Gluconic acid aqueous solution: A task-specific bio-based solvent for ring-opening reactions of dihydropyrans

Article abstract of DOI:10.1016/j.tet.2012.11.076

Gluconic acid aqueous solution (GAAS) that is a largely available bio-based chemical was proved to be an effective task-specific medium for ring-opening reactions of dihydropyrans. In the presence of nucleophiles, such as indoles, 1,3-cyclohexanediones, N,N-dimethylaniline, N-methylaniline, 2-naphthol, and resorcin, a series of 2-substituted 1, 3-dicarbonyl compounds were synthesized in good to excellent yields. The first example of ring-opening of oxa-Pictet-Spengler product with nucleophiles was also described. These results not only demonstrate the feasibility of using GAAS as a sustainable solvent, but also offer an effective way for the ring-opening reactions of dihydropyrans with nucleophiles. Because these reactions proceeded with excellent atom-economy in a sustainable bio-based solvent, the present method was thus characterized by many properties of green chemistry, such as green solvent, atom-economy, and utilization of bio-based chemicals.

Full text of DOI:10.1016/j.tet.2012.11.076

Tetrahedron 69 (2013) 1057e1064
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Gluconic acid aqueous solution: a task-specific bio-based
solvent for ring-opening reactions of dihydropyrans
,b,
Jie Yang a, Binghua Zhou a, Minghao Li a, Yanlong Gu a
*
a Institute of Physical Chemistry and Industrial Catalysis, Hubei Key Laboratory of Material Chemistry and Service Failure, School of Chemistry and Chemical Engineering,
Huazhong University of Science and Technology, 1037 Luoyu road, Hongshan District, Wuhan 430074, China
b State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Lanzhou 730000, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Gluconic acid aqueous solution (GAAS) that is a largely available bio-based chemical was proved to be an
effective task-specific medium for ring-opening reactions of dihydropyrans. In the presence of nucleo-
philes, such as indoles, 1,3-cyclohexanediones, N,N-dimethylaniline, N-methylaniline, 2-naphthol, and
resorcin, a series of 2-substituted 1, 3-dicarbonyl compounds were synthesized in good to excellent
yields. The first example of ring-opening of oxa-PicteteSpengler product with nucleophiles was also
described. These results not only demonstrate the feasibility of using GAAS as a sustainable solvent, but
also offer an effective way for the ring-opening reactions of dihydropyrans with nucleophiles. Because
these reactions proceeded with excellent atom-economy in a sustainable bio-based solvent, the present
method was thus characterized by many properties of green chemistry, such as green solvent, atom-
economy, and utilization of bio-based chemicals.
Received 5 September 2012
Received in revised form 24 October 2012
Accepted 23 November 2012
Available online 29 November 2012
Keywords:
Green solvent
Gluconic acid aqueous solution
Ring-opening reaction
Dihydropyran
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
based chemicals, such as lactates5 and polyhydroxyalkanoate,6
have also been used as alternative solvents. Non-polar bio-based
Solvents play a pivotal role in many processes such as chemical
reactions, separation, and product purification procedures.1 Cur-
rently, there are only two kinds of solvents that can be used in
chemistry: solvents obtained from petroleum industry (petro-
based solvents) and solvents of agricultural origin (bio-based sol-
vents). Today, many of the most widely used solvents are petro-
based chemicals, which may be classified as volatile organic com-
pounds, and thus they are important atmospheric pollutants con-
sidering their known contributions to effects such as ozone
depletion or global warming.2 Chemicals from agricultural origin
are generally safe and easy to degrade in the environment. There-
fore, compared with the most of petro-based solvents, bio-based
solvents are more eco-friendly. For this reason, replacement of
conventional organic solvents with bio-based one has gained much
attention recently.3
solvents are normally obtained from natural fatty compounds, for
example, biodiesel,7 or terpenes, such as -limonene.8 In order to
D
push the bio-based solvents easily acceptable for industry, some
non-polar compounds that possess a solvent property close to
commonly used THF, were also selected as alternative solvents,
such as 2-methyltetrahydrofuran.9 Because this compound could
be now prepared from bio-based chemicals, it actually falls into the
catalog of non-polar bio-based solvents.
In view of the explosive growth in research on this area, bio-based
solventsmay bethebestcandidate foractingasthenextgenerationof
green solvents after successful developments of the first generation
involving water, ionic liquids, supercritical fluids, perfluorocarbon,
and polyethylene glycol.10 Today, although the great advantages of
bio-based solvents have been well elucidated by some pioneering
studies, owing to the fact that this topic is still in its infancy. Partic-
ularly, we viewed that it should be very interesting to develop a bio-
based solvent that has a specific capacity by means of rationally uti-
lizing its structure. Our recent interest is particularly focusing on
developmentofnew methods with bio-basedsolvents forsustainable
organic synthesis.11 In connection with this research program, we
started, some time ago, a research on exploration of bio-based
chemicals, which possess a functional group that might be able to
assistprogressof anorganicreaction. Duringour investigation, we are
According to the solvent properties, bio-based solvents can be
classified as polar and non-polar. Polar bio-based solvents generally
contain at least one hydroxyl group in the structure, which makes
them behave like an alcohol or even water. Glycerol is a typical
polar bio-based solvent,4 and three hydroxyl groups in its structure
lead this solvent to be highly hydrophilic. Some other polar bio-
attracted by
D-gluconic acid (GA), which is a bio-based chemical and
* Corresponding author. Fax: þ86 (0)27 87 54 45 32; e-mail addresses: yang-
largely available in the market as a 50% of aqueous solution.12 Under
jie2008609@126.com (J. Yang), klgyl@hust.edu.cn (Y. Gu).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.11.076

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J. Yang et al. / Tetrahedron 69 (2013) 1057e1064
normal conditions, gluconic acid aqueous solution (50 wt %, GAAS)
exhibits an equilibrium, in which about 5% of glucono- -lactone is
2-naphthol, and resorcin, affording excellent yields of the corre-
sponding ring-opening products in GAAS solvent.
d
present in the solution at room temperature. Particularly, dissociation
of proton from GA molecule resulted in the aqueous solution to be
slightly acidic. This allowed us to directly use GAAS as a bio-based
solvent for promoting some organic reactions that need assistance
of a weak acid. Out of these considerations, we have recently exam-
ined some organic reactions, including FriedeleCrafts alkylations of
2. Results and discussion
Initially, we studied whether solvent could promote the reaction
of a 2-butoxy-3,4-dihydropyran 1a with indole. As shown in Table 1,
no product was obtained under solvent-free condition (entry 1),
and also in toluene, DCE, nitromethane, DMF, DMSO, polyethylene
glycol 400, glycerol, and water (entries 2e9). Because the mecha-
nism of the model reaction most likely involves an acid-assisted
nucleophilic substitution, an acidic medium should be appropri-
ate for this reaction. We, thus, then examined acetic acid, and in this
case, a product, 3a, was obtained in 79% after 11 h of reaction at
110 ꢀC (entry 10). However, in order to isolate 3a, acetic acid has to
be neutralized by aqueous NaOH solution at the end of the reaction.
