Gluconic acid aqueous solution as a sustainable and recyclable promoting medium for organic reactions

Article abstract of DOI:10.1039/c1gc15411g

For the first time, gluconic acid aqueous solution (GAAS), a biobased weakly acidic liquid, was used as an effective promoting medium for organic reactions, such as the Michael addition of indoles to α,β-unsaturated ketones, the electrophilic ring-opening

Full text of DOI:10.1039/c1gc15411g

View Article Online / Journal Homepage / Table of Contents for this issue
Dynamic Article Links
Green Chemistry
Cite this: Green Chem., 2011, 13, 2204
www.rsc.org/greenchem
PAPER
Gluconic acid aqueous solution as a sustainable and recyclable promoting
medium for organic reactions†
Binghua Zhou,a Jie Yang,a Minghao Lia and Yanlong Gu*a,b
Received 14th April 2011, Accepted 19th May 2011
DOI: 10.1039/c1gc15411g
For the first time, gluconic acid aqueous solution (GAAS), a biobased weakly acidic liquid,
was used as an effective promoting medium for organic reactions, such as the Michael addition
of indoles to a,b-unsaturated ketones, the electrophilic ring-opening reaction of 3,4-dihydropyran
with indoles and Friedel–Crafts alkylation of electron-rich aromatics with benzyl alcohols. The
concept of using GAAS as a solvent for organic reactions not only offers a sustainable candidate
for progress in solvent innovation, but also opens up a new avenue for the utilization of this
biobased polyhydroxylated acid. Among the features that render GAAS as a solvent so interesting
is the ability to act as both the reaction medium and catalyst. Moreover, this methodology offers
significant improvements with regard to the yield of products, simplicity in operation, cost efficiency
and green aspects, in terms of avoiding toxic catalysts and minimizing the generation of waste.
aqueous-based processes.11 As a result, researchers working on
Introduction
green solvents realized that a universal green solvent doesn’t
Many reactions, extractions, separations and other operations
exist. For this reason, other alternatives that could replace
in the chemical process industries involve the use of organic
the traditional solvents in a direct way have to be considered,
solvents. However, large scale uses of these organic solvents are
obviously without discarding others. In addition, the replace-
not only plagued by handling and disposal issues, but can also
ment of volatile organic solvents by new ones has to be done
pose a number of environmental concerns, such as ecotoxicity.1
without stifling the technological development and at moderate
In many cases, conventional organic solvents are regulated as
economical cost. New solvents should lead to at least the same
volatile organic compounds (VOCs). In addition, certain organic
number of benefits as the traditional ones, if not more.12
solvents are under restriction due to their ozone layer depletion
Nowadays, most solvents are prepared from fossil oil reserves.
potential. Therefore, the search for new families of alternative
However, limited supplies of fossil oil and concerns about global
media to replace traditional volatile organic solvents has become
a tremendous challenge in academia and industry.2
warming have created a strong desire to solve the resource issue
in the age “beyond petroleum”. Out of this consideration, the
In the last decade, many promising media have appeared as
utilization of biobased chemicals has attracted much attention.13
innovative solvents, such as water,3 ionic liquids,4 polyethylene
This opens up a new avenue for the progress of solvent
glycol,5 supercritical fluids6 (particularly supercritical carbon
innovation and many naturally available products, such as
dioxide (scCO2))7 and perfluorinated solvents.8 However, the
glycerol,14 soy methyl ester,15 lactate ester16 and D-limonene17
use of these solvents is still limited by many problems, such
amongst others, have been proposed as safer and sustainable
as corrosion problems and the high cost of equipment for
solvents for catalysis, organic reactions and separations. Many
scCO2,9 or high prices and lack of data about the toxicity and
others have also been used as precursors for the synthesis of
biocompatibility of ionic liquids,10 or product separation for
potentially safer green solvents,18 for example, biobased ionic
liquids.19 As compared to the traditional petrochemical-derived
solvents, these biobased solvents exhibit advantages not only
aInstitute of Physical Chemistry and Industrial Catalysis, School of
in minimizing solvent waste, but also in improving laboratory
Chemistry and Chemical Engineering, Hubei Key Laboratory of
safety. Furthermore, good biocompatibility and known com-
Material Chemistry and Service Failure, Huazhong University of Science
prehensive data about the toxicity also allow these biobased
solvents to be easily acceptable by both the environment and
industry. Despite these promising achievements, due to the
fact that research on biobased solvents is still at the level of
academic study, the importance of biobased solvents needs to
be documented, regarding both necessity and versatility. At this
and Technology (HUST), 1037 Luoyu road, Hongshan District, Wuhan,
430074, China. E-mail: klgyl@hust.edu.cn; Fax: (0)86-(0)27-87 54 45
32
bState Key Laboratory for Oxo Synthesis and Selective Oxidation,
Lanzhou Institute of Chemical Physics, Lanzhou, 730000, China
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c1gc15411g
2204 | Green Chem., 2011, 13, 2204–2211
This journal is
The Royal Society of Chemistry 2011
©

View Article Online
point, one of the main tasks for researchers in this area is to
search for new biobased solvent that possess a specific capacity.
Gluconic acid (GA) is an organic compound with
molecular formula C6H12O7 and condensed structural formula
HOCH2(CHOH)4COOH. This polyhydroxylated acid occurs
naturally in fruit, honey, kombucha tea and wine. It is used
as a food additive, as an acidity regulator. It is also used in
cleaning products, as it dissolves mineral deposits, especially in
alkaline solution. GA is prepared in industry by the oxidation
of glucose20 and, recently, cellulose has also been used as a raw
material for the preparation of GA.21 It is normally available
as an aqueous solution, which is composed of an equilibrium
mixture of GA and the g- and d-lactones. The equilibrium
between the free acid and the two lactones is affected by
the mixture’s concentration and temperature. Under normal
conditions, GA 50% exhibits a stable equilibrium, in which
about 5% of glucono-d-lactone is present in the solution at
room temperature, contributing to its clear to light yellow color
with low level corrosiveness and toxicity.
In light of the above description, we viewed that gluconic acid
aqueous solution (GAAS) might be a good candidate for acting
as a biobased green solvent. The reasons are multifold: (i) an
aqueous solution of GA is an inexpensive industrial product and
largely available in the market, which allows the use of GAAS as
a large quantity solvent to be practically feasible; (ii) GA and the
g- and d-lactones are characterized by many hydroxyl groups,
which makes these species highly hydrophilic and immiscible
with non-polar organic solvents and, consequently, allows an
easy product separation by extraction and the following recovery
of the solvent; (iii) dissociation of a proton from a GA molecule
results in a weakly acidic property of the aqueous solution,
which makes this solvent no longer neutral and this can be
a great means of promoting some organic reactions that need
the assistance of a weak acid; (iv) GA is stable at its boiling
point, even in concentrated alkaline solutions. However, it is
easily and totally degraded in waste water treatment plants
(98% after 2 days). These properties allow not only a successful
use of this aqueous solution at relatively high temperatures,
but also an easy post-treatment for the waste solvent. Out
of these considerations, we believe it would be worthwhile
to investigate the use of GAAS as a solvent for organic
reactions.
