An unexpected tandem enantioselective Michael addition/oxa-nucleophilic rearrangement reaction of β,γ-unsaturated α-keto esters catalyzed by cinchona alkaloids

Article abstract of DOI:10.1016/j.tetasy.2008.11.007

Cinchona alkaloids were found to catalyze an enantioselective Michael addition/oxa-nucleophilic rearrangement reaction of β,γ-unsaturated α-keto esters 1 and malonates 2. Using the optimum catalyst quinine 4a, a series of the rearranged products 3 were obtained with up to 98% yield and 82% ee under mild reaction conditions.

Full text of DOI:10.1016/j.tetasy.2008.11.007

Tetrahedron: Asymmetry 19 (2008) 2608–2615
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
An unexpected tandem enantioselective Michael addition/oxa-nucleophilic
rearrangement reaction of b,c-unsaturated
a-keto esters catalyzed
by cinchona alkaloids
Hai-Feng Wang a, Chang-Wu Zheng a, Ying-Quan Yang b, Zhuo Chai a, Gang Zhao a,
*
a Laboratory of Modern Synthetic Organic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 FengLin Lu, Shanghai 200032, China
b Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 October 2008
Accepted 11 November 2008
Cinchona alkaloids were found to catalyze an enantioselective Michael addition/oxa-nucleophilic rear-
rangement reaction of b,c-unsaturated a-keto esters 1 and malonates 2. Using the optimum catalyst qui-
nine 4a, a series of the rearranged products 3 were obtained with up to 98% yield and 82% ee under mild
reaction conditions.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
and formal [3+3] annulations.7 However, to the best of our knowl-
edge, the reaction of b,c-unsaturated a-keto esters catalyzed by
Organocatalytic asymmetric carbon–carbon bond-forming reac-
tions have emerged as a powerful tool for the construction of var-
ious organic molecules, so they have attracted intensive research
interests in recent years.1 Among the various catalysts used in this
field, cinchona alkaloids and their derivatives have demonstrated
distintive catalytic proficiency in numerous reactions.2 On the
cinchona alkaloids has not been reported.
Recently, we have employed compound 1 as a substrate in
asymmetric aqueous ketone–ketone aldol reactions to construct
compounds with chiral quarternary carbon centers.8 As
a
continued interest in the chemistry of compounds 1, we envisaged
a double Michael addition between (E)-methyl 2-oxo-4-phenylbut-
3-enoate 1a and (E)-dimethyl 2-(1-hydroxy-3-phenylallylidene)
malonate 2a envisaged to synthesize a synthetically useful chiral
tetrahydropyran-4-one compound. A new compound 3a was iden-
tified as the sole product under the catalysis of quinine (Scheme 1).
Herein, we report the details of this unexpected finding.
other hand, as a type of synthetically useful compounds, b,
c-unsat-
urated -keto esters 1 have been explored in a variety of enantio-
a
selective reactions, such as Diels–Alder and hetero-Diels–Alder
reaction,3 Friedel–Crafts alkylations,4 nucleophilic substitution,
Michael additions and oxa-Michael additions,5 hydrogenations,6
O
CO2Me
CO2Me
CO2Me
Ph
O
OH
O
CO2Me
Ph
CO2Me
H
4a (20 mol%)
Ph
Ph
CO2Me
+
O
CHCl3, rt
CO2Me
1a
2a
O
CO2Me
CO2Me
Ph
Ph
3a
Scheme 1. The unexpected formation of 3a from 1a and 2a catalyzed by quinine.
* Corresponding author.
E-mail address: zhaog@mail.sioc.ac.cn (G. Zhao).
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.11.007

H.-F. Wang et al. / Tetrahedron: Asymmetry 19 (2008) 2608–2615
2609
cinchona alkaloid catalysts examined, quinine provided the best
results in terms of both yield and ee (Table 1, entry 1). Interest-
ingly, quinidine 4b and cinchonine 4c provided the desired rear-
ranged product with the opposite absolute configuration with
much lower yields (Table 1, entries 5 and 6). Notably, the ineffec-
tiveness of catalysts 4g and 4h (Table 1, entries 10 and 11) clearly
2. Results and discussion
Using the reaction of (E)-methyl 2-oxo-4-phenylbut-3-enoate
1a with (E)-dimethyl 2-(1-hydroxy-3-phenylallylidene) malonate
2a as a model reaction, the results of the optimization of the
reaction conditions are summarized in Table 1. Of all the eight
Table 1
Screening of the optimal reaction conditions for 1a and 2a in the presence of 4a
O
CO2Me
H
OH
O
CO2Me
O
4
(20 mol%)
Ph
Ph
CO2Me
+
CO2Me
CO2Me
solvent, rt
CO2Me
Ph
Ph
3a
1a
2a
Entry
Catalyst
Solvent
Yieldb (%)
eec (%)
1
2d
3e
4f
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
4a
4a
4a
4a
4b
4c
4d
4e
4f
4g
4h
4a
4a
4a
4a
4a
4a
4a
4a
4a
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CH2Cl2
CCl4
ClCH2CH2Cl
THF
Et2O
Toluene
CH3CN
EtOAc
Acetone
68
40
18
53
40
29
24
7
78
76
76
76
ꢀ70
ꢀ32
44
n.d.
n.d.
20
g
g
—
—
Trace
33
68
33
18
68
68
84
79
n.d.
73
80
75
63
76
79
71
75
68
81
a
Unless otherwise noted, the reaction was conducted with 0.1 mmol of 1a and 0.2 mmol of 2a in the presence of 20 mol % of 4 in 1.0 mL of solvent at room temperature for
48 h.
b
c
d
e
f
Isolated yield.
Determined by chiral HPLC analysis on a chiral AD column.
0.12 mmol of 2a was used.
10 mol % of 4a was used.
0.1 mmol of 2a and 0.2 mmol of 1a were used.
No reaction occurred and the starting material was recovered.
g
OMe
OMe
OH
N
OH
OH
OH
N
N
N
H
N
N
H
H
N
N
H
Quinine
Quinidine
Cinchonine
Cinchonidine
4a
4b
4c
4d
OH
N
OMe
N
OMe
OH
N
OH
TMSO
OBn
H
N
N
H
N
N
H
H
N
4g
4e
4f
4h
Figure 1. Organocatalysts screened in this study.

2610
H.-F. Wang et al. / Tetrahedron: Asymmetry 19 (2008) 2608–2615
Table 2
Asymmetric Michael addition and rearrangement of b,
c
-unsaturated
a
-keto esters catalyzed by 4aa
O
CO2R2
H
OH
O
COOR4
CO2R4
CO2R4
O
R3
(20 mol %)
CCl4, r. t.
