CuCl-catalyzed stereoselective conjugate addition of Grignard reagents to 2,3-allenoates

Article abstract of DOI:10.1016/j.tet.2012.01.027

CuCl was found to be an efficient catalyst for the conjugate addition of 2,3-allenoates with Grignard reagents to synthesize poly-substituted β,γ-unsaturated alkenoates with high stereoselectivity in good to excellent yields. Primary, secondary, and terti

Full text of DOI:10.1016/j.tet.2012.01.027

Tetrahedron 68 (2012) 2719e2724
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
CuCl-catalyzed stereoselective conjugate addition of Grignard reagents
to 2,3-allenoates
*
Jian He, Zhan Lu, Guobi Chai, Chunling Fu, Shengming Ma
Laboratory of Molecular Recognition and Synthesis, Department of Chemistry, Zhejiang University, 310027 Hangzhou, Zhejiang, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
CuCl was found to be an efficient catalyst for the conjugate addition of 2,3-allenoates with Grignard
Received 18 October 2011
Received in revised form 2 January 2012
Accepted 13 January 2012
Available online 18 January 2012
reagents to synthesize poly-substituted b,g-unsaturated alkenoates with high stereoselectivity in good to
excellent yields. Primary, secondary, and tertiary alkyl, vinyl or phenyl Grignard reagents may all be used.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
2,3-Allenoates
Grignard reagents
Copper-catalysis
Conjugate addition
1. Introduction
phenyl-2,3-butadienoate 1a with CH3MgCl was examined by us-
ing 5 mol % of CuI as the catalyst in the solution of toluene at ꢀ78 ꢁC
Transition metal-catalyzed conjugate addition of carbon anions
to a,b-unsaturated carbonyl compounds is a powerful strategy for
and we were pleased to find that ethyl 2,3-dimethyl-4-phenyl-3(Z)-
butenoate Z-2a was afforded in 86% yield with a high stereo-
selectivity (Z/E >99:1) (entry 1, Table 1). Further screening of the
solvents showed that toluene afforded the best results (compare
entries 2e5 with entry 1, Table 1). It was found that when the re-
action of 1a with CH3MgCl in the presence of CuI was conducted in
diethyl ether, the reaction mixture would be heterogeneous. Thus
the relative low solubility of the reaction intermediate in diethyl
ether may account for the low reactivity (entry 5, Table 1). The
reaction with 10 mol % or 2 mol % of CuI gave very similar results
(entries 6 and 7, Table 1). However, when we reduced the loading of
CuI to 0.5 mol %, the change resulted in a recovery of starting ma-
terial 1a in 3% yield (entry 8, Table 1). In the absence of CuI, the
reaction in toluene and Et2O was quite slow and no reaction oc-
curred in THF (entries 9e11, Table 1). The use of 2.0 equiv of
CH3MgCl led to a lower yield of 71% (entry 12, Table 1). Reducing
the amount of CH3MgCl to 1.5 equiv resulted in an incomplete re-
action with 1a being recovered in 22% yield (entry 13, Table 1). CuCl
(5 mol %) may also be used to complete the conversion (entry 14,
Table 1). Other cuprous or cupric salts failed to afford better results
(entries 15e17, Table 1). Thus, we defined 5 mol % of CuCl, 3 equiv of
Grignard reagents in toluene at ꢀ78 ꢁC as the optimized standard
reaction conditions.
carbonecarbon bond formation.1 Of the various methods utilized,
copper-based catalysts along with organometallic reagents have
shown great potential in this field.2 During the last decade, copper-
catalyzed conjugate addition of Michael acceptors has been well
studied in various aspects.3 Although several examples on the
copper-mediated addition of organometallic reagents to 2,3-
allenoates have been reported,4 stoichiometric or sub-
stoichiometric organocuprate reagents were used in these re-
actions and no example on the catalytic reaction has been reported.
Recently, we found that the iron-catalyzed conjugate addition of
Grignard reagents to 2,3-allenoates has been proven to be an effi-
cient method for the synthesis of
b,g
-unsaturated alkenoates,5,6
which are useful building blocks in organic synthesis. However,
for the development of enantioselective version of this type of re-
action, we showed strong interest in exploring the Cu-catalyzed
such reactions. Herein, we wish to present our recent progress on
the copper-catalyzed stereoselective conjugate addition of
Grignard reagents to 2,3-allenoates.
2. Results and discussion
With the optimized reaction conditions in hand, we explored
the substrate scope of the CuCl-catalyzed conjugate addition re-
action of 2,3-allenoates with Grignard reagents and the results
were summarized in Table 2. R1 could be aryl or alkyl groups; R2
Due to the importance of methylmetalation in natural product
syntheses, in our initial study, the reaction of ethyl 2-methyl-4-
* Corresponding author. E-mail address: masm@mail.sioc.ac.cn (S. Ma).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.01.027

2720
J. He et al. / Tetrahedron 68 (2012) 2719e2724
Table 1
Optimization of reaction conditions
H3C
Ph
CO2Et Ph
+
CH3
Ph
CH3
cat.
CH3MgCl in THF (3 M)
+
solvent
H
CH3
Z-2a
H3C
CO2Et
CO2Et
3 equiv
-78 oC, 1.5 h
1a
3a
Entry
Cat. (mol %)
Solvent
Yield of Z-2a
(%) (Z/E)a
Recovery
Yield
of 1a (%)a
of 3a (%)b
1
2
3
4
5
6
7
8
CuI (5)
CuI (5)
CuI (5)
CuI (5)
CuI (5)
CuI (10)
CuI (2)
CuI (0.5)
d
Toluene
THF
CH2Cl2
n-Hexane
Et2O
Toluene
Toluene
Toluene
Toluene
THF
88 (>99:1)
80 (98:2)
0
2.1
0
64
44
0
2.3
0.6
2.7
0
1.1
3.5
2.7
3.5
4.5
0
1.4
4.5
2.9
1.9
2.3
2.8
1.3
2.1
82 (>99:1)
12 (>99:1)
38 (>99:1)
83 (>99:1)
87 (>99:1)
77 (>99:1)
44 (>99:1)
0
28 (>99:1)
75 (>99:1)
55 (>99:1)
86 (>99:1)
86 (>99:1)
62 (>99:1)
78 (>99:1)
90 (96:4)
0
3
9c
10
11
12d
13e
14
15
16
17
18f
40
92
57
0
22
0
0
23
0
d
d
Et2O
CuI (5)
CuI (5)
CuCl (5)
CuBr (5)
CuCN (5)
CuCl2 (5)
CuCl (5)
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
0
a
Determined by NMR spectroscopy using mesitylene as the internal standard.