Crafts alkylationofelectron-richaromatics withbenzylalcohols,
proceeded well in aqueous solution of GA.
Results and discussion
Initially, the Michael addition of indole (1a) to cyclopent-2-
enone (2a) was selected as a model reaction for evaluating
the efficiency of GAAS. This reaction is usually generally
catalyzed by acid catalysts. Some homogeneous catalysts, in-
cluding InBr3,23 Bi(OTf)3,24 Hf(OTf)4,25 Cu(OTf)2,26 scandium
tris(dodecylsulfate)27 and aluminum tris(dodecylsulfate),28 have
been reported to be effective in this type of reaction. In order to
facilitate the recycling of the catalyst, some solid acids were
also used, such as nanocrystalline titanium(IV) oxide,29 sul-
fonated amorphous carbon,30 a CeCl3·7H2O–NaI combination
supported on a silica gel31 and silica-supported scandium or
sodium with ionic liquids.32 A literature survey also stated that
protic solvents, such as water33 and glycerol,34 have a unique
ability to promote this type of reaction. Considering the fact
that GAAS is a protic solvent, it would not be unreasonable to
expect that GAAS has, to some extent, an ability to promote this
Michael-type reaction. In order to shed light on the efficiency
of the promoting effect of the solvent on the model reaction,
we performed the reaction in the absence of any catalyst. As
shown in Table 1, at 100 ◦C, no product was detected in solvent-
free conditions and also in non-polar organic solvents, such
as toluene and n-butyl acetate (entries 1–3). Similarly, no or
only a trace amount of product was observed in polar aprotic
solvents, such as 1,2-dichloroethane, nitromethane, DMF and
DMSO (entries 4–7). The reaction also proceeded sluggishly in
water and glycerol, which are well known polar protic solvents
(entries 8 and 9). These results verified that the promoting
effect of water and glycerol is far less efficient at pushing the
model reaction toward completion. To our great delight, under
identical conditions, an 83% yield was obtained using GAAS
Table 1 The Michael addition of an indole to cyclopent-2-enone in
different conditionsa
In order to verify whether or not a liquid material can be used
as a new solvent for performing organic reactions, two points
have to be considered: (i) the feasibility of using this liquid as
solvent, which could answer the question whether it will work as
well as a traditional one and (ii) the necessity of using this liquid
as a solvent; in other words, compared to the traditional one,
what is the real advantage of this new solvent that makes this
liquid distinguishable? Because an aqueous solution of GA has
never been used as a solvent for performing organic reactions
before, in order to promote GAAS as a feasible solvent, we
do not evade these questions. In continuation of our research
to explore new biobased solvents,22 herein, we report the use
of GAAS as a promoting medium for organic reactions for
the first time. Some selected reactions that conventionally need
the assistance of an acid catalyst, such as the Michael reaction
of indoles with a,b-unsaturated ketones, the electrophilic ring-
opening reaction of 3,4-dihydropyran with indoles and Friedel–
Entry Solvent
Remark
Yield (%)
1
2
3
4
5
—
toluene
n-butyl acetate
1,2-dichloroethane
CH3NO2
No solvent
0
0
0
0
0
non-polar solvent
non-polar solvent
polar aprotic solvent
polar aprotic solvent
polar aprotic solvent
polar aprotic solvent
polar protic solvent
polar protic solvent
polar protic solvent
polar protic solvent
polar protic solvent
The fourth run of GAAS
20 mmol scale
6
7
DMF
DMSO
< 5
< 5
< 5
< 5
83
46
55
82
82
8
9
water
glycerol
10
11
12
13
14
GAAS (50%)
AcOH
AcOH aqu. (50%)
GAAS (50%)
GAAS (50%)
a Solvent: 1 ml, 1a: 0.5 mmol, 2a: 0.6 mmol, temperature: 100◦C, reaction
time: 10 h.
This journal is
The Royal Society of Chemistry 2011
Green Chem., 2011, 13, 2204–2211 | 2205
©

View Article Online
Table 2 The Michael reaction of different indoles with 2aa
(50%) as the solvent (entry 10). Interestingly, acetic acid and
acetic acid aqueous solution (50%) can also promote the model
reaction, but the yield obtained is inferior to that when GAAS
is used (entries 11 and 12). Furthermore, using acetic acid as
the solvent generates a lot of waste because, in order to isolate
the product, the acid solvent has to be neutralized with an
inorganic base after the reaction. In this regard, GAAS exhibited
a great advantage for facilitating the product isolation. Because
no catalyst was used, the quenching step that is necessary for
stopping a normal acid-catalyzed reaction was omitted. The
unreacted starting materials and the formed product could easily
be extracted by a non-polar organic solution composed of ethyl
acetate and petroleum ether (v/v = 1/1). Because of the fact that
GA and its lactones are characterized by many hydroxyl groups,
a non-polar organic solvent cannot dissolve these hydrophilic
species. As a result, this procedure rules out the possibility of
leaching of the GA and its derivatives from the aqueous phase.
To test the reusability of GAAS, the used GAAS was recycled
3 times, as shown in Table 1; the yield obtained in the fourth
run is still very good (entry 13). Importantly, no significant
change in the pH value and conductivity was observed by testing
GAAS before and after use (see ESI†), indicating good stability
of GAAS under the reaction conditions. The simple operation
also allowed easy scale-up of the reaction and, as shown in Table
1, a 20 mmol reaction also proceeded well in GAAS, indicating
a good effectiveness of our system for practical synthesis (entry
14).
With these results in hand, we then investigated the substrate
scopeoftheGAAS-mediatedMichaeladdition of indoles to a,b-
unsaturated ketones. As shown in Table 2, various substituted in-
doles, such as N-methylindole, 2-methylindole, 6-methylindole,
5-methoxyindole, 5-methoxy-2-methylindole, 6-fluoroindole, 4-
chloroindole and 5-bromoindole, readily react in GAAS with 2a
to form the corresponding adducts in good to excellent yields
(entries 1–8). The scope of the reaction, with respect to the a,b-
unsaturated ketone, was next investigated and also found to be
excellent. As Table 3 illustrates, many a,b-unsaturated ketones
could be employed without significantly affecting the yield of
the Michael adduct (entries 1–4). Particularly, a,b-unsaturated
ketones containing S- or O-heterocycle functionalities were also
applied in the reaction uneventfully. In addition, 3,4-dimethoxy-
b-nitrostyrene (2 g) was also proved to be applicable in the
GAAS system to react with 1c and the corresponding product
was obtained in 99% yield (entry 5).
