Hydrogen transfer reduction of nitriles in DBU based ionic liquids

Article abstract of DOI:10.3998/ark.5550190.0013.812

Raney nickel catalyzed transfer hydrogenation of nitrile was proposed, with formats as hydrogen donor. Three ionic liquids, including [DBUH ⁺][C₂H₅COO^-], [DBUH ⁺][C₃H₇COO^-], and [DBUH ⁺][C₄H₉COO^-], were prepared as reaction medium, and [DBUH⁺][C₄H₉COO ^-] showed the best performance. Various nitriles were reduced with potassium formate as hydrogen donor, and considerable to excellent yields of amines were given. The ionic liquid can be used for 6 times at least, and the reaction process is clean. ARKAT-USA, Inc.

Full text of DOI:10.3998/ark.5550190.0013.812

General Papers
ARKIVOC 2012 (viii) 128-136
Hydrogen transfer reduction of nitriles in DBU based ionic liquids
Xinzhi Chen, Shaodong Zhou, and Chao Qian*
Department of chemical and biological engineering, Zhejiang University. Zheda Road, #38,
Hangzhou, 310027, China
E-mail: chemtec@163.com
Abstract
Raney nickel catalyzed transfer hydrogenation of nitrile was proposed, with formats as hydrogen
donor. Three ionic liquids, including [DBUH+][C2H5COO–], [DBUH+][C3H7COO–], and
[DBUH+][C4H9COO–], were prepared as reaction medium, and [DBUH+][C4H9COO–] showed
the best performance. Various nitriles were reduced with potassium formate as hydrogen donor,
and considerable to excellent yields of amines were given. The ionic liquid can be used for 6
times at least, and the reaction process is clean.
Keywords: Catalytic transfer hydrogenation, reduction of nitriles, DBU based ionic liquid
Introduction
Catalytic transfer hydrogenation plays an important role in organic synthesis. Reduction of nitrile
yields amine. There are many reductants that are used in the reduction of nitrile, such as
hydrogen,1 sodium tetrahydroborate,2 Aluminum,3 lithium aluminium hydride,4 et al. However,
there are only a few reports on transfer hydrogenation system that is available for the reduction
of nitriles. R.C. Mebane, et al. have reported Raney nickel catalyzed transfer hydrogenation of
aliphatic nitrile using 2-propanol as hydrogen donor, and good yields of corresponding amines
were given5. But when we perform their method in the reduction of aromatic nitrile, little
corresponding amine was obtained. E. Mizushima et al. reported similar result, they found low
yield of benzylamine (6%) in RuH2(PPh3)4 catalyzed reduction of benzonitrile with 2-propanol
as hydrogen donor6. The transfer hydrogenation system, Pd/HCOOH, has been also reported to
be used in the reduction of nitrile,7 but it showed bad performance. Raney nickel catalyzed
transfer hydrogenation of nitrile with hydrazine hydrate as hydrogen donor has been reported by
both W.W. Zajac, et al.8 and Q.D. You, et al,9 and moderate yield of corresponding amine was
obtained. Although hydrazine hydrate is an effective hydrogen donor, it is limited by its toxicity
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and explosibility. Recently, a new hydrogen donor, hydrazinium monoformate, was proposed
and used in the reduction of nitrile. It is reported to be so effective that nitriles can be reduced in
a short time with good to excellent yields of corresponding amines10. However, the active
hydrogen comes from hydrazinium, and the formate anion is wasted.
In our recent study, we found that formate can be an effective hydrogen donor in Raney
nickel catalyzed reduction of nitriles if the hydrolysis and alcoholysis can be inhibited.
Hydrolysis and alcoholysis of nitriles is inevitable when water or alcohol is used as solvent, so
choosing an appropriate reaction medium is vital.
In recent years, ionic liquids (ILs) are attracting more and more attention as green and
efficient reaction media for catalytic transfer hydrogenation11. As the solubility of salts is higher
in IL than in organic solvents, we chose an IL as reaction medium. Recently, it was found by our
group that 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) based ILs were superior as catalyst in
some organic reactions such as aza-Michael additions12 and Knoevenagel condensation,13 and we
found it was also a good solvent. DBU based IL is attracting growing attention as it can be
prepared by simple neutralization of DBU and acid. In this work, we prepared several DBU
based ILs as solvent in Raney nickel catalyzed transfer hydrogenation of nitrile.
