A novel catalyst-free tandem reaction for the synthesis of 5-hydroxy-1,5-dihydro-2 h -pyrrol-2-ones in water medium

Article abstract of DOI:10.1055/s-0030-1260049

A novel catalyst-free, water-medium, tandem reaction for the synthesis of 5-hydroxy-1,5-dihydro-2H-pyrrol-2-ones was developed through a one-pot strategy from nitroethylenes and 1,3-dicarbonyl compounds. A series of 1-aryl-2-nitroethenes and 1-nitroalk-1-enes were surveyed to determine the scope of this tandem reaction with moderate to good yield. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0030-1260049

FEATURE ARTICLE
1831
A Novel Catalyst-Free Tandem Reaction for the Synthesis of 5-Hydroxy-1,5-
dihydro-2H-pyrrol-2-ones in Water Medium
5
-Hydroxy-1,5-dihydro
i
-
2
H
-py
n
r
rol-2-onesg-Yu Wu, Kun Li,* Na Wang, Ting He, Xiao-Qi Yu*
Key Laboratory of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu, 610064,
P. R. of China
Fax +86(28)85415886; E-mail: xqyu@tfol.com
Received 30 December 2010
the reaction of a,b-diketones with acetamides,2b,6 nucleo-
Abstract: A novel catalyst-free, water-medium, tandem reaction
philic addition of organometallic reagents,5 selective oxi-
for the synthesis of 5-hydroxy-1,5-dihydro-2H-pyrrol-2-ones was
dation or reduction of pyrrolinones and maleimide
developed through a one-pot strategy from nitroethylenes and 1,3-
derivatives,4,7 and transition-metal-catalyzed coupling,
dicarbonyl compounds. A series of 1-aryl-2-nitroethenes and 1-ni-
troalk-1-enes were surveyed to determine the scope of this tandem oxidative or tandem process.8 Strong nucleophilic re-
reaction with moderate to good yield.
agents, oxidants, reductants, or organometallic reagents
were generally used to promote the reaction. In many cas-
es, the yields or selectivities are far from satisfactory due
to the stepwise approach or several side reactions. There-
fore, finding a novel and efficient approach to build the 5-
hydroxy-1,5-dihydro-2H-pyrrol-2-one framework has at-
tracted a great deal of attention from researchers.
Key words: 5-hydroxy-1,5-dihydro-2H-pyrrol-2-ones, catalyst-
free, water medium, tandem reaction
Introduction
In recent years, water as reaction medium has exhibited
great advantages and potential in modern organic synthe-
sis.9 These include that it is green, inexpensive, nontoxic,
and safe; thus many organic reactions have been devel-
oped in a water medium.10 This includes asymmetric cat-
alytic carbon–carbon bond-formation reactions, radical
reactions, and multicomponent processes. It is particular-
ly important to develop more reactions in water as a me-
dium for research. In the present work, we surprisingly
found a novel catalyst-free tandem reaction for the synthe-
sis of 5-hydroxy-1,5-dihydro-2H-pyrrol-2-ones in a water
medium.
5-Hydroxy-1,5-dihydro-2H-pyrrol-2-ones are important
N-heterocyclic compounds in organic and medicinal
chemistry, that show interesting pharmacological
properties1 and neuritogenic activity.2 It has been reported
that half of the small molecule drugs that received FDA
approval in 2005–2006 contain at least one azole or azine
ring.3 A wide variety of biologically active natural prod-
ucts containing the 5-hydroxy-1,5-dihydro-2H-pyrrol-2-
one or 3,4-epoxy-5-hydroxypyrrolidin-2-one moiety have
been isolated, such as oteromycin (Figure 1), which is an
endothelin receptor antagonist,2a and epolactaene, which
is effective in promoting neural outgrowth and arresting
the cell cycle at the G0/G1 phase in a human neuroblasto-
ma cell line, SH-SY5Y2b etc.
O
O
O
H
N
OH
HO
H
O
Ph
MeO2C
epolactaene
NH
oteromycin
O
Figure 1 The structures of oteromycin and epolactaene
Furthermore, 5-hydroxy-1,5-dihydro-2H-pyrrol-2-ones
are useful intermediates in organic synthesis.4 Some ap-
proaches to the synthesis of the 5-hydroxy-1,5-dihydro-
2H-pyrrol-2-one skeleton have been reported including:
the reaction of a,b-unsaturated ketones with isocyanides,5
Figure 2 The single crystal structure of 5a
In our previous research into the reaction of 1,3-dicarbon-
yl compounds with nitroethylenes, the Michael adduct 3a
and the hydroxyimino-substituted dihydrofuran deriva-
tive 4a were obtained (Scheme 1). Further studies on con-
structing 3,4-dihydro-1,3-oxazin-2-one 6a were carried
out as one-pot tandem reactions. Surprisingly, the 5-hy-
SYNTHESIS 2011, No. 12, pp 1831–1839
x
x.
x
x
.
2
0
1
1
Advanced online publication: 26.05.2011
DOI: 10.1055/s-0030-1260049; Art ID: C11510SS
© Georg Thieme Verlag Stuttgart · New York

1832
M.-Y. Wu et al.
FEATURE ARTICLE
droxy-1,5-dihydro-2H-pyrrol-2-one 5a rather than 6a was the disappearance of the signals at d = 6.27 and 9.01, pro-
found (Scheme 1). The structure of 5a was confirmed by viding additional evidence for the assignment of the struc-
1
X-ray diffraction (Figure 2).11 Comparing the H NMR ture of 5a.
spectrum of 5a with it after adding deuterium oxide led to
Biographical Sketches
Ming-Yu Wu was born in began his Students Innova- Ph.D. in the Yu group. His
Jiangxi province of China. tion Training under the su- current research interests fo-
He entered Sichuan Univer- pervision of Prof. Xiao-Qi cus on green synthesis
sity in 2006 in the college of Yu. After obtaining a B.S. methodology.
chemistry, and in 2008 he degree in 2010, he began his
Kun Li was born in Shan- gree and won a chance to tinued his postdoctoral stud-
dong province of China in study for a doctoral degree ies at Hong Kong University
1980. He obtained his B.S. (under the supervision of with Dr. Patrick-Henry Toy
degree from Yantai Univer- Prof. Xiao-Qi Yu) in 2005. from 2010. His research in-
sity in 2003. In the same After obtaining his Ph.D. in terests focus on biocatalysis
year, he entered Sichuan 2008, he joined the Yu and green synthesis method-
University for his M.Sc. de- group as a lecturer. He con- ology.
