A new synthesis of 2-substituted pyridines via aluminum chloride induced heteroarylation of arenes and heteroarenes

Article abstract of DOI:10.1021/jo047944h

(Chemical Equation Presented) We herein report a new synthesis of 2-(hetero)aryl-substituted pyridines via heteroarylation of arenes/heteroarenes through AlCl₃-induced C-C bond-forming reactions. 2-Halopyridines bearing an electron-withdrawing group were reacted with a number of (hetero)arenes to give 2-aryl/heteroaryl-substituted pyridines in good yields.

Full text of DOI:10.1021/jo047944h

flavor compounds of cocoa,5 tobacco,5 and orange oil.6
Among the diverse approaches that have been discovered
for the synthesis of 2-aryl/heteroaryl pyridines, the
transition-metal-catalyzed cross-couplings have proven
to be an important method and are being utilized
extensively. These include coupling of a 2-halopyridine
with a aryl halide in the presence of (a) (PPh3)4Pd-active
Zn,7a-b (b) lithium naphthalenide-ZnCl2-(PPh3)4Pd,7c (c)
NiBr2byp-Bu4NBF4 under electrolysis,7d (d) (PPh3)4Pd,
Me3SnSnMe3,7e or (e) Pd(OAc)2 under phase-transfer
conditions.7f Alternatively, 2-arylpyridines were pre-
pared via Pd-catalyzed reaction of a 2-halopyridine with
a variety of organometallic reagents namely ArZnCl,8a-b
ArMnCl,8c ArSi(OMe)3,8d Ar2InCl,8e Ar3Bi,8f ArLi,8b
ArMgX,8g or KArBF3.8f The Suzuki coupling of 2-halopy-
ridines with arylboronic acids has been an efficient and
powerful method for the preparation of 2-aryl/heteroaryl
pyridines.9 This carbon-carbon bond-forming reaction
has been employed widely due to the versatile nature of
this protocol, increased functional group toleration, and
improved yields. Despite being quite versatile, the syn-
thesis of 2-aryl/heteroaryl pyridine employing Suzuki
cross-coupling reaction involves the use of expensive
palladium catalyst and therefore may not be suitable for
the large-scale preparation of these compounds. More-
over, in many cases the required boronic acids are either
not available commercially or their preparations often
A New Synthesis of 2-Substituted Pyridines
via Aluminum Chloride Induced
Heteroarylation of Arenes and
Heteroarenes†
Manojit Pal,* Venkateswara Rao Batchu, Indu Dager,
Nalivela Kumara Swamy, and Srinivas Padakanti
Chemistry-Discovery Research, Dr. Reddy’s Laboratories
Ltd., Bollaram Road, Miyapur, Hyderabad 500049, India
manojitpal@drreddys.com
Received November 19, 2004
We herein report a new synthesis of 2-(hetero)aryl-substi-
tuted pyridines via heteroarylation of arenes/heteroarenes
through AlCl3-induced C-C bond-forming reactions. 2-
Halopyridines bearing an electron-withdrawing group were
reacted with a number of (hetero)arenes to give 2-aryl/het-
eroaryl-substituted pyridines in good yields.
(4) (a) Lin, L.-F.; Lee, S.-J.; Chen, C.-T. Heterocycles 1977, 7, 347-
352. (b) Du Priest, M. T.; Schmidt, C. L.; Kuzmich, D.; Williams, S. B.
J. Org. Chem. 1986, 51, 2021-2023.
We describe here the first AlCl3-induced C-C bond-
forming reaction between 2-halopyridines and arenes or
heteroarenes, such reactions being only known using
transition-metal catalysts.
The prevalence of pyridines in nature (e.g., in the
coenzyme vitamin B6 family and in numerous alkaloids)1
and their central role as versatile building bocks in the
synthesis of natural products2 as well as biologically
active compounds3 has led to a continued interest in the
practical synthesis of pyridine derivatives, especially
2-substituted pyridines. For example, 2-arylpyridines are
intermediates in the synthesis of physiologically active
products, such as antitumor compounds.4 Some simple
2-alkyl(aryl)pyridines have been identified as natural
(5) Maarse, H.; Visscher, C. A. In Volatile Compounds in Food;
Grafische Industrie Kreon Zeist: The Netherlands, 1989; Vol II, pp
648, 703, 1059.
(6) Thomas, A. F.; Bassols, F. J. Agric. Food Chem. 1992, 40, 2236-
2243.
