DABCO-catalyzed reaction of phenols or 1,2-diphenols with activated alkynes leading to the formation of alkenoic acid esters or 1,3-dioxole derivatives

Article abstract of DOI:10.1055/s-2006-942437

The reaction of phenols or 1,2-diphenols with activated alkynes took place smoothly and rapidly in the presence of a catalytic amount of 1,4-diazabicyclo[2.2.2]octane (DABCO) at room temperature and resulted in the formation of various alkenoic acid ester

Full text of DOI:10.1055/s-2006-942437

2286
PAPER
DABCO-Catalyzed Reaction of Phenols or 1,2-Diphenols with Activated
Alkynes Leading to the Formation of Alkenoic Acid Esters or 1,3-Dioxole
Derivatives
D
ABCO-Catalyzed Re
i
a
ction
n
of Phenols
o
g
1,2-Diphen
-
w
ith
J
A
ctivate
d
i
A
lkyn
n
e
s
Fan,a Gao-Qiang Li,a Lian-Hua Li,a Shang-Dong Yang,a Yong-Min Liang*a,b
a
b
Received 20 January 2006; revised 27 February 2006
Moreover, the yields are improved significantly (up to
99%).
Abstract: The reaction of phenols or 1,2-diphenols with activated
alkynes took place smoothly and rapidly in the presence of a cata-
lytic amount of 1,4-diazabicyclo[2.2.2]octane (DABCO) at room
temperature and resulted in the formation of various alkenoic acid
esters or 1,3-dioxole derivatives in excellent yields. The scope and
limitations, together with a plausible mechanism of the reaction are
disclosed in this paper.
In our initial experiment, the reaction of various phenols
with dimethyl acetylenedicarboxylate (DMAD) in the
presence of a catalytic amount of DABCO (10 mol%) was
examined. In a typical procedure, DMAD (0.5 mmol),
DABCO (0.05 mmol) and phenols (0.5 mmol) were
stirred in dichloromethane for ten minutes at room tem-
perature to give final products facilely by flash chroma-
tography on silica column. The reaction appears to be
general, with a number of phenols affording conjugate ad-
dition products in excellent yields (Table 1, entries 1–10).
The structures of the products were characterized by spec-
troscopic analysis and further confirmed by X-ray diffrac-
tion of 3 as a representative example (Figure 1).10 In some
cases, the reaction gave alkenoic acid esters as a pair of in-
separable E- and Z-isomers (Table 1, entries 1, 2, 6, 9, 10).
The selectivity of this reaction increases moderately when
the steric bulkiness of the aryl (Ar) substituents increases
(Table 1, entry 7). The phenols with acetyl, nitro or
formyl groups at 2-position generally led to almost quan-
titative E-isomers of the corresponding alkenoic acid es-
ters (Table 1, entries 3–5). This selectivity may be
attributed more to electronic factors than to steric factors
as deduced with the reaction in entry 7. The same effect
was also observed in entry 8.
Key words: phenoles, 1,2-diphenoles, activated alkynes, alkenoic
acid esters, 1,3-dioxoles
The facile reaction of nucleophiles with activated alkynes
has received considerable interest in the past decades. In
most cases, the reaction was viewed as starting from the
initial formation of a zwitterionic intermediate derived
from the addition of nucleophilic trigger to activated
alkyne.1 The vast majority of the previous investigations
demonstrate that triphenyl phosphine,2 pyridine,3
isocyanides4 and a wide range of tertiary amines5 are ex-
cellent nucleophilic triggers for the above-mentioned re-
action. On the basis of these observations and our interest
in DABCO-catalyzed reaction,6 we speculated that DAB-
CO, a tertiary amine base with weak basicity and moder-
ate hindrance, could lead to zwitterion formation and
undergo further reaction with a number of nucleophiles.
Herein, we wish to report our successful investigation on
DABCO-catalyzed reaction of phenols or 1,2-diphenols
with activated alkynes leading to the formation of alkeno-
ic acid esters or 1,3-dioxole derivatives.
We further investigated the reaction of other activated
alkynes, such as benzyl propiolate and methyl propiolate
Although numerous reactions of phenols and 1,2-diphe-
nols with activated alkynes have been reported, many of
them suffer problems including low product yield,7 long
reaction time,8 harsh reaction conditions9 or lack of selec-
tivity.7b,8a The present procedure has circumvented most
of these problems to make it a useful reaction for the syn-
thesis of a wide variety of molecules. With DABCO as a
catalyst, the additions of phenols or 1,2-diphenols to acti-
vated alkynes proceed quickly (completed within a few
minutes) under very mild conditions (at room tempera-
ture) for a wide range of functional groups on the phenols.
