Synthesis of 3-methyl-2-cyclohexenones catalyzed by mercury(II) salts and their microwave assisted BiCl3 catalyzed aldol condensations

Article abstract of DOI:10.1016/j.jorganchem.2010.08.037

HgSO₄ catalyzed hydrative cyclization of 1,6-heptadiynes is present. This reaction proceeded smoothly under the mild condition for differently 4-sustituted 1,6-diynic substrates giving corresponding 3-methyl-2-cyclohexenones with high to excell

Full text of DOI:10.1016/j.jorganchem.2010.08.037

Journal of Organometallic Chemistry 696 (2011) 165e169
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Synthesis of 3-methyl-2-cyclohexenones catalyzed by mercury(II) salts and their
microwave assisted BiCl3 catalyzed aldol condensations
,
a
a
a
b
Chen Zhang a , Bi-Song Wang , Shi-Feng Chen , Shao-Qiao Zhang , Dong-Mei Cui
*
a College of Pharmaceutical Science, Zhejiang University, Hangzhou 310058, PR China
b College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
HgSO4 catalyzed hydrative cyclization of 1,6-heptadiynes is present. This reaction proceeded smoothly
under the mild condition for differently 4-sustituted 1,6-diynic substrates giving corresponding
3-methyl-2-cyclohexenones with high to excellent yield. The microwave assisted aldol condensation of
cyclohexenones under the catalysis of BiCl3 afforded 3-styryl-cyclohexenones with high regio- and
stereo-selectivity.
Received 4 August 2010
Received in revised form
23 August 2010
Accepted 24 August 2010
Available online 1 October 2010
Ó 2010 Elsevier B.V. All rights reserved.
Keywords:
3-Methyl-2-cyclohexenones
Mercury(II) salts
BiCl3
Microwave
Lewis acid
Aldol condensation
1. Introduction
we wish to report the hydrative cyclization of 1,6-diynes in the
presence of HgSO4 and the subsequent of BiCl3 catalyzed aldol
The cyclohexenone derivatives are the starting materials and
intermediates in many important natural products and synthetic
drug syntheses [1]. Many synthetic methods for the construction of
the conjugate cyclohexenone ring have been reported [2]. We have
recently developed hydrative cyclization of 1,6-diynes to produce
3,5-substituted conjugate cyclohexenone ring systems using Au(I)
or Pt(II) as a catalyst [3]. On the other hand, the aldol condensation
is a very classic method for the formation of carbonecarbon bond.
This reaction is important for the synthesis of natural products and
other potentially biologically relevant substances. Control of the
mixed aldol condensation between two different carbonyl
compounds which present several possible sites for enolization is
condensation of the corresponding cyclohexenone derivatives with
aldehydes.
2. Results and discussion
2.1. Mercury(II) salts catalyzed hydrative cyclization of 1,6-
heptadiynes
Our initial studies focused on testing the feasibilities for the
hydrative cyclization of 4,4-di(isopropanoloxycarbonyl)-1,6-hep-
tadiyne (1a), catalyzed by mercury(II) salts (Table 1). The expected
compound 2a was isolated with 71% yield (entry 1) at 70 ꢀC for 3 h
from reaction of 1a with H2O (1000 mol%) using HgSO4 (20 mol%) as
the catalyst and trifluoromethanesulfonate (30 mol%) as the co-
catalyst. To decrease the amount of catalyst (HgSO4) to 5 mol% was
ineffective to this reaction (entry 2), but yield of 2a was reduced to
57% when the amount of HgSO4 was reduced to 1 mol%. We test the
effectives of the amount of H2O, and found that a decrease in the
amount of H2O to 150 mol% should increase formation of 2a (yield
81%, entry 4). However, formation of 2a was decreased to 44% or
23% yield when the solvent had been changed to EtOH or reduced
the amount of additive of trifluoromethanesulfonic acid to 10 mol%
a challenging problem for synthetic chemists [4]. For
a,b-unsatu-
rated ketones, however, not only -position but also ’-position are
g
a
capable of being deprotonated to form alkylation products. In the
literature, Yamamoto and co-workers reported the directed aldol
condensation of
a, b-unsaturated cyclohexenones with aldehydes
to generate -alkylation products by LDA, but this type conden-
g
sation by Lewis acid has not been reported previously [5]. Herein,
* Corresponding author. Tel./fax: þ86 571 88208449.
