Chiral SO/P hybrid ligands: An enantioselective switch in palladium-catalyzed asymmetric allylic etherifications

Article abstract of DOI:10.1016/j.tetasy.2012.03.022

A variety of chiral tert-butanesulfinylphosphine ligands were prepared and applied to the palladium-catalyzed asymmetric allylic etherification of 1,3-diphenylpropenyl acetate with alcohols. Excellent yields and moderate enantioselectivities were obtained

Full text of DOI:10.1016/j.tetasy.2012.03.022

Tetrahedron: Asymmetry 23 (2012) 527–535
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Tetrahedron: Asymmetry
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Chiral SO/P hybrid ligands: an enantioselective switch
in palladium-catalyzed asymmetric allylic etherifications
Junwei Xing a,b,c, Peng Cao b, Jian Liao a,b,c,
⇑
a Key Laboratory of Asymmetric Synthesis and Chirotechnology of Sichuan Province, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, PR China
b Natural Products Research Center, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, PR China
c Graduate School of Chinese Academy of Sciences, Beijing 100049, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A variety of chiral tert-butanesulfinylphosphine ligands were prepared and applied to the palladium-cat-
alyzed asymmetric allylic etherification of 1,3-diphenylpropenyl acetate with alcohols. Excellent yields
and moderate enantioselectivities were obtained. The absolute configuration of the etherification prod-
ucts was evidently switched only through the position change of the substituent on the P-aryl groups.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 29 February 2012
Accepted 29 March 2012
Available online 18 May 2012
1. Introduction
1,3-diphenyl-2-propenyl acetate, high enantioselectivity was
obtained (up to 91% ee) but catalytic activity was relatively low
The control of chirality of newly created stereocenters is of
great importance in synthetic chemistry and the drug industry.
Transition metal-catalyzed asymmetric reactions are powerful
and applicable tools for the construction of optically active com-
pounds. A variety of chiral ligands have been developed for their
use in the control of absolute configuration.1 Generally, the prepa-
ration of two enantiomers requires access to ligands with opposite
absolute configurations. However, the two enantiomers of a chiral
ligand are not always readily available or economically feasible to
synthesize. Therefore, the development of general asymmetric cat-
alytic strategies to produce enantiomeric products from a single
chiral source is an interesting and demanding challenge. Although
the change of the substrate or reaction conditions could reverse the
chirality of the product, a promising strategy would be the ability
to prepare switchable ligands from the same chiral starting mate-
rial via a simple modification of the structure.
The allylic substitution reaction is one of the most popular and
well-documented model reactions for palladium-catalyzed asym-
metric C–C and C–N bond formations.2 In contrast, the enantiose-
lective construction of a C–O bond through an analogous strategy
has rarely been studied due to the relatively low nucleophilicity
of alcohols and their inherently flexible chains.3 Chan observed
that palladium(II)/(Sp,R)-ferro-NPS complex could catalyze the
asymmetric allylic etherification of 1,3-diphenyl-2-propenyl ace-
tate with a wide array of aliphatic alcohols with excellent yields
and enantioselectivities.4 Recently, Zhou reported a series of chiral
ferrocenyl diphosphine-imine ligands containing an ionic salt
group. In the Pd-catalyzed asymmetric allylic etherification of
(40–60% yield).5
Recently, we developed a series of hybrid ligands containing
chiral sulfoxide-auxiliaries and observed some unique features
during transition metal-catalyzed asymmetric reactions.6 As a class
of concise SO/P ligand, the chiral sulfoxide-phosphines were em-
ployed in palladium-catalyzed asymmetric allylic alkylations and
aminations with excellent reactivities and moderate-to-good
enantioselectivities.6b Herein we report a highly reactive and enan-
tioselective-switchable palladium-catalyzed asymmetric allylic
etherification of racemic 1,3-diphenyl-2-propenyl acetate with ali-
phatic alcohols using chiral sulfinylphosphine ligands. The abso-
lute configuration of the product was controlled by the
substituents position of the P-aryl group.
2. Results and discussion
2.1. Preparation of ligands
Ligands L1–L8 were readily prepared in a single step from
substituted (R)-(tert-butylsulfinyl)benzene 1, as shown in
Scheme 1. Deprotonation of 1 with n-BuLi or LDA in THF at
–78 oC, followed by addition of chlorodiarylphosphine gave the tar-
get ligands L1–L8.6a
2.2. Palladium-catalyzed asymmetric allylic etherification
With chiral ligands L1–L8 in hand, we first tested their efficacy
in Pd-catalyzed asymmetric allylic etherification reactions. The
results are summarized in Table 1. The reaction proceeded
smoothly with L1 as the ligand, yielding the product in 95% yield
and with 64% ee after 24 h at 10 oC (Table 1, entry 1). The effect
⇑
Corresponding author.
E-mail address: jliao@cib.ac.cn (J. Liao).
0957-4166/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2012.03.022

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J. Xing et al. / Tetrahedron: Asymmetry 23 (2012) 527–535
S
1. n-BuLi or LDA
S
O
THF, -78oC
O
R2
2. ClPAr2, THF
R2
PAr2
R1
R1
1
L1 - L8
S
S
P
S
P
S
P
O
O
O
O
O
P
O
L2
L4
L3
L1
F
S
S
P
S
P
S
P
O
O
O
O
F
O
P
F
F
O
L5
L8
L6
L7
Scheme 1. Preparation of SO/P ligands.
Table 1
Ligand effects on the asymmetric allylic etherificationa
OH
OAc
OBn
[Pd(η3-C3H5)Cl]2, L
+
CH3CN, Cs2CO3
10oC, 24h
3a
2
Entry
Ligand
Yieldb (%)
eec (%)
Configurationd
1
2
3
4
5
6
7
8
L1
L2
L3
L4
L5
L6
L7
L8
95
95
96
97
98
93
90
97
64
55
56
59
65
20
57
63
(R)
(S)
(S)
(R)
(R)
(S)
(R)
(R)
a
Reaction conditions: 0.2 mmol of 1,3-diphenylpropenyl acetate, 0.6 mmol of benzyl alcohol, 0.6 mmol of cesium
carbonate, 0.004 mmol of [Pd(
3-C3H5)Cl]2 (2.0 mol %), 0.0098 mmol of ligand (4.8 mol %) in 1 mL of CH3CN. Reac-
g
tions were conducted under argon at 10 °C for 24 h.
b
Isolated yield based on 1,3-diphenylpropenyl acetate.
c
Determined by chiral HPLC analysis using a chiral stationary column.
d
The absolute configuration was determined by comparing the specific rotation with the literature data.4
of the differently substituted aryl groups on the phosphine atom in
the ligands on the enantioselectivity was examined. When the aryl
group on the phosphine atom is p-toyl, that is, L5 was used as the
ligand; the ee was 65% and the yield increased to 98% (Table 1, en-
try 5). L4 gave good yield (97%) but the ee decreased to 59% when
the aryl group was m-toyl (Table 1, entry 4). When the aryl group
on the phosphine atom in ligands was o-substituted L2, L3, L6, the
ees decreased to 56–20%. However, we found that chiral ligands L2,
L3, and L6 produced the allylic etherification product with an
opposite absolute configuration compared with other ligands (Ta-
ble 1, entries 2, 3, 6). Both electron-withdrawing (p-F) and elec-
tron-donating (p-MeO) substituents on the phenyl ring on the
phosphine atom of ligands L7, L8 could afford the desired products
in moderate enantioselectivities with good yields (Table 1, entries
7, 8).
In additional studies, ligand L5 was utilized to screen the asym-
metric allylic etherification reaction conditions in terms of the
enantioselectivity and conversion. A variety of solvents, bases,
and temperatures were investigated. The results are summarized
in Table 2.