Entry
1
Indole
Product
Yield (%)
93
1b
1c
1d
1e
3b
2
3
4
3c
3d
3e
99
65
84
5
1f
3f
90
6
1g
1h
3g
3h
74
61
7b
8
1i
3i
73
a Solvent: 1.0 ml, indole derivative: 0.5 mmol, 2a: 0.6 mmol, temperature:
100 ◦C; b 130 ◦C.
bis(indolyl)hydroxyalkyl derivatives not only have unique abili-
ties for enhancing the cytodifferentiating properties of retinoids
in myeloid leukemia cells,36 but also can be used as important
intermediates for the synthesis of cycloalkanoindoles37 that
have been studied for their anti-inflammatory,38 antidepressant39
and analgesic properties.40 In view of the fact that the gener-
ated products are generally used in pharmaceutical synthesis,
particular attention has to be paid to the removal of any
residue metal catalyst in the product. For this purpose, a metal-
free system for the electrophilic ring-opening reaction of 3,4-
dihydropyran with indoles is appealing. Encouraged by the
outstanding performance of GAAS in the above-mentioned
Michael reactions of indoles, we thus treated 3,4-dihydropyran
with indoles in GAAS at 110 ◦C and, after 11 h of reaction,
the expected ring-opening product was obtained in 82% of yield
(Table 4, entry 1). Interestingly, only a trace or small amount
of product was obtained under solvent-free conditions, in
toluene, 1,2-dichloroethane, DMF, DMSO, water and glycerol,
indicating that GAAS has a specific promoting effect on this
reaction (entries 2–8). Acetic acid and an aqueous solution of
All the results of the Michael reactions of indoles in GAAS
demonstrated, for the first time, that GAAS can indeed be used
as an effective promoting medium for organic reactions. The
salient features of using GAAS as a solvent for organic reactions
were observed not only in the way it significantly promotes
the reaction rate in the absence of a catalyst, but also in the
simplification of the work-up procedure and the recycling of
the reaction solvent. These promising results encouraged us
to further explore organic reactions by using GAAS as a dual
solvent–catalyst.
The second reaction we investigated in GAAS was elec-
trophilic ring-opening reactions of 3,4-dihydropyran with in-
doles. This type of reaction has been performed in the presence of
Lewis acids, such as InCl3 and MnCl2, in organic solvents.35 Par-
ticularly when simple 3,4-dihydropyran was used, the generated
2206 | Green Chem., 2011, 13, 2204–2211
This journal is
The Royal Society of Chemistry 2011
©

View Article Online
Table 3 The Michael reaction of 1c with a, b-unsaturated ketonesa
Entry a,b-Unsaturated ketone Product Yield (%)
Table 4 Electrophilic ring-opening reactions of 3, 4-dihydropyran with
indolesa
1
2b
3j 92
2
3
2c
2d
3k 55
3l 58
Entry
Indole
Solvent
Product
Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14b
15b
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1e
1g
1h
1i
GAAS
solvent-free
toluene
1,2-dichloroethane
DMF
DMSO
water
glycerol
AcOH
AcOH aq. (50%)
GAAS
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5b
5c
5d
5e
5f
82
< 5
< 5
< 5
< 5
< 5
25
< 5
55
50
91
81
80
74
4
5
2e
2g
3m 67
3n 99
GAAS
GAAS
GAAS
GAAS
70
a Indole derivative: 1.0 mmol, 4a: 0.75 mmol, solvent: 1.0 ml; tempera-
ture: 110 ◦C, reaction time: 11 h; b 130 ◦C, 14 h.
also an ester group, which are both chemically reactive under
the appropriate conditions, and in order to avoid some possible
side reactions, we had to carefully choose the model reaction
when using GAAS as a solvent.
a Solvent: 1.0 ml, 1c: 0.5 mmol, a,b-unsaturated ketone: 0.6 mmol,
The next reaction we investigated was the Friedel–Crafts
alkylation of indoles with benzyl alcohols. This type of reaction
has been realized by Cozzi and his co-workers in water under
catalyst-free conditions.41 However, we found that at a low tem-
perature of 50 ◦C, water as the solvent is ineffective for promot-
ing the model nucleophilic substitution reaction, perhaps due
to the low reactivity of 4-methoxy-a-methylbenzenemethanol,
6a (Table 5, entry 1). In order to improve the reaction rate,
acid catalysts, such as NbCl5 and triflic acid, have to be used.42
However, the reported acid systems often suffer from a tedious
aqueous work-up procedure because the acid catalyst has to be
removed after the reaction. In order to avoid the quenching step,
we are particularly interested in the possibility of realizing this
reaction by means of utilizing an appropriate solvent. As shown
in Table 5, no or only a trace amount of product was detected in
toluene,> 1,2-dichloroethane, DMF and DMSO (entries 2–5).
Glycerol also exhibited a poor performance, like water as the
solvent, in this reaction (entry 6). Surprisingly, in the GAAS
system, a lot of solid was formed (Fig. 1). By adding water
into the system, the solid product could be directly precipitated
out. After washing with water and drying under atmospheric
pressure, this could be obtained in high purity. NMR analysis
revealed that this solid product is the expected product, 7a, and
the yield reached 97%. The reasons for why 7a could be solidified
in the GAAS system include (i) 7a has a melting point of 156–
157 ◦C and is insoluble in GAAS solvent and (ii) using GAAS
as the solvent allows the reaction to be performed at a relatively
low temperature, 50 ◦C. Therefore, at the reaction temperature,
temperature: 100 ◦C, reaction time: 10 h.
acetic acid (50%) were then examined and only moderate yields
were obtained in the ring-opening reaction (entries 9 and 10).
The advantages of GAAS were also exhibited in the product
isolation. Although the generated product possesses a polar
hydroxyl group, extraction of the product from GAAS is, in fact,
not as difficult as we thought, and a mixture of ethyl acetate and
petroleum ether (v/v = 1/1) is sufficiently enough for removing
the product from GAAS. Many other indoles can also be used
in this reaction and good to excellent yields were obtained in
this system (entries 11–15). With this method, an efficient and
metal-free synthesis of bis(indolyl)hydroxyalkyl derivatives was
accomplished for the first time, indicating again the usefulness
of GAAS as a solvent for organic reactions.
