The synthesis of phosphine oxide-linked bis(oxazoline) ligands and their application in asymmetric allylic alkylation

Article abstract of DOI:10.1016/j.tet.2012.02.078

The phosphine oxide-linked bis(oxazoline) ligands were designed and synthesized in two ways. One is the coupling of Grignard reagent derived from 2-(2-bromophenyl)oxazoline with phenylphosphonic dichloride, another route is the condensation of bis(2-formylphenyl)(phenyl)phosphine oxide with chiral amino alcohols followed by NBS oxidation. These new bis(oxazoline) ligands were applied in Pd-catalyzed asymmetric allylic alkylation reactions and good yields and enantioselectivities were obtained with diphenyl substituted ligand (up to 95% ee).

Full text of DOI:10.1016/j.tet.2012.02.078

Tetrahedron 68 (2012) 3633e3640
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
The synthesis of phosphine oxide-linked bis(oxazoline) ligands and their
application in asymmetric allylic alkylation
*
Yu Jin, Da-Ming Du
School of Chemical Engineering and Environment, Beijing Institute of Technology, Beijing 100081, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The phosphine oxide-linked bis(oxazoline) ligands were designed and synthesized in two ways. One is
the coupling of Grignard reagent derived from 2-(2-bromophenyl)oxazoline with phenylphosphonic
dichloride, another route is the condensation of bis(2-formylphenyl)(phenyl)phosphine oxide with chiral
amino alcohols followed by NBS oxidation. These new bis(oxazoline) ligands were applied in
Pd-catalyzed asymmetric allylic alkylation reactions and good yields and enantioselectivities were
obtained with diphenyl substituted ligand (up to 95% ee).
Received 25 October 2011
Received in revised form 22 February 2012
Accepted 28 February 2012
Available online 8 March 2012
Keywords:
Asymmetric catalysis
Bis(oxazoline)
Ó 2012 Elsevier Ltd. All rights reserved.
Phosphine oxide
Allylic alkylation
1. Introduction
diphenylamine-linked ligands were successfully applied to many
asymmetric reactions, such as asymmetric Henry reaction, Michael
Oxazoline ligand has been recognized as one type of the ‘priv-
ileged ligands’ owing to its ready synthesis, modular nature, and
successful applications in various catalytic asymmetric reactions.
The design, synthesis and applications of chiral oxazoline ligands
have gained much attention in recent years.1 Many types of ligands
with diverse scaffolds have been synthesized from commercially
available amino alcohols in a few steps. Among the various ligands,
some ligand scaffolds can be used in a variety of different asym-
metric transformations, while other ligand scaffolds only can be
applied in specific reactions. To the best of our knowledge, there is
no universal oxazoline ligand suitable for every organic reaction or
every substrate. This situation makes the design of novel oxazoline
ligands and studies on the relationship of ligand structure and
enantioselectivity still a challenging task.
In recent years, the C2-symmetric chiral bis(oxazoline) ligands
L1eL4 with diphenyl bridging backbone (Fig. 1) have been studied
extensively because of their excellent applicability to metal cation
in combination with stereochemical discrimination. Due to the
different bridging linkers, the corresponding bis(oxazoline) ligands
have demonstrated different applications in asymmetric reac-
tions.2e4 For example, ligand L1 with the bridging linker is NH,
which was reported by our group2 and Guiry’s group,3 these
addition, FriedeleCrafts alkylation, NozakieHiyamaeKishi reaction
and so on. The ligand L2 with the bridging linker is O atom was
ꢀ
reported in 2002 by Gomez and co-workers, this diphenyl ether-
linked ligand was applied to the asymmetric allylic alkylation and
up to 89% ee was obtained.4a The good enantioselectivity in
asymmetric allylic alkylation was also obtained with diphenyl
sulfide-linked ligand L3.4b Other bridging groups such as phenyl-
phosphine has also been synthesized and applied in asymmetric
allylic alkylation.4c The bis(oxazoline) ligands containing phosphite
linker5a or phosphite, phosphinite, and phosphane side arms5b
were also reported. However, to our knowledge, the synthesis
and studies on phosphine oxide-linked bis(oxazoline) ligands have
not appeared, although phosphine oxide has well properties to
activate some Lewis acids such as allysilane.5c,5d In this paper, we
designed and synthesized a series of phosphine oxide-linked
bis(oxazoline) ligands L5eL9 and studied their applications in
Pd-catalyzed asymmetric allylic alkylation reactions.
Ph
L5: R1 = Bn, R2 = H
X
L6: R1 = iPr, R2 = H
L7: R1 = tBu, R2 = H
L8: R1 = Ph, R2 = H
P
O
L1: X = NH
L2: X = O
O
N
R
N
R
O
N
O
O
N
L3: X = S
L4: X = P-Ph
R1
R2 L9: R1 = Ph, R2 = Ph
R1
R'
R2
R'
* Corresponding author. Tel./fax: þ0 86 10 68914985; e-mail address: dudm@
bit.edu.cn (D.-M. Du).
Fig. 1. C2-symmetric chiral bis(oxazoline) ligands with diphenyl bridging backbone.
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.02.078

3634
Y. Jin, D.-M. Du / Tetrahedron 68 (2012) 3633e3640
2. Results and discussion
Ph
P
O
HOCH2CH2OH,
Br
Br
O
pTSA
Mg, THF
50 oC, 2 h THF, r.t., 12h
PhPOCl2
2.1. Synthesis of phosphine oxide-linked bis(oxazoline)
ligands
O
reflux, 48 h
89%
CHO
O
O
O
O
75%
4
5
6
The synthesis of oxazoline has been widely described in the
literature and the method of acid derivatives reacting with chiral
amino alcohols followed by cyclization was the most widely used
method.6 At first, we designed to synthesize the phosphine oxide-
linked bis(oxazoline) ligands through mono-oxazoline coupling.
This approach consists of the synthesis of mono-oxazoline semi-
ligand, then two equal parts are joined through a PheP(O)
bridging. The synthesis of mono-oxazoline 3 was initiated from
2-bromobenzoic acid 1, which was converted into the corre-
sponding acid chloride 2 by refluxing in thionyl chloride. Without
further purification, the acid chloride was treated with chiral amino
alcohols and Et3N in CH2Cl2, followed by methanesulfonyl chloride,
and then refluxed under basic conditions to yield the mono-
oxalzoines 3aec.7 The products 3 were then converted to corre-
sponding Grignard reagents and the later reacted with phenyl-
phosphonic dichloride (PhPOCl2) to give the corresponding
bis(oxazoline) ligands L5eL7 (as shown in Scheme 1).
H2N
R1
OH
Ph
P
O
R2
pTSA
NBS
Ph
P
CHO O
acetone/H2O
79%
4A MS,
CH2Cl2
O
N
N
O
CHO
R2
R1
R2
R1
L8 - L9
1 = Ph, R2 = H 26%
1 = R2 = Ph
32%
7
L8:
L9:
R
R
Scheme 2. Synthesis of phosphine oxide-linked bis(oxazoline) ligands L8eL9.
N,O-bis(trimethylsilyl)acetamide (BSA) (3 equiv) and KOAc (acted
as BSA activator) (0.2 equiv).
After screening different solvents (as shown in Table 1), we
found that the best solvent was CHCl3, although in which the re-
activity was lower than toluene, the enantioselectivity was much
higher (up to 60% ee) (Table 1, entry 4 vs entry 8). In protic solvent
such as ethanol, there was no conversion at all (Table 1, entry 7). In
CHCl3, we then studied the effects of ligands L5eL9 in asymmetric
allylic alkylation and found that the reactivity and enantiose-
lectivity were highly depended on the substituent group of oxa-
zoline moiety; the steric bulkiness of the substituent on the
oxazoline affected the asymmetric induction in this allylic alkyl-
ation. To our delight, when the substituent was Ph, both the re-
activity and the enantioselectivity were greatly improved. Ligand
L9 synthesized from (1R,2S)-1,2-dipheny1-2-aminoethanol was
regarded as the best ligand because of the best enantioselectivity
(94% ee) (Table 1, entry 12). Owing to the long reaction time, we
further raised the reaction temperature to improve the activity. The
reaction time could be reduced to 3 days when it was performed at
40 ꢀC and the yield was enhanced to 99% with slightly decrease of
the enantioselectivity (from 94% to 92% ee) (Table 1, entries 13).
H2N
R1
OH
Br
Br
SOCl2
reflux
1) MeSO2Cl, Et3N
Et3N, CH2Cl2
2) NaOH/MeOH/H2O
reflux
COCl
CO2H
2
1
Br
O
MgBr
Ph
P
O
Mg
PhPOCl2
THF, r.t., 12 h
THF, 50 , 2 h
O
N
O
N
N
O
N
R1
R1
R1
R1
3a-c
3a: R1 = Bn
87%
83%
L5 - L7
L5:
R
1 = Bn
35%
51%
3b: R1 = iPr
L6: R1 = iPr
3c:
R
1 = tBu 62%
L7: R1 = tBu 50%
Scheme 1. Synthesis of phosphine oxide-linked bis(oxazoline) ligands L5eL7.