(7) (a) Sakamoto, T.; Kondo, Y.; Murata, N.; Yamanaka, H. Tetra-
hedron Lett. 1992, 33, 5373-5374. (b) Sakamoto, T.; Kondo, Y.; Murata,
N.; Yamanaka, H. Tetrahedron 1993, 49, 9713-9720. (c) Kondo, Y.;
Murata, N.; Sakamoto, T. Heterocycles 1994, 37, 1467-1468. (d)
Gosmini, C.; Lasry, S.; Nedelec, J.-Y.; Perichon, J. Tetrahedron 1998,
54, 1289-1298. (e) Zhang, N.; Thomas, L.; Wu, B. J. Org. Chem. 2001,
66, 1500-1502. (f) Hassan, J.; Hathroubi, C.; Gozzi, C.; Lemaire, M.
Tetrahedron 2001, 57, 7845-7856.
(8) (a) Negishi, E.-i.; Luo, F.-T.; Frisbee, R.; Matsushita, H. Hetero-
cycles 1982, 18, 117-122. (b) Gauthier, D. R.; Szumigala, R. H.;
Dormer, P. G.; Armstrong, J. D.; Volante, R. P.; Reider, P. J. Org. Lett.
2002, 4, 375-378. (c) Riguet, E.; Alami, M.; Cahiez, G. Tetrahedron
Lett. 1997, 38, 4397-4400. (d) Lee, H. M.; Nolan, S. P. Org. Lett. 2000,
2, 2053-2056. (e) Journal; T., Kazuaki; Yorimitsu, H.; Shinokubo, H.;
Matsubara, S.; Oshima, K. Org. Lett. 2001, 3, 1997-2000. (f) Rao, M.
L. N.; Yamazaki, O.; Shimada, S.; Tanaka, T.; Suzuki, Y.; Tanaka, M.
Org. Lett. 2001, 3, 4103-4106. (g) Bonnet, V.; Mongin, F.; Trecourt,
F.; Queguiner, G.; Knochel, P. Tetrahedron 2002, 58, 4429-4438. (h)
Molander, G. A.; Biolatto, B. J. Org. Chem. 2003, 68, 4302-4314.
(9) (a) Feuerstein, M.; Doucet, H.; Santelli, M. J. Organomet. Chem.
2003, 687, 327-336. (b) Leadbeater, N. E.; Marco, M. J. Org. Chem.
2003, 68, 5660-5667. (c) Zhao, Y.; Zhou, Y.; Ma, D.; Liu, J.; Li, L.;
Zhang, T. Y.; Zhang, H. Org. Biomol. Chem. 2003, 1, 1643-1646. (d)
Leadbeater, N. E.; Marco, M. Angew. Chem., Int. Ed. 2003, 42, 1407-
1409. (e) Feuerstein, M.; Doucet, H.; Santelli, M. Tetrahedron Lett.
2001, 42, 5659-5662. (f) Villemin, D.; Frederic, C. Tetrahedron Lett.
2001, 42, 639-642. (g) Stavenuiter, J.; Hamzink, M.; Van der Hulst,
R.; Zomer, G.; Westra, G.; Kriek, E. Heterocycles 1987, 26, 2711-2716.
(h) Feuerstein, M.; Doucet, H.; Santelli, M. J. Organomet. Chem. 2003,
687, 327-336. (i) Adjabeng, G.; Brenstrum, T.; Wilson, J.; Frampton,
C.; Robertson, A.; Hillhouse, J.; McNulty, J.; Capretta, A. Org. Lett.
2003, 5, 953-956. (j) Kogan, V.; Aizenshtat, Z.; Popovitz-Biro, R.;
Neumann, R. Org. Lett. 2002, 4, 3529-3532. (k) Botella, L.; Najera,
C. J. Organomet. Chem. 2002, 663, 46-57. (l) Liu, S.-Y.; Choi, M. J.;
Fu, G. C. Chem. Commun. 2001, 23, 2408-2409. (m) Lohse, O.;
Thevenin, P.; Waldvogel, E. Synlett 1999, 45-48.
† DRL publication no. 459.
(1) For reviews, see: (a) Plunkett, A. O. Nat. Prod. Rep. 1994, 11,
581-590. (b) Daly, J. W.; Pinder, A. R. Nat. Proc. Rep. 1992, 9, 491-
504. (c) Spande, T. F. In The Alkaloids; Brossi, A., Ed.; Academic
Press: New York, 1987; Vol. 31.
