A novel and efficient direct aldol condensation from ketones and aromatic aldehydes catalyzed by proline-TEA through a new pathway

Article abstract of DOI:10.1016/j.tet.2009.04.052

A novel and efficient direct aldol condensation from various ketones and a wide range of aldehydes was catalyzed by l-proline-TEA (triethylamine) in MeOH at room temperature, affording the corresponding (E)-α,β-unsaturated ketones in excellent yields. By

Full text of DOI:10.1016/j.tet.2009.04.052

Tetrahedron 65 (2009) 4826–4833
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A novel and efficient direct aldol condensation from ketones and aromatic
aldehydes catalyzed by proline–TEA through a new pathway
*
*
Jun-feng Wang, Meng Lei, Qin Li, Ze-mei Ge , Xin Wang, Run-tao Li
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel and efficient direct aldol condensation from various ketones and a wide range of aldehydes was
Received 9 February 2009
Received in revised form 8 April 2009
Accepted 14 April 2009
catalyzed by
L
-proline–TEA (triethylamine) in MeOH at room temperature, affording the corresponding
(E)- -unsaturated ketones in excellent yields. By using the method, some complicated (E)-a,b
a,
b
-un-
saturated ketone C-glycosides were obtained from unmodified ketone C-glycosides and aldehydes. This
reaction proceeds through a new pathway, in which the specific intermediate was captured and
identified.
Available online 21 April 2009
Keywords:
Proline
Ó 2009 Elsevier Ltd. All rights reserved.
Aldol Condensation
C-glycosides
New pathway
Intermediate
1. Introduction
development of new routes for the synthesis of C-glycosides has
attracted much attention. Ketone C-glycosides 1 (Fig. 2) have been
Acyclic or cyclic
a
,
b
-unsaturated carbonyl compounds have been
synthesized conveniently for many years.4 However, further
reported tobepotentially importantstructuralcharacteristics insmall
moleculedrugs used topreventortreatcancer.1 Theyarealsoversatile
organic molecules used frequentlyas substrates for carbonyl addition,
conjugate addition, and the Morita–Baylis–Hillman reaction.2
modification of 1 is very limited.5 Thus, we are interested in
transforming the ketone C-glycosides 1 into
a,b-unsaturated ke-
tone C-glycosides 2 (Fig. 2), which should be useful precursors for
achieving new biologically active C-glycoside derivatives.
OH
O
OH
20
H
N
O
O
OH
H
OH
HO
O
HO
HO
HO
HN
OH
HO
HO
O
H
OH
10
OH
Me
Fagomine C-glycoside
OH
β-C-Glycosyl KRN7000
Flavone C-glycoside
Figure 1. C-Glycosides with biological activities.
C-Glycosides as subunits occur in a variety of biologically
important natural products and synthetic compounds. Flavone C-
R1
R1
R3
R3
O
O
HO
glycoside,3a -C-glycoside analogs of KRN7000,3b and fagomine C-
b
HO
HO
HO
Ar
glycoside3c have been reported to exhibit antitumor, antibacterial,
antiviral, and glycosidase inhibitory activities (Fig. 1).3d Therefore,
R2
R2
O
O
2
1b R1= OH R2 = H R3 = CH2OH
1a R1= H R2 = OH R3 = CH2OH
1c R1= H R2 = OH R3 = H
* Corresponding authors. Tel.: þ86 10 82801504; fax: þ86 10 82716956.
E-mail addresses: zmge@bjmu.bjmu.edu.cn (Z.-m. Ge), lirt@mail.bjmu.edu.cn
(R.-t. Li).
Figure 2. Unmodified ketone C-glycosides 1 and (E)-
sides 2.
a,b-unsaturated ketone C-glyco-
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.04.052

J.-f. Wang et al. / Tetrahedron 65 (2009) 4826–4833
4827
Table 1
Aldol and aldol condensation reactions of ketone C-glycoside 1a with aldehydes
OH
O
OH
OH
O
O
L-Proline-TEA
CH3OH or H2O
HO
HO
HO
HO
HO
∗
Ar
Ar
ArCHO
HO
OH
1a
OH
2
OH
O
O
O
OH
3
Entry
ArCHO
Media
Time (h)
2 Yielda (%)
3 Yield (%)/(de %)b
1
2
3
4
p-NO2PhCHO
p-NO2PhCHO
Piperonal
H2O
MeOH
H2O
72
72
24
24
2a (d)
2a (trace)
2b (d)
3a (60/39)
3a (73/20)
3b (0/d)
3b (0/d)
Piperonal
MeOH
2b (98)
a
Isolated yields.
The de values were determined by chiral HPLC analysis.
b
Normally,
a,
b-unsaturated carbonyl compounds are prepared
2. Results and discussion
from aromatic aldehydes and ketones by Claisen–Schmidt con-
densation under strong basic conditions,6 which suffer from several
side reactions and narrow substrate diversity. Mild Lewis acid-
catalyzed tandem Mukaiyama aldol–dehydration reactions have
been described, but require pre-formation of enolates from ke-
tones.7 Many researchers have tried to optimize the reaction con-
ditions to the direction of aldol condensation between alhehydes
and/or ketones.8 However, the reaction always produces mixed
products. Recently, Wang9 and co-workers reported a novel pyr-
rolidine imide-catalyzed aldol condensation from ketones and
aldehydes, with moderate to good yields in DMSO (41–95%). Un-
fortunately, the ketone substrates were limited to acetone and
cyclopentanone, and reactions with other ketone substrates pro-
ceeded very slowly, with low yields.9 Moreover, we found that the
Based on our recent work indicating that dipeptide-organobases
could efficiently catalyze the direct aldol reactions of ketones and
aldehydes in water,10 coupled with our wish to utilize ‘green
chemistry’ methods, we were interested in studying the aldol re-
actions between aldehydes and ketone C-glycosides in water,
expecting to achieve some meaningful chiral C-glycoside de-
rivatives 3.
We first examined the aldol reaction between ketone C-glyco-
side 1a and 4-nitro-benzaldehyde in the presence of 20 mol %
L-proline–TEA at room temperature in water. The desired aldol
product 3a was obtained only in 60% yield, with 39% de (Table 1,
entry 1). Even using methanol as solvent, the yield and enantio-
selectivity did not improve significantly (Table 1, entry 2). However,
using piperonal instead of 4-nitro-benzaldehyde, the aldol con-
densation product 2a was obtained unexpectedly in 98% yield in
methanol, although the reaction did not take place in water (Table
1, entries 3 and 4). This unexpected result diverted our interest to
method is also not feasible for the synthesis of (E)-
ketone C-glycosides. Here we report a novel, simple, mild method
for the preparation of (E)- -unsaturated compounds, which is
applicable to a wide range of ketones and aldehydes. It is particu-
larly efficient for the preparation of (E)- -unsaturated ketone
a,b-unsaturated
a,b
a,
b
explore the efficient synthetic procedure for the (E)-
saturated ketone C-glycosides 2.
a,b-un-
C-glycosides from unmodified ketone C-glycosides.