To our disappointment, the bis(oxazoline) ligands L8 and L9
cannot be synthesized through the above Grignard reagent coupling
method, this may be ascribed to the active benzyl hydrogens in
mono-oxazolines when the substituents in 4- or/and 5-position are
phenyl. So we designed another route to synthesize the phosphine
oxide-linked bis(oxazoline) ligands L8 and L9. This approach was
based on thesynthesis of thebis(2-formylphenyl)(phenyl)phosphine
oxide bridging linker, followed by the formation of the chiral oxazi-
line rings. The synthetic route started with 2-bromobenzaldehyde 4,
which was protected by ethylene glycol to yield 5,8a Compound 5 was
converted to Grignard reagent,8b,8c coupling with PhPOCl2 and then
deprotection to afford the corresponding dicarboxyaldehyde 7.8d The
latter was transformed into L8 or L9 by reacted with corresponding
Table 1
Screening of solvents, ligands and temperature in asymmetric allylic alkylationa
L5-L9 (6 mol %)
MeO2C
CO2Me
Ph
OAc
Ph
Pd(η3-C3H5)Cl]2 (2.5 mol %)
CO2Me
CO2Me
+
Ph
KOAc 0.2 equiv.
BSA 3.0 equiv.
Ph
8a
9a
10a
Entry
Ligand
Solvent
Time(day)
Yield(%)b
ee(%)c
1
2
3
4
5
6
7
8
L5
L5
L5
L5
L5
L5
L5
L5
L6
L7
L8
L9
L9
CH2Cl2
CCl4
ClCH2CH2Cl
Toluene
THF
8
8
8
8
8
8
8
8
8
14
8
55
29
trace
59
18
trace
0
57
23
20
33
40
n.d.
50
17
n.d.
n.d.
60
15
30
ꢁ
chiral amino alcohols in CH2Cl2 in the presence of 4 A molecular
sieves and subsequently oxidized by the N-bromosuccinimide (NBS)
Et2O
EtOH
(as shown in Scheme 2).9
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
9
2.2. Pd-catalyzed asymmetric allylic alkylation
10
11
12
13d
89
73
99
89
94
92
8
3
Allylic alkylation is one of the most versatile methods for
forming different types of carbonecarbon and carboneheteroatom
bonds.10 In order to evaluate the asymmetric catalytic activity of the
new ligands, we decided to investigate the asymmetric allylic al-
kylation reaction. Ligand L5 was used first in order to establish the
optimal reaction conditions for allylic alkylation, in which rac-1,3-
dipenylpropen-1-yl acetate was chosen as the substrate and di-
methyl malonate as the nucleophile (3 equiv) in the presence of
a
The reaction was conducted with (E)-1,3-diphenylprop-2-en-1-yl acetate 8a
(0.5 mmol) and dimethyl malonate 9a (1.5 mmol) in solvent (3 mL) at room
temperature.
b
Isolated yield.
c
Determined by HPLC using a ChiralpakIA column with n-hexane/2-propanol
(90:10) as eluent.
d
The temperature of the reaction is 40 ꢀC.

Y. Jin, D.-M. Du / Tetrahedron 68 (2012) 3633e3640
3635
With the optimized reaction conditions in hand, we further
screened the substrate scope using the ligand L9 in the asymmetric
allylic alkylation reaction. The results are summarized in Table 2.
These reactions demonstrated the broad applicability of ligand L9
to different substrates. Different malonates with various allylic
substrates are all tolerated and good yields and enantioselectivities
were obtained (Table 2, entries 1e12). Diisopropyl malonate gave
lower reactivity and enantioselectivity than dibenzyl malonate
(Table 2, entries 3, 7, 11 vs entries 4, 8, 12). Electron-withdrawing
groups in phenyl of rac-1,3-dipenylpropen-1-yl acetate could im-
prove the activity of the allylic alkylation with the reaction time
reducing at least one day. We further evaluated alkyl allylic acetate,
using 1-cyclohexenyl acetate as substrate, but no reaction occurred
under optimized conditions even after 7 days, this phenomenon
may be ascribed to its low reactivity.
coordinated to Pd(II) ion as bidentate P,N-ligands rather than
bidentate N,N-ligands to give a stereogenic phosphorus atom. The
difference of our ligands with Yamagishi’s ligands is the presence of
the oxide to the P atom. The presence of oxide may prohibit the
coordination of P atom to Pd, but the weak interaction between the O
atom and the Pd may be existed. The oxide may function as an ad-
ditional chelating point to coordinate with Pd and stabilize the
complex. On the basis of the absolute configurations of the products,
a possible transition-state for the asymmetric allylic alkylation re-
action was proposed (Fig. 2). The nucleophile attacks the
h
3-allyl
complex as illustrated in Fig. 2 to affordthe S configured product. The
effort was directed to have a crystal structure of the complex, but we
failed to obtain it at present time.
Table 2
Scope of substrates for Pd-L9-catalyzed asymmetric allylic alkylationa
P
L9 (6 mol %)
R2O2C
R1
CO2R2
R1
Ph
OAc
R1
Pd(η3-C3H5)Cl]2 (2.5 mol %)
O
O
CO2R2
CO2R2
O
R1
+
N
N
KOAc 0.2 equiv.
BSA 3.0 equiv.
Ph
Ph
Pd
8a-c
8a R1 = Ph
8b
1 = 4-ClC6H4
8c R1 = 4-BrC6H4
9a-d
40 o
C
10aa-cd
Ph
Ph
9a R2 = Me
9b R2 = Et
9c R2 = iPr
9d R2 = Bn
Ph
Ph
R
Nu
Fig. 2. Proposed transition-state model.
Entry
Product
Time(day)
Yield (%)b
ee (%)c
1
2
3
4
5
6
7
8
10aa
10ab
10ac
10ad
10ba
10bb
10bc
10bd
10ca
10cb
10cc
10cd
3
3
7
2
2
1
5
1
2
1
5
1
99
99
16
>99
99
99
92
88
74
92
93
85
87
95
92
81
87
95
3. Conclusions
In conclusion, we have designed and synthesized the phosphine
oxide-linked bis(oxazoline) ligands L5eL9 in two ways and applied
them in Pd-catalyzed asymmetric allylic alkylation reactions of
(E)-1,3-diarylprop-2-en-1-yl acetate with malonates. Good enan-
tioselectivities and yields were obtained with ligand L9 (up to 95%
ee, 99% yield). When the nucleophile was 2-cyanoacetate, we could
get the corresponding product with 80% ee and 89:11 dr. Further
application of these ligands in other asymmetric transformations is
under way in our laboratory.
73
>99
>99
>99
71
9
10
11
12
>99
a
The reaction was conducted with allyl acetate substrate 8 (0.5 mmol) and nu-
cleophile 9 (1.5 mmol) in CHCl3 (2 mL) at 40 ꢀC using L9 (6 mol %) and [Pd( 3-C3H5)
h
Cl]2 (2.5 mol %) as catalyst.
b
Isolated yield.
Determined by HPLC by using a ChiralpakIA column.
4. Experimental section
4.1. General remarks
c
Further substrate scope was also investigated as shown in
Scheme 3. (E)-1,3-diphenylprop-2-en-1-yl acetate 8a reacted
with ethyl 2-cyanoacetate 11 to afford (E)-ethyl 2-cyano-3,5-
diphenylpent-4-enoate 12 in 36% yield (89:11 dr; major di-
astereomer 80% ee). In order to elucidate the nature of this type of
ligand, especially the function of O atom, we also used various other
nucleophiles, such as indole, benzylamine, cyclohenanone and
4-hydroxycoumarin, but they all did not take place the alkylation
substitution or no asymmetric induction.
Commercially available compounds were used without further
purification. Solvents were dried according to standard procedures.
Column chromatography was carried out using silica gel (200e300
mesh). Melting points were measured with a XT-4 melting point
apparatus without correction. The 1H NMR spectra were recorded
with Varian Mercury-plus 400 MHz or Bruker Avance DRX
500 MHz spectrometers, while 13C NMR spectra were recorded at
100 or 125 MHz, respectively. Infrared spectra were obtained with
a Perkin Elmer Spectrum One spectrometer. The ESI-MS spectra
were obtained with Bruker APEX IV Fourier Transform mass spec-
trometer. Optical rotations were measured with WZZ-3 spectrom-
eter. The enantiomeric excesses of the products were determined
by chiral HPLC using Agilent HP 1200 instrument with Daicel
ChiralpakIA or IB columns.
EtO2C
Ph
12
36% yield
89:11 dr; 80% ee
CN
Ph
L9 (6 mol %)
Pd(η3-C3H5)Cl]2 (2.5 mol %)
OAc
Ph
CN
CO2Et
+
KOAc 0.2 equiv.
BSA 3.0 equiv.
Ph
8a
11
40 o
C
Scheme 3. Asymmetric allylic alkylation with 2-cyanoacetate as the nucleophile.