Results and Discussion
DBU based ILs were prepared through simple neutralization of DBU and various acids. Three
organic acid, including propionic acids, butyric acid and pentanoic acid, were used to prepare
corresponding ILs, which were [DBUH+][C2H5COO–], [DBUH+][C3H7COO–], and
[DBUH+][C4H9COO–]. The reduction of benzonitrile with sodium formate as hydrogen donor
was selected as model to compare the performance of different reaction media, including water,
ethanol, toluene and the ILs mentioned above. As water is an indispensable component in
formate participated transfer hydrogenation, the optimum amount of water was also explored. It
is clear in Table 1 that the optimum molar ratio n(HCOONa):n(H2O) is 2. The results show that
transfer hydrogenations performed in ILs gave better yields than those performed in other
solvents. Reactions carried out in water and ethanol failed to give considerable yields, and those
can be attributed to hydrolysis and alcoholysis of benzonitrile. The reaction carried out in toluene
took 14 hours to give 80% yield of benzylamine, which could demonstrate the promoting effect
of the DBU based ILs. The comparison also showed the performance order of the three ILs, that
[DBUH+][C2H5COO–]<[DBUH+][C3H7COO–]<[DBUH+][C4H9COO–]. As the acidity order of
the anions is C4H9COOH< C3H7COOH< C2H5COOH, the performance of DBU based IL as
solvent in transfer hydrogenation of nitrile depends on how weak the acidity of anion is. Thus it
can be judged that the promoting effect of DBU based IL probably resulted from its basicity.
Furthermore, we found that the solubility of salt in DBU based IL is low at room temperature,
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while it increases remarkably as the temperature rises. So it is convenient for separation after the
reaction. [DBUH+][C4H9COO–] was chosen as reaction medium for further investigation.
Table 1. Catalytic transfer hydrogenation of benzonitrile in various reaction media
Entry
Reaction medium
Toluene
Yieldd (%)
12b
1
2
3
4
5
6
7
8
9
Toluene
55b
Toluene
53b
Toluene
32b
Water
15c
Ethanol
33c
[DBUH+][C2H5COO–]
[DBUH+][C3H7COO–]
[DBUH+][C4H9COO–]
65c
71c
85c
aReaction conditions: benzonitrile (50 mmol), HCOONa (200mmol), catalyst (Raney nickel, 0.5
g), temperature (70 ºC), time (8 h). bThe hydrogen donor for Entry 1~4 are anhydrous HCOONa,
c
and the molar ratios of n(HCOONa):n(H2O) are 1, 2, 3 and 4 respectively. The hydrogen donor
for Entry 5~8 is HCOONa·2H2O. dGC yield.
After the reaction medium was selected, we compared the performance of different formates,
the results are shown in Table 2. It can be seen that sodium formate, tetraethylammonium
formate and potassium formate showed comparative performance, while reaction using
triethylammonium formate as hydrogen donor did not give any benzylamine. The probable
reason was that triethylammonium formate could decompose to triethylamine and formic acid
when heated, and benzonitrile reacts with formic acid to give benzaldehyde under catalyze of
Raney nickel14. Potassium formate was selected as hydrogen donor for further investigation.
Table 2. Catalytic transfer hydrogenation of benzonitrile in [DBUH+][C4H9COO–] with different
formatesa
Entry
Formate
Yieldb (%)
1
2
3
4
HCOONa
85
89
0
HCOOK
HCOOH(Et3N)
HCOO(Et4N)
86
aReaction conditions: IL (50 mL), benzonitrile (50 mmol), hydrogen donor (200 mmol), water
(400mmol), catalyst (Raney nickel, 0.5 g), temperature (70 ºC), time (8 h). bGC yield.
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We also tried two commonly used reduction catalyst, Pd/C and Pt/C, in the transfer
hydrogenation of benzonitrile to compare with Raney nickel. The results are shown in Table 3.
Whatever the solvent was, almost no reaction occurred when Pd/C was used as catalyst. And the
only product in Pt/C catalyzed reaction was benzamide. Both Pt/C and Pd/C were thus proved to
be inactive in the reduction of nitrile, while Pt/C can be a good catalyst for the hydrolysis of
nitrile.