(2) (a) Wang, Y.; Dong, X.; Larock, R. C. J. Org. Chem. 2003, 68,
3090-3098. (b) Moody, C. J.; Hughes, R. A.; Thompson, S. P.; Alcaraz,
L. Chem. Commun. 2002, 1760-1761. (c) Bach, T.; Heuser, S. Synlett
2002, 2089-2091.
(3) For selected example, see: (a) Sutherland, A.; Gallagher, T.;
Sharples, C. G. V.; Wonnacott, S. J. Org. Chem. 2003, 68, 2475-2478.
(b) Cosford, N. D. P.; Tehrani, L.; Roppe, J.; Schweiger, E.; Smith, N.
D.; Anderson, J.; Bristow, L.; Brodkin, J.; Jiang, X.; McDonald, I.; Rao,
S.; Washburn, M.; Varney, M. A. J. Med. Chem. 2003, 46, 204-206.
(c) Enyedy, I. J.; Sakamury, S.; Zaman, W. A.; Johnson, K. M.; Wang,
S. Biorg. Med. Chem. Lett. 2003, 13, 513-517. (d) Faul, M. M.; Ratz,
A. M.; Sullivan, K. A.; Trankle, W. G.; Winnerroski, L. L. J. Org. Chem.
2001, 66, 5772-5782. Bouras, A.; Boggetto, N.; Benatalah, Z.; de Rosny,
E.; Sicsic, S.; Reboud-Ravaux, M. J. Med. Chem. 1999, 42, 957-962.
(e) Phillips, G.; Davey, D. D.; Eagen, K. A.; Koovakkat, S. K.; Liang,
A.; Ng, H. P.; Pinkerton, M.; Trinh, L.; Whiltow, M.; Beatty, A. M.;
Morrissey, M. M. J. Med. Chem. 1999, 42, 1749-1756.
10.1021/jo047944h CCC: $30.25 © 2005 American Chemical Society
Published on Web 02/11/2005
2376
J. Org. Chem. 2005, 70, 2376-2379

SCHEME 1a
a Reagents and conditions: (a) AlCl3, dichloroethane, 50-80 °C,
12-15 h.
TABLE 1. AlCl3-Induced Heteroarylation of Arenes and
Heteroarenes
FIGURE 1. AlCl3-induced C-C bond-forming reaction.
involve cumbersome synthetic procedures. In our effort
toward the synthesis of various heterocyclic structures,10
we have reported a new approach toward the formation
of Caryl-Caryl bond very recently.11a-c In this approach,
an arene or heteroarene was reacted with the appropriate
heteroaryl chloride in the presence of AlCl3 to generate
a variety of heterocyclic compounds (Figure 1) of potential
biological interest. Herein we now wish to report a novel
and scalable synthesis of 2-aryl/heteroaryl pyridines
using a AlCl3 induced C-C bond-forming reaction. While
the Friedel-Crafts alkylation and acylation have been
used widely and are well documented in the literature,
the present AlCl3-induced heteroarylation, however, has
not been exploited well in organic synthesis.11d
In our earlier approach for the AlCl3-induced het-
eroarylation of arenes and heteroarenes we have utilized
a heteroaryl chloride as a coupling agent that contains
an -NdN-C(Cl)- moiety. We, however, did not explore
the use of a heteroaryl halide containing -NdC(X)-
moiety in our heteroarylation reaction. We anticipated
that the development of such a methodology would be
useful particularly in the synthesis of 2-aryl- and het-
eroaryl-substituted pyridines of medicinal as well as
synthetic value. In the beginning of our study we choose
commercially available 2-bromo-5-nitropyridine 1a (1; X
) Br) as a heteroaryl halide for the heteroarylation of
1,3,5-trimethoxybenzene 2a (Scheme 1). Thus, a mixture
of 1a (1.26 mmol), 2a (1.25 mmol) and AlCl3 (1.51 mmol)
in dichloroethane (10 mL) was stirred at room temper-
ature for 1 h and then at 80 °C for 24h. The pyridine
substrate was completely consumed after 24 h, and the
desired 5-nitro-2-(2,4,6-trimethoxyphenyl)pyridine 3a was
isolated in 80% yield. We then examined the reactivity
of 2-chloro-5-nitropyridine 1b in this AlCl3-induced het-
eroarylation reaction. The interest in using heteroaryl
chlorides stems from the fact that chlorides are available
a Yield of isolated products.
in far greater number and their use is more economical.