SYNTHESIS 2006, No. 14, pp 2286–2292
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Advanced online publication: 26.06.2006
DOI: 10.1055/s-2006-942437; Art ID: F01306SS
© Georg Thieme Verlag Stuttgart · New York
Figure 1 X-ray crystal structure of 3.

PAPER
DABCO-Catalyzed Reaction of Phenols or 1,2-Diphenols with Activated Alkynes
2287
Table 1 Reaction of Phenols with DMADa Table 2 Reaction of Various Phenols with Activated Alkynesa
R2O
H
H
ArO
H
CCO2Me
CCO2Me
DABCO (10 mol%)
CH2Cl2, r.t.
DABCO (10 mol%)
CH2Cl2, r.t.
+
ArOH
OH
HC CCO2R1
R2OH
+
CO2R1
MeO2C
CO2Me
Product Yield (%)b E/Zc
Entry R1
Nucleophile (R2OH) Product Yield (%)b E/Zc
Entry ArOH
1
1
99
50:50
OH
1
Me
11
95
85:15
2
2
99
55:45
2
Me
12
97
> 95:5
OH
OH
Me
3
3
4
5
6
98
92
92
99
> 95:5
> 99:1
> 99:1
40:60
COMe
3
4
Me
Bn
13
14
90
97
E
E
OH
OH
4
5
6
NO2
COCH3
OH
OH
CHO
a All the reactions were performed at r.t. and went to completion with-
in 10 min.
OH
b Isolated yields.
OH
Me
c Determined by 1H NMR (300 MHz) spectra.
Me
diates b and c. Subsequent Michael addition of b to c
forms intermediate d, which then eliminates DABCO to
afford the final product.
7
7
8
92
99
10:90
OH
Me3C
CMe3
Further scope exploration of this process revealed that
1,2-diphenol was another class of suitable nucleophiles
for this reaction. Interestingly, diphenols on treatment
with DMAD in the presence of a catalytic amount of
DABCO (10 mol%) in dichloromethane at room temper-
ature afforded 1,3-dioxole derivatives in good to excellent
yields (Table 3, entries 1–5). The structure of the product
8
E
MeO
OH
OHC
OMe
9
9
95
70
50:50
45:55
OH
1
was revealed by H and 13C NMR analysis. In addition,
10
10
Me
the NMR-based structure was confirmed by X-ray crystal-
lographic analysis of 15 (Figure 2).12 Mechanistically, the
reaction may also involve the initial generation of a zwit-
terionic intermediate a by reaction between DABCO and
DMAD (Scheme 2), which is readily protonated by one of
the two protons of 1,2-diphenol to yield intermediates b
and c. Subsequent Michael addition of b to c forms e.
OH
Me
a All the reactions were performed at r.t. and went to completion with-
in 10 min.
b Isolated yields.
c The E- and Z-isomers were determined by 1H NMR (300 MHz) spec-
tra.
R2O
R3
H
DABCO (10 mol%)
CH2Cl2, r.t.
R2OH
R3C CCO2R1
+
with phenols. We were pleased to find that the results ob-
tained were much better than expected under the same
conditions (0.5 mmol of benzyl or methyl propiolate, 0.5
mmol of phenols, and 0.05 mmol of DABCO, CH2Cl2, at
room temperature). The reaction proceeded smoothly and
rapidly (within 10 min) to give the corresponding conju-
gate addition products in excellent yields with increased
stereoselectivities (Table 2, entries 1–4).
CO2R1
DABCO
– DABCO
R3
N
CO2R1
R2OH
R3
N
CO2R1
H
R3
R2O
CO2R1
H
R2O
N
A proposed mechanism for this reaction is outlined in
Scheme 1 based on the previous investigations of Nozaki
et al.11 Initially, DABCO reacts with the activated alkyne
to generate the zwitterionic intermediate a, which depro-
tonates the nucleophile to give the corresponding interme-
c
N
a
N
b
d
N
Scheme 1 Plausible mechanism for the reaction of various phenols
with activated alkynes.
Synthesis 2006, No. 14, 2286–2292 © Thieme Stuttgart · New York

2288
M.-J. Fan et al.
PAPER
Table 3 Reaction of 1,2-Diols with DMADa
OH
O
O
DABCO (10 mol%)
CH2Cl2, r.t.
