Pd-catalyzed reactions on pyridinium N-heteroarylaminides. Step-by-step synthesis of 3,5-unsymmetrically disubstituted 2-aminopyridines

Article abstract of DOI:10.1016/j.tet.2010.02.036

Suzuki-Miyaura cross-coupling processes on N-pyridinium bromoazinyl aminides allow access to 3,5-disubstituted N-alkyl-2-aminopyridines. The synthetic pathway involves a regioselective bromination of pyridinium N-(pyridin-2-yl)aminide and a subsequent reaction with boronic acids to afford monosubstituted aminides in good yields. An additional bromination in the 5-position of the pyridine ring followed by a coupling reaction gives pyridinium N-(3,5-diarylpyridin-2-yl)aminides. Finally, a regioselective alkylation on the exo-nitrogen and reduction of the N-N bond yields highly substituted 2-aminopyridines.

Full text of DOI:10.1016/j.tet.2010.02.036

Tetrahedron 66 (2010) 2624–2632
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Pd-catalyzed reactions on pyridinium N-heteroarylaminides. Step-by-step
synthesis of 3,5-unsymmetrically disubstituted 2-aminopyridines
*
´
Marta Cordoba, Rafael R. Castillo, M. Luisa Izquierdo, Julio Alvarez-Builla
´
´
´
Departamento de Qu´ımica Organica, Universidad de Alcala, 28871 Alcala de Henares, Madrid, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Suzuki–Miyaura cross-coupling processes on N-pyridinium bromoazinyl aminides allow access to 3,5-
disubstituted N-alkyl-2-aminopyridines. The synthetic pathway involves a regioselective bromination of
pyridinium N-(pyridin-2-yl)aminide and a subsequent reaction with boronic acids to afford mono-
substituted aminides in good yields. An additional bromination in the 5-position of the pyridine ring
Received 22 December 2009
Received in revised form
4 February 2010
Accepted 5 February 2010
Available online 10 February 2010
followed by
a coupling reaction gives pyridinium N-(3,5-diarylpyridin-2-yl)aminides. Finally,
a regioselective alkylation on the exo-nitrogen and reduction of the N–N bond yields highly substituted
Dedicated to Professor Manuel Bernabe´ on
the occasion of his 74th birthday
2-aminopyridines.
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
a regioselective N-alkylation and a reduction process.8 In previous
communications we reported the success of the Suzuki cross-
Palladium-catalyzed Suzuki–Miyaura coupling reactions1 are
amongst the most powerful C–C bond forming reactions from hal-
oarenes. Since the initial development of the reaction numerous
authorshave contributed totheimprovementof theprocess2 through
the use of new catalytic systems,3 the preparation of more reactive or
stable boron reagents such as alkyltrifluoroborates4 or boronate es-
ters5 and the development of greener methods such as the recent use
of water6 or solvent free processes7 among other relevant examples.
As part of our research programme we became focused on the
preparation of different heterobiaryls from N-heteroaryl pyr-
idinium aminides 1 (Fig. 1), which are valuable precursors of
alkylaminoheterocycles and can thus be easily obtained through
coupling reaction on mono- and dibrominated aminides 2, which
resulted in the corresponding arylated N-azinyl pyridinium ami-
nides 3–6 under standard conditions (Fig. 1).9
The reaction on N-3,5-dibromopyrazinyl pyridinium aminide 2d
showed a surprising preference towards position 3 in the oxidative
addition of palladium.9b Further studies demonstrated that al-
though this observed selectivity also appears in the dibrominated
aminide 2c,9c it is much lower in the compound stabilized by a pyr-
idine ring. This behaviour allowed us to prepare disubstituted
2-alkylaminopyrazines with different substituents in the 3- and
5-positions. The key step in this process is selective coupling of the
dibrominated aminide 2d to give 8.9c Unfortunately, however, this
methodology could not be applied to the N-dibromopyridinyl pyr-
idinium aminide 2c to obtain 7, as an intermediate in a regioselective
synthesis of 2-aminopyridines, due tothe lower selectivity found for
compound 2c towards the monocoupling in the 3-position (Fig.1).9b
A continuous effort has been applied to the synthesis and
functionalisation of 2-aminopyridines10 since they are useful
building blocks in the synthesis of fused nitrogen heterocycles.11
Furthermore, some 2-aminopyridine compounds have been used
as ligands in the preparation of metal complexes,12 while other
similar derivatives have shown interesting biological activities.13 In
this paper a step-by-step synthesis of 3,5-disubstituted 2-amino-
pyridines is reported. In this approach it is possible to take ad-
vantage of the selectivity found in the monohalogenation of
N-azinyl pyridinium aminides 114 to introduce an aryl group in the
5-position. A subsequent halogenation/arylation sequence on the
electronically activated 3-position of compounds 3 gives the de-
sired products (Scheme 1).
+
N
N
N
Y
R
R'
1a Y = CH, R = R' = H
3 Y = CH, R' = H, R = Ar
4 Y = N, R' = H, R = Ar
5 Y = CH, R' = R = Ar
6 Y = N, R' = R = Ar
7 Y = CH, R' = Ar, R = Br
8 Y = N, R' = Ar, R = Br
1b Y = N, R = R' = H
2a Y = CH, R' = H, R = Br
2b Y = N, R' = H, R = Br
2c Y = CH, R' = R = Br
2d Y = N, R' = R = Br
Figure 1. N-Pyridinium azinyl aminides.
* Corresponding author. Fax: þ34 91 885 46 86.
E-mail address: julio.alvarez@uah.es (J. Alvarez-Builla).
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.02.036

M. Co´rdoba et al. / Tetrahedron 66 (2010) 2624–2632
2625
H
N
R
Br
[H]
Ar-B(OH)2
Ar
Ar'-B(OH)2
Br
N
NBS
N
R
+
+
+
+
+
N
N
N
N
N
N
N
N
N
N
N
N
N
N
R
Ar
Ar'
Br
Ar
Br
Ar
Ar'
Ar
Ar'
9
12
13
14
2a
3
Scheme 1. Synthetic sequence to 3,5-disubstituted 2-aminopyridines.
2. Results and discussion
The N-(5-bromopyridin-2-yl)pyridinium
Similar behaviour was observed in the bromination of 3e, where
aminide 9e and compound 11 (Fig. 2) were identified. This draw-
back was overcome by slow addition of NBS at low temperature
(ꢀ30 or ꢀ40 ꢁC) to the corresponding aminide 3; the same condi-
tions were used in the synthesis of 9d (Scheme 1, Table 1).