Determined by NMR spectroscopy, if any.
The reaction was carried out for 7 h.
CH3MgCl (2.0 equiv) was applied.
CH3MgCl (1.5 equiv) was applied.
The reaction was quenched at 0 ꢁC.
b
c
d
e
f
Table 2
CuCl-catalyzed conjugate addition of Grignard reagents to 2,3-allenoatesa
R3
R5
R3
R5
R1
R2
R3
R1
CO2R4
+
R1
R2
CO2R4
CuCl (5 mol%)
toluene, -78 oC, time
R5MgCl in THF
3 equiv
+
CO2R4
R2
1
3
2
Entry
R1
R2
R3
R4
R5
Time
(h)
Yield of 2
and 3 (%)b
Ratio
of 2/3c
1
2
3
4
5
6
7
8
Ph
Ph
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
H
Me
Allyl
Me
Me
Me
n-Pr
Me
Ph
Me
Me
Me
allyl
Me
Me
H
Et (1a)
Et (1b)
Et (1c)
Et (1d)
Et (1e)
Et (1f)
Et (1g)
Me (1h)
Et (1a)
Et (1a)
Et (1a)
Et (1b)
Et (1g)
Et (1i)
Et (1j)
Et (1d)
Et (1i)
Me
Me
Me
Me
Me
Me
Me
Me
i-Pr
c-Hex
t-Bu
Ph
Ph
Ph
1.5
1.5
1.5
1.5
1.5
1.5
2.5
2
2
2
2
1.5
2.5
1.5
1.5
2
84 (Z-2a)
90 (Z-2b)
80 (Z-2c)
81 (Z-2d)
83(Z-2e)
87 (Z-2f)
86 (Z-2g)
92 (2h)
92 (Z-2i)
91 (Z-2j)
87 (E-2k)
93 (E-2l)
86 (E-2m)
92 (E-2n)
85 (E-2o)
87 (Z-2p)
80 (Z-2q)
99:1
96:4
98:2
98:2
96:4
p-FC6H4
p-ClC6H4
p-BrC6H4
p-BrC6H4
p-MeOC6H4
Me
Ph
Ph
Ph
Ph
p-MeOC6H4
n-C4H9
n-C7H15
p-ClC6H4
n-C4H9
96:4
>99:1
>99:1
96:4
95:5
>99:1
96:4
>99:1
>99:1
>99:1
>99:1
>99:1
9
10
11
12
13
14
15
16
17
Ph
Me
Me
Vinyld
Vinyld
1.5
a
The reaction was conducted using 0.4 mmol of 2,3-allenoates, 3 equiv of Grignard reagents (solution in THF), and 5 mol % of CuCl in 5 mL of toluene at ꢀ78 ꢁC.
Isolated yields. Product 3 is inseparable from 2.
b
c
Ratio was determined by 1H NMR analysis of the crude products.
d
Vinyl magnesium bromide was used.
could be H or alkyl groups; R3 could be alkyl, allyl or phenyl groups.
Aryl groups with electron-withdrawing and electron-donating
substituents are well tolerated (entries 3e7, Table 2). It should be
mentioned that even the fully substituted allenoate 1h may also be
used to complete the reaction (entry 8, Table 2). In addition to
primary alkyl Grignard reagents, secondary and tertiary Grignard
reagents also afforded the corresponding
b,g-unsaturated alke-
noates in good yields (entries 9e11, Table 2). Furthermore, phenyl

J. He et al. / Tetrahedron 68 (2012) 2719e2724
2721
and vinyl magnesium chloride may also be applied to the conjugate
addition of both 2 and/or 4-alkyl- and 4-aryl-substituted 2,3-
allenoates (entries 12e17, Table 2). The yields of the CuCl-
catalyzed conjugate addition are generally higher than those of
the iron-catalyzed reactions using phenyl magnesium chloride as
the nucleophile.5
temperature. It should also be noted that all the reactions occurred
at the -position of the ester group.
a
3. Conclusions
In summary, we have developed an efficient CuCl-catalyzed
The dienolate intermediate Z-4 derived from the reaction of
CuCl-catalyzed conjugate addition of 1a and CH3MgCl may react
with acetone to form the addition product Z-5. What should be
mentioned is that its reaction with methyl p-toluenesulfonate,
benzyl bromide, or allyl acetate afforded the methylation product
conjugate addition of 2,3-alleonates with Grignard reagents to
synthesize poly-substituted
b,g-unsaturated Z-alkenoates with
high regio- and stereoselectivity. Primary, secondary, and tertiary
alkyl, vinyl, or phenyl groups may be introduced from the readily
available Grignard reagents to the 3-position of 2,3-allenonates.
Good to excellent yields were achieved with a catalytic loading of
CuCl (5 mol %). The in situ formed magnesium dienolate may also
react with different electrophiles to obtain a series of compounds
E-6, 2-benzyl unsaturated alkenoate E-7 or b-ketoester derivative
E-8 with high reversed E-stereoselectivity (Scheme 1), which is in
accordance with our previous report.6 The configurations of the
carbonecarbon double bonds were determined by NOE analysis
(Fig. 1).
containing an allylic quaternary carbon at the
a-position of the
ester group. Compared to iron catalyst, the regioselectivity of the
OH
CH3
CO2Et
H3C
H3C
CH3
CO2Et
H3C
O
p-TsOMe
Ph
-78 oC to rt,
16 h
-78 oC, 2.5 h
CH3
Z-5
yield: 69%
Ph
CH3
H3C
OEt
OM
E-6
Ph
yield: 76%a
E/Z= 13/1b
CH3
Z-4
O
M = MgCl or Cu
CH3
CO2Et
Bn
H3C
CH3
CO2Et
BnBr
AcO
-78 oC to rt,
16 h
-78 oC to rt,
15 h
Ph
CH3
E-7
yield: 64%a
Ph
CH3
E-8
yield: 49%
E/Z = 41/1b
a Contaminated with E-2a.
b Ratio was determined by 1H NMR analysis of the crude products.
Scheme 1. Reactions of in situ generated dienolate intermediate 4 with different electrophiles.
reaction with CuCl was slightly lower. However, due to the differ-
H
H3C OH
ence between copper and iron, the reaction may show a distinct
approach to other tandem transformations, especially the enan-
tioselective form, considering the wide application of copper cat-
alyst in asymmetric synthesis. Further studies in this area including
enantioselective transformations with copper catalyst are being
conducted in our laboratory.