Table 2
Catalyst screening for the aldol condensation reaction
O
O
OH
OH
OH
O
O
O
CHO
O
O
O
O
HO
HO
solvent, rt
HO
HO
HO
HO
OH
OH
OH
2b
O
O
OH
O
1a
3b
Entry
Catalysta
Time (h)
Yield (%)b for product 2b
Yield (%)b for product 3b
1
2
Proline
Pro–Trp
72
72
d
d
0
0
O
O
3c
72
Trace
0
N
H
CF3
NH
4
5
6
7
8
9
10
11
12
13
14
15
16
Proline–TEA
Trp-OH-TEA
Phe-OH-TEA
Leu-OH-TEA
Pro-Trp-TEA
Pro-Leu-TEA
HOAc–TEA
TEA or DABCO
Proline–DABCO
Proline–piperazine
Proline–Me2CHNH2
Proline–AcONa
24
72
72
72
72
72
72
72
26
25
22
72
72
98
54
60
43
Trace
Trace
d
0
0
0
0
0
0
0
0
0
0
0
0
0
d
97
98
97
d
Proline–Na2CO3
d
a
Unless otherwise indicated, all the reactions were carried out in MeOH and the loading of organocatalyst was 20 mol %.
Isolated yields.
The reaction was conducted in DMSO or in MeOH.
b
c

4828
J.-f. Wang et al. / Tetrahedron 65 (2009) 4826–4833
Table 3
Table 4
Solvent screening for the aldol condensation reaction
Effect of proline and TEA loading on the aldol condensation reaction
Entry
Solvent
Time (h)
Yielda (%) for 2b
Yielda (%) for 3b
Entry
Proline loading
(mol %)
TEA loading
(mol %)
Time
(h)
Yielda (%) for
product 2b
1
2
3
4
5
6
7
8
9
MeOH
EtOH
i-PrOH
CH3CN
THF
DMSO
DMF
CHCl3
PhCH3
24
72
72
120
120
120
120
120
120
98
90
85
d
0
0
0
0
0
0
0
0
0
1
2
3
4
5
6
5
10
15
15
15
15
5
10
15
30
60
90
120
72
38
28
27
27
30
92
94
98
98
97
d
Trace
Trace
d
a
Isolated yields.
d
a
Isolated yields.
effective not only for the hexose-derivatized ketone glycosides (1a
and 1b), but also for the pentose-derivatized ketone glycoside (1c).
To further extend the substrate scope, the reactions of piperanol
with other unmodified simple ketones were also explored (Table 6).
Accordingly, a series of acid-base catalysts, including amino
acids, dipeptides, simple organic bases, and their combination,
were screened for the aldol condensation reaction of ketone C-
glycoside 1a with piperonal in methanol at room temperature, and
the results are listed in Table 2.
Amazingly, all the reactions resulted in
a,b-unsaturated com-
pounds without the observation of aldol products as well. Fur-
thermore, we found that tandem aldol condensation reactions took
place easily for the symmetric cyclic ketones especially for cyclo-
hexanone (Table 6, entries 4 and 5). Obviously, the reaction is
a universal method for the formation of a,b-unsaturated carbonyl
compounds, and is applicable to a wide scope of ketone substrates,
including cyclic/acyclic alkyl ketones and aryl ketones.
Neither proline nor Pro–Trp,10 efficient organocatalysts for gen-
eral aldol reactions, showed any catalytic activity (Table 2, entries 1
and 2). Using the reported pyrrolidine imide, an efficient catalyst for
the aldol condensation reaction,9 only trace amount of product was
produced in DMSO or MeOH (Table 2, entry 3). However, the com-
bination of the commercially available amino acids with triethyl-
amine (TEA) could significantly catalyze the reaction, affording the
aldol condensation products 2a in moderate to excellent yields
(Table 2, entries 4–7). Especially, when proline–TEA was used as the
catalyst, theyield increased remarkably to98%. The catalytic effect of
Pro-Trp-TEA and Pro-Leu-TEA was also examined, but only a trace
amount of the desired product was obtained (Table 2, entries 8 and
9). Furthermore, catalyst AcOH–TEA and TEA did not show any cat-
alytic activity (Table 2, entries 10 and 11). Combinations of proline
with various bases were also screened. Organobases, such as DABCO,
piperazine, and isopropylamine were as effective as TEA (Table 2,
entries 12–14), while inorganic bases did not show any catalytic
effect (Table 2, entries 15–16). Therefore, the proline–TEA should be
a suitable acid–base catalyst for this reaction.
Subsequently, the effect of different solvents on the reaction was
studied in the presence of 20 mol % proline–TEA, under the same
conditions (Table 3). We found that high yield was achieved in al-
cohol (Table 3, entries 1–3). In contrast, only trace or no product
was observed in other organic solvents. Comparatively, MeOH was
considered as the most suitable solvent for its high efficiency, low
price, and easy handling.
The reaction of 1a with piperonal was then used as the model,
and the loading amount of proline and TEA was evaluated for their
effect on the reaction efficiency (Table 4). The yield increased from
30% to 94% by increasing proline–TEA loading from 5 mol % to
15 mol %, and the reaction time was also reduced greatly from 120 h
to 38 h (Table 4, entries 1–3). At a constant proline loading of
15 mol %, a little higher loading of TEA could enhance the reaction
efficiency (Table 4, entry 4), while a further increase of TEA did not
improve significantly the reaction (Table 4, entries 5 and 6). Thus,
the combination of 15 mol % of proline and 30 mol % of TEA was
optimal to ensure high reaction efficiency while maintaining
a reasonable reaction time.
Generally, the formation of (E)-a,b-unsaturated carbonyl com-
pounds catalyzed by proline was proposed to be carried out via the
enamine mechanism A11 or the imine mechanism B9,12 (Scheme 1).
Initially, we also thought that the mechanism A should be accept-
able, because the reaction between 1a and p-NO2PhCHO provided
an aldol product instead of an aldol condensation product (Table 1,
entry 2). In order to verify the mechanism with solid evidence, we
tried to capture the key intermediate. The corresponding in-
termediate of the reaction between 1a and 4-methoxy-
benzaldehyde (Table 5, entry 2) was captured carefully by
preparative TLC (CH3OH, Rf¼0.50). It was unexpectedly found,
however, that the structure of the intermediate captured was
a three-component conjugated intramolecular salt VIc, which was
identified by 1H NMR and ESI-TOFþ spectra. On the basis of the
experimental results, we propose a new reaction pathway C. An
asymmetric aldol reaction first takes place via an enamine, forming
the
process to afford a novel intermediate VI. After the leaving of
proline, the -unsaturated ketone C-glycoside 2 is generated.
b-hydroxy-enamine III, which then undergoes a dehydration
a,b
The experimental results are explained readily according to
this newly proposed pathway. Due to the low energy of the
three-component conjugated intermediate VI, the formation of
a,b-unsaturated ketone C-glycosides 2 is easier than the forma-
tion of the aldol product 3. For aldehydes bearing strong elec-
tron-withdrawing groups, it is unfavorable for the dehydration of
b
-hydroxy-enamine intermediate III to form the intermediate VI,
which led to the aldol products with high yield (Table 1, entry 2).