4.2. Synthesis of phosphine oxide-linked bis(oxazoline)
ligands L5eL7
Yamagishi and co-worker reported the synthesis of phosphine-
linked bis(oxazoline) ligands and applied their Pd(II) complexes in
asymmetric alkylation reaction.4c The phosphine-linked bis(oxazo-
line) ligands are very similar to ligands L6 and L7. These ligands
4.2.1. (4S)-4-Benzyl-2-(2-bromophenyl)-4,5-dihydrooxazole
(3a).7a To a round bottom flask, the 2-bromobenzoic acid 1
(1.01 g, 5 mmol) and thionyl chloride (10 mL) were added, and

3636
Y. Jin, D.-M. Du / Tetrahedron 68 (2012) 3633e3640
the mixture were refluxed at 80 ꢀC for 4 h. The redundant
SOCl2 was removed under vacuum to give dark yellow oil. The oil
was dissolved in CH2Cl2 (35 mL), and added dropwise to a solu-
tion of (S)-phenylalaninol (756 mg, 5 mmol), Et3N (2.8 mL,
20 mmol), and CH2Cl2 (10 mL) at 0 ꢀC. After the completion of
addition, the mixture was warmed to room temperature and
stirred overnight.
To this mixture, methanesulfonyl chloride (464 mg, 6 mmol)
was added via syringe at 0 ꢀC. After the completion of addition, the
mixture was warmed to room temperature and stirred for 4 h. The
reaction was quenched by addition of saturated ammonium chlo-
ride (aq), and the mixture was extracted with CH2Cl2 (3ꢁ20 mL).
Then the mixture was concentrated, and the residue was dissolved
in the 1:1 (v/v) mixture of MeOH and water (6 mL), and refluxed in
the presence of NaOH (400 mg, 10 mmol) for another 4 h. After
removing MeOH under vacuum, the mixture was extracted with
CH2Cl2 (3ꢁ20 mL). The combined organic phase was washed with
brine, dried over anhydrous Na2SO4, and concentrated under vac-
uum. The crude product was purified by silica gel column chro-
matography using petroleum ethereEtOAc 5:1 (v/v) as eluent to
afford 3a as yellow oil (1.27 g, 87% yield).
774, 737, 699 cmꢃ1. HRMS (EI): calcd for C38H34N2O3P [MþH]þ
597.23016, found: 597.22906.
4.2.5. Bis(oxazoline) ligand (L6). Prepared according to the general
procedure outlined for L5 using the crumbs of Mg (199 mg,
8.29 mmol), PhPOCl2 (538 mg, 2.76 mmol) and compound 3b
(2.22 g, 8.29 mmol). The product was obtained as yellow solid
(709 mg, 51% yield). Mp 47e49 ꢀC, ½a D20
ꢂ
¼ꢃ58.0 (c 1.00, CH2Cl2). 1H
NMR (400 MHz, CDCl3):
d
0.77 (d, J¼6.4 Hz, 3H, CH3), 0.80 (d,
J¼6.0 Hz, 3H, CH3), 0.86 (d, J¼5.6 Hz, 3H, CH3), 0.91 (d, J¼5.6 Hz, 3H,
CH3), 1.66 (br s, 2H, CH), 3.52e3.54 (m, 1H), 3.69e3.76 (m, 3H), 4.00
(br s, 2H), 7.41e7.63 (m, 10H, ArH), 7.83e7.85 (m, 3H) ppm. 13C NMR
(100 MHz, CDCl3): 18.3, 18.4, 19.1, 19.2, 32.7, 70.6, 70.7, 72.7, 72.8,
3
3
127.8 (d, JCP¼12.3 Hz), 129.5 (d, JCP¼12.3 Hz), 129.6 (d,
3JCP¼12.2 Hz), 130.3 (d, 2JCP¼9.0 Hz), 130.5 (d, 2JCP¼9.1 Hz), 132.1 (d,
2JCP¼9.4 Hz), 130.71, 130.75, 130.78, 131.0, 131.1, 132.1 (d,
2JCP¼9.6 Hz), 133.4 (d, 1JCP¼103.1 Hz), 133.5 (d, 2JCP¼10.6 Hz), 133.6
(d, 2JCP¼10.0 Hz), 133.7 (d, 1JCP¼102.4 Hz), 133.9 (d, 1JCP¼108.1 Hz),
3
3
163.2 (d, JCP¼3.3 Hz), 163.4 (d, JCP¼3.3 Hz) ppm. 31P NMR (85%
H3PO4 as external standard): 31.8 ppm. IR (KBr): n 3058, 2958, 2923,
2871, 1725, 1664, 1588, 1560, 1467, 1437, 1353, 1309, 1246, 1203,
1129, 1108, 1063, 963, 906, 770, 739, 696 cmꢃ1. HRMS (ESI): calcd
for C30H34N2O3P [MþH]þ 501.23016, found: 501.23062.
4.2.2. (4S)-2-(2-Bromophenyl)-4-isopropyl-4,5-dihydrooxazole
(3b).7a Prepared according to the general procedure outlined for 3a
using 2.01 g (10 mmol) 2-bromobenzoic acid 1 and 1.03 g
(10 mmol) (S)-valinol. The product was obtained as yellow oil
(2.22 g, 83% yield).
4.2.6. Bis(oxazoline) ligand (L7). Prepared according to the general
procedure outlined for L5 using the crumbs of Mg (68 mg,
2.85 mmol), PhPOCl2 (195 mg, 1 mmol) and compound 3c
(804.9 mg, 2.85 mmol). The product was obtained as yellow solid
4.2.3. (4S)-2-(2-Bromophenyl)-4-tert-butyl-4,5-dihydrooxazole
(3c).7b Prepared according to the general procedure outlined for 3a
using 1.01 g (5 mmol) 2-bromobenzoic acid 1 and 586 mg (5 mmol)
(S)-tert-leucinol. The product was obtained as yellow oil (868.9 mg,
62% yield).
(246 mg, 50% yield). Mp 69e71 ꢀC, ½a D20
ꢂ
¼ꢃ106.8 (c 1.00, CH2Cl2). 1H
NMR (400 MHz, CDCl3):
d 0.79 (s, 9H, 3 CH3), 0.83 (s, 9H, 3 CH3),
3.46 (t, J¼8.8 Hz,1H, CH), 3.67 (t, J¼8.8 Hz,1H, CH), 3.85 (t, J¼8.8 Hz,
4H, CH), 7.42e7.52 (m, 8H, ArH), 7.67e7.73 (m, 1H, ArH), 7.79e7.89
(m, 4H, ArH) ppm. 13C NMR(100 MHz, CDCl3): 25.86, 25.94, 33.4,
33.5, 68.8, 68.9, 76.0, 127.8 (d, 3JCP¼12.4 Hz), 129.6 (d, 3JCP¼12.0 Hz),
129.7 (d, 3JCP¼11.5 Hz), 130.1 (d, 2JCP¼9.1 Hz), 130.5 (d, 2JCP¼8.9 Hz),
130.8, 131.0, 132.3 (d, 2JCP¼9.7 Hz), 133.5 (d, 1JCP¼102.9 Hz), 133.867
4.2.4. Bis(oxazoline) ligand (L5). To a flame dried Schlenk tube, the
crumbs of Mg (72 mg, 3 mmol) were added under argon, followed
by addition of THF (2 mL). Then the solution of 3a (948.6 mg,
3 mmol) in THF (2 mL) was added at 50 ꢀC. After the completion of
addition, the mixture was refluxed for 2 h. After the disappearance
of the crumbs of Mg, the mixture was cooled to room temperature.
Then the solution of phenylphosphonic dichloride (195 mg,
1 mmol) in THF (2 mL) was added, and the mixture was stirred at
room temperature for overnight. The reaction was quenched by
addition of water (10 mL) and the mixture was extracted with
CH2Cl2 (3ꢁ10 mL). The combined organic phase was washed with
brine, dried over anhydrous Na2SO4, and concentrated under vac-
uum. The crude product was purified by silica gel column chro-
matography using CH2Cl2eMeOH 50:1 (v/v) as eluent to afford L5
2
1
(d, JCP¼11.4 Hz), 133.874 (d, JCP¼103.0 Hz), 134.0 (d,
1JCP¼108.3 Hz), 163.0 (d, JCP¼2.7 Hz), 163.2 (d, JCP¼2.2 Hz) ppm.
3
3
31P NMR (85% H3PO4 as external standard): 31.8 ppm. IR (KBr):
n
3059, 2954, 2903, 2867, 1727, 1663, 1589, 1566, 1477, 1437, 1394,
1356, 1248, 1190, 1130, 1108, 1066, 1027, 963, 904, 767, 739,
695 cmꢃ1. HRMS (ESI): calcd for C32H38N2O3P [MþH]þ 529.26146,
found: 529.26207.