H
H3C
H3C
H3C
O
CH3
CO2Et
Ph
CO2Et
CH3
CO2Et
H3C
H3C
Ph
H
H
H
H
CO2Et
CH3
Ph
CH3
Ph
CH3
Ph
CH3
E-7
Z-5
E-8
E-6
4. Experimental
Fig. 1. NOE study on b,g-unsaturated alkenoate derivatives.
4.1. General information
When methyl p-toluenesulfonate, benzyl bromide, or allylic
acetate was added as the electrophile, the carbonecarbon un-
saturated bond and/or the carbonyl oxygen may coordinate with
the metal to increase the steric hindrance between the coordinated
metal and the phenyl group. This type of interaction led to the
complete conversion of 1,3-(Z)-dienoate Z-4 to 1,3-(E)-dienoate E-4
when the reaction system gradually warmed up to rt (Scheme 2).7
The subsequent reaction with methyl p-toluenesulfonate, benzyl
bromide, or allyl acetate resulted in the formation of E-6, E-7, or E-8.
On the contrary, the reaction with acetone should be very fast,
occurring before the isomerization from Z to E at relatively low
Toluene was distilled with Na wire in the presence of benzo-
phenone. Methyl magnesium chloride (3.0 M solution in THF), iso-
propyl magnesium chloride (2.0 M solution in THF), and tert-butyl
magnesium chloride (1.0 M solution in THF) used in this study were
purchased from Aldrich. cyclo-Hexyl magnesium chloride (1.3 M
solution in THF), phenyl magnesium chloride (1.6 M or 1.8 M so-
lution in THF), and vinyl magnesium bromide (0.7 M solution in
THF) used in this study were purchased from Acros Organics. The
other commercially available chemicals were purchased and used
without additional purification unless noted otherwise. All 1H NMR

2722
J. He et al. / Tetrahedron 68 (2012) 2719e2724
M = MgCl or Cu
CH3
CH3
CO2Et
CH3
L M
n
L M
H
n
H3C
OM
OEt
H3C
OMLn
OEt
ligand (L)
CO2Et
Ph
Ph
H
H
-78 oC to rt
CH3
Ph
CH3
Ph
CH3
E-4
anti-allylic metallic
syn-allylic metallic
intermediate
4
Z-
intermediate
Z-5
E-6/ E-7/ E-8
Scheme 2. Plausible mechanism in the stereoselective reactions.
experiments were measured relative to the signal of tetrame-
thylsilane (0 ppm).
126.8, 115.0 (d, JFC¼20.8 Hz), 60.6, 40.8, 19.4, 15.2, 14.2; 19F NMR
(282 MHz, CDCl3)
d
ꢀ116.0; MS (EI) m/z (%) 237 (Mþþ1, 4.37), 236
(Mþ, 27.66), 163 (100); IR (neat, cmꢀ1) 2980, 2940, 1733, 1651, 1602,
1507, 1450, 1377, 1323, 1225, 1186, 1160, 1093, 1075, 1033; HRMS
calcd for C14H17O2F (Mþ): 236.1213; found: 236.1212.
4.2. General procedure for CuCl-catalyzed conjugate addition
of alkyl/vinyl/aryl magnesium chlorides/bromides to 2,3-
allenoates
4.2.4. Ethyl 4-(p-chlorophenyl)-2,3-dimethyl-3(Z)-butenoate (Z-
2d). The reaction of CuCl (2.0 mg, 0.02 mmol, 5 mol %),1d (93.8 mg,
0.4 mmol), toluene (5 mL), and a solution of CH3MgCl in THF
(0.4 mL, 3 M, 1.2 mmol, 3 equiv) afforded Z-2d (81.1 mg, 81%, Z-2d/
CuCl (5 mol %, 0.02 mmol), 1 (0.4 mmol), and toluene (5 mL)
were added sequentially to a dry Schlenk tube under nitrogen at-
mosphere at rt. A solution of Grignard reagent in THF (3 equiv,
1.2 mmol) was then added by a syringe to the reaction mixture
within 6 min at ꢀ78 ꢁC. After the reaction was over as monitored by
TLC, the reaction mixture was quenched slowly with a saturated
aqueous solution of NH4Cl (2 mL) at ꢀ78 ꢁC, which was followed by
warming up to rt naturally. After extraction with diethyl ether
(15e20 mLꢂ3), the organic layer was washed with diluted HCl (5%,
aqueous), a saturated aqueous solution of NaHCO3, brine sequen-
tially and dried over anhydrous Na2SO4. Filtration, evaporation, and
column chromatography on silica gel (eluent: petroleum ether/
ethyl acetate¼100:1) afforded 2.
3d¼98:2): liquid; 1H NMR (300 MHz, CDCl3)
d 7.31e7.27 (m, 2H,
AreH), 7.21e7.19 (m, 2H, AreH), 6.36 (s, 1H, ]CH), 4.21e4.11 (m,
2H, OCH2), 3.74 (q, J¼7.1 Hz, 1H, CH), 1.83 (d, J¼1.5 Hz, 3H, CH3),
1.29e1.21 (m, 6H, 2ꢂCH3); 13C NMR (75 MHz, CDCl3)
d 173.9, 137.7,
136.0, 132.2, 129.9, 128.3, 126.7, 60.6, 40.9, 19.4, 15.2, 14.2; MS (EI)
m/z (%) 255 (Mþ(37Cl)þ1, 1.30), 254 (Mþ(37Cl), 9.25), 253
(Mþ(35Cl)þ1, 4.20), 252 (Mþ(35Cl), 28.23), 179 (100); IR (neat, cmꢀ1
)
2980, 2939, 1733, 1650, 1593, 1489, 1450, 1377, 1323, 1241, 1185,
1092, 1032, 1015; HRMS calcd for C14H17O325Cl (Mþ): 252.0917;
found: 252.0917.
