Vilsmeier reaction of enaminones: Efficient synthesis of halogenated pyridin-2(1H)-ones

Article abstract of DOI:10.1021/jo801959j

(Chemical Equation Presented) A facile and efficient one-pot synthesis of halogenated pyridin-2(1H)-ones from a series of readily available enaminones under Vilsmeier conditions is described, and a mechanism involving sequential halogenation, formylation, and intramolecular nucleophilic cyclization is proposed.

Full text of DOI:10.1021/jo801959j

the construction of the heterocyclic skeleton from appropriately
substituted acyclic precursors via Guareschi-Thorpe reaction,
intramolecular Dieckmann-type condensation, hetero Diels-Alder
reaction, and metal-mediated cycloaddition. 7-9The develop-
ment of efficient synthetic approaches for such nitrogen-
containing heterocycles has been the focus of intense research
for decades and continues to be an active area of research
today.
Vilsmeier Reaction of Enaminones: Efficient
Synthesis of Halogenated Pyridin-2(1H)-ones
Rui Zhang, Dingyuan Zhang, Yongli Guo, Guangyuan Zhou,
Zijiang Jiang, and Dewen Dong*
Changchun Institute of Applied Chemistry, Chinese Academy
of Sciences, Changchun 130022, China
Halogenated pyridin-2(1H)-ones are an important subset of
pyridin-2(1H)-ones, which have been utilized as useful inter-
mediates for the synthesis of various aza-heterocycles and
evaluated as a scaffold in natural product synthesis.10 Unfor-
tunately, most of the available approaches for accessing pyridin-
2(1H)-ones are not general for the preparation of halogenated
pyridin-2(1H)-ones. Recently the direct synthesis of halogenated
pyridin-2(1H)-ones from acyclic substrates has attracted a lot
dwdong@ciac.jl.cn
ReceiVed September 4, 2008
of interest in research.11,12 During the course of our studies on
13-15
Vilsmeier reactions,
we developed a facile one-pot
synthesis of halogenated pyridin-2(1H)-ones from either cyclo-
propyl amides or cyclic enaminones under Vilsmeier condi-
tions.14 The significance of the protocol relies on the combi-
nation of construction of the pyridin-2(1H)-one skeleton and
creation of its dense substitution patterns. As an expansion of
these studies, we investigated the Vilsmeier reaction of R-mono-
substituted ꢀ-oxo amides and successfully obtained a variety
of halogenated pyridin-2(1H)-ones (Scheme 1).15 It should be
noted that R-unsubstituted ꢀ-oxo amides underwent Vilsmeier
reactions to give halogenated pyridin-2(1H)-ones as a pair of
isomers. In connection with these studies and the aim to extend
the substrate scope and further clarify the mechanism involved,
we prepared a series of enaminones 1 from ꢀ-oxo amides and
A facile and efficient one-pot synthesis of halogenated
pyridin-2(1H)-ones from a series of readily available enami-
nones under Vilsmeier conditions is described, and a
mechanism involving sequential halogenation, formylation,
and intramolecular nucleophilic cyclization is proposed.
Functionalized pyridin-2(1H)-ones and their benzo-/hetero-
fused analogues represent an important class of organic aza-
heterocycles for their presence in numerous natural products
and synthetic organic compounds along with diverse bio-,
physio-, and pharmacological activities.1-3 In addition, func-
tionalized pyridin-2(1H)-ones have been used as versatile
intermediates in the synthesis of a wide range of nitrogen-
containing heterocycles, such as pyridine, piperidine, quino-
lizidine, and indolizidine alkaloids.3,4 Extensive work has
generated many synthetic approaches for pyridin-2(1H)-ones
including the modification of the preconstructed heterocyclic
ring by pyridinium salt chemistry and N-alkylation5,6 or through
(7) (a) Baron, H.; Renfry, H.; Thorpe, J. J. Chem. Soc 1904, 85, 1726. (b)
Aggarwal, V.; Sing, G.; Ila, H.; Junjappa, H. Synthesis 1982, 214. (c) Gibson,
K. R.; Hitzel, L.; Mortishire-Smith, R. J.; Gerhard, U.; Jelley, R. A.; Reeve,
A. J.; Rowley, M.; Nadin, A.; Owens, A. P. J. Org. Chem. 2002, 67, 9354. (d)
Chung, K. H.; Cho, K. Y.; Asami, Y.; Takahashi, N.; Yoshida, S. Heterocycles
1991, 32, 99.
