.38 (d,
3.50e3.52 (m, 1H), 3.19 (s, 3H), 2.69 (s, 1H).
J¼8.0 Hz, 1H), 4.09 (d, J¼8.0 Hz, 1H), 3.73 (s, 3H), 3.64e3.68 (m, 1H),
3.62 (s, 3H), 3.49e3.54 (m, 1H), 3.26 (s, 1H), 3.21 (s, 3H).
4.4.15. Methyl (1S,3R,3aS,6aR)-4,6-dioxo-3-phenyl-5-(4-chlorophenyl)
octahydrocyclopenta[c]pyrrole-1-carboxylate (endo-9).3o White solid,
94% yield, endo/exo >95/5, 90% ee. Chiralpak AS-H column, 40 ꢀC,
215 nm, n-hexane/i-propanol¼80/20, flow rate¼0.8 mL/min, tr¼21.6
4.4.7. Trimethyl (2S,3R,4S,5R)-5-(4-methylphenyl)pyrroli-dine-2,3,4-
tricarboxylate (endo-7g).3o White solid, 93% yield, endo/exo >95/5,
97% ee. Chiralpak AS-H column, 40 ꢀC, 205 nm, n-hexane/i-prop-
and 53.8 min. 1H NMR (400 MHz, CDCl3):
d 7.36e7.38 (m, 4H),
1
anol¼50/50, flow rate¼0.8 mL/min, tr¼6.91 and 13.4 min. H NMR
7.31e7.32 (m, 3H), 7.11e7.12 (m, 2H), 4.54 (d, J¼4.0 Hz, 1H), 4.10 (d,
J¼4.0 Hz, 1H), 3.84 (s, 3H), 3.67e3.68 (m, 1H), 3.51e3.53 (m, 1H), 2.29
(br, 1H).
(400 MHz, CDCl3):
d 7.15e7.17 (m, 2H), 7.06e7.08 (m, 2H), 4.40 (d,
J¼8.0 Hz, 1H), 4.12 (d, J¼12.0 Hz, 1H), 3.75 (s, 3H), 3.66e3.69 (m, 1H),
3.63 (s, 3H), 3.48e3.51 (m, 1H), 3.27 (s, 1H), 3.21 (s, 3H), 2.26 (s, 3H).
4.4.16. 4-t-Butyl 2-methyl (2S,4S,5R)-5-(4-chlorophenyl)pyr-rolidine-
2,4-dicarboxylate (endo-10).3o White solid, 89% yield, endo/exo¼89/11,
67% ee. Chiralpak AS-H column, 40 ꢀC, 230 nm, n-hexane/i-prop-
anol¼90/10, flow rate¼0.8 mL/min, tr¼7.58 and 10.5 min. 1H NMR
4.4.8. Trimethyl (2S,3R,4S,5R)-5-(4-methoxyphenyl)pyrroli-dine-2,3,4-
tricarboxylate (endo-7h).3o White solid, 91% yield, endo/exo >95/5,
97% ee. Chiralpak AS-H column, 40 ꢀC, 205 nm, n-hexane/i-prop-
anol¼50/50, flow rate¼0.8 mL/min, tr¼9.79 and 16.2 min. 1H NMR
(400 MHz, CDCl3): d 7.19e7.25 (m, 4H), 4.35e4.37 (m, 1H), 3.83e3.88
(400 MHz, CDCl3):
d
7.25e7.28 (m, 2H), 6.85e6.87 (m, 2H), 4.48 (d,
(m, 1H), 3.72 (s, 3H), 3.15e3.16 (m, 1H), 2.70 (s, 1H), 2.30e2.38 (m,
1H), 2.20e2.27 (m, 1H), 0.99 (s, 9H).
J¼4.0 Hz, 1H), 4.18 (d, J¼8.0 Hz, 1H), 3.81 (s, 3H), 3.79 (s, 3H),
3.69e3.73 (m, 1H), 3.70 (s, 3H), 3.52e3.55 (m, 1H), 3.28 (s, 3H).