This step generates thus a lot of wastes. As a result, performing the
model ring-opening reaction in acetic acid is not perfect from the
viewpoints of economy and the concept of green chemistry. We
therefore decided to search for an alternative solvent to acetic acid.
Very interestingly, when another acidic medium, GAAS, was used,
3a was also formed with a high selectivity, and the reaction yield
reached to 82% (entry 11). Further investigation revealed that the
ring-opening reaction of 1a with 2a in GAAS also affected by tem-
perature and reaction time, and the optimal condition should be
110 ꢀC and 11 h (entries 12 and 13). It should be noted that, because
of the immiscibility of GAAS with non-polar organic solvent, the
formed product could be easily extracted from the GAAS phase with
an appropriate organic solvent. This method for isolating the re-
action product not only simplifies the operation procedure, but also
offers an easy way for recycling the GAAS. In the model reaction, the
recovered GAAS could be reused at least four times without sig-
nificant loss of activity (entry 14).
indoles with benzyl alcohols and a,b
-unsaturated ketones, in GAAS.13
Although theresults obtained are promising, owingtothesereactions
are rather simple, validity and necessity of using GAAS as solvent for
organic reactions have not been fully demonstrated. Therefore, ap-
plications of GAAS solvent in other organic reactions are appealingly
needed at this moment.
On the other hand, the use of simple heterocycles as substrate in
organic synthesis has gained much attention because heterocycles
displayed in organic transformations a great productivity in creation
of molecularcomplexicityand diversity.14 Dihydropyranderivatives,
which are among the most investigated heterocycles in the past
decade, are widely present in nature-occurring products.15 We have
recently reported a novel ring-opening reaction of 2-alkoxy- or 2-
aryl-3,4-dihydropyrans with nucleophiles,16 which generated a va-
riety of 2-substituted 1,3-dicarbonyl compounds in high yields.
However, these reactions are quite sensitive to the acid strength of
catalyst, and therefore, only mild Lewis acid catalysts, such as MnCl2
and MnBr2 could be applied in these reactions. This resulted in two
disadvantages to this type of reactions including (i) the reaction has
to be conducted in organic solvent, such as nitromethane that is
a volatile, toxic, and explosive solvent, and (ii) difficulty of recycling
the metal Lewis acid catalyst. In view of these facts, we envisaged
that performing the reaction in GAAS solvent might be an ideal
choice for overcoming these problems. In this paper, we disclose the
successful outcome of this endeavor, in which 2-alkoxy-3,4-
dihydropyrans, 2-aryl-3,4-dihydropyrans, and an oxa-Pictete
Spengler adduct reacted readily with many nucleophiles, such as
indoles,1,3-cyclohexanediones, N,N-dimethylaniline, N-methylaniline,
With the optimized system in hand, we probed the scope of the
reaction with respect to both the indole and the dihydropyran
components. As evidenced by the results in Table 2, indoles with
Table 1
Ring-opening reaction of dihydropyran 1a with indole in different solventsa
Entry
Solvent
Temp (ꢀC)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
No solvent
Toluene
DCE
CH3NO2
DMF
DMSO
PEG 400
Glycerol
H2O
CH3CO2H
GAAS
110
110
110
110
110
110
110
110
110
100
110
80
11
11
11
11
11
11
11
11
11
11
11
11
6
0
0
0
0
0
0
0
0
0
79
82
56
72
82
9
10
11
12
13
14b
GAAS
GAAS
GAAS
110
110
11
a
Solvent: 1.0 mL, 1a: 0.25 mmol, 2a: 0.63 mmol.
GAAS was reused in the fourth time.
b

J. Yang et al. / Tetrahedron 69 (2013) 1057e1064
1059
Table 2
Ring-opening reaction of 1a with different indoles in GAASa
Entry
Indole
Product
Yield (%)
1
2
3
4
5
6
2b
2c
2d
2e
2f
3b
3c
3d
3e
3f
71
85
80
78
86
0
2g
d
a
GAAS: 1.0 mL, 1a: 0.25 mmol, indole: 0.63 mmol, 110 ꢀC, 11 h.
different substituent groups smoothly reacted with 1a, producing
the corresponding 2-substituted 1,3-dicarbonyl compounds in
generally good yields (entries 1e5). However, an indole 2g that
contains a strongly electron-withdrawing group, ethoxycarbonyl,
failed to participate in the reaction (entry 6).
The scope of the reaction with respect to 2-butoxy-3,4-
dihydropyran was found also to be very good. As Table 3 illus-
trates, a range of functional groups could be employed without
significantly affecting the reaction yields (entries 1e5). Thus,
dihydropyrans containing an acetyl, phenyl, and methoxy func-
preparative scale (10 mmol) was also examined, and it was found
that the reaction proceeds very well, indicating the usefulness of
our method for practical synthesis (entry 6).
To probe the mechanism of the ring-opening reaction, we treated
a dihydropyran, 1e, in GAAS in the absence of indole. As shown in
Scheme 1, an aldehyde, 4a, was obtained in 24% of yield after 11 h of
reaction at 80 ꢀC. It should be noted that 4a is the only product in this
reaction, and the low yield mainly resulted from incomplete con-
version of 1e. Following treatment of the isolated 4awith 1a in GAAS
resulted in a quantitative formation of 3j. On the basis of these re-
sults, we thus believe that the model reaction should proceed in
tionality readily participated in the reaction.
A reaction in
Table 3
Ring-opening reaction of different 2-butoxy-3,4-dihydropyrans with indoles in GAASa
Entry
3,4-Dihydropyran
Indole
Product
Yield (%)
1b
2
1b
1c
1d
1e
1f
2h
2a
2a
2h
2h
2a
3g
3h
3i
3j
3k
3a
72
66
71
76
76
81
3
4b
5
6c
1a
a
GAAS, 1.0 mL, dihydropyran: 0.25 mmol, indoles: 0.63 mmol, 110 ꢀC, 11 h.
Reaction time: 24 h.