Na Wang received her B.S. supervision of Prof. Xian- es on enzymatic synthesis
from Guizhou University in Fu Lin. Later she joined methodology and enzyme
1998. She obtained her Prof. Xiao-Qi Yu’s group as engineering.
Ph.D. in 2006 from Zhe- a lecturer at Sichuan Uni-
jiang University under the versity. Her research focus-
Ting He was born in She is currently a Ph.D. stu- weight gelators and seeking
Shaanxi province of China dent under the supervision to exploit their catalytic
in 1987. She received her of Prof. Xiao-Qi Yu work- properties.
B.Sc. in chemistry from Si- ing on the design and syn-
chuan University in 2009. thesis of low-molecular-
Xiao-Qi Yu received his sor at Sichuan University; ry of Green and Technology
M.S. and Ph.D. from Si- between 1998 and 2001, he (Sichuan University), Min-
chuan University in 1987 was a research associate at istry of Education. His re-
and 1993. Subsequently, he Hong Kong University with search focuses on gene
was a lecturer and associate Prof. Chi-Ming Che. After transfection, biocatalysis,
professor from 1993 to that, he was acting deputy and green synthesis method-
1999, and then full profes- director in the key laborato- ology.
Synthesis 2011, No. 12, 1831–1839 © Thieme Stuttgart · New York

FEATURE ARTICLE
5-Hydroxy-1,5-dihydro-2H-pyrrol-2-ones
1833
Table 1 Influence of Solvent on the Reactiona
O
OH
NH
O
OH
NH
NO2
O
O
+
O
5a
1a
2a
NO2
O
O
O
O
5a
1a
Entry
Solvent
Yieldb (%)
O
+
NO2
O
O
1
2
H2O
21
84
48
30
20
25
12
7
NOH
3a
4a
DMSO–H2O
DMF–H2O
MeCN–H2O
1,4-dioxane–H2O
THF–H2O
2a
O
3
O
4
N
O
H
5
6a
6
Scheme 1 A novel process for the synthesis of 5-hydroxy-1,5-dihy-
dro-2H-pyrrol-2-ones
7
BuOH–H2O
toluene–H2O
toluene–H2Oc
toluene–H2Od
8
Results and Discussion
9
13
24
With the aim of identifying a novel and efficient process
to synthesize of 5a, the model reaction of pentane-2,4-di-
one (2a) with b-nitrostyrene (1a) was investigated in de-
tail. We first examined the influence of solvent on the
reaction. Several commonly used solvents or mixtures
were screened, the results are shown in Table 1. General-
ly, the reaction did not proceed favorably in all of the or-
ganic solvents examined, but did so successfully in
mixtures of water and organic solvents. It is notable that
this reaction could be carried out in pure water (entry 1),
though a poor yield was obtained due to the low solubility
of the substrates. Among all of the mixtures of water with
organic solvents examined, aprotic polar solvents such as
dimethyl sulfoxide, N,N-dimethylformamide, and aceto-
nitrile were observed as much better than protic solvents
and aprotic nonpolar solvent such as butyl alcohol, tolu-
ene, tetrahydrofuran, and 1,4-dioxane. Dimethyl sulfox-
ide–water mixtures gave the best result. In all of the
mixture solvents with water, only toluene had a poor mis-
cibility with water at 80 °C. This led us to examine phase-
transfer agents; however, low yields were obtained in
these reactions (entries 9 and 10). Thus the dimethyl sul-
foxide–water mixture was chosen as the solvent in the fol-
lowing study.
10
a Reaction conditions: 1a (0.1 mmol), 2a (2 equiv), solvent–H2O (1:1,
1 mL), 80 °C, 12 h.
b Yield was determined by HPLC.
c Et4NCl (10 mg) was added.
d Et4NI (10 mg) was added.
Figure 3 The influence of different water contents on the reaction
of 1a with 2a
enes 1 and 1,3-dicarbonyl compounds 2 were investigated
(Table 2). All these substrates could undergo the desired
reaction to afford corresponding products 5 efficiently.
Among them, 1-aryl-2-nitroethenes 1a–k were more reac-
tive than 1-nitroalk-1-ene 1l, and 1-aryl-2-nitroethenes
with ortho-substituted aryl groups 1h,i were significantly
better. Pentane-2,4-dione (2a) was much more reactive
than heptane-3,5-dione (2b) in the reaction, while ethyl
acetoacetate and diethyl malonate did not work smoothly,
and only trace product was obtained with cyclohexane-
1,3-dione.
Encouraged by these results, we then examined the influ-
ence of the amount of water in the mixture on the yield of
this catalyst-free reaction. The relationship between water
content and yield is a bell-shaped curve, and at 50% water
the highest yields were observed (Figure 3). Thus, at the
outset as the content of water increased, the yield of 5a is
seen to improve, however, once the water content surpass-
es 50%, the yield decreased due to the poor solubility.
To extend the scope of substrates in this novel catalyst-
free, water-medium process, a wide range of nitroethyl-
Synthesis 2011, No. 12, 1831–1839 © Thieme Stuttgart · New York

1834
M.-Y. Wu et al.
FEATURE ARTICLE
Table 2 Synthesis of 5-Hydroxy-1,5-dihydro-2H-pyrrol-2-one
Derivatives 5 with Different Nitroethylenes 1 and Pentane-2,4-dione
(2a) or Heptane-3,5-dione (2b)a
different times, only the Michael product 3a was found
during the first two hours, 3a decreased gradually and
transformed to 4a and 5a within 2–6 hours, but 4a was the
major product. After six hours, 4a and residual 3a had al-
most completely converted into 5a. From the above data,
we could conclude that 3a and 4a were the intermediates
in this tandem reaction.
O
HO
R2
R2
O
O
DMSO–H2O (1:1)
R2
80–90 °C
NO2
NH
R1
+
R2
R1
2
1
O
5
Nicolaou12 and Quai5a proposed a mechanism for the syn-
thesis of 5-hydroxy-1,5-dihydro-2H-pyrrol-2-ones going
through a intermediate (iminolactone) which is very sim-
ilar to 4a. However, our reaction proceeds smoothly when
conducted under argon, while the mechanism reported by
Nicolaou required an oxidant, namely oxygen. When 4a
was dissolved in dimethyl sulfoxide–water at 80 °C, for-
mation of 5a was very slow. However, when a drop of
acetic acid was added, 5a was formed very quickly. On
the other hand, when 3a was used as the starting material,
both 4a and 5a were formed, and 4a could be completely
converted into 5a after several hours. Thus, perhaps a pro-
ton generated from the conversion of 3a into 4a promoted
the transformation of 4a to 5a.