The cross-coupling between compounds 9 and aryl or heter-
oaryl boronic acids, to obtain the corresponding 3,5-disubstituted
aminides 12, was performed under the same conditions
aminide
2a14
–obtained by selective halogenation of N-(pyridin-2-yl)pyr-
idinium aminide 1a8a– was satisfactorily coupled with different
boronic acids under previously reported standard conditions: i.e.,
aminide (1 mmol), boronic acid (1.5 mmol), Pd(PPh3)4 (5 mmol %)
and K2CO3 (10 mmol) in refluxing toluene–ethanol (4:1, v/v)9c to
afford the 5-arylated (or heteroarylated) products 3 in good yields
(Scheme 1, Table 1). These compounds are suitable substrates to
undergo a new bromination process in the 3-position of the pyri-
dine ring to afford the corresponding aminides 9. The halogenation
was accomplished for 3a and 3c under previously reported condi-
tions,15 which involved the use of NBS in dichloromethane at room
temperature. However, when these conditions were applied to 3b,
two compounds were isolated in a 1:1 ratio from the reaction
mixturedthe desired monobrominated aminide 9b and the
dibrominated product 10 (Fig. 2). In compound 10 an additional
bromo-substituent has been incorporated in the para-position of
the activated benzene ring, flanked by the two methyl groups.
+
N
N
N
N
+
N
N
H3C
Br
Br
Br
11
10
S
Br
CH3
Figure 2. Side products obtained from 3b and 3e.
Table 1
Arylation of aminide 2a and bromination of compounds 3
Ar
Compound
Time (h)
Yield (%)
91
Compound
Time (h)
12
Yield (%)
74
3a9a
8
9a15
3b
48
8
71
85
88
9b
12
12
12
87
78
65
3c9c
9c15
3d
8
9d
3e
24
82
9e
4
73

2626
M. Co´rdoba et al. / Tetrahedron 66 (2010) 2624–2632
described to transform the N-(5-bromopyridin-2-yl)pyridinium
aminide 2a into compounds 3. The reactions were complete in
around 24 h and the coupled products were obtained, after pu-
rification by chromatography, in moderate to good yields
(Scheme 1, Table 2).
3. Conclusions
In conclusion, a selective and efficient scheme to prepare a se-
ries of 3,5-unsymmetrically disubstituted 2-aminopyridines 14 is
described. The sequence starts from N-(5-bromopyridin-2-yl)pyr-
idinium aminide 2a and involves a Suzuki arylation to produce 3,
a second bromination to produce 9, and a second Suzuki arylation
to produce 12. A final regioselective alkylation on the exocyclic
nitrogen produces the salts 13 and a subsequent reduction of the
N–N bond completes the synthesis of the 2-aminopyridines 14.
As occurs with other similar compounds,9c when aminides 12
were stirred with benzyl bromides in anhydrous acetone at room
temperature for the times shown in Table 3, a regioselective N-al-
kylation process occurred on the exocyclic nitrogen and the corre-
sponding pyridinium salts 13 were obtained in good to excellent
yields after removal of the solvent under vacuum, trituration of the
crude product with ethyl acetate and removal of the excess alky-
lating agent by filtration. When this reaction was applied to 12g the
dibromide 13g was obtained as a consequence of an additional
alkylation process on the pyridine nitrogen in the 3-pyridyl sub-
stituent (Scheme 1, Table 3).
Finally, amines 14 were obtained by reduction of the corre-
sponding pyridinium salts with zinc (powder) in glacial acetic acid
as a metal/acid system (Scheme 1, Table 3). Acceptable yields were
obtained after purification by column chromatography and crys-
tallization from a suitable solvent.
4. Experimental
4.1. General remarks
All melting points were determined in open capillary tubes on
a Stuart Scientific SMP3 melting point apparatus and are un-
corrected. IR spectra were obtained on a Perkin–Elmer FTIR spec-
trum 2000 spectrophotometer. 1H and 13C NMR spectra were
recorded on a Varian Unity 300 or 500 MHz spectrometer or on
a Varian Mercury VX-300 system at room temperature. Chemical
shifts are given in parts per million (d) downfield from TMS. Cou-
pling constants (J) are in Hertz (Hz) and signals are described as
follows: s, singlet; d, doublet; t, triplet; m, multiplet; br, broad; ap,
apparent. The tentative assignment of proton and carbon reso-
nances was made on the basis of double resonance, NOESY and
TOCSY experiments, two-dimensional H,H- and H,C-correlation
experiments, COSY, HSQC, HMBC or related spectra. In order to
identify the signals in the description of each product, positions of
the pyridinium ring are not labelled, positions of the pyridine ring
are labelled (0), positions of the 5-aryl substituent are labelled (00),
positions of the 3-aryl substituent are labelled (000) and positions of
the aryl ring belonging to the N-benzyl substituent, when present,
are labelled (0000). For reduced compounds 14, the labelling has one
fewer prime label than the precursor (due to the absence of the
pyridinium ring). Elemental analyses were carried out on a Heraeus
Rapid CHN analyzer and were within 0.4% of the theoretical values
for all the new compounds described. Hydration in the solid state
was confirmed by Karl Fischer titration. Low-resolution mass
spectra (MS) were recorded on a Hewlett–Packard 5988A (70 eV)
spectrometer using electron impact (EI) or electrospray (ESI) ioni-
zation and high-resolution analysis (TOF) was performed on an
Agilent 6210 time-of-flight LC/MS. All reagents were obtained from
commercial sources and used without further purification. Solvents
were purified and dried by standard procedures. TLC analyses were
performed on silica gel (Kieselgel 60 F254, Macherey-Nagel) and
spots were visualized under UV light. Column chromatography was
Table 2
Arylation of aminides 9a–e
Ar
Ar0
Compound
Time (h)
24
Yield (%)
77
12a
12b
12c
12d
12e
12f
22
23
24
24
19
93
54
86
71
78
carried out with silica gel 60 (40–63
eluent reported in each case.
mm, Merck) columns, using the
4.2. Preparation of 5-substituted N-(pyridin-2-yl)pyridinium
aminides (3)
General method: Aminide 2a (1 mmol), the corresponding bo-
ronic acid (1.5 mmol) and K2CO3 (10 mmol) were dissolved in
a toluene–ethanol mixture (4:1, 15 mL). Pd(PPh3)4 (5 mmol %) was
added and the mixture was stirred under argon and heated under
reflux for the reaction time indicated in Table 1.
