Facile and rapid access to poly functionalized pyridine derivatives

Article abstract of DOI:10.1002/cjoc.201190178

An efficient and greener protocol for the synthesis of poly functionalized pyridines using tetra-n-butyl ammonium fluoride (TBAF) in water is established. Remarkable advantages of the present synthetic strategy over the others are shorter reaction times,

Full text of DOI:10.1002/cjoc.201190178

FULL PAPER
Facile and Rapid Access to Poly Functionalized Pyridine
Derivatives
Shinde, Pravin V.
Shingate, Bapurao B.
Shingare, Murlidhar S.*
Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad-431004, India
An efficient and greener protocol for the synthesis of poly functionalized pyridines using tetra-n-butyl ammo-
nium fluoride (TBAF) in water is established. Remarkable advantages of the present synthetic strategy over the
others are shorter reaction times, higher isolated yields, reuse of catalytic system, simple work-up procedure and
more especially its applicability to heteryl and aliphatic aldehydes.
Keywords green chemistry, pyridines, tetra-n-butyl ammonium fluoride (TBAF), water chemistry
Introduction
chemists in the synthesis or structure modifications of
pyridine derivatives remains high.
For chemists, “water” is one of the sustainable gifts
from nature, as it can be a surrogate for organic solvents.
In recent times, reactions of water-insoluble organic
compounds that take place in aqueous suspensions are
gaining immense interest because of their high effi-
ciency and straightforward synthetic protocols.1 Innova-
tive studies of organic reactions in aqueous media
demonstrated that Diels-Alder reactions1b,1f,2,3 and
Claisen rearrangements4 of hydrophobic reactants are
accelerated in aqueous solutions. In addition to these
findings, aqueous environments result in reactivity and
selectivity that are unique from reactions in hazardous
organic solvents, and this has been reflected in the de-
velopment of many versatile and innocuous organic re-
actions.5 Consequently, more efficient syntheses of bio-
logically active compounds in aqueous media are highly
desirable.
Pyridine and its derivatives are important motifs
present in a great number of pharmaceuticals and natu-
ral products.6-14 The unique structural array and highly
pronounced biological and physiological activities6-14
displayed by the class of pyridine moieties have made
them attractive synthetic targets. Specifically, 2-amino-
3,5-dicarbonitrile-6-thio-pyridines are considered to be
an important medicinal scaffolds7-14 as they are en-
dowed with PrPSc accumulation in scrapie-infected
mouse neuroblastoma cells (ScN2a),7a IKK-2 for treat-
ing HBV infection7b and modulate androgen receptor
function.7c The current interest in the synthesis of poly-
substituted pyridine derivatives, especially bearing ni-
trile functionality, arises from their potential applica-
tions as potassium channel openers in the treatment of
urinary incontinence,8 and their often use as anti-
prion,7a,9 anti-hepatitis B virus,7b anti-bacterial,10 and
anti-cancer agents.11 Therefore, the interest of organic
The most common approach for the synthesis of
2-amino-3,5-dicarbonitrile-6-thio-pyridines involves the
three component condensation of aldehyde, malononi-
trile and thiol. Various basic9a,14 as well as acid15 cata-
lysts have been utilized for this cyclocondensation reac-
tion. Moreover, silica nanoparticles,16a and nanocrysta-
line magnesium oxide16b were also found to catalyze the
synthesis of polysubstituted pyridines. However, some
of these protocols have significant drawbacks such as
formation of inevitable side products, prolonged reac-
tion times, lower yields, harsh reaction conditions, te-
dious work-up, and the use of expensive and environ-
mentally toxic catalysts as well as solvents. Thus, or-
ganic chemists have challenge to overwhelm these
shortcomings and develop efficient methods for this
nucleus using milder, non-hazardous and inexpensive
reagents. In this endeavor, we wish to disclose task spe-
cific role of TBAF in water for the synthesis of 2-
amino-3,5-dicarbonitrile-6-thio-pyridines.