In our previous study, we found that the solvent used in the
catalysis system had a strong effect on the yields and ee values of
the product catalyzed by the tert-butanesulfinylphosphine ligands
in the palladium-catalyzed asymmetric allylic substitution.6b These

J. Xing et al. / Tetrahedron: Asymmetry 23 (2012) 527–535
529
Table 2
Optimization of the asymmetric allylic etherification reaction parametersa
OH
OAc
OBn
[Pd(η3-C3H5)Cl]2, L5
+
solvent, base, T
3a
2
Entry
Solvent
Base
Temp (°C)
Yieldb(%)
eec(%)
1
2
3
4
5
6
7
8
Cyclohexane
Toluene
Acetone
Ethyl acetate
THF
Dioxane
CH3CN
CH2Cl2
CHCl3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
KOH
NaH
CsF
BSA
Et3N
Cs2CO3
Cs2CO3
Cs2CO3
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
40
80
ꢀ10
95
97
56
95
27
95
97
98
98
38
59
61
Trace
66
NR
NR
99
98
55
20 (R)d
50
57
49
64
22
65
60
59
66
64
57
ND
64
ND
ND
59
52
66
9
10
11
12
13
14
15
16
17e
18f
19g
DMF
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
a
Reaction conditions: 0.2 mmol of 1,3-diphenylpropenyl acetate, 0.6 mmol of benzyl alcohol, 0.6 mmol of base, 0.004 mmol
of [Pd(
3-C3H5)Cl]2 (2.0 mol%), 0.0098 mmol of ligand (4.8 mol%) in 1 mL of solvent. Reactions were conducted under argon
for 24 h.
g
b
Isolated yield based on 1,3-diphenylpropenyl acetate.
Determined by chiral HPLC analysis using a chiral stationary column.
The absolute configuration was determined by comparing the specific rotation with literature data.4
Reaction time is 15 h.
Reaction time is 10 h.
Reaction time is 48 h.
c
d
e
f
g
results indicated that a suitable solvent should be determined first.
Cyclohexane, toluene, ethyl acetate, and dioxane gave good yields
but poor ees (Table 2, entries 1, 2, 4, 6). Conversely, acetone, THF,
and DMF gave moderate ees but low yields (Table 2, entries 3, 5,
10). After a systematic solvent screening, we found that acetonitrile
was the optimal solvent in terms of yield and ee (Table 2, entries 7–
9).
Next, variations in the species of the base used in the catalytic
etherification were also studied (Table 2, entries 11–16). When a
relatively strong base, such as KOH, was used, both the yield and
ee decreased (Table 2, entry 12). The yields were dramatically de-
creased when relatively weak bases K2CO3 and CsF were used
although the ee values were maintained (Table 2, entries 11, 14).
No substrate conversation occurred when organic bases, such as
BSA or Et3N, were used and no product was detected when NaH
was used as the base (Table 2, entries 13, 15, 16). The catalyzed
etherification only proceeded to completion when cesium carbon-
ate was used as the base (Table 2, entry 7).
enantioselectivity was observed for all of the substrates, with up
to 67% ee (R) and 68% ee (S) when L3 and L5 were used. The elec-
tronic nature of the phenyl ring of the benzyl alcohols had no
apparent influence on the enantioselectivity or reactivity. Benzyl
alcohols with both electron-withdrawing and electron-donating
groups afforded the desired products in moderate enantioselectiv-
ities and with good yields (Table 3, entries 1, 3, 5, 7, 8, 10). Para-,
meta- and sterically encumbered ortho-substituted benzyl alcohols
could be successfully employed in the reaction (Table 3, entries 2,
4, 7, 9). Moreover, the phenyl substitution could be extended to
other aromatics and heteroaromatics, such as 1-naphthyl, furanyl,
thiophenyl, and pyridinyl (Table 3, entries 11, 13–15). Further-
more, aliphatic alcohols could also react in this catalyst system.
Methanol underwent reaction to provide the desired product in
excellent yield and moderate ee (Table 3, entry 16).
We also used dimethyl malonate and benzyl amine as nucleo-
philes for the allylic substitution reaction. The results are shown
in Scheme 2. A switch of enantioselectivity was also observed.
Temperature was also an important factor for the etherification.
Increasing the temperature shortened the reaction time, but the
enantioselectivity was lower than that observed at 10 oC (Table 2,
entries 17–18). For the reaction at ꢀ10 oC, the enantioselectivity
did not increase as much as expected and the yield decreased dra-
matically (Table 2, entry 19).
Under the optimal experimental conditions, various benzyl
alcohols were investigated to examine the generality of the reac-
tion and the scope of the switch in stereochemistry. The results
are listed in Table 3. A wide variety of benzyl alcohols with diverse
steric and electronic properties were tested to react with 1,3-
diphenylpropenyl acetate affording the desired products with good
yields and moderate enantioselectivities (Table 3). A reversal of
2.3. Explanation for the reversal of enantioselectivity
According to the generally accepted mechanism of palladium-
catalyzed allylic substitution, there are a number of possible
allylpalladium complex intermediates while palladium
p-allyl
isomerization is a facile process in the solution.3d,7,8 Complex A
and complex B are mixtures of diastereomeric complexes in a rapid
equilibrium in solution. Similarly, complex C is a mixture of
diastereomeric complexes in a rapid equilibrium with complex D
(Schemes 3 and 4).
According to the X-ray structure and the proposed model by
Hiroi et al., a possible mechanism-based configuration shift con-

530
J. Xing et al. / Tetrahedron: Asymmetry 23 (2012) 527–535
Table 3
Enantioselective allylic etherification with a variety of alcohols under L3 and L5a
OAc
OR
[Pd(η3-C3H5)Cl]2 , L
+
ROH
CH3CN, Cs2CO3
10oC, 24h
3b-q
2
Entry
1
ROH
Prod.
L
Yieldb(%)
eec,d(%)
OH
OH
OH
3b
3c
L5
L3
95
90
64 (R)
58 (S)
F
2
3
L5
L3
94
91
60 (R)
54 (S)
Cl
3d
L5
L3
90
93
67 (R)
57 (S)
Cl
OH
4
5
3e
3f
L5
L3
92
95
60 (R)
59 (S)
Br
OH
L5
L3
95
95
67 (R)
56 (S)
Br
OH
OH
6
7
3g
3h
L5
L3
91
88
66 (R)
52 (S)
OH
L5
L3
92
95
63 (R)
55 (S)
8
3i
L5
L3
92
96
65 (R)
55 (S)
O
OH
9
3j
L5
L3
98
93
66 (R)
56 (S)
O
O
OH
10
3k
L5
L3
80
83
65 (R)
60 (S)
O2N
OH
11
12
3l
L5
L3
85
81
67 (R)
54 (S)
OH
3m
L5
L3
72
68
62 (R)
57 (S)
13
14
3n
3o
L5
L3
95
92
65 (R)
61 (S)
OH
OH
O
S
L5
L3
97
95
62 (R)
58 (S)

J. Xing et al. / Tetrahedron: Asymmetry 23 (2012) 527–535
531
Table 3 (continued)
Entry
ROH
Prod.