The course of the reaction was followed by TLC. Once the
starting material had been consumed, the system was allowed to
reach room temperature, the mixture was filtered through Celite
and washed with acetonitrile until colour was no longer observed
in the filtrate. The combined filtrates were evaporated to dryness.
The crude product was purified by flash chromatography on a silica
gel column, with ethanol as the mobile phase, and recrystallized
from a suitable solvent.
12g
24
78

M. Co´rdoba et al. / Tetrahedron 66 (2010) 2624–2632
2627
Table 3
Synthesis of 3,5-disubstituted aminopyridines 14
Ar
Ar0
R
Compound
Time (h)
48
Yield (%)
H
13a
13b
77
60
H
H
24
24
13c
13d
13e
13f
72
71
76
94
H
96
28
28
Me
Me
Me
H
13g
14a
14b
24
24
44
96
63
48
H
H
H
14c
14d
24
24
60
70
Me
Me
14e
14f
24
27
74
71

2628
M. Co´rdoba et al. / Tetrahedron 66 (2010) 2624–2632
4.2.1. N-(5-Phenylpyridin-2-yl)pyridinium aminide (3a). See Ref. 9a.
4.2.2. N-[5-(3,5-Dimethylphenyl)pyridin-2-yl]pyridinium aminide
Compounds 10 and 11 were obtained together with the corre-
sponding monobrominated aminide 9b and 9e, when the addition
of NBS to 3b and 3e was carried out in 3 min, and at room tem-
perature. The compounds obtained in each case were separated by
column chromatography and crystallized from the appropriate
solvent.
(3b). Orange solid (195 mg, 71%, ethanol–ethyl acetate), mp 86–
88 ꢁC; IR (KBr) nmax (cmꢀ1): 1595, 1488, 1379, 1147, 1005, 758, 665;
1H NMR (300 MHz, CD3OD):
d
8.77 (2H, dd, J¼7.0 and 1.3 Hz, H2(6)),
7.99 (1H, tt, J¼7.7 and 1.3 Hz, H4), 7.94 (1H, dd, J¼2.4 and 0.6 Hz,
H60), 7.78 (2H, dd, J¼7.7 and 7.0 Hz, H3(5)), 7.66 (1H, dd, J¼8.8 and
2.4 Hz, H40), 7.10 (2H, br s, H200(600)), 6.90 (1H, br s, H400), 6.60 (1H, d,
4.3.1. N-(3-Bromo-5-phenylpyridin-2-yl)pyridinium aminide (9a).
See Ref. 15.
J¼8.8 Hz, H30), 2.33 (6H, s, CH3); 13C NMR (75 MHz, CD3OD):
d 164.8,
144.8, 144.3, 139.9, 139.3, 137.3, 137.1, 128.8, 128.4, 125.8, 124.3,
112.3, 21.5. MS (EI, m/z): 275 (55, Mþ), 274 (100), 154 (12), 127 (12),
79 (75), 52 (54); HRMS (ESI-TOF, CH3OH): calcd for C18H18N3:
[MþH]þ 276.1501, found 276.1490. Anal. Calcd for C18H17N3$3/
2H2O: C, 71.50; H, 6.67; N, 13.90. Found: C, 71.64; H, 6.30; N, 13.53.
4.3.2. N-[3-Bromo-5-(3,5-dimethylphenyl)pyridin-2-yl]pyridinium
aminide (9b). Orange solid (308 mg, 87%, ethyl acetate), mp 176–
178 ꢁC; IR (KBr) nmax (cmꢀ1): 1588, 1469, 1449, 1380, 847, 766, 672;
1H NMR (300 MHz, CD3OD):
d
8.72 (2H, dd, J¼7.0 and 1.3 Hz, H2(6)),
8.17 (1H, tt, J¼7.7 and 1.3 Hz, H4), 7.92 (1H, d, J¼2.0 Hz H60), 7.90
(2H, m, H3(5)), 7.87 (1H, d, J¼2.0 Hz, H40), 7.08 (2H, ap s, H200(600)),
6.92 (1H, ap s, H400), 2.34 (6H, s, CH3); 13C NMR (75 MHz, CD3OD):
4.2.3. N-[5-(4-Methoxyphenyl)pyridin-2-yl]pyridiniumaminide(3c). See
Ref. 9c.
d 162.0, 146.0, 144.0, 139.9, 139.5, 139.3, 138.7, 129.1, 128.7, 126.3,
124.3, 106.7, 21.5. MS (EI, m/z): 355/353 (63/64, Mþ), 354/352 (100/
91),195 (33), 179 (24), 168 (77), 153 (45), 140 (24),128 (20),115 (32),
79 (81), 52 (61); HRMS (ESI-TOF, CH3OH): calcd for C18H1779BrN3:
[MþH]þ 354.0606, found 354.0602. Anal. Calcd for C18H16BrN3$3/
4H2O (%): C, 58.79; H, 4.80; N, 11.43. Found: C, 58.81; H, 4.64; N,
11.20.
4.2.4. N-[5-(Thiophen-3-yl)pyridin-2-yl]pyridiniumaminide(3d). Orange
solid (223 mg, 88%, ethyl acetate), mp 95–97 ꢁC; IR (KBr) nmax (cmꢀ1):
1597, 1467, 1408, 1390, 1368, 1344, 1150, 767, 666; H NMR (300 MHz,
1
CD3OD):
d
8.79 (2H, dd, J¼7.0 and 1.3 Hz, H2(6)), 8.04 (1H, tt, J¼7.7 and
1.3 Hz, H4), 8.02 (1H, d, J¼2.6 Hz, H60), 7.82 (2H, dd, J¼7.7 and 7.0 Hz,
H3(5)), 7.73 (1H, dd, J¼8.9 and 2.6 Hz, H40), 7.45 (1H, dd, J¼4.9 and
2.9 Hz, H500), 7.40 (1H, dd, J¼2.9 and 1.5 Hz, H200), 7.35 (1H, dd, J¼4.9 and
1.5 Hz, H400), 6.59 (1H, d, J¼8.9 Hz, H30); 13C NMR (75 MHz, CD3OD):
4.3.3. N-[3-Bromo-5-(4-methoxyphenyl)pyridin-2-yl]pyridinium
aminide (9c). See Ref. 15.
d
164.1, 144.7, 144.1, 140.9, 138.3, 136.9, 128.6, 127.2, 126.2, 121.8, 118.5,
112.2. MS (EI, m/z): 253 (57, Mþ), 252 (100), 176 (14), 146 (37), 126 (22),
103 (17), 79 (25), 52 (23); HRMS (ESI-TOF, CH3OH): calcd for C14H12N3S:
[MþH]þ 254.07464, found 254.07431. Anal. Calcd for C14H11N3S$1/
3H2O: C, 64.84; H, 4.53; N, 16.20; S, 12.36. Found: C, 64.58; H, 4.64; N,
16.11; S, 12.37.