4.3. Synthesis of phosphine oxide-linked bis(oxazoline)
ligands (L8 and L9)
4.3.1. 2-(2-Bromophenyl)-1,3-dioxolan (5). This was
a modified
as yellow soild (205.9 mg, 35% yield). Mp 52e54 ꢀC, ½a D20
ꢂ
¼ꢃ70.4
procedure according to literature.8a To a round bottom flask, the2-
bromobenzaldehyde (3.70 g, 20 mmol), ethylene glycol (1.73 mL,
25 mmol), p-toluenesulfonic acid (60.2 mg, 0.35 mmol) and toluene
(30 mL) were added, and the mixture was heated at reflux with
a Dean Stark Trap for 24 h. The reaction was monitored by TCL. After
the completion of the reaction, the mixture was cooled to room
temperature, and the KOHeEtOH solution was added until white
solid appeared. Then the organic phase was washed with water and
brine, dried over anhydrous K2CO3, and concentrated under vac-
uum. The crude product was purified by silica gel column chro-
matography using petroleum ethereEtOAc 100:1 (v/v) as eluent.
The product was obtained as yellow oil (4.08 g, 89% yield).
(c 1.00, CH2Cl2). 1H NMR (500 MHz, CDCl3):
d
2.58 (dd, J¼9.0,
13.5 Hz, 2H, CH2), 3.03e3.08 (m, 2H, CH2), 3.73 (t, J¼8.0 Hz, 1H, CH),
3.78 (t, J¼8.0 Hz, 1H, CH3), 3.97e4.01 (m, 2H, CH), 4.15e4.23 (m, 1H,
CH), 4.29e4.38 (m, 1H, CH), 7.13 (d, J¼7.0 Hz, 2H, ArH), 7.17 (d,
J¼7.5 Hz, 2H, ArH), 7.19e7.31 (m, 6H, ArH), 7.38e7.42 (m, 2H),
7.44e7.49 (m, 3H), 7.53e7.60 (m, 4H), 7.79 (d, J¼7.5 Hz, 1H, ArH),
7.81 (d, J¼7.5 Hz, 1H, ArH),7.86 (dd, J¼3.5, 7.5 Hz, 2H, ArH) ppm. 13C
NMR(100 MHz, CDCl3): 40.9, 67.66, 67.70, 72.2, 126.1, 128.0 (d,
3JCP¼12.4 Hz), 128.18, 128.22, 128.91, 128.93, 129.7 (d, 3JCP¼12.3 Hz),
129.8 (d, 3JCP¼12.0 Hz), 130.3 (d, 2JCP¼9.0 Hz), 130.5 (d, 2JCP¼9.2 Hz),
130.83, 130.86, 130.89, 130.91, 131.18, 131.20, 131.74 (d, 2JCP¼8.9 Hz),
2
131.75, 132.1 (d, JCP¼9.6 Hz), 132.38 (d, 1JCP¼108.2 Hz), 133.23 (d,
2
1JCP¼102.9 Hz), 133.41 (d, JCP¼10.4 Hz), 133.44 (d, 1JCP¼102.6 Hz),
4.3.2. Bis[2-(1,3-dioxolan-2-yl)phenyl](phenyl) phosphine oxide
(6). This was a modified procedure according to literature.8b,8c To
a flame dried Schlenk tube, the crumbs of Mg (427.2 mg, 17.8 mmol)
were added under argon, followed by addition of THF (6 mL).
Then the solution of 2-(2-bromophenyl)-1,3-dioxolan 5 (4.08 g,
3
3
134.0, 138.01, 138.03, 163.7 (d, JCP¼3.2 Hz), 164.0 (d, JCP¼3.3 Hz)
ppm. 31P NMR (85% H3PO4 as external standard): 31.7 ppm. IR
(KBr):
n 3058, 3025, 2894, 1722, 1659, 1603, 1588, 1563, 1495, 1471,
1453, 1437, 1357, 1284, 1247, 1201, 1130, 1108, 1061, 1030, 960, 918,

Y. Jin, D.-M. Du / Tetrahedron 68 (2012) 3633e3640
3637
17.8 mmol) in THF (6 mL) was added at 50 ꢀC. After the completion
of addition, the mixture was heated at reflux for 2 h. After the
disappearance of the crumbs of Mg, the mixture was cooled to
room temperature. Then the solution of PhPOCl2 (1.74 g, 8.9 mmol)
in THF (6 mL) was added, and the mixture was stirred at room
temperature for overnight. The reaction was quenched by addition
of water (20 mL) and the mixture was extracted with CH2Cl2
(3ꢁ20 mL). The combined organic phase was washed with brine,
dried over anhydrous Na2SO4, and concentrated under vacuum. The
crude product was purified by silica gel column chromatography
using petroleum ethereEtOAc 1:1 (v/v) as eluent. The product was
obtained as yellow soild 6 (2.82 g, 75% yield). Mp 157e160 ꢀC 1H
product was obtained as white solid (1.85 g, 32% yield). Mp
117e119 ꢀC, ½a 2D0
ꢂ
¼ꢃ303.2 (c 0.50, CH2Cl2). 1H NMR (400 MHz,
CDCl3):
d
5.29 (d, J¼10.0 Hz, 1H, CH), 5.45 (d, J¼10.0 Hz, 1H, CH),
5.70 (d, J¼9.2 Hz, 2H, CH), 6.60 (d, J¼6.0 Hz, 2H, ArH), 6.72 (s, 2H,
ArH), 6.83e6.96 (m, 13H, ArH), 7.12e7.42 (m, 10H, ArH), 7.60e7.71
(m, 3H, ArH), 7.89e7.97 (m, 2H, ArH), 8.22e8.24(m, 1H, ArH). 13C
NMR(100 MHz, CDCl3): 73.5, 73.7, 85.4, 85.8, 126.1, 126.2, 126.7,
3
126.8, 127.0, 127.2, 127.7, 127.9 (d, JCP¼12.6 Hz), 129.8 (d,
3JCP¼12.3 Hz), 129.9 (d, 3JCP¼12.3 Hz), 130.2 (d, 2JCP¼8.8 Hz), 130.7,
130.8, 131.0 (d, 2JCP¼8.9 Hz), 131.1, 131.2, 132.1 (d, 2JCP¼9.7 Hz), 133.5
(d, 2JCP¼10.5 Hz), 133.7 (d, 1JCP¼108.8 Hz), 134.2 (d, 1JCP¼102.1 Hz),
134.5 (d, 2JCP¼11.1 Hz), 134.7 (d, 1JCP¼103.3 Hz), 135.5, 136.0, 137.5,
3
3
NMR (400 MHz, CDCl3):
d
3.81e3.85 (m, 2H, CH2), 3.95e4.01 (m,
137.7, 164.6 (d, JCP¼3.2 Hz), 165.3 (d, JCP¼3.2 Hz) ppm. 31P NMR
2H, CH2), 6.55 (s, 2H, CH), 7.03e7.09 (m, 2H, ArH), 7.26e7.33 (m, 2H,
ArH), 7.43e7.63 (m, 7H, ArH), 7.85 (dd, J¼7.6 Hz, 1.8 Hz, 2H, ArH)
ppm.
(85% H3PO4 as external standard): 33.8 ppm. IR (KBr): n 3059, 3029,
2932, 1712, 1663, 1604, 1587, 1564, 1496, 1454, 1437, 1330, 1284,
1192, 1109, 959, 919, 893, 738, 698 cmꢃ1. HRMS (ESI): calcd for
C48H38N2O3P [MþH] 721.26146, found: 721.26131.
4.3.3. Bis(2-formylphenyl)(phenyl)phosphine oxide (7)..8d To a round
bottom flask, bis[2-(1,3-dioxolan-2-yl)phenyl](phenyl)phosphine
oxide 6 (4.58 g, 10.85 mmol), pTSA (356 mg, 2 mmol) and acetone
(80 mL) were added. After the solid was dissolved, water (0.8 mL)
was added. Then the mixture was heated at reflux for 2 h. The re-
action was monitored by TLC. After the completion of the reaction,
the mixture was cooled to room temperature, and the acetone was
removed under vacuum. The residue was dissolved in CH2Cl2
(20 mL), washed with water and brine, dried over anhydrous
Na2SO4, and concentrated under vacuum. The crude product was
purified by silica gel column chromatography using petroleum
ethereEtOAc 1:1 (v/v) as eluent. The product was obtained as
yellow solid (2.87 g, 79% yield). Mp 170e172 ꢀC 1H NMR (400 MHz,
4.4. The catalytic asymmetric allylic alkylation
4.4.1. General procedure. To a flame dried Schlenk tube, [Pd(h3
-
C3H3)Cl]2 (4.6 mg, 0.0125 mmol) and ligand L9 (21.6 mg,
0.03 mmol) were added under argon, followed by addition of CHCl3
(2 mL). The solution was stirred at 40 ꢀC for 0.5 h. Then (E)-1,3-
diphenylprop-2-en-1-yl acetate (126 mg, 0.5 mmol) was added,
and the mixture was stirred for 10 min before the addition of nu-
cleophile (1.5 mmol), BSA (0.37 mL, 1.5 mmol) and anhydrous KOAc
(10 mg, 0.10 mmol). After being stirred for indicated time, water
(10 mL) was added and the mixture was extracted with CH2Cl2
(3ꢁ10 mL). and the combined organic phase was dried over an-
hydrous Na2SO4. The solvent was removed under vacuum, and the
residue was purified by flash chromatography using petroleum
ethereEtOAc 20:1 (v/v) as eluent to afford the desired product.