E-mail address: chenzhang@zju.edu.cn (C. Zhang).
0022-328X/$ e see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2010.08.037

166
C. Zhang et al. / Journal of Organometallic Chemistry 696 (2011) 165e169
Table 1
Hg(II) salt catalized hydrative cyclization of 1a.
O
[Hg2+]/Additive
Solvent
i-PrO2C
i-PrO2C
H2O
+
i-PrO2C
i-PrO2C
1
a
2a
Entry
Cat. (mol%)
H2O (mol%)
Additive (mol%)
Solvent
Temp. (ꢀC)
Time (h)
Conv. (%)
Yield of 2 (%)b
1
2
3
4
5
6
7
8
HgSO4 (20)
HgSO4 (5)
HgSO4 (1)
HgSO4 (5)
HgSO4 (5)
HgSO4 (5)
Hg(OAc)2 (20)
Hg(OAc)2 (5)
Hg(OAc)2 (5)
Hg(OAc)2 (5)
HgCl2 (20)
HgCl2 (5)
1000
1000
1000
150
150
150
1000
1000
150
150
1000
150
CF3SO3H (30)
CF3SO3H (30)
CF3SO3H (30)
CF3SO3H (30)
CF3SO3H (30)
CF3SO3H (10)
CF3SO3H (30)
CF3SO3H (30)
CF3SO3H (30)
CF3SO3H (30)
CF3SO3H (30)
CF3SO3H (30)
CF3SO3H (30)
CF3SO3H (30)
MeOH
MeOH
MeOH
MeOH
EtOH
MeOH
MeOH
MeOH
MeOH
EtOH
70
70
70
70
70
70
70
70
70
70
70
70
100
rt
3
3
3
3
3
3
3
3
3
3
3
3
3
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
w5
71
71
57
81
44
23
68
69
71
50
70
17
46
trace
9
10
11
12
13
14
MeOH
MeOH
MeOH
MeOH
HgSO4 (5)
HgSO4 (5)
150
150
10
aThese reaction were carried out at 70 ꢀC in MeOH (2 mL) for 3 h.
b
Isolated yield.
(entries 5 and 6). Non obvious changes of yield of 2a were observed
when mercury(II) acetate was used as catalyst to the same reaction
compared with mercury(II) sulfate, even though the amount
reduced to 5 mol% (entry 7 and 8), 2a was generated with 71% yield
when the amount of H2O was reduced to 150 mol% (entry 9),
changed solvent to ethanol induced to decrease formation of 2a
(entry 10). When mercury(II) dichloride (20 mol%) was used for this
reaction, 2a was isolated with 70% yield (entry 11). We also test the
same reaction by adding H2O with 150 mol%, 2a was obtained with
17% yield (entry 12). According to the results, we fixed the condi-
tions (entry 4) for investigating the scope of mercury(II) sulfonate
catalyzed hydrative cyclization of 1,6-heptadiynes.