(8) (a) Robin, A.; Julienne, K.; Meslin, J. C.; Deniaud, D. Tetrahedron Lett.
2004, 45, 9557. (b) Sainta, F.; Serckx-Poncin, B.; Hesbain-Frisque, A. M.;
Ghosez, L. J. Am. Chem. Soc. 1982, 104, 1428.
(9) (a) Varela, J. A.; Saa, C. Chem. ReV. 2003, 103, 3787. (b) Yamamoto,
Y.; Takagishi, H.; Itoh, K. Org. Lett. 2001, 3, 2117. (c) Padwa, A.; Sheehan,
S. M.; Straub, C. S. J. Org. Chem. 1999, 64, 8648. (d) Padwa, A.; Heidelbaugh,
T. M.; Kuethe, J. T. J. Org. Chem. 2000, 65, 2368.
(10) (a) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. (b) Choi,
W. B.; Houpis, I. N.; Churchill, H.; Molina, O.; Lynch, J. E.; Volante, R. P.;
Reider, P. J.; King, A. O. Tetrahedron Lett. 1995, 36, 4571. (c) Houpis, I. N.;
Choi, W. B.; Reider, P. J.; Molina, O.; Churchill, H.; Lynch, J.; Volante, R. P.
Tetrahedron Lett. 1994, 35, 9355. (d) Domagala, J. M. J. Heterocyclic Chem.
1984, 21, 1705. (e) Thomas, A. D.; Asokan, C. V. Tetrahedon lett. 2002, 43,
2273.
(11) (a) Marcoux, J.-F.; Marcotte, F.-A.; Wu, J.; Dormer, P. G.; Davies, I. W.;
Hughes, D.; Reider, P. J. J. Org. Chem. 2001, 66, 4194. (b) Agami, C.; Dechoux,
L.; Hebbe, S.; Moulinas, J. Synthesis 2002, 79. (c) Adams, J.; Hardin, A.;
Vounatsos, F. J. Org. Chem. 2006, 71, 9895.
(12) Chen, L.; Zhao, Y.; Liu, Q.; Cheng, C.; Piao, C. J. Org. Chem. 2007,
72, 9259.
(13) (a) Sun, S.; Liu, Y.; Liu, Q.; Zhao, Y.; Dong, D. Synlett 2004, 1731.
(b) Liu, Y.; Dong, D.; Liu, Q.; Qi, Y.; Wang, Z. Org. Biomol. Chem. 2004, 2,
28. (c) Wang, K.; Xiang, D.; Liu, J.; Pan, W.; Dong, D. Org. Lett. 2008, 10,
1691.
(14) (a) Xiang, D.; Yang, Y.; Zhang, R.; Liang, Y.; Pan, W.; Huang, J.;
Dong, D. J. Org. Chem. 2007, 72, 8593. (b) Pan, W.; Dong, D.; Wang, K.;
Zhang, J.; Wu, R.; Xiang, D.; Liu, Q. Org. Lett. 2007, 9, 2421.
(15) Xiang, D.; Wang, K.; Liang, Y.; Zhou, G.; Dong, D. Org. Lett. 2008,
10, 345.
(1) (a) Elbein, A. D.; Molyneux, R. J. In Alkaloids: Chemical and Biological
PerspectiVes; Pelletier, S. W., Ed.; Wiley: New York, 1981; Vol. 5, p 1. (b) Li,
Q.; Mitscher, L. A.; Shen, L. L. Med. Res. ReV. 2000, 20, 231. (c) Nagarajan,
M.; Xiao, X. S.; Antony, S.; Kohlhagen, G.; Pommier, Y.; Cushman, M. J. Med.
Chem. 2003, 46, 5712.
(2) (a) Dolle, R. E.; Nicolaou, K. C. J. Am. Chem. Soc. 1985, 107, 1691. (b)
Cox, R. J.; O’Hagan, D. J. Chem. Soc., Perkin Trans. 1 1991, 2537.
(3) (a) Jones, G.; Stanforth, S. P. In Organic Reactions; Paquette, L. A.,
Ed.; Wiley: New York, 1997; Vol. 49, pp 1-330. (b) Scriven, E. F. V. In
ComprehensiVe Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W., Eds.;
Pergamon Press: Oxford, 1984; Vol. 2. (c) Jones, G. Pyridines and Their Benzo
Derivatives: Synthesis. In ComprehensiVe Heterocyclic Chemistry; Boulton, A.,
McKillop, A., Eds.; Pergamon Press: Oxford, 1984; Chapter 2.80, p 395.