On the contrary, for aldehydes with strong electron-donating
groups, such as p-Me2N-PhCHO (Table 5, entry 18), the in-
termediate VI is not only formed easily, but is also quite stable,
making the reaction stop at this stage even at room temperature.
Therefore, when 110 mol % of proline was used, we could obtain
the pure intermediate VIs in 90% overall yield at room temper-
ature within an hour (Scheme 2). And when VIs was heated in
The generality of the reaction was then examined under the
optimal reaction conditions, namely using 15 mol % of
L-proline and
methanol, the corresponding (E)-a,b-unsaturated ketone C-gly-
30 mol % of TEA as catalyst, methanol as solvent and reaction at
room temperature. As shown in Table 5, all reactions proceeded
smoothly, affording the corresponding (E)-a,b-unsaturated ketones
2 in excellent yields, except entry 18. It is clear that the reaction was
applicable to quite a wide scope of aldehydes, including hetero-
aromatic aldehydes and aromatic aldehydes with moderate elec-
tron-withdrawing and electron-donating groups. Meanwhile, it is
coside 2s was also formed in 60% yield. These results further
supported the pathway C. In the proposed route C, the easy
formation of the intermediate VI from III might derived from the
low energy of the conjugated system VI, which also result in the
difficulty for the leaving of proline from the ketoimine VI. And it
is certain that the formation of VI must be assisted by a base
catalyst such as TEA, for only proline could not catalyze the

J.-f. Wang et al. / Tetrahedron 65 (2009) 4826–4833
4829
Table 5
Aldol condensation reactions of ketone C-glycosides and aldehydes
R
R3
1O
R
R1
R3
1O
R3
O
HO
15 % mol Proline
30 % mol TEA, rt
HO
HO
HO
ArCHO
HO
HO
R2
R2
R2
∗
Ar
Ar
O
O
O
1a R1= H R2 = OH R3 = CH2OH
1b R1= OH R2 = H R3 = CH2OH
1c R1= H R2 = OH R3 = H
HO
3
2
Entry
1
Ketones
Aldehydes
Time (h)
28
Yielda (%) for Product 2b–2t
CHO
O
O
1a
1a
2b
98
96
CHO
2
3
27
30
2c
O
CHO
1a
1a
2d
99
95
O
HO
O
CHO
4
29
2e
O
O
CHO
5
6
7
8
1a
1a
1a
1a
29
26
20
19
2f
94
97
91
97
PhH2C
CHO
CHO
2g
2h
2i
F
Br
CHO
CHO
F3C
9
1a
1a
1a
21
28
28
2j
96
90
92
10
11
2k
2l
CHO
CHO
CHO
O
S
S
12
13
1b
1b
28
29
2m
2n
90
92
CHO
O
O
CHO
CHO
O
O
14
15
1c
1c
27
29
2o
2p
97
95
HO
O
O
CHO
CHO
16
1c
29
28
2q
95
98
HO
17
18
1c
1a
2r
2s
O
72
10
CHO
Me2N
10b
60b
19
1a
72
2t
d
CHO
a
Isolated yields.
The reaction was conducted at reflux.
b

4830
J.-f. Wang et al. / Tetrahedron 65 (2009) 4826–4833
Table 6
reaction (Table 2, entry 1). All the phenomena indicate that the
Aldol condensation reactions of various ketones and piperonal
leaving of proline must be the determining step of the reaction,
which also explains why an excess amount of base is favorable
for the reaction.
Entry
1
Ketone Time (h)
Product (2u–2yb)
Yielda (%)
92
O
O
O
O
26
3. Conclusions
(2u)
In conclusion, we have developed an efficient method for the
synthesis of (E)-a,b-unsaturated ketones from direct aldol con-
densation, catalyzed by proline–TEA in methanol. This method has
the advantages of a wide scope of substrates, mild reaction condi-
tions, simple work-up, and high yield. This method has been used
successfully in the synthesis of (E)-a,b-unsaturated ketone C-gly-
cosides, providing a potential application for the synthesis of C-glycoside
derivatives.
O
O
O
O2N
O
O2N
2
3
20
94
O
(2v)
O
O
O
82
80
85
MeO
(2w)
MeO
O
4. Experimental
O
4
29
O
4.1. General procedure for the synthesis of 2 and 3a
O
(2xa)
A mixture of compound 1 (0.5 mmol), an aldehyde (0.6 mmol),
and proline (0.075 mmol)–TEA (0.15 mmol) in 1.0 mL of anhydrous
CH3OH was stirred at room temperature for 19–30 h. The endpoint of
the reaction was monitored by TLC. The resulting mixture was puri-
fied by filtration and/or silica gel chromatography and fractions were
collectedandconcentratedinvacuotoprovideasolidorclearoil2and
3a. The de values of 3a were determined by HPLC analysis with
a Chiralpak AS-H column, 25% isopropyl alcohol in hexane, 1.0 mL/
min, 254 nm, retention times minor 11.9 min, major 17.5 min.
O
9
36
55
O
O
O
O
(2xb)
O
O
O
O
5
29
(2ya)
O
4.1.1. (E)-4-(Benzo[d][1,3]dioxol-5-yl)-1-[3,4,5-trihydroxy-6-
(hydroxymethyl)-tetrahydro-2H-pyran-2-yl]but-3-en-2-one (2b)
Obtained in 98% yield; white powder; mp: 150–152 ꢀC; 1H NMR
O
O
O
O
(2yb)
(300 MHz, D2O):
d
7.47 (d, J¼16.2 Hz, 1H), 7.05 (s, 1H) overlapping
a
Isolated yield. The products were isolated by filtration and silica gel
chromatography.
with 7.04–7.00 (d, J¼8.4 Hz, 1H), 6.75 (d, J¼8.4 Hz, 1H), 6.57 (d,
J¼16.2 Hz, 1H), 5.86 (s, 2H), 3.66–3.62 (m, 2H), 3.51–3.47 (m, 1H),
3.32 (m, 1H), 3.22 (m, 2H), 3.14–2.99 (m, 2H), 2.77 (dd, J¼9.0,
O
COOH
COO-
N+
O
O
R
N
H
COO-
H
Ar
N+
R
R
ArCHO
Ar
2
Ar
IV
H
V
Mechanism B
-H2O
O
COOH
Base
O
N
H
COO-
N+ OH
COO-
OH
N+
ArCHO
Base
R
COOH
N
R
R
Ar
R
R
H
Ar
3
H
III
I
II
H
Base
Mechanism A
-H2O
COO-
OH
O
OMe
COOH
Ar
H2O
O
-Proline
N
N+
HO
HO
R
Ar
Base
R
R
OH
N+
2
Ar
COO-
OH
VIc
VI
OH-
VII
Pathway C
Scheme 1. Proposed mechanisms for the aldol condensation process catalyzed by proline–TEA.
OH
OH
NMe2
CHO
110 mol% proline-TEA
Me2N
O
O
HO
HO
HO
HO
CH3OH
Reflux
2s
OH
N+
OH
COO-
O
VIs
Scheme 2. Synthesis of the intermediate VIs and product 2s.

