Preparation of quarternary ammonium salt-tagged ferrocenylphosphine-imine ligands and their application to palladium-catalyzed asymmetric allylic substitution

Article abstract of DOI:10.1016/j.tetasy.2010.05.047

A series of novel quarternary ammonium salt-modified chiral ferrocenylphosphine-imine ligands have been synthesized and the molecular structure of BIT5 has been determined by single-crystal X-ray diffraction. The applicability of these ligands in asymmetric C*C and C*N bond formation was demonstrated. High enantioselectivity was obtained in the Pd-catalyzed asymmetric substitution of 1,3-diphenyl- 2-propenyl acetate, with dimethyl malonate (up to 94.6% ee) and benzylamine (up to 92.6% ee).

Full text of DOI:10.1016/j.tetasy.2010.05.047

Tetrahedron: Asymmetry 21 (2010) 1874–1884
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Preparation of quarternary ammonium salt-tagged ferrocenylphosphine-imine
ligands and their application to palladium-catalyzed asymmetric allylic
substitution
b
a
a
Hao Yuan a, Zhiming Zhou a, , Jiangliang Xiao , Lixuan Liang , Li Dai
*
a School of Chemical Engineering and the Environment, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100 081, PR China
b Liverpool Centre for Materials and Catalysis, Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of novel quarternary ammonium salt-modified chiral ferrocenylphosphine-imine ligands have
Received 18 April 2010
Accepted 26 May 2010
Available online 28 June 2010
been synthesized and the molecular structure of BIT5 has been determined by single-crystal X-ray
*
*
diffraction. The applicability of these ligands in asymmetric C –C and C –N bond formation was demon-
strated. High enantioselectivity was obtained in the Pd-catalyzed asymmetric substitution of 1,3-diphe-
nyl-2-propenyl acetate, with dimethyl malonate (up to 94.6% ee) and benzylamine (up to 92.6% ee).
Ó 2010 Published by Elsevier Ltd.
1. Introduction
moiety such as a quarternary ammonium salt unit to the ferroce-
nylphosphine-imine through the
p-conjugated benzene ring may
Transition-metal-catalyzed asymmetric allylic substitution has
found wide application in the synthesis of valuable small mole-
cules and complex natural products as one of the most powerful
tools for the enantioselective formation of carbon–carbon and car-
bon–heteroatom bonds.1 In the past decades, a large number of fer-
rocene-based chiral ligands with nitrogen and phosphorus
functional moieties (N,P-ligands) have been prepared and applied
to Pd-catalyzed asymmetric allylic substitutions. Most of them
have been reported to show excellent enantioselectivity.2,3 As an
important class of N,P-ligands, chiral ferrocenylphosphine-imine-
type ligands developed by Hayashi,4 Chung,5 and Zheng6 have pro-
vided satisfied enantioselectivity in asymmetric allylic substitution
and asymmetric hydrosilylation, which could be due to their flex-
ible coordination behavior associated with tunable steric and elec-
tronic properties. It is well known that one of the critical factors in
controlling the regioselectivity and enantioselectivity of the asym-
metric allylic substitution is the nature of the counterion of the cat-
alyst complexes.7 Thus, many researchers focused on the catalytic
effects of salt additives, including quarternary ammonium salts,
halide salts, and surfactants.8 According to several reports, specta-
cular enhancement of the enantioselectivity has been noticed
using the ammonium species or in the presence of halide anions.8,9
However, low reaction rate is still an important limitation to
overcome.1
influence the electron population, thus tune the ‘hard’ nitrogen
atom. Moreover, it is possible that the tagged salt may provide a
feasible access to introduce diverse counterions, while keeping
the chiral inducement regions unperturbed, which may become a
positive factor to catalysis. It is anticipated that such a design will
promise that the cation-anion pairs afford a synergic effect thus
affecting the reaction rates. To the best of our knowledge, there
are no reports on such kind of ligands. Therefore, we herein report
the synthesis of a new type of quarternary ammonium salt tagged
ferrocenylphosphine-imine ligands and the application in Pd-cata-
lyzed asymmetric allylic substitution.
2. Results and discussion
The quarternary ammonium salt-tagged ferrocenylphosphine-
imine ligands were prepared from (R)-1-((S)-2-(diphenylphos-
phino)ferrocenyl)ethylamine ((R,Sp)-PPFNH2) and a variety of dif-
ferent quaternary ammonium derivatives (Scheme 1). The
reaction was carried out in refluxing ethanol in the presence of
anhydrous MgSO4 as dehydrating agent. Then the target ligands
were isolated in nearly quantitative yield. New ligands can be pre-
pared on a gram scale. All compounds are yellow or orange solids,
which are stable on prolonged storage under a dry atmosphere for
several months at room temperature. Interestingly, despite the io-
nic nature, ligands are readily soluble in commonly used solvents
such as CH2Cl2, DMF, and THF. The structure of BIT5 was confirmed
by X-ray crystallography (Fig. 1).
The aforementioned research stimulated us to develop a series
of novel ferrocenylphosphine-imine ligands bearing a quarternary
ammonium salt unit. We envision that introduction of a charged
With the ligand BIT1-a in hand, we first examined its catalytic
activity under the reference experimental conditions.6a,10 On a
0.5 mmol scale, 1,3-diphenyl-2-propenyl acetate 1a reacted with
* Corresponding author. Tel./fax: +86 10 68918982.
E-mail address: zzm@bit.edu.cn (Z. Zhou).
0957-4166/$ - see front matter Ó 2010 Published by Elsevier Ltd.
doi:10.1016/j.tetasy.2010.05.047

H. Yuan et al. / Tetrahedron: Asymmetry 21 (2010) 1874–1884
1875
of choice, while good asymmetric induction can be reached when
the ligand/Pd was 1 (Table 1, entries 2–7). As the basicity of the
acetate increased, the ee value decreased (Table 1, entries 8–12).
Moreover 2.5 equiv of DMM and BSA provided the best enantiose-
lectivity (Table 1, entries 13–16). Lowering or raising the reaction
temperature decreased both the reaction rate and enantioselectiv-
ity (Table 1, entries 17 and 18). THF, acetone, DMF, and CH3CN as
solvents induced similar results. Unexpectedly, changing the sol-
vent to toluene or DMSO led to a weak drop in both conversion
and enantioselectivity (Table 1, entries 19–24). CH2Cl2 gave the
best result with the highest conversion ratio.
Under the optimal experimental conditions, the influence of
substituents in the aryl ring, steric properties of the quarternary
ammonium salt unit, and anions on the catalytic activity and
enantioselectivity were examined, and the results are listed in
Table 2. All the ligands with electron-withdrawing quarternary
ammonium salt unit provided faster reaction rate, higher ee, and
chemical yields than ammonium salt-free ligand L6, which was
consistent with the facts reported by Zheng et al. (Table 2, entries
7 and 12).6c However, in contrast to Zheng’s works,6a meta-substi-
tuent BIT2 did not show better behavior than the para-substituted
ligands BIT1-a (Table 2, entries 7 and 8). Besides, nearly a quanti-
tative yield and moderate ee value (78.0%) were observed with
ligands BIT3, containing the iodide salt on ortho-position (Table 2,
entries 7 and 9). To investigate the effect of the structure of the
quarternary ammonium salt unit, BIT4 and BIT5, with a bulky spa-
CHO
X
NH2
N
N
R
MgSO4
PPh2
PPh2
3
Fe
Fe
(R,Sp)-BIT1-X
EtOH, reflux, 2-5 h
X = Br, I, OTf, OTs,
OAc, NO3, PF6
I
N
BIT1-a = I
BIT1-b = Br
BIT1-c = OTf
BIT1-d = OTs
BIT1-e = OAc
BIT1-f = NO3
BIT1-g = PF6
N
PPh2
Fe
(R,Sp)-BIT2
I
N
N
I
N
N
PPh2
PPh2
Fe
Fe
Fe
(R,Sp)-BIT4
(R,Sp)-BIT3
Br
N
N
N
N
Bn
PPh2
PPh2
(R,Sp)-L6
tial structure and an
a-substituent salt unit, respectively, were
Fe
synthesized and employed in the asymmetric allylic alkylation.
However, they resulted in dramatically inferior chemical yield
and slightly lower ee (Table 2, entries 10 and 11). The ammonium
salt was far from the catalytic center, thus enlarging the bulk, and
had little effect on the enantioselectivity. The chemical yield was
affected by the weak solubility of BIT5, which was also observed
in the asymmetric allylic alkylation of BIT1-b. However, the elec-
tronic properties of ligand BIT4 is different from BIT1-a, in that
the positively charged cation is separated from the benzene ring
(R,Sp)-BIT5
Scheme 1. Synthesis of the quarternary ammonium salt-tagged ligands.
3.0 equiv of dimethyl malonate (DMM) in the presence of 2.0 mol %
[Pd(g
3-C3H5)Cl]2, 5.0 mol % ligand BIT1-a, 3.0 equiv of N,O-
bis(trimethlysilyl)acetamide (BSA), and 2.0 mol % potassium ace-
tate in 4 mL DMF at 20 °C. The reaction completed within 4 hours
in almost quantitative yield with a moderate ee value (80.6%) (Ta-
ble 1, entry 1). The reaction conditions were optimized in order to
improve the enantioselectivity and conversion. A variety of palla-
dium precursors, salt additives, ligand/Pd ratios, equivalents of
nucleophile, solvent, and temperature in asymmetric allylic alkyl-
ation were investigated. The results were summarized in Table 1.
by a methylene group and thus no
p-conjugation occurred with
it, which led to inferior reaction rate. These reports indicated that
in the case of the quarternary ammonium salt-tagged ligands, the
position of substituents influenced the enantioselectivity to a
greater extent than the steric properties. The effects of anions were
also investigated. It appeared that the ligands containing a halide
anion did have a more stimulative effect on enantioselectivity than
ligands containing other anions (Table 2, entries 1–7).
It was shown that [Pd(g
3-C3H5)Cl]2 was the palladium precursor
Figure 1. The crystal structure of ligand BIT5.

1876
H. Yuan et al. / Tetrahedron: Asymmetry 21 (2010) 1874–1884
Table 1
Optimization of asymmetric allylic alkylation reaction parametersa
MeOOC
COOMe
OAc
[Pd(C3H5)Cl]2 (2.5 mol%)
(R,Sp)-BIT1-a (5 mol%)
º
BSA, DMM, LiOAc, 20 C
rac
ee up to 94.6%
N
N
I
PPh2
Fe
(R,Sp)-BIT1-a
Entry
[Pd]
[Pd(
[Pd]/lig. (%/%)
DMM/BBA
Solvent
Base
Time (h)
Temp (°C)
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
g
3-C3H5)Cl]2
4/5
4/5
4/5
5/5
6/5
2.5/2.5
10/10
5/5
5/5
5/5
5/5
5/5
5/5
5/5
5/5
5/5
5/5
5/5
5/5
5/5
5/5
5/5
5/5
5/5
3/3
3/3
3/3
3/3
3/3
3/3
3/3
3/3
3/3
3/3
3/3
3/3
1.5/1.5
2/2
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
LiOAc
NaOAc
KOAc
RbOAc
CsOAc
LiOAc
LiOAc
LiOAc
LiOAc
LiOAc
LiOAc
LiOAc
LiOAc
LiOAc
LiOAc
LiOAc
LiOAc
4
24
24
4
4
8
4
4
3
3
3
3
10
10
4
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
0
40
20
20
20
20
20
20
95
34
26
94
95
48
96
92
96
95
93
94
38
79
93
89
92
47
97
91
51
95
45
95
80.6
74.2
64.8
85.5
85.4
80.2
90.8
91.0
89.1
85.5
85.3
84.9
93.6
93.6
94.5
90.1
92.5
89.2
94.6
93.3
86.9
94.4
91.3
93.3
Pd2(dba)3ꢀCHCl3
Pd(CH3CN)2Cl2
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
g
g
g
g
g
g
g
g
g
g
g
g
g
g
g
g
g
g
g
g
g
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
2.5/2.5
4/4
9
2.5/2.5
2.5/2.5
2.5/2.5
2.5/2.5
2.5/2.5
2.5/2.5
2.5/2.5
2.5/2.5
DMF
DMF
12
12
0.7
1.5
12
2
CH2Cl2
Acetone
Toluene
THF
DMSO
CH3CN
12
1.2
a
b
c
All reactions were performed in 4 mL of solvent with a molar ratio of [Pd]/ligand(BIT1-a)/MOAc/substrate/DMM/BSA = 4–10/4–10/2/100/250–400/250–400.