Combining the results from the 13C NMR analysis of the
reaction process and the experiments described above, we
proposed a mechanism for the conversion of 4a into 5a
(Scheme 2); we note that a similar reaction for an ana-
logue of 4a has been reported.13 It is well known that
oximes undergo Beckman rearrangement to produce
amides under acidic or thermal reaction conditions. How-
ever, we observed formation of 5a, a five-membered-ring-
containing product, rather than six-membered-ring prod-
uct 6a. Thus, based on the above results we propose that
once 4a is formed from 3a, loss of the benzylic proton and
water leads to the formation of highly conjugated interme-
diate I. Hydration of I then leads to II, which can tau-
tomerize to form III. Subsequently, nucleophilic attack by
the amide nitrogen on the ketone carbon leads to IV. Fi-
nally, proton transfer accounts for the formation of 5a.
Entry
1
R1
Ph
4-MeC6H4
R2
Product Yieldb (%)
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
5a
5b
5c
5d
5e
5f
65
61
56
50
60
70
61
92
71
65
53
25
50
48
55
50
50
52
50
75
64
55
trace
2
3
4-MeOC6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
4-F3CC6H4
2-ClC6H4
2-BrC6H4
3-ClC6H4
furan-2-yl
Pr
4
5
6
7
5g
5h
5i
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
5j
5k
5l
Ph
5m
5n
5o
5p
5q
5r
5s
4-MeC6H4
4-MeOC6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
4-F3CC6H4
2-ClC6H4
2-BrC6H4
3-ClC6H4
Pr
Et
Et
Et
Et
Et
Et
Et
5t
Conclusion
Et
5u
5v
5w
We have developed a novel, catalyst-free, water-medium,
tandem process for the synthesis of 5-hydroxy-1,5-dihy-
dro-2H-pyrrol-2-ones from nitroethylenes and 1,3-dicar-
bonyl compounds and this approach have a good
universality. The initial materials are inexpensive or can
be prepared via cost-effective synthesis. In addition, it is
easy to operation and environmentally friendly as a cata-
lyst-free and tandem process in water medium. We be-
lieve that these results could afford a novel access to
functionalize 5-hydroxy-1,5-dihydro-2H-pyrrol-2-ones
and their derivatives.
Et
Et
a The reaction was conducted with nitroethylenes 1 (2 mmol), pen-
tane-2,4-dione (2a) or heptane-3,5-dione (2b) (4 mmol) DMSO–H2O
(1:1, 20 mL), entries 1–12: 80 °C, 12 h; entries 13–24: 90 °C, 48 h.
b Isolated yield.
To understand this water-promoted tandem reaction clear-
ly, we utilized 13C NMR to monitor the progress of the re-
action. The NMR spectra at different times (2, 6, and 12
h, Figure 4) were collected; the chemical shifts of 3a (a, b,
c, and d), 4a (e, f, g, and h), as well as 5a (i, j, k and l) were
compared to determine their existence in the reaction me-
dium. Compounds 3a and 4a could be detected and isolat-
ed. From NMR spectroscopy of the reaction system at
1H and 13C NMR spectra were recorded on a Bruker 400 MHz in-
strument using CDCl3 and DMSO-d6 as the solvent with TMS as an
internal standard at r.t. HPLC was carried out using a Shimadzu or-
ganizer consisting of a LC-2010A HT Integrator, a UV/VIS Detec-
tor. C18 column was used in the HPLC experiments with MeCN–
Synthesis 2011, No. 12, 1831–1839 © Thieme Stuttgart · New York

FEATURE ARTICLE
5-Hydroxy-1,5-dihydro-2H-pyrrol-2-ones
1835
O
O
O
O
OH
O
80 °C
80 °C
H
NH
NO2
N
Ph
Ph
Ph
OH
O
+
3a
5a
H
H+ transfer
– H2O
O
O
O–
O
+NH2
Ph
Ph
N
O
I
IV
O
O
+ H2O
O
O
tautomerization
NH2
NH
Ph
Ph
O
OH
II
III
Scheme 2 The proposed mechanism of the reaction from 4a to 5a
Figure 4 The NMR spectra at different times
H2O (50:50), 0.8 mL/min and UV = 254 nm. HRMS were per-
formed on Bruker Daltonics Bio TOF mass spectrometer. Melting
points were determined on a microscopic apparatus and are uncor-
rected. In some cases (5n,s), low melting points were observed, pre-
sumably owing to the presence of water within the solid products.
Attempts to remove the water (by vacuum drying, heating, etc.)
were unsuccessful.
a larger amount of a white or yellow solid precipitated, stirring con-
tinued for 15 min. Distilled H2O was added until the soln became
clear, then the soln was added dropwise to concd HCl (30 mL) and
a yellow solid precipitated. The yellow solid was filtered and
washed with H2O, then evaporated in a vacuum drying oven. After
recrystallization (EtOH), yellow needle-like crystalloids were ob-
tained.
Nitroalkenes 1; General Procedure
5-Hydroxy-1,5-dihydro-2H-pyrrol-2-ones; General Procedure
Nitroethylene 1 (2 mmol), 1,3-dicarbonyl compound 2 (4 mmol),
DMSO (10 mL), and H2O (10 mL) were added to a 50-mL round-
bottom flask. The mixture was stirred at 80–90 °C for 12–48 h, then
Aldehyde (0.05 mol), MeNO2 (0.05 mol), and MeOH (10–20 mL)
were added to a round-bottom flask and then stirred vigorously.
NaOH soln (10 mL of 10.5 M) was added dropwise in an ice bath,
Synthesis 2011, No. 12, 1831–1839 © Thieme Stuttgart · New York

1836
M.-Y. Wu et al.
FEATURE ARTICLE
brine (20 mL) was added and the soln was extracted with EtOAc (3
× 30 mL). The organic phase was combined and washed with brine
(30 mL), then dried (Na2SO4), filtered, and evaporated in vacuo.
The residue was purified by flash column chromatography (silica
gel, 300–400 mesh) to give the product.
4-Acetyl-3-(4-bromophenyl)-5-hydroxy-5-methyl-1,5-dihydro-
2H-pyrrol-2-one (5f)
Yield: 431.8 mg (70%); white solid; mp 141–143 °C.
1H NMR (400 MHz, TMS, DMSO-d6): d = 9.03 (s, 1 H, NH), 7.65
(d, J = 8.4 Hz, 2 H, HPh), 7.35 (J = 8.4 Hz, 2 H, HPh), 6.29 (s, 1 H,
OH), 2.17 (s, 3 H, CH3), 1.60 (s, 3 H, CH3).
13C NMR (100 MHz, DMSO-d6): d = 200.4, 168.2, 154.5, 133.5,
131.8, 131.6, 129.8, 123.2, 85.7, 31.6, 25.5.
HRMS (ESI): m/z [M + H]+ calcd for C13H13BrNO3: 310.0073;
found: 310.0077.