4a
COOR2
R1
+
H
COOR4
R3
R1
3
4
2a
2b
: R = C6H5, R = Me
: R = Me, R4 = Me
3
1a-p
3a-t
2c: R3 = C6H5, R4 = Et
2d: R3 = C6H5, R4 = i-Pr
3
4
2e
: R = C6H5, R = Bn
Entry
1
R1
R2
2
Time (h)
Product
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
1a
1b
1c
1d
1e
1f
1g
1h
1i
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
Allyl
t-Bu
Bn
p-BrBn
i-Pr
Me
Me
Me
Me
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
2d
2e
48
24
24
24
24
15
48
48
48
48
15
48
48
15
15
48
65
48
48
48
3a
3b
3c
3d
3e
3f
3g
3h
3i
68
87
88
96
92
91
49
51
31
15
72
50
35
70
74
63
70
61
68
98
80
80
80
80
78d
72
79
70
58
54
79
78
79
80d
77d
78
80
82
82
82
4-FC6H4
4-ClC6H4
4-BrC6H4
3-ClC6H4
4-NO2C6H4
4-MeC6H4
4-EtOC6H4
2,4-diClC6H3
2-BrC6H4
Ph
1j
1k
1l
3j
3k
3l
Ph
Ph
Ph
Ph
1m
1n
1o
1p
1d
1d
1d
1d
3m
3n
3o
3p
3q
3r
3s
3t
Ph
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4
a
Unless otherwise noted, the reaction was conducted with 0.1 mmol of 1 and 0.2 mmol of 2 in the presence of 20 mol % of 4a in 1.0 mL of CCl4 at room temperature.
Isolated yield.
Determined by chiral HPLC analysis on a chiral AD column. The absolute configuration of 3d was determined to be (S) by X-ray crystallographic analysis, and the others
b
c
3a–3c, 3e–3t were assigned by assuming that a similar catalytic mechanism was followed.
d
Determined by chiral HPLC analysis on a chiral AS-H column.
highlighted the importance of the hydroxyl group in quinine for
this reaction, and thus suggested a bifunctional role for the cata-
lyst. Lowering the amount of quinine from 20 mol % to 10 mol %
diminished both the yield and the ee value (Table 1, entry 3).
Decreasing the amount of 2a also leads to a significant decrease
in the yield while with much less appreciable effect on the enanti-
oselectivity (Table 1, entries 2 and 4). No apparent difference was
observed when CHCl3, CCl4, and toluene were used as solvent,
except for a slightly higher ee value for CCl4 (Table 1, entry 13).
Higher yields were obtained in the cases of more polar solvents
such as CH3CN, EtOAc, and acetone; however, the enantioselecti-
vity was diminished (Table 1, entries 18–20). Thus, the reaction
was best performed with 20 mol % of quinine 4a in CCl4 at room
temperature (Fig. 1).
With the optimized reaction conditions, the scope of this
reaction was probed with 1 and 2; the results are summarized
in Table 2. In general, the present reaction was rather sensitive
to the electronic nature and steric hinderance of both substrates.
For substrates 1a–j with differently substituted phenyl groups
(R1), those with electron-withdrawing substituents required
shorter reaction times and provided higher yields than the ones
with electron-donating substituents, though no appreciable dif-
ference in the enantioselectivity was observed (Table 2, entries
1–8). However, when the substituents were in the ortho-position
O
CO2Me
H
O
CO2Me
CO2Me
H
Br
3d
Figure 2. X-ray structure of compound 3d.

H.-F. Wang et al. / Tetrahedron: Asymmetry 19 (2008) 2608–2615
2611
OMe
O
H
N
H
CO2R4
CO2R4
R1
O
R3
-O
CO2R4
4a (20 mol%)
R3
O
1
2
2
O
H
CO2R4
R1
N
R2O2C
R2O2C
1
I
II
R3
O-
CO2R4
protonation
O
CO2R4
3
R2O2C
R1
III
Scheme 2. Proposed possible catalytic mechanism for the formation of 3.
of the benzene ring, considerable decreases in both the ee values
and the yields were observed (Table 2, entries 9 and 10). In
addition, alteration of the ester group (R2) of 1 did not have
any significant influence on the enantioselectivity, but a signifi-
cantly lower yield was obtained after a relatively long reaction
time (48 h) for substrate 1m bearing a bulky tert-butyl group
(Table 2, entries 11–16). As for substrates 2c–e with different es-
ter moieties (R4), invariably high ees were achieved and up to
98% yield was obtained for the benzyl-substituted substrate 2e
(Table 2, entries 18–20). It is noteworthy that substrate 2b with
a alkyl group (R3 = Me) also provided the desired product 3q in
70% yield and 80% ee, although a longer reaction time (65 h)
was required (Table 2, entry 17). Furthermore, another feature
of this reaction is the complete Z-selectivity of the newly formed
alkene in products 3. The absolute configuration of product 3d
was determined to be (S) by X-ray crystallographic analysis
(Fig. 2).9
254) were used and compounds were visualized by irradiation
with UV light or by treatment with a solution of phosphomolybdic
acid in ethanol followed by heating. The 1H NMR spectra were
recorded on a DPX-300 or Varian EM-360 (300 MHz). All chemical
shifts (d) are given in ppm. Data are reported as follows: chemical
shift, multiplicity (s = single, d = doublet, t = triplet, q = quartet,
br = broad, and m = multiplet) and coupling constants (Hz),
integration. 13C NMR spectra were recorded on
a DPX-400
(100 MHz). Analytical high-performance liquid chromatography
(HPLC) was carried out on WATERS equipment using a chiral col-
umn. Melting points were determined on a SGW X-4 apparatus,
and are uncorrected. Optical rotations were measured on a JASCO
P-1030 Polarimeter at k = 589 nm. IR spectra were recorded on a
Perkin-Elmer 983G instrument. Elementary analysis was taken
on a Vario EL III elementary analysis instrument. Mass spectra
analysis was performed on API 200 LC/MS system (Applied Biosys-
tems Co. Ltd).
Based on the numerous previous studies on the bifunctional
catalytic activity of cinchona alkaloids,2 a possible mechanism for
the present reaction was proposed (Scheme 2). First, quinine 4a
catalyzed the asymmetric Michael addition of 1 and 2 via dual acti-
vation of both the electrophile 1 and the nucleophile 2 (transition
state I) to produce intermediate II, which then underwent an oxa-
nucleophilic attack at the carbonyl of 2 generating another inter-
mediate III. This intermediate finally rearranged to provide the
product 3 after protonation.
4.2. Typical procedure for the preparation of compounds 2
To a solution of dialkyl malonates (40 mmol) in dry tetrahydro-
furan (100 mL) was added NaH (40 mmol, 60% wt dispersion in
mineral oil) in portions at 0 °C. The mixture was then warmed to
room temperature and stirred for 30 min. Cinnamoyl chloride or
(E)-but-2-enoyl chloride (20 mmol) in dry tetrahydrofuran
(20 mL) was then added over 1 h to the above-mentioned system,
and the resulting mixture was stirred at room temperature until
the completion of the reaction (monitored by TLC). The reaction
mixture was then diluted by the addition of saturated NH4Cl aq
(40 mL), evaporated in vacuo to remove most of the solvent
(THF), and the residue was extracted with dichloromethane
(3 ꢁ 40 mL). The combined organic layers were dried over anhy-
drous Na2SO4, concentrated in vacuo, and the residue was purified
by column chromatography on silica gel, eluted with ethyl acetate
and petroleum ether mixture (1:20) to afford pure products 2.