The reaction was performed in 10 mmol scale.
b
c

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J. Yang et al. / Tetrahedron 69 (2013) 1057e1064
O
O
OEt
OEt
Catalyst
BuO
O
BuO
O
Catalyst
1e
GAAS,
o
80 C, 11 h
O
O
O
H
OEt
N
H
OEt
H O
2
BuO
Catalyst
+
O
3j (99%)
- BuOH
GAAS,
O
o
110 C, 11 h
4a (24%)
(I)
- BuOH
N
H
O
O
OEt
OEt
O
O
HN
HN
Catalyst
(II)
Catalyst
(III)
Scheme 1. Plausible mechanism of the model reaction.
Table 4
a same reaction pathway that we have proposed in the reaction
catalyzed by MnCl2$4H2O.16c In the beginning of the reaction,
dihydropyran 1e was activated with the aid of GAAS to form a cyclic
oxocarbenium ion intermediate (I). This step was generally cata-
lyzed by acid.17 The formation of a linear oxocarbenium ion could be
also possible through a cleavage of CeO bond in the ring, but com-
pared with the cyclic one, it should be much less stable because of
a lack of conjugation effect. Once (I) was formed, it tended to react
with water to form an aldehyde 4a that can further interact with
indole to generate 3j. Additionally, interaction of one molecule of
indole and intermediate (I) might form an intermediate (II). With
the aid of GAAS, intermediate (II) underwent the cleavage of CeO
bond to form a ring-opening intermediate (III) that tended to react
with next indole to generate the final product 3j.
Ring-opening of 2-butoxy-3,4-dihydropyran 1a with 1,3-cyclohexanediones in
GAASa
Interestingly, GAAS-mediated ring-opening reaction of the 3,4-
dihydropyran showed also a good generality with respect to nu-
cleophiles. As shown in Table 4, 1,3-cyclohexanedione derivatives
could be successfully used, and a new class of products that contain
both moieties of 3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione
and 1,3-dicarbonyl compound were obtained in good yields (en-
tries 1e6). Scheme 2 also shows ring-opening reactions of 2-aryl-
3,4-dihydropyrans, 7a and 7b, in GAAS with some nucleophiles,
such as indoles, N,N-dimethylaniline, N-methylaniline, 2-naphthol,
and resorcin. It should be noted that these ring-opening reactions
proceeded in a manner of 100% of atom-economy, thus conferring
to this system a salient feature of green chemistry. All these ex-
amples demonstrated that GAAS is, indeed, a very efficient
Entry
3,4-Dihydropyran
Cyclohexanedione
Product
Yield (%)
1
2
3
4
5
6
1a
1a
1a
1b
1b
1f
5a
5b
5c
5b
5c
5d
6a
6b
6c
6d
6e
6f
74
98
80
96
85
73
a
GAAS: 1.0 mL, 3, 4-dihydropyrane: 0.25 mmol, cyclohexanedione: 0.63 mmol,
110 ꢀC, 11 h.

J. Yang et al. / Tetrahedron 69 (2013) 1057e1064
1061
Scheme 2. Ring-opening reactions of 2-aryl-3,4-dihydropyrans with other nucleophiles.
promoting medium for the ring-opening reactions of 2-substituted
3. Conclusion
3,4-dihydropyrans with nucleophiles.
Inspired by the above-mentioned results, we then investigated
another type of ring-opening reaction by using GAAS as a pro-
moting medium. As shown in Scheme 3, an oxa-PicteteSpengler
reaction product, 12a, could react smoothly with indole and pyrrole
in GAAS to give the ring-opening products in moderate to excellent
yields.18 It should be noted that this type of ring-opening reaction
has not been reported before. By using GAAS as a promoting me-
dium, we thus realized the first example of ring-opening of oxa-
PicteteSpengler product with nucleophile.
In summary, GAAS that is a largely available bio-based chemical
was proved, for the first time, to be an effective task-specific me-
dium for the ring-opening reaction of 2-substituted 3,4-
dihydropyrans with many nucleophiles including indoles, 1,3-
cyclohexanediones, N,N-dimethylaniline, N-methylaniline, 2-
naphthol, and resorcin, which generated a series of 2-substituted
1,3-dicarbonyl compounds in moderate to excellent yields. These
results not only demonstrate the feasibility and necessity of using
GAAS as a sustainable solvent, but also offer an effective way for the
ring-opening reaction of 2-substituted 3,4-dihydropyrans with
nucleophiles. Furthermore, the first example of ring-opening of
oxa-PicteteSpengler product with nucleophile was also described.
In addition to the above-mentioned salient features, GAAS system
also showed good recoverability and recyclability in the ring-
opening reaction, which conferred the present method more sig-
nificant property on the eco-friendliness. Moreover, because these
reactions proceeded with excellent atom-economy in a sustainable
bio-based solvent, the present method was thus characterized by
many properties of green chemistry, such as green solvent, atom-
economy, and utilization of bio-based chemicals.
OH
MeO
MeO
OMe
OMe
1a (1.5 equiv)
o
GAAS, 110 C, 11 h
MeO
MeO
N
H
O
13a (92%)
H
N
MeO
OH
4. Experimental section
4.1. General
OMe
MeO
MeO
OMe
OMe
14a (1.5 equiv)
12a
o
GAAS, 110 C, 11 h
All reactions were conducted in a 10 mL of V-type flask equip-
ped with triangle magnetic stirring. In a typical reaction, gluconic
acid aqueous solution (1.0 mL) was mixed with 1a (57.1 mg,
0.25 mmol) and indole (1a, 73.2 mg, 0.63 mmol) under air. The
mixture was stirred for 11 h at 110 ꢀC. After reaction, the mixture
HN
15a (46%)
Scheme 3. Ring-opening reactions of oxa-PicteteSpengler product 12a with indole or
pyrrole in GAAS.

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J. Yang et al. / Tetrahedron 69 (2013) 1057e1064
was cooled to room temperature and the reaction mixture was
extracted with a mixed solution composed of ethyl acetate and n-
heptane (v/v¼2:1, 6 mLꢁ3). And the desired product, 3a, was ob-
tained by preparative TLC using a mixed solution of ethyl acetate
and petro ether (bp¼60e90 ꢀC) as eluting solvent (the ratio of ethyl
acetate/petroleum ether is 1:6); 79.4 mg, yield¼82%. Tests for
substrate scope, reaction in preparative scale, and experiments
concerning the mechanism were all performed according to the
above-mentioned analogous procedure. The ring-opening re-
actions of 7a and 7b were also performed according to the above-
mentioned analogous procedure.