Isolated yield based on substrate.
Determined by chiral HPLC analysis using a chiral column (Chiralcel AD-H, hexane/i-PrOH = 95:5). The absolute configuration was determined to be (S) by comparing the
specific rotation with a literature value.11
the amount of Et3NMeI to 50 mol % caused a slight increase of
enantioselectivity and a mild decrease of chemical yield (Table 3,
entry 3). The same trend was noticed for the ligands BIT1-f,
BIT1-d, and BIT1-c in other runs. However, the enantioselectivity
was increased to 93.8% by adding 5 mol % Et3NMeI to the asym-
metric allylic alkylation of BIT1-g (Table 3, entry 12). This was
attributed to the poor coordination ability of PF6. Nevertheless
the yields were restricted to a certain extent (entries 5, 6, 8, 10,
and 12). These results experimentally confirmed that the quarter-
nary ammonium iodide-tagged ligands promoted better asymmet-
ric induction than the quarternary ammonium iodide as a co-
catalyst. Interestingly, ligand BIT1-a was next processed in the
asymmetric allylic alkylation in the absence of acetate salt. The
reaction still proceeded to give corresponding product in 48% yield
and 92.6% ee value (Table 3, entry 14), while it is 10% yield using
ammonium salt-free L6 under the same conditions (Table 3, entry
15). This phenomenon may be ascribed to the generation of a base
from BSA with the ammonium salt cations tagged on the ligands.12
The simulative effect of the ammonium iodide may be attrib-
uted to the following reasons. Firstly, the electron-withdrawing
cation moiety strongly affected the electronic properties of the chi-
Table 2
Ligand effects on the asymmetric allylic alkylationa
Entry
Ligand
Time (min)
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
BIT1-g
BIT1-f
BIT1-e
BIT1-d
BIT1-c
BIT1-b
BIT1-a
BIT2
60
90
90
50
90
120
40
60
93
95
94
96
95
56
97
94
91
59
58
42
88.1
87.4
89.9
88.2
88.1
90.8
94.6
84.3
78.0
90.2
90.8
78.2
BIT3
60
10
11
12
BIT4
BIT5
L6
120
120
240
a
All the reaction were performed in 4 mL of CH2Cl2 at 20 °C with a molar ratio of
3-C3H5)Cl]2/ligand/LiOAc/substrate/DMM/BSA = 5/5/2/100/250/250.
Isolated yield based on substrate.
[Pd(
g
b
c
Determined by chiral HPLC analysis using a chiral column (Chiralcel AD-H,
hexane/i-PrOH = 95:5). The absolute configuration was determined to be (S) by
comparing the specific rotation with a literature value.11
An improvement of the enantioselectivity was observed in the
asymmetric allylic alkylation by adding Et3NMeI and NaI as a co-
catalyst (Table 3, entries 1 and 2). However, further increasing
ral ligands though the p-conjugated benzene ring and imine bond,
which increased the catalytic activity of the Pd-complex and accel-
erated the reaction rate. Secondly, the ligand provided an effective

H. Yuan et al. / Tetrahedron: Asymmetry 21 (2010) 1874–1884
1877
Table 3
Table 4
Salt addition effects on the asymmetric allylic alkylationa
Scope of AAA with BIT1-aa
Entry
Ligand
Salt (equiv)
Time (min)
Yieldb (%)
eec (%)
[Pd(C3H5)Cl]2
1
2
3
4
5
6
7
8
9
10
11
12
13
14d
15d
L6
L6
L6
L6
NaI (5%)
Et3NMeI (5%)
Et3NMeI (50%)
—
Et3NMeI (5%)
Et3NMeI (50%)
—
Et3NMeI (5%)
—
NaI (5%)
—
240
240
240
240
120
120
90
90
50
120
90
90
32
36
33
42
74
41
95
53
96
62
95
75
93
48
10
83.6
84.0
85.8
78.2
89.8
90.2
87.4
89.2
88.2
88.6
88.1
93.8
88.1
92.6
71.1
OR1
Nu
(2.5 mol%)
Ligand
(5 mol%)
BIT1-f
BIT1-f
BIT1-f
BIT1-d
BIT1-d
BIT1-c
BIT1-c
BIT1-g
BIT1-g
BIT1-a
L6
BSA, Nu-H,
rac
º
LiOAc, 20 C
2a, Nu = CH(COOMe)2
2b, Nu = CH(COOEt)2
2c, Nu = C(Me)(COOMe)2
2d, Nu = CH(COOBn)2
2e, Nu = AcCH(COOEt)
1a, R1 = Ac
1b, R1 = Benzoyl
Et3NMeI (5%)
60
240
240
Entry
Sub.
Nu-H
Time (min)
Yieldb (%)
ee (%)
Config.
—
—
1
2
3
4
5
6
7
8
9
1b
1a
1b
1a
1b
1a
1b
1a
1b
2a
2b
2b
2c
2c
2d
2d
2e
2e
40
40
40
40
40
40
40
90
90
96
95
93
94
93
95
95
48
16
93.0c
94.0e
93.8e
90.4g
91.0g
91.6h
91.0h
Sd
Sf
Sf
Sf
Sf
Sf
Sf
a
All the reactions were performed in 4 mL of CH2Cl2 at 20 °C with a molar ratio of
3-C3H5)Cl]2/ligand/LiOAc/substrate/CH2(CO2Me)2/BSA = 5/5/2/100/250/250.
[Pd(
g
b
Isolated yield based on substrate.
Determined by chiral HPLC analysis using a chiral column (Chiralcel AD-H,
c
hexane/i-PrOH = 95:5). The absolute configuration was determined to be (S) by
comparing the specific rotation with a literature value.11
66.2 (A), 55.4 (B)i
75.1 (A), 74.1 (B)i
d
The reaction was performed without acetate salt.
a
All the reaction were performed in 4 mL of CH2Cl2 at 20 °C with a molar ratio of
3-C3H5)Cl]2/ligand/LiOAc/substrate/CH2(CO2Me)2/BSA = 5/5/2/100/250/250.
Isolated yield based on substrate.
and feasible access to introduce the iodine anion. Then, equilibra-
[Pd(
g
tion between exo-syn–syn and endo-syn–syn
p-allyl palladium
b
c
intermediates became rapid in the presence of an iodine anio-
n,7a,7d,9c which is important for obtaining high enantioselectivity.
Thirdly, the ammonium salts generated the necessary base with
BSA and an ammonium counterion. Iodine ion would attack the sil-
icon of BSA forming trimethylsilyl iodide. This base then deproto-
nated dimethyl malonate and provided the nucleophile for the
malonate addition with an ammonium counterion present.12a
In addition, we tested the scope of the asymmetric allylic alkyl-
ation catalyzed by BIT1-a. The results are shown in Table 4. Ligand
BIT1-a also showed excellent catalytic activity and chiral induction
for the asymmetric allylic alkylation of different substrates and
various nucleophiles (Table 4). The similar yields and enantioselec-
tivities of the products were gained in the asymmetric allylic alkyl-
ation of 1b. When 2e was used as a nucleophile, the alkylation
products were obtained in inferior yields and moderate enantiose-
lectivities. No de value was checked. Moreover, alkylation using 1b
afforded diastereomer B with an opposite absolute configuration
(Table 4, entries 8 and 9). In addition, excepting 2e, all of the reac-
tions were remarkably fast and nearly total conversion was
achieved in 40 min at room temperature.
Determined by chiral HPLC analysis using a chiral column (Chiralcel AD-H,
hexane/i-PrOH = 95:5).
d
The absolute configuration was determined by the specific rotation with a lit-
erature value.11
e
Determined by chiral HPLC analysis using a chiral column (Chiralcel AD-H,
hexane/i-PrOH = 95:5).
f
The absolute configuration was determined by the specific rotation with a lit-
erature value.13
g
Determined by chiral HPLC analysis using a chiral column (Chiralcel AD-H + AD-
H, hexane/i-PrOH = 99:1).
h
Determined by chiral HPLC analysis using a chiral column (Chiralcel AD-H,
hexane/i-PrOH = 90:10).
i
Determined by chiral HPLC analysis using a chiral column (Chiralcel AD-H + AD-
H, hexane/i-PrOH = 98:2). Diastereomer A: 72.1, 98.1 (major), diastereomer B: 76.5,
79.5 (major).
chemical yield (37–57%) and high enantiomeric excess (up to
84.2–92.6%) were received in all cases (Table 6, entries 1–11). Li-
gand BIT4 provided the highest enantioselectivity. In comparison
with L6 (Table 6, entry 12) better results were achieved with the
use of the quarternary ammonium salt-tagged ligands. The impor-
tance of the iodine anion was demonstrated with the increased
enantioselectivity obtained. Thus, the presence of a quarternary
ammonium salt and iodine anion was the key to high enantioselec-
tivity in asymmetric allylic amination, which was also found in
asymmetric allylic alkylation.
*
Having achieved enantioselective C –C bond formation, we ex-
tended the applications of this kind of ligands to the asymmetric
*
C –N bond formation reaction. At the beginning, in the asymmetric
allylic amination of 1a with benzylamine, employing BIT1-a as the
chiral auxiliary, product 3a was obtained in 8.0% ee value and 47%
yield (Table 5, entry 2). This disappointing result stimulated us to
investigate the influence of several parameters, including palla-
dium precursors, ligand/Pd ratios, and solvents. The results are
summarized in Table 5. Noteworthy is the effect of the solvent
and palladium source on enantioselectivity. The higher enantiose-
lectivity (32.2%) was obtained with using Pd2(dba)3ꢀCHCl3 as a
source of palladium (Table 5, entries 1–3). The influence of loading
of metal and ligand was investigated for the range of 4:5, 5:5, 6:5,
5:10, and 10:10 (Table 5, entries 2 and 4–7). The 5:5 M ratio of
Pd2(dba)3ꢀCHCl3 to BIT1-a proved to be the best condition (Table 5,
entry 1). Moreover DMF was found to be the optimal solvent for
the reaction according to the chemical yield and the enantioselec-
tivity (Table 5, entries 1 and 8–12). Besides, the variance of the
temperature was adverse to enantioselectivity or the yield.
To extend the scope of the asymmetric allylic amination cata-
lyzed by the Pd2(dba)3ꢀCHCl3 complex of ligand BIT4, some other
substrates and nitrogen nucleophilic compounds were applied in
the catalytic system. The results of the allylic substitution under
the optimum conditions are listed in Table 7. As shown in Table 7,
morpholine and pyrroline demonstrated moderate chemical and
enantiomeric excess (Table 7, entries 6–9). Potassium phthalimide
and PhCONHNH2 provided similar results to benzylamine. More-
over, all reactions were finished in 120 min.