4.2.5. Ethyl 4-(p-bromophenyl)-2,3-dimethyl-3(Z)-butenoate (Z-
2e). The reaction of CuCl (2.0 mg, 0.02 mmol, 5 mol %), 1e
(113.0 mg, 0.4 mmol), toluene (5 mL), and a solution of CH3MgCl in
THF (0.4 mL, 3 M, 1.2 mmol, 3 equiv) afforded Z-2e5a (98.6 mg, 83%,
4.2.1. Ethyl 2,3-dimethyl-4-phenyl-3(Z)-butenoate (Z-2a). The re-
action of CuCl (2.0 mg, 0.02 mmol, 5 mol %),1a (80.2 mg, 0.4 mmol),
toluene (5 mL), and a solution of CH3MgCl in THF (0.4 mL, 3 M,
1.2 mmol, 3 equiv) afforded Z-2a5a (73.1 mg, 84%, 99% in purity):
Z-2e/3e¼96:4): liquid; 1H NMR (300 MHz, CDCl3)
d 7.44 (d,
liquid; 1H NMR (300 MHz, CDCl3)
d 7.35e7.19 (m, 5H, AreH), 6.42 (s,
J¼8.4 Hz, 2H, AreH), 7.15 (d, J¼8.4 Hz, 2H, AreH), 6.33 (s, 1H, ]CH),
4.22e4.11 (m, 2H, OCH2), 3.74 (q, J¼7.0 Hz,1H, CH),1.83 (d, J¼1.5 Hz,
3H, CH3), 1.29e1.21 (m, 6H, 2ꢂCH3).
1H, ]CH), 4.23e4.08 (m, 2H, OCH2), 3.82 (q, J¼7.1 Hz, 1H, CH), 1.84
(d, J¼1.5 Hz, 3H, CH3), 1.28e1.22 (m, 3H, 2ꢂCH3).
4.2.2. Ethyl 2-allyl-3-methyl-4-phenyl-3(Z)-butenoate (Z-2b). The
reaction of CuCl (2.0 mg, 0.02 mmol, 5 mol %), 1b (90.9 mg,
0.4 mmol), toluene (5 mL), and a solution of CH3MgCl in THF
(0.4 mL, 3 M, 1.2 mmol, 3 equiv) afforded Z-2b (87.9 mg, 90%, Z-2b/
4.2.6. Ethyl 4-(p-bromophenyl)-3-methyl-2-propyl-3(Z)-butenoate
(Z-2f). The reaction of CuCl (2.1 mg, 0.021 mmol, 5.3 mol %), 1f
(124.6 mg, 0.4 mmol), toluene (5 mL), and a solution of CH3MgCl in
THF (0.4 mL, 3 M, 1.2 mmol, 3 equiv) afforded Z-2f5a (113.3 mg, 87%,
3b¼96:4): liquid; 1H NMR (300 MHz, CDCl3)
d 7.35e7.19 (m, 5H,
Z-2f/3f¼96:4): liquid; 1H NMR (300 MHz, CDCl3)
d 7.47e7.40 (m,
AreH), 6.49 (s, 1H, ]CH), 5.65e5.52 (m, 1H, ]CH), 5.04e4.92 (m,
2H, 2ꢂ]CH), 4.25e4.10 (m, 2H, OCH2), 3.79 (t, J¼7.7 Hz, 1H, CH),
2.66e2.55 (m,1H, one proton of CH2), 2.36e2.25 (m, 1H, one proton
of CH2), 1.85 (d, J¼1.5 Hz, 3H, CH3), 1.27 (t, J¼7.1 Hz, 3H, CH3); 13C
2H, AreH), 7.18e7.14 (m, 2H, AreH), 6.40 (s, 1H, ]CH), 4.17 (q,
J¼7.1 Hz, 2H, OCH2), 3.61 (dd, J1¼8.3 Hz, J2¼6.8 Hz, 1H, CH), 1.82 (d,
J¼1.5 Hz, 3H, CH3), 1.80e1.71 (m, 1H, one proton of CH2), 1.60e1.47
(m, 1H, one proton of CH2), 1.28 (t, J¼7.1 Hz, 3H, CH3), 1.21e1.01 (m ,
2H, CH2), 0.77 (t, J¼7.2 Hz, 3H, CH3).
NMR (75 MHz, CDCl3) d 173.0, 137.4, 135.2, 134.6, 129.4, 128.7, 128.1,
126.4, 116.3, 60.6, 46.3, 33.9, 19.7, 14.2; MS (EI) m/z (%) 245 (Mþþ1,
1.31), 244 (Mþ, 7.13), 129 (100); IR (neat, cmꢀ1) 3079, 3023, 2979,
1732, 1642,1492,1443, 1368, 1336,1272,1231,1180,1112,1031. Anal.
Calcd for C16H20O2: C, 78.65; H, 8.25. Found: C, 78.78; H, 8.24.
4.2.7. Ethyl 2,3-dimethyl-4-(p-methoxyphenyl)-3(Z)-butenoate (Z-
2g). The reaction of CuCl (2.2 mg, 0.022 mmol, 5.5 mol %), 1g
(92.0 mg, 0.4 mmol), toluene (5 mL), and a solution of CH3MgCl in
THF (0.4 mL, 3 M, 1.2 mmol, 3 equiv) afforded Z-2g5b (84.7 mg,
4.2.3. Ethyl 4-(p-fluorophenyl)-2,3-dimethyl-3(Z)-butenoate (Z-
2c). The reaction of CuCl (2.0 mg, 0.02 mmol, 5 mol %), 1c (87.4 mg,
0.4 mmol), toluene (5 mL), and a solution of CH3MgCl in THF
(0.4 mL, 3 M, 1.2 mmol, 3 equiv) afforded Z-2c (74.9 mg, 80%, Z-2c/
86%): liquid; 1H NMR (300 MHz, CDCl3)
d 7.23e7.19 (m, 2H, AreH),
6.90e6.83 (m, 2H, AreH), 6.36 (s, 1H, ]CH), 4.23e4.09 (m, 2H,
OCH2), 3.86e3.78 (m, 4H, CHþCH3), 1.82 (d, J¼1.2 Hz, 3H, CH3),
1.29e1.22 (m, 6H, 2ꢂCH3).