3. Conclusion
In conclusion, we have reported the tandem enantioselective
Michael addition/oxa-nucleophilic rearrangement reaction of b,c-
unsaturated
loids, and
discussed.
a
a
-keto esters catalyzed by bifunctional cinchona alka-
possible catalytic mechanism was also briefly
4. Experimental
4.1. General
4.2.1. (E)-Dimethyl 2-(1-hydroxy-3-phenylallylidene)-
malonate 2a
White solid. Yield 58%. Mp 72–74 °C. 1H NMR (300 MHz, CDCl3)
d: 3.84 (d, J = 5.4 Hz, 6H), 7.02 (d, J = 15 Hz, 1H), 7.35–7.37 (m, 3H),
7.51–7.53 (m, 2H), 7.64 (d, J = 15 Hz, 1H), 13.32 (s, 1H); 13C NMR
(100 MHz, CDCl3) d: 52.3, 52.4, 99.3, 119.0, 128.2, 128.9, 130.1,
135.0, 140.8, 166.4, 171.8, 172.3; MS (EI): m/z 262 (M+). Anal. Calcd
Unless otherwise indicated, chemicals and solvents were pur-
chased from commercial suppliers and purified by standard tech-
niques. Flash column chromatography was performed using silica
gel. For thin-layer chromatography (TLC), silica gel plates (HSGF

2612
H.-F. Wang et al. / Tetrahedron: Asymmetry 19 (2008) 2608–2615
for C14H14O5: C, 64.12; H, 5.38. Found: C, 64.02; H, 5.36. IR (KBr)
2954, 1759, 1733, 1632, 1549, 1442, 1375, 1088 cmꢀ1
m
4.3.2. (S,Z)-Trimethyl 4-(cinnamoyloxy)-2-(4-fluorophenyl)-
.
but-3-ene-1,1,4-tricarboxylate 3b
White solid. Yield 87%. Mp 96–98 oC. ½a D26
¼ ꢀ80:5 (c 1.0,
ꢂ
4.2.2. (E)-Dimethyl 2-(1-hydroxybut-2-enylidene)malonate 2b
CHCl3). 1H NMR (300 MHz, CDCl3) d: 3.55 (s, 3H), 3.76 (d,
J = 4.5 Hz, 6H), 3.89 (d, J = 10.2 Hz, 1H), 4.51 (t, J = 10.2 Hz, 1H),
6.56 (d, J = 15.9 Hz, 1H), 6.74 (d, J = 10.2 Hz, 1H), 6.96–7.02 (m,
2H), 7.20–7.26 (m, 2H), 7.40–7.44 (m, 3H), 7.54–7.62 (m, 2H),
7.80 (d, J = 15.9 Hz, 1H); 19F NMR (282 MHz, CDCl3) d: ꢀ114.7;
13C NMR (100 MHz, CDCl3) d: 41.5, 52.6, 52.7, 53.0, 56.8, 115.7,
115.9 (d, JC–F = 8.9 Hz), 128.4, 128.8, 129.0, 129.5 (d, JC–F = 8.2 Hz),
130.9, 134.0, 134.1 (d, JC–F = 2.0 Hz), 138.9, 147.5, 162.0 (d,
JC–F = 244.9 Hz), 162.1, 164.1, 167.3, 167.5; MS (ESI): m/z 488.2
([M+H2O]+); HRMS (ESI): calculated for C25H23FO8 (M+):
Colorless liquid. Yield 30%. 1H NMR (300 MHz, CDCl3) d: 1.92 (d,
J = 6.6 Hz, 3H), 3.82 (s, 6H), 6.32 (d, J = 15 Hz, 1H), 6.87–6.99 (m,
1H), 13.14 (s, 1H); 13C NMR (100 MHz, CDCl3) d: 18.7, 52.2, 52.3,
98.0, 123.0, 141.0, 166.4, 171.8, 172.0; MS (EI): m/z 200 (M+);
HRMS (EI): calculated for C9H12O5 (M+): 200.0685. Found:
200.0687; IR (Film)
m 2955, 1760, 1733, 1647, 1568, 1443, 1087,
963 cmꢀ1
.
4.2.3. (E)-Diethyl 2-(1-hydroxy-3-phenylallylidene)-
malonate 2c10
470.1377. Found: 470.1386; IR (KBr)
m 2955, 1758, 1634, 1603,
Colorless liquid. Yield 69%. 1H NMR (300 MHz, CDCl3) d: 1.27–
1.39 (m, 6H), 4.27–4.37 (m, 4H), 7.05 (d, J = 15.6 Hz, 1H), 7.36–
7.41 (m, 3H), 7.50–7.53 (m, 2H), 7.64 (d, J = 15.6 Hz, 1H), 13.31
(s, 1H).
1510, 1436, 983, 766 cmꢀ1. The enantiomeric excess was deter-
mined by HPLC (Chiralpak AD column, hexane/i-PrOH 80:20, flow
rate 0.75 mL/min; tminor = 24.2 min; tmajor = 34.9 min, k = 254 nm).
4.3.3. (S,Z)-Trimethyl 2-(4-chlorophenyl)-4-(cinnamoyloxy)but-
4.2.4. (E)-Diisopropyl 2-(1-hydroxy-3-phenylallylidene)-
malonate 2d
3-ene-1,1,4-tricarboxylate 3c
White solid. Yield 88%. Mp 123–125 oC. ½a D27
¼ ꢀ144:0 (c 1.0,
ꢂ
White waxy solid. Yield 75%. 1H NMR (300 MHz, CDCl3) d: 1.33
(t, J = 6.6 Hz, 12H), 5.13–5.25 (m, 2H), 7.04 (d, J = 15.6 Hz, 1H),
7.36–7.41 (m, 3H), 7.51–7.53 (m, 2H), 7.62 (d, J = 15.6 Hz, 1H),
13.24 (s, 1H); 13C NMR (100 MHz, CDCl3) d: 21.5, 21.8, 64.6, 68.7,
69.2, 70.1, 100.8, 119.0, 128.0, 128.8, 129.8, 135.2, 140.0, 165.6,
170.9, 171.0; MS (EI): m/z 318 (M+); HRMS (EI): calculated for
CHCl3). 1H NMR (300 MHz, CDCl3) d: 3.56 (s, 3H), 3.76 (d,
J = 4.5 Hz, 6H), 3.90 (d, J = 10.2 Hz, 1H), 4.50 (t, J = 10.2 Hz, 1H),
6.56 (d, J = 15.9 Hz, 1H), 6.73 (d, J = 10.2 Hz, 1H), 7.19 (d,
J = 8.1 Hz, 2H), 7.28 (d, J = 8.1 Hz, 2H), 7.40–7.44 (m, 3H), 7.52–
7.60 (m, 2H), 7.80 (d, J = 15.9 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d: 41.6, 52.6, 52.7, 53.0, 56.6, 115.8, 128.4, 128.5, 128.9, 129.0,
129.2, 130.9, 133.5, 133.9, 136.9, 139.1, 147.6, 162.0, 164.1,
167.2, 167.4; MS (ESI): m/z 504 ([M+H2O]+). Anal. Calcd for
C18H22O5 (M+): 318.1467. Found: 318.1471; IR (KBr)
1723, 1634, 1383, 1275, 1020, 971, 693 cmꢀ1
m 2982,
.