CDCl3):
d
¼7.21e7.28 (m, 2H, ArH), 7.53e7.77 (m, 9H), 8.17e8.23 (m,
2H, ArH) 10.74 (s, 2H, CHO) ppm.
4.3.4. Bis(oxazoline) ligand (L8). In a round bottom flask equipped
with a bubbler, compound 7 (334.3 mg, 1 mmol) was dissolved in
dry CH2Cl2 (10 mL). (S)-2-phenylglycinol (302.4 mg, 2 mmol) was
4.4.2. Dimethyl
2-[(1S,2E)-1,3-diphenyl-2-propen-1-yl]malonate
(10aa). Prepared according to the general procedure using (E)-1,3-
diphenyl-2-propen-1-yl acetate (126 mg, 0.5 mmol) and dimethyl
malonate (0.17 mL, 1.5 mmol), while the reaction time was 3 days.
The desired product was obtained as colorless oil (160 mg, 99%
yield). The ee was determined by chiral HPLC with a Daicel Chir-
alpakIA column (n-hexane/2-propanol¼90:10, flow rate 0.5 mL/
min, detection at 254 nm, minor enantiomer tR¼15.9 min, major
ꢁ
added and followed by 4 A molecular sieves (1 g). The mixture was
stirred at room temperature for overnight. N-bromsuccinimide
(356 mg, 2 mmol) was added while the reaction mixture was
cooled with a water bath. After 1 h, the solid byproducts and the
molecular sieves were removed by filtration and the filtrate was
washed with aqueous saturated NaHCO3 solution, Na2S2O5 solution
and brine. The organic phase was dried with anhydrous MgSO4,
filtrated and concentrated to dryness. The crude product was pu-
rified by silica gel column chromatography using CH2Cl2eMeOH
50:1 (v/v) as eluent to afford L8 as white solid (146 mg, 26% yield).
enantiomer tR¼19.3 min). ½a D30
ꢂ ¼ꢃ11.3 (c¼2.3, CH2Cl2; 92% ee).
(Ref. 11 ½a 2D0
ꢂ
¼ꢃ11.2, c¼1.04, CHCl3; 86% ee), 1H NMR (400 MHz,
CDCl3):
d
¼3.50 (s, 3H, CH3), 3.69 (s, 3H, CH3), 3.96 (d, J¼10.8 Hz, 1H,
CH), 4.27 (t, J¼9.6 Hz, 1H, CH), 6.33 (dd, J¼15.6, 8.8 Hz, 1H,]CH),
6.48 (d, J¼16.0 Hz, 1H,]CH), 7.16e7.30 (m, 10H, ArH) ppm.
Mp 89e91 ꢀC, ½a 2D0
ꢂ
¼ꢃ53.2 (c 0.50, CH2Cl2). 1H NMR (400 MHz,
CDCl3):
d 3.83e3.97 (m, 2H, CH), 4.37e4.53 (m, 2H, CH), 4.91e5.13
(m, 2H, CH), 7.18e7.27 (m, 8H, ArH), 7.37e7.65 (m, 10H, ArH),
7.69e7.84 (m, 3H, ArH), 7.96e7.81 (m, 2H, ArH) ppm. 13C
NMR(100 MHz, CDCl3): 69.9, 70.0, 74.9, 75.0, 126.8, 126.9, 127.2,
4.4.3. Diethyl 2-[(1S,2E)-1,3-diphenyl-2-propen-1-yl]malonate (10ab).
Prepared according to the general procedure using (E)-1,3-diphenyl-
2-propen-1-yl acetate (126 mg, 0.5 mmol) and diethyl malonate
(0.23 mL, 1.5 mmol), while the reaction time was 3 days. The desired
product was obtained as colorless oil (174 mg, 99% yield). The ee was
determined by chiral HPLC with a Daicel ChiralpakIA column
(n-hexane/2-propanol¼90:10, flow rate 0.5 mL/min, detection at
254 nm, minor enantiomer tR¼15.6 min, major enantiomer
3
127.8, 128.0, 128.1, 128.36, 128.41, 129.85 (d, JCP¼12.3 Hz), 129.91
3
3
2
(d, JCP¼12.5 Hz), 130.0 (d, JCP¼13.4 Hz), 130.8 (d, JCP¼8.9 Hz),
130.89, 130.98, 131.04, 131.3 (d, 2JCP¼11.3 Hz), 131.6, 131.7, 132.2 (d,
2JCP¼9.7 Hz), 133.49 (d, JCP¼10.9 Hz), 133.58 (d, JCP¼10.6 Hz),
2
2
1
1
133.61 (d, JCP¼107.9 Hz), 133.7 (d, JCP¼103 Hz), 133.8 (d,
1JCP¼101.7 Hz), 164.9 (d, JCP¼3.3 Hz), 165.1 (d, JCP¼3.7 Hz) ppm.
tR¼19.5 min).
½ ꢂ ¼ꢃ8.6 (c¼3.9, CH2Cl2; 88% ee). (Ref. 12
a 3D0
3
3
31P NMR (85% H3PO4 as external standard): 34.1 ppm. IR (KBr):
n
½
a 2D5
ꢂ
¼ꢃ17.2, c¼1.02, CHCl3; 97% ee). 1H NMR (400 MHz, CDCl3):
3060, 3030, 2924, 2854, 1712, 1659, 1630, 1588, 1578, 1565, 1496,
1467, 1450, 1438, 1359, 1303, 1193, 1130, 1109, 1060, 949, 761, 735,
695 cmꢃ1. HRMS (EI): calcd for C36H30N2O3P [MþH] 569.19886,
found: 569.19923.
d¼0.98 (t, J¼6.8 Hz, 3H, CH3),1.18 (t, J¼6.8 Hz, 3H, CH3), 3.92e3.96 (m,
3H, CHþCH2), 4.12e4.19 (m, 2H, CH2), 4.27 (t, J¼9.6, Hz, 1H, CH), 6.35
(dd, J¼15.6, 8.4 Hz, 1H,]CH), 6.48 (d, J¼15.6 Hz, 1H,]CH), 7.16e7.31
(m, 10H, ArH) ppm.
4.3.5. Bis(oxazoline) ligand (L9). Prepared according to the general
procedure outlined for L8 using compound 7 (2.67 g, 8 mmol) and
(1R,2S)-2-amino-1,2-dipheny1ethanol (3.41 g, 16 mmol). The
4.4.4. Diisopropyl 2-[(1S,2E)-1,3-diphenyl-2-propen-1-yl]malonate
(10ac). Prepared according to the general procedure using (E)-1,3-
diphenyl-2-propen-1-yl acetate (126 mg, 0.5 mmol) and

3638
Y. Jin, D.-M. Du / Tetrahedron 68 (2012) 3633e3640
diisopropyl malonate (282 mg, 1.5 mmol), while the reaction time
was 7 days. The desired product was obtained as colorless oil
(30.4 mg, 16% yield). The ee was determined by chiral HPLC with
a Daicel ChiralpakIA column (n-hexane/2-propanol¼90:10, flow
rate 0.5 mL/min, detection at 254 nm, minor enantiomer
0.5 mmol) and diisopropyl malonate (282 mg, 1.5 mmol), while the
reaction time was 5 days. The desired product was obtained as
white solid (164 mg, 73% yield). The ee was determined by
chiral HPLC with
a Daicel ChiralpakIA column (n-hexane/2-
propanol¼85:15, flow rate 1.0 mL/min, detection at 254 nm, mi-
tR¼12.4 min, major enantiomer tR¼14.9 min). ½a D30
ꢂ ¼ꢃ6.5 (c¼1.0,
nor enantiomer tR¼9.4 min, major enantiomer tR¼14.0 min). Mp
CH2Cl2; 74% ee). 1H NMR (400 MHz, CDCl3):
d
¼0.97 (d, J¼6.0 Hz, 3H,
85e86 ꢀC, ½a 3D0
ꢂ
¼þ0.66 (c¼2.4, CH2Cl2; 87% ee). 1H NMR (400 MHz,
CH3), 1.05 (d, J¼6.0 Hz, 3H, CH3), 1.16 (d, J¼6.0 Hz, 3H, CH3), 1.22 (d,
J¼6.0 Hz, 3H, CH3), 3.86 (d, J¼10.8 Hz, 1H, CH), 4.24 (t, J¼9.6 Hz, 1H,
CH), 4.78e4.84 (m, 1H, CH), 4.98e5.06 (m, 1H, CH), 6.33 (dd, J¼15.6,
8.4 Hz, 1H,]CH), 6.46 (d, J¼15.6 Hz, 1H,]CH), 7.18e7.31 (m, 10H,
ArH) ppm.