Table 3. Reaction between benzonitrile and HCOOK catalyzed by Pd/C and Pt/Ca
Entry Reaction medium
Product (yieldb) in
Pd/C catalyzed
reaction
Product (yieldb) in Pt/C
catalyzed reaction
1
2
3
Water
Benzamide (2%)
Benzamide (<1%)
Benzamide (>99%)
Benzamide (30%)
Benzamide (40%)
Toluene
[DBUH+][C4H9COO–] Benzamide (<1%)
aReaction conditions: Rolvent (50 mL), benzonitrile (50 mmol), HCOOK(200 mmol), water(400
mmol), catalyst (0.5 g), temperature (70 ºC), time (8 h).bGC yield.
With the optimized reaction condition obtained, we expanded our study to other nitriles, and
the results are summarized in Table 4. Generally various nitriles were reduced with good yields
of corresponding amines. The reduction product of 4-chlorobenzonitrile was benzylamine, and
the nitro group in 4-nitrobenzonitrile was reduced to amino. So it can be concluded that this
transfer hydrogenation system is also available in dehalogenation and reduction of nitro. It
should be noted that the reduction of aliphatic nitriles took much shorter time than that of
aromatic nitriles (Table 4, Entry 1 and 2). This can be attributed to the conjugation of C≡N bond
and benzene ring, which reduced the electron density of the cyano group so that the
hydrogenation is unfavorable. In order to exclude the effect of steric hindrance to the reaction,
transfer hydrogenation of phenylacetonitrile was performed. It is clear in Table 4 that
phenylacetonitrile was reduced in short time with good yield of phenylethylamine (Table 4,
Entry 8), in agreement with our assumption. It took longer time for the transfer hydrogenation of
2-methylbenzonitrile, probable due to the steric hindrance of the ortho methyl group.
Subsequently, the reusability of [DBUH+][C4H9COO–] was investigated, and transfer
hydrogenation of benzonitrile was selected as the model reaction. After the reaction in every
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cycle, amine and unconverted nitrile was extracted with ethyl acetate, and the salts deposited at
room temperature. After filtration, the IL was washed by ethyl ether and dried at 70 ºC under
vacuum for 2 hours. Then it was ready to reuse in next cycle. The results are shown in Table 5. It
can be seen that the performance of [DBUH+][C4H9COO–] maintained even when it was recycled
for 6 times.
Table 4. Catalytic transfer hydrogenation of different nitrilesa
Entry
R
Time (h)
Product
GC yield Isolated yield
(except for Entry
11)
(%)
(%)
1
2
Ethyl
n-Propyl
3
3
90
88
89
91
70
78
81
87
85
78
-
85
82
86
87
65
71d
74
84
83
75
70
1a
1b
1c
1d
1e
1c
1g
1h
1i
3
Phenyl
8
4
4-Tolyl
8
5
2-Tolyl
14
8
6
4-Chlorophenyl
4-Methoxyphenyl
Benzyl
4-Nitrophenylb
1H-indol-2-yl
Isophthalonitrilec
7
8
8
4
9
8
10
11
8
1j
10
1k
aReaction conditions: IL (50 mL), nitriles (50 mmol), HCOOK (200 mmol, except for Entry 9
b
and 11), n(HCOOK):n(H2O)=1:2, catalyst (Raney nickel, 0.5 g), temperature (70 ºC). The
c
amount of HCOOK added is 600 mmol. The amount of HCOOK added is 400mmol d The
product is benzonitrile.
Table 5. Reusability of [DBUH+][C4H9COO–] for transfer hydrogenation of benzonitrilea
Cycle
Time
Yieldb (%)
1
2
3
4
5
6
8
8
8
8
8
8
89
87
88
87
85
87
aReaction conditions: IL (50 mL), benzonitrile (50 mmol), HCOOK (200 mmol), water
(400mmol), catalyst (Raney nickel, 0.5 g), temperature (70 ºC). bGC yield.
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Conclusions
Raney nickel catalyzed transfer hydrogenation of nitrile using formate as hydrogen donor was
proposed. Compared to previously used hydrogen donors, such as hydrazine and hydrazinium
monoformate, formate is less expensive and less hazardous. Three ILs, including
[DBUH+][C2H5COO–], [DBUH+][C3H7COO–] and [DBUH+][C4H9COO–], were prepared as
reaction medium. DBU based IL could promote the transfer hydrogenation obviously, and
[DBUH+][C4H9COO–] gave the best performance. Compared with commonly used organic and
inorganic solvents, DBU based ILs showed obvious advantage. The preparation of a DBU based
IL is simple and the IL can be reused for 6 times at least. The reaction proposed is clean and
environmentally benign.