C25H23ClO8: C, 61.67; H, 4.76. Found: C, 61.40; H, 4.60. IR (KBr)
m
4.2.5. (E)-Dibenzyl 2-(1-hydroxy-3-phenylallylidene)-
malonate 2e
2954, 1740, 1634, 1492, 1436, 1309, 1132, 766 cmꢀ1. The enantio-
meric excess was determined by HPLC (Chiralpak AD column, hex-
ane/i-PrOH 80:20, flow rate 0.75 mL/min; tminor = 25.3 min;
tmajor = 36.2 min, k = 254 nm).
Yellow liquid. Yield 72%. 1H NMR (300 MHz, CDCl3) d: 5.27 (s,
4H), 7.00 (d, J = 15.6 Hz, 1H), 7.32–7.34 (m, 15H), 7.62 (d,
J = 15.6 Hz, 1H), 13.30 (s, 1H); 13C NMR (100 MHz, CDCl3) d: 67.2,
68.0, 99.4, 119.0, 127.9, 128.1, 128.2, 128.3, 128.6, 128.7, 128.8,
129.0, 130.0, 135.0, 135.2, 135.6, 140.9, 165.7, 171.2, 172.7; MS
(EI): m/z 414 (M+); HRMS (EI): calculated for C26H22O5 (M+):
4.3.4. (S,Z)-Trimethyl 2-(4-bromophenyl)-4-(cinnamoyloxy)-
but-3-ene-1,1,4-tricarboxylate 3d
White solid. Yield 96%. Mp 126–128 oC. ½a D27
¼ ꢀ136:0 (c 1.0,
ꢂ
414.1467. Found: 414.1472; IR (film)
m
3031, 1725, 1631, 1450,
CHCl3). 1H NMR (300 MHz, CDCl3) d: 3.56 (s, 3H), 3.76 (d,
J = 4.8 Hz, 6H), 3.90 (d, J = 10.2 Hz, 1H), 4.48 (t, J = 10.2 Hz, 1H),
6.56 (d, J = 16.2 Hz, 1H), 6.73 (d, J = 10.2 Hz, 1H), 7.13 (d,
J = 8.1 Hz, 2H), 7.38–7.46 (m, 5H), 7.52–7.60 (m, 2H), 7.79 (d,
J = 16.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) d: 41.7, 52.6, 52.7,
53.0, 56.5, 115.8, 121.7, 128.4, 128.5, 129.0, 129.6, 130.9, 132.0,
133.9, 137.4, 139.1, 147.6, 162.0, 164.1, 167.2, 167.4; MS (ESI):
m/z 547.8 ([M+H2O]+). Anal. Calcd for C25H23BrO8: C, 56.51; H,
1396, 1353, 1087, 752 cmꢀ1
.
4.3. Typical procedure for the preparation of compounds 3
A mixture of b, -unsaturated -keto ester 1 (0.1 mmol), com-
c
a
pound 2 (0.2 mmol) and quinine (0.02 mmol) in 1.0 mL of tetracar-
bonchloride was stirred at room temperature for the appropriate
times until the disappearance of 1 (monitored by TLC). The reaction
mixture was then concentrated, and the residue was purified by
flash column chromatography on silica gel (ethyl acetate/petro-
leum ether = 1:5) to give the desired products 3.
4.36. Found: C, 56.47; H, 4.23. IR (KBr)
m 2954, 1740, 1634,
1436, 1310, 1132, 766, 682 cmꢀ1. The enantiomeric excess was
determined by HPLC (Chiralpak AD column, hexane/i-PrOH
80:20, flow rate 0.75 mL/min; tminor = 25.8 min; tmajor = 38.0 min,
k = 254 nm).
4.3.1. (S,Z)-Trimethyl 4-(cinnamoyloxy)-2-phenylbut-3-ene-
1,1,4-tricarboxylate 3a
4.3.5. (S,Z)-Trimethyl 2-(3-chlorophenyl)-4-(cinnamoyloxy)but-
White waxy solid. Yield 68%. ½a D25
ꢂ
¼ ꢀ156:4 (c 1.5, CHCl3). 1H
3-ene-1,1,4-tricarboxylate 3e
NMR (300 MHz, CDCl3) d: 3.53 (s, 3H), 3.75 (d, J = 2.4 Hz, 6H),
3.95 (d, J = 10.5 Hz, 1H), 4.53 (t, J = 10.5 Hz, 1H), 6.57 (d,
J = 15.6 Hz, 1H), 6.77 (d, J = 10.5 Hz, 1H), 7.23–7.33 (m, 5H), 7.42–
7.44 (m, 3H), 7.57–7.60 (m, 2H), 7.80 (d, J = 15.6 Hz, 1H); 13C
NMR (100 MHz, CDCl3) d: 42.2, 52.4, 52.5, 52.8, 56.6, 115.9,
127.6, 127.7, 128.3, 128.8, 128.9, 129.0, 130.7, 133.9, 138.2,
138.7, 147.2, 162.1, 164.1, 167.2, 167.5; MS (ESI): m/z 470.2
([M+H2O]+); HRMS (ESI): calculated for C25H24O8 (M+): 452.1471.
White solid. Yield 92%. Mp 103–105 oC. ½a D27
¼ ꢀ116:8 (c 1.0,
ꢂ
CHCl3). 1H NMR (300 MHz, CDCl3) d: 3.57 (s, 3H), 3.76 (d,
J = 5.7 Hz, 6H), 3.91 (d, J = 10.2 Hz, 1H), 4.50 (t, J = 10.2 Hz, 1H),
6.57 (d, J = 15.6 Hz, 1H), 6.73 (d, J = 10.2 Hz, 1H), 7.12–7.17 (m,
1H), 7.20–7.25 (m, 3H), 7.39–7.44 (m, 3H), 7.57–7.60 (m, 2H),
7.80 (d, J = 15.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) d: 41.8, 52.6,
52.7, 53.0, 56.4, 115.8, 126.0, 127.9, 128.0, 128.2, 128.4, 129.0,
130.1, 130.9, 133.9, 134.6, 139.2, 140.4, 147.6, 162.0, 164.1,
167.1, 167.3; MS (ESI): m/z 504 ([M+H2O]+). Anal. Calcd for
Found: 452.1469; IR (KBr)
m 2955, 1740, 1634, 1451, 1436, 1311,
1131, 983 cmꢀ1. The enantiomeric excess was determined by HPLC
(Chiralpak AD column, hexane/i-PrOH 80:20, flow rate 0.75 mL/
min; tminor = 22.4 min; tmajor = 28.6 min, k = 254 nm).