CDCl3):
d
¼1.01 (d, J¼4.4 Hz, 3H, CH3), 1.08 (d, J¼4.0 Hz, 3H, CH3),
1.16 (d, J¼4.4 Hz, 3H, CH3), 1.21 (d, J¼4.4 Hz, 3H, CH3), 3.81 (d,
J¼10.8 Hz, 1H, CH), 4.19e4.24 (m, 1H, CH), 4.82e4.87 (m, 1H, CH),
5.00e5.05 (m, 1H, CH), 6.28 (dd, J¼15.6, 8.4 Hz, 1H,]CH), 6.40 (d,
J¼15.6 Hz, 1H,]CH), 7.22e7.29 (m, 18H, ArH) ppm. 13C NMR
(100 MHz, CDCl3):
d¼21.3, 21.5, 21.6, 48.2, 57.6, 69.0, 69.2, 127.5,
4.4.5. Dibenzyl
2-[(1S,2E)-1,3-diphenyl-2-propen-1-yl]malonate
128.6, 128.7, 129.3, 129.6, 130.7, 132.8, 133.2, 135.1, 138.7, 166.6,
167.0 ppm. IR (KBr): 3067, 3033, 2982, 2935, 2881, 1740, 1714,
(10ad). Prepared according to the general procedure using (E)-1,3-
diphenyl-2-propen-1-yl acetate (126 mg, 0.5 mmol) and dibenzyl
malonate (426 mg, 1.5 mmol), while the reaction time was 2 days.
The desired product was obtained as colorless oil (238 mg, > 99%
yield). The ee was determined by chiral HPLC with a Daicel Chir-
alpakIA column (n-hexane/2-propanol¼95:5, flow rate 1.0 mL/min,
detection at 254 nm, minor enantiomer tR¼21.8 min, major enan-
n
1647, 1593, 1492, 1468, 1456, 1375, 1303, 1259, 1202, 1167, 1102,
1013, 982, 915, 841, 830, 800 cmꢃ1. HRMS (ESI): calcd for
C24H26Cl2NaO4 [MþNa]þ 471.11004, found: 471.10961.
4.4.9. Dibenzyl
2-[(1S,2E)-1,3-bis(4-chlorophenyl)-2-propen-1-yl]
malonate (10bd). Prepared according to the general procedure
using (E)-1,3-bis(4-chlorophenyl)-2-propen-1-yl acetate (161 mg,
0.5 mmol) and dibenzyl malonate (426 mg, 1.5 mmol), while the
reaction time was 1 day. The desired product was obtained as white
solid (273 mg, > 99% yield). The ee was determined by chiral HPLC
with aDaicel ChiralpakIA column (n-hexane/2-isopropanol¼80:20,
flow rate 1.0 mL/min, detection at 254 nm, minor enantiomer
tR¼16.6 min, major enantiomer tR¼23.7 min). Mp 73e74 ꢀC,
a 30
tiomer tR¼25.2 min). ½ ꢂD ¼ꢃ2.85 (c¼7.9, CH2Cl2; 92% ee). (Ref. 13
½
a 2D5
ꢂ
¼ꢃ7.1, c¼1.0, CHCl3; 95% ee). 1H NMR (300 MHz, CDCl3):
d
¼4.06 (d, J¼10.8 Hz, 1H, CH), 4.32 (t, J¼9.6 Hz, 1H, CH), 4.89 (s, 2H,
CH2), 5.07 (ABq, J¼12.4 Hz, 2H, CH2), 6.31 (dd, J¼15.6, 8.4 Hz, 1H,]
CH), 6.40 (d, J¼15.6 Hz, 1H,]CH), 7.17e7.27 (m, 20H, ArH) ppm.
4.4.6. Dimethyl
2-[(1S,2E)-1,3-bis(4-chlorophenyl)-2-propen-1-yl]
malonate (10ba). Prepared according to the general procedure
using (E)-1,3-bis(4-chlorophenyl)-2-propen-1-yl acetate (161 mg,
0.5 mmol) and dimethyl malonate (0.17 mL, 1.5 mmol), while the
reaction time was 2 days. The desired product was obtained as
colorless oil (196 mg, > 99% yield). The ee was determined by
½
a 3D0
ꢂ
¼þ2.56 (c¼8.8, CH2Cl2; 95% ee). 1H NMR (400 MHz, CDCl3):
d
¼3.96 (d, J¼10.8 Hz, 1H, CH), 4.24 (dd, J¼10.8, 8.0 Hz, 1H, CH), 4.96
(AB q, J¼12.4 Hz, 2H, CH2), 5.11 (AB q, J¼12.4 Hz, 2H, CH2), 6.21 (dd,
J¼15.6, 8.0 Hz,1H,]CH), 6.30 (d, J¼16.0 Hz,1H,]CH), 7.04e7.30 (m,
18H, ArH) ppm. 13C NMR (100 MHz, CDCl3):
d¼48.4, 57.5, 67.2, 67.4,
chiral HPLC with
a
Daicel ChiralpakIA column (n-hexane/2-
127.6, 128.18, 128.24, 128.29, 128.38, 128.40, 128.49, 128.54, 128.8,
129.0, 129.2, 131.0, 133.0, 133.3, 135.1, 138.2, 166.8, 167.2 ppm. IR
propanol¼85:15, flow rate 1.0 mL/min, detection at 254 nm, mi-
nor enantiomer tR¼10.6 min, major enantiomer tR¼15.7 min).
(KBr):
n 3065, 3033, 2947, 2890, 1753, 1735, 1587, 1491, 1456, 1410,
½
a 3D0
ꢂ
¼þ1.7 (c¼2.6, CH2Cl2; 93% ee). (Ref. 13 ½a D25
ꢂ
¼ꢃ3.1; c¼1.0,
1380, 1327, 1265, 1213, 1153, 1093, 1013, 972, 839, 825, 799, 741,
CHCl3; 97% ee). 1H NMR (400 MHz, CDCl3):
d
¼3.54 (s, 3H, CH3), 3.70
697 cmꢃ1
567.11004, found: 567.11019.
.
HRMS (ESI): calcd for C32H26Cl2NaO4 [MþNa]þ
(s, 3H, CH3), 3.90 (d, J¼10.8 Hz, 1H, CH), 4.25 (t, J¼9.6 Hz, 1H, CH),
6.27 (dd, J¼15.6, 8.4 Hz, 1H,]CH), 6.41 (d, J¼16.0 Hz, 1H,]CH),
7.22e7.30 (m, 8H, ArH) ppm.
4.4.10. Dimethyl 2-[(1S,2E)-1,3-bis(4-bromophenyl)-2-propen-1-yl]
malonate (10ca). Prepared according to the general procedure us-
ing (E)-1,3-bis(4-bromophenyl)-2-propen-1-yl acetate (205 mg,
0.5 mmol) and dimethyl malonate (0.17 mL, 1.5 mmol), while the
reaction time was 2 days. The desired product was obtained as
colorless oil (240 mg, > 99% yield). The ee was determined by chiral
HPLC with a Daicel ChiralpakIA column (n-hexane/2-propanol
85:15, flow rate 1.0 mL/min, detection at 254 nm, minor enantio-
4.4.7. Diethyl
2-[(1S,2E)-1,3-bis(4-chlorophenyl)-2-propen-1-yl]
malonate (10bb). Prepared according to the general procedure
using (E)-1,3-bis(4-chlorophenyl)-2-propen-1-yl acetate (161 mg,
0.5 mmol) and diethyl malonate (0.23 mL, 1.5 mmol), while the
reaction time was 1 days. The desired product was obtained as
white solid (208 mg, 99% yield). The ee was determined by
chiral HPLC with
a
Daicel ChiralpakIA column (n-hexane/2-
mer tR¼12.5 min, major enantiomer tR¼18.4 min). ½a D30
ꢂ ¼þ7.1
propanol¼85:15, flow rate 1.0 mL/min, detection at 254 nm, mi-
(c¼3.9, CH2Cl2; 92% ee). (Ref. 13 ½a D25
ꢂ ¼þ3.1; c¼1.0, CHCl3; 97% ee).
nor enantiomer tR¼10.5 min, major enantiomer tR¼16.8 min). Mp
1H NMR (400 MHz, CDCl3):
d
¼3.54 (s, 3H, CH3), 3.69 (s, 3H, CH3),
80e82 ꢀC, ½a 3D0
ꢂ
¼þ1.69 (c¼3.3, CH2Cl2; 85% ee). 1H NMR (400 MHz,
3.91 (d, J¼10.4 Hz, 1H, CH), 4.23 (t, J¼9.2 Hz, 1H, CH), 6.28 (dd,
J¼15.6, 8.0 Hz, 1H,]CH), 6.39 (d, J¼15.6 Hz, 1H,]CH), 7.16 (d,
J¼6.4 Hz, 4H, ArH), 7.38 (d, J¼7.2 Hz, 2H, ArH), 7.44 (d, J¼7.2 Hz, 2H,
ArH) ppm.