J.-f. Wang et al. / Tetrahedron 65 (2009) 4826–4833
4831
15.5 Hz, 1H); 13C NMR (75 MHz, DMSO-d6):
142.1, 128.9, 125.3, 124.9, 108.6, 106.7, 101.6, 80.7, 78.1, 75.8, 73.6,
70.3, 61.1, 43.3. Anal. Calcd for C17H20O8: C 57.95, H 5.72; found: C
57.83, H 5.74.
d
197.9, 149.4, 148.1,
128.5,128.5,125.9, 80.7, 78.1, 75.8, 73.6,70.2,61.1, 43.3,21.1;HRMS-ESI
(m/z): [MþNa]þ calculated for C17H22O6Na 345.1314, found 345.1309.
4.1.7. (E)-4-(4-Fluorophenyl)-1-[3,4,5-trihydroxy-6-(hydroxy-
methyl)-tetrahydro-2H-pyran-2-yl]but-3-en-2-one (2h)
Obtained in 91% yield; white powder; mp: 158–160 ꢀC; 1H NMR
4.1.2. (E)-4-(4-Methoxyphenyl)-1-[3,4,5-trihydroxy-6-(hydroxy-
methyl)-tetrahydro-2H-pyran-2-yl]but-3-en-2-one (2c)
(500 MHz, DMSO-d6):
d
7.80 (m, 1H), 7.59 (d, J¼16.5 Hz, 1H), 7.26 (t,
Obtained in 96% yield; white powder; mp: 152–154 ꢀC; 1H NMR
J¼9.0 Hz, 1H), 6.92 (d, J¼16.5 Hz, 1H), 5.05 (d, J¼5.5 Hz, 1H), 4.92 (d,
J¼4.5 Hz, 1H), 4.85 (d, J¼5.0 Hz, 1H), 4.34 (t, J¼5.7 Hz, 1H), 3.64–
3.57 (m, 2H), 3.41–3.35 (m, 1H), 3.19–3.15 (m, 1H), 3.10–3.03 (m,
2H), 2.98–2.93 (m, 2H), 2.78 (dd, J¼8.7, 16.5 Hz, 1H); 13C NMR
(300 MHz, DMSO-d6):
d
7.68 (d, J¼8.7 Hz, 2H), 7.56 (d, J¼16.2 Hz,
1H), 6.99 (d, J¼8.7 Hz, 2H), 6.82 (d, J¼16.2 Hz, 1H), 5.06 (d,
J¼6.0 Hz, 1H), 4.94 (d, J¼4.5 Hz, 1H), 4.87 (d, J¼4.5 Hz, 1H), 4.36 (t,
J¼5.4 Hz, 1H), 3.80 (s, 3H), 3.64–3.56 (m, 2H), 3.40–3.36 (m, 1H),
3.18–3.16 (m, 1H), 3.08–3.07 (m, 2H), 2.98–2.89 (m, 2H), 2.77 (dd,
(125 MHz, DMSO-d6):
d
198.0, 163.2 (d, 1JC–F¼248.0Hz), 140.8, 131.2,
3
3
2
130.7 (d, JC–F¼8.7 Hz), 130.7 (d, JC–F¼8.7 Hz), 126.7, 115.9 (d, JC–
J¼8.4, 16.2 Hz, 1H); 13C NMR (75 MHz, DMSO-d6):
d
197.9, 161.1,
¼21.0 Hz), 115.9 (d, 2JC–F¼21.0 Hz), 80.7, 78.1, 75.8, 73.6, 70.3, 61.1,
F
142.0, 130.4, 130.3, 127.1, 124.6, 114.5, 114.4, 80.7, 78.2, 75.9, 73.6,
70.3, 61.1, 55.4, 43.2. Anal. Calcd for C17H22O7: C 60.35, H 6.55;
found: C 60.32, H 6.55.
43.4; HRMS-ESI (m/z): [MþNa]þ calculated for C16H19FO6Na
349.1063, found 349.1052.
4.1.8. (E)-4-(3-Bromophenyl)-1-[3,4,5-trihydroxy-6-(hydroxy-
methyl)-tetrahydro-2H-pyran-2-yl]but-3-en-2-one (2i)
4.1.3. (E)-4-(2-Methoxyphenyl)-1-[3,4,5-trihydroxy-6-(hydroxy-
methyl)-tetrahydro-2H-pyran-2-yl]but-3-en-2-one (2d)
Obtained in 97% yield; white powder; mp: 148–150 ꢀC; 1H NMR
Obtained in 99% yield; colorless oil; 1H NMR (300 MHz, DMSO-
(300 MHz, DMSO-d6):
d
7.96 (s, 1H), 7.73 (d, J¼7.8 Hz, 1H), 7.60 (d,
d6):
d
7.77 (d, J¼16.2 Hz, 1H), 7.71 (d, J¼7.8 Hz, 1H), 7.43–7.38 (m,
J¼7.8 Hz, 1H), 7.54 (d, J¼16.2 Hz, 1H), 7.37 (t, J¼7.5 Hz, 1H), 7.02
(d, J¼16.2 Hz, 1H), 5.05 (d, J¼6.0 Hz, 1H), 4.92 (d, J¼4.8 Hz, 1H), 4.85
(d, J¼4.5 Hz, 1H), 4.34 (t, J¼5.7 Hz, 1H), 3.65–3.56 (m, 2H), 3.39–
3.34 (m, 1H), 3.17–3.13 (m, 1H), 3.10–3.05 (m, 2H), 2.98–2.90 (m,
2H), 2.77 (dd, J¼8.7, 16.5 Hz, 1H); 13C NMR (75 MHz, DMSO-d6):
1H), 7.08 (d, J¼7.8 Hz, 1H), 7.00–6.95 (m, 1H) overlapping with 6.95
(d, J¼16.2 Hz, 1H), 5.09 (d, J¼5.4 Hz, 1H), 4.98 (d, J¼3.6 Hz, 1H), 4.90
(d, J¼3.9 Hz, 1H), 4.36 (t, J¼5.4 Hz, 1H), 3.86 (s, 3H), 3.63–3.54 (m,
2H), 3.40–3.36 (m, 1H), 3.16–3.14 (m, 1H), 3.11–3.05 (m, 2H), 2.96–
2.90 (m, 2H), 2.72 (dd, J¼8.7, 16.2 Hz, 1H); 13C NMR (75 MHz,
d
198.0, 140.2, 137.1, 132.8, 131.0, 130.9, 128.1, 127.4, 122.3, 80.7, 78.1,
DMSO-d6):
d
198.0, 158.1, 136.4, 132.1, 128.3, 126.8, 122.7, 120.8,
75.7, 73.6, 70.3, 61.1, 43.7. Anal. Calcd for C16H19BrO6: C 49.63, H
4.95; found: C 49.90, H 5.13.
111.8, 80.7, 78.1, 75.8, 73.6, 70.2, 61.1, 55.7, 43.8; HRMS-ESI (m/z):
[MþNa]þ calculated for C17H22O7Na 361.1263, found 361.1262.