Quaternary ammonium fluorides, particularly tetra-
alkyl ammonium fluorides, have been widely recog-
nized as a convenient, organic-soluble source of naked
fluoride ion. Their utility in modern organic synthesis
has been well documented for a range of fluo-
ride-assisted reactions,17 fluorination,18 deprotection of
silyl groups19 and desilylation20 reactions. Moreover, it
is evident from the literature that fluoride ions have in-
voked enormous interest as a green and potential cata-
lyst21,22 to construct carbon-carbon and carbon-het-
eroatom bonds in various organic transformations such
as Knoevenagel condensation, Michael addition and O,
N, S-alkylation reactions. The potential ability of the
fluoride ion to act as a base might be predicted on con-
sidering the strength of the H—F bond, solvent used for
dissolution, amount of water that is present, and the
*
E-mail: prof_msshingare@rediffmail.com; Fax: 0091-240-2403113; Tel.: 0091-240-2403311
Received September 29, 2010; revised January 7, 2011; accepted January 19, 2011.
Chin. J. Chem. 2011, 29, 1049— 1054
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1049

Shinde et al.
Table 1 Screening of catalysts and solventsa
FULL PAPER
countercation. They react under essentially neutral con-
ditions and are therefore often associated with clean
reactions where side reactions are kept to a minimum.21
Considering these sets of data and for exploitation of
applications of TBAF in synthetic organic chemistry,
attempt has been made for its use in pyridine synthesis.
Entry Catalyst Solvent
Temperature/℃ Time/h Yieldb/%
1
2
3
4
5
6
7
8
9
TBACl Water
TBAB Water
80
80
6
6
1
1
1
8
4
1
1
1
1
1
1
1
1
36
32
KF
Water
Water
80
79
CsF
80
86
Results and discussion
TBAF Water
TBAF Water
TBAF Water
TBAF Water
80
94
r.t.
87
On preliminary basis, one-pot three-component
condensation reaction of p-chlorobenzaldehyde (1a),
malononitrile (2) and thiophenol (3a) at 80 ℃ was
considered as a standard model reaction (Scheme 1).
Keeping the significance of above discussed aspects and
in the context of green chemistry, it has been decided to
prefer water as a solvent in our initial study for opti-
mizing catalyst. For establishing the effectiveness of the
catalysts, reaction was carried out using different fluo-
rides as well as their halide analogs such as chloride and
bromide. Fluoride ion was found to be more active
among the used halides (Table 1, Entries 1—5). The
reactions carried out in the presence of tetra-n-butyl
ammonium chloride (TBACl) and tetra-n-butyl ammo-
nium bromide (TBAB) were sluggish and incomplete
even after 6 h with 36% and 32% yields, respectively.
KF and CsF afforded the desired products in 79% and
86% yields respectively, whereas in the presence of
tetra-n-butyl ammonium fluoride (TBAF) the product
was obtained in excellent yield (94%).
60
90
100
80
78
TBAF
—
52
10 TBAF DMF
11 TBAF THF
80
Trace
28
Reflux
80
12 TBAF MeCN
13 TBAF Ethanol
14 TBAF Methanol
15 TBAF Toluene
39
Reflux
Reflux
80
60
67
86
a
Reaction conditions: 1a (1 mmol), 2 (2 mmol), 3a (1 mmol),
catalyst (10 mol %), in solvent (5 mL); b isolated yields.
pletion in excellent yield (94%).
After finalizing the catalyst (TBAF) for this reaction,
the next target was to choose proper solvent because of
the variable basicity and solubility shown by ionic fluo-
rides as well as the possibility of solvent participation in
subsequent reactions. Various solvents like DMF, THF,
acetonitrile, ethanol, methanol and toluene [Figure 1(A),
Table 1, Entries 9—15] have been tested and compared
their results with water mediated reaction. Prior to using
solvents, reaction was examined under neat conditions,
but reaction failed to afford more than 52% yield in 1 h.