Having reaction conditions being established, various 1,6-diynes
were subjected to the reaction with water in order to investigate the
reaction scope and several represent active results are summarized
in Table 2. 5,5-Dimethoxycarbonyl and 5,5-diethoxycarbonyl
substituted 3-methyl-2-hexenones (2b and 2c) were obtained with
highyield (Table 2, entries 2 and 3). Various 4-substituted 1,6-diynes
wereinvestigated, and the hydrative cyclizationproceeded in mostly
good efficiencies. The 5,5-di(alkoxycarbonyl)-substituted cyclohex-
2-enones (2d and 2e) were isolated with high yields (entries 4 and
5). The cyclic products with different substituent group pairs, such as
diphenylphosphoryl and ethoxycarbonyl (2f), or phenyl and
methoxycarbonyl (2h), or with single ethoxycarbonyl substituented
(2i) were obtained with excellent yield respectively (entries 6, 8 and
9). From reaction of 1g, compound 2h was also obtained with 11%
yield which was formed from 2g via esterification of nitrile group
(entry 7). Only 2b was isolated with 45% yield from the reaction of 1j.
PPh3AuNO3, CuCN, orHgClasthecatalyst; however, thecondensation
product 4a was formed in very low yield (entries 1e7, Table 3). When
we used the BiCl3 (10 mol%) as the catalyst, the yield of 4a improved
significantly (entries 8e13, Table 3). The best result was obtained by
conductingthereactionin150ꢀCfor1 h affording4ain91%yield with
perfect oxo-regioselectivity and high E-selectivity (entry 8, Table 3).
It is remarkable to note that the reaction proceeded extremely well
in the absence of any solvent (entries 14e16). To further assess the
scope of this process, we have examined the aldol condensation of
several cyclohexenones with aldehydes under the optimized reaction
conditions in entry 8 of Table 3. The cyclohexenone with substituted
group pairs, such as dimethoxycarbonyl 2b is well tolerated, the
corresponding adducts being formed in 50% (entry 3, Table 4).
Various aldehydes were then examined, not only benzaldehyde but
also electron-donating groups on benzene ring of benzaldehydes
gave good isolated yields of the corresponding adducts (entries 2e5).
In all cases, adducts were obtained with high selectivity.
3. Conclusion
In conclusion, we have described a useful process of mercury(II)
salts-catalyzed hydrative cyclization of 1,6-heptadiyne to provide
3-methyl-5-substituted-2-derivatives, advantages of the present
method are the easily accessible starting materials, mild conditions,
lack of coproducts and the fact that several types of functional
groups were tolerated. We also have developed a directed micro-
wave associated aldol condensation of the corresponding 3-methyl-
5-substituted-2-hexenone derivatives with aromatic aldehydes
catalyzed by BiCl3 with perfect regioselectivity and high E-selectivity.
2.2. Microwave assisted BiCl3 catalyzed aldol condensation of
cyclohexenones with aldehydes
4. Experemental
Microwave dielectric heating causes an extremely rapid and
uniform energy transfer to the reactants of chemical reactions. This
will minimize by-product formation and increase product yields.
Next we studied an improved, microwave assisted aldol condensa-
tion of methyl 3-mehyl-5-oxo-1-phenylcyclohex-3-ene-1-carbox-
ylate (2h) with 2,3-dimethoxy (3a) (Table 3). Our initial experiments
were conducted using Hg(OTf)2, Bi(NO3)3$5H2O, Fe(OTf)2, PPh3AuCl3,
4.1. General
Under otherwise noted, materials were obtained from comm-
ercial suppliers and used without further purification. Diynes were
prepared by the procedures in the literature. Thin layer chroma-
tography (TLC) was performed using silica gel 60 F254 and visualized
using UV light. Column chromatography was performed with silica

C. Zhang et al. / Journal of Organometallic Chemistry 696 (2011) 165e169
Table 2 (continued)
167
Table 2
Mercury(II) sulfate catalyzed hydrative cyclization of 4-substituted 1,6-
Entry
Diynes 1
Product 2
Yield (%)b
heptadiynes.a
O
O
R1
R2
HgCl2 / CF3SO3H
MeOH, 70 °C, 3h
H2O
R1
R2
+
EtO2C
9
90
45
CO2Et
1
2
1i
2i
2j
O
Entry
Diynes 1
Product 2
Yield (%)b
HO2C
O
10
CO2Me
CO2Me
HO2C
i-PrO2C
i-PrO2C
1j
1
81
CO2i-Pr
CO2i-Pr
a
1a
All the reactions were performed with 1 (0.5 mmol), H2O (0.75 mmol), and
catalyst (HgSO4, 5 mol%) refluxed at 70 ꢀC in MeOH (2 mL).