4.1.9. (E)-4-[3-(Trifluoromethyl)phenyl]-1-[3,4,5-trihydroxy-6-
(hydroxymethyl)-tetrahydro-2H-pyran-2-yl]but-3-en-2-one (2j)
Obtained in 96% yield; white powder; mp: 142–145 ꢀC; 1H
4.1.4. (E)-4-(3-Hydroxy-4-methoxyphenyl)-1-[3,4,5-trihydroxy-6-
(hydroxymethyl)-tetrahydro-2H-pyran-2-yl]but-3-en-2-one (2e)
Obtained in 95% yield; white powder; mp: 198–199 ꢀC; 1H NMR
NMR (500 MHz, DMSO-d6):
d
8.11 (s, 1H), 8.05 (d, J¼8.0 Hz, 1H),
(300 MHz, DMSO-d6):
d
9.22 (s, 1H), 7.47 (d, J¼16.5 Hz, 1H), 7.14 (d,
7.77 (d, J¼8.0 Hz, 1H), 7.68 (d, J¼16.5 Hz, 1H) overlapping with
7.66 (m, 1H), 5.09 (d, J¼5.5 Hz, 1H), 4.98 (br, 1H), 4.89 (br, 1H),
4.35 (t, J¼5.5 Hz, 1H), 3.66–3.58 (m, 2H), 3.42–3.38 (m, 1H), 3.20–
3.17 (m, 1H), 3.11–3.05 (m, 2H), 3.00–2.94 (m, 2H), 2.81 (dd, J¼9.0,
J¼9.1 Hz, 1H) overlapping with 7.13 (s, 1H), 6.97 (d, J¼9.1 Hz, 1H),
6.68 (d, J¼16.2 Hz, 1H), 5.05 (d, J¼5.4 Hz, 1H), 4.94 (d, J¼4.5 Hz, 1H),
4.87 (d, J¼4.8 Hz, 1H), 4.36 (t, J¼5.4 Hz, 1H), 3.82 (s, 3H), 3.64–3.57
(m, 2H), 3.41–3.35 (m, 1H), 3.18–3.16 (m, 1H), 3.12–3.05 (m, 2H),
2.99–2.89 (m, 2H), 2.77 (dd, J¼9.0, 16.2 Hz, 1H); 13C NMR (75 MHz,
16.5 Hz, 1H); 13C NMR (125 MHz, DMSO-d6):
d 198.1, 140.1, 135.8,
2
132.0, 130.0, 129.8 (q, JC–F¼31.1 Hz), 128.6, 126.5, 125.1, 124.0 (q,
1JC–F¼273.8 Hz), 80.7, 78.1, 75.7, 73.6, 70.3, 61.1, 43.7; HRMS-ESI
(m/z): [MþNa]þ calculated for C17H19F3O6Na 399.1031, found
399.1029.
DMSO-d6): d 197.8,150.1,146.7,142.5,127.3,124.5,121.6,114.3,112.0,
80.7, 78.2, 75.9, 73.6, 70.3, 61.1, 55.7, 43.2. Anal. Calcd for C17H22O8:
C 57.62, H 6.26; found: C 57.40, H 5.96.
4.1.5. (E)-4-[4-(Benzyloxy)-3-methoxyphenyl]-1-[3,4,5-trihydroxy-
6-(hydroxymethyl)-tetrahydro-2H-pyran-2-yl]but-3-en-2-one (2f)
Obtained in 94% yield; white powder; mp: 134–135 ꢀC; 1H NMR
4.1.10. (E)-4-(Furan-2-yl)-1-[3,4,5-trihydroxy-6-(hydroxymethyl)-
tetrahydro-2H-pyran-2-yl]but-3-en-2-one (2k)
Obtained in 90% yield; colorless oil; 1H NMR (500 MHz, DMSO-
(300 MHz, DMSO-d6):
d
7.53 (d, J¼16.2 Hz, 1H), 7.47–7.36 (m, 6H),
d6):
d
7.86 (d, J¼2.0 Hz, 1H), 7.40 (d, J¼16.0 Hz, 1H), 6.98 (d,
7.25 (dd, J¼1.8, 8.4 Hz, 1H), 7.09 (d, J¼8.4 Hz, 1H), 6.87 (d, J¼16.2 Hz,
1H), 5.14 (s, 2H), 5.06 (d, J¼5.4 Hz,1H), 4.95 (d, J¼4.8 Hz,1H), 4.87 (d,
J¼4.5 Hz, 1H), 4.36 (t, J¼5.7 Hz, 1H), 3.83 (s, 3H), 3.64–3.57 (m, 2H),
3.41–3.36(m,1H), 3.18–3.16(m,1H), 3.08–3.07(m, 2H), 2.98–2.90(m,
2H), 2.78 (dd, J¼8.7, 16.2 Hz, 1H); 13C NMR (75 MHz, DMSO-d6):
J¼3.5 Hz, 1H), 6.65 (dd, J¼1.5, 3.5 Hz, 1H), 6.59 (d, J¼16.0 Hz, 1H),
5.03 (d, J¼6.0 Hz, 1H), 4.90 (m, 1H), 4.84 (d, J¼5.0 Hz, 1H), 4.31 (t,
J¼5.7 Hz, 1H), 3.60–3.56 (m, 2H), 3.40–3.36 (m, 1H), 3.17–3.14 (m,
1H), 3.09–3.01 (m, 2H), 2.95–2.90 (m, 2H), 2.74 (dd, J¼8.5, 16.0 Hz,
1H); 13C NMR (125 MHz, DMSO-d6):
d 197.5, 150.6, 145.9, 128.8,
d
197.9, 149.9, 149.2, 142.4, 136.8, 128.5, 128.5, 128.0, 127.9, 127.6,
123.6, 116.4, 112.9, 80.7, 78.1, 75.9, 73.5, 70.2, 61.1, 43.3; HRMS-ESI
(m/z): [MþNa]þ calculated for C15H20O6Na 321.0951, found
321.0943.