In DMF, reaction rate becomes lethargic after Knoeve-
nagel condensation of aldehyde and malononitrile. In
comparison, THF and acetonitrile carried out the sub-
sequent reactions, but afforded lower yields. Ethanol
and methanol were found to be compatible with the re-
action conditions with moderate yields along with some
side products. Reaction in toluene proceeded smoothly
in agreement with water. But its tedious work up pro-
cedure, toxicity and hazardous nature confined its use
for this reaction.
Scheme 1 Standard model reaction
During this experiment, it was observed that solid
compound precipitates out after addition of catalytic
amount of TBAF indicating the rapid Knoevenagel con-
densation of aldehyde and malononitrile. Afterward,
heating the reaction mass at 80 ℃ started to convert
the white solid intermediate into the yellow solid via
subsequent Michael addition, which finally on
S-alkylation, cyclization and air oxidation afforded the
pale yellow coloured crude product.
Temperature of 80 ℃ was intentionally chosen as
most of the fluorides are thermally unstable above 80
℃.22 For evaluation of temperature effect, this reaction
was performed at room temperature, 60, 80 ℃ and
reflux conditions (Table 1, Entries 5—8). Reaction at
room temperature and 60 ℃ afforded product in good
yields but it takes longer reaction period for completion,
while at reflux condition the product was obtained in
lower yield, since catalyst becomes unstable above 80
℃. At 80 ℃, reaction proceeds smoothly towards com-
We were pleased to find that among the conditions
screened [Figure 1(A)], the corresponding pyridine was
obtained quantitatively with TBAF at 80 ℃ in water. It
is known that TBAF in water produces an equilibrium
in which tetra-n-butyl ammonium hydroxide (TBAOH)
and HF are present,20e so one may speculate the
－
2
possibility of catalysis of this reaction by TBAOH. But,
this possibility has been ruled out considering the
following points: (i) KF and CsF afford the products in
good yields (79% and 86%, respectively) and reaction
in toluene also proceeds smoothly confirming the assis-
tance of fluoride ion to catalyze the reaction, where
chances of TBAOH formation in reaction mixture are
eliminated. (ii) Even it has been studied and proved that
1050
www.cjc.wiley-vch.de
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 1049— 1054

Facile and Rapid Access to Poly Functionalized Pyridine Derivatives
ion and organic molecule resulting in transfer of elec-
tron density from the anion to organic substrate. Water
is only able to solvate and mask fluoride ion if more
powerful H-bond e-acceptor than itself is absent. In-
crease in the thiols reactivity seems reasonable to as-
sume the importance of H-bonding base like reactions
of the anion.21 One more aspect that could be helpful for
bringing the reaction in favor of water is hydrophobic
interactions which induce favorable aggregation of or-
ganic substrates in water.
In a simplified way, to understand the role of TBAF
it should be noted that in water TBAF gets dissociated
to afford tetra-n-butyl ammonium cation and fluoride
anion. Cationic species bind with the organic substrates
(electrophiles) to increase their electrophilicity and
fluoride ion (which plays major role) behaves as a base
in the presence of H-bond e-acceptors (organic sub-
strates/nucleophiles), and enhances their nucleophilicity.
In this manner, major role of fluoride ion as a base and
assistance of tetra-n-butyl ammonium cation accelerates
the rate of reaction. Plausible mechanism involved in
the synthesis of highly substituted pyridines is depicted
with the help of Figure 2.
To determine the appropriate concentration of the
catalyst (TBAF), we investigated the model reaction at
different concentrations of TBAF such as 0, 2.5, 5, 10
and 15 mol%. The product was formed in trace, 58%,
77%, 94%, and 94% yields, respectively (Table 2). This
indicates that 10 mol% of TBAF is sufficient to carry
out the reaction smoothly.