Gluconic acid lactone was also present in the GAAS, although
this lactone is normally only formed in small amount. Therefore,
the reactivity of gluconic acid lactone in the presence of 1a,
2a, 3a, 4a and 5a was then investigated. In order to facilitate
detection of the reaction, the reactions were conducted under
two conditions: with (i) acetic acid and (ii) InCl3 (10 mol
%)/DCE. In both cases, no significant reaction was observed,
indicating that gluconic acid lactone is quite stable toward
these compounds (see ESI†). Therefore, the potential effects
of gluconic acid lactone on these reactions were precluded.
However, in view of the fact that gluconic acid lactone is a
compound that contains not only many hydroxyl groups, but
This journal is
The Royal Society of Chemistry 2011
Green Chem., 2011, 13, 2204–2211 | 2207
©

View Article Online
Table 5 Friedel–Crafts alkylation of indoles with benzyl alcoholsa
waste water treatment plants. Therefore, the negative effect of the
waste GAAS solution on the environment could be minimized.
It should also be noted that, for the Friedel–Crafts alkylations
of indoles with benzyl alcohols, this is the first example of
isolation of the reaction product without the use of silica column
chromatography. Unfortunately, this method only works for 7a,
while for the other alkylation reactions the formed products have
to be isolated with conventional methods because no fine solid
could be observed at the end of the reaction. In spite of this
fact, the yields obtained in the alkylations of indoles with benzyl
alcohols in the GAAS system are still very good (entries 8–17).
Many indoles and benzyl alcohols could be uneventfully used.
Inspired by these promising results, we then investigated the
alkylation reactions of some basic nucleophiles with 6a, which
are normally difficult to be used in conventional acid catalyst
systems. As shown in Scheme 1, in the GAAS system, both N,N-
dimethylaniline and antipyrine react readily with 6a to form the
corresponding alkylation products in high yields. In particular,
no strong interaction between the basic product and GAAS
could be observed. Thus, the formed products could be easily
extracted by an organic solvent. These results again indicated
the usefulness of GAAS for organic synthesis.
Entry Indole Alcohol Solvent
Product Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15b
16b,c
17b,c
1a
1a
1a
1a
1a
1a
1a
1b
1c
1e
1g
1h
1i
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6b
6c
6d
4c
water
toluene
1,2-dichloroethane 7a
DMF
7a
7a
50
< 5
< 5
0
7a
7a
7a
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
DMSO
glycerol
GAAS
GAAS
GAAS
GAAS
GAAS
GAAS
GAAS
GAAS
GAAS
GAAS
GAAS
0
20
97
80
99
81
90
81
98
50
95
90
70
1a
1a
1a
1a
Conclusion
In conclusion, GAAS was demonstrated to be a promising
green solvent for performing organic reactions for the first time.
The concept of using GAAS as a solvent for organic reactions
not only offers a sustainable candidate for progress in solvent
innovation, but also opens a new avenue for utilization of this
biobased polyhydroxylated acid. Among the features that render
GAAS as a solvent so interesting is the ability to act as both
the reaction medium and catalyst. Many reactions, including
Michael addition of indoles to a,b-unsaturated ketones, elec-
trophilic ring-opening reaction of 3,4-dihydropyran with indoles
and Friedel–Crafts alkylations of carbon-based nucleophiles
with benzyl alcohols, proceeded very well in GAAS without
the use of any additional catalyst. Moreover, this methodology
offers significant improvements, with regard to the yield of
products, simplicity of operation, cost efficiency and green
aspects, in terms of avoiding toxic catalysts and of minimizing
the generation of waste. The strong hydrogen bond network
and weak acidic environment should be partially responsible for
the excellent performance of GAAS. Furthermore, in view of
the fact that GAAS is a hydrophilic solvent that may not be
able to dissolve lipophilic compounds well under the reaction
conditions, a rate acceleration resulting from the “on water”
a Benzyl alcohol: 0.5 mmol, indole: 0.55 mmol, solvent: 1.0 ml; temper-
ature: 50 ◦C, reaction time: 6 h; b 80 ◦C; c 8 h.
Fig. 1 The solid product formed at the end of the model reaction.
7a could be formed as a solid. This isolation method is quite
simple, but during washing of the solid a lot of waste water
containing GAAS was also generated. Fortunately, the waste
aqueous solution containing GAAS could easily be degraded in
Scheme 1 The GAAS-mediated electrophilic alkylation of 6a with basic nucleophiles.
2208 | Green Chem., 2011, 13, 2204–2211 This journal is The Royal Society of Chemistry 2011
©

View Article Online
effect might also be involved in the reaction system.43 However,
despite the observed beneficial effects exerted by GAAS on all
of these reactions, the exact nature of this influence cannot be
ascribed to a single effect, such as the acidic environment or “on-
water” effect, but rather to a combination of several factors. We
will extend our research along these lines in order to shed light
on these factors.
7.29 (m, 1H), 8.46 (bs, 1H); 13C NMR (CDCl3): 31.0, 33.9, 38.1,
47.0, 110.2, 119.2, 120.7, 121.0, 122.8, 123.8, 126.1, 138.2, 220.1;
IR (cm-1) 3340, 3128, 3059, 2962, 2890, 1731, 1615, 1486, 1427,
1397, 1339, 1255, 1231, 1188, 1164, 1136, 1044, 940, 827, 773,
738, 679, 613, 572; HRMS m/z (ESI†) calcd for C13H12ClNNaO
[M + Na]+ 256.0505, found 256.0493.
4-(2-Methyl-1H-indol-3-yl)-4-(2-thienyl)-2-butanone
(3l).
1
Red oil, H NMR (CDCl3): 1.98 (s, 3H), 2.03 (d, J = 2.8 Hz,
2H), 2.34 (s, 3H), 3.33 (dd, Ja = 7.6 Hz, Jb = 16.8 Hz, 1H); 3.42
(q, J = 8.0 Hz, 1H); 5.01 (t, J = 7.6 Hz, 1H), 6.74–6.79 (m, 1H),
6.83 (dd, Ja = 3.6 Hz, Jb = 4.8 Hz, 1H), 6.99 (dt, Ja = 1.2 Hz,
Jb = 8.0 Hz, 1H), 7.03–7.09 (m, 2H), 7.17 (t, J = 7.6 Hz, 1H),
7.42 (d, J = 8.0 Hz, 1H), 7.88 (bs, 1H); 13C NMR (CDCl3):
12.0, 30.8, 32.9, 49.5, 110.7, 112.9, 119.1, 119.2, 120.9, 123.5,
123.7, 126.6, 126.9, 132.1, 135.5, 149.0, 207.4; IR (cm-1) 3401,
3057, 2962, 2918, 1709, 1617, 1583, 1488, 1460, 1432, 1359,
1300, 1245, 1162, 1133, 1040, 966, 848, 827, 743, 699, 601, 584,
530; HRMS m/z (ESI†) calcd for C17H17NNaOS [M + Na]+
306.0929, found 306.0925.
