Synthesis of urea derivatives from CO2 and amines catalyzed by polyethylene glycol supported potassium hydroxide without dehydrating agents

Article abstract of DOI:10.1055/s-0029-1219799

Polyethylene glycol supported potassium hydroxide (KOH/PEG1000) was developed as a recyclable catalyst for facile synthesis of urea derivatives from amines and CO₂ without utilization of additional dehydrating agents. Primary aliphatic amines, secondary aliphatic amines, and diamines can be converted into the corresponding urea derivatives in moderate yields. Furthermore, the catalyst can be recovered after a simple separation procedure, and reused over 5 times with retention of high activity. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1219799

1
276
LETTER
Synthesis of Urea Derivatives from CO and Amines Catalyzed by
2
Polyethylene Glycol Supported Potassium Hydroxide without
Dehydrating Agents
S
D
ynthesis of
U
rea
e
D
erivative s- Lin Kong, Liang-Nian He,* Jin-Quan Wang
State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, P. R. of China
Fax +86(22)23504216; E-mail: heln@nankai.edu.cn
Received 28 December 2009
7
starting materials such as lactic acid. As a continuation of
our previous investigations on utilization of PEG, we
herein report that a KOH/PEG1000-catalyzed processes
Abstract: Polyethylene glycol supported potassium hydroxide
KOH/PEG1000) was developed as a recyclable catalyst for facile
synthesis of urea derivatives from amines and CO without utiliza-
8
(
2
tion of additional dehydrating agents. Primary aliphatic amines, for the synthesis of urea derivatives from amines and CO
2
secondary aliphatic amines, and diamines can be converted into the without using any dehydrating agent (Scheme 1).
corresponding urea derivatives in moderate yields. Furthermore, the
catalyst can be recovered after a simple separation procedure, and
reused over 5 times with retention of high activity.
O
O
RNH2
RHN
R2N
NHR
NR2
KOH/PEG1000
Key words: amine, carbon dioxide, polyethylene glycol, urea, sup-
ported catalyst
+
CO2
+
2
H O
2
R NH
Urea derivatives are an important class of carbonyl com- Scheme 1 KOH/PEG-catalyzed synthesis of symmetrical urea from
amine and CO2
pounds and useful chemical intermediates in the synthesis
of pharmaceuticals, agricultural chemicals, and dyes; and
they are also used as antioxidants in gasoline and addi- In the preliminary study, n-butylamine was selected as a
1
tives in plastics. On the other hand, conventionally pre- model substrate to test this protocol. The reactions were
parative methodologies of urea derivatives are based on conducted without any dehydrating agents. The results are
the use of dangerous reagents such as phosgene and isocy- summarized in Table 1. Without a catalyst, the reaction
2
anates. Nowadays, replacement of these hazardous re- did not occur at all (Table 1, entry 1). PEG1000 itself also
agents in chemical processes is one of the main goals in gave no product (entry 2). To our delight, inorganic bases
green chemistry. Therefore, the synthesis of ureas starting such as NaOH, KOH, Na CO , K CO , and Cs CO were
2
3
2
3
2
3
from CO has drawn much attention because CO is a re- found to be active for the reaction (entries 3, 5, 7, 9, 11).
2
2
newable, abundant, cheap, and nontoxic source of func- The catalytic performance seemed to be strongly depen-
tional carbon unit. In this regard, successful routes to urea dent on its basicity. Generally a stronger base could favor
derivatives directly from CO and amines have been re- the formation of dibutylurea and KOH was found to show
2
3
ported. However, stoichiometric or excessive dehydrat- the best activity among the tested bases. More interesting-
ing agents such as diorganophosphites, carbodiimides,
propargyl alcohols, and P4S10 are usually required to tion (entry 3 vs. 4, 5 vs. 6, 7 vs. 8, 9 vs. 10, and 11 vs. 12).
reach significant product yields. Accordingly, it is desir- In particular, KOH/PEG1000 showed good activity (entry
able to develop simple and environmentally benign pro- 10). It is worth mentioning that urea is the only product
3
a
3b
ly, PEG1000 as support was found to facilitate the reac-
3
d
3e
cesses for the synthesis of substituted ureas from amines formed in all these reactions and no byproduct was detect-
4
and CO in the absence of dehydrating agent.
ed by GC (see Supplementary Information).