It is noteworthy to point out that, recently, recycling
and reuse of TBAF in water23 has been successfully
achieved. Hence we carried out this experiment for the
present reaction and it was observed that this catalytic
system could be recovered and reused without any sig-
nificant loss in its catalytic activity. Recovery process is
very easy and convenient to carry out. On completion of
reaction, filtrate obtained after simple filtration can be
Figure 1 (A) Solvent effect on product yield, and (B) recycling
and reuse of TBAF.
equilibrium generated due to addition of water to TBAF
shifts towards the side of TBAF rather than TBAOH
20e
－
due to presence of HF . (iii) Literature reveals that
2
TBAF does not react with water in the presence of or-
ganic substrates, since organic molecules act as more
powerful H-bond e-acceptors than water.21 This dra-
matic influence of water over the other solvents could
be attributed to H-bonding which must have played im-
portant role in the basic behavior of fluoride anion. In
the presence of powerful H-bond e-acceptors (organic
substrates), fluoride ions bond with them and enhance
their nucleophilicity, due to H-bonding between fluoride
Figure 2 Plausible mechanism for the synthesis of pyridines.
Chin. J. Chem. 2011, 29, 1049— 1054
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1051

Shinde et al.
FULL PAPER
Table 2 Concentration effect, recycling and reuse of TBAFa
Various heteryl aldehydes were well tolerated to afford
excellent yields. Interestingly, aliphatic aldehydes such
as acetaldehyde and propionaldehyde also gave the de-
sired product in moderate yields. All the results are
compiled in Table 3. Formation of the desired product
Entry
TBAF/mol%
Yieldb/%
1
2
0
2.5
5
Trace
58
1
3
77
was confirmed with the help of IR, H NMR, and mass
4c
10
15
94, 89, 86, 79, 47
94
spectroscopic data.
Comparative study of the developed protocol with
the known methods reveals the following advantages: (i)
This strategy is higher yielding under mild reaction
conditions. (ii) All the reported methods have been per-
formed in either organic solvents or ethanol except our
previous one,15b in contrast, we have used greener
aqueous medium. (iii) Most of the known strategies in-
cluding our previous one fail for aliphatic aldehydes,
whereas, developed method keeps the potential to utilize
aliphatic aldehydes. (iv) In comparison to others, cata-
lyst used in this route can be reused up to four runs
without loss of significant reactivity.
5
a
Reaction conditions: 1a (1 mmol), 2 (2 mmol), 3a (1 mmol), in
water (5 mL) at 80 ℃ for 60 min; b isolated yields; c catalyst was
reused for four times.
reused directly for model reaction [Figure 1(B) and Ta-
ble 2, Entry 4].
In order to extend the scope of the reaction and to
generalize the procedure, variety of electronically di-
vergent aldehydes with respect to thiophenol and
o-aminothiophenol were examined. The reaction was
straightforward for the wide range of aryl aldehydes.
Table 3 Synthesis of 2-amino-3,5-dicarbonitrile-6-thio-pyridinesa
Entry
Compd.
R
R'
Time/min
60
Yieldb/%
m.p.c/℃
1
2
4a
4b
4c
4d
4e
4f
4-ClC6H4
H
94
92
90
92
87
95
89
91
90
96
92
93
64
62
91
91
88
90
96
89
92
221—222
216—218
226—228
240—241
315—316
289—290
208—210
218—220
225—227
23—232
Ph
H
H
50
50
3
4-FC6H4
4
4-MeOC6H4
4-HOC6H4
4-NO2C6H4
4-MeC6H4
4-HO-3-MeOC6H3
3,4-(MeO)2C6H3
Piperonyl
2-Thienyl
2-Furyl
H
65
5
H
70
6
H
45
7
4g
4h
4i
H
50
8
H
55
9
H
65
10
11
12
13
14
15
16
17
18
19
20
21
4j
H
85
4k
4l
H
120
120
420
630
45
210—212
178—180
228—230
146—147
226—228
234—236
229—231
172—173
207—208
208—210
232—233
H
4m
4n
4o
4p
4q
4r
4s
Me
H
Et
H
Ph
NH2
NH2
NH2
NH2
NH2
NH2
NH2
4-ClC6H4
4-MeOC6H4
4-HOC6H4
4-NO2C6H4
4-MeC6H4
4-HO-3-MeOC6H3
70
55
60
50
4t
60
4u
55
a Reaction conditions: 1 (1 mmol), 2 (2 mmol), 3 (1 mmol), TBAF (10 mol%), in water (5 mL) at 80 ℃; b isolated yields; c melting points
match with literature reports.14c,14d,15
1052
www.cjc.wiley-vch.de
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 1049— 1054

Facile and Rapid Access to Poly Functionalized Pyridine Derivatives
Conclusions
dine-3,5-dicarbo-nitrile (4k) 1H NMR (DMSO-d6,
400 MHz) δ: 7.94 (d, J＝4.8 Hz, 1H, ArH), 7.61 (brs,
2H, NH2), 7.45—7.42 (m, 2H, ArH), 7.35—7.32 (m, 3H,
ArH), 7.24 (d, J＝4.0 Hz, 1H, ArH), 6.68 (t, J＝4.0 Hz,
1H, ArH); IR (KBr) v: 3438, 3360, 3210, 2984, 2210,
In summary, a facile, economic, and green protocol
for one-pot multicomponent cyclocondensation of al-
dehydes, malononitrile, and thiols has been described.