L
Yieldb(%)
88
eec,d(%)
15
3p
L5
53 (R)
OH
N
L3
L5
L3
85
98
97
68 (S)
62 (R)
55 (S)
16
CH3OH
3q
a
Reaction conditions: 0.2 mmol of 1,3-diphenylpropenyl acetate, 0.6 mmol of benzyl alcohol, 0.6 mmol of cesium carbonate, 0.004 mmol of [Pd(
g
3-C3H5)Cl]2 (2.0 mol %),
0.0098 mmol of ligand (4.8 mol %) in 1 mL of CH3CN. Reactions were conducted under argon at 10 °C for 24 h.
b
Isolated yield based on 1,3-diphenylpropenyl acetate.
c
Determined by chiral HPLC analysis using a chiral stationary column.
d
The absolute configuration was determined by comparing the specific rotation with the literature data.4
O
O
L5 98% yield
63% ee (S)
OAc
Ph
O
O
[Pd(η3-C3H5)Cl]2,
O
O
+
Ph
O
+
O
CH3CN, BSA,
LiOAc 10oC,24h
L3
96% yield
53% ee (R)
4
NH2
L5 99% yield
62% ee (R)
[Pd(η3-C3H5)Cl]2,
OAc
Ph
NHBn
Ph
CH3CN, BSA,
Ph
Ph
LiOAc 10oC,24h
L3 98% yield
63% ee (S)
5
Scheme 2. Asymmetric allylic alkylation and amination with chiral ligands L5 and L3.
between the o-tolyl group on the phosphine atom in ligand and
the proximal phenyl substituent on the -allyl moiety makes com-
plex C favored. Thus, the product is given in an (S)-enriched config-
uration. The driving force is the formation of the less sterically
strained complex C (Scheme 4).
p
Nu-
S
P
O
S
P
O
Nu-
Pd
Pd
(p-tol)2
(p-tol)2
complex A
complex B
Nu-
S
P
O
S
P
O
favored
disfavored
Nu-
Pd
Pd
(o-tol)2
(o-tol)2
O
O
complex D
complex C
(S)
(R)
disfavored
favored
Scheme 3. Proposed model for the allylic substitution in the presence of chiral
ligand L5.
O
O
trolled by ligands is shown in Schemes 3 and 4. Hiroi has suggested
(R)
that the greater
p-accepting ability of a phosphinite when com-
(S)
pared to the sulfoxide supports nucleophilic substitution trans to
Scheme 4. Proposed model for the allylic substitution in the presence of chiral
ligand L3.
the phosphorus atom.9
In the reaction solution, complex A and complex B are mixtures
of diastereomeric complexes in a rapid equilibrium. The non-bond-
ing interaction between the t-butyl sulfoxide group on the ligand
3. Conclusion
and the proximal phenyl substituent on the p-allyl moiety makes
complex B more favored. Therefore, the formation of the (R)-en-
riched product is favored.
On the other hand, in the case of ligand L3, the o-tolyl group is a
more sterically hindered bulky group than the p-tolyl group in li-
gand L5 controlling the nucleophilic addition process. In the reac-
A series of chiral tert-butanesulfinylphosphine ligands have
been designed and synthesized. These ligands were successfully
applied to the palladium-catalyzed allylic etherification of 1,3-
diphenylpropenyl acetate with benzyl alcohol as the nucleophile.
We have found that chiral SO-P heterodonor ligands L3 and L5
gave the corresponding reaction products in the opposite absolute
configuration with moderate ees in good yields. The substituted
tion solution, complex
C and complex D are mixtures of
diastereomeric complexes in rapid equilibrium. The steric strain

532
J. Xing et al. / Tetrahedron: Asymmetry 23 (2012) 527–535
position of the aryl groups on the phosphorus atom acts as a key
effect in switching the product’s chirality. The steric bulkiness of
the P-aryl group is sufficient enough to control the orientation of
the nucleophile attack to give products with a different absolute
configuration. Further studies focused on palladium-catalyzed
asymmetric allylic substitutions using these ligands are underway
in our laboratories.
7.50 (m, 1H); 7.37–7.32 (m, 1H); 7.29–7.18 (m, 4H); 7.09–7.07
(m, 2H); 6.89–6.88 (m, 1H); 6.80–6.79 (m, 1H); 6.67–6.66 (m,
1H); 2.36 (d, J = 9.4 Hz, 6H); 1.28 (s, 9H). 13C NMR (75 MHz, CDCl3):
d 146.41 (d, J = 25 Hz); 142.54 (d, J = 27 Hz); 142.11 (d, J = 27 Hz);
137.56 (d, J = 18.3 Hz); 134.32 (d, J = 9.5 Hz); 133.88; 133.65;
133.15 (d, J = 13.2 Hz); 132.89; 131.17; 130.25 (d, J = 2.3 Hz);
130.19; 129.38; 129.03 (d, J = 7.1 Hz); 127.00 (d, J = 3.5 Hz);
126.32; 58.02; 23.55 (d, J = 4.4 Hz); 21.47 (d, J = 11.3 Hz); 21.19
(d, J = 13.1 Hz). 31P NMR (121 MHz, CDCl3): d ꢀ27.5 (s). HRMS
(EI) for C24H28OPS (M+H): calcd 395.1598, found 395.1593.
4. Experimental
4.1. General methods
4.2.4. (R)-(2-(tert-butylsulfinyl)phenyl)di-m-tolylphosphine L4
The compound was prepared in a similar manner to that de-
scribed above. White solid; yield 37%; ½a D20
¼ þ237(c 0.152, CHCl3).
ꢁ
All experiments were carried out under an argon atmosphere
using standard Schlenk techniques unless otherwise noted. Com-
mercial reagents were used as received without purification. All
reactions were monitored by TLC. Flash column chromatography
was carried out using silica gel at increased pressure. Commercial
grade solvents were dried and purified by standard literature pro-
cedures. The 1H NMR (300 MHz), 13C NMR (75 MHz), and 31P NMR
(121 MHz) spectra were recorded on a Brucker-300 spectrometer.
Optical rotation data were recorded on a Perkin–Elmer Polarime-
ter-341. Enantiomeric excess was determined by HPLC analysis
on chiral stationary columns in comparison with the authentic
racemates. Column chromatography was performed using silica
gel (200–300 mesh) eluting with ethyl acetate and petroleum
ether.
1H NMR (300 MHz, CDCl3): d 7.95–7.90 (m, 1H); 7.59–7.52 (m, 1H);
7.38–7.35 (m, 1H);7.26–7.01 (m, 8H); 6.94–6.90 (m, 1H); 2.29 (d,
J = 10.8 Hz, 6H); 1.32 (s, 9H). 13C NMR (75 MHz, CDCl3): d 146.11
(d, J = 25 Hz); 138.64 (d, J = 19.6 Hz); 138.06; 138.05 (d,
J = 15.8 Hz); 135.43 (d, J = 22.8 Hz); 135.41; 134.25 (d, J = 11 Hz);
134.08; 133.96 (d, J = 12.7 Hz); 131.01; 130.70 (d, J = 17.3 Hz);
130.20 (d, J = 16.5 Hz); 129.68 (d, J = 7 Hz); 129.37; 128.47 (d,
J = 3.2 Hz); 128.38 (d, J = 3.6 Hz); 126.54 (d, J = 6.3 Hz); 58.46;
23.64 (d, J = 5 Hz); 21.37 (d, J = 3.5 Hz). 31P NMR (121 MHz, CDCl3):
d ꢀ14.7 (s). HRMS (EI) for C24H28OPS (M+H): calcd 395.1598, found
395.1593.
4.2.5. (R)-(2-(tert-butylsulfinyl)phenyl)di-p-tolylphosphine L5
The compound was prepared in a similar manner to that de-
scribed above. White solid; yield 66%; ½a D20
¼ þ289 (c 0.31, CHCl3).