CCO2Me
CCO2Me
CO2Me
CO2Me
R
+
R
OH
Entry
1
Nucleophile
Product
Yield (%)b
95
OH
15
OH
OH
2
3
16
17
71
91
Br
OH
OH
OH
Me3C
4
5
18
19
80
97
OH
Me
OH
OH
OH
a All the reactions were performed at r.t. and went to completion within 10 min.
b Isolated yields.
OH
O
O
DABCO (10 mol%)
CH2Cl2, r.t.
CCO2Me
CCO2Me
CO2Me
CO2Me
R
+
R
OH
–DABCO
R
DABCO
O–
CO2Me
MeO2C
CO2Me
O
MeO2C
N
–
H
N
H
f
a
N
N
R
OH
CO2Me
MeO2C
CO2Me
H
OH
O–
O
–
MeO2C
N
R
N
H
N
e
N
b
c
Scheme 2 Plausible mechanism for the reaction of 1,2-diphenols with DMAD.
It deprotonates the second phenolic group immediately to classes of heterocycles, such as 1,4-dioxane, piperazinone
form intermediate f, which then undergoes cyclization to and morpholine derivatives (Scheme 3).
deliver 1,3-dioxole derivative and DABCO to be recy-
cled.
Further comparative studies demonstrated that DABCO
was the optimal catalyst for the addition of phenols and
It should be noted that when ethane-1,2-diol, ethane-1,2- cyclization of 1,2-diols. Triphenylphosphine, which is
diamine or 2-aminoethanol was used in this reaction, dif- commonly employed in the traditional conjugate addition
ferent results were obtained under the same conditions as reaction, was ineffective in promoting reactions of phe-
those described above. The new synthetic procedure was nols and 1,2-diols (Table 4, entries 3 and 5). Although
found to be an effective method for the synthesis of other other amine catalysts such as triethylamine, 1,8-diazabi-
Synthesis 2006, No. 14, 2286–2292 © Thieme Stuttgart · New York

PAPER
DABCO-Catalyzed Reaction of Phenols or 1,2-Diphenols with Activated Alkynes
2289
O
O
O
OH
OH
DABCO (10 mol%)
CH2Cl2, r.t.
CCO2CH3
CCO2CH3
+
CO2CH3
H
N
O
NH2
NH2
CH2Cl2, r.t.
CCO2CH3
CCO2CH3
+
N
H
CO2CH3
O
H
N
OH
CH2Cl2, r.t.
CCO2CH3
CCO2CH3
+
Figure 2 X-ray crystal structure of 15.
O
NH2
CO2CH3
cyclo[5.4.0]undec-7-ene (DBU) and 4-methylmorpholine
provided the same catalytic abilities, the yields were re-
duced owing to the formation of many by-products
(Table 4, entries 1, 2, 4, 6–9).
Scheme 3 Reaction of ethane-1,2-diol, ethane-1,2-diamine or 2-
aminoethanol with DMAD.
1
Co., Ltd.). H NMR spectra were recorded at 300 MHz in CDCl3
In conclusion, we have developed an efficient, DABCO-
catalyzed reaction of diphenols or 1,2-diphenols with ac-
tivated alkynes, which provides an easy access to the cor-
responding alkenoic acid esters or 1,3-dioxole derivatives
in good to excellent yields under very mild conditions.
Additional work aimed at obtaining further extension of
this reaction is in progress.
and 13C NMR spectra were recorded at 75 MHz in CDCl3 using
TMS as internal standard on a Varian Mercury Plus 300BB MHz
NMR spectrometer. Mass spectra were recorded by the EI method
on a HP5998 MS spectrometer. IR spectra were obtained on a Nico-
let AVATAR 360 FT-IR spectrometer. Microanalyses were per-
formed on a VarioEL instrument.
Reaction of Various Phenols with Activated Alkynes; General
Procedure
DMAD (0.5 mmol), DABCO (0.05 mmol) and phenols (0.5 mmol)
were stirred in CH2Cl2 (4 mL) at r.t. for 10 min. The solvent was
evaporated under reduced pressure and the residue was purified by
flash chromatography on silica column to give the final products.