Experimental Section
General procedure for preparation of ILs [DBUH+][C2H5COO–], [DBUH+][C3H7COO–]
and [DBUH+][C4H9COO–]
To a 100 mL three-necked flask cooled by ice bath, added DBU. Then carboxylic acid (0.9
equiv.) was added dropwise under stirring. After addition, the reaction mixture was stirred at
room temperature for 10 h. The unconverted residue was washed by ethyl ether, and the IL was
dried under vacuum at 70 ºC for 10 h to afford a light yellow viscous liquid.
1
[DBUH+][C2H5COO–]. H NMR (CH3OH-d4, 400 MHz, ppm): δ=1.08 (t, 3H), 1.64-1.84 (m,
6H), 2.00-2.06 (m, 2H), 2.13 (m, 2H, J = 7.6 Hz), 2.70-2.81 (m, 2H), 3.35 (t, 2H, J = 5.7 Hz),
3.45-3.48 (m, 1H), 3.55 (t, 2H, J = 5.9 Hz), 3.60-3.62 (m, 2H); 13C NMR (CH3OH-d4, 100 MHz,
ppm): δ=10.1, 19.1, 23.6, 26.2, 28.6, 30.7, 32.1, 37.9, 48.2, 53.9, 166.0, 177.6; Anal. Calcd for
[DBUH+][C2H5COO–]: C 63.68, H 9.80, N 12.38, O 14.14. Found: C 63.71, H 9.75, N 12.42, O
14.03.
[DBUH+][C3H7COO–]. 1H NMR (CH3OH-d4, 400 MHz, ppm): δ=0.93 (t, 3H), 1.55-1.65 (m, 2H,
J = 7.4 Hz), 1.71-1.83 (m, 6H), 2.00-2.06 (m, 2H), 2.10-2.13 (m, 2H), 2.70-2.80 (m, 2H), 3.35 (t,
2H, J = 5.8 Hz), 3.44-3.48 (m, 1H), 3.55 (t, 2H, J = 5.9 Hz), 3.59-3.62 (m, 2H); 13C NMR
(CH3OH-d4, 100 MHz, ppm): δ=13.3, 19.1, 19.6, 23.6, 26.2, 28.6, 32.1, 37.9, 40.0, 48.2, 53.9,
166.0, 177.6; Anal. Calcd for [DBUH+][C3H7COO–]: C 64.97, H 10.07, N 11.66, O 13.31.
Found: C 65.01, H 9.97, N 11.75, O 13.27.
[DBUH+][C4H9COO–]. 1H NMR (CH3OH-d4, 400 MHz, ppm): δ=0.91 (t, 3H), 1.29-1.39 (m, 2H,
J = 7.3 Hz), 1.53-1.60 (m, 2H), 1.65-1.82 (m, 6H), 2.00-2.06 (m, 2H), 2.12-2.16 (m, 2H),
2.68-2.77 (m, 2H), 3.34 (t, 2H, J = 5.7 Hz), 3.44-3.47 (m, 1H), 3.54 (t, 2H, J = 5.9 Hz),
3.60-3.61 (m, 2H); 13C NMR (CH3OH-d4, 100 MHz, ppm): δ=13.0, 19.0, 22.5, 23.6, 26.1, 28.58,
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28.6, 32.2, 37.7, 47.8, 53.9, 166.0, 177.6; Anal. Calcd for [DBUH+][C4H9COO–]: C 66.10, H
10.30, N 11.01, O 12.58. Found: C 66.21, H 10.24, N 11.10, O 12.45.
General procedure for catalytic transfer hydrogenation of nitriles
To a 100 mL three-necked flask added [DBUH+][C4H9COO–] (50 mL), nitrile (50 mmol),
sodium formate (250 mmol) and Raney nickel (0.5 g). Then the mixture was heated to 70 ºC and
reacted for 8 hours under stirring. After the reaction was completed, the mixture was cooled to
20 ºC and filtered, the filtrate was extracted with ethyl acetate for 3 times. The organic solution
was washed by dilute hydrochloric acid, the inorganic layer was separated and neutralized with
sodium hydroxide. The inorganic layer was extracted with ethyl acetate, then the product can be
obtained after removing ethyl acetate under vacuum at 60 ºC. The IL after filtration and
extraction was washed by ethyl ether and dried under vacuum at 70 ºC for 2 hours, then it was
ready for reuse. The catalyst was recycled by washing the deposit with water and filtering, but it
cannot be reused unless it is activated by hydrogen.