All the reactions proceed under essentially neutral con-
ditions reducing the possibility of unwanted side reac-
tions. In addition, present method offers marked im-
provements with regard to operational simplicity, reac-
tion time, high isolated yields of products, and green-
ness of procedure, avoiding hazardous organic solvents
and toxic catalysts. This process is less laborious than
our previously reported procedure15b and provides a
better, clean and practical alternative to the existing
protocols.
－1
1617, 1512, 1257, 1064, 722 cm ; ES-MS m/z: 335.07
(M＋).
2-Amino-4-(furan-2-yl)-6-phenylsulfanylpyridine-
3,5-dicarbo-nitrile(4l)
1H NMR (DMSO-d6, 400
MHz) δ: 7.93 (d, J＝5.2 Hz, 1H, ArH), 7.79 (brs, 2H,
NH2), 7.58—7.54 (m, 3H, ArH), 7.48—7.46 (m, 3H,
ArH), 7.26 (t, J＝4.0 Hz, 1H, ArH); IR (KBr) v: 3380,
3328, 3210, 2992, 2215, 165＋0, 1518, 1264, 1029, 766
－1
cm ; ES-MS m/z: 319.09 (M ).
2-Amino-4-ethyl-6-phenylsulfanylpyridine-3,5-di-
carbonitrile (4n) 1H NMR (DMSO-d6, 400 MHz) δ:
7.69 (brs, 2H, NH2), 7.56—7.54 (m, 2H, ArH), 7.47—
7.44 (m, 3H, ArH), 2.71 (q, J＝7.6 Hz, 2H, CH2CH3),
1.20 (t, J＝7.6 Hz, 3H, CH2CH3); IR (KBr) v: 3425,
3148, 2218, 1639, 1547, 147＋6, 1263, 1177, 1024, 748
Experimental section
General
All chemicals were purchased and used without any
further purification. Melting points were recorded on a
Veego apparatus and are uncorrected. Infrared spectra
were recorded on a Bruker spectrophotometer in a KBr
－1
cm ; ES-MS m/z: 281.08 (M ).
2-Amino-4-(4-hydroxy-3-methoxyphenyl)-6-(2-
amino-phenylsulfanyl)pyridine-3,5-dicarbonitrile (4u)
1H NMR (DMSO-d6, 400 MHz) δ: 9.65 (brs, 1H, OH),
7.57 (brs, 2H, NH2-(pyridine ring)), 7.25—7.23 (dd, J＝
1.6 Hz, 8.0 Hz, 1H, ArH), 7.20—7.15 (t, J＝8.0 Hz, 1H,
ArH), 7.12 (d, J＝1.6 Hz, 1H, ArH), 6.98—6.91 (m, 2H,
ArH), 6.77 (d, J＝8.0 Hz, 1H, ArH), 6.57 (t, J＝8.0 Hz,
1H, ArH), 5.37 (brs, 2H, NH2-thiophenol ring), 3.80 (s,
3H, OCH3); IR (KBr) v: 3473, 3348, 3290, 2958, 2212,
－1
disc, and the absorption bands are expressed in cm . 1H
NMR spectra were recorded on a Varian AS 400 MHz
spectrometer in DMSO-d6, chemical shifts (δ) are rela-
tive to TMS. Mass spectra were recorded on a macro
mass spectrometer (Waters) by electro-spray (ES)
method.