3. Conclusion
In conclusion, we have designed and synthesized a novel class
of quarternary ammonium salt-tagged ferrocenylphosphine-imine
ligands BIT1a–f, BIT2–5, and determined the crystal structure of
BITL5. These ligands were evaluated in the Pd-catalyzed asymmet-
ric allylic substitution and provided the corresponding products in
All of the ligands were tested in asymmetric allylic amination
and the results are summarized in Table 6. In general, moderate

1878
H. Yuan et al. / Tetrahedron: Asymmetry 21 (2010) 1874–1884
Table 5
Optimization of asymmetric allylic amination reaction parametersa
Bn
OAc
HN
[Pd]
(R,Sp)-BIT1-a
NH2Bn
rac
Entry
[Pd]
[Pd(
[Pd]/Lig. (%/%)
Solvent
Temp (°C)
Yieldb (%)
eec (%)
Config.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
g
3-C3H5)Cl]2
5/5
5/5
5/5
4/5
6/5
10/10
5/10
5/5
5/5
5/5
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DMF
DMSO
CH3CN
Acetone
THF
20
20
20
20
20
20
20
20
20
20
20
20
0
47
48
38
32
34
46.
26
56
49
18
8
8.0
32.2
19.8
20.0
18.2
27.4
32.6.
89.2
84.6
85.0
78.2
33.4
89.4
77.2
(S)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
Pd2(dba)3ꢀCHCl3
Pd(dba)2
Pd2(dba)3ꢀCHCl3
Pd2(dba)3ꢀCHCl3
Pd2(dba)3ꢀCHCl3
Pd2(dba)3ꢀCHCl3
Pd2(dba)3ꢀCHCl3
Pd2(dba)3ꢀCHCl3
Pd2(dba)3ꢀCHCl3
Pd2(dba)3ꢀCHCl3
Pd2(dba)3ꢀCHCl3
Pd2(dba)3ꢀCHCl3
Pd2(dba)3ꢀCHCl3
5/5
5/5
5/5
5/5
9
15
52
DMF
DMF
40
a
b
c
All reactions were performed in 4 mL of solvent with a molar ratio of [Pd]/ligand(BIT1-a)/substrate/BnNH2 = 4–10/4–10/100/300 in 2 h.
Isolated yield based on substrate.
Determined by chiral HPLC analysis using a chiral column (Chiralcel OJ-H, hexane/i-PrOH = 90:10). The absolute configuration was determined by comparing the specific
rotation with a literature value.14
without further purification. [Pd(g
3-C3H5)Cl]2, Pd(CH3CN)2Cl2,
Table 6
Ligand effects on the asymmetric allylic aminationa
and Pd2(dba)3ꢀCHCl3 were purchased from Alfa Aesar. (R,Sp)-
PPFNH2 was prepared using the literature method.4,6a–c NMR spec-
tra were recorded at 300 or 400 MHz. Chemical shifts (d) were
given in ppm relative to TMS for 1H NMR; to residual solvent peak
for 13C NMR, and to H3PO4 as external standard for 31P NMR. Spe-
cific rotations were measured on a Perkin–Elmer 341 polarimeter.
IR spectra were measured in cmꢁ1 on Nicolet Magna IR-560. Enan-
tiomeric excesses were determined by Knauer HPLC system on
Chiralpak AD-H column.
Entry
Ligand
Time (min)
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
BIT1-g
BIT1-f
BIT1-e
BIT1-d
BIT1-c
BIT1-b
BIT1-a
BIT2
90
120
120
90
120
120
60
40
48
31
37
39
42
56
57
37
46
41
12
87.2
85.2
85.2
84.2
86.4
87.8
89.2
88.4
84.6
92.6
87.2
72.6
80
BIT3
80
10
11
12
BIT4
90
4.2. Preparation of ligands
BIT5
L6
120
90
4.2.1. BIT1-a
a
All the reaction were performed in 4 mL of DMF at 20 °C with a molar ratio of
4.2.1.1.
4-Formyl-N,N,N-trimethyl-Benzenaminium
iodide
3a18
.
To a solution of 4-(dimethylamino)benzaldehyde (14.9 g,
Pd2(dba)3ꢀCHCl3/ligand/substrate/BnNH2 = 5/5/100/300.
b
Isolated yield based on substrate.
Determined by chiral HPLC analysis using a chiral column (Chiralcel OJ-H,
0.1 mol) in acetone (50 mL) was added CH3I (42.3 g, 0.3 mol). The
solution was stirred for 8 h at 70 °C in a screw-capped vial. At
the conclusion of the reaction the 4-formyl-N,N,N-trimethyl-benz-
enaminium iodide salt precipitated from solution. The precipitate
was isolated by filtration, washed with ethyl ether, and the resid-
ual solvent was removed in vacuo. White solid; yield = 94%;
mp = 168–169 °C; 1H NMR (300 MHz, DMSO-d6): d 3.67 (s, 9H,
CH3), 8.16 (d, 2H, Ph-H, J = 8.7 Hz), 8.24 (d, 2H, Ph-H, J = 8.7 Hz),
10.12 (s, 1H, CHO).
c
hexane/i-PrOH = 90:10). The absolute configuration was determined to be (R) by
comparing the specific rotation with a literature value.14
high yields and enantioselectivities. In particular, much higher
reaction rates were observed. Ligands BIT1-a and BIT4, bearing a
quarternary ammonium iodide salt fragment, appeared to be the
best. The dramatic effect of the quarternary ammonium salt unit
on the enantioselectivity has been demonstrated. Further applica-
tions of the ligands in other type of asymmetric reactions are in
progress.
4.2.1.2. BIT1-a. 4-Formyl-N,N,N-trimethyl-benzenaminium io-
dide 3a (291 mg, 1 mmol), (R,Sp)-PPFNH2 (433 mg, 1.05 mmol),
and MgSO4 (500 mg) were added in absolute alcohol in a dried
Schlenk tube under argon, and then stirred at reflux temperature
for 4 h. MgSO4 was removed by filtration. After removing the sol-
vent under vacuum, the crude product was obtained as a yellow
solid. The residue was purified by washing with ethyl ether. After
being recrystallized from CH2Cl2, 638 mg (93% yield) of the target
compound BITL1-a was gained. Yellow solid; mp = 175–176 °C;
4. Experimental
4.1. General methods
All reactions were carried out under argon atmosphere unless
otherwise noted. Air- or water-sensitive liquids and solutions were
transferred via a syringe or a stainless steel cannula. All solvents
were degassed and dried by using standard methods prior to
use.17 Commercially available reagents were used as received
½
a 2D5
ꢂ
¼ ꢁ354:3 (c 0.6, CH2Cl2); IR (KBr) 3428 (w), 1640 (s), 1473
(s), 1433 (s), 1105 (m), 746 (s), 698 (s); 1H NMR (300 MHz,
DMSO-d6): d 1.56 (d, 3H, J = 6.6 Hz, CHCH3), 3.57 (s, 9H, CH3),

H. Yuan et al. / Tetrahedron: Asymmetry 21 (2010) 1874–1884
1879
Table 7
tube under argon, and then stirred at reflux temperature for 3 h.
MgSO4 was removed by filtration. After removing the solvent un-
der vacuum, the crude product was obtained as a yellow solid.
The residue was purified by washing with ethyl ether. After being
recrystallized from EtOH, 607 mg (95% yield) of the target com-
pound BIT1-b was gained. Yellow solid; mp = 165–167 °C;
Scope of the asymmetric allylic amination with BIT4a
Pd2(dba)3 CHCl3
(2.5 mol%)
OR1
Nu
Ligand
(5 mol%)
½
a 2D5
ꢂ
¼ ꢁ369:0 (c 0.6, CH2Cl2); IR (KBr) 3399 (w), 1642 (s), 1476
Nu-H,
(s), 1433 (s), 752 (s), 700 (m); 1H NMR (300 MHz, DMSO-d6): d
1.56 (d, 3H, J = 6.6 Hz, CHCH3), 3.63 (s, 9H, CH3), 4.06 (s, 5H, unsub-
stituted Cp-H), 3.69–4.68 (m, 3H, substrated Cp-H), 4.82 (m, 1H,
CHMe), 6.88–7.77 (m, 14H, Ph-H), 8.14 (s, 1H, N@CH); 13C NMR
(75 MHz, DMSO-d6): d 21.36 (CHMe), 56.26 (NMe3), 63.64 (d,
J = 5.2 Hz, Cp), 68.96 (CHMe), 69.10 (Cp), 69.37 (Cp0), 71.21 (Cp),
74.85 (d, J = 9.2 Hz, Cp), 95.88 (d, J = 22.9 Hz, Cp), 120.02 (Ph-C),
127.36 (Ph-C), 127.58 (d, J = 6.2 Hz, Ph-C), 128.05 (d, J = 8.0 Hz,
Ph-C), 128.74 (Ph-C), 129.05 (Ph-C), 131.84 (d, J = 18.5 Hz, Ph-C),
134.72 (d, J = 21.1 Hz, Ph-C), 136.74 (Ph-C), 136.90 (d, J = 9.2 Hz,
Ph-C), 138.59 (d, J = 9.9 Hz, Ph-C), 147.96 (Ph-C–NMe3), 157.40
(N@C). 31P NMR (120 MHz, DMSO-d6): d ꢁ24.15; MALDI: m/
z = 559.4, M+, ESI, m/z = 78.9, 80.9 Mꢁ; Anal. Calcd for
rac
4a, Nu = NHBn
1a, R1 = Ac
4b, Nu = Benzoylhydrazine
4c, Nu = Phthalimide
4d, Nu = Pyrrolidine
4e, Nu = Morpholine
1b, R1 = Benzoyl
Entry
Sub.
Nu-H
Time (min)
Yieldb (%)
ee (%)
Config.
1
2
3
4
5
6
7
8
9
1b
1a
1b
1a
1b
1a
1b
1a
1b
4a
4b
4b
4c
4c
4d
4d
4e
4e
90
40
40
120
120
20
20
30
30
39
44
31
34
27
63
52
39
35
89.2c
91.4d
90.3d
89.9e
89.0e
40.2f
39.6f
33.5f
32.0f
(R)c
(R)d
(R)d
(R)e
(R)e
(R)f
(R)f
(R)f
(R)f
C34H36BrFeN2P: C, 63.87; H, 5.68; N, 4.38. Found: C, 63.66; H,
5.65; N, 4.09.
a
All the reactions were performed in 4 mL of DMF at 20 °C with a molar ratio of
Pd2(dba)3ꢀCHCl3/ligand/substrate/BnNH2 = 5/5/100/300.