CDCl3):
d
¼1.05 (t, J¼5.8 Hz, 3H, CH3), 1.19 (t, J¼5.8 Hz, 3H, CH3), 3.86
(d, J¼10.8 Hz, 1H, CH), 3.97e4.01 (m, 2H, CH2), 4.14e4.26 (m, 3H,
CHþCH2), 6.27 (dd, J¼15.6, 8.4 Hz, 1H,]CH), 6.41 (d, J¼15.6 Hz,
1H,]CH), 7.22e7.29 (m, 8H, ArH) ppm. 13C NMR (100 MHz, CDCl3):
d
¼13.8, 14.1, 48.4, 57.5, 61.5, 61.7, 127.5, 128.6, 128.8, 129.3, 129.6,
4.4.11. Diethyl
2-[(1S,2E)-1,3-bis(4-bromophenyl)-2-propen-1-yl]
130.8, 132.9, 133.3, 135.1, 138.6, 167.1, 167.5 ppm. IR (KBr): 3030,
n
malonate (10cb). Prepared according to the general procedure us-
ing (E)-1,3-bis(4-bromophenyl)-2-propen-1-yl acetate (205 mg,
0.5 mmol) and diethyl malonate (0.23 mL, 1.5 mmol), while the
reaction time was 1 days. The desired product was obtained as
white solid (254 mg, > 99% yield). The ee was determined by chiral
HPLC with a Daicel ChiralpakIA column (n-hexane/2-propanol
85:15, flow rate 1.0 mL/min, detection at 254 nm, monor enantio-
mer tR¼12.2 min, major enantiomer tR¼19.5 min). Mp 58e60 ꢀC,
2984, 2937, 2896, 1760, 1715, 1594, 1493, 1464, 1415, 1388, 1370,
1332, 1254, 1179, 1142, 1095, 1032, 1012, 970, 851, 830, 809, 717,
703 cmꢃ1
.
HRMS (ESI): calcd for C22H22Cl2NaO4 [MþNa]þ
443.07874, found: 443.07787.
4.4.8. Diisopropyl 2-[(1S,2E)-1,3-bis(4-chlorophenyl)-2-propen-1-yl]
malonate (10bc). Prepared according to the general procedure us-
ing (E)-1,3-bis(4-chlorophenyl)-2-propen-1-yl acetate (161 mg,
½
a 3D0
ꢂ
¼þ4.39 (c¼5.1, CH2Cl2; 81% ee). 1H NMR (400 MHz, CDCl3):

Y. Jin, D.-M. Du / Tetrahedron 68 (2012) 3633e3640
3639
d
¼1.05 (t, J¼7.0 Hz, 3H, CH3), 1.20 (t, J¼7.0 Hz, 3H, CH3), 3.86 (d,
enantiomer tR¼34.7 min, major enantiomer tR¼38.6 min; minor
J¼10.8 Hz, 1H, CH), 3.96e4.02 (m, 2H, CH2), 4.15e4.24 (m, 3H,
CHþCH2), 6.29 (dd, J¼16.0, 8.0 Hz, 1H,]CH), 6.40 (d, J¼15.6 Hz,
1H,]CH), 7.15e7.19 (m, 4H, ArH), 7.38e7.45 (m, 4H, ArH) ppm. 13C
NMR (100 MHz, CDCl3):
121.4, 127.8, 129.4, 129.7, 130.9, 131.6, 131.7, 135.5, 139.1, 167.1,
167.5 ppm. IR (KBr): 3029, 2981, 2936, 2901, 2873, 1755, 1726,
diastereomer: tR¼112.6 min, tR¼154.3 min). ½a D30
ꢂ ¼þ14.6 (c¼1.9,
CH2Cl2; 80% ee for major diastereomer, 0% ee for minor di-
astereomer). 1H NMR (400 MHz, CDCl3):
3.87e3.93 (m, 1H, CH), 4.15e4.17 (m, 2H, CH2), 4.21e4.25 (m, 1H,
CH), 6.41e6.52 (m, 1H, CH), 6.54e6.62 (m, 1H, CH), 7.25e7.38 (m,
10H, ArH) ppm.
d
¼1.15e1.19 (m, 3H, CH3),
d¼13.8, 14.1, 48.4, 57.3, 61.5, 61.6, 121.0,
n
1588, 1488, 1464, 1446, 1388, 1369, 1331, 1253, 1174, 1136, 1098,
1072, 1031, 1009, 969, 858, 825, 800, 718 cmꢃ1. HRMS (ESI): calcd
for C22H22Br2NaO4 [MþNa]þ 530.97771 (79Br), found: 530.97774
Acknowledgements
(
79Br), 532.97567 (81Br).
We are grateful for financial support from the National Natural
Science Foundation of China (Grant Nos. 20772006, 21072020), the
Science and Technology Innovation Program of Beijing Institute of
Technology (Grant No. 2011CX01008), and the Development
Program for Distinguished Young and Middle-aged Teachers of
Beijing Institute of Technology.
4.4.12. Diisopropyl 2-[(1S,2E)-1,3-bis(4-bromophenyl)-2-propen-1-
yl]malonate (10cc). Prepared according to the general procedure
using (E)-1,3-bis(4-bromophenyl)-2-propen-1-yl acetate (205 mg,
0.5 mmol) and diisopropyl malonate (282 mg, 1.5 mmol), while the
reaction time was 5 days. The desired product was obtained as
white solid (191 mg, 71% yield). The ee was determined by chiral
HPLC with a Daicel ChiralpakIA column (n-hexane/2-propanol
85:15, flow rate 1.0 mL/min, detection at 254 nm, minor enantio-
mer tR¼10.6 min, major enantiomer tR¼15.8 min). Mp 90e92 ꢀC,
Supplementary data
Supplementary data related to this article can be found online at
doi:10.1016/j.tet.2012.02.078.
a 30
½ ꢂD ¼þ5.8 (c¼1.6, CH2Cl2; 87% ee). 1H NMR (400 MHz, CDCl3):
d
¼1.01 (d, J¼6.0 Hz, 3H, CH3), 1.07 (d, J¼6.0 Hz, 3H, CH3), 1.16 (d,
References and notes
J¼6.0 Hz, 3H, CH3), 1.21 (d, J¼6.0 Hz, 3H, CH3), 3.79 (d, J¼10.8 Hz,
1H, CH), 4.20 (t, J¼9.6 Hz,1H, CH), 4.81e4.86 (m, 1H, CH), 4.99e5.04
(m, 1H, CH), 6.28 (dd, J¼15.6, 8.0 Hz, 1H,]CH), 6.38 (d, J¼15.6 Hz,
1H,]CH), 7.14e7.18 (m, 4H, ArH), 7.38 (d, J¼8.4 Hz, 2H, ArH), 7.43
1. For selected reviews, see: (a) Ghosh, A. K.; Mathivanan, P.; Cappiello, J. Tetra-
hedron: Asymmetry 1998, 9, 1e45; (b) Johnson, J. S.; Evans, D. A. Acc. Chem. Res.
2000, 33, 325e335; (c) Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000, 33,
336e345; (d) Rechavi, D.; Lemaire, M. Chem. Rev. 2002, 102, 3467e3494; (e)
McManus, H. A.; Guiry, P. J. Chem. Rev. 2004, 104, 4151e4202; (f) Desimoni, G.;
Faita, G.; Jørgensen, K. A. Chem. Rev. 2006, 106, 3561e3651; (g) Fraile, J. M.;
Garcıa, J. I.; Mayoral, J. A. Coord. Chem. Rev. 2008, 252, 624e646; (h) Hargaden,
G. C.; Guiry, P. J. Chem. Rev. 2009, 109, 2505e2550.
(d, J¼8.0 Hz, 2H, ArH) ppm. 13C NMR (100 MHz, CDCl3):
¼21.2,
d
21.49, 21.54, 48.2, 57.5, 68.9, 69.1, 120.8, 121.2, 127.7, 129.6, 129.7,
130.7, 131.5, 131.6, 135.4, 139.2, 166.5, 166.9 ppm. IR (KBr):
n 3064,
2. (a) Lu, S.-F.; Du, D.-M.; Zhang, S.-W.; Xu, J. Tetrahedron: Asymmetry 2004, 15,
3433e3441; (b) Du, D.-M.; Lu, S.-F.; Fang, T.; Xu, J. J. Org. Chem. 2005, 70,
3712e3715; (c) Lu, S.-F.; Du, D.-M. J. Am. Chem. Soc. 2006, 128, 7418e7419; (d)
Lu, S.-F.; Du, D.-M.; Xu, J. Org. Lett. 2006, 8, 2115e2118; (e) Liu, H.; Xu, J.; Du, D.-
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Asian J. 2008, 3, 1111e1121; (g) Liu, H.; Du, D.-M. Eur. J. Org. Chem. 2010, 11,
2121e2131.