4.3.4. N-[3-Bromo-5-(thiophen-3-yl)pyridin-2-yl]pyridinium ami-
nide (9d). Orange solid (216 mg, 65%, ethyl acetate–hexane), mp
148–150 ꢁC; IR (KBr) nmax (cmꢀ1): 1584, 1472,1445,1387, 1165,1155,
1030, 1015, 777, 764, 742, 676; 1H NMR (300 MHz, CD3OD):
d 8.74
(2H, dd, J¼6.9 and 1.4 Hz, H2(6)), 8.19 (1H, tt, J¼7.7 and 1.4 Hz, H4),
8.02 (1H, d, J¼2.2 Hz, H60), 7.97 (1H, d, J¼2.2 Hz, H40), 7.92 (2H, dd,
J¼7.7 and 6.9 Hz, H3(5)), 7.47 (1H, dd, J¼4.9 and 3.0 Hz, H500), 7.44
(1H, dd, J¼3.0 and 1.8 Hz, H200), 7.34 (1H, dd, J¼4.9 and 1.8 Hz, H400);
4.2.5. N-[5-(Benzo[b]thiophen-3-yl)pyridin-2-yl]pyridinium aminide
(3e). Orange solid (248 mg, 82%, ethyl acetate–hexane), mp 145–
147 ꢁC; IR (KBr) nmax (cmꢀ1): 1654, 1647, 1521, 1474, 1381, 1139, 762,
13C NMR (75 MHz, CD3OD):
d 161.6, 146.0, 143.7, 139.9, 139.5, 139.4,
734; 1H NMR (300 MHz, CD3OD):
d
8.83 (2H, dd, J¼6.9 and 1.3 Hz,
128.6, 127.3, 126.2, 122.0, 118.7, 106.7. MS (EI, m/z): 333/331 (22/21,
Mþ), 332/330 (31/27), 173 (34), 146 (100), 79 (32), 52 (26); HRMS
(ESI-TOF, CH3OH): calcd for C14H1179BrN3S: [MþH]þ 331.9857,
found 331.9835. Anal. Calcd for C14H10BrN3S$H2O (%): C, 48.01; H,
3.45; N, 12.00; S, 9.15. Found: C, 48.27; H, 3.25; N, 12.17; S, 9.34.
H2(6)), 8.10 (1H, tt, J¼7.7 and 1.3 Hz, H4), 7.90 (5H, m, H3(5), H60,
H400 and H700), 7.67 (1H, dd, J¼8.8 and 2.6 Hz, H40), 7.43 (1H, s, H200),
7.40 (2H, m, H500 and H600), 6.69 (1H, d, J¼8.8 Hz, H30); 13C NMR
(75 MHz, CD3OD):
d 165.0, 146.3, 144.8, 142.1, 139.2, 138.8, 138.1,
136.6, 128.6, 125.4, 125.3, 123.9, 123.5, 122.8, 120.7, 112.1. MS (EI,
m/z): 303 (69, Mþ), 302 (100), 226 (59), 224 (27), 196 (86), 171 (22),
151 (37), 79 (81), 52 (64); HRMS (ESI-TOF, CH3OH): calcd for
C18H14N3S: [MþH]þ 304.09029, found 304.09209. Anal. Calcd for
C18H13N3S$2/3H2O: C, 68.55; H, 4.58; N, 13.32; S, 10.17. Found: C,
68.54; H, 4.35; N, 13.41; S, 9.92.
4.3.5. N-[5-(Benzo[b]thiophen-3-yl)-3-bromopyridin-2-yl]pyr-
idinium aminide (9e). Orange solid (279 mg, 73%, ethyl acetate), mp
81–83 ꢁC; IR (KBr) nmax (cmꢀ1): 1588, 1470, 1439, 1419, 1387, 1145,
760, 734; 1H NMR (300 MHz, CD3OD):
d
8.77 (2H, dd, J¼7.0 and
1.4 Hz, H2(6)), 8.21 (1H, tt, J¼7.7 and 1.4 Hz, H4), 7.92 (5H, m, H3(5),
H60, H40, H700 or H400), 7.83 (1H, m, H700 or H400), 7.46 (1H, s, H200), 7.41
(2H, m, H500 and H600); 13C NMR (75 MHz, CD3OD):
d 162.0, 146.0,
4.3. Synthesis of 3-bromo-5-substituted N-(pyridin-2-
yl)pyridinium aminides (9)
145.6, 142.0, 141.3, 139.4, 139.0, 135.2, 128.6, 125.5, 125.4, 123.9,
123.3 (two overlapped signals), 121.0, 106.3. MS (EI, m/z): 383/381
(33/16, Mþ), 382/380 (13/14), 303 (14), 223 (15), 196 (54), 129 (18),
111 (21), 97 (36), 95 (27), 83 (50), 71 (50), 69 (77), 57 (99), 55 (100);
HRMS (ESI-TOF, CH3OH): calcd for C18H1379BrN3S: [MþH]þ
381.99929, found 382.00081. Anal. Calcd for C18H12BrN3S$1/2H2O
(%): C, 55.25; H, 3.35; N, 10.74; S, 8.19. Found: C, 55.24; H, 3.65; N,
10.81; S, 7.95.
General method: To a stirred solution of the corresponding
aminide 3 (1 mmol) in dichloromethane (8 mL) at room tempera-
ture, a solution of NBS (1.1 mmol) in the same solvent (15 mL) was
added. The mixture was stirred until starting material was no
longer detected by TLC. The solvent was evaporated in vacuo and
the product was purified by chromatography on silica gel, using
ethanol as eluent and then crystallized from a suitable solvent and
identified.
The procedure was used with dropwise addition of the de-
scribed NBS solution over 30 min, and low temperature in the case
of compounds 9b (ꢀ40 ꢁC) and 9d and 9e (ꢀ30 ꢁC), in order to avoid
bromination of the aromatic substituent at the 5-position of the
pyridine ring.