ꢁ
4.2. Synthesis of ligands L1–L8
1H NMR (300 MHz, CDCl3): d 7.98–7.94 (m, 1H); 7.54–7.49 (m, 1H);
7.38–7.34 (m, 1H); 7.16–7.04 (m, 9H); 2.33 (d, J = 12.8 Hz, 6H);
1.31 (s, 9H). 13C NMR (75 MHz, CDCl3): d 146.07 (d, J = 24.7 Hz);
139.12 (d, J = 19.8 Hz); 138.85 (d, J = 3.2 Hz); 133.84; 133.74 (d,
J = 19.7 Hz); 133.26 (d, J = 20 Hz); 132.32 (d, J = 2.3 Hz); 132.19
(d, J = 6 Hz); 131.02; 129.46 (d, J = 2.3 Hz); 129.37 (d, J = 3.1 Hz);
129.28; 126.57 (d, J = 6.3 Hz); 58.44; 23.69 (d, J = 5 Hz); 21.25 (d,
J = 2.3 Hz). 31P NMR (121 MHz, CDCl3): d ꢀ15.7 (s). HRMS (EI) for
4.2.1. (R)-(2-(tert-Butylsulfinyl)-6-methoxyphenyl)-
diphenylphosphine L1
The compound was prepared as described in the literature.6a At
ꢀ78 °C, LDA (2.2 mL, 2.0 M in heptane, 4.4 mmol) was added drop-
wise to a solution of 1-(R)-(-)-tert-butylsulfinyl-3-methoxyben-
zene (848 mg, 4.0 mmol) in tetrahydrofuran (10 mL). The
resulting mixture was stirred for 0.5 h at ꢀ78 °C. Chlorodiphenyl-
phosphine (0.8 mL, 4.4 mmol, 1.1 equiv) in tetrahydrofuran
(5 mL) was added to the mixture and the temperature was in-
creased to room temperature slowly. The reaction mixture was
passed through a plug of Celite and silica gel. The filtrate was con-
centrated under reduced pressure to give the crude product, which
was purified by flash column chromatography (silica gel, 50%
C24H28OPS (M+H): calcd 395.1598, found 395.1593.
4.2.6. (R)-(2-(tert-butylsulfinyl)phenyl)bis(2-fluorophenyl)-
phosphine L6
The compound was prepared in a similar manner to that de-
scribed above. White solid; yield 61%; ½a D20
¼ þ307 (c 0.248,
ꢁ
CHCl3). 1H NMR (300 MHz, CDCl3): d 8.00–7.96 (m, 1H); 7.60–
7.57 (m, 1H); 7.44–7.37 (m, 3H); 7.14–7.00 (m, 5H); 6.89–6.86
(m, 1H); 6.70–6.66 (m, 1H); 1.36 (s, 9H). 13C NMR (75 MHz, CDCl3):
d 165.55; 162.35; 146.03 (d, J = 26.2); 135.17 (d, J = 18.1 Hz);
134.38; 134.01; 131.45; 131.39; 130.03; 126.74 (d, J = 6.5 Hz);
124.95; 124.72 (d, J = 3.1 Hz); 121.12 (dd, J = 18.9 Hz, J = 38.4 Hz);
115.28 (dd, J = 2.9 Hz, J = 22.8 Hz); 58.67; 23.35 (d,J = 5.3 Hz). 31P
NMR (121 MHz, CDCl3): d ꢀ36.04 (t, J = 134 Hz). HRMS (EI) for
EtOAc–hexane) under
a nitrogen atmosphere to afford L1
(0.744 g, 47% yield) as a white solid.
4.2.2. (R)-(2-(tert-Butylsulfinyl)-5-methoxyphenyl)di-o-
tolylphosphine L2
The compound was prepared in a similar manner to that de-
scribed above. White solid; yield 48%; ½a D20
¼ þ267 (c 0.134,
ꢁ
CHCl3). 1H NMR (300 MHz, CDCl3): d 7.91–7.87 (m, 1H); 7.26–
7.18 (m, 4H); 7.11–7.01 (m, 3H); 6.79–6.77 (m, 1H); 6.71–6.68
(m, 1H); 6.37 (s, 1H); 3.64 (s, 3H); 2.36 (d, J = 12.3 Hz, 6H); 1.27
C22H22F2OPS (M+H): calcd 403.1097, found 403.1092.
(s, 9H). 13C NMR (75 MHz, CDCl3):
d 161.64; 142.57 (d,
4.2.7. (R)-(2-(tert-butylsulfinyl)phenyl)bis(4-fluorophenyl)-
phosphine L7
J = 27.1 Hz); 142.08 (d, J = 27.3 Hz); 139.63 (d, J = 20.0 Hz);
137.14 (d, J = 23.7 Hz); 134.08 (d, J = 4.3 Hz); 133.69; 133.34 (d,
J = 13.6 Hz); 132.99; 130.20 (d, J = 9.5 Hz); 129.10; 128.77 (d,
J = 6.2 Hz); 126.35 (d, J = 4.7 Hz); 119.35; 114.35; 57.77; 55.13;
23.48 (d, J = 4.3 Hz); 21.46 (d, J = 12 Hz); 21.18 (d, J = 13.9 Hz).
31P NMR (121 MHz, CDCl3): d ꢀ26.6 (s). HRMS (EI) for C25H30O2PS
(M+H): calcd 425.1704, found 425.1698.
The compound was prepared in a similar manner to that de-
scribed above. White solid; yield 67%; ½a D20
¼ þ255 (c 0.208,
ꢁ
CHCl3). 1H NMR (300 MHz, CDCl3): d 8.00–7.92 (m, 1H); 7.58–
7.54 (m, 1H); 7.45–7.40 (m, 1H); 7.26–6.99 (m, 9H); 1.31 (s, 9H).
13C NMR (75 MHz, CDCl3):
d 165.11; 161.78; 146.09 (d,
J = 24.7 Hz); 138.23 (d, J = 19.2 Hz); 135.65 (dd, J = 21.3 Hz,
J = 8 Hz); 135.22 (dd, J = 21.5 Hz, J = 8.1 Hz); 133.47; 131.33;
131.01; 130.86; 129.74; 126.92 (d, J = 6.2 Hz); 116.09 (dd,
J = 20.9 Hz, J = 1.4 Hz); 115.99 (dd, J = 20.9 Hz; J = 2.2 Hz); 58.61;
23.62 (d, J = 4.9 Hz). 31P NMR (121 MHz, CDCl3): d ꢀ16.1 (s). HRMS
(EI) for C22H22F2OPS (M+H): calcd 403.1097, found 403.1092.
4.2.3. (R)-(2-(tert-butylsulfinyl)phenyl)di-o-tolylphosphine L3
The compound was prepared in a similar manner to that de-
scribed above. White solid; yield 43%; ½a D20
¼ þ351 (c 0.146,
ꢁ
CHCl3). 1H NMR (300 MHz, CDCl3): d 7.98–7.95 (m, 1H); 7.59–

J. Xing et al. / Tetrahedron: Asymmetry 23 (2012) 527–535
533
4.2.8. (R)-(2-(tert-butylsulfinyl)phenyl)bis(4-
methoxyphenyl)phosphine L8
4.3.3. (E)-(3-((2-Chlorobenzyl)oxy)prop-1-ene-1,3-diyl)-
dibenzene 3c
The compound was prepared in a similar manner to that de-
(R)-3c: White solid; yield 94%; ee 60%; ½a D20
ꢁ
¼ ꢀ13 (c 0.138, tol-
scribed above. White solid; yield 30%; ½a D20
ꢁ
¼ þ241 (c 0.182,
uene). 1H NMR (300 MHz, CDCl3): d 7.66 (d, J=7.3 Hz, 1H); 7.54–
7.46 (m, 2H); 7.46–7.26 (m, 11H); 6.74 (d, J = 15.9 Hz, 1H); 6.46–
6.38 (m, 1H); 5.12 (d, J = 7 Hz); 4.79–4.67 (m, 2H). 13C NMR
CHCl3). 1H NMR (300 MHz, CDCl3): d 7.93–7.92 (m, 1H); 7.52–
7.49 (m, 1H); 7.40–7.37 (m, 1H); 7.20–08 (m, 4H); 7.04–7.01 (m,
1H); 6.90–6.82 (m, 4H); 3.80 (d, J = 10 Hz, 6H); 1.30 (s, 9H). 13C
(75 MHz, CDCl3):
d 140.92; 136.47; 136.23; 132.80; 131.72;
NMR (75 MHz, CDCl3):
d
160.24 (d, J = 2.4 Hz); 145.66 (d,
129.99; 129.18; 129.00; 128.50; 127.75; 127.03; 126.86; 126.73;
126.61; 82.38; 67.44. HPLC (Chiralcel OJ-H column, 254 nm, 99/
1 = n-hexane/iso-propanol, flow = 0.5 ml/min), tR = 46.1 min (min-
or), tR = 51.7 min (major). (S)-3c: White solid; yield 90%; ee 54%;
J = 24.3 Hz); 139.72 (d, J = 24.5 Hz); 135.22 (d, J = 21.1 Hz);
134.76 (d, J = 21.1 Hz); 133.505; 131.01; 129.15; 126.56 (d,
J = 6.2 Hz); 126.54 (d, J = 24 Hz); 114.35; 114.25 (d, J = 1.5 Hz);
58.39; 55.11 (d, J = 2.9 Hz); 23.64 (d, J = 4.9 Hz). 31P (121 MHz,
CDCl3): d ꢀ17.0 (s). HRMS (EI) for C24H28O3PS (M+H): calcd
427.1497, found 427.1491.