4.4.17. Methyl (1S,3R,3aS,6aR)-3-(4-chlorophenyl)octahydro-4-
oxocyclopenta[c]pyrrole-1-carboxylate (endo-11).4 White solid, 91%
yield, endo/exo >95/5, 99% ee. Chiralpak AS-H column, 40 ꢀC, 215 nm,
n-hexane/i-propanol¼80/20, flow rate¼1.0 mL/min, tr¼22.7 and
4.4.9. Trimethyl (2S,3R,4S,5R)-5-(4-nitrophenyl)pyrrolidine-2,3,4-
tricarboxylate (endo-7i).3o White solid, 96% yield, endo/exo >95/5,
95% ee. Chiralpak AS-H column, 40 ꢀC, 205 nm, n-hexane/i-prop-
anol¼50/50, flow rate¼0.8 mL/min, tr¼37.1 and 43.7 min. 1H NMR
30.6 min. 1H NMR (400 MHz, CDCl3)
d
7.29 (s, 4H), 4.48 (d, J¼9.6 Hz,
(400 MHz, CDCl3):
d
8.11e8.14 (m, 2H), 7.51e7.53 (m, 2H), 4.52 (d,
1H), 4.14 (d, J¼7.2 Hz, 1H), 3.83 (s, 3H), 3.24 (m, 1H), 2.91 (t, 1H), 2.58
J¼8.0 Hz, 1H), 4.14 (d, J¼8.0 Hz, 1H), 3.77 (s, 3H), 3.66e3.74 (m, 1H),
(br s, 1H), 2.20e2.01 (m, 3H), 1.86e1.84 (m, 1H).
3.63 (s, 3H), 3.59e3.61 (m, 1H), 3.21 (s, 3H), 2.95 (br, 1H).
4.4.18. Methyl (2S,3R,4S,5R)-4-benzoyl-3-phenyl-5-(4-chlorophenyl)
pyrrolidine-2-carboxylate (endo-12).4 White solid, 65% yield, endo/
exo¼2/1, 99% ee. Chiralpak AS-H column, 40 ꢀC, 215 nm, n-hexane/i-
propanol¼80/20, flow rate¼1.0 mL/min, tr¼8.49 and 12.3 min. 1H
4.4.10. Trimethyl
(2S,3R,4S,5R)-5-(4-trifluoromethylphenyl)-pyrroli-
dine-2,3,4-tricarboxylate (endo-7j).3o White solid, 97% yield, endo/exo
>95/5, 98% ee. Chiralpak AS-H column, 40 ꢀC, 205 nm, n-hexane/i-
propanol¼50/50, flow rate¼0.8 mL/min, tr¼5.87 and 7.15 min. 1H
NMR (400 MHz, CDCl3): d 7.56 (d, 2H), 7.26e7.44 (m, 8H), 7.06 (s, 4H),
NMR (400 MHz, CDCl3):
d
7.58e7.60 (m, 2H), 7.49e7.51 (m, 2H), 4.55
5.01 (d, J¼8.8 Hz, 1H), 4.53 (t, 1H), 4.23 (d, J¼8.8 Hz, 1H), 4.11 (t, 1H),
(d, J¼8.0 Hz, 1H), 4.20 (d, J¼8.0 Hz, 1H), 3.82 (s, 3H), 3.73e3.78 (m,
3.75 (s, 3H), 2.81 (br, 1H).
1H), 3.70 (s, 3H), 3.61e3.65 (m, 1H), 3.26 (s, 3H), 3.07 (br, 1H).
4.4.19. Methyl (2S,3R,4S,5R)-4-benzoyl-3,5-di(4-chlorophenyl) pyrrolidine-
2-carboxylate (endo-13).4 White solid, yield 78%, endo/exo¼91/9, 91% ee.
Chiralpak AS-H, 40 ꢀC, 215 nm, n-hexane/i-propanol¼80/20, flow
4.4.11. Trimethyl (2S,3R,4S,5R)-5-(naphthalen-2-yl)pyrroli-dine-2,3,4-
tricarboxylate (endo-7k).3o White solid, 90% yield, endo/exo >95/5,
98% ee. Chiralpak AS-H column, 40 ꢀC, 205 nm, n-hexane/i-prop-
anol¼50/50, flow rate¼0.8 mL/min, tr¼9.19 and 17.1 min. 1H NMR
rate¼1.0 mL/min, tr¼9.0 and 11.2 min. 1H NMR (400 MHz, CDCl3):
d 7.57
(d, J¼8.0 Hz, 2H), 7.46 (t, 1H), 7.29e7.33 (m, 5H), 7.02e7.08 (m, 4H), 4.99
(d, J¼8.0 Hz, 1H), 4.49 (t, 1H), 4.17 (d, J¼8.0 Hz, 1H), 4.10 (t, 1H), 3.74 (s,
3H), 2.78 (br, 1H).