2a
2b
2c
2d
2e
2f
b
Isolated yields after column chromatography.
Compound 2h was obtained with 11% yield as by-product.
O
c
MeO2C
2
3
4
5
6
7
8
80
78
82
83
85
33c
91
gel (mesh 300e400).1H NMR and 13C NMR spectrawere recorded on
a Bruker Avance 400 MHz or 500 MHz spectrometer in CDCl3 with
Me4Si as an internal standard. Data are reported as follows: chemical
CO2Me
CO2Me
MeO2C
1b
shifts in ppm (
d
), multiplicity (s ¼ singlet, d ¼ doublet, t ¼ triplet,
O
q ¼ quartet, br ¼ broad and m ¼ multiplet), coupling constant (Hz)
and integration. Infrared spectra (IR) were obtained on a 370 FT-IR
spectrometer; absorptions are reported in cmꢁ1. Mass spectra (MS)
and high resolution mass spectra (HRMS) were obtained at the
Zhejiang University of Technology Mass Spectrometry Facility.
EtO2C
CO2Et
CO2Et
EtO2C
1c
O
4.2. General procedure for the hydrative cyclization of diynes
MeO
To a reactor containing diyne (0.5 mmol), methanol (2 mL), and
H2O (150 mol%) under nitrogen HgSO4 (5 mol%) and TfOH (30 mo%
l) were added. The resulting yellow solution was then sealed and
OMe
OMe
MeO
1d
O
O
Table 3
BzO
Lewis acid catalyzed aldol condensation of 2h with 3a.a
O
OBz
OBz
BzO
O
CHO
OMe
OMe
OMe
LA, MV
Ph
CO2Me
1e
MeO
+
Ph
CO2Me
O
2h
3a
4a
(Ph)2P
O
.
P(Ph)2
CO2Et
EtO2C
Entry
Cat. (mol%)
Hg(SO3CF3)2
Bi(NO3)3$5H2O
PPh3AuCl3
PPh3AuNO3
CuCN
Fe(SO3CF3)2
HgCl
BiCl3
BiCl3
BiCl3
BiCl3
BiCl3
BiCl3
BiCl3
BiCl3
BiCl3
Solvent
Temp.
Time
(h)
Yield of
(ꢀC)
4a (%)b
1f
1
2
3
4
5
6
7
8
e
150
150
150
150
150
150
150
150
150
150
200
100
100
150
150
150
1
1
1
1
1
1
1
1
2
3
1
1
3
3
3
3
14
O
e
trace
trace
trace
trace
11
trace
91
82
32
55
27
33
Ph
e
e
e
Ph
CN
NC
e
e
1g
e
2g
2h
9
e
O
10
11
12
13
14
15
16
e
Ph
e
e
Ph
e
MeO2C
THF
DME
MeCN
trace
trace
trace
CO2Me
1h
a
All the reactions were performed with 2h (0.14 mmol), 3a (0.56 mmol), and
catalyst (10 mol%).
b
Isolated yields after column chromatography.

168
C. Zhang et al. / Journal of Organometallic Chemistry 696 (2011) 165e169
Table 4
The condensation reaction of 3-methyl-2-cyclohexenones with aromatic benzaldehydea:
O
O
O
BiCl3
R1
R2
R1
R2
+
Ar
H
Mw, 150°C, 1 h
Ar
2
3
4
.