2
Polyethylene glycol (PEG) and its derivatives are com- We next evaluated the effect of PEG molecular weight
monly known to be inexpensive, thermally stable, almost (MW). It is found that the MW has a significant impact on
negligible vapor pressure, toxicologically innocuous, and the catalytic activity of KOH/PEG. PEG with MW of
environmentally benign media for chemical reactions and 600–6000 gave a similar yield under otherwise identical
5
phase-transfer catalyst (PTC). Notably, PEG is able to conditions (entries 10, 16–20). However, ethylene glycol
coordinate with metal cations, whereby could act as an ex- had no activity (entry 13 vs. 9) and PEG200 also dis-
cellent PTC as well as an additive for a number of organic played a poor result (entry 14), hinting the requirement of
5
a,6
reactions. In addition, unlike most volatile organic sol- a minimum molecular weight of at least 200 for optimal
9
vents, PEG can be also prepared from biomass-based activity. On the other hand, PEG20000 was inactive (en-
try 21), presumably due to the increased mass-transport
limitation and the cage effect. Furthermore, our results
showed that the activity also changed with amount of cat-
alyst used (entries 10, 22–24). In comparison with PEG-
SYNLETT 2010, No. 8, pp 1276–1280
Advanced online publication: 23.03.2010
DOI: 10.1055/s-0029-1219799; Art ID: W20609ST
x
x.
x
x.
2
0
1
0
©
Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Urea Derivatives
1277
supported organic bases such as pyridine/PEG, Et N/ Table 1 Catalyst Effecta
3
PEG, and DBU/PEG, KOH/PEG also showed a better cat-
Entry
Catalyst
–
Conversion (%)b Yield (%)b
alytic activity (entries 10 vs. 25–27). Given the goal of the
present work, we chose 10 mol% KOH/PEG1000 as a
benchmark catalyst for further investigations in terms of
its readily availability, simpler workup procedure, cata-
lyst recycling as well as economical considerations.
1
1.8
1.5
0
2
PEG1000
Na CO
0
3
4.5
3.8
2
3
In addition to its environmentally benign characteristics,
the advantages of using PEG as support in the present
study could be outlined as follows. First, it is assumed that
PEG1000 can form complexes through coordinating the
potassium cation such as crown ethers do, which results in
an increase in basicity of KOH. Second, the ‘CO2-
expansion of PEG’ effect leads to changes in the physical
properties of the reaction mixture, such as lowered viscos-
ity, increased gas/liquid diffusion rates, and solubility of
the reactants, thereby improving the synthetic process.
Third, another merit of using PEG is the ease of catalyst
separation.
4c
5
Na CO /PEG1000
13.6
11.3
23.5
14.3
25.8
15.9
40.5
17.5
35.5
9.1
2
3
NaOH
9.2
6 c
7
NaOH/PEG1000
K CO
22.8
11.0
17.8
14.1
37.2
13.9
31.2
15.0
19.8
27.2
37.4
37.8
36.8
35.0
30.0
6.4
1
1
2
3
8
K CO /PEG1000
2
3
9
KOH
1
1
1
0c
1
KOH/PEG1000
Cs CO
2
3
In fact, this work shows that PEG as a support could en-
hance the reaction, which could be explained with the pro-
2c
Cs CO /PEG1000
2 3
posed mechanism. As depicted in Scheme 2, the reaction 13d
involves two steps, that is, formation of the ammonium
KOH + ethylene glycol 17.3
1
4
KOH/PEG200
KOH/PEG400
KOH/PEG600
KOH/PEG800
KOH/PEG2000
KOH/PEG4000
KOH/PEG6000
KOH/PEG20000
KOH/PEG1000
KOH/PEG1000
KOH/PEG1000
pyridine/PEG1000
23.3
34.5
41.8
46.1
40.3
37.9
34.0
17.7
19.5
31.3
42.3
3.2
carbamate (an exothermic step) and dehydration to the
4
e
urea (an endothermic step). In this reaction, PEG could 15
+
–
form [R NH ·PEG] [R NCO ] , and thus could increase
2
2
2
2
+
6
1
16
the thermodynamic stability of [R NH ] . Indeed, H
2
2
NMR measurement also supported the complexation of
1
1
1
2
7
8
9
0
1
1
PEG with ammonium cation. Increasing the basicity of
the base with the help of PEG could also facilitate forma-
1
2
tion of the ammonium carbamate salt. On the other hand,
PEG can act as a physical dehydrating agent since PEG is
strongly hygroscopic.