4-Acetyl-5-hydroxy-5-methyl-3-phenyl-1,5-dihydro-2H-pyrrol-
2-one (5a)
Yield: 300.1 mg (65%); white solid; mp 135–137 °C.
1H NMR (400 MHz, DMSO-d6): d = 9.01 (s, 1 H, NH), 7.47–7.38
(m, 5 H, HPh), 6.27 (s, 1 H, OH), 2.12 (s, 3 H, CH3), 1.62 (s, 3 H,
CH3).
13C NMR (100 MHz, DMSO-d6): d = 200.6, 168.6, 154.1, 134.7,
130.7, 129.6, 129.5, 128.8, 85.6, 31.5, 25.6.
HRMS (ESI): m/z [M + Na]+ calcd for C13H13NO3Na: 254.0788;
found: 254.0784.
4-Acetyl-5-hydroxy-5-methyl-3-[4-(trifluoromethyl)phenyl]-
1,5-dihydro-2H-pyrrol-2-one (5g)
Yield: 364.7 mg (61%); white solid; mp 135–137 °C.
1H NMR (400 MHz, DMSO-d6): 9.08 (s, 1 H, NH), 7.81 (d, J = 8.4
Hz, 2 H, HPh), 7.61 (J = 8.4 Hz, 2 H, HPh), 6.36 (s, 1 H, OH), 2.19
(s, 3 H, CH3), 1.62 (s, 3 H, CH3).
13C NMR (100 MHz, DMSO-d6): d = 200.0, 168.0, 155.6, 134.9,
133.4, 130.3, 130.1, 129.8, 129.5 129.2, 128.6, 125.9, 125.6, 125.6,
125.5, 123.2, 85.8, 31.6, 25.4.
4-Acetyl-5-hydroxy-5-methyl-3-(4-tolyl)-1,5-dihydro-2H-pyr-
rol-2-one (5b)
Yield: 300.3 mg (61%); white solid; mp 120–121 °C.
1H NMR (400 MHz, DMSO-d6): d = 8.94 (s, 1 H, NH), 7.30 (d,
J = 8 Hz, 2 H, HPh), 7.25 (d, J = 8.0 Hz, 2 H, HPh), 6.20 (s, 1 H, OH),
2.34 (s, 3 H, CH3), 2.11 (s, 3 H, CH3), 1.60 (s, 3 H, CH3).
HRMS (ESI): m/z [M + H]+ calcd for C14H13F3NO3: 300.0842;
found: 300.0854.
13C NMR (100 MHz, DMSO-d6): d = 200.8, 168.7, 153.5, 139.3,
4-Acetyl-3-(2-chlorophenyl)-5-hydroxy-5-methyl-1,5-dihydro-
2H-pyrrol-2-one (5h)
Yield: 485.3 mg (92%); white solid; mp 126–128 °C.
134.5, 129.5, 129.4, 127.8, 85.6, 31.5, 25.7, 21.4.
HRMS (ESI): m/z [M + Na]+ calcd for C14H15NO3Na: 268.0944;
found: 268.0945.
1H NMR (400 MHz, DMSO-d6): d = 9.03 (s, 1 H, NH), 7.56 (d,
J = 8.4 Hz, 1 H, HPh), 7.48–7.41 (m, 2 H, HPh), 7.30 (d, J = 8.8 Hz,
1 H, HPh), 6.28 (s, 1 H, OH), 2.02 (s, 3 H, CH3), 1.67 (s, 3 H, CH3).
13C NMR (100 MHz, DMSO-d6): d = 196.9, 167.7, 153.8, 137.1,
132.8, 131.5, 131.0, 130.9, 129.8, 127.5, 86.2, 30.8, 26.1.
HRMS (ESI): m/z [M + H]+ calcd for C13H13ClNO3: 266.0578;
found: 266.0577.
4-Acetyl-5-hydroxy-3-(4-methoxyphenyl)-5-methyl-1,5-dihy-
dro-2H-pyrrol-2-one (5c)
Yield: 291.5 mg (56%); white solid; mp 112–115 °C.
1H NMR (400 MHz, DMSO-d6): d = 8.93 (s, 1 H, NH), 7.37 (d,
J = 8.8 Hz, 2 H, HPh), 7.01 (J = 8.8 Hz, 2 H, HPh), 6.17 (s, 1 H, OH),
3.79 (s, 3 H, OCH3), 2.13 (s, 3 H, CH3), 1.60 (s, 3 H, CH3).
13C NMR (100 MHz, DMSO-d6): d = 200.8, 168.9, 160.5, 152.5,
4-Acetyl-3-(2-bromophenyl)-5-hydroxy-5-methyl-1,5-dihydro-
2H-pyrrol-2-one (5i)
Yield: 436.9 mg (71%); white solid; mp 128–131 °C.
134.2, 131.1, 122.8, 114.3, 85.5, 55.6, 31.4, 25.7.
HRMS (ESI): m/z [M + Na]+ calcd for C14H15NO4Na: 284.0893;
found: 284.0898.
1H NMR (400 MHz, DMSO-d6): d = 9.05 (s, 1 H, NH), 7.72 (d,
J = 8.0 Hz, 1 H, HPh), 7.49–7.28 (m, 3 H, HPh), 6.23 (s, 1 H, OH),
1.99 (s, 3 H, CH3), 1.68 (s, 3 H, CH3).
13C NMR (100 MHz, DMSO-d6): d = 195.9, 167.1, 152.5, 138.9,
132.6, 132.4, 130.6, 130.6, 127.6, 122.4, 85.7, 30.5, 25.6.
HRMS (ESI): m/z [M + H]+ calcd for C13H13BrNO3: 310.0073;
found: 310.0077.
4-Acetyl-3-(4-fluorophenyl)-5-hydroxy-5-methyl-1,5-dihydro-
2H-pyrrol-2-one (5d)
Yield: 248.7 mg (50%); white solid; mp 140–142 °C.
1H NMR (400 MHz, DMSO-d6): d = 9.00 (s, 1 H, NH), 7.46–7.43
(m, 2 H, HPh), 7.29 (t, J = 9.0 Hz, 2 H, HPh), 6.25 (s, 1 H, OH), 2.15
(s, 3 H, CH3), 1.60 (s, 3 H, CH3).
13C NMR (100 MHz, DMSO-d6): d = 205.2, 173.2, 167.8 (d, JF-C
252 Hz), 158.8, 138.3, 136.5 (d, JF-C = 9 Hz), 131.8, 120.6 (d, JF-C
21 Hz), 90.4, 36.3, 30.3.
HRMS (ESI): m/z [M + Na]+ calcd for C13H12FNO3Na: 272.0693;
found: 272.0702.