Entry
Cyclohexenone
Aldehyde
Product
Yieldb (Z/E)c
O
O
CHO
OMe
OMe
OMe
Ph
Ph
MeO
1
91 (100:6)
CO2Me
CO2Me
3a
2h
4a
O
O
O
CHO
Ph
CO2Me
Ph
2
66 (100:5)
CO2Me
3b
2h
4b
O
O
O
CHO
OMe
CO2Me
CO2Me
CO2Me
MeO
3
50 (100:3)
CO2Me
OMe
MeO
2b
3c
4c
CHO
O
O
Ph
Ph
4
51 (100:0)
CO2Me
CO2Me
OMe
MeO
2h
3d
4d
CHO
OMe
Ph
MeO
MeO
Ph
CO2Me
5
37 (100:0)
MeO
OMe
CO2Me
OMe
3e
2h
4e
a
All the reactions were performed with 2 (0.14 mmol), 3 (0.56 mmol), and catalyst (10 mol%).
Isolated yields after column chromatography.
b
c
Determined by 1H NMR analysis.
stirred at 70 ꢀC for 3e10 h until the starting diyne was consumed, as
judged by TLC. The mixture was quenched with a saturated solution
of NaHCO3 and then extracted with ethyl acetate (20 mL ꢂ 3). The
organic layer was washed with brine, dried over Na2SO4 and
concentrated in vacuo. The residue was purified by column chro-
matography (silica gel) (Eluent: hexane/ethyl acetate) to yield the
corresponding products in an analytically pure form.
yellow solution was then sealed and reacted at 150 ꢀC for 1e3 h
under the MW condition. The mixture was quenched with a satu-
rated solution of NaHCO3 and then extracted with ethyl acetate
(20 mL ꢂ 3). The organic layer was washed with brine, dried over
Na2SO4 and concentrated in vacuo. The residue was purified by
column chromatography (silica gel) (Eluent: hexane/ethyl acetate)
to yield the corresponding products.
4.3. General procedure for the aldol condensation of 3-methyl-2-
cyclohexenone with aldehydes
4.3.1. (E)-Methyl 3-(2,3-dimethoxystyryl)-5-oxo-1-phenylcyclohex-
3-enecarboxylate (4a) (E/Z ¼ 100:6)
Mp: 139e142 ꢀC; 1H NMR (400 MHz, CDCl3)
d
2.95 (d, J ¼ 13 Hz,
To a reactor containing 3-methyl-2-cyclohexenone (0.14 mmol)
and aldehyde (0.56 mmol) BiCl3 (5 mol%) was added. The resulting
1H), 3.07 (d, J ¼ 13 Hz, 1H), 3.30 (d, J ¼ 13 Hz, 1H), 3.58 (d,
J ¼ 13 Hz,1H), 3.64 (s, 3H), 3.87 (s, 3H), 3.88 (s, 3H), 6.09 (s,1H), 6.91

C. Zhang et al. / Journal of Organometallic Chemistry 696 (2011) 165e169
169
(t, J ¼ 21 Hz, 2H), 7.05 (t, J ¼ 13 Hz, 1H), 7.18 (d, J ¼ 6 Hz, 1H), 7.30 (t,
J ¼ 13 Hz, 1H), 7.37 (t, J ¼ 12 Hz, 2H), 7.41 (d, J ¼ 6 Hz, 2H), 7.50
1H), 3.64 (s, 3H), 3.87 (s, 3H), 3.90 (s, 6H), 6.10 (s,1H), 6.74 (s, 2H), 6.82
(d, J ¼ 13 Hz,1H), 7.10 (d, J ¼ 13 Hz,1H), 7.30 (t, J ¼ 11 Hz,1H), 7.38 (t,
J ¼ 12 Hz, 2H), 7.42 (d, J ¼ 6 Hz, 2H); 13C NMR (100 MHz, CDCl3)
(d, J ¼ 13 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 197.1, 174.0, 154.9,
153.0,147.7,130.3,129.9,129.8, 129.0, 127.8,127.7,125.7,124.3,118.2,
113.0, 61.3, 55.8, 52.9, 51.7, 46.0, 34.4. HRMS (EI) for C24H24O5: calcd.