4.2.3. BIT1-c
b
Isolated yield based on substrate.
c
4.2.3.1. 4-Formyl-N,N,N-trimethyl-benzenaminium trifluoro-
Determined by chiral HPLC analysis using a chiral column (Chiralcel OJ-H,
methanesulfonate 3c19
. To a solution of 4-(dimethylamino)-
hexane/i-PrOH = 90:10). The absolute configuration was determined to be R by
comparing the specific rotation with a literature value.14
benzaldehyde (3.73 g, 35 mmol) in AcOEt (25 mL) was added tri-
fluoromethanesulfonic acid methyl ester (4.1 g, 25 mmol). The
solution was stirred for 24 h at 25 °C. At the conclusion of the reac-
tion the 4-formyl-N,N,N-trimethyl-benzenaminium trifluorometh-
anesulfonate salt precipitated from solution. The precipitate was
isolated by filtration, washed with AcOEt, and the residual solvent
was removed in vacuo. White solid; yield = 94%; mp = 108–110 °C;
1H NMR (300 MHz, DMSO-d6): d 3.65 (s, 9H, CH3), 8.16 (d, 2H, Ph-H,
J = 9 Hz), 8.22 (d, 2H, Ph-H, J = 9 Hz), 10.11 (s, 1H, CHO).
d
Determined by chiral HPLC analysis using a chiral column (Chiralcel OJ-H,
hexane/i-PrOH = 85:15). The absolute configuration was determined to be R by
comparing the specific rotation with a literature value.15
e
Determined by chiral HPLC analysis using a chiral column (Chiralcel OD-H,
hexane/i-PrOH = 98:2). The absolute configuration was determined to be R by
comparing the specific rotation with a literature value.3g
f
Determined by chiral HPLC analysis using a chiral column. The absolute con-
figuration was determined to be R by comparing the specific rotation with a liter-
ature value.16
4.06 (s, 5H, unsubstituted Cp-H), 3.68–4.67 (m, 3 H, substrated Cp-
H), 4.82 (m, 1H, CHMe), 6.87–7.77 (m, 14H, Ph-H), 8.14 (s, 1H,
N@CH); 13C NMR (75 MHz, DMSO-d6): d 21.42 (CHMe), 56.35
(NMe3), 63.74 (d, J = 5.6 Hz, Cp), 69.02 (CHMe), 69.21 (Cp), 69.43
(Cp0), 71.26 (Cp), 74.91 (d, J = 8.7 Hz, Cp), 95.94 (d, J = 23.5 Hz,
Cp), 120.10 (Ph-C), 127.41 (Ph-C), 127.64 (d, J = 5.6 Hz, Ph-C),
128.11 (d, J = 7.4 Hz, Ph-C), 128.81 (d, Ph-C), 129.13 (Ph-C),
131.90 (d, J = 17.9 Hz, Ph-C), 134.77 (d, J = 21.0 Hz, Ph-C), 136.75
(Ph-C), 136.95 (d, J = 9.3 Hz, Ph-C), 138.65 (d, J = 9.3 Hz, Ph-C),
148.10 (Ph-C–NMe3), 157.49 (N@C); 31P NMR (120 MHz, DMSO-
d6): d ꢁ24.16; MALDI: m/z = 559.4, M+, ESI, m/z = 127 Mꢁ; Anal.
Calcd for C34H36FeIN2P: C, 59.49; H, 5.29; N, 4.08. Found: C,
59.49; H, 5.22; N, 4.00.
4.2.3.2. BIT1-c. 4-Formyl-N,N,N-trimethyl-benzenaminium tri-
fluoromethanesulfonate (313 mg, 1 mmol), (R,Sp)-PPFNH2 (433
mg, 1.05 mmol), and MgSO4 (500 mg) were added in absolute alco-
hol in a dried Schlenk tube under argon, and then stirred at reflux
temperature for 3 h. MgSO4 was removed by filtration. After
removing the solvent under vacuum, the crude product was ob-
tained as a yellow solid. The residue was purified by washing with
ethyl ether. After being recrystallized from CH2Cl2 and hexane,
666 mg (94% yield) of the target compound BIT1-c was gained. Yel-
low solid; mp = 126–129 °C; ½a D25
¼ ꢁ353:9 (c 0.6, CH2Cl2); IR (KBr)
ꢂ
3464 (w), 1643 (s), 1495 (m), 1260 (s); 1H NMR (300 MHz, DMSO-
d6): d 1.57 (d, 3H, J = 6.3 Hz, CHCH3), 3.31 (s, 9H, CH3), 4.06 (s, 5H,
unsubstituted Cp-H), 3.69–4.68 (m, 3H, substrated Cp-H), 4.82 (m,
1H, CHMe), 6.87–7.77 (m, 14H, Ph-H), 8.13 (s, 1H, N@CH); 13C NMR
(75 MHz, DMSO-d6): d 21.40 (CHMe), 56.04 (NMe3), 63.61 (d,
J = 6.2 Hz, Cp), 69.07 (CHMe), 69.24 (Cp), 69.40 (Cp0), 71.131 (Cp),
74.89 (d, J = 8.6 Hz, Cp), 94.76 (d, J = 22.9 Hz, Cp), 118.65 (CF3),
121.80 (Ph-C), 127.11 (Ph-C), 127.55 (d, J = 4.8 Hz, Ph-C), 128.10
(d, J = 8.0 Hz, Ph-C), 129.05 (d, J = 13.6 Hz, Ph-C), 129.71 (Ph-C),
131.94 (d, J = 17.9 Hz, Ph-C), 134.75 (d, J = 21.7 Hz, Ph-C), 136.83
(d, J = 9.2 Hz, Ph-C), 137.27 (Ph-C), 138.74 (d, J = 9.2 Hz, Ph-C),
146.81 (Ph-C), 157.78 (C@N); 31P NMR (120 MHz, DMSO-d6): d
ꢁ24.36; ESI m/z = 559.1, M+, ESI, m/z = 148.9 Mꢁ; Anal. Calcd for
C35H36FeN2O3PS: C, 59.33; H, 5.12; N, 3.95. Found: C, 59.59; H,
5.03; N, 3.94.
4.2.2. BIT1-b
4.2.2.1. 4-Formyl-N,N,N-trimethyl-benzenaminium bromide
3b. To a solution of 4-(dimethylamino)benzaldehyde (1.49 g,
10 mol) in acetone (5 mL) was added CH3Br (2.82 g, 30 mmol).
The solution was stirred for 8 h at 70 °C in a screw-capped vial.
At the conclusion of the reaction the 4-formyl-N,N,N-trimethyl-
benzenaminium bromide salt precipitated from solution. The pre-
cipitate was isolated by filtration, washed with ethyl ether, and
residual solvent was removed in vacuo. White solid; yield = 92%;
mp = 221–223 °C; 1H NMR (300 MHz, DMSO-d6): d 3.69 (s, 9H,
CH3), 8.13 (d, 2H, Ph-H, J = 9 Hz), 8.25 (d, 2H, Ph-H, J = 9 Hz),
10.16 (s, 1H, CHO).
4.2.4. BIT1-d
4.2.2.2. BIT1-b. 4-Formyl-N,N,N-trimethyl-benzenaminium bro-
mide (244 mg, 1 mmol), (R,Sp)-PPFNH2 (433 mg, 1.05 mmol), and
MgSO4 (500 mg) were added in absolute alcohol in a dried Schlenk
4.2.4.1. 4-Formyl-N,N,N-trimethyl-benzenaminium p-toluene-
sulfon-ate 3d. To a solution of 4-formyl-N,N,N-trimethyl-benze-
naminium iodide (1.455 g, 5 mmol) in water (5 mL) was added

1880
H. Yuan et al. / Tetrahedron: Asymmetry 21 (2010) 1874–1884
AgOTs (1.395 g, 5 mmol). The solution was stirred for 4 h at 25 °C.
At the conclusion of the reaction the AgI precipitated from solu-
tion. The precipitate was isolated by filtration. The filtrate was con-
centrated under reduced pressure. The white solid was dried in
vacuo. yield = 98%; mp = 249–251 °C; 1H NMR (300 MHz, DMSO-
d6): d 2.28 (s, 3H, Ph-CH3), 3.66 (s, 9H, N(CH3)3), 7.11 (d, 2H, Ph-
H, J = 7.8 Hz), 7.74 (d, 2H, Ph-H, J = 7.8 Hz), 8.14 (d, 2H, Ph-H,
J = 9 Hz), 8.22 (d, 2H, Ph-H, J = 9 Hz), 10.11 (s, 1H, CHO).
J = 8.3 Hz, Ph-C), 127.93 (d, J = 9.9 Hz, Ph-C), 128.63 (Ph-C),
128.94 (Ph-C), 131.71 (d, J = 24.7 Hz, Ph-C), 134.58 (d, J = 28 Hz,
Ph-C), 136.63 (Ph-C), 136.76 (d, J = 12.3 Hz, Ph-C), 138.47 (d,
J = 13.2 Hz, Ph-C), 147.76 (Ph-C–NMe3), 157.25 (N@C); 31P NMR
(120 MHz, DMSO-d6): d ꢁ24.15; MALDI m/z = 559.4, M+, ESI, m/
z = 59 Mꢁ; Anal. Calcd for C36H39FeN2O2P: C, 69.91; H, 6.36; N,
4.53. Found: C, 69.92; H, 6.66; N, 4.41.
4.2.6. BIT1-f
4.2.4.2. BIT1-d. 4-Formyl-N,N,N-trimethyl-benzenaminium p-tol-
uenesulfonate (335 mg, 1 mmol), (R,Sp)-PPFNH2 (433 mg,
1.05 mmol), and MgSO4 (500 mg) were added in absolute alcohol
in a dried Schlenk tube under argon, and then stirred at reflux tem-
perature for 3 h. MgSO4 was removed by filtration. After removing
the solvent under vacuum, the crude product was obtained as a
yellow solid. The residue was purified by washing with ethyl ether.
After recrystallized from EtOH, 680 mg (93% yield) of the target
compound BIT1-d was gained. Yellow solid; mp = 178–181 °C;
4.2.6.1.
4-Formyl-N,N,N-trimethyl-benzenaminium
nitrate
3f. To a solution of 4-formyl-N,N,N-trimethyl-benzenaminium io-
dide (1.455 g, 5 mmol) in water (5 mL) was added AgNO3
(849.4 mg, 5 mmol). The solution was stirred for 2 h at 25 °C. At
the conclusion of the reaction the AgI precipitated from solution.
The precipitate was isolated by filtration. The filtrate was concen-
trated under reduced pressure. The white solid was dried in vacuo.
Yield = 94%; mp = 151–153 °C; 1H NMR (300 MHz, DMSO-d6): d
3.70 (s, 9H, CH3), 8.15 (d, 2H, Ph-H, J = 9 Hz), 8.30 (d, 2H, Ph-H,
J = 9 Hz), 10.12 (s, 1H, CHO).
½
a 2D5
ꢂ
¼ ꢁ368:29 (c 0.6, CH2Cl2); IR (KBr) 3467 (w), 1643 (s), 1473
(m), 1192 (s), 749 (s), 697 (s); 1H NMR (300 MHz, DMSO-d6): d
1.56 (d, 3H, J = 6.6 Hz, CHCH3), 2.28 (s, 3H, Ph-CH3), 3.56 (s, 9H,
N(CH3)3), 4.06 (s, 5H, unsubstituted Cp-H), 3.69–4.67 (s, 3 H, sub-
strated Cp-H), 4.82 (m, 1H, CHMe), 6.86–7.76 (m, 14H, Ph-H),
7.11 (d, 2H, Ph-H, J = 7.5 Hz), 7.75 (d, 2H, Ph-H, J = 7.5 Hz), 8.13
(s, 1H, N@CH); 13C NMR (75 MHz, DMSO-d6): d 21.38 (CH3),
21.99 (CHMe), 58.86 (NMe3), 63.945 (Cp), 69.012 (CHMe), 69.606
(Cp), 70.007 (Cp0), 71.786 (Cp), 75.43 (Cp), 96.53 (d, J = 23.6 Hz,
Cp), 120.56 (Ph-C), 126.06 (Ph-C), 127.95 (Ph-C), 128.17 (Ph-C),
128.67 (Ph-C), 129.39 (Ph-C), 139.70 (Ph-C), 132.46 (d,
J = 18.0 Hz, Ph-C), 135.33 (d, J = 20.8 Hz, Ph-C), 137.22 (Ph-C),
137.52 (d, J = 9.2 Hz, Ph-C), 138.27 (Ph-C), 139.35 (d, J = 9.9 Hz,
Ph-C), 146.19 (Ph-C), 148.548 (Ph-C), 158.98 (C@N); 31P NMR
(80 MHz, DMSO-d6): d ꢁ24.73 (s, 1P, PPh2); ESI m/z = 559.1, M+,
ESI, m/z = 171.0 Mꢁ; Anal. Calcd for C41H43FeN2O3PS: C, 67.39; H,
5.93; N, 3.83. Found: C, 67.17; H, 6.03; N, 3.81.