3c¼98:2): liquid; 1H NMR (300 MHz, CDCl3)
d 7.27e7.20 (m, 2H,
AreH), 7.05e6.95 (m, 2H, AreH), 6.37 (s, 1H, ]CH), 4.23e4.09 (m,
2H, OCH2), 3.75 (q, J¼7.1 Hz, 1H, CH), 1.83 (d, J¼1.5 Hz, 3H, CH3),
4.2.8. Methyl 3,4-dimethyl-2-phenyl-3-pentenoate (2h). The re-
action of CuCl (2.2 mg, 0.022 mmol, 5.5 mol %), 1h (80.5 mg,
0.4 mmol), toluene (5 mL), and a solution of CH3MgCl in THF
1.29e1.21 (m, 6H, 2ꢂCH3); 13C NMR (75 MHz, CDCl3)
d 174.0, 161.5
(d, JFC¼244.1 Hz), 137.1, 133.6 (d, JFC¼3.5 Hz), 130.2 (d, JFC¼7.4 Hz),

J. He et al. / Tetrahedron 68 (2012) 2719e2724
2723
(0.4 mL, 3 M, 1.2 mmol, 3 equiv) afforded 2h (79.6 mg, 92%): liquid;
1H NMR (300 MHz, CDCl3)
7.33e7.20 (m, 5H, AreH), 4.96 (s, 1H,
7H, AreH), 6.92 (d, J¼8.7 Hz, 2H, AreH), 6.74 (s, 1H, ]CH),
4.19e4.07 (m, 3H, CHþOCH2), 3.82 (s, 3H, OCH3), 1.25 (d, J¼6.9 Hz,
3H, CH3), 1.20 (t, J¼7.1 Hz, 3H, CH3).
d
CH), 3.72 (s, 3H, OCH3), 1.81 (d, J¼1.5 Hz, 3H, CH3), 1.74 (s, 3H, CH3),
1.63 (d, J¼1.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3)
d 173.3, 138.2,
129.3, 128.23, 128.21, 126.6, 124.7, 53.4, 51.8, 21.1, 20.6, 15.6; MS (EI)
m/z (%) 218 (Mþ, 0.03), 145 (100); IR (neat, cmꢀ1) 3062, 3027, 2994,
2950, 2922, 2862, 1740, 1602, 1496, 1451, 1434, 1376, 1308, 1232,
1196, 1161, 1122, 1011. Anal. Calcd for C14H18O2: C, 77.03; H, 8.31.
Found: C, 77.03; H, 8.53.
4.2.14. Ethyl 2-methyl-3-phenyl-3(E)-octenoate (E-2n). The re-
action of CuCl (2.0 mg, 0.02 mmol, 5 mol %), 1i (73.0 mg, 0.4 mmol),
toluene (5 mL), and a solution of phenyl magnesium chloride in THF
(0.67 mL, 1.8 M, 1.2 mmol, 3 equiv) afforded E-2n5b (96.3 mg, 92%):
liquid; 1H NMR (300 MHz, CDCl3)
d 7.30e7.18 (m, 5H, AreH), 5.64 (t,
J¼7.4 Hz, 1H, ]CH), 4.16e4.06 (m, 2H, OCH2), 3.80 (q, J¼7.2 Hz, 1H,
CH), 2.32e2.13 (m, 2H, CH2), 1.52e1.34 (m, 4H, 2ꢂCH2), 1.29 (d,
J¼7.2 Hz, 3H, CH3), 1.15 (t, J¼7.1 Hz, 3H, CH3), 0.93 (t, J¼7.1 Hz, 3H,
CH3).
4.2.9. Ethyl 2-methyl-3-(iso-propyl)-4-phenyl-3(Z)-butenoate (Z-
2i). The reaction of CuCl (2.0 mg, 0.02 mmol, 5 mol %), 1a (79.6 mg,
0.4 mmol), toluene (5 mL), and a solution of i-PrMgCl in THF
(0.6 mL, 2 M, 1.2 mmol, 3 equiv) afforded Z-2i (89.1 mg, 92%, Z-2i/
3i¼96:4): liquid; 1H NMR (300 MHz, CDCl3)
d
7.35e7.18 (m, 5H,
4.2.15. Ethyl 3-phenyl-3(E)-undecenoate (E-2o). The reaction of
CuCl (1.0 mg, 0.01 mmol, 5 mol %), 1j (43.5 mg, 0.2 mmol), toluene
(2.5 mL), and a solution of phenyl magnesium chloride in THF
(0.38 mL, 1.6 M, 0.6 mmol, 3 equiv) afforded E-2o5a (49.2 mg, 85%):
AreH), 6.50 (s, 1H, ]CH), 4.17e4.09 (m, 2H, OCH2), 3.85 (q,
J¼6.9 Hz, 1H, CHH), 2.41 (hept, J¼6.9 Hz, 1H, CH), 1.28e1.23 (m, 6H,
2ꢂCH3), 1.17 (d, J¼6.9 Hz, 3H, CH3), 1.11 (d, J¼7.0 Hz, 3H, CH3); 13C
NMR (75 MHz, CDCl3)
d
174.5, 148.1, 138.0, 128.7, 128.1, 126.3, 125.2,
liquid; 1H NMR (300 MHz, CDCl3)
d 7.39e7.35 (m, 2H, AreH),
60.5, 41.3, 29.7, 24.9, 24.2, 15.7, 14.2; MS (EI) m/z (%) 247 (Mþþ1,
3.59), 246 (Mþ, 18.47), 145 (100); IR (neat, cmꢀ1) 3059, 3024, 2963,
2935, 2872, 1732, 1643, 1599, 1494, 1462, 1444, 1377, 1323, 1236,
1186, 1092, 1057, 1028; HRMS calcd for C16H22O2 (Mþ): 246.1620;
found: 246.1623.
7.32e7.25 (m, 2H, AreH), 7.23e7.18 (m, 1H, AreH), 5.94 (t, J¼7.4 Hz,
1H, ]CH), 4.09 (q, J¼7.1 Hz, 2H, CO2CH2), 3.50 (s, 2H, CH2CO), 2.21
(q, J¼7.4 Hz, 2H, CH2), 1.52e1.42 (m, 2H, CH2), 1.39e1.23 (m, 8H,
4ꢂCH2), 1.18 (t, J¼7.2 Hz, 3H, CH3), 0.89 (t, J¼6.8 Hz, 3H, CH3).