4.3.6. N-[3-Bromo-5-(4-bromo-3,5-dimethylphenyl)pyridin-2-yl]-
pyridinium aminide (10). This compound was obtained together
with 9b by addition of NBS to 3b at room temperature. Orange solid
(ethyl acetate), mp 74–76 ꢁC; IR (KBr) nmax (cmꢀ1): 1590, 1474, 1443,
1406, 1372, 1326, 1147, 1025, 669; 1H NMR (300 MHz, CD3OD):
d
8.74 (2H, dd, J¼6.9 and 1.3 Hz, H2(6)), 8.20 (1H, tt, J¼7.7 and
1.3 Hz, H4), 7.96 (1H, d, J¼2.3 Hz H60), 7.92 (2H, dd, J¼7.7 and 6.9 Hz,

M. Co´rdoba et al. / Tetrahedron 66 (2010) 2624–2632
2629
H3(5)), 7.91 (1H, d, J¼2.3 Hz, H40), 7.25 (2H, s, H200(600)), 2.45 (6H, s,
137.2, 130.5, 129.2, 128.4, 128.0, 127.2, 126.2, 125.0, 121.5, 118.2. MS
(EI, m/z): 329 (71, Mþ), 328 (72), 252 (39), 251 (58), 250 (100), 222
(33), 205 (16), 79 (29), 52 (16); HRMS (ESI-TOF, CH3OH): calcd for
C20H16N3S: [MþH]þ 330.1065, found 330.1071. Anal. Calcd for
C20H15N3S$1/3H2O: C, 71.62; H, 4.71; N, 12.53; S, 9.56. Found: C,
71.37; H, 5.02; N, 12.75; S, 9.21.
CH3); 13C NMR (75 MHz, CD3OD):
d 162.0, 146.2, 144.2, 139.8 (two
overlapped signals), 139.6, 137.5, 128.7, 126.4, 126.3, 125.3, 106.7,
24.0. MS (EI, m/z): 435/433/431 (7/14/7, Mþ), 434/432/430 (12/20/
10, Mꢀ1), 358/356/354 (50/100/52), 196 (50); HRMS (ESI-TOF,
CH3OH): calcd for C18H1679Br2N3: [MþH]þ 431.9711, found
431.9697.
4.4.3. N-[3-(Benzo[b]thiophen-3-yl)-5-phenylpyridin-2-yl]pyr-
idinium aminide (12c). Orange solid (205 mg, 54%, ethanol), mp
94–96 ꢁC; IR (KBr) nmax (cmꢀ1): 1593, 1425, 1382, 1296, 1145, 761;
4.3.7. N-[5-(Benzo[b]-2-bromothiophen-3-yl)-3-bromopyridin-2-yl]-
pyridinium aminide (11). This compound was obtained together
with 9e by addition of NBS to 3e at room temperature. Orange solid
(ethyl acetate–hexane), mp 189–191 ꢁC; IR (KBr) nmax (cmꢀ1): 1591,
1472, 1439, 1420, 1388, 1331, 1145, 761, 676; 1H NMR (300 MHz,
1H NMR (300 MHz, CD3OD):
d
8.76 (2H, dd, J¼7.0 and 1.3 Hz, H2(6)),
8.14 (1H, tt, J¼7.7 and 1.3 Hz, H4), 8.10 (1H, d, J¼2.3 Hz, H60), 7.96
(1H, m, H7000 or H4000), 7.87 (2H, dd, J¼7.7 and 7.0 Hz, H3(5)), 7.86
(1H, m, and H4000 or H7000), 7.79 (1H, d, J¼2.3 Hz, H40), 7.74 (1H, s,
H2000), 7.57 (2H, dd, J¼8.3 and 1.3 Hz, H200(600)), 7.41 (4H, m, H300(500),
H5000 and H6000), 7.28 (1H, tt, J¼7.3 and 1.3 Hz, H400). 13C NMR
CD3OD):
d
8.76 (2H, dd, J¼6.9 and 1.3 Hz, H2(6)), 8.21 (1H, tt, J¼7.7
and 1.3 Hz, H4), 7.93 (2H, dd, J¼7.7 and 6.9 Hz, H3(5)), 7.83 (1H, m,
H700), 7.75 (1H, d, J¼2.0, H60), 7.73 (1H, d, J¼2.0 Hz, H40), 7.56 (1H, m,
H400), 7.38 (2H, m, H500 and H600); 13C NMR (75 MHz, CD3OD):
(75 MHz, CD3OD):
d 161.6, 145.9, 144.9, 141.7, 139.8, 139.4, 138.7,
d
162.4, 147.4, 146.2, 142.2, 141.1, 139.9, 139.8, 135.0, 128.8, 126.2,
138.4, 135.6, 130.0, 128.7, 127.6, 126.7, 126.5, 125.6, 125.4, 125.1,
124.6, 123.7,119.1. MS (EI, m/z): 379 (3, Mþ), 301 (36), 300 (100),198
(49), 181 (25), 152 (26), 150 (31), 79 (77), 52 (55); HRMS (ESI-TOF,
CH3OH): calcd for C24H18N3S: [MþH]þ 380.1221, found 380.1299.
Anal. Calcd for C24H17N3S$3/2H2O (%): C, 70.91; H, 4.96; N, 10.34; S,
7.89. Found: C, 70.51; H, 4.63; N, 10.09; S, 7.72.
126.1,123.5,123.0,118.0,114.0,105.8. MS (EI, m/z): 463/461/459 (18/
34/17, Mþ), 462/460/458 (33/56/27, Mꢀ1), 386/384/382 (4/9/5),
276/274 (32/32), 230 (21), 222 (47), 221 (30), 196 (18), 195 (40), 194
(29), 151 (23), 79 (100), 52 (74); HRMS (ESI-TOF, CH3OH): calcd for
C18H1279Br2N3S: [MþH]þ 459.9119, found 459.9116. Anal. Calcd for
C18H11Br2N3S$2H2O(%): C, 43.48; H, 3.04; N, 8.45; S, 6.45. Found: C,
43.78; H, 2.64; N, 8.58; S, 6.19.
4.4.4. N-[5-(Benzo[b]thiophen-3-yl)-3-phenylpyridin-2-yl]pyr-
idinium aminide (12d). Orange solid (326 mg, 86%, ethanol–ethyl
acetate), mp 83–85 ꢁC; IR (KBr) nmax (cmꢀ1): 1616, 1594, 1471, 1457,
4.4. Synthesis of unsymmetrical 3,5-disubstituted aminides 12
1430, 1385, 1325, 1144, 760, 699; 1H NMR (500 MHz, CD3OD):
d 8.76
General method: Pd(PPh3)4 (5 mmol %), the corresponding bo-
ronic acid (1.5 mmol), the corresponding aminide 9 (1 mmol) and
K2CO3 (10 mmol) were suspended in a mixture of toluene–ethanol
(4:1,15 mL). The mixture was stirred and heated under reflux under
argon until the starting material was no longer detected by TLC (see
Table 2). The system was then allowed to reach room temperature,
the mixture was filtered through Celite and the residue was washed
well with acetonitrile. The filtrates were combined and evaporated
to dryness. The aminide 12 was purified by flash chromatography
on a silica gel column, using ethanol as eluent, and recrystallized
from the appropriate solvent.