All reagents were used directly as obtained commercially unless
otherwise noted. Melting points were determined on a microscopic
apparatus and are uncorrected. Column chromatography was car-
ried out on silica gel (200–300 mesh, Qingdao Haiyang Chemical
Table 4 Reaction of Nucleophiles with Activated Alkynes Catalyzed by Various Catalystsa
Entry
1
Nucleophile
Activated alkynes
DMAD
Catalyst
DBU
Time (h)
1
Product
Yield (%)b
80
E/Zc
OH
1
30:70
2
3
DMAD
DMAD
Et3N
Ph3P
21
24
1
3
78
35:65
–
No reaction
COMen
OH
4
5
DMAD
DMAD
Et3N
Ph3P
24
24
3
60
0
40:60
–
15
OH
OH
6
7
8
9
DMAD
DBU
4
4
15
15
15
11
74
81
81
73
–
DMAD
Et3N
–
DMAD
4-Methylmorpholine
Et3N
4
–
Methyl propiolate
17
99:1
OH
a All the reactions were performed at r.t. in the presence of 10 mol% base.
b Isolated yields.
c Determined by 1H NMR (300 MHz) spectra.
Synthesis 2006, No. 14, 2286–2292 © Thieme Stuttgart · New York

2290
M.-J. Fan et al.
PAPER
Reactions of Ethane-1,2-diol, Ethane-1,2-diamine or 2-Amino-
ethanol with DMAD; Ethane-1,2-diol as an Example; Typical
Procedure
DMAD (0.5 mmol), DABCO (0.05 mmol) and ethane-1,2-diol (3
mmol for 1,2-diol, 0.5 mmol for other nucleophiles) were stirred in
CH2Cl2 (4 mL) at r.t. for 10 min. For the reaction of 2-aminoethanol,
the reaction time needed to be extended to 10 h. The solvent was
evaporated under reduced pressure and the residue was purified by
flash chromatography on silica column to give the final products.
1H NMR (300 MHz, CDCl3): d = 10.29 (s, 1 H), 7.21–8.00 (m, 4 H),
5.25 (s, 1 H), 3.94 (s, 3 H), 3.71 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 187.6, 165.1, 162.5, 159.8, 155.0,
136.0, 129.1, 127.6, 126.8, 121.5, 101.5, 53.2, 51.9.
MS (EI, 70 eV): m/z (%) = 264 (0.19) [M+], 233 (1.94), 205 (86.57),
173 (100).
Anal. Calcd for C13H12O6: C, 59.09; H, 4.58. Found: C, 59.32; H,
4.34.
1
6
Mixture of Z- and E-isomers; known compounds.13
Mixture of Z- and E-isomers.
IR (KBr): 2954, 2844, 1726, 1637, 1269, 1132, 817 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.94–7.43 (m, 10 H), 6.54 (s, 1 H),
5.12 (s, 1 H), 3.90 (s, 3 H), 3.72 (s, 3 H), 3.69 (s, 3 H), 3.66 (s, 3 H).
1H NMR (300 MHz, CDCl3): d = 6.60–7.09 (m, 5 H), 6.53 (s, 1 H),
4.99 (s, 1 H), 3.96 (s, 3 H), 3.74 (s, 3 H), 3.71 (s, 3 H), 3.68 (s, 3 H),
2.36 (s, 3 H), 2.34 (s, 3 H), 2.28 (s, 3 H), 2.22 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 165.8, 163.8, 163.3, 162.5, 161.1,
152.7, 150.6, 148.6, 136.1, 132.7, 132.3, 131.8, 129.5, 127.9, 127.3,
126.8, 120.6, 114.1, 113.3, 96.7, 96.6, 52.7, 52.6, 51.5, 51.3, 20.5,
20.4, 15.8, 15.2.
13C NMR (75 MHz, CDCl3): d = 165.7, 163.7, 163.2, 162.5, 160.8,
156.4, 152.8, 149.7, 130.1, 129.5, 126.2, 123.2, 120.6, 115.9, 114.8,
98.7, 98.6, 52.9, 51.7, 51.5.
MS (EI, 70 eV): m/z (%) = 236 (5.67) [M+], 205 (9.69), 177 (100),
77 (32.72).
2
MS (EI, 70 eV): m/z (%) = 264 (21.14) [M+], 233 (15.90), 205 (100).
Mixture of Z- and E-isomers.
Anal. Calcd for C14H16O5: C, 63.63; H, 6.10. Found: C, 63.31; H,
5.76.
IR (KBr): 2956, 2852, 1743, 1717, 1663, 1260, 1133, 767 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.83–7.20 (m, 8 H), 6.54 (s, 1 H),
5.12 (s, 1 H), 3.90 (s, 3 H), 3.71 (s, 3 H), 3.68 (s, 3 H), 3.65 (s, 3 H),
2.33 (s, 3 H), 2.28 (s, 3 H).
7
Z-Isomer.