4.2.16. Ethyl
4-(p-chlorophenyl)-2-methyl-3-vinyl-3(Z)-butenoate
4.2.10. Ethyl 3-(cyclo-hexyl)-2-methyl-4-phenyl-3(Z)-butenoate (Z-
2j). The reaction of CuCl (2.2 mg, 0.022 mmol, 5.5 mol %), 1a
(81.8 mg, 0.4 mmol), toluene (5 mL), and a solution of c-HexMgCl in
THF (0.9 mL, 1.3 M, 1.2 mmol, 3 equiv) afforded Z-2j5a (105.9 mg,
(Z-2p). The reaction of CuCl (2.0 mg, 0.02 mmol, 5 mol %), 1d
(95.0 mg, 0.4 mmol), toluene (5 mL), and a solution of vinyl mag-
nesium bromide in THF (1.8 mL, 0.7 M, 1.2 mmol, 3 equiv) afforded
Z-2p5b (92.4 mg, 87%): liquid; 1H NMR (300 MHz, CDCl3)
91%, Z-2j/3j¼95:5): liquid; 1H NMR (300 MHz, CDCl3)
d
7.36e7.19
d 7.34e7.31 (m, 2H, AreH), 7.27e7.24 (m, 2H, AreH), 6.64 (s, 1H, ]
(m, 5H, AreH), 6.46 (s, 1H, ]CH), 4.21e4.07 (m, 2H, OCH2), 3.84 (q,
J¼7.0 Hz, 1H, CH), 2.05e1.92 (m, 1H, CH), 1.79e1.62 (m, 5H, five
protons of cyclo-hexyl), 1.36e1.18 (m, 11H, five protons of cyclo-
hexylþ2ꢂCH3).
CH), 6.31 (dd, J1¼17.7 Hz, J2¼11.2 Hz, 1H, ]CH), 5.34 (d, J¼17.7 Hz,
1H, ]CH), 5.14 (d, J¼11.2 Hz, 1H, ]CH), 4.19e4.10 (m, 2H, OCH2),
3.86 (q, J¼7.2 Hz, 1H, CH), 1.36 (d, J¼7.2 Hz, 3H, CH3), 1.23 (t,
J¼7.2 Hz, 3H, CH3).
4.2.11. Ethyl 3-(tert-butyl)-2-methyl-4-phenyl-3(E)-butenoate (E-
2k). The reaction of CuCl (2.0 mg, 0.02 mmol, 5 mol %), 1a (81.4 mg,
0.4 mmol), toluene (5 mL), and a solution of t-BuMgCl in THF
(1.2 mL, 1 M, 1.2 mmol, 3 equiv) afforded E-2k5b (90.7 mg, 87%):
4.2.17. Ethyl 2-methyl-3-vinyl-3(Z)-octenoate (Z-2q). The reaction
of CuCl (2.0 mg, 0.02 mmol, 5 mol %), 1i (71.0 mg, 0.4 mmol), tolu-
ene (5 mL), and a solution of vinyl magnesium bromide in THF
(1.8 mL, 0.7 M, 1.2 mmol, 3 equiv) afforded Z-2q5b (65.7 mg, 80%)
(eluent: petroleum ether (bp¼30e60 ꢁC)/diethyl ether¼50:1): liq-
liquid; 1H NMR (300 MHz, CDCl3)
d 7.30e7.25 (m, 2H, AreH),
7.21e7.16 (m,1H, AreH), 7.14e7.11 (m, 2H, AreH), 6.56 (s,1H, ]CH),
4.10e3.87 (m, 2H, OCH2), 3.44 (q, J¼7.3 Hz, 1H, CH), 1.24e1.15 (m,
15H, 5ꢂCH3).
uid; 1H NMR (300 MHz, CDCl3)
d
6.20 (dd, J1¼17.7 Hz, J2¼11.1 Hz,
1H, ]CH), 5.60 (t, J¼7.4 Hz, 1H, ]CH), 5.11 (d, J¼17.7 Hz, 1H, ]CH),
4.92 (d, J¼11.1 Hz, 1H, ]CH), 4.13 (q, J¼7.2 Hz, 2H, OCH2), 3.62 (q,
J¼7.2 Hz, 1H, CH), 2.20e2.03 (m, 2H, CH2), 1.45e1.30 (m, 7H,
2ꢂCH2þCH3), 1.22 (t, J¼7.1 Hz, 3H, CH3), 0.91 (t, J¼7.1 Hz, 3H, CH3).
4.2.12. Ethyl 2-allyl-3,4-diphenyl-3(E)-butenoate (E-2l). The re-
action of CuCl (1.9 mg, 0.019 mmol, 4.8 mol %), 1b (91.1 mg,
0.4 mmol), toluene (5 mL), and a solution of phenyl magnesium
chloride in THF (0.76 mL, 1.6 M, 1.2 mmol, 3 equiv) afforded E-2l
(114.1 mg, 93%, E-2l/3l¼96:4): liquid; 1H NMR (300 MHz, CDCl3)
4.3. Stereocontrollable reactions of the dienolate
intermediate Z-4 with different electrophiles
d
7.44e7.24 (m, 10H, AreH), 6.85 (s, 1H, ]CH), 5.65e5.52 (m, 1H, ]
4.3.1. Addition reaction of acetone with the organometallic in-
termediate Z-4. 4.3.1.1. Synthesis of ethyl 2-(10-hydroxyl-10-methyl-
ethyl)-2,3-dimethyl-4-phenyl-3(Z)-butenoate (Z-5). The reaction of
CuCl (2.0 mg, 0.02 mmol, 5 mol %), 1a (0.0810 g, 0.4 mmol), and
toluene (5 mL) with a solution of CH3MgCl in THF (0.4 mL, 3 M,
1.2 mmol, 3 equiv) formed the solution at ꢀ78 ꢁC after 1.5 h. To this
solution was slowly added acetone (0.15 mL, d¼0.79 g/mL, 0.1185 g,
2 mmol, 5 equiv) at ꢀ78 ꢁC. After 2.5 h as monitored by TLC, the
reaction mixture was quenched slowly with a saturated aqueous
solution of NH4Cl (2 mL) at ꢀ78 ꢁC followed by warming up to rt
naturally. After extraction with diethyl ether (3ꢂ15 mL), the organic
layer was washed subsequently with diluted HCl (5%, aqueous),
a saturated aqueous solution of NaHCO3, brine, and dried over
anhydrous Na2SO4. Evaporation and column chromatography on
silica gel (eluent: hexane/ethyl acetate¼30:1) afforded Z-5
CH), 4.92e4.82 (m, 2H, 2ꢂ¼CH), 4.20 (q, J¼7.2 Hz, 2H, OCH2), 4.03
(dd, J1¼8.7 Hz, J2¼6.3 Hz, 1H, CH), 2.68e2.59 (m, 1H, one proton of
CH2), 2.30e2.19 (m, 1H, one proton of CH2), 1.25 (t, J¼7.1 Hz, 3H,
CH3); 13C NMR (75 MHz, CDCl3)
d 173.3, 140.8, 139.6, 137.3, 135.4,
132.9, 128.8, 128.3, 128.1, 127.8, 127.3, 127.0, 116.4, 60.9, 45.9, 33.9,
14.1; MS (EI) m/z (%) 307 (Mþþ1, 3.43), 306 (Mþ, 14.06), 191 (100);
IR (neat, cmꢀ1) 3057, 2980, 1729, 1641, 1600, 1495, 1445, 1367, 1254,
1187, 1116, 1074, 1030. Anal. Calcd for C21H22O2: C, 82.32; H, 7.24.