Propylamine (1a). Analyzed by GC-MS, MS (EI): m/z (rel. int.) 59 (9), 41 (5), 30 (100), 28 (8),
identical with commercial sample.
Butylamine (1b). Analyzed by GC-MS, MS (EI): m/z (rel. int.) 73 (7), 30 (100), 28 (5), identical
with commercial sample.
1
Benzylamine (1c). H NMR (CDCl3, 400 MHz, ppm): δ=1.34 (s, 2H), 3.62 (s, 2H), 7.07-7.19
(m, 5H); 13C NMR (CDCl3, 100 MHz, ppm): δ=46.2, 126.5, 126.9, 128.3, 143.4 15.
1
4-Methylbenzylamine (1d): H NMR (CDCl3, 400 MHz, ppm): δ=1.45 (brs, 2H), 2.32 (s, 3H),
13
3.89 (s, 2H), 7.12 (d, 2H, J = 8.0 Hz), 7.20 (d, 2H, J = 8.0 Hz); C NMR (CDCl3, 100 MHz,
ppm): δ=21.2, 46.0, 126.8, 129.7, 136.0, 140.7 16.
1
2-Methylbenzylamine (1e). H NMR (CDCl3, 400 MHz, ppm): δ=1.64 (brs, 2H), 2.31 (s, 3H),
13
3.78 (s, 2H), 7.15-7.22(m, 3H), 7.27 (d, 1H, J = 6.7 Hz); C NMR (CDCl3, 100 MHz, ppm):
δ=18.7, 43.9, 126.1, 126.7, 126.9, 130.2, 135.4, 141.1 17.
1
4-Methoxybenzylamine (1g). H NMR (CDCl3, 400 MHz, ppm): δ= 1.52 (brs, 2H), 3.73 (s,
3H), 3.76 (s, 2H), 6.84 (d, 2H, J = 8.8Hz), 7.17 (d, 2H, J = 8.5Hz); 13C NMR (CDCl3, 100 MHz,
ppm): δ=45.7, 55.2, 114.0, 128.5, 134.1, 158.7 15.
2-Phenethylamine (1h). 1H NMR (CDCl3, 400 MHz, ppm): δ=1.19 (s, 2H), 2.75 (t, 2H), 2,89 (t,
2H), 7.02-7.37 (m, 5H) 18; 13C NMR (CDCl3, 100 MHz, ppm): δ=40.5, 44.2, 126.1, 128.0, 128.7,
140.2 19.
1
4-aminobenzylamine (1i). H NMR (CDCl3, 400 MHz, ppm): δ= 2.02 (brs, 2H), 3.61 (s, 2H),
13
4.79 (s, 2H), 6.52 (d, 2H, J = 8.0Hz), 6.98 (d, 2H, J = 8.0Hz)20; C NMR (CDCl3, 100 MHz,
ppm): δ=46.1, 115.0, 128.4, 132.9, 147.221.
1
(1H-indol-2-yl)methanamine (1j). H NMR (DMSO-d6, 400 MHz, ppm): δ= 3.84 (s, 2H), 6.22
(s, 1H), 6.93 (t, 1H, J = 8.0Hz), 7.01 (t, 1H, J = 7.8Hz), 7.30 (d, 1H, J = 7.8Hz), 7.44 (d, 1H, J
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13
= 8.0Hz), 8.57 (s, 2H), 10.94 (brs, 1H); C NMR (DMSO-d6, 100 MHz, ppm): δ=57.4, 98.2,
111.1, 118.9, 119.6, 120.4, 128.5, 136.4, 141.822.
1
1,3-Phenylenedimethanamine (1k). H NMR (DMSO-d6, 400 MHz, ppm): δ= 2.59 (brs, 4H),
13
3.73 (s, 4H), 7.18 (d, 2H, J = 7.8 Hz), 7.24 (dd, 1H, J = 6.7, 6.5 Hz), 7.31 (s, 1H); C NMR
(DMSO-d6, 100 MHz, ppm): δ=46.1, 125.3, 126.1, 128.3, 144.2. EI-HRMS calcd for C8H12N2
(M+): 136.1000, found: 136.1002.
Acknowledgements
We acknowledge the funding support by a grant from the National Natural Science Foundation
of China (21076183, 21006087), and we are also grateful to Dr. Ying, A.G., who have given us
important suggestions and provided us materials for ionic liquid preparation.