=
=
4-Acetyl-3-(3-chlorophenyl)-5-hydroxy-5-methyl-1,5-dihydro-
2H-pyrrol-2-one (5j)
Yield: 345 mg (65%); white solid; mp 137–139 °C.
1H NMR (400 MHz, DMSO-d6): d = 9.05 (s, 1 H, NH), 7.52–7.45
(m, 3 H, HPh), 7.30 (d, J = 7.2 Hz, 1 H, HPh), 6.31 (s, 1 H, OH), 2.18
(s, 3 H, CH3), 1.60 (s, 3 H, CH3).
13C NMR (100 MHz, DMSO-d6): d = 200.2, 168.1, 155.0, 133.4,
133.1, 132.7, 130.7, 129.4, 129.0, 128.2, 85.7, 31.6, 25.4.
HRMS (ESI): m/z [M + H]+ calcd for C13H13ClNO3: 266.0578;
found: 266.0577.
4-Acetyl-3-(4-chlorophenyl)-5-hydroxy-5-methyl-1,5-dihydro-
2H-pyrrol-2-one (5e)
Yield: 320 mg (60%); white solid; mp 139–140 °C.
1H NMR (400 MHz, DMSO-d6): d = 9.03 (s, 1 H, NH), 7.52 (d,
J = 8.4 Hz, 2 H, HPh), 7.42 (J = 8.8 Hz, 2 H, HPh), 6.28 (s, 1 H, OH),
2.16 (s, 3 H, CH3), 1.60 (s, 3 H, CH3).
13C NMR (100 MHz, DMSO-d6): d = 200.4, 168.3, 154.5, 134.5,
133.4, 131.3, 129.5, 128.9, 85.7, 31.6, 25.5.
HRMS (ESI): m/z [M + H]+ calcd for C13H13ClNO3: 266.0578;
4-Acetyl-3-(furan-2-yl)-5-hydroxy-5-methyl-1,5-dihydro-2H-
pyrrol-2-one (5k)
Yield: 232.5 mg (53%); white solid; mp 124–126 °C.
found: 266.0577.
Synthesis 2011, No. 12, 1831–1839 © Thieme Stuttgart · New York

FEATURE ARTICLE
5-Hydroxy-1,5-dihydro-2H-pyrrol-2-ones
1837
1H NMR (400 MHz, DMSO-d6): d = 8.99 (s, 1 H, NH), 7.84 (s, 1 H,
HAr), 7.16 (d, J = 3.2 Hz, 1 H, HAr), 6.63 (d, J = 1.6 Hz, 1 H, HAr),
6.31 (s, 1 H, OH), 2.04 (s, 3 H, CH3), 1.51 (s, 3 H, CH3).
6.29 (s, 1 H, OH), 2.49–2.44 (m, 1 H, CH2), 2.40–2.33 (m, 1 H,
CH2), 1.96–1.85 (m, 2 H, CH2), 0.89 (t, J = 7.2 Hz, 3 H, CH3), 0.79
(t, J = 7.2 Hz, 3 H, CH3).
13C NMR (100 MHz, DMSO-d6): d = 201.5, 166.9, 150.3, 145.6,
13C NMR (150 MHz, DMSO-d6): d = 204.2, 169.0, 163.5, 162.9 (d,
JF-C = 244.5 Hz), 153.5, 133.5, 131.5 (d, JF-C = 7.5 Hz), 127.0, 116.0
(d, JF-C = 22.5 Hz), 88.8, 36.8, 30.3, 8.4, 7.7.
145.5, 120.6, 113.2, 112.5, 86.0, 32.2, 25.4.
HRMS (ESI): m/z [M + Na]+ calcd for C11H11NO4Na: 244.0580;
found: 244.0579.
HRMS (ESI): m/z [M + Na]+ calcd for C15H16FNO3Na: 300.1006;
found: 300.1056.
4-Acetyl-5-hydroxy-5-methyl-3-propyl-1,5-dihydro-2H-pyrrol-
2-one (5l)
Yield: 96 mg (25%); white solid; mp 90–93 °C.
3-(4-Chlorophenyl)-5-ethyl-5-hydroxy-4-propionyl-1,5-dihy-
dro-2H-pyrrol-2-one (5q)
Yield: 292.4 mg (50%); white solid; mp 90–92 °C.
1H NMR (400 MHz, DMSO-d6): d = 9.71 (s, 1 H, NH), 7.06 (s, 1 H,
OH), 3.38 (s, 3 H, CH3), 3.36 (m, 2 H, CH2), 2.50 (s, 3 H, CH3),
2.46–2.37 (m, 2 H, CH2), 1.85 (t, J = 7.4 Hz, 3 H, CH3).
13C NMR (100 MHz, DMSO-d6): d = 198.1, 169.5, 151.2, 141.6,
85.8, 31.4, 26.2, 25.9, 21.8, 14.4.
HRMS (ESI): m/z [M + Na]+ calcd for C10H15NO3Na: 220.0944;
found: 220.0953.
1H NMR (600 MHz, DMSO-d6): d = 8.89 (s, 1 H, NH), 7.52 (d,
J = 8.4 Hz, 2 H, HPh), 7.39 (d, J = 8.4 Hz, 2 H, HPh), 6.34 (s, 1 H,
OH), 2.49–2.46 (m, 1 H, CH2), 2.41–2.34 (m, 1 H, CH2), 1.95–1.85
(m, 2 H, CH2), 0.89 (t, J = 6.0 Hz, 3 H, CH3), 0.79 (t, J = 7.2 Hz, 3
H, CH3).
13C NMR (150 MHz, DMSO-d6): d = 204.1, 168.8, 154.1, 134.4,
133.3, 131.0, 129.4, 129.0, 88.8, 36.9, 30.3, 8.3, 7.6.
5-Ethyl-5-hydroxy-3-phenyl-4-propionyl-1,5-dihydro-2H-pyr-
rol-2-one (5m)
HRMS (ESI): m/z [M + Na]+ calcd for C15H16ClNO3Na: 316.0711;
found: 316.0722.
Yield: 260.2 mg (50%); white solid; mp 110–112 °C.
3-(4-Bromophenyl)-5-ethyl-5-hydroxy-4-propionyl-1,5-dihy-
dro-2H-pyrrol-2-one (5r)
Yield: 350.5 mg (52%); white solid; mp 91–93 °C.
1H NMR (600 MHz, DMSO-d6): d = 8.87 (s, 1 H, NH), 7.63 (d,
J = 8.4 Hz, 2 H, HPh), 7.30 (d, J = 8.4 Hz, 2 H, HPh), 6.36 (s, 1 H,
OH), 2.48–2.44 (m, 1 H, CH2), 2.40–2.33 (m, 1 H, CH2), 1.93–1.86
(m, 2 H, CH2), 0.88 (t, J = 7.2 Hz, 3 H, CH3), 0.77 (t, J = 7.2 Hz, 3
H, CH3).