Found: C, 82.52; H, 7.28.
4.2.13. Ethyl
4-(p-methoxyphenyl)-2-methyl-3-phenyl-3(E)-bute-
noate (E-2m). The reaction of CuCl (2.0 mg, 0.02 mmol, 5 mol %), 1g
(92.6 mg, 0.4 mmol), toluene (5 mL), and a solution of phenyl
magnesium chloride in THF (0.67 mL, 1.8 M, 1.2 mmol, 3 equiv)
afforded E-2m5b (105.8 mg, 86%) (eluent: petroleum ether/ethyl
(76.0 mg, 69%): liquid; 1H NMR (300 MHz, CDCl3)
5H, AreH), 6.65 (s, 1H, ]CH), 4.07 (br, 1H, OH), 3.94e3.74 (m, 2H,
d 7.30e7.15 (m,
acetate¼60:1): liquid; 1H NMR (300 MHz, CDCl3)
d 7.37e7.23 (m,

2724
J. He et al. / Tetrahedron 68 (2012) 2719e2724
CH2), 2.04 (d, J¼1.8 Hz, 3H, CH3), 1.31 (s, 3H, CH3), 1.26 (s, 3H, CH3),
1.20 (t, J¼7.2 Hz, 3H, CH3), 1.15 (s, 3H, CH3); 13C NMR (75 MHz,
4.3.4. Coupling reaction of allyl acetate with the organometallic in-
termediate Z-4. 4.3.4.1. Synthesis of ethyl 2,3-dimethyl-2-
methylcarbonyl-4-phenyl-3(E)-butenoate (E-8). The reaction of
CuCl (2.0 mg, 0.02 mmol, 5 mol %), 1a (0.0798 g, 0.4 mmol), and
toluene (5 mL) with a solution of CH3MgCl in THF (0.4 mL, 3 M,
1.2 mmol, 3 equiv) formed the solution at ꢀ78 ꢁC after 1.5 h. To this
solution was added allyl acetate (0.22 mL, d¼0.93 g/mL, 0.2046 g,
2 mmol, 5 equiv) at ꢀ78 ꢁC. After 16 h as monitored by TLC, the
reaction mixture was sequentially quenched with a saturated
aqueous solution of NH4Cl (2 mL) at 0 ꢁC. After extraction with
diethyl ether (3ꢂ15 mL), the organic layer was washed sub-
sequently with diluted HCl (5%, aqueous), a saturated aqueous so-
lution of NaHCO3, brine, and dried over anhydrous Na2SO4.
Evaporation and column chromatography on silica gel (eluent:
petroleum ether/ethyl acetate¼100:1 to 30:1) afforded E-86
CDCl3)
d 176.5, 139.3, 136.8, 130.3, 128.9, 127.3, 126.1, 74.9, 60.6,
58.54, 27.8, 26.5, 26.1, 22.5, 13.8; MS (EI) m/z (%) 277 ((MþþH), 2.10),
259 (MþþHꢀ18, 15.97), 185 (Mþꢀ91, 100); IR (neat, cmꢀ1) 3523,
2983, 2928, 1709, 1462, 1388, 1249, 1173, 1101, 1023. Anal. Calcd for
C17H24O3: C, 73.88; H, 8.75. Found: C, 73.96; H, 8.93.
4.3.2. Coupling reaction of methyl p-toluenesulfonate with the or-
ganometallic intermediate Z-4. 4.3.2.1. Synthesis of ethyl 2,2,3-
trimethyl-4-phenyl-3(E)-butenoate (E-6). The reaction of CuCl
(2.0 mg, 0.02 mmol, 5 mol %), 1a (0.0802 g, 0.4 mmol), and toluene
(5 mL) with a solution of CH3MgCl in THF (0.4 mL, 3 M, 1.2 mmol,
3 equiv) formed the solution at ꢀ78 ꢁC after 1.8 h. To this solution
was added methyl p-toluenesulfonate (0.3726 g, 2 mmol, 5 equiv)
at ꢀ78 ꢁC followed by warming up to rt naturally after 1 h. After
16 h as monitored by TLC, the reaction mixture was sequentially
quenched with a saturated aqueous solution of NH4Cl (2 mL) at
0 ꢁC. After extraction with diethyl ether (3ꢂ15 mL), the organic
layer was washed as usual and dried over anhydrous Na2SO4.
Evaporation and column chromatography on silica gel (eluent:
petroleum ether/ethyl acetate¼100:1) afforded E-6 ((61.4 mg
(pure) and 10.7 mg (mixture of E-6 and E-2a, molar ratio by NMR:
82:18, content of E-6: 83% by weight), combined yield: 76%: liquid;
(50.6 mg, 49%): liquid; 1H NMR (300 MHz, CDCl3)
d 7.38e7.32 (m,
2H, AreH), 7.27e7.22 (m, 3H, AreH), 6.40 (s, 1H, ]CH), 4.26 (q,
J¼7.0 Hz, 2H, OCH2), 2.29 (s, 3H, CH3), 1.87 (d, J¼1.2 Hz, 3H, CH3),
1.61 (s, 3H, CH3), 1.31 (t, J¼7.1 Hz, 3H, CH3); 13C NMR (CDCl3,
75 MHz)
d 205.6, 171.9, 137.2, 136.1, 129.0, 128.6, 128.1, 126.8, 67.1,
61.4, 27.2, 19.7, 16.4, 14.0.
Acknowledgements
1H NMR (300 MHz, CDCl3)
d 7.35e7.30 (m, 2H, AreH), 7.25e7.17 (m,
We greatly acknowledge the financial support from the National
Basic Research Program of China (2011CB808700) and the National
Natural Science Foundation of China (20732005). S.M. is a Qiu Shi
Adjunct Professor at Zhejiang University. We thank Mr. Y. Liu in this
group for reproducing the results presented in entries 6, 9, and 12
in Table 2 and E-6 in Scheme 1.