13C NMR (75 MHz, CDCl3): d = 165.8, 163.8, 163.2, 162.5, 161.2,
154.3, 150.5, 149.9, 136.0, 132.7, 130.5, 129.9, 120.3, 115.8, 114.9,
114.3, 98.1, 98.0, 52.8, 51.6, 51.4, 20.6, 20.4.
MS (EI, 70 eV): m/z (%) = 250 (12.42) [M+], 219 (11.23), 191 (100),
107 (25.73), 91 (33.62).
IR (KBr): 2958, 2871, 1731, 1650, 1263, 1200, 818 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.04–7.37 (m, 3 H), 6.49 (s, 1 H),
3.71 (s, 3 H), 3.69 (s, 3 H), 1.46 (s, 9 H), 1.29 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 164.3, 162.9, 152.8, 149.8, 145.4,
137.0, 124.5, 123.4, 113.6, 52.9, 51.8, 34.9, 34.4, 31.6, 31.5, 29.8,
29.6.
Anal. Calcd for C13H14O5: C, 62.39; H, 5.64. Found: C, 62.46; H,
5.52.
MS (EI, 70 eV): m/z (%) = 348 (40.11) [M+], 333 (100), 115 (85.37),
91 (99.42).
3
Anal. Calcd for C20H28O5: C, 68.94; H, 8.10. Found: C, 68.90; H,
7.98.
IR (KBr): 2961, 2852, 1749, 1722, 1683, 1637, 1281, 1210, 1133,
787 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.15–7.88 (m, 4 H), 5.18 (s, 1 H),
E-Isomer.
3.94 (s, 3 H), 3.69 (s, 3 H), 2.63 (s, 3 H).
IR (KBr): 2957, 2871, 1756, 1724, 1635, 1211, 1132, 826 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.92–7.41 (m, 3 H), 5.16 (s, 1 H),
3.96 (s, 3 H), 3.67 (s, 3 H), 1.35 (s, 9 H), 1.32 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 166.2, 163.7, 161.6, 149.2, 148.8,
140.8, 124.7, 124.3, 121.5, 97.9, 53.1, 51.6, 34.8, 34.7, 31.4, 30.3,
29.7.
13C NMR (75 MHz, CDCl3): d = 197.2, 165.3, 162.8, 159.6, 151.5,
133.9, 131.2, 130.9, 126.6, 121.8, 100.4, 53.2, 51.8, 30.8.
MS (EI, 70 eV): m/z (%) = 278 (0.71) [M+], 247 (1.96), 219 (94.31),
177 (100).
Anal. Calcd for C14H14O6: C, 60.43; H, 5.07. Found: C, 60.38; H,
5.17.
MS (EI, 70 eV): m/z (%) = 348 (16.59) [M+], 333 (94.79), 115
(26.15), 91 (27.85), 57 (100).
4
Anal. Calcd for C20H28O5: C, 68.94; H, 8.10. Found: C, 68.98; H,
8.01.
IR (KBr): 2958, 2853, 1745, 1717, 1643, 1531, 1368, 1223, 1134,
789 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.32–8.09 (m, 4 H), 5.27 (s, 1 H),
3.92 (s, 3 H), 3.71 (s, 3 H).
8
IR (KBr): 2952, 2886, 2851, 2790, 1751, 1722, 1689, 1647, 1590,
1226, 1137, 826 cm–1.
13C NMR (75 MHz, CDCl3): d = 165.2, 162.4, 158.4, 146.1, 141.8,
135.3, 127.3, 126.5, 123.9, 102.2, 53.4, 52.2.
1H NMR (300 MHz, CDCl3): d = 10.40 (s, 1 H), 6.33 (s, 2 H), 5.52
(s, 1 H), 3.92 (s, 3 H), 3.91 (s, 3 H), 3.89 (s, 3 H), 3.74 (s, 3 H).
MS (EI, 70 eV): m/z (%) = 281 (0.81) [M+], 250 (2.64), 222 (48.25),
122 (100).
13C NMR (75 MHz, CDCl3): d = 187.7, 165.1, 163.6, 162.4, 159.3,
157.2, 111.9, 103.4, 95.9, 56.2, 53.5, 51.9.
Anal. Calcd for C12H11NO7: C, 51.25; H, 3.94; N, 4.98. Found: C,
51.19; H, 3.52; N, 4.83.
MS (EI, 70 eV): m/z (%) = 324 (20.5) [M+], 293 (9.4), 265 (99.3),
233 (90.3), 69 (100).
5
Anal. Calcd for C15H16O8: C, 55.56; H, 4.97. Found: C, 55.76; H,
5.26.