13C NMR (150 MHz, DMSO-d6): d = 208.9, 173.5, 158.8, 138.1,
136.7, 136.0, 134.5, 127.9, 93.6, 41.7, 35.0, 13.1, 12.4.
HRMS (ESI): m/z [M + Na]+ calcd for C15H16BrNO3Na: 362.0206;
1H NMR (600 MHz, DMSO-d6): d = 8.83 (s, 1 H, NH), 7.46–7.42
(m, 3 H, HPh), 7.37–7.35 (m, 2 H, HPh), 6.28 (s, 1 H, OH), 2.47–2.41
(m, 1 H, CH2), 2.37–2.30 (m, 1 H, CH2), 1.99–1.86 (m, 2 H, CH2),
0.87 (t, J = 7.2 Hz, 3 H, CH3), 0.80 (t, J = 7.2 Hz, 3 H, CH3).
13C NMR (150 MHz, DMSO-d6): d = 230.8, 168.7, 153.0, 134.2,
13.1, 129.1, 128.8, 128.4, 88.3, 36.3, 29.8, 7.9, 7.2.
HRMS (ESI): m/z [M + Na]+ calcd for C15H17NO3Na: 282.1101;
found: 282.1102.
5-Ethyl-5-hydroxy-4-propionyl-3-(4-tolyl)-1,5-dihydro-2H-
pyrrol-2-one (5n)
Yield: 262.2 mg (48%); white solid; mp 65–70 °C.
found: 362.0180.
1H NMR (600 MHz, DMSO-d6): d = 8.79 (s, 1 H, NH), 7.26 (d,
J = 8.4 Hz, 2 H, HPh), 7.24 (d, J = 8.4 Hz, 2 H, HPh), 6.23 (s, 1 H,
OH), 2.46–2.39 (m, 1 H, CH2), 2.38–2.32 (m, 1 H, CH2), 2.33 (s, 3
H, CH3), 1.99–1.85 (m, 2 H, CH2), 0.87 (t, J = 7.2 Hz, 3 H, CH3),
0.78 t, J = 7.2 Hz, 3 H, CH3).
13C NMR (150 MHz, DMSO-d6): d = 204.5, 169.3, 152.8, 139.3,
134.5, 129.5, 129.2, 127.7, 88.7, 36.7, 30.3, 21.4, 8.4, 7.7.
5-Ethyl-5-hydroxy-4-propionyl-3-(4-(trifluoromethyl)phenyl)-
1,5-dihydro-2H-pyrrol-2-one (5s)
Yield: 326.8 mg (50%); white solid; mp 60–63 °C.
1H NMR (600 MHz, DMSO-d6): d = 8.98 (s, 1 H, NH), 7.82 (d,
J = 8.4 Hz, 2 H, HPh), 7.60 (d, J = 7.8 Hz, 2 H, HPh), 6.43 (s, 1 H,
OH), 2.59–2.52 (m, 1 H, CH2), 2.44–2.38 (m, 1 H, CH2), 1.97–1.91
(m, 2 H, CH2), 0.91 (t, J = 7.2 Hz, 3 H, CH3), 0.83 (t, J = 7.5 Hz, 3
H, CH3).
13C NMR (150 MHz, DMSO-d6): d = 203.9, 168.6, 155.3, 134.7,
133.2, 130.1, 129.7, 129.5, 125.8, 125.7, 125.4, 123.6, 88.9, 37.0,
30.2, 8.3, 7.6.
HRMS (ESI): m/z [M + Na]+ calcd for C16H19NO3Na: 296.1257;
found: 296.1257.
5-Ethyl-5-hydroxy-3-(4-methoxyphenyl)-4-propionyl-1,5-dihy-
dro-2H-pyrrol-2-one (5o)
Yield: 317.3 mg (55%); white solid; mp 115–117 °C.
HRMS (ESI): m/z [M + H]+ calcd for C16H17F3NO3: 328.1155;
found: 328.1146.
1H NMR (600 MHz, DMSO-d6): d = 8.78 (s, 1 H, NH), 7.33 (d,
J = 9.0 Hz, 2 H, HPh), 7.00 (d, J = 8.4 Hz, 2 H, HPh), 6.20 (s, 1 H,
OH), 3.79 (s, 3 H, CH3), 2.47–2.35 (m, 2 H, CH2), 1.97–1.91 (m, 1
H, CH2), 1.90–1.84 (m, 1 H, CH2), 0.89 (t, J = 7.2 Hz, 3 H, CH3),
0.77 (t, J = 7.2 Hz, 3 H, CH3).
13C NMR (150 MHz, DMSO-d6): d = 204.6, 169.4, 160.5, 151.8,
134.1, 130.8, 122.8, 114.4, 88.6, 55.7, 36.6, 30.4, 8.4, 7.8.
3-(2-Chlorophenyl)-5-ethyl-5-hydroxy-4-propionyl-1,5-dihy-
dro-2H-pyrrol-2-one (5t)
Yield: 440 mg (75%); white solid; mp 95–98 °C.
1H NMR (600 MHz, DMSO-d6): d = 8.86 (s, 1 H, NH), 7.56–7.55
(m, 1 H, HPh), 7.47–7.42 (m, 2 H, HPh), 7.28 (d, J = 6.6 Hz, 1 H,
HPh), 6.28 (s, 1 H, OH), 2.40–2.33 (m, 1 H, CH2), 2.31–2.24 (m, 1
H, CH2), 2.14–2.08 (m, 1 H, CH2), 1.96–1.90 (m, 1 H, CH2), 0.82
(t, J = 7.2 Hz, 3 H, CH3), 0.80 (t, J = 7.5 Hz, 3 H, CH3).
HRMS (ESI): m/z [M + Na]+ calcd for C16H19NO4Na: 312.1206;
found: 312.1206.
13C NMR (150 MHz, DMSO-d6): d = 200.6, 168.4, 153.1, 136.7,
5-Ethyl-3-(4-fluorophenyl)-5-hydroxy-4-propionyl-1,5-dihy-
dro-2H-pyrrol-2-one (5p)
Yield: 277.3 mg (50%); white solid; mp 84–86 °C.
132.7, 131.6, 131.0, 130.8, 129.9, 127.6, 89.6, 36.1, 30.5, 8.5, 7.6.
HRMS (ESI): m/z [M + Na]+ calcd for C15H16ClNO3Na: 316.0711;
found: 316.0722.