(t, J¼7.2 Hz, 3H), 2.07 (d, J¼5.6 Hz, 6H), 1.80e2.06 (m, 2H),
2.10e2.25 (m, 1H), 2.47 (q, J¼7.2 Hz, 1H), 3.77 (s, 3H), 4.05 (q,
J¼7.2 Hz, 2H), 2.04e2.30 (m, 1H), 4.36 (t, J¼8.0 Hz, 1H), 6.78 (d,
J¼8.8 Hz, 2H), 6.92 (t, J¼8.0 Hz, 2H), 6.98 (t, J¼7.6 Hz, 2H), 7.07 (t,
J¼6.8 Hz, 2H), 7.57 (d, J¼8.0 Hz, 2H), 7.71 (d, J¼7.6 Hz, 2H), 7.79 (d,
J¼8.8 Hz, 2H); 13C NMR (CDCl3): 12.4, 12.5, 14.0, 28.5, 32.5, 34.9,
54.2, 55.5, 61.4, 110.4, 113.9, 114.0, 118.9, 119.0, 119.2, 120.3, 120.4,
128.1, 128.2, 129.1, 131.0, 131.3, 135.2, 163.8, 170.5, 194.2; IR (cmꢂ1):
3394, 2960, 2934, 1729, 1672, 1599, 1575, 1512, 1461, 1424, 1302,
1260, 1172, 1027, 843, 743; HRMS m/z (ESI) calcd for C33H34N2NaO4
[MþNa]þ 545.2416; found 545.2402.
4.2. Spectroscopic data of new compounds
4.2.6. Methyl 2-acetyl-4-(1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-
xanthen-9-yl)butanoate (6a). Yellow pale liquid; 1H NMR
(CDCl3): 1.40e1.48 (m, 2H), 1.57e1.65 (m, 2H), 1.98e2.09 (m, 4H),
2.22 (s, 3H), 2.33 (ddd, Ja¼6.4 Hz, Jb¼10 Hz, Jc¼16.4 Hz, 2H),
2.43e2.54 (m, 4H), 2.60 (dt, Ja¼5.2 Hz, Jb¼17.6 Hz, 2H), 3.47 (t,
J¼7.2 Hz, 1H), 3.70 (s, 3H), 3.80 (t, J¼4.8 Hz, 1H); 13C NMR (CDCl3):
20.4, 23.7, 24.9, 27.1, 27.2, 29.5, 31.4, 37.0, 52.3, 58.8, 115.3, 115.3,
165.7, 165.8, 170.1, 197.2, 197.3, 203.3; IR (cmꢂ1): 2953, 2873, 1743,
1715, 1665, 1620, 1454, 1432, 1383, 1201, 1174, 1131, 1063, 1011,
957, 899, 534; HRMS m/z (ESI) calcd for C20H24NaO6 [MþNa]þ
383.1471; found 383.1464.
4.2.1. Ethyl 2-butoxy-6-phenyl-3,4-dihydro-2H-pyran-5-carboxylate
1
(1f).19 Colorless liquid; H NMR (CDCl3): 0.93 (t, J¼7.6 Hz, 3H), 1.01
(t, J¼6.8 Hz, 3H), 1.39 (sext, J¼7.6 Hz, 2H), 1.61 (quint, J¼6.8 Hz, 2H),
1.83e1.93 (m, 1H), 1.93e2.02 (m, 1H), 2.47e2.57 (m, 2H), 3.61 (td,
Ja¼6.8 Hz, Jb¼9.6 Hz, 1H), 3.81 (s, 3H), 3.91 (td, Ja¼6.4 Hz, Jb¼9.2 Hz,
1H), 3.97 (q, J¼7.2 Hz, 2H), 5.19 (dd, Ja¼2.8 Hz, Jb¼4.0 Hz, 1H), 6.87
(td, Ja¼1.6 Hz, Jb¼8.8 Hz, 2H), 7.29 (td, Ja¼2.4 Hz, Jb¼8.8 Hz, 2H); 13
C
NMR (CDCl3): 13.9, 13.9, 18.8, 19.4, 26.2, 31.7, 55.3, 59.8, 68.6, 98.5,
103.8, 113.0, 129.3, 130.0, 159.6, 160.1, 168.6; IR (cmꢂ1): 2958, 2935,
2872, 1710, 1690, 1629, 1608, 1578, 1511, 1463, 1371, 1339, 1293, 1248,
1175, 1155, 1125, 1057, 954, 905, 833, 784, 759; HRMS m/z (ESI) calcd
for C19H26NaO5 [MþNa]þ 357.1678; found 357.1669.
4.2.7. Methyl 2-acetyl-4-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-
octahydro-1H-xanthen-9-yl)butanoate (6b). White solid; mp:
114e116 ꢀC; 1H NMR (CDCl3): 1.12 (d, J¼8.4 Hz, 12H), 1.47e1.55 (m,
2H), 1.59e1.67 (m, 2H), 2.20 (s, 3H), 2.25 (d, J¼16 Hz, 2H), 2.32 (d,
J¼16 Hz, 2H), 2.38 (d, J¼17.6 Hz, 2H), 2.44 (d, J¼17.6 Hz, 2H), 3.46 (t,
J¼7.2 Hz, 1H), 3.69 (s, 3H), 3.77 (t, J¼4.4 Hz, 1H); 13C NMR (CDCl3):
24.0, 25.0, 27.3, 27.3, 29.3, 31.2, 31.9, 40.8, 40.8, 50.8, 52.2, 58.8, 114.0,
114.1, 164.1, 164.2, 170.0, 197.0, 197.1, 203.0; IR (cmꢂ1): 2959, 2934,
1727, 1657, 1620, 1443, 1384, 1291, 1241, 1203, 1164, 1143, 1065, 1004,
899, 830, 577; HRMS m/z (ESI) calcd for C24H32NaO6 [MþNa]þ
439.2097; found 439.2081.
4.2.2. Methyl 2-acetyl-5,5-bis(6-methyl-1H-indol-3-yl)pentanoate
(3f). Brown liquid; 1H NMR (CDCl3): 1.82e2.00 (m, 2H), 2.07e2.17
(m, 2H), 2.37 (s, 6H), 3.41 (t, J¼7.2 Hz, 1H), 3.62 (s, 3H), 4.36 (t,
J¼7.2 Hz, 1H), 6.66 (dd, Ja¼1.6 Hz, Jb¼7.2 Hz, 2H), 6.83 (d, J¼8.4 Hz,
2H), 6.95 (s, 2H), 7.39 (d, J¼8.0 Hz, 2H), 7.69 (s, 2H); 13C NMR
(CDCl3): 21.8, 27.2, 28.9, 33.3, 34.1, 52.5, 59.8, 111.4, 119.0, 119.2,
120.9, 121.3, 124.8, 124.9, 131.5, 137.2, 170.6, 203.9; IR (cmꢂ1): 3406,
2951, 2920, 1738, 1709, 1625, 1455, 1359, 1340, 1279, 1224, 1153,
1093, 802, 732; HRMS m/z (ESI) calcd for C26H28N2NaO3 [MþNa]þ
439.1998; found 439.1983.