124.9, 123.0, 113.1, 110.7, 80.7, 78.2, 75.9, 73.6, 70.3, 69.8, 61.1, 55.7,
43.2. Anal. Calcd for C24H28O8: C 64.85, H 6.35; found: C 64.60, H 6.24.
4.1.6. (E)-4-p-Tolyl-1-[3,4,5-trihydroxy-6-(hydroxymethyl)-
tetrahydro-2H-pyran-2-yl]but-3-en-2-one (2g)
4.1.11. (E)-4-(Thiophen-2-yl)-1-[3,4,5-trihydroxy-6-(hydroxy-
methyl)-tetrahydro-2H-pyran-2-yl]but-3-en-2-one (2l)
Obtained in 97% yield; white powder; mp: 158–160 ꢀC; 1H NMR
Obtained in 92% yield; white powder; mp: 149–151 ꢀC; 1H NMR
(300 MHz, DMSO-d6):
d
7.62 (d, J¼8.1 Hz, 2H) overlapping with 7.57
(500 MHz, DMSO-d6):
d
7.76 (d, J¼16.5 Hz,1H), 7.73 (d, J¼5.0 Hz,1H),
(d, J¼15.9 Hz, 1H), 7.24 (d, J¼7.8 Hz, 2H), 6.90 (d, J¼16.5 Hz, 1H), 5.10
(d, J¼5.4 Hz, 1H), 5.01 (br, 1H), 4.93 (br, 1H), 4.39 (t, J¼5.7 Hz, 1H),
3.64–3.55 (m, 2H), 3.43–3.37 (m,1H), 3.19–3.14 (m,1H), 3.12–3.05 (m,
2H), 2.99–2.92 (m, 2H), 2.79 (dd, J¼8.7, 16.2 Hz, 1H), 2.33 (s, 3H); 13C
7.55 (d, J¼3.5 Hz, 1H), 7.16 (dd, J¼3.5, 5.0 Hz, 1H), 6.60 (d, J¼16.5 Hz,
1H), 5.03 (d, J¼6.0 Hz, 1H), 4.90 (d, J¼4.5 Hz, 1H), 4.84 (d, J¼5.0 Hz,
1H), 4.31 (t, J¼6.0 Hz, 1H), 3.61–3.56 (m, 2H), 3.41–3.36 (m, 1H),
3.19–3.15 (m, 1H), 3.10–3.02 (m, 2H), 2.96–2.90 (m, 2H), 2.76 (dd,
NMR (75 MHz, DMSO-d6):
d
198.1, 142.1, 140.4, 131.8, 129.6, 129.6,
J¼9.0, 16.5 Hz, 1H); 13C NMR (125 MHz, DMSO-d6):
d 197.5, 139.5,

4832
J.-f. Wang et al. / Tetrahedron 65 (2009) 4826–4833
134.9, 132.3, 129.9, 128.6, 125.3, 80.7, 78.1, 75.9, 73.6, 70.3, 61.1, 43.2.
Anal. Calcd for C14H18O6S: C 53.49, H 5.77; found: C 53.39, H 5.89.
4.1.17. (E)-4-(4-Methoxyphenyl)-1-(3,4,5-trihydroxy-tetrahydro-
2H-pyran-2-yl)but-3-en-2-one (2r)
Obtained in 98% yield; white powder; mp: 120–122 ꢀC; 1H NMR
4.1.12. (E)-4-(Thiophen-2-yl)-1-[3,4,5-trihydroxy-6-(hydroxy-
methyl)-tetrahydro-2H-pyran-2-yl]but-3-en-2-one (2m)
Obtained in 90% yield; white powder; mp: 174–176 ꢀC; 1H NMR
(300 MHz, DMSO-d6):
d
7.68 (d, J¼8.7 Hz, 2H), 7.55 (d, J¼15.9 Hz,
1H), 7.00 (d, J¼9.0 Hz, 2H), 6.77 (d, J¼16.2 Hz, 1H), 5.09 (d, J¼5.7 Hz,
1H), 4.98 (d, J¼4.5 Hz, 1H), 4.93 (d, J¼5.7 Hz, 1H), 3.80 (s, 3H), 3.64
(dd, J¼5.1, 10.8 Hz, 1H), 3.55 (td, J¼2.4, 9.3 Hz, 1H), 3.25 (td, J¼5.1,
9.3 Hz, 1H), 3.11 (td, J¼4.8, 10.2 Hz, 1H), 2.99–2.95 (m, 1H), 2.94–
2.92 (m, 1H), 2.87 (d, J¼2.4 Hz, 1H), 2.77 (dd, J¼9.3, 15.9 Hz, 1H); 13C
(500 MHz, DMSO-d6):
d
7.76 (d, J¼16.0 Hz, 1H), 7.73 (d, J¼5.0 Hz,
1H), 7.56 (d, J¼3.5 Hz, 1H), 7.16 (dd, J¼4.0, 4.5 Hz, 1H), 6.59 (d,
J¼16.0 Hz, 1H), 4.67 (d, J¼4.0 Hz, 1H), 4.63 (d, J¼4.5 Hz, 1H), 4.42 (d,
J¼5.0 Hz, 1H), 4.28 (t, J¼6.0 Hz, 1H), 3.82 (t, J¼6.5 Hz, 1H), 3.65–3.57
(m, 2H), 3.42–3.37 (m,1H), 3.32 (m, 2H), 3.03 (m,1H), 2.94–2.84 (m,
NMR (75 MHz, DMSO-d6):
d 198.2, 161.2, 142.2, 130.3, 130.3, 126.9,
124.7, 114.4, 114.4, 78.2, 77.2, 73.6, 69.9, 69.7, 55.3, 42.9. Anal. Calcd
for C16H20O6$0.25H2O: C 61.43, H 6.61; found: C 61.40, H 6.35.
2H); 13C NMR (125 MHz, DMSO-d6):
d
197.3, 139.3, 134.9, 132.5,
129.9, 128.6, 125.2, 81.2, 74.7, 74.1, 70.3, 61.5, 42.0. Anal. Calcd for
C14H18O6S$0.5H2O: C 52.00, H 5.92; found: C 52.11, H 5.95.
4.1.18. (E)-4-[4-(Dimethylamino)phenyl]-1-[3,4,5-trihydroxy-6-
(hydroxymethyl)-tetrahydro-2H-pyran-2-yl]but-3-en-2-one (2s)
Obtained in 60% yield; yellow powder; mp: 226–228 ꢀC; 1H NMR
4.1.13. (E)-4-(Benzo[d][1,3]dioxol-5-yl)-1-[3,4,5-trihydroxy-6-
(hydroxymethyl)-tetrahydro-2H-pyran-2-yl]but-3-en-2-one (2n)
Obtained in 92% yield; white powder; mp: 170–171 ꢀC; 1H NMR
(300 MHz, DMSO-d6):
d
7.54 (d, J¼9.0 Hz, 2H)overlappingwith7.49(d,
J¼16.2 Hz, 1H), 6.72 (d, J¼9.0 Hz, 2H) overlapping with 6.67 (d,
J¼16.2 Hz, 1H), 5.03 (d, J¼5.4 Hz, 1H), 4.92 (br, 1H), 4.86 (d, J¼3.6 Hz,
1H), 4.34 (t, J¼5.7 Hz, 1H), 3.63–3.57 (m, 2H), 3.34 (m, 1H), 3.17–3.11
(m,1H), 3.08–3.04(m, 2H), 2.98(s,6H)overlappingwith2.98–2.85 (m,
(500 MHz, DMSO-d6):
d
7.51 (d, J¼16.0 Hz, 1H), 7.40 (d, J¼1.5 Hz,
1H), 7.21 (dd, J¼1.5, 8.0 Hz, 1H), 6.97 (d, J¼8.5 Hz, 1H), 6.80 (d,
J¼16.0 Hz, 1H), 6.08 (s, 2H), 4.67 (d, J¼2.5 Hz, 1H), 4.63 (d, J¼5.0 Hz,
1H), 4.42 (d, J¼4.5 Hz, 1H), 4.29 (t, J¼5.5 Hz, 1H), 3.84 (t, J¼6.0 Hz,
1H), 3.65–3.63 (m, 1H), 3.58–3.57 (m, 1H), 3.41–3.37 (m, 1H), 3.37–
3.28 (m, 2H), 3.04–3.01 (m, 1H), 2.94–2.84 (m, 2H); 13C NMR
2H), 2.73(dd, J¼8.7,15.9 Hz,1H); 13C NMR (75 MHz, DMSO-d6):
d197.4,
151.8, 143.1, 130.2, 130.2, 121.6, 121.6, 111.8, 111.8, 80.7, 78.2, 76.0, 73.6,
70.3,61.1, 43.0, 39.7, 39.7. Anal.CalcdforC18H25NO6$0.3H2O:C60.59, H
7.23, N 3.93; found: C 60.48, H 6.97, N 3.92.