C25H23ClO8: C, 61.67; H, 4.76. Found: C, 61.62; H, 4.68. IR (KBr) m
2954, 1757, 1634, 1595, 1575, 1435, 1311, 767 cmꢀ1; The enantio-
meric excess was determined by HPLC (Chiralpak AS-H column,

H.-F. Wang et al. / Tetrahedron: Asymmetry 19 (2008) 2608–2615
2613
hexane/i-PrOH 80:20, flow rate 0.75 mL/min; tminor = 13.6 min;
tmajor = 15.0 min, k = 254 nm).
1436, 1132, 982, 766, 579 cmꢀ1. The enantiomeric excess was
determined by HPLC (Chiralpak AD column, hexane/i-PrOH
80:20, flow rate 0.75 mL/min; tminor = 21.9 min; tmajor = 33.6 min,
k = 254 nm).
4.3.6. (S,Z)-Trimethyl 4-(cinnamoyloxy)-2-(4-nitrophenyl)but-
3-ene-1,1,4-tricarboxylate 3f
White solid. Yield 91%. Mp 131–133 oC. ½a D27
ꢂ
¼ ꢀ145:2 (c 1.0,
4.3.10. (S,Z)-Trimethyl 2-(2-bromophenyl)-4-(cinnamoyloxy)-
CHCl3). 1H NMR (300 MHz, CDCl3) d: 3.58 (s, 3H), 3.78 (d,
J = 2.7 Hz, 6H), 3.96 (d, J = 9.9 Hz, 1H), 4.63 (t, J = 9.9 Hz, 1H), 6.55
(d, J = 15.9 Hz, 1H), 6.75 (d, J = 9.9 Hz, 1H), 7.38–7.50 (m, 5H),
7.52–7.60 (m, 2H), 7.79 (d, J = 15.9 Hz, 1H), 8.17 (d, J = 8.7 Hz,
2H); 13C NMR (100 MHz, CDCl3) d: 42.1, 53.0, 53.1, 53.4, 56.4,
115.7, 124.3, 127.6, 128.7, 129.2, 129.3, 131.3, 134.0, 140.1,
146.1, 147.5, 148.1, 162.0, 164.3, 167.2, 167.3; MS (ESI): m/z
515.2 ([M+H2O]+). Anal. Calcd for C25H23NO10: C, 60.36; H, 4.66;
but-3-ene-1,1,4-tricarboxylate 3j
White waxy solid. Yield 15%. ½a D27
ꢂ
¼ ꢀ22:9 (c 0.53, CHCl3). 1H
NMR (300 MHz, CDCl3) d: 3.59 (s, 3H), 3.76 (d, J = 12.3 Hz, 6H),
4.05 (d, J = 9.6 Hz, 1H), 5.07 (t, J = 9.6 Hz, 1H), 6.50 (d, J = 16.2 Hz,
1H), 6.90 (d, J = 9.6 Hz, 1H), 7.05–7.11 (m, 1H), 7.26–7.30 (m,
2H), 7.39–7.45 (m, 3H), 7.49–7.60 (m, 3H), 7.76 (d, J = 16.2 Hz,
1H); 13C NMR (100 MHz, CDCl3) d: 41.1, 52.5, 52.7, 52.8, 55.4,
116.0, 124.3, 127.8, 128.0, 128.4, 128.9, 129.0, 129.5, 130.7,
133.5, 134.0, 137.8, 139.5, 147.1, 162.1, 163.9, 167.2, 167.5; MS
(ESI): m/z 547.9 ([M+H2O]+); HRMS (ESI): calculated for C25H23BrO8
N, 2.82. Found: C, 60.27; H, 4.61; N, 2.66. IR (KBr)
m 2955, 1736,
1634, 1523, 1436, 1350, 1130, 858 cmꢀ1. The enantiomeric excess
was determined by HPLC (Chiralpak AD column, hexane/i-PrOH
80:20, flow rate 0.75 mL/min; tminor = 57.1 min; tmajor = 97.4 min,
k = 254 nm).
(M+): 530.0576. Found: 530.0577; IR (KBr)
m 2955, 1737, 1634,
1472, 1435, 1311, 1133, 765 cmꢀ1. The enantiomeric excess was
determined by HPLC (Chiralpak AD column, hexane/i-PrOH
80:20, flow rate 0.75 mL/min; tminor = 23.4 min; tmajor = 29.1 min,
k = 254 nm).
4.3.7. (S,Z)-Trimethyl 4-(cinnamoyloxy)-2-p-tolylbut-3-ene-
1,1,4-tricarboxylate 3g
White solid. Yield 49%. Mp 92–94 oC. ½a D27
ꢂ
¼ ꢀ125:3 (c 1.2,
4.3.11. (S,Z)-4-Ethyl 1,1-dimethyl 4-(cinnamoyloxy)-2-
CHCl3). 1H NMR (300 MHz, CDCl3) d: 2.29 (s, 3H), 3.54 (s, 3H),
3.75 (d, J = 1.5 Hz, 6H), 3.93 (d, J = 10.2 Hz, 1H), 4.49 (t,
J = 10.2 Hz, 1H), 6.58 (d, J = 15.6 Hz, 1H), 6.74 (d, J = 10.2 Hz, 1H),
7.04–7.18 (m, 4H), 7.40–7.44 (m, 3H), 7.52–7.60 (m, 2H), 7.80 (d,
J = 15.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) d: 21.0, 41.9, 52.5,
52.6, 52.9, 56.7, 116.0, 127.6, 128.4, 128.9, 129.3, 129.6, 130.8,
134.0, 135.2, 137.3, 138.5, 147.3, 162.2, 164.2, 167.4, 167.7; MS
(ESI): m/z 484.2 ([M+H2O]+). Anal. Calcd for C26H26O8: C, 66.94;
phenylbut-3-ene-1,1,4-tricarboxylate 3k
White waxy solid. Yield 72%. ½a D27
ꢂ
¼ ꢀ95:7 (c 1.7, CHCl3). 1H
NMR (300 MHz, CDCl3) d: 1.25 (t, J = 7.2 Hz, 3H), 3.51 (s, 3H),
3.74 (s, 3H), 3.94 (d, J= 10.5 Hz, 1H), 4.20 (q, J = 7.2 Hz, 2H), 4.52
(t, J = 10.5 Hz, 1H), 6.57 (d, J = 15.9 Hz, 1H), 6.72 (d, J = 10.5 Hz,
1H), 7.23–7.31 (m, 5H), 7.32–7.40 (m, 3H), 7.51–7.54 (m, 2H),
7.79 (d, J = 15.9 Hz, 1H); 13C NMR (100 MHz, CDCl3) d: 14.0, 42.3,
52.6, 52.9, 56.7, 61.7, 116.1, 127.6, 127.8, 128.4, 128.6, 128.9,
130.8, 134.0, 138.4, 139.0, 147.2, 161.7, 164.2, 167.3, 167.6; MS
(ESI): m/z 484.2 ([M+NH4]+); HRMS (ESI): calculated for C26H26O8
H, 5.62. Found: C, 66.85; H, 5.57. IR (KBr)
m 2955, 1738, 1634,
1450, 1436, 1309, 1133, 766 cmꢀ1. The enantiomeric excess was
determined by HPLC (Chiralpak AD column, hexane/i-PrOH
80:20, flow rate 0.75 mL/min; tminor = 21.5 min; tmajor = 26.5 min,
k = 254 nm).