We also examined influence of the reaction parameters on 21
the reaction. The results are listed in Table 2. The product
2
2e
14.1
29.9
39.3
0
yield increased rapidly with reaction temperature up to
4
23 K (entries 1–4), whereas, further increase in the tem- 23f
perature caused a decrease in the yield (entry 5 vs. 4), pre-
sumably because the reversible formation of the
2
4g
4
d,e
ammonium carbamate is an exothermic step.
25
We also found that the product yield was sensitive to the
2
6
7
Et N/PEG1000
4.6
3.5
3
CO pressure. At low pressure range from 2 to 10 MPa, an
2
2
DBU/PEG1000
20.9
17.6
increase in pressure could facilitate the reaction because
CO is a reactant, and the solubility of CO in the reaction
a
2
2
Reaction conditions: n-butylamine (4 mmol), catalyst (0.4 mmol, 10
phase increases with increasing pressure (entries 4, 6–9).
mol%), 8 MPa CO , 423 K, 6 h.
2
b
On the other hand, too high CO pressure could decrease
Detected by GC using biphenyl as an internal standard.
PEG-supported catalysts were prepared according to a reported pro-
2
c
polarity of the reaction medium, and also diluted the con-
centration of the reactants, leading to a decrease of the re-
action rate (entries 4, 9–11). Therefore, the optimal
pressure was around 8 MPa (entries 4, 6–11). In addition,
1
0
cedure.
d
Physical mixture of KOH (22.4 mg) and ethylene glycol (24.8 mg).
e
f
1
5
mol% catalyst used.
mol% catalyst used.
g
1
0 hours were required for completion of the reaction (en-
15 mol% catalyst used.
tries 4, 12–16). So the appropriate reaction conditions
would be 423 K, 8 MPa CO pressure, and 10 hours.
2
into the corresponding urea derivatives in moderate yields
entries 1–11). The linear amines showed better reactivity
than the branched ones (entries 1 vs. 2 and 3 vs. 4), prob-
ably due to the steric effect. It is noteworthy that second-
Using this protocol, the synthesis of other symmetrical
urea derivatives was successfully achieved using various
(
1
0,13
amines (Table 3).
Primary aliphatic amines, second-
ary aliphatic amines, and diamines could be converted
ary amines could also react with CO in the presence of
2
Synlett 2010, No. 8, 1276–1280 © Thieme Stuttgart · New York

1
278
D.-L. Kong et al.
LETTER
2
R2NH
+
CO2
KOH/PEG1000 to furnish tetrasubstituted urea deriva-
tives (entries 7 and 8). Furthermore, diamines could give
the cyclic urea derivatives (entries 9–11) in good yield
and selectivity. However, aniline was found to be unreac-
tive, and only starting material was recovered (entry 12).
This could be ascribed to the weaker basicity of the aro-
matic amine.
PEG
+
[
R2NCOO]–
2 2
[R NH ⋅PEG]
KOH
+
OH–
+
Table 3 Substrate Scope of This Approacha
–
R2NCOO] K+
[R NH ⋅PEG]
[
+
2
2
Entry
Amine
Conversion (%)b Yield (%)c
H2O
PEG
1
2
3
4
5
6
7
8
9
n-BuNH2
t-BuNH2
n-PrNH2
62.5
40.1
67.5
64.3
52.6
45.8
40.0
52.3
83.6
79.4
54.1
–
[
R2NCOO] K+
+
R2NH
32.9
58.3
O
K+
H
R2N
C
O–
NR2
i-PrNH
CyNH
BnNH2
2
56.0
48.9
2
42.0
KOH
n-Bu NH
36.7
2
O
Et NH
47.9
2
R2N
NR2
ethane-1,2-diamine
propane-1,2-diamine
82.0
Scheme 2 A possible reaction pathway for the formation of urea
1
0
75.1
Table 2 Screening Reaction Conditionsa
11
cyclohexane-1,2-diamine 79.3
PhNH2 2.2
74.2
1
2
no reaction
Entry
Temp
K)
Pressure
(MPa)
Time
(h)
Conversion Yield
b
b
(
(%)
(%)
a
Reaction was conducted at 8 MPa CO , 423 K for 10 h in a 50 mL
2
stainless steel autoclave containing amine (4 mmol), KOH/PEG1000
1
2
3
4
5
6
7
8
9
323
373
393
423
443
423
423
423
423
423
423
423
423
423
423
423
8
8
6
6
2.4
12.1
18.2
40.5
38.6
12.4
25.7
33.9
40.7
37.9
38.3
10.4
28.4
53.6
62.5
65.1
0
(
0.4 mmol, 10 mol%).