References
1. (a) Addis, D.; Enthaler, S.; Junge, K.; Wendt, B.; Beller, M. Tetrahedron Lett. 2009, 50,
3654. (b) Enthaler, S.; Junge, K.; Addis, D.; Erre, G.; Beller, M. Chem. Sus. Chem. 2008,
1(12), 1006. (c) Enthaler, S.; Junge, K.; Addis, D.; Erre, G.; Beller, M. Chem. Eur. J. 2008,
14, 9191.
2. Xie, X.; Liotta, C. L.; Eckert, C. A. Ind. Eng. Chem. Res. 2004, 43, 7907.
3. Sarmah, B. K.; Barua, N. C., Tetrahedron 1991, 47, 8587.
4. Suda, K.; Hino, F.; Yijima, C., J. Org. Chem. 1986, 51, 4232.
5. Mebane, R. C.; Jensen, D. R.; Rickerd, K. R.; Gross, B. H. Synthetic. Commun. 2003, 33,
3373.
6. Mizushima, E.; Yamaguchi, M.; Yamagishi, T. J. Mol. Catal. a-Chem. 1999, 148 (1-2), 69.
7. Moiseev, I. I.; Tsirkov, G. A.; Gekhman, A. E.; Vargaftik, M. N. Mendeleev. Commun.
1997, (1), 1.
8. Zajac, W. W.; Siuda, J. F.; Nolan, M. J.; Santosus.Tm. J. Org. Chem. 1971, 36, 3539.
9. You, Q. D.; Zhou, H. Y.; Wang, Q. Z.; Lei, X. H. Acta Chim. Sinica 1993, 51, 85.
10. (a) Gowda, S.; Gowda, D. C. Tetrahedron 2002, 58, 2211. (b) Gowda, S.; Gowda, B. K. K.;
Gowda, D. C. Synthetic. Commun. 2003, 33, 281.
11. (a) Hut'ka, M.; Toma, S. Monatsh. Chem. 2008, 139, 793. (b) Hut'ka, M.; Toma, S. Monatsh.
Chem. 2009, 140, 1189. (c) Baan, Z.; Finta, Z.; Keglevich, G.; Hermecz, I. Green Chem.
2009, 11, 1937. (d) Kawasaki, I.; Tsunoda, K.; Tsuji, T.; Yamaguchi, T.; Shibuta, H.;
Uchida, N.; Yamashita, M.; Ohta, S. Chem. Commun. 2005, 2134.
12. Ying, A. G.; Wang, L. M.; Deng, H. X.; Chen, J. H.; Chen, X. Z.; Ye, W. D. Arkivoc 2009,
(xi), 288.
Page 135
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General Papers
ARKIVOC 2012 (viii) 128-136
13. Ying, A. G.; Liu, L.; Wu, G. F.; Chen, X. Z.; Ye, W. D.; Chen, J. H.; Zhang, K. Y. Chem.
Res. Chinese U. 2009, 25, 876.
14. Vanes, T.; Staskun, B. Org. Synth. 1988, 50-9, 631.
15. Haddenham, D.; Pasumansky, L.; DeSoto, J.; Eagon, S.; Singaram, B. J. Org. Chem. 2009,
74, 1964.
16. Kruger, T.; Vorndran, K.; Linker, T. Chem-Eur. J. 2009, 15, 12082.
17. Huang, W. H.; Zavalij, P. Y.; Isaacs, L. Org. Lett. 2008, 10, 2577.
18. Cho, S. D.; Song, S. Y.; Kim, K. H.; Zhao, B. X.; Ahn, C.; Joo, W. H.; Yoon, Y. J.; Falck, J.
R.; Shin, D. S. B Kor. Chem. Soc. 2004, 25, 415.
19. Border, C. L.; Craik, D. J.; Shehan, B. P. Magn. Reson. Chem. 1993, 31, 222.
20. King, J. F.; Rathore, R.; Lam, J. Y. L.; Guo, Z. R.; Klassen, D. F. J. Am. Chem. Soc. 1992,
114, 3028.
21. Brown, N. C.; Gambino, J.; Wright, G. E. J. Med. Chem. 1977, 20, 1186.
22. Fodor, L.; Csomos, P.; Mandity, I.; Bernath, G. Tetrahedron 2007, 63, 4983.
Page 136
©ARKAT-USA, Inc.