General experimental procedure
－1
1625, 1533, 1281, 1020, 756 cm ; ES-MS m/z: 390.02
(M＋).
A mixture of aldehyde 1 (1 mmol), malononitrile 2
(2 mmol), thiophenol 3 (1 mmol) and TBAF ((1.0 mol/L
in THF) (10 mol%)) in water (5 mL) was stirred at 80
℃. Reaction progress was monitored by TLC [V(ethyl
acetate)∶V(n-hexane)＝1∶7]. After completion of the
reaction, obtained solid product was collected by simple
filtration and washed with water. The crude product 4
was recrystallized from aqueous ethanol to obtain pure
product without any need of further purification.
Acknowledgement
Authors are thankful to the Head, Department of
Chemistry, Dr. Babasaheb Ambedkar Marathwada
University, Aurangabad, for providing the laboratory
facility.
References
Spectroscopic data for representative compounds
2-Amino-4-(4-chlorophenyl)-6-phenylsulfanylpyr-
idine-3,5-dicarbo-nitrile (4a) 1H NMR (DMSO-d6,
400 MHz) δ: 7.83 (brs, 2H, NH2), 7.64 (d, J＝8.0 Hz,
2H, ArH), 7.59 (d, J＝8.0 Hz, 2H, ArH), 7.57 (d, J＝8.0
Hz, 2H, ArH), 7.49—7.46 (m, 3H, ArH); IR (KBr) v:
3489, 3342, 3221, 2216, 1628, 1544, 1487, 1259, 1091,
1
(a) Rideout, D. C.; Breslow, R. J. Am. Chem. Soc. 1980, 102,
7816.
(b) Lubineau, A. J. Org. Chem. 1986, 51, 2142.
(c) Pirrung, M. C.; Sarma, K. D. J. Am. Chem. Soc. 2004,
126, 444.
(d) Narayan, S.; Muldoon, J.; Finn, M. G.; Fokin, V. V.;
Kolb, H. C.; Sharpless, K. B. Angew. Chem., Int. Ed. 2005,
44, 3275.
(e) Price, B. K.; Tour, J. M. J. Am. Chem. Soc. 2006, 128,
12899.
＋
－ 1
839, 791 cm ; ES-MS m/z: 363.04 (M ), 365.03
(M＋＋2).
2-Amino-4-(benzo[d][1,3]dioxol-5-yl)-6-phenylsul-
fanylpyridine-3,5-dicarbonitrile (4j)
1H NMR
(DMSO-d6, 400 MHz) δ: 7.72 (brs, 2H, NH2), 7.57—
7.55 (m, 2H, ArH), 7.48—7.46 (m, 3H, ArH), 7.14 (d,
J＝1.2 Hz, 1H, Ar-H), 7.07 (d, J＝8.0 Hz, 1H, ArH),
7.03—7.00 (m, 1H, ArH), 6.12 (s, 2H, OCH2O); IR
(KBr) v: 3458, 3338, 32－29, 2907, 2217, 1636, 1558,
(f) Gonzalez-Cruz, D.; Tejedo, D.; de Armas, P.; Gar-
cia-Tellado, F. Chem. Eur. J. 2007, 13, 4823.
(g) El-Batta, A.; Jiang, C.; Zhao, W.; Anness, R.; Cooksy, A.
L.; Bergdahl, M. J. Org. Chem. 2007, 72, 5244.
(a) Breslow, R.; Maitra, U.; Rideout, D. Tetrahedron Lett.