4.2.8. Methyl 2-acetyl-4-(3,6-dimethyl-1, 8-dioxo-2,3,4,5,6,7,8,9-
octahydro-1H-xanthen-9-yl)butanoate (6c). Colorless liquid; 1H
NMR (CDCl3): 1.12 (t, J¼5.6 Hz, 6H),1.39e1.51 (m, 2H),1.52e1.63 (m,
2H), 2.0e2.5 (m, 1H), 2.07e2.10 (m, 1H), 2.20 (t, J¼3.6 Hz, 3H),
2.22e2.41 (m, 4H), 2.45e2.62 (m, 4H), 3.39e3.49 (m, 1H), 3.69 (t,
J¼2.0 Hz, 3H), 3.78 (t, J¼4.4 Hz, 1H); 13C NMR (CDCl3): 20.7, 20.8,
23.6, 23.7, 23.7, 24.8, 25.1, 28.0, 28.0, 28.3, 29.4, 29.5, 30.8, 30.8, 31.5,
34.8, 34.8, 35.3, 35.3, 35.4, 45.0, 45.3, 52.3, 58.7, 58.8, 58.8, 58.9,
114.4, 114.5, 114.5, 114.8, 114.9, 114.9, 164.6, 164.7, 164.7, 165.4, 164.5,
164.6, 170.1, 170.1, 197.1, 197.2, 197.2, 197.3, 203.2, 203.3; IR (cmꢂ1):
2956,1743,1715,1667, 1621, 1455,1433, 1384, 1359,1290,1187,1134,
1004, 946, 917, 885, 732, 648, 596, 550; HRMS m/z (ESI) calcd for
4.2.3. Ethyl 2-acetyl-5,5-bis(2-methyl-1H-indol-3-yl)pentanoate (3g).
Brown liquid; 1H NMR (CDCl3): 1.18 (t, J¼7.2 Hz, 3H), 1.87e1.95 (m,
2H), 2.08 (s, 3H), 2.19 (s, 3H), 2.20 (s, 3H), 2.34e2.46 (m, 2H), 3.43 (t,
J¼7.6 Hz, 1H), 4.10 (q, 7.2 Hz, 2H), 4.38 (t, J¼7.6 Hz, 1H), 6.96 (t,
J¼7.2 Hz, 2H), 6.99 (t, J¼7.6 Hz, 2H), 7.13 (d, J¼7.6 Hz, 2H), 7.59 (d,
J¼7.6 Hz, 2H), 7.76 (d, J¼2.8 Hz, 2H); 12.6, 12.6, 14.1, 27.1, 28.7, 32.3,
34.9, 60.0, 61.4, 110.3, 114.0, 119.1, 119.2, 119.2, 120.5, 128.2, 128.2,
131.1, 131.1, 135.2, 170.0, 203.6; IR (cmꢂ1): 3394, 2933, 2869, 1732,
1708, 1618, 1583, 1523, 1488, 1461, 1362, 1325, 1301, 1225, 1152, 1096,
1016, 744; HRMS m/z (ESI) calcd for C27H30N2NaO3 [MþNa]þ
453.2154; found 453.2149.
C
22H28NaO8 [MþNa]þ 411.1784; found 411.1764.
4.2.4. Ethyl 2-benzoyl-5,5-di(2-methyl-1H-indol-3-yl)pentanoate (3j).
Brown solid; mp: 150e152 ꢀC; 1H NMR (CDCl3): 1.08 (t, J¼7.2 Hz, 3H),
1.84e2.01 (m, 1.5H), 22.04e2.11 (m, 1.5H), 2.14 (d, J¼5.2 Hz, 6H),
2.43e2.53 (m, 1H), 4.06 (q, J¼7.2 Hz, 2H), 4.27e4.36 (m, 1H), 4.39 (t,
J¼8.0 Hz, 1H), 6.93 (t, J¼7.6 Hz, 2H), 6.99 (t, J¼7.2 Hz, 2H), 7.11 (t,
J¼7.6 Hz, 2H), 7.34 (t, J¼8.0 Hz, 2H), 7.47e7.52 (m, 1H), 7.70 (d,
J¼8.0 Hz, 2H), 7.73 (d, J¼8.0 Hz, 2H), 7.81 (dd, Ja¼0.8 Hz, Jb¼8.0 Hz,
2H); 13C NMR (CDCl3): 12.5, 12.5, 14.0, 19.2, 18.4, 30.6, 32.4, 34.9, 54.4,
61.4, 65.7, 110.4, 113.9, 114.0, 119.0, 119.0, 119.2, 120.4, 120.4, 128.2,
128.6, 128.7, 128.9, 131.2, 133.4, 135.2, 136.2, 170.2, 195.7; IR (cmꢂ1):
3394, 2957, 2930, 1727, 1678, 1618, 1581, 1489, 1461, 1326, 1300, 1243,
756, 742, 698; HRMS m/z (ESI) calcd for C32H32N2NaO3 [MþNa]þ
515.2311; found 515.2295.
4.2.9. Ethyl 2-acetyl-4-(3,3,6,6-tetramethyl-1, 8-dioxo-2,3,4,5,6,7,8,9-
octahydro-1H-xanthen-9-yl)butanoate (6d). Yellow pale liquid; 1H
NMR (CDCl3): 1.12 (d, J¼9.6 Hz, 12H), 1.24 (t, J¼7.2 Hz, 3H),
1.49e1.55 (m, 2H), 1.58e1.66 (m, 2H), 2.20 (s, 3H), 2.23e2.34 (m,
4H), 2.34e2.46 (m, 4H), 3.41 (t, J¼3.2 Hz, 1H), 3.78 (t, J¼4.4 Hz, 1H),
4.14 (dd, Ja¼7.2 Hz, Jb¼14.4 Hz, 2H); 13C NMR (CDCl3): 14.0, 23.9,
25.1, 27.4, 29.3, 29.3, 31.0, 32.0, 40.8, 50.9, 59.1, 61.2, 114.0, 114.1,
164.1, 164.2, 169.6, 197.0, 197.1, 203.2; IR (cmꢂ1): 2960, 2251, 1739,
1715,1664,1624,1467,1453,1426,1382,1337,1290,1243,1197,1163,
1138, 1002, 916, 861, 732; HRMS m/z (ESI) calcd for C25H34NaO6
[MþNa]þ 453.2253; found 453.2237.