(2H, dd, J¼7.0 and 1.2 Hz, H2(6)), 8.09 (1H, tt, J¼7.8 and 1.2 Hz, H4),
7.94 (1H, m, H400 or H700), 7.93 (1H, d, J¼2.3 Hz, H60), 7.91 (1H, m, H400
or H700), 7.85 (2H, dd, J¼7.8 and 7.0 Hz, H3(5)), 7.77 (2H, dd, J¼8.1
and 1.3 Hz, H2000(6000)), 7.58 (1H, d, J¼2.3 Hz, H40), 7.47 (1H, s, H200),
7.45 (2H, dd, J¼8.1 and 7.4 Hz, H3000(5000)), 7.41 (2H, m, H500 and H600),
7.34 (1H, tt, J¼7.4 and 1.3 Hz, H4000). 13C NMR (75 MHz, CD3OD):
d
163.1, 145.6, 145.4, 142.1, 140.9, 139.3, 139.1, 138.0, 136.5, 130.5,
129.2, 128.5, 128.0, 125.4, 125.3, 124.7, 124.0, 123.5, 122.7, 120.7. MS
(EI, m/z): 379 (66, Mþ), 378 (68), 302 (50), 301 (68), 300 (100), 299
(44), 272 (33), 255 (23), 79 (45), 52 (31); HRMS (ESI-TOF, CH3OH):
calcd for C24H18N3S: [MþH]þ 380.1221, found 380.1181. Anal. Calcd
for C24H17N3S$1/2H2O (%): C, 73.82; H, 5.16; N, 10.76; S, 8.21. Found:
C, 73.59; H, 5.39; N, 10.53; S, 8.10.
4.4.1. N-[5-Phenyl-3-(thiophen-3-yl)pyridin-2-yl]pyridinium
ami-
nide (12a). Orange solid (253 mg, 77%, ethanol), mp 165–167 ꢁC; IR
(KBr) nmax (cmꢀ1): 1591, 1472, 1433, 1381, 1302, 1145, 797, 765, 757,
4.4.5. N-[5-(3,5-Dimethylphenyl)-3-(4-methoxyphenyl)pyridin-2-
yl]pyridinium aminide (12e). Red solid (271 mg, 71%, ethanol–ethyl
acetate), mp 72–74 ꢁC; IR (KBr) nmax (cmꢀ1): 1592, 1509, 1440, 1400,
696, 643, 501; 1H NMR (300 MHz, CD3OD):
d
8.74 (2H, dd, J¼6.9 and
1.3 Hz, H2(6)), 8.06 (1H, tt, J¼7.7 and 1.3 Hz, H4), 7.98 (1H, dd, J¼3.2
and 1.3 Hz, H2000), 7.91 (1H, d, J¼2.3 Hz, H60), 7.83 (3H, m, H3(5) and
H40), 7.67 (1H, dd, J¼5.3 and 1.3 Hz, H4000), 7.55 (2H, ap dd, J¼8.2 and
1.3 Hz, H200(600)), 7.45 (1H, dd, J¼5.3 and 3.2 Hz, H5000), 7.41 (2H, ap
dd, J¼8.2 and 7.3 Hz, H300(500)), 7.26 (1H, tt, J¼7.3 and 1.3 Hz, H400);
1375, 1320, 1242, 1143, 831; 1H NMR (300 MHz, CD3OD):
d 8.67 (2H,
dd, J¼6.9 and 1.3 Hz, H2(6)), 7.98 (1H, tt, J¼7.7 and 1.3 Hz, H4), 7.88
(1H, d, J¼2.4 Hz, H60), 7.76 (2H, dd, J¼7.7 and 6.9 Hz, H3(5)), 7.66
(2H, d, J¼8.9 Hz, H2000(6000)), 7.54 (1H, d, J¼2.4 Hz, H40), 7.13 (2H, ap s,
H200(600)), 6.98 (2H, d, J¼8.9 Hz, H3000(5000)), 6.91 (1H, ap s, H400), 3.84
13C NMR (75 MHz, CD3OD):
d 163.0, 145.2, 143.7, 140.7, 140.1, 137.7,
136.3, 129.9, 129.5, 128.4, 127.2, 126.5, 125.3, 125.2, 124.2, 119.4. MS
(EI, m/z): 329 (10, Mþ), 251 (25), 250 (100), 222 (16), 125 (12), 79
(52), 52 (36); HRMS (ESI-TOF, CH3OH): calcd for C20H16N3S:
[MþH]þ 330.1065, found 330.1029. Anal. Calcd for C20H15N3S$2/
5H2O: C, 71.36; H, 4.73; N, 12.48; S, 9.52. Found: C, 71.10; H, 4.62; N,
12.27; S, 9.23.
(3H, s, OCH3), 2.34 (6H, s, CH3); 13C NMR (75 MHz, CD3OD):