3031, 2979, 2935, 2881, 1738, 1714, 1647, 1589, 1488, 1468, 1456,
1375, 1304, 1259, 1202, 1168, 1102, 1073, 1010, 981, 914, 839, 827,
797 cmꢃ1
.
HRMS (ESI): calcd for C24H26Br2NaO4 [MþNa]þ
559.00901 (79Br), found: 559.01034 (79Br), 561.00669 (81Br).
4.4.13. Dibenzyl 2-[(1S,2E)-1,3-bis(4-bromophenyl)-2-propen-1-yl]
malonate (10cd). Prepared according to the general procedure
using (E)-1,3-bis(4-bromophenyl)-2-propen-1-yl acetate (205 mg,
0.5 mmol) and dibenzyl malonate (426 mg, 1.5 mmol), while the
reaction time was 1 days. The desired product was obtained as
white solid (316 mg, > 99% yield). The ee was determined by
chiral HPLC with a Daicel ChiralpakIA column (n-hexane/2-
propanol 80:20, flow rate 1.0 mL/min, detection at 254 nm, mi-
nor enantiomer tR¼19.3 min, major enantiomer tR¼26.9 min). Mp
3. (a) McManus, H. A.; Guiry, P. J. J. Org. Chem. 2002, 67, 8566e8573; (b) McManus,
H. A.; Cozzi, P. G.; Guiry, P. J. Adv. Synth. Catal. 2006, 348, 551e558; (c) Har-
gaden, G. C.; McManus, H. A.; Cozzi, P. G.; Guiry, P. J. Org. Biomol. Chem. 2007, 5,
763e766; (d) Coeffard, V.; Aylward, M.; Guiry, P. J. Angew. Chem., Int. Ed. 2009,
48, 9152e9155.
ꢀ
4. (a) Gomez, M.; Jansat, S.; Muller, G.; Maestro, M. A.; Mahía, J. Organometallics
2002, 21, 1077e1087; (b) Du, X.; Liu, H.; Du, D.-M. Tetrahedron: Asymmetry
2010, 21, 241e246; (c) Yamagishi, T.; Ohnuki, M.; Kiyooka, T.; Masui, D.; Sato, K.;
Yamaguchi, M. Tetrahedron: Asymmetry 2003, 14, 3275e3279.
5. (a) Braunstein, P.; Naud, F.; Pfaltz, A.; Rettig, S. J. Organometallics 2000, 19,
ꢀ
2676e2683; (b) Castillo, M. R.; Castillon, S.; Claver, C.; Fraile, J. M.; Gual, A.;
80e81 ꢀC,
(400 MHz, CDCl3):
½
a 3D0
ꢂ
¼þ4.85 (c¼6.7, CH2Cl2; 95% ee). 1H NMR
Martín, M.; Mayoral, J. A.; Sola, E. Tetrahedron 2011, 67, 5402e5408; (c) Take-
uchi, K.; Takeda, T.; Fujimoto, T.; Yamamoto, I. Tetrahedron 2007, 63,
5319e5322; (d) Simonini, V.; Benaglia, M.; Benincori, T. Adv. Synth. Catal. 2008,
350, 561e564.
6. (a) Muller, D.; Umbricht, G.; Weber, B.; Pfaltz, A. Helv. Chim. Acta 1991, 74,
232e240; (b) Corey, E. J.; Imai, N.; Zhang, H.-Y. J. Am. Chem. Soc. 1991, 113,
728e729; (c) Nishiyama, H.; Kondo, M.; Nakamura, T.; Itoh, K. Organometallics
1991, 10, 500e508; (d) Denmark, S. E.; Nakajima, N.; Nicaise, O. J.-C.; Faucher,
A.-M.; Edwards, J. P. J. Org. Chem. 1995, 60, 4884e4892; (e) Desimoni, G.; Faita,
G.; Mella, M. Tetrahedron 1996, 52, 13649e13654; (f) Evans, D. A.; Peterson, G.
S.; Johnson, J. S.; Barnes, D. M.; Campos, K. R.; Woerpel, K. A. J. Org. Chem. 1998,
63, 4541e4544; (g) Clayden, J.; Clayton, J.; Harvey, R. A.; Karlubikova, O. Synlett
2009, 2836e2838.
d
¼3.96 (d, J¼10.8 Hz, 1H, CH), 4.23 (dd, J¼10.8,
7.6 Hz, 1H, CH), 4.96 (s, 2H, CH2), 5.11 (ABq, J¼12.0 Hz, 2H, CH2),
6.21 (dd, J¼16.0, 7.6 Hz, 1H,]CH), 6.28 (d, J¼15.6 Hz, 1H,]CH),
7.02e7.09 (m, 6H, ArH), 7.21e7.28 (m, 8H, ArH), 7.33e7.37 (m, 4H,
ArH) ppm. 13C NMR (100 MHz, CDCl3):
d
¼48.5, 57.4, 67.3, 67.4,
121.2, 121.4, 127.9, 128.21, 128.26, 128.33, 128.40, 128.44, 128.51,
128.54, 129.1, 129.6, 131.1, 131.5131.8, 135.3, 138.7, 166.8,
167.2 ppm. IR (KBr):
n 3065, 3031, 2959, 1755, 1734, 1587, 1497,
1488, 1455, 1409, 1380, 1324, 1266, 1215, 1169, 1122, 1071, 1009,
976, 907, 824, 797, 748, 730, 697 cmꢃ1. HRMS (ESI): calcd for
C32H26Br2NaO4 [MþNa]þ 655.00901(79Br), found: 655.00966
7. (a) Zhou, Q.-L.; Pfaltz, A. Tetrahedron 1994, 50, 4467e4478; (b) Tani, K.; Be-
henna, D. C.; McFadden, R. M.; Stoltz, B. M. Org. Lett. 2007, 9, 2529e2531; (c)
Sedelmeier, J.; Hammerer, T.; Bolm, C. Org. Lett. 2008, 10, 917e920.
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Tomcufcik, A. S.; Wright, W. B. Jr.; Meyer, W. E. U.S. Patent 4,892,885, Chem.
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Q.; Poss, M. A.; Thottathil, J. K.; Singh, J.; Humora, M. J.; Kissick, T. P.; Boyhan, B.
Org. Process Res. Dev. 1997, 1, 14e19; (d) Rancurel, C.; Daro, N.; Borobia, O. B.;
Herdtweck, E.; Sutter, J.-P. Eur. J. Org. Chem. 2003, 167e171.
(
79Br), 657.00655 (81Br).
4. 4.14. (E)-Ethyl 2-cyano-3, 5-diphenylpent-4-enoate
(12).14 Prepared according to the general procedure using (E)-
1,3-diphenyl-2-propen-1-yl acetate (126 mg, 0.5 mmol) and ethyl
2-cyanoacetate (170 mg, 1.5 mmol), while the reaction time was 5
days. The desired product was obtained as colorless oil (55 mg,
36% yield). The ee was determined by chiral HPLC on Daicel
Chiralpak IB column (n-hexane/2-propanol¼99:1, flow rate
0.5 mL/min, detection at 254 nm, major diastereomer: minor
€
9. Hahn, B. T.; Tewes, F.; Frohlich, R.; Glorius, F. Angew. Chem., Int. Ed. 2010, 49,
1143e1146.
ꢂ
ꢀ
10. For selected examples, see: (a) Mata, Y.; Pamies, O.; Diegueza, M. Adv. Synth.
Catal. 2009, 351, 3217e3234; (b) Cheung, H. Y.; Yu, W.-Y.; Au-Yeung, T. T. L.;
€
Zhou, Z.; Chan, A. S. C. Adv. Synth. Catal. 2009, 351, 1412e1422; (c) Noel, T.; Bert,
K.; Van der Eycken, E.; Van der Eycken, J. Eur. J. Org. Chem. 2010, 4056e4061; (d)
Lemasson, F.; Gais, H.-J.; Runsink, J.; Raabe, G. Eur. J. Org. Chem. 2010,

3640
Y. Jin, D.-M. Du / Tetrahedron 68 (2012) 3633e3640
2157e2175; (e) Zhao, X.; Liu, D.; Xie, F.; Liu, Y.; Zhang, W. Org. Biomol. Chem.
2011, 9, 1871e1875; (f) Faller, J. W.; Wilt, J. C. Org. Lett. 2005, 7, 633e636; (g) Liu,
12. Tanaka, Y.; Mino, T.; Akita, K.; Sakamoto, M.; Fujita, T. J. Org. Chem. 2004, 69,
6679e6687.
Z.; Cao, Z.; Du, H. Org. Biomol. Chem. 2011, 9, 5369e5372.
11. Polet, D.; Alexakis, A.; Tissot-Croset, K.; Corminboeuf, C.; Ditrich, K. Chem.dEur.
J. 2006, 12, 3596e3609.
13. Kinoshita, N.; Kawabata, T.; Tsubaki, K.; Bando, M.; Fuji, K. Tetrahedron 2006, 62,
1756e1763.
14. Liu, J.; Chen, G.; Xing, J.; Liao, J. Tetrahedron: Asymmetry 2011, 22, 575e579.