1983, 24, 1901.
2
＋
1
1492, 1251, 1037, 825 cm ; ES-MS m/z: 373.14 (M ).
2-Amino-4-(thiophene-2-yl)-6-phenylsulfanylpyri-
(b) Breslow, R.; Maitra, U. Tetrahedron Lett. 1984, 25,
Chin. J. Chem. 2011, 29, 1049— 1054
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1053

Shinde et al.
FULL PAPER
1239.
14 (a) Evdokimov, N. M.; Magedov, I. V.; Kireev, A. S.;
Kornienko, A. Org. Lett. 2006, 8, 899.
(c) Breslow, R. Acc. Chem. Res. 1991, 24, 159.
3
4
5
(a) Grieco, P. A.; Garner, P.; He, Z. Tetrahedron Lett. 1983,
24, 1897.
(b) Grieco, P. A.; Yoshida, K.; Garner, P. J. Org. Chem.
1983, 48, 3137.
(a) Gajewski, J. J. Acc. Chem. Res. 1997, 30, 219.
(b) Gajewski, J. J. In Organic Synthesis in Water, Ed.:
Grieco, P. A., Blackie Academic and Professional, London,
UK, 1998.
(b) Evdokimov, N. M.; Kireev, A. S.; Yakovenko, A. A.;
Antipin, M. Y.; Magedov, I. V.; Kornienko, A. J. Org.
Chem. 2007, 72, 3443.
(c) Mamgain, R.; Singh, R.; Rawat, D. S. J. Heterocycl.
Chem. 2009, 46, 69.
(d) Guo, K.; Thompson, M. J.; Chen, B. J. Org. Chem. 2009,
74, 6999.
(e) Ranu, B. C.; Jana, R.; Sowmiah, S. J. Org. Chem. 2007,
72, 3152.
(a) Li, C.-J. Chem. Rev. 1993, 93, 2023.
(b) Kobayashi, S.; Manabe, K. Chem. Eur. J. 2002, 8, 4094.
(c) Kobayashi, S.; Manabe, K. Acc. Chem. Res. 2002, 35,
209.
(d) Lindstrom, U. M. Chem. Rev. 2002, 102, 2751.
(e) Li, C.-J. Chem. Rev. 2005, 105, 3095.
(f) Li, C.-J.; Chan, T.-H. Comprehensive Organic Reactions
in Aqueous Media, 2nd ed., Wiley, Hoboken, NJ, 2007.
(g) Lindstrom, U. M. Organic Reactions in Water, Black-
well, Oxford, UK, 2007.
Cocco, M. T.; Congiu, C.; Lilliu, V.; Onnis, V. Eur. J. Med.
Chem. 2005, 40, 1365.
(a) Perrier, V.; Wallace, A. C.; Kaneko, K.; Safar, J.;
Prusiner, S. B.; Cohen, F. E. Proc. Nat. Acad. Sci. U. S. A.
2000, 97, 6073.
(b) Chen, H.; Zhang, W.; Tam, R.; Raney, A. K. WO
2005058315, 2005 [Chem. Abstr. 2005, 143, 97338].
(c) Nirschl, A. A.; Hamann, L. G. US 2005182105, 2005
[Chem. Abstr. 2005, 143, 222525].
Harada, H.; Watanuki, S.; Takuwa, T.; Kawaguchi, K.;
Okazaki, T.; Hirano, Y.; Saitoh, C. WO 2002006237, 2002
[Chem. Abstr. 2002, 136, 118474].
(a) Reddy, T. R. K.; Mutter, R.; Heal, W.; Guo, K.; Gillet, V.
J.; Pratt, S.; Chen, B. J. Med. Chem. 2006, 49, 607.
(b) May, B. C. H.; Zorn, J. A.; Witkop, J.; Sherrill, J.; Wal-
lace, A. C.; Legname, G.; Prusiner, S. B.; Cohen, F. E. J.
Med. Chem. 2007, 50, 65.
(f) Singh, K. N.; Singh, S. K. ARKIVOC 2009, (xiii), 153.