Detected by GC using biphenyl as an internal standard.
Isolated yield.
b
11.2
16.2
37.2
34.5
11.3
20.6
25.4
38.1
32.1
29.8
9.2
c
8
6
8
6
A series of experiments was subsequently conducted to
test the catalyst recycling ability. The workup of the reac-
tion was performed by extraction with diethyl ether. The
recovered catalyst was then subjected to a second run of
the reaction without replenishment of fresh catalyst. The
results showed that the supported catalyst could be reused
for 5 times without loss of catalytic activity (runs 1–5,
Table 4).
8
6
2
6
4
6
6
6
10
12
17
8
6
Table 4 Catalyst Repetitiona
1
1
1
1
1
1
0
1
2
3
4
5
6
6
Run
1
Catalyst
Conversion (%)b Yield (%)b
6
1st (fresh catalyst) 62.5
57.0
54.6
56.6
55.6
54.9
2
2
2nd
3rd
4th
5th
61.6
63.3
61.5
61.7
8
4
26.6
48.1
57.0
57.4
3
8
8
4
8
10
12
5
1
8
a
Reaction was run at 8 MPa CO , 423 K for 10 h in a 50 mL stainless
a
2
Reaction was conducted in a 50 mL stainless steel autoclave contain-
ing n-butylamine (4 mmol), KOH/PEG1000 (0.4 mmol, 10 mol%).
Detected by GC.
steel autoclave containing n-butylamine (4 mmol), KOH/PEG1000
(
0.4 mmol, 10 mol%).
Detected by GC using biphenyl as an internal standard.
b
b
Synlett 2010, No. 8, 1276–1280 © Thieme Stuttgart · New York

LETTER
Synthesis of Urea Derivatives
1279
In summary, we developed a simple process for the syn-
(5) Selected examples using PEG as media for chemical
reactions and phase-transfer catalyst, see: (a) Totten, G. E.;
Clinton, N. A.; Matlock, P. L. J. Macromol. Sci. Rev.
Macromol. Chem. Phys. 1998, C38, 77. (b) Naik, S. D.;
Doraiswamy, L. K. AIChE J. 1998, 44, 612. (c) Guo, Z.; Li,
M.; Willauer, H. D.; Huddleston, J. G.; April, G. C.; Rogers,
R. D. Ind. Eng. Chem. Res. 2002, 41, 253. (d) Ottani, S.;
Vitalini, D.; Comelli, F.; Castellari, C. J. Chem. Eng. Data
2002, 47, 1197. (e) Cortright, R. D.; Sanchez-Castillo, M.;
Dumesic, J. A. Appl. Catal., B 2002, 39, 353. (f) Chen, J.;
Spear, S. K.; Huddleston, J. G.; Holbrey, J. H.; Swatloski,
R. P.; Rogers, R. D. Ind. Eng. Chem. Res. 2004, 43, 5358.
thesis of symmetrical ureas from amines and CO without
2
using any dehydrating agents. Notably inorganic base/
PEG1000 proved to be an efficient and recyclable cata-
lyst, and PEG1000 as a support could enhance the reac-
tion. The catalyst could also be recovered after a simple
separation procedure, and reused over 5 times with reten-
tion of high activity. This process presented here could
show much potential application in industry due to its
simplicity and ease of catalyst recycling.
(g) Chen, J.; Spear, S. K.; Huddleston, J. G.; Holbrey, J. H.;
Rogers, R. D. J. Chromatogr., B: Anal. Technol. Biomed.
Life Sci. 2004, 807, 145. (h) Chen, J.; Spear, S. K.;
Huddleston, J. G.; Rogers, R. D. Green Chem. 2005, 7, 64.
6) Aresta, M.; Quaranta, E. Tetrahedron 1992, 48, 1515.
7) Cortright, R. D.; Sanchez-Castillo, M.; Dumesic, J. A. Appl.
Catal., B 2002, 39, 353.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
(
(
Acknowledgment
We are grateful to the National Natural Science Foundation of Chi-
na (Grant Nos. 20672054, 20872073) and the 111 project (B06005),
and the Committee of Science and Technology of Tianjin for finan-
cial support.
(8) (a) Wang, J.-Q.; He, L.-N. New J. Chem. 2009, 33, 1637.
(b) Wang, J.-Q.; He, L.-N.; Miao, C.-X.; Gao, J.