4.2.10. Ethyl 2-acetyl-4-(3,6-dimethyl-1,8-dioxo-2,3,4,5,6,7,8,9-
octahydro-1H-xanthen-9-yl)butanoate (6e). Yellow pale liquid; 1H
NMR (CDCl3): 1.12 (t, J¼5.6 Hz, 6H), 1.24 (tt, Ja¼1.2 Hz, Jb¼7.2 Hz,
3H), 1.37e1.52 (m, 2H), 1.52e1.63 (m, 2H), 2.03 (dd, Ja¼12.8 Hz,
4.2.5. Ethyl 2-(4-methoxy)benzoyl-5,5-di(2-methyl-1H-indol-3-yl)
pentanoate (3k). Brown solid; mp: 92e94 ꢀC; 1H NMR (CDCl3): 1.08

J. Yang et al. / Tetrahedron 69 (2013) 1057e1064
1063
Jb¼16.4 Hz, 1H), 2.14e2.19 (m, 1H), 2.20 (t, J¼3.6 Hz, 3H), 2.22e2.42
(m, 4H), 2.44e2.64 (m, 4H), 3.34e3.45 (m, 1H), 3.78 (dd, Ja¼3.6 Hz,
Jb¼7.6 Hz, 1H), 4.10e4.19 (m, 2H); 13C NMR (CDCl3): 14.0, 20.6, 20.8,
23.5, 23.6, 24.9, 25.1, 28.0, 28.0, 28.3, 29.3, 29.4, 30.7, 31.4, 34.7, 34.8,
35.3, 35.3, 45.0, 45.3, 59.0, 59.0, 59.1, 59.1, 61.2, 114.4, 114.4, 114.8,
114.8, 114.9, 164.5, 164.6, 165.3, 165.4, 165.5, 169.5, 169.6, 169.6,
197.0, 197.1, 197.2, 203.2, 203.3; IR (cmꢂ1): 2958, 2932, 1740, 1714,
1667, 1622, 1455, 1431, 1384, 1290, 1239, 1187, 1135, 1005, 946, 863,
732, 649, 605, 570, 551; HRMS m/z (ESI) calcd for C23H30NaO6
[MþNa]þ 425.1940; found 425.1932.
(cmꢂ1): 3394, 2954, 2933, 1738, 1712, 1611, 1583, 1511, 1484, 1456,
1433, 1358, 1339, 1300, 1248, 1181, 1148, 1112, 1036, 936, 910, 821,
779, 739; HRMS m/z (ESI) calcd for C23H24ClNNaO4 [MþNa]þ
436.1292; found 436.1289.
4.2.15. Methyl 2-acetyl-5-(4-methoxyphenyl)-5-(4-dimethylnophenyl)
pentanoate (9a). Yellow liquid; 1H NMR (CDCl3): 1.68e2.00 (m, 4H),
2.14 (s, 3H), 2.87 (s, 6H), 3.42 (t, J¼7.2 Hz, 1H), 3.69 (s, 3H), 3.69e3.78
(m, 4H), 6.65 (dd, Ja¼1.2 Hz, Jb¼8.4 Hz, 2H), 6.79 (dd, Ja¼1.6 Hz,
Jb¼8.4 Hz, 2H), 7.05 (quint, J¼3.2 Hz, 2H), 7.11 (quint, J¼3.2 Hz, 2H);
13C NMR (CDCl3): 27.0, 28.7, 33.7, 40.8, 49.4, 52.4, 55.2, 59.7, 59.7,
112.9, 113.9, 128.2, 128.3, 128.3, 128.6, 128.6, 132.7, 132.9, 137.3, 137.5,
149.2, 157.9, 170.2, 203.1; IR (cmꢂ1): 2998, 2953, 2801, 1743, 1715,
1612, 1583, 1514, 1445, 1353, 1247, 1210, 1178, 1035, 948, 815, 547;
HRMS m/z (ESI) calcd for C23H29NnaO4 [MþNa]þ 406.1994; found
406.1989.
4.2.11. Ethyl 4-(1,8-dioxo-3,6-diphenyl-2,3,4,5,6,7,8,9-octahydro-1H-
xanthen-9-yl)-2-(4-methoxybenzoyl)butanoate (6f). White solid;
mp: 75e77 ꢀC; 1H NMR (CDCl3): 1.17 (q, 7.2 Hz, 3H), 1.50e1.99 (m,
4H), 2.50e2.99 (m, 8H), 3.30e3.51 (m, 2H), 3.84 (d, J¼6.8 Hz, 3H),
3.94 (br s, 1H), 4.07e4.33 (m, 3H), 6.94 (dd, Ja¼2.8 Hz, Jb¼8.8 Hz,
2H), 7.20e7.30 (m, 7H), 7.35 (q, J¼6.4 Hz, 3H), 7.97 (dt, Ja¼2.0 Hz,
Jb¼13.2 Hz, 2H); 13C NMR (CDCl3): 14.1, 19.2, 24.5, 25.6, 25.8, 30.1,
30.6, 31.2, 34.3, 34.4, 34.9, 38.3, 38.4, 38.7, 39.0, 43.9, 44.0, 44.1,
53.6, 55.5, 55.5, 61.3, 61.3, 113.9, 114.9, 115.0, 126.7, 126.7, 126.7,
127.1, 127.2, 128.8, 128.9, 129.2, 129.3, 131.1, 142.1, 142.2, 142.2, 142.3,
163.9, 163.9, 164.4, 165.1, 165.2, 165.2, 169.9, 170.0, 193.8, 196.2,
196.5; IR (cmꢂ1): 2935, 1735, 1667, 1600, 1511, 1453, 1423, 1385,
1258,1181,1134,1028, 991, 914, 843, 764, 700; HRMS m/z (ESI) calcd
for C39H38NaO7 [MþNa]þ 641.2515; found 641.2497.
4.2.16. Methyl 2-acetyl-5-(4-methoxyphenyl)-5-(4-N-methylamino-
phenyl)pentanoate (9b). Yellow liquid; 1H NMR (CDCl3): 1.62e1.80
(m, 2H), 1.80e1.95 (m, 2H), 2.09 (s, 3H), 2.73 (s, 3H), 3.37 (t, J¼7.2 Hz,
1H), 3.56 (br s, 1H), 3.65 (s, 3H), 3.67 (s, 1H), 3.70 (s, 3H), 6.47 (d,
J¼8.4 Hz, 2H), 6.74 (d, J¼8.4 Hz, 2H), 6.95 (dd, Ja¼3.6 Hz, Jb¼8.4 Hz,
2H), 7.05 (dd, Ja¼3.2 Hz, Jb¼8.8 Hz, 2H); 13C NMR (CDCl3): 13.8, 19.2,
26.9, 28.7, 28.7, 30.6, 30.9, 33.7, 49.4, 52.4, 55.2, 59.7, 59.7, 65.6, 112.6,
113.9, 128.4, 128.4, 128.6, 128.6, 128.9, 130.9, 133.3, 133.5, 137.3, 137.5,
147.7,157.9,170.2, 203.1; IR (cmꢂ1): 3414, 2953, 2933,1741,1714,1613,
1583, 1513, 1454, 1439, 1358, 1247, 1179, 1151, 1035, 821, 556; HRMS m/
z (ESI) calcd for C22H27NNaO4 [MþNa]þ 392.1838; found 392.1831.