(M+): 466.1628. Found: 466.1625; IR (KBr)
m 2955, 1736, 1635,
1435, 1370, 1134, 766, 701 cmꢀ1; The enantiomeric excess was
determined by HPLC (Chiralpak AD column, hexane/i-PrOH
80:20, flow rate 0.75 mL/min; tminor = 20.9 min; tmajor = 22.5 min,
k = 254 nm).
4.3.8. (S,Z)-Trimethyl 4-(cinnamoyloxy)-2-(4-ethoxyphenyl)-
but-3-ene-1,1,4-tricarboxylate 3h
White solid. Yield 51%. Mp 85–87 oC. ½a D27
ꢂ
¼ ꢀ122:2 (c 1.25,
4.3.12. (S,Z)-4-Allyl 1,1-dimethyl 4-(cinnamoyloxy)-2-
CHCl3). 1H NMR (300 MHz, CDCl3) d: 1.37 (t, J = 6.9 Hz, 3H), 3.54
(s, 3H), 3.75 (d, J = 3.9 Hz, 6H), 3.89 (d, J = 10.2 Hz, 1H), 3.97 (q,
J = 6.9 Hz, 2H), 4.46 (t, J = 10.2 Hz, 1H), 6.57 (d, J = 16.2 Hz, 1H),
6.74 (d, J = 10.2 Hz, 1H), 6.81 (d, J = 8.7 Hz, 2H), 7.14 (d, J = 8.7 Hz,
2H), 7.38–7.44 (m, 3H), 7.52–7.59 (m, 2H), 7.79 (d, J = 16.2 Hz,
1H); 13C NMR (100 MHz, CDCl3) d: 14.8, 41.6, 52.5, 52.6, 52.9,
56.9, 63.3, 114.8, 116.0, 128.4, 128.8, 128.9, 129.4, 130.0, 130.8,
134.0, 138.4, 147.3, 158.3, 162.2, 164.2, 167.4, 167.7; MS (ESI):
m/z 514.2 ([M+H2O]+). Anal. Calcd for C27H28O9: C, 65.31; H, 5.68.
phenylbut-3-ene-1,1,4-tricarboxylate 3l
White waxy solid. Yield 50%. ½a D27
ꢂ
¼ ꢀ108:7 (c 1.0, CHCl3). 1H
NMR (300 MHz, CDCl3) d: 3.52 (s, 3H), 3.75 (s, 3H), 3.95 (d,
J = 10.2 Hz, 1H), 4.54 (t, J = 10.2 Hz, 1H), 4.66 (d, J = 5.7 Hz, 2H),
5.20–5.33 (m, 2H), 5.83–5.96 (m, 1H), 6.58 (d, J = 15.9 Hz, 1H),
6.78 (d, J = 10.2 Hz, 1H), 7.23–7.33 (m, 5H), 7.38–7.44 (m, 3H),
7.53–7.62 (m, 2H), 7.80 (d, J = 15.9 Hz, 1H); 13C NMR (100 MHz,
CDCl3) d: 42.3, 52.6, 52.9, 56.7, 66.1, 116.0, 118.5, 127.6, 127.8,
128.4, 128.8, 128.9, 129.2, 130.8, 131.5, 134.0, 138.3, 138.8,
147.3, 161.4, 164.2, 167.3, 167.6; MS (ESI): m/z 496.2
([M+H2O]+); HRMS (ESI): calculated for C27H26O8 (M+): 478.1628.
Found: C, 65.29; H, 5.68. IR (KBr)
m 2954, 1744, 1635, 1511,
1436, 1310, 1129, 767 cmꢀ1. The enantiomeric excess was deter-
mined by HPLC (Chiralpak AD column, hexane/i-PrOH 80:20, flow
rate 0.75 mL/min; tminor = 31.8 min; tmajor = 44.9 min, k = 254 nm).
Found: 478.1636. IR (KBr)
m 2955, 1736, 1634, 1495, 1133, 982,
766, 701 cmꢀ1; The enantiomeric excess was determined by HPLC
(Chiralpak AD column, hexane/i-PrOH 80:20, flow rate 0.75 mL/
min; tminor = 21.4 min; tmajor = 23.0 min, k = 254 nm).
4.3.9. (S,Z)-Trimethyl 4-(cinnamoyloxy)-2-(2,4-dichloro-
phenyl)but-3-ene-1,1,4-tricarboxylate 3i
White waxy solid. Yield 31%. ½a D27
ꢂ
¼ ꢀ50:2 (c 0.8, CHCl3). 1H
4.3.13. (S,Z)-4-tert-Butyl 1,1-dimethyl 4-(cinnamoyloxy)-2-
NMR (300 MHz, CDCl3) d: 3.60 (s, 3H), 3.76 (d, J = 9.6 Hz, 6H),
4.03 (d, J = 9.0 Hz, 1H), 4.98 (t, J = 9.0 Hz, 1H), 6.49 (d, J = 15.6 Hz,
1H), 6.85 (d, J = 9.0 Hz, 1H), 7.15–7.26 (m, 2H), 7.35 (s, 1H), 7.40–
7.44 (m, 3H), 7.54–7.56 (m, 2H), 7.74 (d, J = 15.6 Hz, 1H); 13C
NMR (100 MHz, CDCl3) d: 38.4, 52.6, 52.8, 52.9, 55.0, 115.7,
127.4, 127.5, 128.4, 129.0, 129.9, 130.4, 130.8, 133.9, 134.0,
134.4, 134.8, 139.7, 147.4, 161.9, 163.9, 167.1, 167.4; MS (ESI):
m/z 538 ([M+H2O]+); HRMS (ESI): calculated for C25H22Cl2O8
phenylbut-3-ene-1,1,4-tricarboxylate 3m
White waxy solid. Yield 35%. ½a D27
ꢂ
¼ ꢀ96:7 (c 0.7, CHCl3). 1H
NMR (300 MHz, CDCl3) d: 1.44 (s, 9H), 3.50 (s, 3H), 3.74 (s, 3H),
3.93 (d, J = 10.5 Hz, 1H), 4.50 (t, J = 10.5 Hz, 1H), 6.53–6.61 (m,
2H), 7.18–7.36 (m, 5H), 7.38–7.42 (m, 3H), 7.52–7.60 (m, 2H),
7.78 (d, J = 16.5 Hz, 1H); 13C NMR (100 MHz, CDCl3) d: 27.9, 42.3,
52.5, 52.9, 56.8, 82.4, 116.2, 127.4, 127.5, 127.9, 128.3, 128.8,
128.9, 130.7, 134.1, 138.6, 140.0, 146.9, 160.7, 164.2, 167.4,
167.6; MS (ESI): m/z 512.2 ([M+H2O]+); HRMS (ESI): calculated
(M+): 520.0692. Found: 520.0684; IR (KBr)
m 2955, 1737, 1634,

2614
H.-F. Wang et al. / Tetrahedron: Asymmetry 19 (2008) 2608–2615
for C28H30O8 (M+): 494.1941. Found: 494.1944; IR (KBr)
m
2954,
(ESI): m/z 468.9 ([M+H]+). Anal. Calcd for C20H21BrO8: C, 51.59;
1739, 1635, 1496, 1370, 1311, 1120, 766 cmꢀ1. The enantiomeric
excess was determined by HPLC (Chiralpak AD column, hexane/i-
PrOH 80:20, flow rate 0.75 mL/min; tminor = 12.6 min; tmajor = 13.9
min, k = 254 nm).