1H NMR (600 MHz, DMSO-d6): d = 8.86 (s, 1 H, NH), 7.42 (q,
J1 = 6.0 Hz, J2 = 9.0 Hz, 2 H, HPh), 7.29 (t, J = 9.0 Hz, 2 H, HPh),
Synthesis 2011, No. 12, 1831–1839 © Thieme Stuttgart · New York

1838
M.-Y. Wu et al.
FEATURE ARTICLE
3-(2-Bromophenyl)-5-ethyl-5-hydroxy-4-propionyl-1,5-dihy-
dro-2H-pyrrol-2-one (5u)
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
Yield: 431.2 mg (64%); white solid; mp 101–103 °C.
1H NMR (600 MHz, DMSO-d6): d = 8.89 (s, 1 H, NH), 7.72 (d,
J = 8.4 Hz, 1 H, HPh), 7.50–7.16 (m, 3 H, HPh), 6.22 (s, 1 H, OH),
2.43–2.21 (m, 2 H, CH2), 2.14–2.07 (m, 1 H, CH2), 1.99–1.93 (m, 1
H, CH2), 0.85–0.80 (m, 6 H, CH3).
Primary Data for this article are available online at
http://www.thieme-connect.com/ejournals/toc/synthesis and can be
cited using the following DOI: 10.4125/pd0012th.
13C NMR (150 MHz, DMSO-d6): d = 200.1, 168.5, 152.3, 138.7,
133.1, 133.0, 131.4, 131.1, 128.1, 122.8, 89.7, 36.1, 3.4, 8.7, 7.7.
Acknowledgment
HRMS (ESI): m/z [M + Na]+ calcd for C15H16BrNO3Na: 360.0206;
found: 360.0180.
This work was financially supported by the National Science Foun-
dation of China (No. 20725206, 20732004, 21001077, and
20121001), Specialized Research Fund for the Doctoral Program of
Higher Education (20100181120040), Program for Changjiang
Scholars and Innovative Research Team in University (IRT 0846),
the Key Project of Chinese Ministry of Education in China, we also
thank the Sichuan University Analytical & Testing Center for NMR
analysis. We highly appreciate the suggestion of Dr. P.-H. Toy
(Hong Kong University) on the mechanism.
3-(3-Chlorophenyl)-5-ethyl-5-hydroxy-4-propionyl-1,5-dihy-
dro-2H-pyrrol-2-one (5v)
Yield: 322 mg (55%); white solid; mp 94–97 °C.
1H NMR (600 MHz, DMSO-d6): d = 8.75 (s, 1 H, NH), 7.30–7.26
(m, 3 H, HPh), 7.11 (d, J = 7.2 Hz, 1 H, HPh), 6.21 (s, 1 H, OH), 2.38–
2.31 (m, 1 H, CH2), 2.26–2.19 (m, 1 H, CH2), 1.79–1.72 (m, 2 H,
CH2), 0.72 (t, J = 7.5 Hz, 3 H, CH3), 0.63 (t, J = 7.5 Hz, 3 H, CH3).
13C NMR (150 MHz, DMSO-d6): d = 204.0, 168.7, 154.7, 133.5,
133.0, 132.6, 130.8, 129.4, 128.7, 127.9, 88.9, 27.0, 30.2, 8.3, 7.6.
References
(1) Toja, E.; Gorini, C.; Barzaghi, F.; Galliani, G. US 4885307,
1989.
(2) (a) Singh, S. B.; Goetz, M. A.; Jones, E. T.; Bills, G. F.;
Giacobbe, R. A.; Herranz, L.; Stevens-Miles, S.; Williams,
D. L. Jr. J. Org. Chem. 1995, 60, 7040. (b) Kakeya, H.;
Onozawa, C.; Sato, M.; Arai, K.; Osada, H. J. Med. Chem.
1997, 40, 391.
HRMS (ESI): m/z [M + Na]+ calcd for C15H16ClNO3Na: 316.0711;
found: 316.0722.
5-Ethyl-5-hydroxy-4-propionyl-3-propyl-1,5-dihydro-2H-pyr-
rol-2-one (5w)
Yield: 17 mg (4%); white solid; isomeric mixture; mp 80–82 °C.
1H NMR (600 MHz, DMSO-d6): d = 8.44 (8.41) (s, 1 H, NH), 6.20
(6.18) (s, 1 H, OH), 2.89–2.86 (m, 1 H, CH2), 2.72–2.63 (m, 1 H,
CH2), 2.29–2.15 (m, 1 H, CH2), 1.49–1.37 (m, 1 H, CH2), 1.00–0.88
(m, 8 H, CH2, CH3, CH3), 0.85 (q, J = 7.8 Hz, 3 H).
13C NMR (150 MHz, DMSO-d6): d = 202.1 (201.7), 170.8 (170.6),
152.1 (150.8), 141.1 (139.7), 91.0 (90.6), 70.8 (69.1), 36.2 (36.0),
26.2 (26.0), 21.9 (21.9), 18.1 (17.9), 14.3 (14.2), 7.8 (7.6).
(3) http://www.centrewatch.com/patient/drugs/
drugdirectories.html
(4) (a) Coleman, R. S.; Walczak, M. C.; Campbell, E. L. J. Am.
Chem. Soc. 2005, 127, 16038. (b) Uno, H.; Yayamn, A.;
Suzuki, H. Tetrahedron 1992, 48, 8353. (c) Snider, B. B.;
Neubert, B. J. J. Org. Chem. 2004, 69, 8952. (d) Pin, F.;
Comesse, S.; Garrigues, B.; Marchalin, Š.; Daïch, A. J. Org.
Chem. 2007, 72, 1181.
(5) (a) Quai, M.; Frattini, S.; Vendrame, U.; Mondoni, M.;
Dossena, S.; Cereda, E. Tetrahedron Lett. 2004, 45, 1413.
(b) Fan, M. J.; Qian, B.; Zhao, L. B.; Liang, Y. M.
Tetrahedron 2007, 63, 8987. (c) Adib, M.; Mahdavi, M.;
Noghani, M. A.; Bijanzadeh, H. R. Tetrahedron Lett. 2007,
48, 8056.
(6) (a) Howard, E. G.; Lindsey, R. V. Jr.; Theobald, C. W. J. Am.
Chem. Soc. 1959, 81, 4355. (b) Birru, W.; Fernley, R. T.;
Graham, L. D.; Grusovin, J.; Hill, R. J.; Hofmann, A.;
Howell, L.; James, P. J.; Jarvis, K. E.; Johnson, W. M.;
Jones, D. A.; Leitner, C.; Liepa, A. J.; Lovrecz, G. O.; Lu,
L.; Nearn, R. H.; Driscoll, B. J. O.; Phan, T.; Pollard, M.;
Turner, K. A.; Winkler, D. A. Bioorg. Med. Chem. 2010, 18,
5647.