d 163.0,
160.2, 144.9, 143.6, 139.9, 139.4, 137.3, 137.2, 133.3, 131.5, 128.8,
128.3, 125.9, 124.6, 124.3, 114.6, 55.7, 21.5. MS (EI, m/z): 381 (93,
Mþ), 380 (93), 302 (100), 287 (52), 260 (42), 259 (74), 217 (15), 216
(13), 190 (14), 151 (29), 143 (19), 128 (24), 79 (79), 52 (44); HRMS
(ESI-TOF, CH3OH): calcd for C25H24N3O: [MþH]þ 382.1919, found
382.1909. Anal. Calcd for C25H23N3O$2H2O: C, 71.92; H, 6.52; N,
10.06. Found: C, 71.96; H, 6.33; N, 9.66.
4.4.2. N-[3-Phenyl-5-(thiophen-3-yl)pyridin-2-yl]pyridinium ami-
nide (12b). Red solid (306 mg, 93%, ethanol–diethyl ether), mp 63–
65 ꢁC; IR (KBr) nmax (cmꢀ1): 1594, 1472, 1456, 1430, 1387, 1145, 778,
4.4.6. N-[3-(3,5-Dimethylphenyl)-5-(4-methoxyphenyl)pyridin-2-
yl]pyridinium aminide (12f). Red solid (297 mg, 78%, ethanol–ethyl
acetate), mp 77–79 ꢁC; IR (KBr) nmax (cmꢀ1): 1589, 1442, 1405, 1373,
699; 1H NMR (300 MHz, CD3OD):
d
8.75 (2H, dd, J¼6.9 and 1.3 Hz,
H2(6)), 8.11 (1H, tt, J¼7.6 and 1.3 Hz, H4), 8.03 (1H, d, J¼2.3 Hz, H60),
7.85 (2H, dd, J¼7.6 and 6.9 Hz, H3(5)), 7.73 (2H, dd, J¼8.1 and 1.2 Hz,
H2000(6000)), 7.68 (1H, d, J¼2.3 Hz, H40), 7.46 (4H, m, H3000(5000), H200
and H500), 7.39 (1H, m, H400), 7.36 (1H, tt, J¼7.4 and 1.2 Hz, H4000). 13C
1327, 1145, 1013; 1H NMR (300 MHz, CD3OD):
d
8.67 (2H, dd, J¼6.9
and 1.3 Hz, H2(6)), 7.99 (1H, tt, J¼7.7 and 1.3 Hz, H4), 7.87 (1H, d,
J¼2.4 Hz, H60), 7.77 (2H, dd, J¼7.7 and 6.9 Hz, H3(5)), 7.52 (1H, d,
J¼2.4 Hz, H40), 7.44 (2H, d, J¼8.9 Hz, H200(600)), 7.30 (2H, s, H2000(6000)),
NMR (75 MHz, CD3OD):
d 162.6, 145.1, 143.6, 141.0, 140.9, 137.6,

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M. Co´rdoba et al. / Tetrahedron 66 (2010) 2624–2632
6.98 (1H, s, H4000), 6.96 (2H, d, J¼8.9 Hz, H300(500)), 3.82 (3H, s, OCH3),
(500 MHz, CD3OD):
d
8.86 (1H, d, J¼2.3 Hz, H60), 8.74 (2H, dd, J¼6.9
2.37 (6H, s, CH3); 13C NMR (75 MHz, CD3OD):
d
162.6, 160.0, 145.0,
and 1.3 Hz, H2(6)), 8.46 (1H, tt, J¼7.7 and 1.3 Hz, H4), 8.09 (1H, d,
J¼2.3 Hz, H40), 7.91 (1H, dd, J¼4.2 and 1.7 Hz, H500), 7.85 (2H, dd,
J¼7.7 and 6.9 Hz, H3(5)), 7.61 (2H, m, H200 and H400), 7.48 (5H, m,
H20000(60000), H40000 and H30000(50000)), 7.28 (3H, m, H2000(6000) and H4000),
7.23 (2H, m, H3000(5000)), 5.07 (2H, s, CH2); 13C NMR (75 MHz,
143.3, 140.9, 138.6, 137.4, 137.3, 132.6, 129.5, 128.3, 128.2, 127.6,
125.7, 125.4, 115.3, 55.7, 21.5. MS (EI, m/z): 381 (53, Mþ), 304 (48),
303 (56), 302 (77), 287 (100), 259 (23), 151 (15), 144 (15), 122 (16),
79 (16), 52 (76); HRMS (ESI-TOF, CH3OH): calcd for C25H24N3O:
[MþH]þ 382.1919, found 382.1958. Anal. Calcd for C25H23N3O: C,
77.49; H, 6.16; N, 10.84. Found: C, 77.66; H, 6.33; N, 10.56.
CD3OD): d 154.7, 148.8, 146.6, 140.4, 139.3, 138.7, 135.8, 133.5, 133.3,
131.6, 131.2, 131.0, 130.9 (two overlapped signals), 130.8, 130.7,
130.4, 129.4, 127.7, 124.6, 61.7. MS (EI, m/z): 420 (2, MþꢀBr), 340
(45), 339 (42), 264 (19), 263 (100), 237 (30), 236 (70), 170 (13), 106
(16), 79 (40), 52 (15); HRMS (ESI-TOF, CH3OH): calcd for C27H22N3S:
[MꢀBr]þ 420.1534, found 420.1523. Anal. Calcd for C27H22BrN3S$2/
3H2O: C, 63.28; H, 4.59; N, 8.20; S, 6.26. Found: C, 63.06; H, 4.36; N,
8.04; S, 6.18.
4.4.7. N-[5-(4-Methoxyphenyl)-3-(pyridin-3-yl)pyridin-2-yl]pyr-
idinium aminide (12g). Orange solid (276 mg, 78%, ethanol–ethyl
acetate), mp 169–171 ꢁC; IR (KBr) nmax (cmꢀ1): 1598, 1514, 1467,
1442, 1416, 1402, 1382, 1281, 1247, 1143, 826, 768, 708; 1H NMR
(300 MHz, CD3OD):
d
8.92 (1H, dd, J¼2.3 and 0.6 Hz, H2000), 8.74 (2H,
dd, J¼6.9 and 1.3 Hz, H2(6)), 8.48 (1H, dd, J¼4.9 and 1.6 Hz, H6000),
8.24 (1H, ap dt, J¼7.9 and 2.0 Hz, H4000), 8.05 (1H, tt, J¼7.7 and
1.3 Hz, H4), 7.94 (1H, d, J¼2.3 Hz, H60), 7.82 (2H, dd, J¼7.7 and
6.9 Hz, H3(5)), 7.62 (1H, d, J¼2.3 Hz, H40), 7.51 (1H, ddd, J¼7.9, 4.9
and 1.0 Hz, H5000), 7.47 (2H, d, J¼8.9 Hz, H200(600)), 6.98 (2H, d,
J¼8.9 Hz, H300(500)), 3.83 (3H, s, OCH3); 13C NMR (75 MHz, CD3OD):
4.5.3. 1-{N-[3-(Benzo[b]thiophen-3-yl)-5-phenylpyridin-2-yl]-N-
benzylamino}pyridinium bromide (13c). Brown solid (396 mg, 72%,
ethanol–ethyl acetate), mp 63–65 ꢁC; IR (KBr) nmax (cmꢀ1): 1616,
1430, 766, 700; 1H NMR (300 MHz, CD3OD):
d
8.95 (1H, d, J¼2.4 Hz,
H60), 8.31 (2H, dd, J¼7.0 and 1.3 Hz, H2(6)), 8.27 (1H, tt, J¼7.7 and
1.3 Hz, H4), 8.15 (1H, d, J¼2.4 Hz, H40), 8.00 (1H, m, H4000 or H7000),
7.78 (2H, dd, J¼8.3 and 1.3 Hz, H200(600)), 7.68 (2H, dd, J¼7.7 and
7.0 Hz, H3(5)), 7.58 (1H, s, H2000), 7.50 (6H, m, H5000, H6000, H7000 or
H4000, H400 and H300(500)), 7.24 (3H, m, H20000(60000) and H40000), 7.13 (2H,
d
162.7, 160.1, 150.6, 147.9, 145.2, 144.9, 139.2, 137.8, 137.5, 132.3,
128.4 (two overlapped signals),127.6,125.5,124.9,120.4, 115.4, 55.7.