Experimental section
All of the reactions were conducted in a 10 ml V-type flask
equipped with a triangular magnetic stirrer bar. In a typical
reaction, gluconic acid aqueous solution (1.0 ml) was mixed
with an indole (1a, 58.5 mg, 0.50 mmol) and cyclopent-2-enone
(2a, 49.3 mg, 0.60 mmol) under air. The mixture was stirred for
10 h at 100 ◦C. After reaction, the mixture was cooled to room
temperature and the reaction mixture was extracted with a mixed
solution composed of ethyl acetate and heptane (v/v = 2/1,
6 ml ¥ 3). After concentration of the combined organic phase
under reduced pressure, the desired product, 3a, was obtained
by preparative TLC using a mixed solution of ethyl acetate and
◦
4-(2-Methyl-1H-indol-3-yl)-4-(2-furyl)-2-butanone
(3m).
petroleum ether (40–60 C) as the eluting solvent (the ratio of
1
Red oil, H NMR (CDCl3): 2.01 (s, 3H), 2.35 (s, 3H), 3.22 (q,
J = 8.0 Hz, 1H), 3.34 (dd, Ja = 6.0 Hz, Jb = 15.6 Hz, 1H), 4.83
(t, J = 7.2 Hz, 1H), 5.94 (d, J = 3.2 Hz, 1H), 6.22 (q, J = 1.6 Hz,
1H), 6.99 (dt, Ja = 0.8 Hz, Jb = 8.0 Hz, 1H), 7.06 (dt, Ja = 0.8
Hz, Jb = 8.0 Hz, 1H), 7.18 (d, J = 8.0 Hz, 1H), 7.27 (s, 1H),
7.43 (d, J = 7.6 Hz, 1H), 7.92 (bs, 1H); 13C NMR (CDCl3):
11.9, 30.7, 31.4, 46.8, 105.6, 110.2, 110.6, 110.8, 119.0, 119.2,
120.9, 127.1, 132.2, 135.5, 141.1, 156.9, 207.4; IR (cm-1) 3401,
3115, 3056, 2919, 1710, 1616, 1586, 1501, 1460, 1429, 1359,
1301, 1246, 1161, 1076, 1010, 968, 912, 884, 806, 739, 597, 534,
505; HRMS m/z (ESI†) calcd for C17H17NNaO2 [M + Na]+
290.1157, found 290.1146.
ethyl acetate/petroleum ether was 1/7). 82.7 mg, yield = 83%.
The recovered GAAS phase could be reused after 20 min of
treatment at 70 ◦C under reduced pressure. The 20 mmol scale
reaction of 1a and 2a was performed in a 100 ml flask using
an increased amount of GAAS (60 ml) as the medium. Other
reactions and examination of substrate scope were all performed
according to similar procedures.
Spectroscopic data of new compounds
3-(6-Methyl-1H-indol-3-yl)cyclopentanone (3d). Red oil, 1H
NMR (CDCl3): 2.00–2.14 (m, 1H), 2.16–2.43 (m, 4H), 2.45 (d,
J = 8.0 Hz, 3H), 2.56–2.76 (m, 1H), 3.64 (sext, J = 7.2 Hz, 1H),
6.81 (d, J = 6.0 Hz, 1H), 6.96 (t, J = 7.6 Hz, 1H), 7.10 (d, J =
7.6 Hz, 1H), 7.48 (t, J = 8.0 Hz, 1H), 8.11 (bs, 1H); 13C NMR
(CDCl3): 21.8, 30.0, 33.9, 38.3, 45.4, 111.5, 118.3, 118.8, 119.5,
121.2, 124.5, 132.2, 137.3, 220.0; IR (cm-1) 3405, 3082, 2936,
2917, 1733, 1626, 1551, 1457, 1401, 1339, 1311, 1284, 1231, 1152,
1098, 1037, 978, 907, 855, 800, 733, 648, 580; HRMS m/z (ESI)
calcd for C14H15NNaO [M + Na]+ 236.1051, found 236.1045.
6-Fluoro-e-(6-fluoro-1H -indol-3-yl)-1H -indole-3-pentanol
(5d). Red oil, 1H NMR (CDCl3): 1.24–1.37 (m, 2H), 1.40–1.53
(m, 2H), 2.06 (q, J = 7.6 Hz, 2H), 2.36 (bs, 1H), 3.45 (t, J =
6.8 Hz, 2H), 4.26 (t, J = 7.2 Hz, 1H), 6.70 (dt, Ja = 2.0 Hz, Jb
= 9.6 Hz, 2H), 6.75 (d, J = 2.0 Hz, 2H), 6.83 (dd, Ja = 2.0 Hz,
Jb = 9.6 Hz, 2H), 7.34 (dd, Ja = 5.6 Hz, Jb = 8.8 Hz, 2H), 8.24
(bs, 2H); 13C NMR (CDCl3): 24.4, 32.7, 34.0, 35.4, 62.8, 97.4,
97.6, 107.5, 107.7, 119.8, 120.1, 120.2, 121.9, 121.9, 123.6, 136.5,
136.6, 158.6, 160.9; IR (cm-1) 3420, 3067, 2937, 2861, 1713, 1625,
1553, 1496, 1455, 1404, 1342, 1303, 1252, 1217, 1139, 1090, 1042,
993, 950, 907, 836, 804, 732, 606; HRMS m/z (ESI†) calcd for
C21H20F2N2NaO [M + Na]+ 377.1441, found 377.1430.
3-(2-Methyl-5-methoxy-1H-indol-3-yl)cyclopentanone (3f).
1
Red oil, H NMR (CDCl3): 2.14–2.34 (m, 2H), 2.34–2.40 (m,
4H), 2.40–2.58 (m, 2H), 2.73 (dd, Ja = 12.0 Hz, Jb = 18.4 Hz,
1H), 3.50–3.62 (m, 0.6H), 3.68–3.78 (m, 0.4H), 3.82 (s, 3H),
6.77 (dd, Ja = 2.4 Hz, Jb = 8.8 Hz, 1H), 6.98 (d, J = 2.4 Hz,
1H), 7.14 (d, J = 8.8 Hz, 1H), 8.09 (bs, 1H); 29.6, 34.5, 39.5,
44.1, 56.2, 101.8, 110.1, 111.4, 111.4, 127.3, 130.8, 132.2, 153.6,
220.1, 220.1; IR (cm-1) 3397, 3063, 2955, 2908, 2831, 2248,
1735, 1625, 1586, 1484, 1400, 1364, 1284, 1253, 1216, 1152,
1097, 1032, 909, 827, 732, 621, 568; HRMS m/z (ESI†) calcd
for C15H17NNaO2 [M + Na]+ 266.1157, found 266.1148.