392.1624. Found 392.1617.
d 196.9,174.0,154.3,153.4,139.9,136.0,131.3,128.9,127.9,127.8,127.5,
125.7, 125.5, 104.5, 61.0, 56.1, 52.9, 51.6, 45.8, 34.5. HRMS (EI) for
C23H30O6: calcd. 402.2042. Found 402.2047.
4.3.2. (E)-Methyl 5-oxo-1-phenyl-3-styrylcyclohex-3-
enecarboxylate (E/Z ¼ 100:5)
Appendix A. Supplementary information
1H NMR (400 MHz, CDCl3): major:
d
2.95 (d, J ¼ 13 Hz, 1H), 3.04
(d, J ¼ 13 Hz,1H), 3.30 (d, J ¼ 13 Hz,1H), 3.55 (d, J ¼ 13 Hz,1H), 3.64 (s,
3H), 3.83 (s, 3H), 6.09 (s,1H), 6.92 (d, J ¼ 13 Hz,1H), 7.16 (d, J ¼ 13 Hz,
1H), 7.30 (m, 2H), 7.37 (t, J ¼ 12 Hz, 4H), 7.41 (d, J ¼ 6 Hz, 2H), 7.51 (d,
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.jorganchem.2010.08.037.
J ¼ 6 Hz, 2H); minor:
d
6.22 (d, J ¼ 9.6 Hz,1H), 6.83 (d, J ¼ 9.6 Hz,1H);
13C NMR (100 MHz, CDCl3)
d
196.8, 174.0, 154.3, 140.0, 135.9, 135.7,
References
129.3, 128.9, 128.6, 127.8, 127.7, 127.4, 125.7, 52.8, 51.6, 45.9, 34.5.
HRMS (EI) for C22H20O3: calcd. 332.1412. Found 332.1413.
[1] (a) For examples: E.J. Corey, X.-M. Cheng, The Logic of Chemical Synthesis.
Wiley & Sons, New York, 1989;
4.3.3. (E)-Dimethyl 3-(3,4-dimethoxystyryl)-5-oxocyclohex-3-ene-
(b) T.-L. Ho, Symmetry: A Basis for Synthesis Design. Wiley& Sons, New York,
1995;
(c) C. Girlanda-Junges, F. Keyling-Bilger, Gaby Schmitt, B. Luu, Tetrahedron 54
(1998) 7735;
(d) A. Braca, N. De tommasi, L.-D. Bari, C. Pizza, M. Politi, I. Morelli, J. Nat. Prod.
64 (2001) 892.
1,1-dicarboxylate (4c) (E/Z ¼ 100:3)
Mp: 139e142 ꢀC; 1H NMR (400 MHz, CDCl3) major:
d 2.96 (s, 2H),
3.23 (s, 2H), 3.76 (s, 6H), 3.92 (s, 3H), 3.93 (s, 3H), 6.05 (s, 1H), 6.72
(d, J ¼ 13 Hz, 1H), 6.86 (d, J ¼ 7.0 Hz, 1H), 7.08 (m, 3H); minor: 5.68
(d, J ¼ Hz,1H); 13C NMR (100 MHz, CDCl3)
d 196.9,174.1,154.8,150.3,
149.2, 140.0, 136.0, 128.9, 127.8, 125.7, 121.6, 111.0, 109.1, 55.9, 51.6,
45.8,34.4. HRMS (EI) for C20H22O7: calcd. 374.1366. Found 374.1356.