IR (KBr): 2956, 2853, 1750, 1719, 1693, 1639, 1214, 1132, 788
cm–1.
Synthesis 2006, No. 14, 2286–2292 © Thieme Stuttgart · New York

PAPER
DABCO-Catalyzed Reaction of Phenols or 1,2-Diphenols with Activated Alkynes
2291
9
Anal. Calcd for C14H12O3: C, 73.67; H, 5.30. Found: C, 73.51; H,
5.24.
Solid; mp 52–54 °C. Mixture of Z- and E-isomers.
IR (KBr): 2953, 2849, 1751, 1726, 1640, 1210, 1132 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.19–7.92 (m, 14 H), 6.70 (s, 1 H),
5.19 (s, 1 H), 3.96 (s, 3 H), 3.73 (s, 3 H), 3.72 (s, 3 H), 3.68 (s, 3 H).
14
IR (KBr): 1714, 1684, 1648, 1222, 1128, 950, 763, 699 cm–1.
1H NMR (300M Hz, CDCl3): d = 7.05–7.82 (m, 10 H), 5.63–5.67
(d, J = 12.3 Hz, 1 H), 5.17 (s, 2 H), 2.56 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 197.2, 166.1, 158.4, 154.2, 135.7,
133.7, 130.4, 129.7, 128.3, 128.0, 125.1, 118.7, 102.9, 65.8, 31.1.
MS (EI, 70 eV): m/z (%) = 296 (0.05) [M+], 190 (2.81), 161 (29.88),
145 (36.07), 91 (100).
13C NMR (75 MHz, CDCl3): d = 165.9, 163.9, 162.7, 160.9, 154.4,
150.4, 149.8, 133.9, 133.8, 131.5, 130.5, 130.2, 130.0, 127.8, 127.7,
127.6, 127.1, 127.0, 126.6, 126.3, 126.2, 124.7, 119.9, 117.9, 115.5,
115.4, 110.7, 99.1, 53.2, 53.1, 52.1, 51.8.
MS (EI, 70 eV): m/z (%) = 286 (23.1) [M+], 255 (11.0), 227 (91.4),
115 (100).
Anal. Calcd for C18H16O4: C, 72.96; H, 5.44. Found: C, 72.92; H,
5.46.
Anal. Calcd for C16H14O5: C, 67.13; H, 4.93. Found: C, 67.31; H,
4.59.
15
10
Solid; mp 58–60 °C.
IR (KBr): 2959, 2854, 1751, 1483, 1224, 1154, 1069, 755 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.87 (s, 4 H), 3.85 (s, 3 H), 3.72
(s, 3 H), 3.35 (s, 2 H).
13C NMR (75 MHz, CDCl3): d = 168.0, 166.0, 146.3, 122.2, 109.6,
109.0, 53.3, 52.2, 40.7.
Mixture of Z- and E-isomers.
IR (KBr): 2954, 2851, 1749, 1726, 1637, 1267, 1173, 1133, 780
cm–1.
1H NMR (300 MHz, CDCl3): d = 6.94–7.06 (m, 6 H), 6.09 (s, 1 H),
4.81 (s, 1 H), 3.95 (s, 3 H), 3.71 (s, 3 H), 3.63 (s, 3 H), 3.51 (s, 3 H),
2.24 (s, 6 H), 2.20 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 166.0, 164.3, 163.4, 162.4, 160.1,
152.0, 150.7, 148.9, 130.1, 129.7, 129.2, 128.7, 126.4, 125.0, 105.1,
95.3, 53.0, 52.8, 51.5, 16.4, 15.5.
MS (EI, 70 eV): m/z (%) = 252 (9.20) [M+], 193 (76.05), 151 (100).
Anal. Calcd for C12H12O6: C, 57.14; H, 4.80. Found: C, 57.19; H,
4.85.
MS (EI, 70 eV): m/z (%) = 264 (11.4) [M+], 232 (54.4), 205 (100).
16
Anal. Calcd for C14H16O5: C, 79.37; H, 8.88. Found: C, 79.56; H,
8.68.
IR (KBr): 2956, 2851, 1746, 1482, 1223, 1156, 1076 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.72–7.11 (m, 3 H), 3.85 (s, 3 H),
3.72 (s, 3 H), 3.35 (s, 2 H).
11
IR (KBr): 2951, 2844, 1716, 1650, 1592, 1226, 1123, 760, 692
13C NMR (75 MHz, CDCl3): d = 167.6, 165.4, 147.3, 146.2, 145.9,
cm–1.