4-Chloro-e-(4-chloro-1H-indol-3-yl)-1H-indole-3-pentanol
(5e). Red solid, mp: 148–150 ◦C, 1H NMR (CDCl3): 1.43–1.60
(m, 4H), 1.96 (q, J = 7.2 Hz, 2H), 2.16 (bs, 1H), 3.50 (t, J =
6.0 Hz, 2H), 5.62 (t, J = 7.2 Hz, 1H), 6.50 (d, J = 1.6 Hz, 2H),
6.88–6.97 (m, 4H), 7.03 (dd, Ja = 1.2 Hz, Jb = 7.6 Hz, 2H),
8.19 (d, J = 1.6 Hz, 2H); 13C NMR (CDCl3): 24.5, 32.8, 33.5,
38.3, 62.9, 110.1, 120.3, 121.3, 122.1, 123.2, 123.6, 126.4, 138.2;
IR (cm-1) 3424, 3123, 2937, 2855, 1709, 1612, 1562, 1426, 1338,
1281, 1250, 1186, 1144, 1102, 1033, 996, 93, 819, 773, 739, 625,
586, 516; HRMS m/z (ESI†) calcd for C21H20Cl2N2NaO [M +
Na]+ 409.0850, found 409.0837.
3-(4-Chloro-1H-indol-3-yl)cyclopentanone (3h). Red solid,
mp: 110–111 ◦C, 1H NMR (CDCl3): 2.07 (qd, Ja = 4.0 Hz, Jb =
17.2 Hz, 1H), 2.28–2.46 (m, 3H), 2.49–2.60 (m, 1H), 2.82 (dd,
Ja = 8.0 Hz, Jb = 18.4 Hz, 1H), 4.21 (quint, J = 8.4 Hz, 1H), 7.00
(d, J = 2.0 Hz, 1H), 7.08 (d, J = 2.0 Hz, 1H), 7.09 (s, 1H), 7.23–
This journal is
The Royal Society of Chemistry 2011
Green Chem., 2011, 13, 2204–2211 | 2209
©

View Article Online
3-[1-(4-Methoxyphenyl)ethyl]-5-methoxy-1H-indole
(7d).
126.7, 126.9, 127.1, 129.0, 129.2, 133.4, 137.2, 142.6, 157.4; IR
(cm-1) 3370, 3011, 2963, 1723, 1631, 1605, 1460, 1483, 1460,
1336, 1261, 1225, 1172, 1100, 1020, 921, 861, 810, 769, 745,
668, 549; HRMS m/z (ESI†) calcd for C21H19NNaO [M + Na]+
324.1364, found 324.1358.
Red oil, 1H NMR (acetone-d6): 1.63 (d, J = 7.2 Hz, 3H), 3.66 (s,
3H), 3.72 (s, 3H), 4.28 (q, J = 7.2 Hz, 1H), 6.71 (dd, Ja = 2.4 Hz,
Jb = 8.8 Hz, 1H), 6.78–6.83 (m, 3H), 7.14 (d, J = 1.6 Hz, 1H),
7.20–7.27 (m, 3H), 9.83 (bs, 1H); 13C NMR (acetone-d6): 22.1,
36.1, 54.5, 54.9, 101.4, 111.1, 111.7, 113.4, 120.4, 122.1, 127.4,
128.2, 132.4, 139.4, 153.5, 157.9; IR (cm-1) 3417, 3030, 2960,
2932, 2833, 1717, 1611, 1582, 1510., 1484, 1455, 1300, 1244,
1211, 1175, 1089, 1034, 921, 833, 798, 734, 634, 560; HRMS
m/z (ESI†) calcd for C18H19NNaO2 [M + Na]+ 304.1313, found
304.1301.
4-[1-(4-Met◦hoxyphenyl)ethyl]antipyrine (11a). White solid,
1
mp: 111–112 C, H NMR (CDCl3): 1.66 (d, J = 7.6 Hz, 3H),
2.04 (s, 3H), 2.92 (s, 3H), 3.74 (s, 3H), 3.97 (q, J = 7.2 Hz, 1H),
6.81 (td, Ja = 2.4 Hz, Jb = 11.6 Hz, 2H), 7.20 (sept, J = 4.0 Hz,
1H), 7.35 (d, J = 8.8 Hz, 2H), 7.40 (d, J = 4.4 Hz, 4H); 13C NMR
(CDCl3): 11.3, 19.3, 33.8, 36.2, 55.2, 113.7, 114.8, 123.4, 125.9,
128.3, 129.0, 135.5, 137.5, 152.7, 157.9, 165.6; IR (cm-1) 3042,
2993, 2965, 1658, 1593, 1511, 1454, 1398, 1343, 1272, 1246, 1178,
1135, 1057, 1030, 831, 751, 694, 654, 588; HRMS m/z (ESI†)
calcd for C20H22N2NaO2 [M + Na]+ 345.1579, found 345.1555.
3-[1-(4-Methoxyp◦henyl)ethyl]-6-fluoro-1H-indole (7e). Red
1
solid, mp: 138–139 C, H NMR (acetone-d6): 1.63 (d, J = 7.2
Hz, 3H), 3.72 (s, 3H), 4.29 (q, J = 7.2 Hz, 1H), 6.69 (ddd,
Ja = 2.4 Hz, Jb= 8.8 Hz, Jc = 10.8 Hz, 1H), 6.80 (td, Ja = 2.8
Hz, Jb = 9.6 Hz, 2H), 7.09 (dd, Ja = 2.4 Hz, Jb = 10.4 Hz,
1H), 7.17–7.23 (m, 3H), 7.24 (dd, Ja = 5.2 Hz, Jb = 8.4 Hz,
1H), 10.10 (bs, 1H); 13C NMR (acetone-d6): 22.1, 36.0, 54.5,
97.0, 97.3, 106.6, 106.8, 113.5, 120.1, 120.2, 120.9, 121.9, 122.0,
123.8, 128.2, 139.2, 158.0, 160.8; IR (cm-1) 3398, 3001, 2969,
2931, 2862, 1894, 1725, 1609, 1550, 1510, 1456, 1401, 1338,
1301, 1234, 1173, 1023, 967, 947, 836, 805, 727, 600, 558; HRMS
m/z (ESI†) calcd for C17H16FNNaO [M + Na]+ 292.1114, found
292.1106.
Acknowledgements
The authors thank the National Natural Science Fundation
of China for the financial support (20903042). The authors
are also grateful to Ms. Ping Liang and all of the other staff
members in the Analytical and Testing Center of HUST for
their supportive and constant contributions to our work. The
Program for New Century Excellent Talents in the University
of China and Chutian Scholar Program of the Hubei provincial
government are also acknowledged.