HRMS (ESI): m/z [M + K]+ calcd for C12H19NO3K: 264.0997;
found: 264.1220.
3-(2-Nitro-1-phenylethyl)pentane-2,4-dione (3a)
White solid; mp 96–98 °C.
1H NMR (400 MHz, CDCl3): d = 7.35–7.29 (m, 3 H, HPh), 7.20–
7.17 (m, 2 H, HPh), 4.63 (dd, J = 3.2, 5.2 Hz, 2 H, CH2), 4.37 (d,
J = 10.8 Hz, 1 H, CH), 4.27–4.21 (m, 1 H, CH), 2.30 (s, 3 H, CH3),
1.94 (s, 3 H, CH3).
13C NMR (100, MHz, CDCl3): d = 201.8, 201.0, 136.0, 129.4,
128.6, 127.9, 78.2, 70.8, 42.8, 30.4, 29.5.
MS (ESI): m/z = 272.1 [M + Na]+.
(7) (a) Gavina, F.; Costero, A. M.; Andreu, M. R.; Carda, M.;
Luis, S. V. J. Am. Chem. Soc. 1988, 110, 4017. (b) Mase,
N.; Nishi, T.; Hiyoshi, M.; Ichihara, K.; Bessho, J.; Yoda,
H.; Takabe, K. J. Chem. Soc., Perkin Trans. 1 2002, 707.
(c) Coleman, R. S.; Liu, P.-H. Org. Lett. 2004, 6, 577.
(d) Rudler, H.; Parlier, A.; Ousmer, M.; Vaissermann, J. Eur.
J. Org. Chem. 1999, 3315. (e) Clayden, J.; Turnbull, R.;
Pinto, I. Tetrahedron: Asymmetry 2005, 16, 2235.
(f) Anselmi, C.; Camparini, A.; Scotton, M. J. Heterocycl.
Chem. 1983, 20, 687.
1-[5-(Hydroxyimino)-2-methyl-4-phenyl-4,5-dihydrofuran-3-
yl]ethanone (4a)
White solid; mp 140–142 °C.
1H NMR (400 MHz, CDCl3): d = 7.48 (s, 1 H, OH), 7.36–7.27 (m,
3 H, HPh), 7.19–7.17 (m, 2 H, HPh), 4.90 (d, J = 2 Hz, 1 H, CH), 2.51
(d, J = 1.6 Hz, 3 H, CH3), 1.97 (s, 3 H, CH3).
13C NMR (100 MHz, CDCl3): d = 193.9, 164.2, 157.9, 138.2, 129.3,
128.1, 127.5, 117.6, 49.3, 29.8, 14.3.
HRMS (ESI): m/z [M + H]+ calcd for C13H14NO3: 232.0968; found:
232.0974.
Synthesis 2011, No. 12, 1831–1839 © Thieme Stuttgart · New York

FEATURE ARTICLE
5-Hydroxy-1,5-dihydro-2H-pyrrol-2-ones
1839
(8) (a) Ma, S.; Xie, H. J. Org. Chem. 2002, 67, 6575. (b)Clark,
A. J.; Dell, C. P.; McDonagh, J. M.; Geden, J.; Mawdsley, P.
Org. Lett. 2003, 5, 2063. (c) Rosas, N.; Cabrera, A.;
Sharma, P.; Arias, J. L.; Garcia, J. L.; Arzoumanian, H.
J. Mol. Catal. A: Chem. 2000, 156, 103. (d) Arzoumanian,
H.; Jean, M.; Nuel, D.; Garcia, J. L.; Rosas, N.
2009, 13, 1820. (e) Senra, J. D.; Malta, L. F. B.; da Costa,
M. E. H. M.; Michel, R. C.; Aguiar, L. C. S.; Simas, A. B.
C.; Antunes, O. A. C. Adv. Synth. Catal. 2009, 351, 2411.
(f) Vishnumaya, M. R.; Singh, V. K. J. Org. Chem. 2009, 74,
4289. (g) Perchyonok, V. T.; Lykakis, I. N. Curr. Org.
Chem. 2009, 13, 573. (h) El-Batta, A.; Jiang, C. C.; Zhao,
W.; Anness, R.; Cooksy, A. L.; Bergdahl, M. J. Org. Chem.
2007, 72, 5244. (i) Bhardwaj, V. K.; Singh, N.; Hundal, M.
S.; Hundal, G. Tetrahedron 2006, 62, 7878. (j) Abe, H.;
Mawatari, Y.; Teraoka, H.; Fujimoto, K.; Inouye, M. J. Org.
Chem. 2004, 69, 495.
Organometallics 1997, 16, 2726. (e) Yang, L.; Lei, C. H.;
Wang, D. X.; Huang, Z. T.; Wang, M. X. Org. Lett. 2010, 12,
3918.
(9) (a) Li, C. J. Chem. Rev. 2005, 105, 3095. (b) Herrerías, C.
I.; Yao, X. Q.; Li, Z. P.; Li, C. J. Chem. Rev. 2007, 107,
2546. (c) Gruttadauria, M.; Giacalone, C.; Notoa, N. Adv.
Synth. Catal. 2009, 351, 33. (d) Chanda, A.; Fokin, V. V.
Chem. Rev. 2009, 109, 725. (e) Butler, R. N.; Coyne, A. G.
Chem. Rev. 2010, 110, 6302.
(11) CCDC 800819 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge crystallographic Data Centre via
www.ccdc.cam.ac.uk/data _request/cif.
(10) (a) Paradowska, J.; Stodulski, M.; Mlynarski, J. Angew.
Chem. Int. Ed. 2009, 48, 2. (b) Gottardo, M.; Scarso, A.;
Paganelli, S.; Strukul, G. Adv. Synth. Catal. 2010, 352,
2251. (c) Monopoli, A.; Calo, V.; Ciminale, F.; Cotugno, P.;
Angelici, C.; Cioffi, N.; Nacci, A. J. Org. Chem. 2010, 75,
3908. (d) Kumaravel, K.; Vasuki, G. Curr. Org. Chem.
(12) Nicolaou, K. C.; Baran, P. S.; Zhong, Y. L.; Fong, K. C.;
Choi, H. S. J. Am. Chem. Soc. 2002, 124, 2190.
(13) (a) Hrnčiar, P.; Čulak, I. Collect. Czech. Chem. Commun.
1984, 49, 1421. (b) Barange, D. K.; Raju, B. R.; Kavala, V.;
Kuo, C. W.; Tu, Y. C.; Yao, C. F. Tetrahedron 2010, 66,
3754.
Synthesis 2011, No. 12, 1831–1839 © Thieme Stuttgart · New York