H, 4.51. Found: C, 51.42; H, 4.57. IR (KBr) m 2955, 1738, 1653,
1488, 1436, 1312, 1151, 827 cmꢀ1. The enantiomeric excess was
determined by HPLC (Chiralpak AD column, hexane/i-PrOH
80:20, flow rate 0.75 mL/min; tminor = 17.2 min; tmajor = 22.4 min,
k = 254 nm).
4.3.14. (S,Z)-4-Benzyl 1,1-dimethyl 4-(cinnamoyloxy)-2-
phenylbut-3-ene-1,1,4-tricarboxylate 3n
4.3.18. (S,Z)-1,1-Diethyl 4-methyl 2-(4-bromophenyl)-4-
White solid. Yield 70%. Mp 107–109 oC. ½a D27
ꢂ
¼ ꢀ85:9 (c 1.0,
(cinnamoyloxy)but-3-ene-1,1,4-tricarboxylate 3r
CHCl3). 1H NMR (300 MHz, CDCl3) d: 3.51 (s, 3H), 3.73 (s, 3H),
3.95 (d, J = 10.5 Hz, 1H), 4.54 (t, J = 10.5 Hz, 1H), 5.20 (dd, J = 12.3,
3.0 Hz, 2H), 6.57 (d, J = 15.9 Hz, 1H), 6.78 (d, J = 10.5 Hz, 1H),
7.20–7.38 (m, 10H), 7.40–7.44 (m, 3H), 7.52–7.60 (m, 2H), 7.80
(d, J = 15.9 Hz, 1H); 13C NMR (100 MHz, CDCl3) d: 42.3, 52.6, 52.9,
56.7, 67.3, 116.0, 127.7, 127.9, 128.1, 128.3, 128.4, 128.5, 128.9,
129.0, 129.3, 130.8, 134.0, 135.3, 138.3, 138.8, 147.4, 161.6,
164.2, 167.3, 167.6; MS (ESI): m/z 546.2 ([M+H2O]+). Anal. Calcd
for C31H28O8: C, 70.44; H, 5.34. Found: C, 70.42; H, 5.30. IR (KBr)
White solid. Yield 61%. Mp 112–114 oC. ½a D26
¼ ꢀ147:4 (c 1.0,
ꢂ
CHCl3). 1H NMR (300 MHz, CDCl3) d: 1.06 (t, J = 7.2 Hz, 3H), 1.25
(t, J = 7.2 Hz, 3H), 3.76 (s, 3H), 3.85 (d, J = 10.5 Hz, 1H), 3.96–4.07
(m, 2H), 4.13–4.26 (m, 2H), 4.46 (t, J = 10.5 Hz, 1H), 6.55 (d,
J = 16.2 Hz, 1H), 6.74 (d, J = 10.5 Hz, 1H), 7.13 (d, J = 8.1 Hz, 2H),
7.38–7.46 (m, 5H), 7.52–7.58 (m, 2H), 7.78 (d, J = 16.2 Hz, 1H);
13C NMR (100 MHz, CDCl3) d: 13.8, 13.9, 41.6, 52.5, 56.6, 61.7,
62.0, 115.8, 121.5, 128.4, 128.7, 129.0, 129.7, 130.9, 131.9, 133.9,
137.6, 139.0, 147.5, 162.0, 164.1, 166.8, 167.0; MS (ESI): m/z
575.8 ([M+H2O]+). Anal. Calcd for C27H27BrO8: C, 57.97; H, 4.86.
m
2955, 1740, 1634, 1496, 1434, 1380, 1131, 766 cmꢀ1. The
enantiomeric excess was determined by HPLC (Chiralpak AS-H
Found: C, 57.96; H, 4.85. IR (KBr)
m 2955, 1734, 1635, 1308,
column, hexane/i-PrOH 80:20, flow rate 0.75 mL/min; tminor
15.2 min; tmajor = 16.3 min, k = 254 nm).
=
1133, 861, 766, 682 cmꢀ1. The enantiomeric excess was deter-
mined by HPLC (Chiralpak AD column, hexane/i-PrOH 80:20, flow
rate 0.75 mL/min; tminor = 24.1 min; tmajor = 36.8 min, k = 254 nm).
4.3.15. (S,Z)-4-(4-Bromobenzyl) 1,1-dimethyl 4-
(cinnamoyloxy)-2-phenylbut-3-ene-1,1,4-tricarboxylate 3o
4.3.19. (S,Z)-1,1-Diisopropyl 4-methyl 2-(4-bromophenyl)-4-
White solid. Yield 74%. Mp 113–115 oC. ½a D27
ꢂ
¼ ꢀ79:7 (c 1.0,
(cinnamoyloxy)but-3-ene-1,1,4-tricarboxylate 3s
CHCl3). 1H NMR (300 MHz, CDCl3) d: 3.51 (s, 3H), 3.73 (s, 3H),
3.94 (d, J = 10.2 Hz, 1H), 4.53 (t, J = 10.2 Hz, 1H), 5.13 (s, 2H), 6.56
(d, J = 15.9 Hz, 1H), 6.78 (d, J = 10.2 Hz, 1H), 7.18–7.32 (m, 7H),
7.40–7.50 (m, 5H), 7.52–7.60 (m, 2H), 7.78 (d, J = 15.9 Hz, 1H);
13C NMR (100 MHz, CDCl3) d: 42.3, 52.6, 52.9, 56.6, 66.4, 115.9,
122.3, 127.7, 127.9, 128.4, 128.9, 129.0, 129.5, 129.8, 130.9,
131.7, 134.0, 134.3, 138.2, 138.6, 147.5, 161.5, 164.2, 167.3,
167.6; MS (ESI): m/z 626 ([M+H2O]+). Anal. Calcd for C31H27BrO8:
White solid. Yield 68%. Mp 127–129 oC. ½a D28
¼ ꢀ163:1 (c 1.0,
ꢂ
CHCl3). 1H NMR (300 MHz, CDCl3) d: 1.05 (dd, J = 13.5, 6.0 Hz,
6H), 1.24 (d, J = 6.0 Hz, 6H), 3.70–3.81 (m, 4H), 4.43 (t,
J = 10.2 Hz, 1H), 4.81–4.89 (m, 1H), 5.02–5.11 (m, 1H), 6.54 (d,
J = 16.2 Hz, 1H), 6.74 (d, J = 10.2 Hz, 1H), 7.12 (d, J = 8.1 Hz, 2H),
7.32–7.48 (m, 5H), 7.52–7.60 (m, 2H), 7.78 (d, J = 16.2 Hz, 1H);
13C NMR (100 MHz, CDCl3) d: 21.3, 21.5, 21.6, 41.6, 52.5, 56.9,
69.4, 69.7, 115.8, 121.4, 128.4, 128.9, 129.0, 129.7, 130.9, 131.8,
134.0, 137.7, 138.9, 147.5, 162.1, 164.1, 166.4, 166.6; MS (MALDI):
m/z 609.1 ([M+Na]+). Anal. Calcd for C29H31BrO8: C, 59.29; H, 5.32.