3-[1-(4-Methoxyphenyl)ethyl]-4-chloro-1H-indole (7f). Yel-
low solid, mp: 170–172 ◦C, 1H NMR (acetone-d6): 1.62 (d, J =
7.2 Hz, 3H), 2.85 (s, 3H), 3.72 (s, 3H), 4.90 (q, J = 6.8 Hz, 1H),
6.78 (td, Ja = 3.2 Hz, Jb = 10.0 Hz, 2H), 6.92 (dd, Ja = 0.8 Hz,
Jb = 7.6 Hz, 1H), 7.01 (t, J = 7.6 Hz, 1H), 7.15 (d, J = 8.4 Hz,
2H), 7.24 (d, J = 1.6 Hz, 1H), 7.34 (d, J = 8.0 Hz, 1H), 10.37 (bs,
1H); 13C NMR (acetone-d6): 23.6, 35.7, 54.5, 110.4, 113.4, 119.7,
121.0, 121.9, 123.6, 125.6, 128.4, 138.6, 140.0, 157.8; IR (cm-1):
3351, 3058, 2964, 1723, 1645, 1610, 1509, 1421, 1338, 1232, 1179,
1142, 1024, 939, 829, 782, 751, 634, 613, 572; HRMS m/z (ESI†)
calcd for C17H16ClNNaO [M + Na]+ 308.0818, found 308.0802.
References
1 J. H. Clark and S. J. Tavener, Org. Process Res. Dev., 2007, 11, 149–
155.
2 (a) F. M. Kerton, Alternative Solvents for Green Chemistry, RSC
Green Chemistry Series, ed. J. Clark, 2009; (b) W. Leitner, Green
Chem., 2007, 9, 923; (c) W. Leitner, Green Chem., 2009, 11, 603.
3 (a) C.-J. Li and L. Chen, Chem. Soc. Rev., 2006, 35, 68–82; (b) S.
Kobayashi, Pure Appl. Chem., 2007, 79, 235–245.
4 (a) N. V. Plechkova and K. R. Seddon, Chem. Soc. Rev., 2008, 37,
123–150; (b) Y. Gu and G. Li, Adv. Synth. Catal., 2009, 351, 817–847.
5 J. Chen, S. K. Spear, J. G. Huddleston and R. D. Rogers, Green
Chem., 2005, 7, 64–82.
3-[1-(4-Methoxyphenyl)ethyl]-5-bromo-1H-indole (7g). Red
1
oil, H NMR (acetone-d6): 1.63 (d, J = 7.2 Hz, 3H), 3.72 (s,
6 J. F. Brennecke, Chem. Ind., 1996, 831–834.
7 C. A. Eckert, B. L. Knutson and P. G. Debenedetti, Nature, 1996,
383, 313–318.
3H), 4.30 (q, J = 7.2 Hz, 1H), 6.81 (td, Ja = 2.8 Hz, Jb = 9.6
Hz, 2H), 7.15 (dd, Ja = 2.0 Hz, Jb = 8.4 Hz, 1H), 7.20 (td, Ja =
3.2 Hz, Jb = 10.0 Hz, 2H), 7.27 (d, J = 1.6 Hz, 1H), 7.33 (d,
J = 4.8 Hz, 1H), 7.44 (d, J = 2.0 Hz, 1H), 10.2 (bs, 1H); 13C
NMR (acetone-d6): 22.2, 35.8, 54.5, 111.3, 113.1, 113.6, 120.5,
121.6, 123.1, 123.8, 128.1, 128.8, 135.8, 139.0, 158.1; IR (cm-1)
3424, 3063, 2962, 2930, 2870, 2835, 1699, 1610, 1582, 1509, 1457,
1371, 1299, 1243, 1177, 1099, 962, 882, 832, 795, 756, 662, 588,
554; HRMS m/z (ESI†) calcd for C17H16BrNNaO [M + Na]+
352.0313, found 352.0311.
8 I. T. Horvath, Acc. Chem. Res., 1998, 31, 641–650.
9 (a) Green Chemistry Using Liquid and Supercritical Carbon Dioxide,
ed. J. M. DeSimone, C. Hill and W. Tumas, 2003, Oxford University
Press, USA; (b) J. Sherman, B. Chin, P. Huibers, R. Garcia-Valls and
T. Hatton, Environ. Health Perspect., 1998, 106(Suppl. 1), 253–271.
10 (a) Ionic Liquids as Green Solvents: Progress and Prospects, ed. R. D.
Rogers and K. R. Seddon, ACS Pub, 2003; (b) D. Coleman and N.
Gathergood, Chem. Soc. Rev., 2010, 39, 600.
11 M. N. William, Green Solvents for Chemistry: Perspectives and
Practice, 2003, Oxford University Press, USA.
12 S. Aparicio and R. Alcalde, J. Phys. Chem. B, 2009, 113, 14257–
14269.
13 (a) N. Armaroli and V. Balzani, Angew. Chem., Int. Ed., 2007, 46, 52–
66; (b) D. M. Alonso, J. Q. Bond and J. A. Dumesic, Green Chem.,
2010, 12, 1493–1513; (c) A. Corma, S. Iborra and A. Velty, Chem.
Rev., 2007, 107, 2411–2502.
14 (a) Y. Gu and F. Jerome, Green Chem., 2010, 12, 1127–1138; (b) A.
Karam, N. Villandier, M. Delample, C. K. Koerkamp, J.-P. Douliez,
R. Granet, P. Krausz, J. Barrault and F. Je´roˆme, Chem.–Eur. J., 2008,
14, 10196–10200; (c) J. Francos and V. Cadierno, Green Chem., 2010,
12, 1552–1555.
15 S. Salehpour and M. A. Dube, Green Chem., 2008, 10, 321–326.
16 S. Aparicio and R. Alcalde, Green Chem., 2009, 11, 65–78.
1-(6¢-Methoxy-2-naphthyl)ethyl-1H-indole
(7h). White
◦
1
solid, mp: 176–178 C, H NMR (acetone-d6): 1.75 (d, J = 7.2
Hz, 3H), 2.86 (s, 3H), 3.87 (s, 3H), 4.51 (q, J = 7.2 Hz, 1H), 6.84
(dt, Ja = 0.8 Hz, Jb = 8.0 Hz, 1H), 7.02 (dt, Ja = 1.2 Hz, Jb = 8.0
Hz, 1H), 7.09 (dd, Ja = 2.8 Hz, Jb = 9.2 Hz, 1H), 7.21 (d, J =
2.4 Hz, 1H), 7.27 (d, J = 1.6 Hz, 1H), 7.32 (d, J = 8.0 Hz, 1H),
7.36 (d, J = 8.4 Hz, 1H), 7.40 (dd, Ja = 2.0 Hz, Jb = 8.8 Hz, 1H),
7.67 (d, J = 8.4 Hz, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.76 (s, 1H),
10.06 (bs, 1H); 13C NMR (acetone-d6): 21.9, 36.9, 54.7, 100.0,
105.7, 111.2, 118.3, 118.4, 119.2, 120.3, 121.2, 121.6, 125.0,
2210 | Green Chem., 2011, 13, 2204–2211
This journal is
The Royal Society of Chemistry 2011
©

View Article Online
17 (a) M. Virot, V. Tomao, C. Ginies, F. Visinoni and F. Chemat, J.