4.2.6.2. BIT1-f. 4-Formyl-N,N,N-trimethyl-Benzenaminium ni-
trate (226 mg, 1 mmol), (R,Sp)-PPFNH2 (433 mg, 1.05 mmol) and
MgSO4 (500 mg) were added in absolute alcohol in a dried Schlenk
tube under argon, and then stirred at reflux temperature for 3 h.
MgSO4 was removed by filtration. After removing the solvent un-
der vacuum, the crude product was obtained as a yellow solid.
The residue was purified by washing with ethyl ether. After recrys-
tallized from CH2Cl2 and hexane, 597 mg (96% yield) of the target
compound BIT1-f was gained. Yellow solid; mp = 151–152 °C;
½
a 2D5
ꢂ
¼ ꢁ355:7 (c 0.6, CH2Cl2); IR (KBr) 3421 (w), 1642 (s), 1477
(m), 1384 (s); 1H NMR (300 MHz, DMSO-d6): d 1.58 (d, 3H,
J = 6.6 Hz, CHCH3), 3.53 (s, 9H, CH3), 4.05 (s, 5H, unsubstituted
Cp-H), 3.70–4.68 (m, 3H, substrated Cp-H), 4.83 (m, 1H, CHMe),
6.78–7.89 (m, 14H, Ph-H), 8.11 (s, 1H, N@CH); 13C NMR (75 MHz,
DMSO-d6): d 21.34 (CHMe), 56.32 (NMe3), 63.79 (d, J = 6.3 Hz,
Cp), 69.00 (CHMe), 69.14 (Cp), 69.43 (Cp0), 71.22 (Cp), 74.91 (d,
J = 10.8 Hz, Cp), 95.91 (d, J = 22.9 Hz, Cp), 119.90 (Ph-C), 127.339
(Ph-C), 127.60 (d, J = 6.3 Hz, Ph-C), 128.08 (d, J = 7.3 Hz, Ph-C),
128.83 (Ph-C), 129.08 (Ph-C), 131.78 (d, J = 18.5 Hz, Ph-C), 134.76
(d, J = 20.3 Hz, Ph-C), 136.84 (Ph-C), 136.95 (d, J = 9.9 Hz, Ph-C),
138.65 (d, J = 9.9 Hz, Ph-C), 147.89 (Ph-C), 157.41 (C@N); 31P
NMR (120 MHz, DMSO-d6): d ꢁ24.12; ESI m/z = 559.2, M+, ESI, m/
z = 62 Mꢁ; Anal. Calcd for C34H36FeN3O3P: C, 65.71; H, 5.84; N,
6.76. Found: C, 66.13; H, 5.63; N, 6.37.
4.2.5. BIT1-e
4.2.5.1. 4-Formyl-N,N,N-trimethyl-benzenaminium acetate
3e. To a solution of 4-formyl-N,N,N-trimethyl-benzenaminium io-
dide (1.455 g, 5 mmol) in water (5 mL) was added AgOAc
(834.6 mg, 5 mmol). The solution was stirred for 2 h at 25 °C. At
the conclusion of the reaction the AgI precipitated from solution.
The precipitate was isolated by filtration. The filtrate was concen-
trated under reduced pressure. The white solid was dried in vacuo.
Yield = 97%; mp = 132–135 °C; 1H NMR (300 MHz, DMSO-d6): d
1.53 (s, 3H, CH3), 3.70 (s, 9H, CH3), 8.15 (d, 2H, Ph-H, J = 9 Hz),
8.30 (d, 2H, Ph-H, J = 9 Hz), 10.12 (s, 1H, CHO).
4.2.7. BIT1-g
4.2.7.1. 4-Formyl-N,N,N-trimethyl-benzenaminium hexafluoro-
phosphate 3g. To a solution of 4-formyl-N,N,N-trimethyl-benze-
naminium iodide (1.455 g, 5 mmol) in water (5 mL) was added
NH4PF6 (984 mg, 6 mmol). The solution was stirred for 4 h at
25 °C. At the conclusion of the reaction the 4-formyl-N,N,N-tri-
methyl-benzenaminium hexafluorophosphate precipitated from
solution. The precipitate was isolated by filtration, washed with
water. The white solid was dried in vacuo. Yield = 91%;
mp = 170–171 °C; 1H NMR (300 MHz, DMSO-d6): d 3.67 (s, 9H,
CH3), 8.17 (d, 2H, Ph-H, J = 8.4 Hz), 8.23 (d, 2H, Ph-H, J = 8.4 Hz),
10.12 (s, 1H, CHO).
4.2.5.2. BIT1-e. 4-Formyl-N,N,N-trimethyl-benzenaminium ace-
tate (223 mg, 1 mmol), (R,Sp)-PPFNH2 (433 mg, 1.05 mmol), and
MgSO4 (500 mg) were added in absolute alcohol in a dried Schlenk
tube under argon, and then stirred at reflux temperature for 3 h.
MgSO4 was removed by filtration. After removing the solvent un-
der vacuum, the crude product was obtained as a yellow solid.
The residue was purified by washing with ethyl ether. After recrys-
tallized from CH2Cl2 and hexane, 569 mg (92% yield) of the target
compound BIT1-e was gained. Yellow solid; mp = 149–152 °C;
½
a 2D5
ꢂ
¼ ꢁ345:0 (c 0.6, CH2Cl2); IR (KBr) 3412 (w), 1640 (s), 1569
(s), 1407 (m); 1H NMR (300 MHz, DMSO-d6): d 1.49 (s, 3H, COCH3),
1.56 (d, 3H, J = 6.3 Hz, CHCH3), 3.57 (s, 9H, CH3), 4.05 (s, 5H, unsub-
stituted Cp-H), 3.68–4.67 (m, 3H, substrated Cp-H), 4.81 (m, 1H,
CHMe), 6.87–7.77 (m, 14H, Ph-H), 8.13 (s, 1H, N@CH); 13C NMR
4.2.7.2. BIT1-g. 4-Formyl-N,N,N-trimethyl-benzenaminium hexa-
fluorophosphate (309 mg, 1 mmol), (R,Sp)-PPFNH2 (433 mg,
1.05 mmol), and MgSO4 (500 mg) were added in CH2Cl2 in a dried
Schlenk tube under argon, and then stirred at room temperature
for 3 h. MgSO4 was removed by filtration. After removing the sol-
vent under vacuum, the crude product was obtained as a yellow
solid. The residue was purified by washing with ethyl ether. After
being recrystallized from EtOH, 669 mg (95% yield) of the target
(75 MHz, DMSO-d6):
d 21.15 (CHMe), 22.04 (COMe), 55.22
(NMe3), 63.56 (d, J = 8.3 Hz, Cp), 68.84 (CHMe), 69.02 (Cp), 69.25
(Cp0), 70.99 (d, J = 9 Hz, Cp), 74.72 (d, J = 13.1 Hz, Cp), 95.75 (d,
J = 30.4 Hz, Cp), 119.86 (Ph-C), 127.22 (Ph-C), 127.46 (d,

H. Yuan et al. / Tetrahedron: Asymmetry 21 (2010) 1874–1884
1881
compound BIT1-g was gained. Yellow solid; mp = 205–206 °C;
¼ ꢁ364:75 (c 0.6, CH2Cl2); IR (KBr) 3264 (w), 1643 (s), 1495
CH3), 7.97 (m, 2H, Ph-H), 8.11 (m, 1H, Ph-H), 8.33 (dd, 1H, Ph-H,
J1 = 7.2 Hz, J2 = 2.1 Hz), 10.22 (s, 1H, CHO).
½ ꢂ
a 2D5
(m), 844 (s); 1H NMR (300 MHz, DMSO-d6): d 1.57 (d, 3H,
J = 6.3 Hz, CHCH3), 3.57 (s, 9H, CH3), 4.06 (s, 5H, unsubstituted
Cp-H), 3.70–4.68 (m, 3H, substrated Cp-H), 4.83 (m, 1H, CHMe),
6.87–7.77 (m, 14H, Ph-H), 8.14 (s, 1H, N@CH); 13C NMR
(100 MHz, DMSO-d6): d 22.08 (CHMe), 55.04 (NMe3), 64.48 (Cp),
69.72 (CHMe), 69.89 (Cp), 70.14 (Cp0), 71.98 (Cp), 75.63 (d,
J = 9.9 Hz, Cp), 96.63 (d, J = 23.3 Hz, Cp), 120.59 (Ph-C), 128.03
(Ph-C), 128.30 (d, J = 5.8 Hz, Ph-C), 128.80 (d, J = 7.6 Hz, Ph-C),
129.55 (Ph-C), 129.81 (Ph-C), 132.62 (d, J = 18.3 Hz, Ph-C), 135.48
(d, J = 20.9 Hz, Ph-C), 137.58 (Ph-C), 137.60 (d, J = 23.7 Hz, Ph-C),
139.42 (d, J = 20.3 Hz, Ph-C), 148.60 (Ph-C–NMe3), 158.11 (N@C);
31P NMR (80 MHz, DMSO-d6): d ꢁ24.33, ꢁ143.21 (m, J = 686 Hz,
PF6); MALDI m/z = 559.4, M+, ESI, m/z = 145 Mꢁ; Anal. Calcd for
4.2.9.2. BIT3. 2-Formyl-N,N,N-trimethyl-benzenaminium iodide
(291 g, 1 mmol), (R,Sp)-PPFNH2 (433 mg, 1.05 mmol), and MgSO4
(500 mg) were added in absolute alcohol in a dried Schlenk tube
under argon, and then stirred at reflux temperature for 3 h. MgSO4
was removed by filtration. After removing the solvent under vac-
uum, the crude product was obtained as a yellow solid. The residue
was purified by washing with ethyl ether. After being recrystal-
lized from CH2Cl2 and hexane, 652 mg (95% yield) of the target
compound BIT3 was gained. Yellow solid; mp = 170–171 °C;
½
a 2D5
ꢂ
¼ ꢁ339:85 (c 0.6, CH2Cl2); IR (KBr) 3431 (w), 1638 (s), 1481
(s), 748 (s), 699 (s); 1H NMR (300 MHz, DMSO-d6): d 1.56 (d, 3H,
J = 4.2 Hz, CHCH3), 3.56 (s, 9H, CH3), 4.056 (s, 5H, unsubstituted
Cp-H), 3.68–4.67 (m, 3H, substrated Cp-H), 4.83 (m, 1H, CHMe),
6.87–7.89 (m, 14H, Ph-H), 8.136 (s, 1H, N@CH); 13C NMR
(100 MHz, DMSO-d6): d 21.26 (CHMe), 56.22 (NMe3), 63.704 (Cp),
69.03 (CHMe), 69.33 (d, J = 22.3 Hz, Cp), 69.94 (Cp0), 71.28 (Cp),
74.89 (d, J = 12.3 Hz, Cp), 95.64 (d, J = 30.5 Hz, Cp), 122.63 (Ph-C),
123.13 (Ph-C), 124.12 (Ph-C), 127.05 (Ph-C), 127.50 (d, J = 8.2 Hz,
Ph-C), 128.09 (d, J = 9.1 Hz, Ph-C), 129.11 (Ph-C), 130.03 (Ph-C),
130.78 (Ph-C), 131.99 (d, J = 24.7 Hz, Ph-C), 133.26 (Ph-C), 134.72
(d, J = 31 Hz, Ph-C), 136.77 (d, J = 11.5 Hz, Ph-C), 137.32 (d,
J = 27.2 Hz, Ph-C), 138.75 (d, J = 13.2 Hz, Ph-C), 147.12 (Ph-C–
NMe3), 156.79 (N@C); 31P NMR (80 MHz, DMSO-d6): d ꢁ24.17;
MALDI m/z = 559.4, M+, ESI, m/z = 127 Mꢁ; Anal. Calcd for
C34H36F6FeN2P2: C, 57.97; H, 5.15; N, 3.98. Found: C, 57.94; H,
5.21; N, 3.91.