(4) (a) Torres, M.; Gil, S.; Parra, M. Curr. Org. Chem. 2005, 9, 1757. (b)
Jayasinghe, L.; Abbas, H. K.; Jacob, M. R.; Herath, W. H. M. W.; Nanayakkara,
N. P. D. J. Nat. Prod. 2006, 69, 439. (c) Angibaud, P. R.; Venet, M. G.; Filliers,
W.; Broeckx, R.; Ligny, Y. A.; Muller, P.; Poncelet, V. S.; End, D. W. Eur. J.
Org. Chem. 2004, 479. (d) Litvinov, V. P. Russ. Chem. ReV. 2003, 72, 69.
(5) (a) Decker, H. Chem. Ber. 1892, 25, 443. (b) Comins, D. L.; Saha, J. K.
J. Org. Chem. 1996, 61, 9623. (c) Du, W. Tetrahedron 2003, 59, 8649.
(6) (a) Comins, D. L.; Gao, J. L. Tetrahedron Lett. 1994, 35, 2819. (b) Hu,
T.; Li, C. Org. Lett. 2005, 7, 2035. (c) Cristau, H.-J.; Cellier, P. P.; Spindler,
J.-F.; Taillefer, M. Chem. Eur. J. 2004, 10, 5607.
9504 J. Org. Chem. 2008, 73, 9504–9507
10.1021/jo801959j CCC: $40.75 2008 American Chemical Society
Published on Web 11/12/2008

SCHEME 1
SCHEME 2. Reaction of 1a with Vilsmeier Reagent
PBr3/DMF
examined their reaction behaviors toward Vilsmeier conditions.
By this research, we achieved an efficient synthesis of substi-
tuted pyridin-2(1H)-ones bearing formyl and halo substituents
at the 3 and 4 positions, respectively. Herein, we wish to report
our experimental results and present a proposed mechanism for
the cyclization.
revealed that 3.0 equiv of PBr3/DMF was effective for the
pyridin-2(1H)-one synthesis and the yield of 2a1 depended on
the reaction temperature. The optimal results were obtained
when the reaction of 1a was performed with 4.0 equiv of PBr3/
DMF at 125 °C for 1.0 h, whereby the reaction exclusively
afforded 2a1 in 68% yield (Table 1, entry 1).
Enaminones and related compounds possessing the conjugated
system N-CdC-CdO are versatile synthetic intermediates that
combine the ambident nucleophilicity of enamines with the
ambident eletrophilicity of enones.16 So far, they have found a
broad spectrum of applications in the synthesis of R- and
ꢀ-amino acid compounds,17 alkaloids,18 peptides,19 and other
aza-heterocyclic compounds.20 Recently, Elmaati and co-
workers described the synthesis of 2-[(dimethylamino)methyl-
ene]-3-oxo-N-phenylbutanamide 1a, an enaminone, by the
reaction of 3-oxo-N-phenylbutanamide with N,N-dimethyl for-
mamide dimethyl acetal (DMFDMA) in xylene under reflux.21
In the present work, we improved the Elmaati synthesis
conditions and successfully prepared a series of enaminones 1
from commercially available ꢀ-oxo amides and DMFDMA in
the presence of K2CO3 in DMF at room temperature in good
yields (up to 80%). With substrates 1 in hand, we selected 1a
as a model compound to examine its reaction behavior under
Vilsmeier conditions.
TABLE 1. Vilsmeier Reactions of Enaminones 2a
entry
1
Ar
X
2
yields (%)b
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1a
1b
1c
1d
1e
1f
Ph
Br
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
Cl
Cl
Cl
Cl
2a1
2b1
2c1
2d1
2e1
2f1
2g1
2a2
2b2
2c2
2d2
2e2
2f2
68
67
70
57
63
56
65
85
68
76
70
81
84
79
2-MeOC6H4
4-MeC6H4
2-MeC6H4
4-ClC6H4
2,4-Me2C6H3
5-Cl-2-MeOC6H3
Ph
2-MeOC6H4
4-MeC6H4
2-MeC6H4
4-ClC6H4
2,4-Me2C6H3
5-Cl-2-MeOC6H3
9
10
11
12
13
14
Thus, the reaction of 1a with Vilsmeier reagent PBr3/DMF
(5.0 equiv) was first attempted at room temperature. The
resulting mixture quickly turned brown and became viscous.