½
a 2D0
ꢁ
¼ þ8 (c 0.12, toluene). HPLC (Chiralcel OJ-H column,
254 nm, 99/1 = n-hexane/iso-propanol, flow = 0.5 ml/min),
tR = 40.5 min (major), tR = 47.1 min (minor).
4.3.4. (E)-(3-((3-Chlorobenzyl)oxy)prop-1-ene-1,3-diyl)-
dibenzene 3d
4.3. Typical procedure for the palladium-catalyzed asymmetric
allylic etherification
(R)-3d: Colorless oil; yield 90%; ee 67%; ½a D20
¼ ꢀ12 (c 0.142,
ꢁ
toluene). 1H NMR (300 MHz, CDCl3): d 7.51–7.26 (m, 14H); 6.69
(d, J = 15.9 Hz, 1H); 6.43–6.36 (m, 1H); 5.06 (d, J = 6.9 Hz); 4.64–
4.54 (m, 2H). 13C NMR (75 MHz, CDCl3): d 140.78; 140.51;
136.38; 134.23; 131.72; 129.90; 129.61; 128.56; 128.51; 127.80;
127.79; 127.59; 126.88; 126.58; 125.56; 81.96; 69.30. HPLC (Chi-
ralcel OJ-H column, 254 nm, 96/4 = n-hexane/iso-propanol,
flow = 0.5 ml/min), tR = 27.6 min (minor), tR = 29.3 min (major).
Under an argon atmosphere, to a dried Schlenk flask, ligand L5
(3.5 mg, 4.4 mol %), [Pd(g
3–C3H5)Cl]2 (1.4 mg, 2.0 mol %), and ce-
sium carbonate (200 mg, 0.6 mmol) were added, followed by addi-
tion of CH3CN (1.0 mL). The mixture was stirred at room
temperature for 30 min, and then rac-1,3-diphenyl-2-propenyl
acetate (50 mg, 0.2 mmol) was added to the reaction system via
(S)-3d: Colorless oil; yield 93%; ee 57%; ½a D20
¼ þ8 (c 0.212, tolu-
ꢁ
a syringe. The nucleophile (63
lL, 0.6 mmol) was then added to
ene). HPLC (Chiralcel OJ-H column, 254 nm, 96/4 = n-hexane/iso-
propanol, flow = 0.5 ml/min), tR = 27.2 min (major), tR = 29.8 min
(minor).
the mixture. Conversion was monitored by TLC; the reaction
was diluted with Et2O, washed with saturated NH4Cl (aq), satu-
rated NaHCO3 (aq), and brine. The combined aqueous solutions
were extracted with CH2Cl2. The combined organic phase was
dried over MgSO4, filtered, concentrated in vacuo, and purified
by flash chromatography (petroleum ether/ethyl acetate = 200:1,
V/V).
4.3.5. (E)-(3-((3-Bromobenzyl)oxy)prop-1-ene-1,3-diyl)-
dibenzene 3e
(R)-3e: Colorless oil; yield 92%; ee 60%; ½a D20
¼ ꢀ10 (c 0.168, tol-
ꢁ
uene). 1H NMR (300 MHz, CDCl3): d 7.58 (s, 1H); 7.48–7.24 (m,
13H); 6.67 (d, J = 15.9 Hz, 1H); 6.41–6.34 (m, 1H); 5.04 (d,
J = 7 Hz, 2H); 4.61–4.52 (m, 2H). 13C NMR (75 MHz, CDCl3): d
140.79; 136.41; 131.78; 130.57; 129.95; 129.92; 128.60; 128.54;
127.85; 127.83; 126.92; 126.62; 126.09; 122.51; 82.01; 69.30.
HPLC (Chiralcel OJ-H column, 254 nm, 96/4 = n-hexane /iso-propa-
nol, flow = 0.5 ml/min), tR = 31.7 min (minor), tR = 35.2 min (ma-
4.3.1. (E)-(3-(Benzyloxy)prop-1-ene-1,3-diyl)dibenzene 3a
(R)-3a: Colorless oil; yield 97%; ee 65%; ½a D20
¼ ꢀ13 (c 0.202, tol-
ꢁ
uene). 1H NMR (300 MHz, CDCl3): d 7.49–7.26 (m,15H); 6.66 (d,
J = 15.9 Hz, 1H); 6.41–6.39 (m, 1H); 5.05 (d, J = 6.9 Hz, 1H); 4.57
(s, 2H). 13C NMR (75 MHz, CDCl3): d 141.08; 138.67; 136.52;
131.50; 130.22; 128.49; 128.48; 128.34; 127.67; 127.49; 126.94;
126.56; 81.54; 70.05. HPLC (Chiralcel OJ-H column, 254 nm, 98/
2 = n-hexane/iso-propanol, flow = 1.0 ml/min), tR = 18.3 min (min-
or), tR = 22.2 min (major). (S)-3a: Colorless oil; yield 96%; ee 56%;
jor). (S)-3e: Colorless oil; yield 95%; ee 59%; ½a D20
¼ þ6 (c 0.148,
ꢁ
toluene). HPLC (Chiralcel OJ-H column, 254 nm, 96/4 = n-hexane/
iso-propanol, flow = 0.5 ml/min), tR = 30.8 min (major), tR =
36.0 min (minor).
½
a 2D0
ꢁ
¼ þ9 (c 0.136, toluene). HPLC (Chiralcel OJ-H column,
4.3.6. (E)-(3-((4-Bromobenzyl)oxy)prop-1-ene-1,3-diyl)-
254 nm, 98/2= n-hexane/iso-propanol, flow = 1.0 ml/min), tR =
dibenzene 3f
18.0 min (major), tR = 22.3 min (minor).
(R)-3f: Colorless oil; yield 95%; ee 67%; ½a D20
¼ ꢀ19 (c 0.222, tol-
ꢁ
uene). 1H NMR (300 MHz, CDCl3): d 7.55–7.28 (m, 14 Hz); 6.69 (d,
J = 15.9 Hz, 1H); 6.43–6.40 (m, 1H); 5.05 (d, J = 7 Hz, 1H);4.62–4.53
(m,2H). 13C NMR (75 MHz, CDCl3): d 140.82; 137.40; 136.37;
131.64; 131.42; 129.93; 129.27; 128.54; 128.50; 127.77; 126.87;
126.56; 121.31; 81.75; 69.28. HPLC (Chiralcel OJ-H column,
254 nm, 98/2 = n-hexane/iso-propanol, flow = 1.0 ml/min), tR =
35.1 min (minor), tR = 39.6 min (major). (S)-3f: Colorless oil; yield
4.3.2. (E)-(3-((2-Fluorobenzyl)oxy)prop-1-ene-1,3-diyl)-
dibenzene 3b
(R)-3b: White solid; yield 95%; ee 64%; ½a D20
¼ ꢀ8 (c 0.158, tol-
ꢁ
uene). 1H NMR (300 MHz, CDCl3): d 7.57–7.52 (m, 1H); 7.52–7.50
(m, 2H); 7.46–7.35 (m, 4H); 7.30–7.28 (m, 5H); 7.22–7.20 (m,
1H); 7.19–7.09 (m, 1H); 6.72 (d, J = 15.9 Hz, 1H); 6.45–6.37 (m,
1H); 5.10 (d, J = 7 Hz, 1H); 4.76–4.66 (m, 2H). 13C NMR (75 MHz,
94%; ee 56%; ½a 2D0
¼ þ12 (c 0.172, toluene). HPLC (Chiralcel OJ-H
ꢁ
CDCl3):
d 160.69 (d, J = 245.2 Hz). 140.97; 136.53; 131.76;
column, 254 nm, 98/2 = n-hexane/iso-propanol, flow = 1.0 ml/
min), tR = 33.2 min (major), tR = 40.1 min (minor).