3H, AreH), 6.43 (s, 1H, ]CH), 4.15 (q, J¼7.1 Hz, 2H, OCH2), 1.81 (d,
J¼1.2 Hz, 3H, CH3), 1.41 (s, 6H, 2ꢂCH3), 1.24 (t, J¼6.9 Hz, 3H, CH3);
13C NMR (75 MHz, CDCl3)
d 176.7, 140.8, 138.2, 129.0, 127.9, 126.1,
124.0, 60.6, 48.9, 24.6, 15.5, 14.1; MS (EI) m/z (%) 233 (Mþþ1, 4.83),
232 (Mþ, 28.85), 159 (100); IR (neat, cmꢀ1) 2980, 1730, 1645, 1600,
1446, 1382, 1253, 1144, 1107, 1028; HRMS calcd for C15H20O2 (Mþ):
232.1463; found: 232.1470.
Supplementary data
4.3.3. Coupling reaction of benzyl bromide with the organometallic
intermediate Z-4. 4.3.3.1. Synthesis of ethyl 2-benzyl-2,3-dimethyl-
4-phenyl-3(E)-butenoate (E-7). The reaction of CuCl (2.1 mg,
0.021 mmol, 5.2 mol %), 1a (0.0820 g, 0.4 mmol), and toluene
(5 mL) with a solution of CH3MgCl in THF (0.4 mL, 3 M, 1.2 mmol,
3 equiv) formed the solution at ꢀ78 ꢁC after 1.5 h. To this solution
was added benzyl bromide (0.24 mL, d¼1.44 g/mL, 0.3456 g,
2 mmol, 5 equiv) at ꢀ78 ꢁC followed by warming up to rt naturally
after 0.5 h. After 15 h as monitored by TLC, the reaction mixture was
sequentially quenched with a saturated aqueous solution of NH4Cl
(2 mL). After extraction with diethyl ether (3ꢂ15 mL), the organic
layer was washed subsequently with diluted HCl (5%, aqueous),
a saturated aqueous solution of NaHCO3, brine, and dried over
anhydrous Na2SO4. Evaporation and column chromatography on
silica gel (eluent: petroleum ether/ethyl acetate¼100:1) afforded E-
7 (83.8 mg (mixture of E-7 and E-2a, molar ratio by NMR: 94:6),
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2012.01.027.
References and notes
1. Perlmutter, P. Conjugate Addition Reactions in Organic Synthesis; Pergamon: Ox-
ford, 1992.
2. Krause, N. Modern Organocopper Chemistry; Wiley-VCH: Weinheim, 2002.
3. For some representative examples, see: (a) Mueller, A. J.; Jennings, M. P. Org. Lett.
2007, 9, 5327; (b) Bausch, C. C.; Johnson, J. S. J. Org. Chem. 2008, 73, 1575; (c)
Chea, H.; Sim, H.-S.; Yun, J. Adv. Synth. Catal. 2009, 351, 855; (d) Gao, M.; Thorpe,
S. B.; Santos, W. L. Org. Lett. 2009, 11, 3478; (e) Hendrix, A. J. M.; Jennings, M. P.
Org. Lett. 2010, 12, 2750; (f) Tobisu, M.; Fujihara, H.; Koh, K.; Chatani, N. J. Org.
Chem. 2010, 75, 4841; For some recent copper-catalyzed asymmetric Michael
additions, see: (g) Wang, S.-Y.; Song, P.; Loh, T.-P. Adv. Synth. Catal. 2010, 352,
3185; (h) Palais, L.; Babel, L.; Quintard, A.; Belot, S.; Alexakis, A. Org. Lett. 2010, 12,
1988; (i) Rudolph, A.; Bos, P. H.; Meetsma, A.; Minnaard, A. J.; Feringa, B. L.
Angew. Chem., Int. Ed. 2011, 50, 5834.
4. (a) Berlan, J.; Battiono, J.-P.; Koosha, K. Bull. Soc. Chim. Fr. II 1979, 3e4, 183; (b)
Knight, J. G.; Ainge, S. W.; Bater, C. A.; Eastman, T. P.; Harwood, S. J. J. Chem. Soc.,
Perkin Trans. 1 2000, 3188; (c) Bryson, T. A.; Smith, D. C.; Krueger, S. A. Tetra-
hedron Lett. 1977, 18, 525; (d) Waizumi, N.; Itoh, T.; Fukuyama, T. Tetrahedron Lett.
1998, 39, 6015; (e) Dieter, R. K.; Lu, K. Tetrahedron Lett. 1999, 40, 4011; (f) Dieter,
R. K.; Lu, K.; Velu, S. E. J. Org. Chem. 2000, 65, 8715.
5. (a) Lu, Z.; Chai, G.; Ma, S. J. Am. Chem. Soc. 2007, 129, 14546; (b) Chai, G.; Lu, Z.; Fu,
C.; Ma, S. Adv. Synth. Catal. 2009, 351, 1946.
6. Lu, Z.; Chai, G.; Zhang, X.; Ma, S. Org. Lett. 2008, 10, 3517.
7. When the reaction of 1a with CH3MgCl under standard conditions was quenched
at 0 ꢁC instead of ꢀ78 ꢁC, the Z/E ratio dropped to 96:4 (entry 18, Table 1), which
clearly supports the hypothesis of isomerization from 1,3-(Z)-dienoate Z-4 to 1,3-
(E)-dienoate E-4 at higher temperature. See also Ref. 6.
64%): liquid; 1H NMR (300 MHz, CDCl3)
d 7.34e7.29 (m, 2H, AreH),
7.27e7.16 (m, 6H, AreH), 7.12e7.09 (m, 2H, AreH), 6.20 (s, 1H, ]
CH), 4.18 (q, J¼7.1 Hz, 2H, OCH2), 3.21 (d, 1H, J¼13.2 Hz, one proton
of CH2), 3.10 (d, 1H, J¼13.2 Hz, one proton of CH2), 1.86 (s, 3H, CH3),
1.30e1.24 (m, 6H, 2ꢂCH3); 13C NMR (75 MHz, CDCl3)
d 175.8, 138.7,
138.1, 137.6, 130.6, 128.9, 128.0, 127.7, 126.3, 126.2, 126.1, 60.7, 53.4,
41.8, 21.3, 16.0, 14.1; MS (ESI) m/z (%) 309 ((MþH)þ, 100); IR (neat,
cmꢀ1) 3059, 3027, 2980, 2936, 1728, 1601, 1494, 1453, 1375, 1232,
1100, 1025; HRMS calcd for C21H24O2Naþ (MþNaþ): 331.1669;
found: 331.1664.