The reaction proceeded smoothly (monitored by TLC) and
furnished a product (37% yield) after workup and purification
by column chromatography of the resulting mixture. From the
spectral and analytical data, the product was characterized as
4-bromo-2-oxo-1-phenyl-1,2-dihydropyridine-3-carbaldehyde
2a1 (Scheme 2). It should be mentioned that side products were
obtained from the reaction system as an inseparable mixture
by column chromatography over silica gel.
1g
2g2
a Reagents and conditions: (i) for entries 1-7, PBr3/DMF (4.0 equiv),
125 °C, 1.0-1.5 h; (ii) for entries 8-14, POCl3/DMF (4.0 equiv), 125
°C, 0.5-1.0 h. b Isolated yields.
Under the identical conditions as for 2a1 in Table 1, entry 1,
a series of reactions of enaminones 1 was subjected to PBr3/
DMF (4.0 equiv) at 125 °C, and some of the results are
summarized in Table 1. The efficiency of the cyclization proved
to be suitable for enaminones 1b-g, affording the corresponding
substituted pyridin-2(1H)-ones 2b-g in good yields (Table 1,
entries 2-7). The versatility of this pyridin-2(1H)-one synthesis
was further evaluated by performing the enaminones 1 with
another Vilsmeier reagent POCl3/DMF under the similar condi-
tions (Table 1, entries 8-14). The results demonstrated the
efficiency and synthetic interest of the cyclization reaction with
respect to varied Vilsmeier reagents and substrates 1 bearing
variable amide groups.
It should be noted that the richness of the functionality,
e.g., halogen and formyl groups, of the pyridin-2(1H)-ones
of type 2 obtained may render them extremely versatile as
synthons in other synthetic transformations. For example, the
neighboring halogen and formyl groups make it possible to
establish new C-C and C-N bonds and may provide a ready
access to the ring-fused heterocycles. Recently, Wittman and
Ni reported a novel class of 3-(1H-benzo[d]imidazol-2-yl)-
pyridin-2(1H)-one as potent kinase inhibitors (Chart 1).22 In
our ongoing research, we are focusing on the synthesis of
substituted 3-(1H-benzo[d]imidazol-2-yl)-pyridin-2(1H)-ones
using pyridin-2(1H)-ones 2 as the scaffolds, and the related
results will be published in due course.
These results and our previous studies14,15 encouraged us to
optimize the reaction conditions, including reaction temperature
and the ratio of Vilsmeier reagent PBr3/DMF to 1a, with the
aim of improving the yield of 2a1. A series of experiments
(16) Greenhill, J. V. Chem. Soc. ReV. 1977, 6, 277.
(17) (a) Jerphagnon, T.; Renaud, J.-L.; Demonchaux, P.; Ferreira, P.; Bruneau,
C. AdV. Synth. Catal. 2004, 346, 33. (b) Dai, Q.; Yang, W.; Zhang, X. Org.
Lett. 2005, 7, 5343. (c) Kubryk, M.; Hansen, K. B. Tetrahedron: Asymmetry
2006, 17, 205. (d) Lubell, W. D.; Kitamura, M.; Noyori, R. Tetrahedron:
Asymmetry 1991, 2, 543.
(18) (a) David, C.; Blot, J.; Bellec, C.; Fargeau-Bellasoued, M.-C.; Haviari,
G.; Ce´le´rier, J.-P.; Lhommet, G.; Gramain, J.-C.; Gardette, D. J. Org. Chem.
1999, 64, 3122. (b) Michael, J. P.; Parsons, A. S. Tetrahedron 1996, 52, 2199.
(c) Ferraz, H; M, C.; de Oliveira, E. O.; Payret-Arrua, M. E.; Brandt, C. A. J.
Org. Chem. 1995, 60, 7357.
(19) Beholz, L. G.; Benovsky, P.; Ward, D. L.; Barta, N. S.; Stille, J. R. J.
Org. Chem. 1997, 62, 1033.
(20) (a) Elassar, A.-Z. A.; El-Khair, A. A. Tetrahedron 2003, 59, 8463. (b)
Agami, C.; Dechoux, L.; Hebbe, V. Tetrahedron Lett. 2002, 43, 2521. (c)
Hassneen, H. M.; Abdallah, T. A. Molecules 2003, 8, 333. (d) Sklenicka, H. M.;
Hsung, R. P.; McLaughlin, M. J.; Wie, L.; Gerasyuto, A. I.; Brennessel, W. B.