130.05; 129.96 (d, J = 4.4 Hz).; 129.20 (d, J = 8.0 Hz).; 128.55;
128.53; 127.78; 127.08; 126.94; 126.64; 125.60 (d, J = 14.6 Hz).;
124.05 (d, J = 3.5 Hz).; 115.18 (d, J = 21.2 Hz); 82.21; 63.90 (d,
J = 3.9 Hz). HPLC (Chiralcel OJ-H column, 254 nm, 99/1 = n-hex-
ane/iso-propanol, flow = 1.0 ml/min), tR = 21.6 min (minor), tR =
26.9 min (major). (S)-3b: White solid; yield 90%; ee 58%;
4.3.7. (E)-(3-((2-Methylbenzyl)oxy)prop-1-ene-1,3-diyl)-
dibenzene 3g
(R)-3g: White solid; yield 91%; ee 66%; ½a D20
¼ ꢀ7(c 0.144, tolu-
ꢁ
ene). 1H NMR (300 MHz, CDCl3): d 7.55–7.26 (m, 14H); 6.74 (d,
J = 15.9 Hz, 1H); 6.49–6.41 (m, 1H); 5.12 (d, J = 6.9 Hz, 1H); 4.71–
4.60 (m, 1H); 2.42 (s, 3H). 13C NMR (75 MHz, CDCl3): d 141.11;
136.70; 136.53; 136.20; 131.39; 130.31; 130.17; 128.59; 128.47;
½
a 2D0
ꢁ
¼ þ5 (c 0.168, toluene). HPLC (Chiralcel OJ-H column,
254 nm, 99/1 = n-hexane/iso-propanol, flow = 1.0 ml/min), tR =
21.1 min (major), tR = 27.6 min (minor).

534
J. Xing et al. / Tetrahedron: Asymmetry 23 (2012) 527–535
127.69; 127.67; 127.65; 127.01; 126.92; 126.55; 125.73; 81.72;
68.63; 18.90. HPLC (Chiralcel OJ-H column, 254 nm, 99/1 = n-hex-
ane/iso-propanol, flow = 0.5 ml/min), tR = 57.0 min (major),
tR = 71.3 min (minor). (S)-3g: White solid; yield 88%; ee 52%;
254 nm, 90/10 = n-hexane/iso-propanol, flow = 0.5 ml/min), tR =
69.5 min (minor), tR = 79.4 min (major).
4.3.12. (E)-1-(((1,3-Diphenylallyl)oxy)methyl)naphthalene 3l
½
a 2D0
ꢁ
¼ þ4 (c 0.156, toluene). HPLC (Chiralcel OJ-H column,
(R)-3l: White solid; yield 85%; ee 67%; ½a D20
¼ ꢀ17 (c 0.176, tol-
ꢁ
254 nm, 99/1 = n-hexane/iso-propanol, flow = 0.5 ml/min), tR =
uene). 1H NMR (300 MHz, CDCl3): d 8.12–8.10 (m, 1H); 7.89–7.81
(m, 2H); 7.58–7.33 (m, 14H); 6.67 (d, J = 15.9 Hz, 1H); 6.48–6.41
(m, 1H); 5.16 (d, J = 6.9 Hz, 1H); 5.08 (s, 2H). 13C NMR (75 MHz,
52.5 min (minor), tR = 61.5 min (major).
CDCl3):
d 141.06; 136.53; 133.77; 133.71; 131.74; 131.67;
4.3.8. (E)-(3-((4-Methylbenzyl)oxy)prop-1-ene-1,3-diyl)-
130.22; 128.50; 127.71; 127.03; 126.58; 126.36; 126.08; 125.70;
125.22; 124.05; 81.72; 68.61. HPLC (Chiralcel OJ-H column,
254 nm, 96/4 = n-hexane/iso-propanol, flow = 0.5 ml/min), tR =
46.6 min (minor), tR = 52.5 min (major). (S)-3l: White solid; yield
dibenzene 3h
(R)-3h: Colorless oil; yield 92%; ee 63%; ½a D20
¼ ꢀ13 (c 0.244,
ꢁ
toluene). 1H NMR (300 MHz, CDCl3): d 7.52–7.22 (m, 14H); 6.69
(d, J = 15.9 Hz, 1H); 6.45–6.37 (m, 1H); 5.07 (d, J = 6.9 Hz, 1H);
4.62 (s, 2H); 2.42 (s, 3H). 13C NMR (75 MHz, CDCl3): d 141.16;
137.17; 136.56; 135.28; 131.41; 130.32; 129.03; 128.47; 127.82;
127.65; 127.63; 126.95; 126.55; 81.29; 69.91; 21.15. HPLC (Chiral-
cel OJ-H column, 254 nm, 98/2 = n-hexane/iso-propanol, flow =
1.0 ml/min), tR = 16.7 min (minor), tR = 19.8 min (major). (S)-3h:
81%; ee 54%; ½a 2D0
¼ þ12 (c 0.188, toluene). HPLC (Chiralcel OJ-H
ꢁ
column, 254 nm, 96/4 = n-hexane/iso-propanol, flow = 0.5 ml/
min), tR = 46.4 min (major), tR = 55.9 min (minor).
4.3.13. ((E)-3-(Cinnamyloxy)prop-1-ene-1,3-diyl)dibenzene 3m
(R)-3m: Colorless oil; yield 72%; ee 62%; ½a D20
¼ ꢀ19 (c 0.122,
ꢁ
Colorless oil; yield 95%; ee 55%; ½a D20
¼ þ10 (c 0.214, toluene).
ꢁ
toluene). 1H NMR (300 MHz, CDCl3): d 7.46–7.24 (m, 15H); 6.69–
6.61 (m, 2H); 6.39–6.31 (m, 2H); 5.06 (d, J = 7 Hz, 1H); 4.28–4.17
(m, 2H). 13C NMR (75 MHz, CDCl3): d 141.05; 136.69; 136.49;
132.36; 131.49; 130.17; 128.54; 128.50; 127.71; 127.61; 126.92;
126.57; 126.45; 126.09; 81.71; 68.88. HPLC (Chiralcel OJ-H col-
umn, 254 nm, 50/50 = n-hexane /iso-propanol, flow = 0.5 ml/min),
tR = 26.7 min (minor), tR = 29.6 min (major). (S)-3m: Colorless oil;
HPLC (Chiralcel OJ-H column, 254 nm, 98/2 = n-hexane /iso-propa-
nol, flow = 1.0 ml/min), tR = 16.2 min (major), tR = 20.2 min
(minor).
4.3.9. (E)-(3-((3-Methoxybenzyl)oxy)prop-1-ene-1,3-diyl)-
dibenzene 3i
(R)-3i: Colorless oil; yield 92%; ee 65%; ½a D20
¼ ꢀ15 (c 0.168, tol-
ꢁ
yield 68%; ee 57%; ½a D20
ꢁ
¼ þ17 (c 0.098, toluene). HPLC (Chiralcel
uene). 1H NMR (300 MHz, CDCl3): d 7.51–7.27 (m, 11H); 7.01–7.00
(m, 2H); 6.90–6.88 (m, 1H); 6.68 (d, J = 15.9 Hz, 1H); 6.43–6.36 (m,
1H); 5.06 (d, J = 6.9 Hz, 1H); 4.61 (s, 2H); 3.84 (s, 3H). 13C NMR
OJ-H
column,
254 nm, 50/50 = n-hexane /iso-propanol,
flow = 0.5 ml/min), tR = 26.1 min (major), tR = 29.7 min (minor).