ChemSusChem 2009, 2, 755. (c) Wang, J.-Q.; He, L.-N.;
Miao, C.-X. Green Chem. 2009, 11, 1013. (d) Wang, J.-L.;
He, L.-N.; Dou, X.-Y.; Wu, F. Aust. J. Chem. 2009, 62, 917.
(
e) Du, Y.; Wu, Y.; Liu, A.-H.; He, L.-N. J. Org. Chem.
References and Notes
2008, 73, 4709. (f) Wang, J.-Q.; Cai, F.; Wang, E.; He, L.-N.
Green. Chem. 2007, 9, 882. (g) Tian, J.-S.; Maio, C.-X.;
Wang, J.-Q.; Cai, F.; Du, Y.; Zhao, Y.; He, L.-N. Green
Chem. 2007, 9, 566. (h) Dou, X.-Y.; Wang, J.-Q.; Wang, E.;
He, L.-N. Synlett 2007, 3058. (i) Du, Y.; Wang, J.-Q.; Chen,
J.-Y.; Cai, F.; Tian, J.-S.; Kong, D.-L.; He, L.-N.
Tetrahedron Lett. 2006, 47, 1271.
(
1) Selected examples utilizing ureas in the synthesis of
pharmaceuticals, agricultural chemicals, dye chemistry,
see: (a) Vishnyakova, T. P.; Golubeva, I. A.; Glebova, E. V.
Russ. Chem. Rev. (Engl. Transl.) 1985, 54, 249.
(
b) Getman, D. P.; DeCrescenzo, G. A.; Heintz, R. M.; Reed,
K. L.; Talley, J. J.; Bryant, M. L.; Clare, M.; Houseman, K.
A.; Marr, J. J.; Mueller, R. A.; Vazquez, M. L.; Shieh, H. S.;
Stallings, W. C.; Stegeman, R. A. J. Med. Chem. 1993, 36,
(
9) Totten, G. E.; Clinton, N. A. J. Macromol. Sci. Rev.
Macromol. Chem. Phys. 1988, C28, 293.
10) Typical Procedure for the Preparation of KOH/
(
(
2
(
1
88. (c) Matsuda, K. Med. Res. Rev. 1994, 14, 271.
d) Bigi, F.; Maggi, R.; Sartori, G. Green Chem. 2000, 2,
40. (e) Bartolo, G.; Salerno, G.; Mancuso, R.; Costa, M.
PEG1000
PEG1000 (4.0 g), KOH (0.224 g, 4 mmol) and water (20
mL) were mixed and stirred for 2–3 h. Water was then
vaporized under reduced pressure. Finally, the residue was
dried under vacuum to give the supported catalyst. See:
Alvaro, M.; Baleizao, C.; Carbonell, E.; Ghoul, E. M.;
Garcia, H.; Gigante, B. Tetrahedron 2005, 61, 12131.
J. Org. Chem. 2004, 69, 4741. (f) Estevez-Souza, A.;
Pissinate, K.; Nascimento, M. G.; Grynberg, N. F.;
Echevaria, A. Bioorg. Med. Chem. 2006, 14, 492.
(
(
2) (a) Shriner, R. L.; Horne, W. H.; Cox, R. F. B. Org. Synth.
1
943, 2, 453. (b) Nowick, J. S.; Powell, N. A.; Nguyen,
1
11) In the H NMR spectra, the chemical shift for NH peak of
T. M.; Noronha, G. J. Org. Chem. 1992, 57, 7364.
Et NH/CDCl /CO was shifted to upfield from d = 5.947 to
5
charts were provided on pS15 in the Supplementary
Information.
2
3
2
3) For examples of the reaction of amines with CO to afford
1
2
.194 ppm after adding PEG to the solution. The H NMR
ureas by using dehydrating agents, see: (a) Yamazaki, N.;
Higashi, F.; Iguchi, T. Tetrahedron Lett. 1974, 13, 1191.
(b) Ogura, H.; Takeda, K.; Tokue, R.; Kobayashi, T.
(
(
12) Abribat, B.; Bigot, Y. L.; Gaset, A. Synth. Commun. 1994,
Synthesis 1978, 394. (c) Nomura, R.; Yamamoto, M.;
Matsuda, H. Ind. Eng. Chem. Res. 1987, 26, 1056.
2
4, 2091.
13) General Procedure for the Synthesis of Urea from
Amines and CO2
(d) Fournier, J.; Bruneau, C.; Dixneuf, P. H.; Lgcolier, S.