4.2.12. Methyl 2-acetyl-5-(2-methyl-1H-indol-3-yl)-5-(p-methoxyphe-
nyl)pentanoate (8a). Red oil; 1H NMR (CDCl3): 1.66e1.96 (m, 2H),
1.97e2.07 (m, 2H), 2.09 (d, J¼6.4 Hz, 1H), 2.12e2.25 (m, 2H), 2.29 (d,
J¼6.0 Hz, 3H), 3.32e3.48 (m, 1H), 3.61 (d, J¼6.4 Hz, 1.5H), 3.66 (d,
J¼6.0 Hz, 1.5H), 3.70 (d, J¼6.0 Hz, 2.7H), 3.77 (d, J¼5.6 Hz, 0.3H),
4.04e4.16 (m, 1H), 6.76 (t, J¼2.4 Hz, 2H), 6.97 (dd, Ja¼5.2 Hz,
Jb¼12.0 Hz, 1H), 7.03 (q, J¼6.8 Hz, 1H), 7.12e7.30 (m, 3H), 7.46 (br s,
1H); 13C NMR (CDCl3): 12.2, 12.3, 27.2, 27.3, 28.6, 29.0, 32.2, 32.3, 41.1,
41.2, 52.4, 52.4, 55.3, 59.6, 59.8, 110.5, 113.4, 113.5, 113.7, 119.1, 119.2,
119.2, 120.8, 127.6, 127.7, 128.5, 128.6, 131.6, 131.6, 135.5, 137.1, 137.1,
157.7, 170.4, 203.4, 203.4; IR (cmꢂ1): 3399, 2953, 1739, 1712, 1612,
1582, 1511, 1489, 1460, 1436, 1359, 1300, 1246, 1179, 1152, 1034, 971,
911, 831, 742, 596, 533; HRMS m/z (ESI) calcd for C24H27NNaO4
[MþNa]þ 416.1838; found 416.1825.
4.2.17. Methyl 2-acetyl-5-(2-hydroxynaphthalen-1-yl)-5-(p-methox-
yphenyl)pentanoate (10a). Brown liquid; 1H NMR (CDCl3):
1.60e1.94 (m, 2H), 2.04 (s, 1.6H), 2.06 (s, 1.4H), 2.21e2.45 (m, 2H),
3.40 (t, J¼7.2 Hz, 0.45H), 3.50 (t, J¼7.6 Hz, 0.55H), 3.62 (s, 1.5H), 3.66
(s, 1.5H), 3.71 (d, J¼2.4 Hz, 3H), 4.98 (br s, 1H), 5.82 (br s, 1H), 6.78
(dd, Ja¼4.0 Hz, Jb¼8.8 Hz, 2H), 7.00 (d, J¼8.8 Hz, 1H), 7.21e7.33 (m,
3H), 7.38 (s, 1H), 7.60 (d, J¼8.8 Hz, 1H), 7.74 (d, J¼8.0 Hz, 1H), 7.98
(br s, 1H); 13C NMR (CDCl3): 13.8, 19.2, 22.6, 26.8, 27.0, 28.5, 28.9,
29.7, 29.9, 30.6, 43.8, 52.4, 52.4, 55.2, 59.4, 59.8, 65.7, 114.0, 118.9,
119.0, 121.6, 121.8, 123.0, 126.4, 127.9, 128.5, 128.8, 128.9, 129.7,
129.8, 130.9, 131.0, 133.4, 133.4, 135.9, 152.0, 152.1, 157.9, 170.4,
170.4, 203.8; IR (cmꢂ1): 3416, 3002, 2954, 1735, 1711, 1671, 1623,
1609, 1583, 1511, 1457, 1437, 1360, 1248, 1180, 1149, 1034, 911, 815,
733; HRMS m/z (ESI) calcd for C25H26NaO5 [MþNa]þ 429.1678;
found 429.1663.
4.2.13. Ethyl 2-acetyl-5-(6-fluoro-1H-indol-3-yl)-5-(p-methoxyphe-
nyl)pentanoate (8b). Brown liquid; 1H NMR (CDCl3): 1.22 (dd,
Ja¼7.2 Hz, Jb¼12.4 Hz, 3H), 1.76e2.01 (m, 3H), 2.02e2.12 (m, 1H),
2.14 (d, J¼9.2 Hz, 3H), 3.44 (q, J¼7.6 Hz, 1H), 3.71 (s, 3H), 4.06 (t,
J¼6.4 Hz, 1H), 4.16 (q, J¼6.8 Hz, 2H), 6.70e6.82 (m, 3H), 6.91 (d,
J¼2.0 Hz, 1H), 6.95 (d, J¼5.6 Hz, 2H), 7.14 (d, J¼7.2 Hz, 2H),
7.22e7.29 (m, 1H), 8.27 (br s, 1H); 13C NMR (CDCl3): 14.1, 14.1, 26.8,
26.9, 28.7, 29.0, 33.7, 33.9, 41.9, 42.0, 55.2, 59.8, 59.9, 61.5, 97.3, 97.6,
107.7, 108.0, 113.9, 119.6, 119.7, 120.0, 120.1, 121.5, 121.5, 123.5, 123.5,
128.7, 128.7, 136.5, 136.6, 136.8, 158.0, 158.7, 161.1, 169.9, 170.0,
203.6; IR (cmꢂ1): 3413, 2934,1734,1711,1626,1611,1589,1551,1510,
1457, 1343, 1302, 1248, 1178, 1142, 1034, 952, 912, 834, 806, 733;
HRMS m/z (ESI) calcd for C24H26FNNaO4 [MþNa]þ 434.1744; found
434.1736.