(125 MHz, DMSO-d6): d 197.8, 149.4, 148.1, 142.1, 128.9, 125.2, 124.9,
108.6,106.7, 101.6, 81.2, 74.8, 74.1, 70.4, 67.2, 61.6, 42.1; ESI-TOFþ (m/z):
[MþNa]þ calculated for C22H29NO8Na 375.1056, found 375.1733.
4.1.19. (E)-1-(Benzo[d][1,3]dioxol-5-yl)pent-1-en-3-one (2u)
Obtained in 92% yield; white powder; 1H NMR (300 MHz,
4.1.14. (E)-4-(Benzo[d][1,3]dioxol-5-yl)-1-(3,4,5-trihydroxy-
tetrahydro-2H-pyran-2-yl)but-3-en-2-one (2o)
CDCl3):
d
7.47 (t, J¼16.2 Hz, 1H), 7.06–7.01 (m, 2H), 6.82 (d, J¼7.8 Hz,
1H), 6.58 (t, J¼15.9 Hz, 1H), 6.01 (s, 2H), 2.67 (q, J¼7.2 Hz, 2H), 1.16
(t, J¼7.2 Hz, 3H).
Obtained in 97% yield; white powder; mp: 96–98 ꢀC; 1H NMR
(300 MHz, DMSO-d6):
d
7.51 (d, J¼16.2 Hz, 1H), 7.40 (d, J¼1.2 Hz,
1H), 7.21 (dd, J¼1.5, 8.1 Hz, 1H), 6.97 (d, J¼8.1 Hz, 1H), 6.79 (d,
J¼16.2 Hz, 1H), 6.09 (s, 2H), 5.10 (d, J¼5.7 Hz, 1H), 4.99 (d, J¼4.5 Hz,
1H), 4.94 (d, J¼5.1 Hz, 1H), 3.64 (dd, J¼5.1, 10.8 Hz, 1H), 3.57 (td,
J¼2.7, 9.5 Hz, 1H), 3.25 (td, J¼5.1, 9.5 Hz, 1H), 3.11 (td, J¼4.5, 8.6 Hz,
1H), 2.99–2.96 (m, 1H), 2.92 (t, J¼4.2 Hz, 1H), 2.87 (d, J¼2.7 Hz, 1H),
4.1.20. (E)-3-(Benzo[d][1,3]dioxol-5-yl)-1-(3-nitrophenyl)prop-2-
en-1-one (2v)
Obtained in 94% yield; yellow powder; 1H NMR (300 MHz,
CDCl3):
d
8.82 (t, J¼2.1 Hz, 1H), 8.45–8.44 (m, 1H), 8.42–8.41 (m,
1H), 8.36–8.35 (m, 1H), 8.33–8.32 (m, 1H), 7.82 (d, J¼15.3 Hz, 1H),
7.71 (t, J¼7.8 Hz, 1H), 7.37 (d, J¼15.3 Hz, 1H), 7.20–7.15 (m, 2H), 6.87
(d, J¼8.1 Hz, 1H), 6.06 (s, 2H).
2.76 (dd, J¼9.3, 15.9 Hz, 1H); 13C NMR (75 MHz, DMSO-d6):
d 198.2,
149.4, 148.1, 142.3, 128.9, 125.3, 125.1, 108.6, 106.7, 101.7, 78.2, 77.2,
73.6, 70.0, 69.8, 43.1. Anal. Calcd for C16H18O7$0.5H2O: C 58.00, H
5.78; found: C 58.23, H 6.01.
4.1.21. (E)-3-(Benzo[d][1,3]dioxol-5-yl)-1-(4-methoxyphenyl)prop-
2-en-1-one (2w)
4.1.15. (E)-4-(3-Hydroxy-4-methoxyphenyl)-1-(3,4,5-trihydroxy-
tetrahydro-2H-pyran-2-yl)but-3-en-2-one (2p)
Obtained in 80% yield; yellow powder; 1H NMR (300 MHz,
CDCl3):
d
8.03 (d, J¼9.0 Hz, 2H), 7.73 (d, J¼15.6 Hz, 1H), 7.38 (d,
Obtained in 95% yield; white powder; mp: 198–200 ꢀC; 1H NMR
J¼15.6 Hz, 1H), 7.17–7.11 (m, 2H), 6.98 (d, J¼9.0 Hz, 2H), 6.85 (d,
(300 MHz, DMSO-d6):
d
9.22 (s, 1H), 7.45 (d, J¼16.5 Hz, 1H), 7.13 (d,
J¼7.8 Hz, 2H), 6.03 (s, 2H), 3.89 (s, 3H).
J¼9.1 Hz,1H) overlapping with 7.11 (s,1H), 6.96 (d, J¼9.1 Hz,1H), 6.64
(d, J¼16.2 Hz, 1H), 5.07 (d, J¼6.0 Hz, 1H), 4.97 (d, J¼4.5 Hz, 1H), 4.92
(d, J¼4.8 Hz, 1H), 3.81 (s, 3H), 3.66–3.61 (m, 1H), 3.56–3.50 (m, 1H),
3.27–3.22 (m, 1H), 3.18–3.06 (m, 1H), 2.98–2.85 (m, 3H), 2.76 (dd,
4.1.22. (E)-2-(Benzo[d][1,3]dioxol-5-ylmethylene)cyclo-
pentanone (2xa)
Obtained in 85% yield; white powder; 1H NMR (300 MHz,
J¼9.0,15.6 Hz,1H); 13C NMR (75 MHz, DMSO-d6):
d
198.1,150.1,146.7,
CDCl3):
d
7.31 (t, J¼2.7 Hz, 1H), 7.06 (d, J¼9.3 Hz, 1H), 7.05 (s, 1H),
142.7, 127.2, 124.5, 121.6, 114.2, 111.9, 78.2, 77.3, 73.6, 69.9, 69.8, 55.6,
42.9. Anal. Calcd for C16H20O7: C 59.25, H 6.22; found: C 59.00, H 6.33.
6.86 (d, J¼7.8 Hz, 2H), 6.02 (s, 2H), 2.97–2.92 (m, 2H), 2.43–2.37 (m,
2H), 2.09–2.01 (m, 2H).