124.9, 122.2, 113.6, 108.9, 53.4, 52.2, 40.3.
1H NMR (300 MHz, CDCl3): d = 7.79–7.84 (d, J = 12.3 Hz, 1 H),
7.05–7.40 (m, 5 H), 5.55–5.59 (d, J = 12.3 Hz, 1 H), 3.72 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 167.6, 159.1, 155.7, 129.9, 124.9,
117.9, 101.7, 51.3.
MS (EI, 70 eV): m/z (%) = 330 (4.59) [M+], 332 (4.14), 229 (51.13),
193 (100).
Anal. Calcd for C12H11BrO6: C, 43.53; H, 3.35. Found: C, 43.47; H,
3.28.
MS (EI, 70 eV): m/z (%) = 178 (62.5) [M+], 147 (100), 77 (56.3).
17
Anal. Calcd for C10H10O3: C, 67.41; H, 5.66. Found: C, 67.56; H,
5.59.
IR (KBr): 2959, 2870, 1749, 1222, 1158, 1078 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.73& ndash;6.92 (m, 3 H), 3.82
(s, 3 H), 3.70 (s, 3 H), 3.31 (s, 2 H), 1.26 (s, 9 H).
12
Solid; mp 34–36 °C.
IR (KBr): 2955, 1705, 1651, 1234, 1129, 795, 772 cm–1.
13C NMR (75 MHz, CDCl3): d = 168.2, 166.4, 146.5, 146.2, 144.2,
118.8, 110.0, 108.2, 106.9, 106.8, 53.5, 52.3, 41.0, 34.9, 31.7.
1H NMR (300 MHz, CDCl3): d = 7.10–8.10 (m, 8 H), 5.62–5.66 (d,
J = 12.3 Hz, 1 H), 3.73 (s, 3 H).
MS (EI, 70 eV): m/z (%) = 308 (10.41) [M+], 249 (85.94), 207
(49.38), 59 (100).
13C NMR (75 MHz, CDCl3): d = 167.6, 159.7, 151.7, 134.6, 127.8,
126.9, 126.4, 125.6, 125.5, 125.0, 121.3, 112.8, 102.0, 51.3.
Anal. Calcd for C16H20O6: C, 62.33; H, 6.54. Found: C, 62.22; H,
6.33.
MS (EI, 70 eV): m/z (%) = 228 (62.5) [M+], 197 (19.3), 115 (100).
18
Anal. Calcd for C14H12O3: C, 73.67; H, 5.30. Found: C, 73.43; H,
5.13.
Solid; mp 52–53 °C.
IR (KBr): 2923, 2854, 1746, 1221, 1162, 1075 cm–1.
13
1H NMR (300 MHz, CDCl3): d = 6.64–6.75 (m, 3 H), 3.84 (s, 3 H),
3.72 (s, 3 H), 3.33 (s, 2 H), 2.27 (s, 3 H).
Solid; mp 62–64 °C.
IR (KBr): 2950, 1724, 1653, 1254, 1168, 1128, 846, 755 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.92–7.96 (d, J = 12.3 Hz, 1 H),
7.22–7.85 (m, 7 H), 5.63–5.67 (d, J = 12.3 Hz, 1 H), 3.75 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 168.0, 166.1, 146.3, 144.2, 132.1,
122.1, 109.7, 109.6, 108.3, 53.3, 52.2, 40.6, 21.1.
MS (EI, 70 eV): m/z (%) = 266 (10.25) [M+], 207 (55.87), 165 (100),
59 (65.10).
13C NMR (75 MHz, CDCl3): d = 167.6, 158.9, 153.5, 133.8, 130.8,
130.2, 127.7, 127.3, 126.9, 125.4, 118.5, 113.4, 102.1, 51.4.
Anal. Calcd for C13H14O6: C, 58.64; H, 5.30. Found: C, 58.60; H,
5.53.
MS (EI, 70 eV): m/z (%) = 228 (72.8) [M+], 197 (25.4), 115 (100).
Synthesis 2006, No. 14, 2286–2292 © Thieme Stuttgart · New York

2292
19
M.-J. Fan et al.
PAPER
(5) (a) Shi, Y.-L.; Shi, M. Org. Lett. 2005, 7, 3057. (b) Zhao,
Solid; mp 55–57 °C.