Chromatogr., A, 2008, 1196–1197, 147–152; (b) P. S. Kulkarni, C.
Brazinha, C. A. M. Afonso and J. G. Crespo, Green Chem., 2010, 12,
1990.
18 (a) H. Garc´ıa-Mar´ın, J. C. van der Toorn, J. A. Mayoral, J. I. Garc´ıa
and I. W. C. E. Arends, Green Chem., 2009, 11, 1605–1609; (b) O.
Aschenbrenner, S. Supasitmongkol, M. Taylor and P. Styring, Green
Chem., 2009, 11, 1217–1221.
19 (a) G. Imperato, B. Koenig and C. Chiappe, Eur. J. Org. Chem., 2007,
1049–1058; (b) F. Bellina, A. Bertoli, B. Melai, S. Scalesse, F. Signori
and C. Chiappe, Green Chem., 2009, 11, 622–629.
20 X. Liang, C.-J. Liu and P. Kuai, Green Chem., 2008, 10, 1318–
1322.
21 (a) X. Tan, W. Deng, M. Liu, Q. Zhang and Y. Wang, Chem.
Commun., 2009, 7179–7181; (b) A. Onda, T. Ochi and K. Yanagisawa,
Catal. Commun., 2010, 12, 421.
31 G. Bartoli, M. Bartolacci, M. Bosco, G. Foglia, A. Giuliani, E.
Marcantoni, L. Sambri and E. Torregiani, J. Org. Chem., 2003, 68,
4594–4597.
32 (a) Y. Gu, C. Ogawa, J. Kobayashi, Y. Mori and S. Kobayashi, Angew.
Chem., Int. Ed., 2006, 45, 7217–7220; (b) Y. Gu, C. Ogawa and S.
Kobayashi, Org. Lett., 2007, 9, 175–178.
33 (a) P. Wu, Y. Wan and J. Cai, Synlett, 2008, 1193–1198; (b) H.-B.
Zhang, L. Liu, Y.-L. Liu, Y.-J. Chen, J. Wang and D. Wang, Synth.
Commun., 2007, 37, 173–181.
34 Y. Gu, J. Barrault and F. Je´roˆme, Adv. Synth. Catal., 2008, 350,
2007–2012.
35 (a) J. S. Yadav, B. V. S. Reddy, G. Satheesh, A. Prabhakar and A. C.
Kunwar, Tetrahedron Lett., 2003, 44, 2221–2224; (b) M. Li, C. Tang,
J. Yang and Y. Gu, Chem. Commun., 2011, 47, 4529–4531.
36 C. Pisano, P. Kollar, M. Giann´ı, Y. Kalac, V. Giordano, F. F. Ferrara,
R. Tancredi, A. Devoto, A. Rinaldi, A. Rambaldi, S. Penco, M.
Marzi, G. Moretti, L. Vesci, O. Tinti, P. Carminati, M. Terao and E.
Garattini, Blood, 2002, 100, 3719–3730.
37 G. Giannini, M. Marzi, G. P. Moretti, S. Penco, M. O. Tinti, S. Pesci,
F. Lazzaro and F. De Angelis, Eur. J. Org. Chem., 2004, 2411–2420.
38 A. A. Asselin, L. G. Humber, T. A. Dobson and J. Komlossy, J. Med.
Chem., 1976, 19, 787–792.
22 (a) F. He, P. Li, Y. Gu and G. Li, Green Chem., 2009, 11, 1768–1773;
(b) M. Li, C. Chen, F. He and Y. Gu, Adv. Synth. Catal., 2010, 352,
519–530.
23 M. Bandini, P. G. Cozzi, M. Giacomini, P. Melchiorre, S.
Selva and A. Umani-Ronchi, J. Org. Chem., 2002, 67, 3700–
3704.
24 M. M. Alam, R. Varala and S. R. Adapa, Tetrahedron Lett., 2003,
39 A. A. Asselin, L. G. Humber and J. Komlossy, J. Med. Chem., 1976,
19, 792–797.
44, 5115–5119.
25 M. Kawatsura, S. Aburatani and J. Uenishi, Synlett, 2005, 2492–
2494.
26 J. S. Yadav, B. V. S. Reddy, G. Baishya, K. V. Reddy and A. V.
Narsaiah, Tetrahedron, 2005, 61, 9541–9544.
40 D. J. Davies, P. J. Garratt, D. A. Tocher and S. Vonhoff, J. Med.
Chem., 1998, 41, 451–467.
41 (a) P. G. Cozzi and L. Zoli, Angew. Chem., Int. Ed., 2008, 47, 4162–
4166; (b) P. G. Cozzi and L. Zoli, Green Chem., 2007, 9, 1292–1295.
42 (a) M. Yasuda, T. Somyo and A. Baba, Angew. Chem., Int. Ed., 2006,
45, 793–796; (b) K. Motokura, N. Nakagiri, T. Mizugaki, K. Ebitani
and K. Kaneda, J. Org. Chem., 2007, 72, 6006–6015; (c) J. S. Yadav,
D. C. Bhunia, K. V. Krishna and P. Srihari, Tetrahedron Lett., 2007,
48, 8306–8310; (d) J. Le Bras and J. Muzart, Tetrahedron, 2007, 63,
7942–7948; (e) P. Srihari, D. C. Bhunia, P. Sreedhar and J. S. Yadav,
Synlett, 2008, 1045–1049.
27 K. Manabe, N. Aoyama and S. Kobayashi, Adv. Synth. Catal., 2001,
343, 174–176.
28 H. Firouzabadi, N. Iranpoor and F. Nowrouzi, Chem. Commun.,
2005, 789–791.
29 M. L. Kantam, S. Laha, J. Yadav, B. M. Choudary and B. Sreedhar,
Adv. Synth. Catal., 2006, 348, 867–872.
30 J. Ma, S. Ng, Y. Yong, X.-Z. Luo, X. Wang and X.-W. Liu, Chem.–
Asian J., 2010, 5, 778–782.
43 R. N. Butler and A. G. Coyne, Chem. Rev., 2010, 110, 6302–6337.
This journal is
The Royal Society of Chemistry 2011
Green Chem., 2011, 13, 2204–2211 | 2211
©