4.1.16. (E)-4-(4-Hydroxy-3-methoxyphenyl)-1-(3,4,5-trihydroxy-
tetrahydro-2H-pyran-2-yl)but-3-en-2-one (2q)
4.1.23. (2E,5E)-2,5-Bis(benzo[d][1,3]dioxol-5-ylmethylene)-
cyclopentanone (2xb)
Obtained in 95% yield; white powder; mp: 209–211 ꢀC; 1H NMR
Obtained in 9% yield; yellow powder; 1H NMR (300 MHz,
(300 MHz, DMSO-d6):
d
9.65 (s, 1H), 7.49 (d, J¼16.2 Hz, 1H), 7.30 (d,
CDCl3):
d
7.70 (s, 2H), 7.02 (d, J¼11.0 Hz, 2H), 6.99 (s, 2H), 6.84 (d,
J¼1.8 Hz, 1H), 7.13 (dd, J¼2.1, 8.7 Hz, 1H), 6.80 (d, J¼8.1 Hz, 1H), 6.75
(d, J¼15.9 Hz, 1H), 5.09 (d, J¼5.7 Hz, 1H), 4.98 (d, J¼4.5 Hz, 1H), 4.92
(d, J¼5.1 Hz, 1H), 3.82 (s, 3H), 3.66–3.61 (m, 1H), 3.58–3.50 (m, 1H),
3.30–3.20 (m, 1H), 3.14–3.06 (m, 1H), 2.98–2.85 (m, 3H), 2.76 (dd,
J¼8.0 Hz, 2H), 6.00 (s, 4H), 3.07 (s, 4H).
4.1.24. (E)-2-(Benzo[d][1,3]dioxol-5-ylmethylene)-
cyclohexanone (2ya)
J¼9.3, 15.6 Hz, 1H); 13C NMR (75 MHz, DMSO-d6):
d
198.0, 149.4,
Obtained in 36% yield; yellow powder; 1H NMR (500 MHz,
147.9, 142.9, 125.9, 123.9, 123.3, 115.6, 111.3, 78.2, 77.2, 73.6, 69.9,
69.7, 55.7, 42.9. Anal. Calcd for C16H20O7$0.6H2O: C 57.34, H 6.38;
found: C 57.14, H 6.44.
CDCl3):
d
7.43 (t, J¼2.0 Hz, 1H), 6.93 (d, J¼8.0 Hz, 1H), 6.92 (s, 1H),
6.83 (d, J¼8.0 Hz, 1H), 6.00 (s, 2H), 2.82 (ddd, J¼2.0 Hz, 2H), 2.52 (t,
J¼7.0 Hz, 2H), 1.94–1.89 (m, 2H), 1.80–1.75 (m, 2H).

J.-f. Wang et al. / Tetrahedron 65 (2009) 4826–4833
4833
4.1.25. (2E,6E)-2,6-Bis(benzo[d][1,3]dioxol-5-ylmethylene)-
cyclohexanone (2yb)
Basic Research Development Program (Grant No. 2004CB-
719900).
Obtained in 55% yield; yellow powder; 1H NMR (300 MHz,
CDCl3):
d
7.70 (s, 2H), 7.00 (d, J¼7.8 Hz, 2H), 6.98 (s, 2H), 6.85 (d,
Supplementary data
J¼8.4 Hz, 2H), 6.00 (s, 4H), 2.90–2.87 (m, 4H), 1.82–1.78 (m, 2H).
1H NMR, 13C NMR, HRMS and elemental analysis spectra for all
the products are provided as supplementary data. Supplementary
data associated with this article can be found in the online version,
at doi:10.1016/j.tet.2009.04.052.
4.1.26. 4-Hydroxy-4-(4-nitrophenyl)-1-[3,4,5-trihydroxy-6-
(hydroxymethyl)-tetrahydro-2H-pyran-2-yl]butan-2-one (3a)
Obtained in 73% yield; colorless oil; 1H NMR (300 MHz, D2O):
d
8.05 (d, J¼8.7 Hz, 1H), 7.42 (d, J¼8.7 Hz, 1H), 5.17–5.13 (m, 1H),
3.62–3.52 (m, 2H), 3.48–3.43 (m, 1H), 3.31–3.21 (m, 1H), 3.19–3.15
References and notes
(m, 2H), 3.05–2.85 (m, 3H), 2.80 (dd, J¼3.0, 16.5 Hz, 1H), 2.60–2.49
(m, 1H); 13C NMR (75 MHz, D2O):
d 213.2, 153.0, 149.7, 129.6, 129.5,
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4.2.1. Compound VIc
Yellow powder. 1H NMR (500 MHz, CD3OD):
d
7.99 (d, J¼15.5 Hz,
1H), 7.75 (d, J¼9.0 Hz, 2H), 7.03 (d, J¼8.5 Hz, 2H) overlapping with
6.99 (d, J¼16.0 Hz, 1H), 4.98 (dd, J¼4.0, 8.5 Hz, 1H), 4.39–4.31 (m,
1H), 4.26–4.21 (m, 1H), 3.87 (s, 3H), 3.83–3.81 (m, 1H), 3.78–3.74
(m, 1H), 3.72–3.68 (m, 1H), 3.65–3.54 (m, 2H), 3.36–3.15 (m, 4H),
2.50–2.42 (m, 1H), 2.40–2.33 (m, 1H), 2.20–1.96 (m, 2H). ESI-TOFþ
(m/z): [(MþH)þ] calculated for C22H30NO8 436.1971; found
436.2695; [(MþNa)þ] calculated for C22H29NO8Na 458.1791; found
458.2539.
4.2.2. Compound VIs
Obtained in 90% yield; red powder; 1H NMR (300 MHz, CD3OD):
d
7.92 (d, J¼15.3 Hz, 1H), 7.63 (d, J¼9.0 Hz, 2H), 6.78 (d, J¼9.3 Hz,
2H) overlapping with 6.77 (d, J¼13.8 Hz, 1H), 4.61 (br, 1H), 4.35–
4.28 (m, 1H), 4.17–4.13 (m, 1H), 3.77 (dd, J¼2.4, 11.7 Hz, 1H), 3.68–
3.51 (m, 3H), 3.31–3.10 (m, 5H), 3.10 (s, 6H), 2.48–2.39 (m, 1H),
2.34–2.28 (m, 1H), 2.14–2.06 (m, 2H); 13C NMR (75 MHz, CD3OD):
d
175.2, 174.2, 155.5, 154.9, 133.8, 133.8, 123.1, 113.1, 113.1, 112.9, 81.7,
81.2, 79.4, 75.5, 71.4, 69.6, 62.8, 55.8, 40.2, 40.2, 35.1, 31.8, 24.4. ESI-
TOFþ (m/z): [(MþH)þ] calculated for C23H33N2O7 449.2288; found
449.3670; [(MþNa)þ] calculated for C23H32N2O7Na 471.2107; found
471.3553.
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Acknowledgements
This research was supported by the funds of National Natural
Science Foundation of China (No. 20572004) and the Major State
12. Saito, S.; Yamamoto, H. Acc. Chem. Res. 2004, 37, 570–579.