[2] (a) D.D. Phillips, A.W. Johnson, J. Org. Chem. 21 (1956) 587;
(b) H. Rubinstein, J. Org. Chem. 27 (1962) 3886;
(c) G. Stork, R.L. Danheiser, B. Ganem, J. Am. Chem. Soc. 95 (1973) 3414;
(d) P.L. Stotter, K.A. Hill, J. Org. Chem. 38 (1973) 2576;
(e) M.E. Kuehne, W.H. Parsons, J. Org. Chem. 42 (1977) 3408;
(f) W.G. Dauben, D.M. Michno, J. Org. Chem. 42 (1977) 682;
(g) B.-D. Chong, Y.-I. Ji, S.-S. Oh, J.-D. Yang, W. Baik, S. Koo, J. Org. Chem. 62
(1997) 9323;
(h) G.P.-J. Hareau, M. Koiwa, S. Hikichi, F. Sato, J. Am. Chem. Soc. 121 (1999)
3640;
(i) F.Y. Zhang, E. Corey, J. Org. Lett. 2 (2000) 1097.
4.3.4. (E)-Methyl 3-(4-methoxystyryl)-5-oxo-1-phenylcyclohex-3-
enecarboxylate (4d)
Mp: 91e95 ꢀC; 1H NMR (400 MHz, CDCl3) major:
d 2.95 (d,
J ¼ 13 Hz, 1H), 3.02 (d, J ¼ 13 Hz, 1H), 3.29 (d, J ¼ 13 Hz, 1H), 3.56 (d,
J ¼ 13 Hz,1H), 3.65 (s, 3H), 3.85 (s, 3H), 6.07 (s,1H), 6.76 (d, J ¼ 13 Hz,
1H), 6.91 (d, J ¼ 7 Hz, 2H), 7.12 (d, J ¼ 13 Hz,1H), 7.30 (t, J ¼ 12 Hz,1H),
7.37 (t, J ¼ 12 Hz, 2H), 7.42 (d, J ¼ 6 Hz, 2H), 7.47 (d, J ¼ 7 Hz, 2H). 13C
[3] (a) C. Zhang, D.-M. Cui, L.-Y. Yao, B.-S. Wang, Y.-Z. Hu, T. Hayashi, J. Org. Chem.
73 (2008) 7811;
(b) D.-M. Cui, Y.-N. Ke, D.-W. Zhuang, Q. Wang, C. Zhang, Tetrahedron. Lett. 51
(2010) 980;
NMR (100 MHz, CDCl3) major: d 196.8,174.0,160.7,154.8,140.1,135.7,
(c) C. Zhang, J.-F. Qi, D.-M. Cui, Q. Wang, X.-L. Wang, Molecules 15 (2010) 5045.
[4] (a) O.H. House, in: R. Breslow (Ed.), Modern Synthetic Reactions, W.A. Benjamin,
Inc., Menlo Park, CA, 1972 (Chapter 10 and references therein);
(b) C.H. Heathcock, in: B.M. Trost (Ed.), ComprehensiVe Organic Synthesis, vol.
2, Pergamon Press, Oxford, 1991 (Chapter 1.5 and references therein);
(c) C.H. Heathcock, in: R. Scheffold (Ed.), Modern Synthetic Methods 1992, vol.
6, VHCA and VCH, Basel, Weinheim, and New York, 1992 (Chapter 1 and
references therein).
128.9, 128.5, 127.7, 126.8, 126.8, 126.4, 125.7, 114.4, 55.3, 52.8, 51.6,
45.9, 34.5; HRMS (EI) for C23H22O4: calcd. 362.1518. Found 362.1511.
4.3.5. (E)-Methyl 5-oxo-1-phenyl-3-(3,4,5-trimethoxystyryl)
cyclohex-3-enecarboxylate (4e)
Mp: 105e109 ꢀC; 1H NMR (400 MHz, CDCl3)
1H), 3.04 (d, J ¼ 13 Hz, 1H), 3.30 (d, J ¼ 13 Hz, 1H), 3.57 (d, J ¼ 14 Hz,
d
2.96 (d, J ¼ 13 Hz,
[5] (a) S. Saito, M. Shiozawa, M. Ito, H. Yamamoto, J. Am. Chem. Soc. 120 (1998) 813;
(b) Y. Hatanaka, I. Kuwajima, J. Org. Chem. 51 (1986) 1934.