IR (KBr): 2955, 1741, 1234, 1166, 1074 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.66–7.69 (m, 2 H), 7.33–7.36 (m,
2 H), 7.17 (s, 2 H), 3.85 (s, 3 H), 3.74 (s, 3 H), 3.42 (s, 2 H).
13C NMR (75 MHz, CDCl3): d = 167.9, 165.9, 146.5, 130.4, 127.2,
124.7, 109.8, 104.4, 53.5, 52.3, 40.5.
MS (EI, 70 eV): m/z (%) = 302 (7.0) [M+], 243 (56.6), 201 (100),
114 (59.1).
G.-L.; Shi, Y.-L.; Shi, M. Org. Lett. 2005, 7, 4527.
(c) Zhao, G.-L.; Shi, M. J. Org. Chem. 2005, 70, 9975.
(d) Ding, H.; Ma, C.; Yang, Y.; Wang, Y. Org. Lett. 2005, 7,
2125.
(6) (a) Yang, Z.; Fan, M.; Mu, R.; Liang, Y. Tetrahedron 2005,
61, 9140. (b) Fan, M.; Guo, L.; Liu, X.; Liu, W.; Liang, Y.
Synthesis 2005, 391. (c) Fan, M.; Yan, Z.; Liang, Y. J. Org.
Chem. 2005, 70, 8204.
(7) (a) Gudi, M. N.; Hiriyakkanavar, J. G.; George, M. V. Indian
J. Chem. 1969, 7, 971. (b) Gupta, R. K.; George, M. V.
Tetrahedron 1975, 31, 1263.
(8) (a) Stoermer, M. J.; Fairlie, D. P. Aust. J. Chem. 1995, 48,
677. (b) Kodomari, M.; Sakamoto, T.; Yoshitomi, S. J.
Chem. Soc., Chem. Commun. 1990, 9, 701.
(9) (a) Nagarajan, K.; Rangarao, V.; Shah, R. K. Indian J. Chem.
1971, 9, 971. (b) Davies, S. G.; Mobbs, B. E. J. Chem. Soc.,
Perkin Trans. 1 1987, 2597.
(10) Crystal data of 3 have been deposited in CCDC as deposition
number 295601: C14H14O6, MW = 278.25, T = 296 (2) K,
l = 0.71073 Å, Monoclinic space group P2(1)/c, a = 10.046
(2) Å, b = 18.482 (4) Å, c = 7.566 (1) Å, a = 90.00°, b = 95.32
(2)°, g = 90.00°, V = 1398.7 (5) Å3, Z = 4, Dc = 1.321 mg/m3,
m = 0.104 mm–1, F(000) = 584, Crystal size 0.58 × 0.52 ×
0.50 mm, Independent reflections 2600 [R(int) = 0.0103],
Reflections collected 3009, Refinement method, full-matrix
least-squares on F2, Goodness-of-fit on F2 1.083, Final R
indices [I > 2s(I)] R1 = 0.0387, wR2 = 0.1116, R indices (all
data) R1 = 0.0627, wR2 = 0.1197, Extinction coefficient
0.119 (6), Largest diff. peak and hole 0.233 and –0.166 eÅ–3.
(11) Nozaki, K.; Sato, N.; Ikeda, K.; Takaya, H. J. Org. Chem.
1996, 61, 4516.
(12) Crystal data of 15 have been deposited in CCDC as
deposition number 295602: C12H12O6, MW = 252.22, T =
296 (2) K, l = 0.71073 Å, Orthorhombic space group Pbca,
a = 7.314 (1) Å, b = 17.931 (4) Å, c = 18.351 (5) Å, a =
90.00°, b = 90.00°, g = 90.00°, V = 2406.52 (67) Å3, Z = 8,
Dc = 1.392 mg/m3, m = 0.113 mm–1, F(000) = 1056, Crystal
size 0.60 × 0.34 × 0.34 mm, Independent reflections 2769
[R(int) = 0.0385], Reflections collected 3481, Refinement
method, full-matrix least-squares on F2, Goodness-of-fit on
F2 0.902, Final R indices [I > 2s(I)] R1 = 0.0827, wR2 =
0.0975, R indices (all data) R1 = 0.0393, wR2 = 0.0879,
Extinction coefficient 0.0098 (7), Largest diff. peak and hole
0.169 and –0.161 eÅ–3.
Anal. Calcd for C16H14O6: C, 63.57; H, 4.67. Found: C, 63.56; H,
4.48.
Acknowledgment
We thank the NSF-20021001, NSF-20572038 and the ‘Hundred
Scientist Program’ from the Chinese Academy of Sciences for fi-
nancial support of this work.
References
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Synthesis 2006, No. 14, 2286–2292 © Thieme Stuttgart · New York