Encouragingly, the chloro derivative 1b was found to be
equally effective in this reaction affording the product
3a in 76% yield. The results of this study are summarized
in Table 1. It is evident from Table 1 that 3a could be
isolated in almost same yield regardless of the use of
2-chloro- or 2-bromopyridine (entries 1 and 2, Table 1).
A similar observation was noted by Kelly and Lang in a
reactivity studies of pyridine substituted with bromine
and triflate in the presence of palladium catalysts.12a The
use of relatively less electron-rich arenes12b such as 2,4-
dimethoxybenzene (2b) and benzene-1,3-diol (2c) in place
of 2a was also examined which afforded the desired
product, i.e., 3b and 3c, respectively, in acceptable yields
(entries 3-6, Table 1). It is noteworthy that the het-
eroarylation of benzene-1,3-diol (2c) occurred at the ring
carbon rather than oxygen.12c
(10) For example, see: (a) Pal, M.; Rao, V. V.; Srinivas P.; Murali
N.; Akhila V.; Premkumar M.; Rao, C. S.; Misra, P.; Ramesh M.; Rao
Y. K. Indian J. Chem. 2003, 42B, 593-601. (b) Pal, M.; Veeramaneni,
V. R.; Nagaballi, M.; Kalleda, S. R.; Misra, P.; Casturi, S. R.;
Yeleswarapu, K. R. Bioorg. Med. Chem. Lett. 2003, 13, 1639-1643.
(c) Pal, M.; Madan, M.; Srinivas, P.; Pattabiraman, V. R.; Kalleda, S.
R.; Akhila, V.; Ramesh, M.; Rao Mamidi, N. V. S.; Casturi, S. R.; Malde,
A.; Gopalakrishnan, B.; Yeleswarapu, K. R. J. Med. Chem. 2003, 46,
3975-3984.
(11) (a) Pal, M.; Batchu, V. R.; Khanna, S.; Yeleswarapu, K. R.
Tetrahedron 2002, 58, 9933-9940. (b) Pal, M.; Batchu, V. R.; Para-
suraman, K.; Yeleswarapu, K. R. J. Org. Chem. 2003, 68, 6806-6809.
Also see: (c) Pal, M.; Dakarapu, R.; Padakanti, S. J. Org. Chem. 2004,
69, 2913-2916. (d) For the synthesis of 2- and 4-(2,4-dihydroxyphenyl)-
quinoline via condensation reaction of 2- and 4-chloroquinoline with
resorcinol in the presence of AlCl3, see: Kepinskaya, I. B.; Makarova,
Z. S.; Koptyug, V. A. Zh. Org. Khim. 1980, 16, 1263-1268. Chem. Abstr.
1980, 93, 185326.
Since the planned strategy toward the synthesis of
2-arylpyridines via AlCl3-induced C-C bond formation
(12) (a) Kelly, T. R.; Lang, F. J. Org. Chem. 1996, 61, 4623-4633.
(b) The use of arenes possessing a single electron-donating group such
as anisole, N,N-dimethylaniline, was examined. These arenes failed
to react with 1b under the condition studied. (c) Merchant, J. R.;
Kulkarni, S. D.; Venkatesh, M. S. Indian J. Chem. Sect. B 1980, 914-
916.
J. Org. Chem, Vol. 70, No. 6, 2005 2377

TABLE 2. AlCl3-Induced Heteroarylation of Arenes and
Heteroarenes
worked well it was of interest to test the generality and
scope of this process by conducting further experiments
and then comparing its merit with other methods espe-
cially those catalyzed by transition metal complexes or
salts. We therefore focused on the reaction of other
2-chloropyridine derivatives such as 2-chloro-3-nitropy-
ridine 1c and 2-chloro-3-cyanopyridine 1d with various
arenes and heteroarenes.13 The isolated yields of products
after column chromatography are shown in Table 2.