4.2.8. BIT2
4.2.8.1.
3-Formyl-N,N,N-trimethyl-benzenaminium
iodide
3h. To a solution of 3-(dimethylamino)benzaldehyde (1.49 g,
10 mmol) in acetone (5 mL) was added CH3I (4.23 g, 30 mmol).
The solution was stirred for 8 h at 70 °C in a screw-capped vial.
At the conclusion of the reaction the 3-formyl-N,N,N-trimethyl-
benzenaminium iodide salt precipitated from solution. The precip-
itate was isolated by filtration, washed with ethyl ether, and the
residual solvent was removed in vacuo. White solid; yield = 84%;
mp = 211–213 °C; 1H NMR (300 MHz, DMSO-d6): d 3.67 (s, 9H,
CH3), 7.86–8.47 (m, 4H, Ph-H), 10.12 (s, 1H, CHO).
C34H36FeIN2P: C, 59.49; H, 5.29; N, 4.08. Found: C, 59.61; H, 5.66;
N, 4.13.
4.2.8.2. BIT2. 3-Formyl-N,N,N-trimethyl-benzenaminium iodide
(291 g, 1 mmol), (R,Sp)-PPFNH2 (433 mg, 1.05 mmol), and MgSO4
(500 mg) were added in absolute alcohol in a dried Schlenk tube
under argon and then stirred at reflux temperature for 3 h. MgSO4
was removed by filtration. After removing the solvent under vac-
uum, the crude product was obtained as a yellow solid. The residue
was purified by washing with ethyl ether. After recrystallized from
CH2Cl2 and hexane, 618 mg (90% yield) of the target compound
4.2.10. BIT4
4.2.10.1. 4-Formyl-N,N,N-trimethyl-benzenemethanaminium,
iodide 3j20
. To a solution of 4-((dimethylamino)methyl)benzalde-
hyde (816 mg, 5 mmol) in AcOEt (5 mL) was added CH3I (2.115 g,
15 mmol). The solution was stirred for 12 h at 25 °C in a screw-
capped vial. At the conclusion of the reaction the 4-formyl-N,N,N-
trimethyl-benzenemethanaminium iodide salt precipitated from
solution. The precipitate was isolated by filtration, washed with
AcOEt, and residual solvent was removed in vacuo. White solid;
yield = 92%; mp = 201–204 °C; 1H NMR (300 MHz, DMSO-d6): d
3.08 (s, 9H, N(CH3)3), 4.67 (s, 2H, CH2), 7.79 (d, 2H, Ph-H,
J = 7.8 Hz), 8.06 (d, 2H, Ph-H, J = 7.8 Hz), 10.12 (s, 1H, CHO).
BIT2 was gain. Yellow solid; mp = 170–172 °C; ½a D25
¼ ꢁ347:2 (c
ꢂ
0.6, CH2Cl2); IR (KBr) 3434 (w), 1642 (s), 1583 (s), 1476 (s), 1434
(s), 748 (s), 686 (s); 1H NMR (300 MHz, DMSO-d6): d 1.59 (d, 3H,
J = 4.8 Hz, CHCH3), 3.53 (s, 9H, CH3), 4.06 (s, 5H, unsubstituted
Cp-H), 3.70–4.69 (m, 3H, substrated Cp-H), 4.86 (m, 1H, CHMe),
6.81–7.89 (m, 14H, Ph-H), 8.12 (s, 1H, N@CH); 13C NMR
(100 MHz, DMSO-d6): d 21.58 (CHMe), 56.48 (NMe3), 63.74 (d,
J = 6.8 Hz, Cp), 69.20 (CHMe), 69.38 (d, J = 3.7 Hz, Cp), 69.56 (Cp0),
71.31 (d, J = 4.9 Hz, Cp), 75.07 (d, J = 9.1 Hz, Cp), 95.94 (d,
J = 23.5 Hz, Cp), 118.83 (Ph-C), 121.97 (Ph-C), 127.27 (Ph-C),
127.70 (d, J = 6 Hz, Ph-C), 128.25 (d, J = 7.8 Hz, Ph-C), 129.20 (d,
J = 17.9 Hz, Ph-C), 129.86 (Ph-C), 132.11 (d, J = 18.2 Hz, Ph-C),
134.91 (d, J = 21.1 Hz, Ph-C), 137.01 (d, J = 9.1 Hz, Ph-C), 137.45
(Ph-C), 138.89 (d, J = 10 Hz, Ph-C), 146.99 (Ph-C–NMe3), 157.93
(N@C); 31P NMR (120 MHz, DMSO-d6): d ꢁ24.28; MALDI m/
z = 559.4, M+, ESI, m/z = 127 Mꢁ; Anal. Calcd for C34H36FeIN2P: C,
59.49; H, 5.29; N, 4.08. Found: C, 59.21; H, 5.42; N, 4.03.
4.2.10.2. BIT4. 4-Formyl-N,N,N-trimethyl-benzenemethanamini-
um, iodide (305 mg, 1 mmol), (R,Sp)-PPFNH2 (433 mg, 1.05 mmol),
and MgSO4 (500 mg) were added in absolute alcohol in a dried
Schlenk tube under argon, and then stirred at reflux temperature
for 3 h. MgSO4 was removed by filtration. After removing the sol-
vent under vacuum, the crude product was obtained as a yellow
solid. The residue was purified by washing with ethyl ether. After
recrystallized from EtOH, 651 mg (93% yield) of the target com-
pound BIT4 was gained. Yellow solid; mp = 149–151 °C;
½
a 2D5
ꢂ
¼ ꢁ352:3 (c 0.6, CH2Cl2); IR (KBr) 3423 (w), 1706 (s), 1643
(s), 1479 (s), 1432 (s), 749 (s), 696 (s); 1H NMR (300 MHz,
DMSO-d6): d 1.55 (d, 3H, J = 6 Hz, CHCH3), 2.96 (s, 9H, N(CH3)3),
4.01 (s, 5H, unsubstituted Cp-H), 3.69–4.64 (s, 3H, substrated Cp-
H), 4.79 (m, 1H, CHMe), 4.44 (s, 2H, CH2), 6.82–7.44 (m, 14H, Ph-
H), 8.08 (s, 1H, N@CH); 13C NMR (75 MHz, DMSO-d6): d 20.25
(CHMe), 52.04 (NMe), 56.75 (Ph-CH2–N), 64.58 (d, J = 6.5 Hz, Cp),
68.41 (CHMe), 69.33 (Cp), 69.54 (Cp0), 71.67 (Cp), 75.22 (Cp),
95.46 (d, J = 23.0 Hz, Cp), 126.75 (Ph-C), 127.55 (d, J = 6.5 Hz, Ph-
C), 127.89 (d, J = 8.6 Hz, Ph-C), 128.44 (Ph-C), 128.89 (Ph-C),
129.11 (Ph-C), 132.17 (Ph-C), 132.47 (Ph-C), 135.26 (d,
J = 18.6 Hz, Ph-C), 137.22 (Ph-C), 137.40 (Ph-C), 139.22 (Ph-C),
160.70 (C@N); 31P NMR (120 MHz, DMSO-d6): d ꢁ24.54 (s, 1P,
PPh2); ESI m/z = 573.2, M+, ESI, m/z = 126.9 Mꢁ; Anal. Calcd for
4.2.9. BIT3
4.2.9.1.
2-Formyl-N,N,N-trimethyl-benzenaminium
iodide
3i. To
a solution of 2-(dimethylamino)benzaldehyde (1.49 g,
10 mmol) in acetone (5 mL) was added CH3I (4.23 g, 30 mmol).
The solution was stirred for 8 h at 70 °C in a screw-capped vial.
At the conclusion of the reaction the 2-formyl-N,N,N-trimethyl-
benzenaminium iodide salt precipitated from solution. The precip-
itate was isolated by filtration, washed with ethyl ether, and resid-
ual solvent was removed in vacuo. White solid; yield = 32%;
mp = 213–215 °C; 1H NMR (300 MHz, DMSO-d6): d 3.77 (s, 9H,

1882
H. Yuan et al. / Tetrahedron: Asymmetry 21 (2010) 1874–1884
C35H38FeIN2P: C, 60.02; H, 5.47; N, 4.00. Found: C, 59.77; H, 5.66; N,
3.95.
CH3), 3.96 (d, 1H, CH(COOEt)2, J = 10.8 Hz), 4.27 (dd, 1H,
CHCH(COOEt)2, J = 10.8, 8.4 Hz), 6.33 (dd, 1H, PhCH@CH, J = 8.4,
15.6 Hz), 6.48 (d, 1H, PhCH@CH, J = 16 Hz,), 7.21–7.34 (m, 10H,
Ph-H); HPLC (Chiralpak AD-H column, 254 nm, 95:5 hexane/iso-
propanol, flow = 1.0 mL/min) tR = 17.48 min, 12.90 min.
4.2.11. BIT5
4.2.11.1. N-(4-Formylphenyl)-N,N-dimethyl-benzenemethana-
minium, bromide 3k. To a solution of 2-(dimethylamino)benzal-
dehyde (1.49 g, 10 mmol) in CH3CN (10 mL) was added bro-
momethyl-benzene (5.13 g, 30 mmol). The solution was stirred for
12 h at 25 °C. At the conclusion of the reaction the N-(4-formylphe-
nyl)-N,N-dimethyl-benzenemethanaminium bromide salt precipi-
tated from solution. The precipitate was isolated by filtration,
washed with AcOEt, and the residual solvent was removed in vacuo.
White solid; yield = 92%; mp = 137–139 °C; 1H NMR (300 MHz,
DMSO-d6): d 3.70 (s, 6H, CH3), 5.21 (s, 1H, CH2), 7.10 (d, 2H, Ph-H,
J = 7.8 Hz), 7.33 (d, 2H, Ph-H, J = 7.8 Hz), 8.02 (d, 2H, Ph-H, J = 9 Hz),
8.07 (d, 2H, Ph-H, J = 9 Hz), 10.13 (s, 1H, CHO).
4.3.2. (S)-Ethyl-2-carboethoxy-3,5-diphenylpent-4-enoate 2b
Colorless oil; yield = 96%; ee = 94.0%;
½
a 2D5
ꢂ
¼ ꢁ16:9 (c 1.0,
CHCl3); 1H NMR (400 MHz, CDCl3): d 1.01 (t, 3H, CH2CH3, J =
7.2 Hz), 1.20 (t, 3H, CH2CH3, J = 7.2 Hz), 3.91 (d, 1H, CH(COOEt)2,
J = 10.8 Hz), 3.97 (q, 2H, CH2, J = 7.2 Hz), 4.17 (q, 2H, CH2, J =
7.2 Hz), 4.26 (dd, 1H, CHCH(COOEt)2, J = 8.4, 10.8 Hz), 6.34 (dd,
1H, PhCH@CH, J = 8.4, 16 Hz), 6.47 (d, 1H, PhCH@CH, J = 16 Hz),
7.17–7.26 (m, 10H, Ph-H); HPLC (Chiralpak AD-H column,
254 nm, 95:5 hexane/isopropanol, flow = 1.0 mL/min) tR = 15.28
min, 11.60 min.