(400 MHz, CDCl3):
d 7.75e7.79 (m, 4H), 7.38e7.44 (m, 3H), 4.60 (d,
J¼8.0 Hz, 1H), 4.20 (d, J¼8.0 Hz, 1H), 3.80 (s, 3H), 3.73e3.77 (m, 1H),
3.63e3.66 (m, 5H), 3.12 (s, 3H).
Acknowledgements
4.4.12. Trimethyl (2S,3R,4S,5R)-5-(2-thienyl)pyrrolidine-2,3,4-
tricarboxylate (endo-7l).3o White solid, 83% yield, endo/exo¼91/9, 79%
ee. Chiralpak AS-H column, 40 ꢀC, 205 nm, n-hexane/i-propanol¼50/
50, flow rate¼0.8 mL/min, tr¼7.04 and 14.4 min. 1H NMR (400 MHz,
We are grateful for the financial support from the Dalian In-
stitute of Chemical Physics (CAS). F.-Z. Han also thanks the National
Natural Science Foundation of China (21402102) for the financial
support.
CDCl3): d 7.22e7.23 (m, 1H), 7.03e7.04 (m,1H), 6.95e6.97 (m, 1H), 4.65
(d, J¼4.0 Hz, 1H), 4.18 (d, J¼12.0 Hz, 1H), 3.80 (s, 3H), 3.72 (s, 3H),
3.68e3.71 (m, 1H), 3.52e3.55 (m, 1H), 3.43 (s, 3H), 3.02 (br, 1H).
Supplementary data
4.4.13. Trimethyl (2S,3R,4S,5R)-2-methyl-5-(4-chlorophenyl)-pyrroli-
dine-2,3,4-tricarboxylate (endo-7n).3o White solid, 82% yield, endo/
exo¼93/7, 98% ee. Chiralpak AS-H column, 40 ꢀC, 230 nm, n-hexane/i-
propanol¼90/10, flow rate¼0.8 mL/min, tr¼8.66 and 9.53 min. 1H
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2015.01.003.
NMR (400 MHz, CDCl3):
d
7.25e7.35 (m, 4H), 4.61 (d, J¼8.0 Hz, 1H),
References and notes
3.80 (s, 3H), 3.75 (s, 3H), 3.45e3.48 (m, 1H), 3.26e3.30 (m, 1H), 3.26
(s, 3H), 1.69 (s, 3H).
1. (a) Togni, A.; Hayashi, T. Ferrocenes. Homogeneous Catalysis, Organic Synthesis,
Material Science; VCH: Weinheim, Germany, 1995; (b) Richards, C. J.; Locke, A.
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Tetrahedron: Asymmetry 1998, 9, 2377; (c) Arrayas, R. G.; Adrio, J.; Carretero, J. C.
4.4.14. Trimethyl (2S,3S,4S,5R)-5-(4-chlorophenyl)pyrroli-dine-2,3,4-
tricarboxylate (endo-8).3o White solid, 92% yield, endo/exo¼94/6,
93% ee. Chiralpak AS-H column, 40 ꢀC, 205 nm, n-hexane/i-prop-
anol¼90/10, flow rate¼0.8 mL/min, tr¼9.90 and 10.5 min. 1H NMR
ꢁ
ꢁ
ꢁ
Angew. Chem., Int. Ed. 2006, 45, 7674; (d) Stepnicka, P. Ferrocenes: Ligands, Ma-
terials and Biomolecules; John Wiley & Sons: Chichester, UK, 2008; (e) Dai, L.-X.;
Hou, X.-L. Chiral Ferrocenes in Asymmetric Catalysis; Wiley-VCH: Weinheim,
ꢁ
Germany, 2010; (f) Drusan, M.; Sebesta, R. Tetrahedron 2014, 70, 759.
Please cite this article in press as: Han, F.-Z.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.01.003

F.-Z. Han et al. / Tetrahedron xxx (2015) 1e7
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Please cite this article in press as: Han, F.-Z.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.01.003