Based on the results summarized in Table 2 it is evident
that the heteroarylation reaction proceeds well in the
presence of various aryl or heteroaryl reactants. Unlike
the transition-metal-catalyzed reactions, no homocoupled
products, i.e., bipyridyl or biaryl derivatives, were iso-
lated in the present case. Generally, electron-rich arenes
afforded better yields of products (entries 1 and 5, Table
2) than those having fewer electron-donating groups. This
is in contrast to the palladium-catalyzed cross-coupling
process where an electron-rich aryl halide furnished
lower yields of product.14 Additionally, the presence of a
group at the C-3 position of 2-halopyridine ring afforded
a lower yield of product in the Pd-catalyzed reaction due
to a possible steric hindrance.7e This trend was not
observed in the present AlCl3-mediated synthesis of
2-arylpyridines (entry 1, Table 1 vs entry 1, Table 2).
With these efficient conditions in hand for the reaction
with electron-rich arenes, we then investigated the
reaction of nitrogen containing heteroarenes. Due to our
long-term interest in the synthesis of a variety of indole
derivatives11b,c,15 we employed a few indoles as hetero-
arenes in this AlCl3-induced C-C bond-forming reaction.
Both 2-chloro-3-nitropyridine 1c and 2-chloro-3-cyanopy-
ridine 1d were reacted with N-protected indoles, e.g.,
N-methyl- and N-ethylindole separately and the corre-
sponding 3-(2-pyridyl)indoles were isolated in moderate
yields (entries 3, 4 and 6, 7, Table 2). The reaction,
however, was also successful when indole without N-
protection was used (entry 8, Table 2) indicating that the
N-protection was not a prerequisite for successful het-
eroarylation of indoles. It is noteworthy that 3-(2-pyridyl)-
a Yield of isolated products.
(13) (a) All the arenes, heteroarenes, and 2-chloropyridines are
available commercially. (b) Typical procedure for the synthesis of 3d:
A mixture of 2-chloro-3-nitropyridine 1c (0.20 g, 1.26 mmol), 1,3,5-
trimethoxybenzene (0.21 g, 1.25 mmol), and AlCl3 (0.20 g, 1.51 mmol)
in dichloroethane (10 mL) was stirred at 25 °C for 1 h under a nitrogen
atmosphere. The reaction mixture was then stirred at 75-80 °C for
24 h. After completion, the mixture was poured into ice-cold water (100
mL), stirred for 10 min, and then extracted with chloroform (3 × 30
mL). The organic layers were collected, combined, washed with water
(2 × 30 mL), dried over anhydrous Na2SO4, and concentrated under
vacuum. The residue was purified by column chromatography using
ethyl acetate-petroleum ether to afford the expected product as a light
yellow solid: mp 170-172 °C; 1H NMR (200 MHz, CDCl3) δ 8.90-
8.87 (dd, J ) 1.4, 1.4 Hz, 1H), 8.28-8.23 (dd, J ) 1.4, 1.7 Hz, 1H),
7.43-7.37 (m, 1H), 6.20 (s, 2H), 3.85 (s, 6H, OCH3), 3.70 (s, 3H, OCH3);
νmax (KBr, cm-1) 1526, 1418, 1355; Mass (CI method, isobutane) 291
(M++1), 261 (M+-30, 100%); 13C NMR (50 MHz, CDCl3) 162.3 (2C),
158.2, 152.3, 148.9, 147.3, 131.7, 122.0, 107.9, 90.9 (2C), 55.7 (OCH3),
55.3 (2C, OCH3); HPLC 99.10%, Inertsil ODS 3V (250 × 4.6 mm),
mobile phase 0.01 M KH2PO4/acetonitrile, 0/40, 5/40, 30/70, 40/70, 45/
40, 50/40, 1.0 mL/min, 210 nm, retention time 11.1 min.
indoles, useful synthetic precursors for indole alkaloids,
were prepared via a Pd(0)-catalyzed heteroarylation of
3-indolylzinc derivatives earlier.16 The method however,
required a complicated preparation of 3-indolylzinc de-
rivative, i.e., (1-silyl-3-indolyl)zinc which was generated
from 3-bromo-1-(tert-butyldimethylsilyl)indole by halogen-
metal exchange with t-BuLi followed by transmetalation
of the resulting 3-lithioindole with ZnCl2. The present
AlCl3-mediated heteroarylation of indoles therefore is a
straightforward process in comparison of the Pd(0)-
catalyzed heteroarylation of 3-indolylzinc derivative.