4.2.18. Ethyl 2-acetyl-5-(2,4-dihydroxyphenyl)-5-(4-methoxyphenyl)
pentanoate (11a). Colorless liquid; 1H NMR (CDCl3): 1.20 (t,
J¼7.2 Hz, 3H), 1.85 (m, 4H), 2.13 (d, 3.6 Hz, 3H), 3.46 (dd, Ja¼16.4 Hz,
Jb¼6.8 Hz, 1H), 4.12 (m, 3H), 6.26 (s, 1H), 6.34 (dd, Ja¼14.8 Hz,
Jb¼8.4 Hz, 2H), 6.58 (s, 1H), 6.76 (d, J¼8.4 Hz, 2H), 7.12 (d, J¼8.4 Hz,
2H); 13C NMR: 13.7, 14.0, 14.1, 19.1, 26.6, 26.7, 28.8, 28.9, 30.5, 32.5,
42.1, 42.3, 55.2, 59.6, 59.7, 60.7, 61.8, 65.9, 103.3, 107.6, 107.7, 107.8,
113.8, 123.1, 123.3, 128.6, 128.8, 128.9, 130.3, 131.1, 136.2, 136.4,
154.3, 154.4, 154.9, 157.0, 157.7, 170.2, 170.3, 204.9; IR (cmꢂ1): 3401,
3033, 2959, 2935, 2870, 2837, 1727, 1699, 1607, 1511, 1456, 1369,
1302,1246,1212,1178,1149,1112,1033, 974, 910, 839, 732, 632, 552;
HRMS m/z (ESI) calcd for C22H26NaO6 [MþNa]þ 409.1627; found
409.1619.
4.2.14. Methyl 2-acetyl-5-(4-chloro-1H-indol-3-yl)-5-(p-methoxyphe-
nyl)pentanoate (8c). Yellow liquid; 1H NMR (CDCl3): 1.78e2.00 (m,
3H), 2.05e2.13 (m, 1H), 2.13 (s, 1.5H), 2.17 (s, 1.5H), 3.47 (dd,
Ja¼6.8 Hz, Jb¼14.4 Hz, 1H), 3.67 (s, 1.5H), 3.70 (s, 1.5H), 3.73 (d,
J¼0.8 Hz, 3H), 4.77 (t, J¼8.0 Hz, 1H), 6.79 (dd, Ja¼2.8 Hz, Jb¼8.8 Hz,
2H), 6.88 (d, J¼2.4 Hz, 0.5H), 6.92 (d, J¼2.0 Hz, 0.5H), 6.97e7.02 (m,
2H), 7.13e7.21 (m, 3H), 8.44 (br s, 1H); 13C NMR (CDCl3): 27.0, 27.1,
28.8, 29.0, 35.5, 35.7, 41.3, 41.4, 52.4, 52.4, 55.2, 59.6, 59.8,110.1,113.8,
113.8, 120.3, 120.6, 120.7, 122.4, 123.0, 123.5, 123.6, 126.1, 129.1, 129.1,
136.9, 137.1, 138.0, 157.9, 157.9, 170.3, 170.4, 203.5, 203.5, 203.6; IR
4.2.19. 3-[(3,4-Dimethoxyphenyl)(4,5-dimethoxy-2-hydroxyethyl-
1
phenyl)methyl]-1H-indole (13a). Red oil; H NMR (CDCl3): 1.73 (br s,
1H), 2.89 (dt, Ja¼1.2 Hz, Jb¼6.4 Hz, 2H), 3.54 (s, 3H), 3.69e3.76 (m,
5H), 3.83 (s, 3H), 3.85 (s, 3H), 5.79 (s, 1H), 6.47 (d, J¼1.2 Hz, 1H), 6.59
(s, 1H), 6.64 (dd, Ja¼2.0 Hz, Jb¼8.4 Hz, 1H), 6.72e6.78 (m, 3H), 6.96 (t,
J¼7.6 Hz, 1H), 7.13 (t, J¼8.0 Hz, 1H), 7.21 (d, J¼8.0 Hz, 1H), 7.29 (d,
J¼8.0 Hz, 1H), 8.28 (s, 1H); 13C NMR (CDCl3): 35.7, 43.9, 55.8, 55.8,

1064
J. Yang et al. / Tetrahedron 69 (2013) 1057e1064
2. Clark, J. H.; Tavener, S. J. Org. Process Res. Dev. 2007, 11, 149e155.
3. (a) Kerton, F. M. Alternative Solvents for Green Chemistry. In RSC Green Chemistry
Series; Clark, J., Ed.; The Royal Society of Chemistry: Cambridge, 2009; (b) Leitner,
W. Green Chem. 2007, 9, 923; (c) Leitner, W. Green Chem. 2009, 11, 603.
55.9, 63.5, 110.8, 111.2, 112.4, 113.2, 113.3, 119.3, 119.8, 120.0, 121.0,
122.1, 124.3, 126.9, 128.5, 134.8, 136.6, 136.8, 147.2, 147.4, 148.7; HRMS
m/z (ESI) calcd for C27H29NNaO5 [MþNa]þ 470.1943; found 470.1946.
ꢀ
4. (a) Gu, Y.; Jerome, F. Green Chem. 2010, 12, 1127e1138; (b) A. E.Díaz-Alvarez, J.
Francos, B. Lastra-Barreira, P. Crochet, V.Cadierno, Chem. Commun. 6208e6227.
5. (a) Aparicio, S.; Alcalde, R. Green Chem. 2009, 11, 65e78; (b) Aparicio, S.;
Alcalde, R. J. Phys. Chem. B 2009, 113, 14257e14269; (c) Pereira, C. S. M.; Silva, V.
M. T. M.; Rodrigues, A. E. Green Chem. 2011, 13, 2658e2671.
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Jb¼5.2 Hz, 6H), 5.64 (s, 1H), 5.75 (s, 1H), 6.11 (t, J¼2.8 Hz, 1H), 6.50
(d, J¼2.8 Hz, 1H), 6.61 (d, J¼8 Hz, 1H), 6.67 (s, 1H), 6.70 (s, 1H), 6.72
(d, J¼2.8 Hz, 1H), 6.77 (dd, Ja¼2.8 Hz, Jb¼8 Hz, 1H), 7.98 (s, 1H); 13
C
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Acknowledgements
The authors thank for National Natural Science Foundation of
China for the financial support (20903042 and 21173089). This work
was also supported by Specialized Research Fund for the Doctoral
Program of Higher Education (20090142120081). The authors are
also grateful for all the other staff members in the Analytical and
Testing Center of HUST. The Program for new Century Excellent
Talents in the University of China (NCET-10-0383) and Chutian
Scholar Program of the Hubei Provincial Government are also ack-
nowledged. This work was also supported by the Fundamental
Research Funds for the Central Universities (2011TS023).
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi:10.1016/j.tet.2012.11.076.
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References and notes
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€
€
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