C, 61.29; H, 4.48. Found: C, 61.40; H, 4.58. IR (KBr)
m 2954, 1737,
1634, 1491, 1451, 1435, 1132, 700 cmꢀ1. The enantiomeric excess
was determined by HPLC (Chiralpak AS-H column, hexane/i-PrOH
80:20, flow rate 0.75 mL/min; tminor = 18.4 min; tmajor = 22.0 min,
k = 254 nm).
Found: C, 59.42; H, 5.36. IR (KBr)
m 2982, 1732, 1635, 1488, 1100,
983, 911, 766 cmꢀ1. The enantiomeric excess was determined by
HPLC (Chiralpak AD column, hexane/i-PrOH 80:20, flow rate
0.75 mL/min; tminor = 19.2 min; tmajor = 30.5 min, k = 254 nm).
4.3.16. (S,Z)-4-Isopropyl 1,1-dimethyl 4-(cinnamoyloxy)-2-
phenylbut-3-ene-1,1,4-tricarboxylate 3p
4.3.20. (S,Z)-1,1-Dibenzyl 4-methyl 2-(4-bromophenyl)-4-
White waxy solid. Yield 63%. ½a D27
ꢂ
¼ ꢀ108:7 (c 1.4, CHCl3). 1H
(cinnamoyloxy)but-3-ene-1,1,4-tricarboxylate 3t
NMR (300 MHz, CDCl3) d: 1.24 (d, J = 6.0 Hz, 6H), 3.52 (s, 3H),
3.75 (s, 3H), 3.95 (d, J = 10.5 Hz, 1H), 4.53 (t, J = 10.5 Hz, 1H),
5.01–5.09 (m, 1H), 6.58 (d, J = 15.6 Hz, 1H), 6.68 (d, J = 10.5 Hz,
1H), 7.20–7.38 (m, 5H), 7.40–7.44 (m, 3H), 7.52–7.60 (m, 2H),
7.78 (d, J = 15.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) d: 21.6, 21.7,
42.3, 52.5, 52.9, 56.7, 69.5, 116.1, 127.6, 127.9, 128.2, 128.4,
128.8, 128.9, 130.8, 134.1, 138.5, 139.4, 147.1, 161.2, 164.2,
167.3, 167.6; MS (ESI): m/z 498.2 ([M+H2O]+); HRMS (ESI): calcu-
White waxy solid. Yield 98%. ½a D27
ꢂ
¼ ꢀ115:1 (c 1.0, CHCl3). 1H
NMR (300 MHz, CDCl3) d: 3.75 (s, 3H), 3.98 (d, J = 10.2 Hz, 1H),
4.51 (t, J = 10.2 Hz, 1H), 4.98 (s, 2H), 5.17 (dd, J = 9.9, 12.0 Hz,
2H), 6.49 (d, J = 16.2 Hz, 1H), 6.73 (d, J = 10.2 Hz, 1H), 7.06 (d,
J = 7.8 Hz, 4H), 7.20–7.38 (m, 10H), 7.40–7.46 (m, 3H), 7.48–7.59
(m, 2H), 7.74 (d, J = 16.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) d:
41.8, 52.5, 56.7, 67.5, 67.7, 115.7, 121.7, 128.2, 128.3, 128.4,
128.5, 128.6, 128.9, 129.6, 130.9, 132.0, 133.9, 134.8, 135.0,
137.2, 139.1, 147.6, 161.9, 164.1, 166.5, 166.7; MS (MALDI): m/z
705.1 ([M+Na]+); HRMS (MALDI): calculated for C37H31O8BrNa
lated for C27H28O8 (M+): 480.1784. Found: 480.1789; IR (KBr)
m
2954, 1738, 1634, 1495, 1136, 1101, 980, 765 cmꢀ1. The enantio-
meric excess was determined by HPLC (Chiralpak AD column, hex-
ane/i-PrOH 80:20, flow rate 0.75 mL/min; tminor = 16.3 min;
tmajor = 17.6 min, k = 254 nm).
([M+Na]+): 705.1088. Found: 705.1095; IR (KBr)
m 2954, 1733,
1634, 1488, 1131, 981, 766, 698 cmꢀ1. The enantiomeric excess
was determined by HPLC (Chiralpak AD column, hexane/i-PrOH
80:20, flow rate 0.75 mL/min; tminor = 60.1 min; tmajor = 71.9 min,
k = 254 nm).
4.3.17. (S,Z)-Trimethyl 2-(4-bromophenyl)-4-((E)-but-2-
enoyloxy)but-3-ene-1,1,4-tricarboxylate 3q
White solid. Yield 70%. Mp 111–113 oC. ½a D26
¼ ꢀ98:4 (c 1.65,
ꢂ
CHCl3). 1H NMR (300 MHz, CDCl3) d: 1.96 (d, J = 6.6 Hz, 3H), 3.55
(s, 3H), 3.72 (d, J = 5.4 Hz, 6H), 3.86 (d, J = 10.2 Hz, 1H), 4.42 (t,
J = 10.2 Hz, 1H), 5.97 (d, J = 15.6 Hz, 1H), 6.65 (d, J = 10.2 Hz, 1H),
7.08–7.18 (m, 3H), 7.41 (d, J = 8.1 Hz, 2H); 13C NMR (100 MHz,
CDCl3) d: 18.3, 41.6, 52.5, 52.7, 52.9, 56.4, 120.8, 121.6, 128.1,
129.5, 132.0, 137.4, 138.9, 148.2, 162.0, 163.5, 167.2, 167.3; MS
Acknowledgments
The generous financial support from the National Natural Sci-
ence Foundation of China, QT Program, Shanghai Natural Science
Council, and Excellent Young Scholars Foundation of NNSF is grate-
fully acknowledged.

H.-F. Wang et al. / Tetrahedron: Asymmetry 19 (2008) 2608–2615
2615
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