Moreover, although the successful Friedel-Crafts acy-
lation of indole is an indirect method17 (as the method
involves N-protection, acylation, and N-deprotection
(14) It has been observed that the yields of cross-coupled products
in a palladium-catalyzed reaction are higher when phenyl bromide is
substituted with electron-withdrawing groups. These groups make aryl
bromide more electron deficient and thus facilitate the oxidative
addition to Pd(0). For phenyl bromides substituted with electron-
donating groups, the desired coupled products were obtained in much
lower yields. For related studies, see ref 7e.
(16) (a) Amat, M.; Hadida, S.; Pshenichnyi, G.; Bosch, J. J. Org.
Chem. 1997, 62, 3158-3175. (b) For a list of references on other
methods see ref 16a.
(17) (a) Ketcha, D. M.; Gribble, G. W. J. Org. Chem. 1985, 50, 5451-
5457. (b) Le Borgne, M.; Marchand, P.; Delevoye-Seiller, B.; Robert,
J.-M.; Le Baut, G.; Hartmann, R. W.; Palzer, M. Bioorg. Med. Chem.
Lett. 1999, 9, 333-336. (c) Jiang, J.; Gribble, G. W. Synth. Commun.
2002, 32, 2035-2040.
(15) Pal, M.; Subramanian, V.; Batchu, V. R.; Dager, I. Synlett 2004,
1965-1969.
2378 J. Org. Chem., Vol. 70, No. 6, 2005

process to limit polymerization) the present process
however can be carried out without any N-protection.
The heteroarylation of arenes and heteroarenes were
usually carried out at 75-80 °C as no reaction was
observed at lower temperature. The duration of the
reaction was 24 h. An attempt to reduce the reaction time
failed as the reaction ended up with either lesser yield
of products or recovery of the starting materials.
The strategy developed here was to synthesize 2-arylpy-
ridines using cheaper as well as commercially available
raw materials in order to make the process amenable for
the scale-up synthesis of this class of compounds. The
strategy worked well for electron rich arenes and was
extended to heteroarenes such as indoles. Both arenes
and indoles participated in the reaction through their
Friedel-Crafts active positions. The electron-withdraw-
ing substituents were tolerated on the pyridyl ring. In
other words the presence of electron-withdrawing groups
perhaps facilitated the heteroarylation reaction by in-
creasing the electron deficiency in the pyridyl ring. The
role of the electron-withdrawing group was further
supported by the observation that 2-chloropyridine did
not react with the electron rich arene 2a under the
reaction condition employed.18 From the viewpoint of
mechanism of the reaction, this electron deficiency,
however, did not prevent the complexation of AlCl3 with
the nitrogen of 2-chloropyridine moiety that is followed
by a nucleophilic attack at the adjacent chlorine bearing
carbon atom. It is evident that the nucleophilicity of the
reacting arenes or heteroarenes is crucial in such cases
and therefore the reaction proceeds smoothly with elec-
tronrich arenes or heteroarenes leading to the formation
of 3.
In conclusion, we have demonstrated for the first time
that 2-halopyridines could be utilized as an efficient
heteroarylating agent for arenes and heteroarenes in the
presence of AlCl3 in a one-pot reaction. 2-Halopyridine
derivatives are commercially available or can be readily
made. The process does not involve the use of expensive
catalysts or complex ligands. Unlike the transition-metal-
catalyzed reactions no homocoupled products were iso-
lated as byproducts. The methodology therefore has
advantages over the transition-metal-mediated synthe-
sis especially in the large-scale preparation of 2-aryl-
or heteroarylpyridines. The process could be viewed as
a useful alternative to the Suzuki coupling reactions
(when applied to a similar type of C-C bond forma-
tion reaction) as preparations of required boronic acids
are often cumbersome. Since the bond-forming reac-
tion between Csp2-centers allows the preparation of a
range of polyfunctional heterocycles of pharmaceutical
and agrochemical interest we believe that the present
methodology despite having few limitations would find
practical applications in organic as well as medicinal
chemistry.
Acknowledgment. We sincerely thank Dr. A. Ven-
kateswarlu, Dr. R. Rajagopalan, Prof. J. Iqbal of Dr.
Reddy’s Laboratories Limited, Hyderabad, India, and
Dr. U. Saxena and Dr. I. Khanna of Reddy US Thera-
peutics, Norcross, GA, for their constant encouragement.
We also thank Dr. K. Vyas and his group for analytical
and spectral support.
Supporting Information Available: Characterization
data for all new compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
(18) No product was detected in the reaction mixture even after 4
days.
JO047944H
J. Org. Chem, Vol. 70, No. 6, 2005 2379