15 (a) Sridhar, M.; Ramanaiah, B. C.; Narsaiah, C.; Mahesh, B.;
Kumaraswamy, M.; Mallu, K. K. R.; Ankathi, V. M.; Rao,
P. S. Tetrahedron Lett. 2009, 50, 3897.
(b) Shinde, P. V.; Sonar, S. S.; Shingate, B. B.; Shingare, M.
S. Tetrahedron Lett. 2010, 51, 1309.
16 (a) Banerjee, S.; Sereda, G. Tetrahedron Lett. 2009, 50,
6959.
(b) Kantam, M. L.; Mahendar, K.; Bhargava, S. J. Chem.
Sci. 2010, 122, 63.
6
7
17 (a) Mori, A.; Kawashima, J.; Shimada, T.; Suguro, M.; Hir-
abayashi, K.; Nishihara, Y. Org. Lett. 2000, 2, 2935.
(b) Barluenga, J.; Andina, F.; Fernandez-Rodriguez, M. A.;
Garcia-Garcia, P.; Merino, I.; Aguilar, E. J. Org. Chem.
2004, 69, 7352.
18 Crouch, R. D. Tetrahedron 2004, 60, 5833.
19 (a) Capperucci, A.; Degl'Innocenti, A.; Leriverend, C.;
Metzner, P. J. Org. Chem. 1996, 61, 7174.
(b) Sirol, S.; Courmarcel, J.; Mostefai, N.; Riant, O. Org.
Lett. 2001, 3, 4111.
8
9
(c) Denmark, S. E.; Sweis, R. F. J. Am. Chem. Soc. 2001,
123, 6439.
(d) Mattson, A. E.; Zuhl, A. M.; Reynolds, T. E.; Scheidt, K.
A. J. Am. Chem. Soc. 2006, 128, 4932.
20 (a) Albanese, D.; Landini, D.; Penso, M. J. Org. Chem.
1998, 63, 9587.
10 Levy, S. B.; Alekshun, M. N.; Podlogar, B. L.; Ohemeng,
K.; Verma, A. K.; Warchol, T.; Bhatia, B.; Bowser, T.;
Grier, M. US 2005124678, 2005 [Chem. Abstr. 2005, 143,
53440].
11 Anderson, D. R.; Stehle, N. W.; Kolodziej, S. A.; Reinhard,
E. J. WO 2004055015, 2004 [Chem. Abstr. 2004, 141,
89018].
(b) Shellhamer, D. F.; Horney, M. J.; Pettus, B. J.; Pettus, T.
L.; Stringer, J. M.; Heasley, V. L.; Syvret, R. G.; Dobrolsky
Jr., J. M. J. Org. Chem. 1999, 64, 1094.
(c) Fan, R.-H.; Zhou, Y.-G.; Zhang, W.-X.; Hou, X.-L.; Dai,
L.-X. J. Org. Chem. 2004, 69, 335.
(d) Yin, J.; Zarkowsky, D. S.; Thomas, D. W.; Zhao, M. M.;
Huffman, M. A. Org. Lett. 2004, 6, 1465.
12 Fredholm, B. B.; Ijzerman, A. P.; Jacobson, K. A.; Klotz,
K.-N.; Linden, J. Pharmacol. Rev. 2001, 53, 527.
13 Guo, K.; Mutter, R.; Heal, W.; Reddy, T. R. K.; Cope, H.;
Pratt, S.; Thompson, M. J.; Chen, B. Eur. J. Med. Chem.
2008, 43, 93.
(e) Sun, H.; DiMagno, S. G. J. Am. Chem. Soc. 2005, 127,
2050.
21 Clark, J. H. Chem. Rev. 1980, 80, 429.
22 Kumar, M. B. Synlett 2002, 2125.
23 Gao, S.; Tsai, C. H.; Yao, C.-F. Synlett 2009, 949.
(E1009296 Li, L.)
1054
www.cjc.wiley-vch.de
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 1049— 1054