(75 MHz, CDCl3):
d 159.67; 141.03; 140.00; 136.50; 131.52;
4.3.14. (E)-2-(((1,3-Diphenylallyl)oxy)methyl)furan 3n
130.16; 129.36; 128.49; 127.69; 126.94; 126.55; 119.89; 113.09;
112.97; 81.52; 69.91; 55.13. HPLC (Chiralcel OJ-H column,
254 nm, 50/50 = n-hexane/iso-propanol, flow = 0.5 ml/min), tR =
17.0 min (minor), tR = 18.7 min (major). (S)-3i: Colorless oil; yield
(R)-3n: Colorless oil; yield 95%; ee 65%; ½a D20
¼ ꢀ4 (c 0.128, tol-
ꢁ
uene). 1H NMR (300 MHz, CDCl3): d 7.48–7.26 (m, 11H); 6.66 (d,
J = 15.9 Hz, 1H); 6.40–6.33 (m, 3H); 5.06 (d, J = 7 Hz, 1H); 4.55 (s,
2H). 13C NMR (75 MHz, CDCl3): d 151.71; 142.76; 140.68; 136.42;
131.81; 129.79; 128.51; 128.46; 127.74; 127.72; 126.99; 126.56;
110.20; 109.34; 81.35; 62.06. HPLC (Chiralcel OJ-H column,
254 nm, 95/5 = n-hexane /iso-propanol, flow = 1.0 ml/min),
tR = 13.7 min (minor), tR = 17.5 min (major). (S)-3n: Colorless oil;
95%; ee 55%; ½a 2D0
¼ þ12 (c 0.184, toluene). HPLC (Chiralcel OJ-H
ꢁ
column, 254 nm, 50/50 = n-hexane /iso-propanol, flow = 0.5 ml/
min), tR = 16.9 min (major), tR = 18.9 min (minor).
yield 92%; ee 61%; ½a D20
ꢁ
¼ þ3 (c 0.132, toluene). HPLC (Chiralcel
4.3.10. (E)-(3-((3,4-Dimethoxybenzyl)oxy)prop-1-ene-1,3-diyl)
dibenzene 3j
OJ-H
column,
254 nm, 95/5 = n-hexane /iso-propanol,
(R)-3j: Colorless oil; yield 98%; ee 66%; ½a D20
¼ ꢀ19 (c 0.14, tol-
ꢁ
flow = 1.0 ml/min), tR = 13.3 min (major), tR = 18.0 min (minor).
uene). 1H NMR (300 MHz, CDCl3): d 7.48–7.25 (m, 10H); 6.96–6.88
(m, 3H); 6.65 (d, J = 15.9 Hz, 1H); 6.42–6.40 (m, 1H); 5.04 (d,
J = 6.9 Hz, 1H); 4.56 (s, 2H); 3.90 (s, 3H); 3.89 (s, 3H). 13C NMR
4.3.15. (E)-2-(((1,3-Diphenylallyl)oxy)methyl)thiophene 3o
(R)-3o: Colorless oil; yield 97%; ee 62%; ½a D20
¼ ꢀ20 (c 0.138, tol-
ꢁ
uene). 1H NMR (300 MHz, CDCl3): d 7.49–7.27 (m, 11H); 7.04–7.02
(m, 2H); 6.65 (d, J = 15.9 Hz, 1H); 6.42–6.39 (m, 1H); 5.10 (d,
J=7 Hz, 1H); 4.78 (s, 2H). 13C NMR (75 MHz, CDCl3): d 141.14;
140.73; 136.41; 131.87; 129.79; 128.51; 128.49; 127.75; 126.98;
126.57; 126.29; 125.74; 80.98; 64.56. HPLC (Chiralcel OJ-H col-
umn, 254 nm, 95/5 = n-hexane /iso-propanol, flow = 1.0 ml/min),
tR = 14.3 min (minor), tR = 17.1 min (major). (S)-3o: Colorless oil;
(75 MHz, CDCl3):
d 148.87; 148.41; 141.05; 136.43; 131.41;
130.77; 130.18; 128.43; 127.63; 127.62; 126.91; 126.47; 120.21;
111.03; 110.82; 81.20; 69,93; 55.79; 55.70. HPLC (Chiralcel OJ-H
column, 254 nm, 50/50 = n-hexane /iso-propanol, flow = 0.5 ml/
min), tR = 23.6 min (minor), tR = 28.1 min (major). (S)-3j: Colorless
oil; yield 95%; ee 56%; ½a D20
¼ þ16 (c 0.208, toluene). HPLC (Chiral-
ꢁ
cel OJ-H column, 254 nm, 50/50 = n-hexane /iso-propanol,
flow = 0.5 ml/min), tR = 23.4 min (major), tR = 29.1 min (minor).
yield 95%; ee 58%; ½a D20
ꢁ
¼ þ16 (c 0144, toluene). HPLC (Chiralcel
OJ-H
column,
254 nm, 95/5 = n-hexane /iso-propanol,
4.3.11. (E)-(3-((4-Nitrobenzyl)oxy)prop-1-ene-1,3-diyl)-
flow = 1.0 ml/min), tR = 14.2 min (major), tR = 17.9 min (minor).
dibenzene 3k
(R)-3k:Colorless oil; yield 80%; ee 65%; ½a D20
¼ ꢀ26 (c 0.122, tol-
ꢁ
4.3.16. (E)-2-(((1,3-Diphenylallyl)oxy)methyl)pyridine 3p
uene). 1H NMR (300 MHz, CDCl3): d 8.22 (d, J = 8.7 Hz, 1H); 7.57–
7.27 (m, 12H); 6.70 (d, J = 15.9 Hz, 1H); 6.41–6.34 (m, 1H); 5.56
(d, J = 6.9 Hz, 1H); 4.75–4.63 (m, 2H). 13C NMR (75 MHz, CDCl3):
(R)-3p Colorless oil; yield 88%; ee 53%; ½a D20
¼ ꢀ6 (c 0.194, tol-
ꢁ
uene). 1H NMR (300 MHz, CDCl3): d 8.56–8.85 (m, 1H); 7.73–7.68
(m, 1H); 7.59–7.56 (m, 1H); 7.50–7.47 (m, 2H); 7.42–7.37 (m,
4H); 7.34–7.29 (m, 3H); 7.26–7.23 (m, 1H); 7.21–7.16 (m, 1H);
6.70 (d, J = 15.9 Hz, 1H); 6.42–6.40 (m, 1H); 5.11 (d, J = 7 Hz, 1H);
4.80–4.68 (m, 2H). 13C NMR (75 MHz, CDCl3): d 158.65; 148.94;
140.76; 136.53; 136.36; 131.78; 129.77; 128.49; 128.43; 127.73;
127.71; 126.82; 126.55; 122.17; 121.26; 82.51; 71.11. HPLC (Chi-
ralcel OJ-H column, 254 nm, 90/10 = n-hexane /iso-propanol,
d
147.19; 146.10; 140.46; 136.18; 131.95; 129.50; 128.62;
128.53; 127.95; 127.91; 127.65; 126.78; 126.56; 123.52; 82.50;
68.88. HPLC (Chiralcel OJ-H column, 254 nm, 90/10 = n-hexane /
iso-propanol,
tR = 80.3 min (minor). (S)-3k:Colorless oil; yield 83%; ee 60%;
¼ þ19 (c 0.13, toluene). HPLC (Chiralcel OJ-H column,
flow = 0.5 ml/min),
tR = 68.3 min
(major),
½ ꢁ
a 2D0

J. Xing et al. / Tetrahedron: Asymmetry 23 (2012) 527–535
535
flow = 1.0 ml/min), tR = 10.1 min (minor), tR = 10.8 min (major).