J. Am. Chem. Soc. 2002, 124, 10435. (e) Irlapati, N. R.; Baldwin, J. E.; Adlington,
R. M.; Pritchard, G. J.; Cowley, A. Org. Lett. 2003, 5, 2351. (f) Navarro-Vazquez,
A.; Garcia, A.; Dominguez, D. J. Org. Chem. 2002, 67, 3213.
(21) Elmaa, T. A.; Said, S.; Elentin, N. A.; Sofan, M.; Khodeir, N. Pol.
J. Chem. 2002, 76, 945.
J. Org. Chem. Vol. 73, No. 23, 2008 9505

CHART 1. Structure of Substituted 3-(1H-Benzo[d]imidazol-
2-yl)-pyridin-2(1H)-ones
SCHEME 4. Plausible Mechanism of the Reaction of
Enaminones 1 under Vilsmeier Conditions
To gain insight into the mechanism of the cyclization of
enaminones 1, the reaction of 1b with 4.0 equiv of POCl3/ DMF
was performed at room temperature for 10 min and then
quenched with water. After workup and purification by column
chromatography of the resulting mixture, 4-chloro-2-oxo-1,2-
dihydropyridine-3-carbaldehyde 2b2, 4-chloro-2-oxo-1,2-dihy-
dropyridine-3,5-dicarbaldehyde 3b2, and 3-chloro-2-formyl-but-
2-enamide 4b2 were obtained in 26%, 12%, and 33% yields,
respectively (Scheme 3).
SCHEME 3. Reaction of 1b with Vilsmeier Reagent
POCl3/DMF
In summary, a facile and efficient one-pot synthesis of
halogenated pyridin-2(1H)-ones of type 2 is developed from
the Vilsmeier reactions of enaminones 1, which involves
sequential halogenation, formylation, and intramolecular
nucleophilic cyclization reactions. The simple execution,
readily available substrates, mild conditions, high yields, and
wide range of synthetic potential of the products make this
protocol very attractive. Synthetic transformations using the
functionalized pyridin-2(1H)-ones 2 as scaffolds are currently
under investigation in our laboratory.
On the basis of all of the results obtained together with
our previous studies,14,15 a plausible mechanism for the
cyclization of enaminone 1 is presented in Scheme 4. The
overall transformation commences from the halogenation of
1, mediated by Vilsmeier reagent (VR),23,24 to generate
enolate A that can be transformed into compound 4 upon
treatment with water. Activated by the adjacent enolate and
aryl groups, the amino group of A undergoes Vilsmeier-Haack
reaction to generate intermediate B. An intramolecular
cyclization reaction of B gives intermediate C, which sheds
dimethylamine to afford intermediate D. In another pathway,
further formylation of intermediate B leads to the formation
of intermediate E, followed by an intramolecular cyclization
to F. At high temperature, 125 °C for example, F undergoes
deformylation to give D also. Upon treatment with water, D
is finally converted into the pyridin-2(1H)-one of type 2,
whereas F is converted into the pyridin-2(1H)-one of type
3.
Experimental Section
Typical Procedure for the Synthesis of Substituted
Pyridin-2(1H)-ones 2. Synthesis of 2a1. The Vilsmeier reagent
was prepared by adding PBr3 (8.0 mmol) dropwise into ice-
cold dry DMF (5 mL) under stirring. The mixture was then
stirred for 15 min at 0 °C. To the above Vilsmeier reagent was
added 1a (2.0 mmol) as a solution in DMF (20 mL). The mixture
was heated to 125 °C and stirred for 1.0 h. After cooling to
room temperature, the resulting mixture was poured into
saturated aqueous NaCl (100 mL), which was extracted with
dichloromethane (3 × 30 mL). The combined organic phase was
washed with water, dried over anhydrous MgSO4, filtered, and
evaporated in vacuo. The crude product was purified by flash
silica gel chromatography (petroleum ether/ethyl acetate ) 4:1,
(22) (a) Velaparthi, U.; Liu, P.; Balasubramanian, B.; Carboni, J.; Attar, R.;
Gottardis, M.; Li, A.; Greer, A.; Zoeckler, M.; Wittman, M. D.; Vyas, D. Bioorg.