4.2.11.2.
BIT5. N-(4-Formylphenyl)-N,N-dimethyl-benzeneme-
4.3.3. (S)-Ethyl-2-carboethoxy-2-methyl-3,5-diphenylpent-4-
thanaminium, bromide (320 mg, 1 mmol), (R,Sp)-PPFNH2 (433 mg,
1.05 mmol), and MgSO4 (500 mg) were added in absolute alcohol
in a dried Schlenk tube under argon, and then stirred at reflux tem-
perature for 3 h. MgSO4 was removed by filtration. After removing
the solvent under vacuum, the crude product was obtained as a
yellow solid. The residue was purified by washing with ethyl ether.
After being recrystallized from EtOH, 687 mg (96% yield) of the tar-
get compound BIT5 was gain. Yellow solid; mp = 154–156 °C;
enoate 2c
Colorless oil; yield = 97%; ee = 91.0%;
½
a 2D5
ꢂ
¼ ꢁ29:9 (c 0.6,
CHCl3); 1H NMR (300 MHz, CDCl3):
d
1.16 (t, 3H, CH2CH3,
J = 7.2 Hz), 1.25 (t, 3H, CH2CH3, J = 7.2 Hz), 1.47 (s, 3H, CH3), 4.08
(q, 2H, CH2, J = 7.2 Hz), 4.18 (q, 2H, CH2, J = 7.2 H), 4.30 (d, 2H,
CHCMe, J = 8.8 Hz), 6.45 (d, 1H, PhCH@CH, J = 16 Hz), 6.70 (dd,
1H, PhCH@CH, J = 8.8, 16 Hz), 7.17–7.26 (m, 10H, Ph-H); HPLC
(Chiralpak AD-H + AD-H, 254 nm, 99:1 hexane/isopropanol,
flow = 0.3 mL/min) tR = 81.1 min, 76.4 min.
½
a 2D5
ꢂ
¼ ꢁ376:25 (c 0.6, CH2Cl2); IR (KBr) 3412 (w), 1640 (s), 1593
(s), 1437 (s), 746 (s), 699 (s); 1H NMR (300 MHz, DMSO-d6): d
1.54 (d, 3H, J = 6.6 Hz, CHCH3), 3.28 (s, 9H, N(CH3)3), 4.02 (s, 5H,
unsubstituted Cp-H), 3.68–4.64 (s, 3H, substrated Cp-H), 4.79 (m,
1H, CHMe), 4.99 (s, 2H, CH2), 6.87–7.39 (m, 14H, Ph-H), 7.02 (d,
2H, Ph-H, J = 7.5 Hz), 7.63 (d, 2H, Ph-H, J = 7.5 Hz), 8.07 (s, 1H,
N@CH); 13C NMR (75 MHz, DMSO-d6): d 20.29 (CHMe), 48.26
(NMe), 64.44 (d, J = 7.2 Hz, Cp), 68.87 (Cp), 69.34 (CHMe), 69.51
(Cp0), 71.71 (Cp), 73.07 (Bn-C), 75.32 (d, J = 10.2 Hz, Cp), 95.43 (d,
J = 26.5 Hz, Cp), 121.16 (Ph-C), 127.42 (Ph-C), 127.63 (d,
J = 5.8 Hz, Ph-C), 127.86 (d, J = 8.5 Hz, Ph-C), 128.66, 129.01,
129.39. 130.67, 132.43, 132.54, 135.12 (d, J = 18.5 Hz, Ph-C),
137.22 (d, J = 18.5 Hz, Ph-C), 137.49 (Ph-C), 139.55 (d, J = 9.7 Hz,
Ph-C), 145.537 (Ph-C), 159.28 (C@N); 31P NMR (120 MHz, DMSO-
d6): d ꢁ24.24 (s, 1P, PPh2); MALDI m/z = 635.3, M+, ESI, m/
z = 78.9, 80.9 Mꢁ; Anal. Calcd for C40H40BrFeN2P: C, 67.15; H,
5.64; N, 3.92. Found: C, 67.41; H, 5.58; N, 3.99.
4.3.4. (S)-Phenylmethyl-2-carbophenylmethoxy-3,5-
diphenylpent-4-enoate 2d
Colorless oil; yield = 98%; ee = 91.6%; ½a D25
¼ ꢁ7:9 (c 1.6, CHCl3);
ꢂ
1H NMR (300 MHz, CDCl3): d 4.05 (d, 1H, CH (COOBn)2, J = 10.8 Hz),
4.29 (dd, 1H, CHCH(COOBn)2, J = 8.4, 10.8 Hz), 4.90 (d, 1H, CH2Ph,
J = 12.2 Hz), 4.94 (d, 1H, CH2Ph, J = 12.2 Hz), 5.07 (d, 1H, CH2Ph,
J = 12.2 Hz), 5.12 (d, 1H, CH2Ph, J = 12.2 Hz), 6.30 (dd, 1H,
PhCHCH@CH, J = 8.4, 16 Hz), 6.42 (d, 1H, PhCHCH@CH, J = 16 Hz),
6.97–7.26 (m, 20H, Ph-H); HPLC (Chiralpak AD-H, 254 nm, 90:10
hexane/isopropanol, flow = 1.0 mL/min) tR = 19.7 min, 16.3 min.
4.3.5. 2-Acetyl-2-methyl-3,5-diphenylpent-4-enoic acid ethyl
ester 2e
Colorless oil; yield = 48%; ee = 66.2%, de = 0%; 1H NMR
(300 MHz, CDCl3): d 1.07–1.25 (m, 3H, CH2CH3), 1.38 (s, 3H,
COCH3), 2.17–2.21 (m, 3H), 4.02–4.23 (m, 2H), 4.29 (d, 1H,
J = 8.2 Hz), 6.38–6.51 (m, 1H), 6.62–6.90 (m, 1H), 7.16–7.48 (m,
10H); HPLC (Chiralpak AD-H + AD-H, 254 nm, 99:1 hexane/isopro-
panol, flow = 0.3 mL/min) diastereomer A: 72.1 min, 98.1 min, dia-
stereomer B: 76.5 min, 79.5 min.
4.3. General procedure for the palladium-catalyzed allylic
alkylation
AT first, [Pd(g
3-C3H5)Cl]2(4.6 mg, 0.0125 mmol) and ligand
(0.025 mmol) were dissolved in dry solvent (1 mL) in a dried
Schlenk tube under argon, and then stirred at room temperature.
After 1 h, 1a or 1b (0.5 mmol) and LiOAc or other salt (0.01 mmol)
were added and the mixture was stirred for another 20 min. Final-
ly, the mixture was kept at the proper temperature. To this solu-
tion were successively added dimethylmalonate or other
nucleophile (1.25 mmol) and N,O-bis-(trimethylsilyl)acetamide
(0.31 mL, 1.25 mmol). The reaction was monitored by TLC. After
completion, the reaction mixture was diluted with CH2Cl2
(20 mL) and washed twice with saturated aqueous NH4Cl. The or-
ganic phase was dried over anhydrous Na2SO4 and then concen-
trated under reduced pressure. The residue was purified by
preparative TLC (petroleum ether/ethyl acetate 10:1) to give the
product.
4.4. General procedure for the palladium-catalyzed allylic
amination
Pd2(dba)3ꢀCHCl3
(15.4 mg,
0.0125 mmol)
and
ligand
(0.025 mmol) were dissolved in dry solvent (1 mL) in a dried
Schlenk tube under argon, and then stirred at room temperature.
After 1 h, 1a or 1b (0.5 mmol) was added and the mixture was stir-
red for another 20 min. Finally, the mixture was kept at the proper
temperature. To this solution was successively added benzylamine
(1.5 mmol). The reaction was monitored by TLC. After completion,
the reaction product was purified by preparative TLC (petroleum
ether/ethyl acetate 8:1) to give the product.
4.4.1. (R,E)-N-Benzyl-1,3-diphenylprop-2-en-1-amine 4a
4.3.1. (S)-Methyl-2-carbomethoxy-3,5-diphenylpent-4-enoate 2a
Yellow oil; yield = 46%; ee = 92.6%; ½a D25
¼ ꢁ18:8 (c 0.15, CHCl3);
ꢂ
White solid; yield = 97%; ee = 94.6%; ½a D25
ꢂ
¼ ꢁ17:0 (c 1.5, etha-
1H NMR (300 MHz, CDCl3): d 3.80 (s, 2H, PhCH2), 4.42 (d, 1H,
CHNHBn, J = 7.2 Hz), 6.36 (dd, 1H, PhCHCH@CH, J = 7.2, 15.9 Hz),
nol);1H NMR (400 MHz, CDCl3): d 3.52 (s, 3H, CH3), 3.70 (s, 3H,

H. Yuan et al. / Tetrahedron: Asymmetry 21 (2010) 1874–1884
1883
6.60 (d, 1H, PhCHCH@CH, J = 15.9 Hz), 7.17–7.46 (m, 15H, Ph-H);
HPLC (Chiralcel OJ-H, 254 nm, 90:10 hexane/isopropanol,
flow = 0.6 mL/min) tR = 18.7 min, 23.3 min.
polarization effects. All the calculations were carried out with SHEL-
XL-97 program with anisotropic thermal parameters for the non-
hydrogen atoms.22 All hydrogen atoms were placed in the calcu-
lated positions and refined isotropically using a riding model. The
Flack parameter is 0.001(4) with 2470 Friedel pairs.23 CCDC refer-
ence number is 765322. Crystal data, data collection, and refine-
4.4.2. (R,E)-N-(1,3-Diphenylallyl)benzohydrazide 4b
Pale solid; yield = 44%; ee = 91.4%; ½a D25
¼ ꢁ35:7 (c 0.73, CHCl3);
ꢂ
1H NMR (300 MHz, CDCl3): d 4.92 (d, 1H, CHNH, J = 7.9 Hz), 6.42
(dd, 1H, PhCHCH@CH, J = 7.9, 15.8 Hz), 6.74 (d, 1H, PhCHCH@CH,
J = 15.8 Hz), 7.17–7.76 (m, 15H, Ph-H); HPLC (Chiralcel OJ-H,
ment parameters are given in Table
structure is presented in Figure 1.
8 and the molecular
254 nm,
85:15
hexane/isopropanol,
flow = 0.5 mL/min)
Acknowledgment
tR = 28.2 min, 32.6 min.
This research was financially supported by National Natural Sci-
ence Foundation of China (20572009).
4.4.3. (R,E)-N-(1,3-Diphenylallyl)phthalimide 4c
Colorless oil; yield = 34%; ee = 89.9%;
½
a 2D5
ꢂ
¼ ꢁ19:7 (c 1.7,
CHCl3); 1H NMR (300 MHz, CDCl3): d 4.12 (d, 1H, CHN, J = 8.4 Hz),
6.76 (dd, 1H, PhCHCH@CH, J = 8.4, 15.9 Hz), 7.04 (d, 1H,
PhCHCH@CH, J = 15.9 Hz), 7.27–7.86 (m, 14H, Ph-H); HPLC (Chiral-
cel OD-H, 254 nm, 98:2 hexane/isopropanol, flow = 0.4 mL/min)
tR = 29.9 min, 39.0 min.
References
1. Reviews: (a) Pfaltz, A.; Lautens, M.. In Comprehensive Asymmetric Catalysis;
Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: New York, 1999; Vol. 2,
pp 833–881; (b) Tsuji, J. Palladium Reagents and Catalysts: Innovations in Organic
Synthesis; Wiley: New York, 1996. pp 276–297; (c) Trost, B. M.; Van Vranken, D.