Research Program of China (973 Program, 2010CB833300) and
Chengdu Institute of Biology, CAS (Y0B1051100).
(S)-3p: Colorless oil; yield 90%; ee 68%; ½a D20
¼ þ14 (c 0.152, tolu-
ꢁ
ene). HPLC (Chiralcel OJ-H column, 254 nm, 90/10 = n-hexane /iso-
propanol, flow = 1.0 ml/min), tR = 10.1 min (major), tR = 11.7 min
(minor).
References
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4.3.17. (E)-(3-Methoxyprop-1-ene-1,3-diyl)dibenzene 3q
(R)-3q: Colorless oil; yield 98%; ee 62%; ½a D20
¼ þ9(c 0.164, tol-
ꢁ
uene). 1H NMR (300 MHz, CDCl3): d 7.43–7.22 (m, 10H); 6.65 (d,
J = 15.9 Hz, 1H); 6.35–6.27 (m, 1H); 4.83 (d, J = 7 Hz, 1H); 3.41 (s,
3H). 13C NMR (75 MHz, CDCl3): d 140.99; 136.53; 131.43; 130.09;
128.49; 128.25; 127.69; 126.81; 126.55; 84.28; 56.40. HPLC (Chi-
ralcel OJ-H column, 254 nm, 96/4 = n-hexane/iso-propanol,
flow = 0.5 ml/min), tR = 22.4 min (minor), tR = 24.5 min (major).
(S)-3q: Colorless oil; yield 97%; ee 55%; ½a D20
¼ ꢀ7 (c 0.138, tolu-
ꢁ
ene). HPLC (Chiralcel OJ-H column, 254 nm, 96/4 = n-hexane /iso-
propanol, flow = 0.5 ml/min), tR = 22.5 min (major), tR = 25.4 min
(minor).
4.3.18. (S,E)-Dimethyl 2-(1,3-diphenylallyl)malonate 4
(S)-4: Colorless oil; yield 98%; ee 63%; ½a D20
¼ ꢀ12 (c 0.268,
ꢁ
CHCl3). 1H NMR (300 MHz, CDCl3): d 7.32–7.19 (m, 10H); 6.48 (d,
J = 15.7 Hz, 1H); 6.35 (dd, J = 15.9 Hz, J = 8.4 Hz, 1H); 4.27 (dd,
J = 10.8 Hz, J = 8.4 Hz, 1H); 3.96 (d, J = 10.8 Hz, 1H); 3.70 (s, 3H);
3.51 (s, 3H). HPLC (Chiralcel IA column, 254 nm, 95/5 = n-hexane
/iso-propanol, flow = 1.0 ml/min), tR = 9.8 min (minor), tR =
12.0 min (major). (R)-4: Colorless oil; yield 96%; ee 53%;
4. Lam, F. L.; Au-Yeung, T. T.; Kwong, F. Y.; Zhou, Z.; Wong, K. Y.; Chan, A. S. C.
Angew. Chem., Int. Ed. 2008, 47, 1280–1283.
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M. Tetrahedron: Asymmetry 2011, 22, 1379–1389.
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Deng, J.-G.; Liao, J. Tetrahedron: Asymmetry 2009, 20, 1953–1956; (c) Lang, F.; Li,
D.; Chen, J.-M.; Chen, J.; Li, L. C.; Cun, L. F.; Zhu, J.; Deng, J.-G.; Liao, J. Adv. Synth.
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Z.; Cun, L.-F.; Liao, J. Chem. Eur. J. 2011, 17, 5242–5245; (e) Xing, J.-W.; Chen, G.-
H.; Cao, P.; Liao, J. Eur. J. Org. Chem. 2011, 6, 1230–1236; (f) Liu, J.-B.; Chen, G.-H.;
Xing, J.-W.; Liao, J. Tetrahedron: Asymmetry 2011, 22, 575–579; (g) Chen, G.-H.;
Gui, J.-Y.; Li, L.-C.; Liao, J. Angew. Chem. Int. Ed. 2011, 50, 7681–7685.
7. (a) Tsuji, J.; Minami, I. Acc. Chem. Res. 1987, 20, 140–145; (b) Auburn, P. R.;
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Acc. Chem. Res. 1993, 26, 339–345; (d) Trost, B. M.; Toste, F. D. J. Am. Chem. Soc.
1999, 121, 4545–4554; (e) Togni, A.; Burckhardt, U.; Gramlich, V.; Pregosin, P. S.;
Salzmann, R. J. Am. Chem. Soc. 1996, 118, 1031–1037.
8. For selected examples of reversal in enantioselectivity for the Pd-catalyzed
asymmetric allylic substitutions, see (a) Hoarau, O.; Ait-Haddou, H.; Daran, J.-C.;
Cramailere, D.; Balavoine, G. G.-A. Organometallics 1999, 18, 4718–4723; (b)
Chelucci, G.; Pinna, G. A.; Saba, A.; Valenti, R. Tetrahedron: Asymmetry 2000, 11,
4027–4036; (c) Li, X.-G.; Cheng, X.; Ma, J.-A.; Zhou, Q.-L. J. Organomet. Chem.
2001, 640, 65–71; (d) Sibi, M. P.; Liu, M. Curr. Org. Chem. 2001, 5, 719–755; (e)
Anderson, J.-C.; Cubbon, R.-J.; Harling, J.-D. Tetrahedron: Asymmetry 1999, 10,
2829–2832; (f) Zhang, W.; Shi, M. Tetrahedron: Asymmetry 2004, 15, 3467–3476;
(g) Danjo, H.; Higuchi, M.; Yada, M.; Imamoto, T. Tetrahedron Lett. 2004, 45. 606–
606; (h) Haddou, H.-A.; Hoarau, O.; Cramailere, D.; Pezet, F.; Daran, J.-C.;
Balavoine, G. G.-A. Chem. Eur. J. 2004, 10, 699–707; (i) Frolander, A.; Lutsenko, S.;
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Zhang, W.-B. Tetrahedron Lett. 2008, 49, 1012–1015.
½
a 2D0
ꢁ
¼ þ8 (c 0.280, CHCl3). HPLC (Chiralcel IA column, 254 nm,
95/5 = n-hexane /iso-propanol, flow = 1.0 ml/min), tR = 9.8 min
(major), tR = 12.1 min (minor).
4.3.19. (R,E)-N-Benzyl-1,3-diphenylprop-2-en-1-amine 5
(R)-5: Colorless oil; yield 99%; ee 62%; ½a D20
¼ ꢀ13 (c 0.156,
ꢁ
CHCl3). 1H NMR (300 MHz, CDCl3): d 7.47–7.22 (m, 15H); 6.60 (d,
J = 16.8 Hz, 1H); 6.36 (dd, J = 7.5 Hz, J = 16.8 Hz, 1H); 4.42 (d,
J = 7.5 Hz, 1H); 3.80 (d, J = 13.2 Hz, 1H); 1.75 (s, 1H). HPLC (Chiral-
cel OJ-H column, 254 nm, 96/4 = n-hexane/iso-propanol, flow =
0.5 ml/min), tR = 33.1 min (minor), tR = 37.5 min (major). (S)-5:
Colorless oil; yield 98%; ee 63%; ½a D20
¼ þ14 (c 0.194, CHCl3).
ꢁ
HPLC(Chiralcel OJ-H column, 254 nm, 96/4 = n-hexane /iso-propa-
nol, flow = 0.5 ml/min), tR = 32.4 min (major), tR = 38.9 min
(minor).
Acknowledgments
We are grateful for support from the NSFC (20872139 and
21072186), the West Light Foundation of CAS, the National Basic
9. Hiroi, K.; Suzuki, Y.; Kawagishi, R. Tetrahedron Lett. 1999, 40, 715–718.