Med. Chem. Lett. 2006, 16, 421. (b) Ni, Z.-J.; Barsanti, P.; Brammeier, N.; Diebes,
A.; Poon, D. J.; Ng, S.; Pecchi, S.; Pfister, K.; Renhowe, P. A.; Ramurthy, S.;
Wagman, A. S.; Bussiere, D. E.; Le, V.; Zhou, Y.; Jansen, J. M.; Ma, S.; Gesner,
T. G. Bioorg. Med. Chem. Lett. 2006, 16, 3121. (c) Wittman, M.; Carboni, J.;
Attar, R.; Balasubramanian, B.; Balimane, P.; Brassil, P.; Beaulieu, F.; Chang,
C.; Clarke, W.; Dell, J.; Eummer, J.; Frennesson, D.; Gottardis, M.; Greer, A.;
Hansel, S.; Hurlburt, W.; Jacobson, B.; Krishnananthan, S.; Lee, F. Y.; Li, A.;
Lin, T.-A.; Liu, P.; Ouellet, C.; Sang, X.; Saulnier, M. G.; Stoffan, K.; Sun, Y.;
Velaparthi, U.; Wong, H.; Yang, Z.; Zimmermann, K.; Zoeckler, M.; Vyas, D.
J. Med. Chem. 2005, 48, 5639. (d) Wittman, M. D.; Balasubramanian, B.; Stoffan,
K.; Velaparthi, U.; Liu, P.; Krishnanathan, S.; Carboni, J.; Li, A.; Greer, A.;
Attar, R.; Gottardis, M.; Chang, C.; Jacobson, B.; Sun, Y.; Hansel, S.; Zoeckler,
M.; Vyas, D. M. Bioorg. Med. Chem. Lett. 2007, 17, 974. (e) Velaparthi, U.;
Liu, P.; Balasubramanian, B.; Carboni, J.; Attar, R.; Gottardis, M.; Li, A.; Greer,
A.; Zoeckler, M.; Wittman, D. M.; Vyas, D. Bioorg. Med. Chem. Lett. 2007,
17, 3072.
1
v/v) to give 2a1 as a white solid (68%): mp 187-189 °C; H
NMR (500 MHz, CDCl3): δ 6.40 (d, J ) 7.0 Hz, 1H), 7.37 (d,
J ) 7.0 Hz, 2H), 7.49-7.54 (m, 4H), 10.40 (s, 1H); 13C NMR
(23) (a) The Vilsmeier Reaction of Non-Aromatic Compounds. In Organic
Reactions; Jones, G., Stanforth, S. P., Eds.; John Wiley and Sons: New York,
2000; Vol. 56, p 355. (b) Jutz, C. Iminium Salts in Organic Chemistry In
AdVances in Organic Chemistry; Bo¨hme, H., Viehe, H. G., Eds.; John Wiley:
New York, 1976; Vol. 9, Part I, p 225.
(24) (a) Marson, C. M. Tetrahedron 1992, 48, 3659. (b) Tebby, J. C.; Willetts,
S. E. Phosphorus Sulfur 1987, 30, 293. (c) Meth-Cohn, O.; Tarnowski, B. AdV.
Heterocycl. Chem. 1981, 31, 207. (d) Reichardt, C. J. Prakt. Chem. 1999, 341,
609. (e) Gangadasu, B.; Narender, P.; Bharath Kumar, S.; Ravinder, M.; Ananda
Rao, B.; Ramesh, Ch.; China Raju, B.; Jayathirtha Rao, V. Tetrahedron 2006,
62, 8398. (f) Thomas, A. D.; Asokan, C. V. Tetrahedron 2004, 60, 5069.
9506 J. Org. Chem. Vol. 73, No. 23, 2008

(100 MHz, CDCl3): δ 109.6, 122.0, 126.2, 129.4, 129.6, 139.1,
141.8, 150.5, 161.4, 188.4. Anal. Calcd for C12H8BrNO2: C,
51.83; H, 2.90; N, 5.04. Found: C, 51.64; H, 2.97; N, 5.12.
Supporting Information Available: Experimental details,
full characterization data, and copies of NMR spectra for
compounds 1-4. This material is available free of charge
via the Internet at http://pubs.acs.org.
Acknowledgment. Financial support of this research by the
National Natural Science Foundation of China (20572013 and
20711130229), the Ministry of Education of China (105061),
and the Department of Science and Technology of Jilin
Province (20050309) is greatly acknowledged.
JO801959J
J. Org. Chem. Vol. 73, No. 23, 2008 9507