L. Chem. Rev. 1996, 96, 395–422; (d) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003,
103, 2921–2944; (e) Lu, Z.; Ma, S. Angew. Chem., Int. Ed. 2008, 47, 258–297; (f)
Lu, Z.; Ma, S. Angew. Chem., Int. Ed. 2008, 120, 264–266.
4.4.4. (R,E)-1-(1,3-Diphenylallyl)pyrrolidine 4d
Pale solid; yield = 64%; ee = 40.2%; ½a D25
ꢂ
¼ ꢁ2:4 (c 1.0, CHCl3); 1H
2. Reviews:
(a)
Hayashi,
T.
Asymmetric
Catalysis
With
Chiral
Ferrocenylphosphine Ligands. In Ferrocenes: Homogeneous Catalysis, Organic
Synthesis, Materials Science; Togni, A., Hayashi, T., Eds.; VCH: Weinheim, 1995;
pp 105–142. Chapter 2; (b) Togni, A. New Chiral Ferrocenyl Ligands for
Asymmetric Catalysis. In Metallocenes; Togni, A., Halterman, R. L., Eds.; Wiley-
VCH: Weinheim, 1998; Vol. 2, pp 685–721. Chapter 11; (c) Arrayás, R. G.; Adrio,
A.; Carretero, J. C. Angew. Chem., Int. Ed. 2006, 45, 7674–7715; (d) Barbaro, P.;
Bianchini, C.; Giambastiani, G.; Parisel, S. L. Coord. Chem. Rev. 2004, 248, 2131–
2150; (e) Colacot, T. J. Chem. Rev. 2003, 103, 3101–3118; (f) Richards, C. J.;
Locke, A. J. Tetrahedron: Asymmetry 1998, 9, 2377–2407.
NMR (300 MHz, CDCl3): d 1.79–1.84 (m, 4H), 2.43–2.58 (m, 4H),
3.76 (d, 1H, CHN, J = 8.4 Hz), 6.36 (dd, 1H, PhCHCH@CH, J = 8.4,
15.8 Hz), 6.54 (d, 1H, PhCHCH@CH, J = 15.9 Hz), 7.17–7.46 (m,
10H, Ph-H); HPLC (Chiralcel OJ-H, 254 nm, 200:1 hexane/isopropa-
nol, flow = 0.2 mL/min) tR = 38.3 min, 40.7 min.
4.4.5. (R,E)-4-(1,3-Diphenylallyl)morpholine 4e
Pale solid; yield = 39%; ee = 33.5%; ½a D25
¼ ꢁ3:8 (c 0.34, CHCl3);
ꢂ
3. (a) Hou, X. L.; Sun, N. Org. Lett. 2004, 6, 4399–4401; (b) Anderson, J. C.;
Osborme, J. Tetrahedron: Asymmetry 2005, 16, 931–934; (c) Kloetzing, R. J.;
Knochel, P. Tetrahedron: Asymmetry 2006, 17, 116–123; (d) Li, X. S.; Li, Q.; Wu,
X. H.; Gao, Y. G.; Xu, D. C.; Kong, L. C. Tetrahedron: Asymmetry 2007, 18, 629–
634; (e) Zhang, K.; Peng, Q.; Hou, X. L.; Wu, Y. D. Angew. Chem., Int. Ed. 2008, 47,
1741–1744; (f) Kato, M.; Nakamura, T.; Ogata, K.; Fukuzawa, S.-I. Eur. J. Org.
1H NMR (300 MHz, CDCl3): d 2.36–2.57 (m, 4H), 3.70–3.73 (m,
4H), 3.79 (d, 1H, CHN, J = 8.6 Hz), 6.36 (dd, 1H, PhCHCH@CH,
J = 8.6, 15.8 Hz), 6.58 (d, 1H, PhCHCH@CH, J = 15.9 Hz), 7.21–7.46
(m, 10H, Ph-H); HPLC (Chiralcel OD-H, 254 nm, 90:10 hexane/iso-
propanol, flow = 1.0 mL/min) tR = 6.4 min, 13.2 min.
ˇ
Chem. 2009, 30, 5232–5238; (g) Šebesta, R.; Bilcík, F. Tetrahedron: Asymmetry
2009, 20, 1892–1896.
4. Hayashi, T.; Hayashi, C.; Uozumi, Y. Tetrahedron: Asymmetry 1995, 6, 2503–
2506.
4.5. X-ray structure determination of BIT5
5. Lee, J. H.; Son, S. U.; Chung, Y. K. Tetrahedron: Asymmetry 2003, 14, 2109–2133.
6. (a) Hu, X. P.; Dai, H. C.; Bai, C. M.; Chen, H. L.; Zheng, Z. Tetrahedron: Asymmetry
2004, 15, 1065–1068; (b) Tetrahedron: Asymmetry 2003, 14, 3415–3421.; (c)
Hu, X. P.; Dai, H. C.; Hu, X. Q.; Chen, H. L.; Wan, J. W.; Bai, C. M.; Zheng, Z.
Tetrahedron: Asymmetry 2002, 13, 1687–1693; (d) Hu, X. P.; Bai, C. M.; Dai, H.
C.; Chen, H. L.; Zheng, Z. J. Mol. Catal. A: Chem. 2004, 218, 107–112; (e) Hu, X. P.;
Chen, H. L.; Zheng, Z. Adv. Synth. Catal. 2005, 347, 541–548.
7. (a) Burckhardt, U.; Baumann, M.; Togni, A. Tetrahedron: Asymmetry 1997, 8,
155–159; (b) Trost, B. M.; Bunt, R. C. J. Am. Chem. Soc. 1994, 116, 4089–4090; (c)
Sennhenn, P.; Gabrer, B.; Helmchen, G. Tetrahedron Lett. 1994, 35, 8589–8598;
(d) Cho, C.-W.; Son, J.-H.; Ahn, K. H. Tetrahedron: Asymmetry 2006, 17, 2240–
2246.
8. (a) Cook, G. R.; Shaanker, P. S. Tetrahedron Lett. 1998, 39, 4991–4994; (b)
Gilberston, S. R.; Chang, C.-W. T. Chem. Commun. 1997, 975–976; (c) Brunel, J.
M.; Faure, B. J. Mol. Catal. A: Chem. 2004, 212, 61–64; (d) Kawatsura, M.;
Uozumi, Y.; Hayashi, T. Chem. Commun. 1998, 217–218; (e) Gilberston Sinou,
D.; Rabeyrin, C.; Nguefack, C. Adv. Synth. Catal. 2003, 345, 357–363; (f) Evans, L.
A.; Fey, N.; Harvey, J. N.; Hose, D.; Lloyd-Jones, G. C.; Murray, p.; Orpen, A. G.;
Osborne, R.; Owen-Smith, G. J. J.; Purdie, M. J. Am. Chem. Soc. 2008, 130, 14471–
14473; (g) Bäckcall, J. E.; Byström, S. E.; Nordberg, R. E. J. Org. Chem. 1984, 49,
4619–4631; (h) Fukuzawa, S.; Yamamoto, M.; Hosaka, M.; Kikuchi, S. Eur. J. Org.
Chem. 2007, 5540–5545.
9. (a) Lloyd-Jones, G. C.; Stephen, S. C. Chem. Commun. 1998, 2321–2322; (b)
Malaisé, G.; Barloy, L.; Osborn, J. A.; Kyritsakas, N. C.R. Chim. 2002, 5, 289–296;
(c) Fagnou, K.; Lauten, M. Angew. Chem., Int. Ed. 2002, 41, 26–47.
10. Trost, B. M.; Murphy, D. J. Organometallics 1985, 4, 1143–1145.
11. von Matt, P.; Pfaltz, A. Angew. Chem., Int. Ed. Engl. 1993, 32, 566–568.
12. (a) Brown, J. M.; Hulmes, D. I.; Guiry, P. J. Tetrahedron 1994, 50, 4493–4506; (b)
Gilbertson, S. R.; Chang, C.-W. T. J. Org. Chem. 1998, 63, 8424–8431; (c)
Chelucci, G.; Pinna, G. A.; Saba, A.; Sanna, G. J. Mol. Catal. A: Chem. 2000, 159,
423–427; (d) Mancheño, O. G.; Peiego, J.; Cabrera, S.; Arrayás, R. G.; Llamas, T.;
Carretero, J. C. J. Org. Chem. 2003, 68, 3679–3686.
A yellow block single-crystal of BIT5 was selected and mounted
on a glass fiber. The data were collected by a Rigaku Saturn CCD
area dector diffractometer equipped with a graphite-monochro-
mated Mo Ka radiation (k = 0.71073 Å) using a x and u scan mode
at 113(2) K. The collected data were reduced by using program
CrystalClear.21 The reflection data were also corrected for Lorentz-
Table 8
Crystallographic data and structure refinement for BIT5a
Compound reference
Chemical formula
Formula mass
Crystal system
a (Å)
BIT5
C40H40BrFeN2P
715.47
Monoclinic
10.160(2)
8.9557(19)
19.031(4)
90.00
101.633(3)
90.00
1696.1(7)
113(2)
P2(1)
2
12884
5945
0.0286
0.0215
0.0367
0.0262
0.0372
b (Å)
c (Å)
a
(°)
b (°)
(°)
c
Unit cell volume (Å3)
Temperature (K)
Space group
No. of formula units per unit cell (Z)
No. of reflections measured
No. of independent reflections
Rint
13. Tanaka, Y.; Mino, T.; Akita, K.; Sakamoto, M.; Fujita, T. J. Org. Chem. 2004, 69,
6679–6687.
14. Tetsuhiro, N.; Takamasa, M.; Yuichi, A.; Takashi, F.; Yasumasa, H. Org. Lett.
2005, 7, 4447–4450.
15. Dana, P.; Rocío, M.; Sonia, S.; Anton, V.; Miquel, A. P. Adv. Synth. Catal. 2009,
351, 1539–1556.
Final R1 values (I >2
r(I))
Final wR(F2) values (I >2
r
(I))
Final R1 values (all data)
Final wR(F2) values (all data)
a
2
R1 =
R
||F0| ꢁ |Fc||/
R
|F0|, wR2 = [
R
(F0 ꢁ Fc2)2/
R .
w(F02)2]1/2

1884
H. Yuan et al. / Tetrahedron: Asymmetry 21 (2010) 1874–1884
16. Chen, J.; Lang, F.; Li, D.; Cun, L.; Zhu, J.; Deng, J.; Liao, J. Tetrahedron: Asymmetry
2009, 20, 1953–1956.
20. Durand, G.; Polidori, A.; Ouari, O.; Tordo, P.; Geromel, V.; Rustin, P.; Pucci, B. J.
Med. Chem. 2003, 46, 5230–5237.
17. Casey, M.; Leonard, J.; Lygo, B. Advance Practical Organic Chemistry; Blackie:
New York, 1990.
18. Yavari, I.; Riazi-Kermani, F. Synth. Commun. 1995, 25, 2923–2928.
19. Poethko, T.; Schottelius, M.; Thumshirn, G.; Hersel, U.; Herz, M.; Henriksen, G.;
Kessler, H.; Schwaiger, M.; Wester, H.-J. J Nucl. Med. 2004, 45, 892–902.
21. In Molecular Structure Corporation, Rigaku. Crystalclear. Version 1.30. MSC, The
Woodlands, Texas, USA, and Rigaku Corporation, Tokyo, Japan, 2001.
22. Sheldrick, G. M. in SHELXS97 and SHELXL97. University of Göttingen: Germany,
1997.
23. Flack, H. D. Acta Crystallogr., A 1983, 39, 876–881.