J. Org. Chem. 1991, 56, 4456. (e) Nomura, R.; Hasegawa,
Y.; Ishimoto, M.; Toyosaki, T.; Matsuda, H. J. Org. Chem.
A 50 mL autoclave reactor was charged with amine (4
mmol), KOH/PEG1000 (0.4 mmol). CO was introduced
into the autoclave, and then the mixture was stirred at desired
temperature for 15 min to allow equilibration. Finally, the
pressure was adjusted to the reaction pressure (e.g., 8 MPa),
and the mixture was stirred continuously. When the reaction
finished, the reactor was cooled in ice-water and CO was
ejected slowly. An aliquot of sample was taken from the
resultant mixture for GC analysis. The catalyst (KOH/
PEG1000) was separated by adding Et O and cooling and
recovered by a simple filtration. The products were further
2
1
992, 57, 7339. (f) Tai, C.-C.; Huck, M. J.; McKoon, E. P.;
Woo, T.; Jessop, P. G. J. Org. Chem. 2002, 67, 9070.
g) Porwanski, S.; Menuel, S.; Marsura, X.; Marsura, A.
(
Tetrahedron Lett. 2004, 45, 5027.
4) For examples of the reaction of amines with CO to afford
(
2
2
ureas without dehydrating agents, see: (a) Shi, F.; Deng, Y.;
SiMa, T.; Peng, J.; Gu, Y.; Qiao, B. Angew. Chem. Int. Ed.
2
003, 42, 3257. (b) Munshi, P.; Heldebrant, D. J.; McKoon,
2
E. P.; Kelly, P. A.; Tai, C.-C.; Jessop, P. G. Tetrahedron
Lett. 2003, 44, 2725. (c) Shi, F.; Zhang, Q.; Ma, Y.; He, Y.;
Deng, Y. J. Am. Chem. Soc. 2005, 127, 4182. (d) Ion, A.;
Parvulescu, V.; Jacobs, P.; Vos, D. D. Green Chem. 2007, 9,
1
13
identified by H NMR and C NMR spectroscopy, which
are consistent with those reported in the literature and in
good agreement with the assigned structures (see electronic
Supplementary Information).
14
158. (e) Jiang, T.; Ma, X.; Zhou, Y.; Liang, S.; Zhang, J.;
Han, B. Green Chem. 2008, 10, 465.
Synlett 2010, No. 8, 1276–1280 © Thieme Stuttgart · New York

1
280
D.-L. Kong et al.
LETTER
Fitzgerald, D. J. Org. Biomol. Chem. 2005, 3, 3678.
1
,3-Dibutylurea (Table 3, Entry 1)
1
H NMR (300 MHz, CDC1 ): d = 0.91 (t, 6 H, J = 7.2 Hz),
(e) Orito, K.; Horibata, A.; Nakamura, T.; Ushito, H.;
Nagasaki, H.; Yuguchi, M.; Yamashita, S.; Yamazaki, T.;
Tokuda, M. J. Org. Chem. 2006, 71, 5951. (f) Porwanski,
S.; Menuel, S.; Marsurab, X.; Marsura, A. Tetrahedron Lett.
2004, 45, 5027. (g) Nudelman, N. S.; Lewkowicz, E. S.;
Pérez, D. G. Synthesis 1990, 917. (h) El-Faham, A.;
Khattab, S. N.; Abdul-Ghani, M.; Albericio, F. Eur. J. Org.
Chem. 2006, 1563. (i) Mizuno, T.; Takahashib, J.; Ogawa,
A. Tetrahedron 2002, 58, 7805.
3
1
(
4
.30–1.40 (m, 4 H), 1.41–1.51 (m, 4 H), 3.14 (q, 4 H), 4.61
br d, NH). 13C { H} NMR (75.5 MHz, CDCl ): d = 158.5,
l
3
0.3, 32.4, 20.0, 13.8.
(
14) (a) Nomura, R.; Hasegawa, Y.; Ishimoto, M.; Toyosaki, T.;
Matsuda, H. J. Org. Chem. 1992, 57, 7339. (b) Aue, D. H.;
Thomas, D. J. Org. Chem. 1975, 40, 2356. (c) Becker, J.
Y.; Zinger, B.; Yatziv, S. J. Org. Chem. 1987, 52, 2783.
(
d) Lee, J.; Chubb, A. J.; Moman, E.; McLoughlin, B. M.;
Sharkey, C. T.; Kelly, J. G.; Nolan, K. B.; Devocelle, M.;
Synlett 2010, No. 8, 1276–1280 © Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.