MS (EI, m/z): 354 (49, Mþ), 353 (41), 277 (100), 276 (92), 275 (27),
262 (24), 260 (62), 233 (27), 232 (30), 205 (19), 79 (97), 52 (47);
HRMS (ESI-TOF, CH3OH): calcd for C22H19N4O: [MþH]þ 355.1559,
found 355.1552. Anal. Calcd for C22H18N4O$2/3H2O: C, 72.11; H,
5.32; N, 15.29. Found: C, 72.16; H, 5.29; N, 15.06.
m, H30000(50000)); 13C NMR (75 MHz, CD3OD):
d 155.1, 147.5, 147.4,
147.0, 141.3, 141.2, 138.5, 137.4, 137.3, 134.9, 132.9, 130.9, 130.4, 130.0,
129.8, 129.4,128.2, 128.1, 126.6, 126.0, 125.8, 124.2, 123.7,116.2, 60.8.
MS (EI, m/z): 470 (<2, MþꢀBr), 392 (11), 302 (19), 301 (25), 91
(100), 82 (15), 80 (16), 79 (37), 65 (24), 52 (25), 51 (25); HRMS (ESI-
TOF, CH3OH): calcd for C31H24N3S: [MꢀBr]þ 470.1691, found
470.1690. Anal. Calcd for C31H24BrN3S: C, 67.63; H, 4.39; N, 7.63; S,
5.82. Found: C, 67.48; H, 4.39; N, 7.89; S, 5.53.
4.5. Reaction of 3,5-disubstituted N-(pyridin-2-yl)pyridinium
aminides (12) with benzyl bromides
General method: In a dry round-bottomed flask, the corre-
sponding aminide (1 mmol) was dissolved in anhydrous acetone
(11 mL). After addition of the corresponding benzyl bromide
(3.5 mmol) the mixture was stirred at room temperature for the
time indicated in Table 3, until the starting aminide was no longer
detected by TLC. Once the reaction was complete, the solvent was
evaporated in vacuo and the residue was triturated with ethyl ac-
etate in an ultrasonic bath. The resulting suspension was filtered
and the solid was washed well with ethyl acetate to remove excess
benzyl bromide. The isolated salts 13 were used without further
purification in the next step.
4.5.4. 1-{N-[5-(Benzo[b]thiophen-3-yl)-3-phenylpyridin-2-yl]-N-
benzylamino}pyridinium bromide (13d). White solid (391 mg, 71%,
ethanol–ethyl acetate), mp 181–183 ꢁC; IR (KBr) nmax (cmꢀ1): 1615,
1466, 1432, 1403, 1064, 765, 736, 700, 683, 474; 1H NMR (500 MHz,
CD3OD):
d
8.82 (2H, dd, J¼7.0 and 1.3 Hz, H2(6)), 8.79 (1H, d,
J¼2.3 Hz, H60), 8.49 (1H, tt, J¼7.8 and 1.3 Hz, H4), 8.04 (1H, d,
J¼2.3 Hz, H40), 8.03 (1H, m, H700 or H400), 7.96 (1H, m, H400 or H700),
7.89 (2H, dd, J¼7.8 and 7.0 Hz, H3(5)), 7.86 (1H, s, H200), 7.50 (7H, m,
H20000(60000), H40000 and H30000(50000), H500 and H600), 7.28 (5H, m, H2000(6000),
H4000 and H3000(5000)); 13C NMR (75 MHz, CD3OD):
d 154.4, 148.1,
4.5.1. 1-{N-Benzyl-N-[5-phenyl-3-(thiophen-3-yl)pyridin-2-yl]ami-
no}pyridinium bromide (13a). Beige solid (385 mg, 77%, ethanol),
mp 182–184 ꢁC; IR (KBr) nmax (cmꢀ1): 1616, 1466, 1435, 1359, 772,
148.0, 147.5, 142.2, 141.9, 138.5, 137.7, 134.8, 133.8,132.7, 132.2, 130.7,
130.4, 130.1, 130.0 (two signals), 129.9, 129.6, 127.2, 126.0, 124.2,
123.0, 116.2, 60.7. MS (EI, m/z): 470 (<2, MþꢀBr), 390 (31), 389 (28),
313 (55), 286 (53), 79 (100), 52 (45), 51 (26); HRMS (ESI-TOF,
CH3OH): calcd for C31H24N3S: [MꢀBr]þ 470.1691, found 470.1696.
Anal. Calcd for C31H24BrN3S: C, 67.63; H, 4.39; N, 7.63; S, 5.82.
Found: C, 67.87; H, 4.58; N, 7.52; S, 5.78.
759, 719, 697, 686, 674; 1H NMR (300 MHz, CD3OD):
d 8.88 (2H, dd,
J¼6.9 and 1.4 Hz, H2(6)), 8.77 (1H, d, J¼2.3 Hz, H60), 8.51 (1H, tt,
J¼7.7 and 1.4 Hz, H4), 8.10 (1H, d, J¼2.3 Hz, H40), 7.93 (2H, dd, J¼7.7
and 6.9 Hz, H3(5)), 7.75 (2H, ap dd, J¼8.2 and 1.3 Hz, H200(600)), 7.64
(1H, dd, J¼5.0 and 2.9 Hz, H5000), 7.60 (1H, dd, J¼2.9 and 1.5 Hz,
H2000), 7.53 (3H, m, H400 and H300(500)), 7.46 (1H, dd, J¼5.0 and 1.5 Hz,
H4000), 7.31 (5H, s, H20000(60000), H40000 and H30000(50000)), 5.10 (2H, s, CH2);
4.5.5. 1-{N-[5-(3,5-Dimethylphenyl)-3-(4-methoxyphenyl)pyridin-2-
yl]-N-[(4-methyl)benzyl]-amino}pyridinium bromide (13e). White
solid (430 mg, 76%, ethanol–ethyl acetate), mp 182–184 ꢁC; IR (KBr)
nmax (cmꢀ1): 1608, 1514, 1441, 1256, 1181, 1029, 847, 839, 700; 1H
13C NMR (75 MHz, CD3OD):
d 154.5, 148.0, 147.8, 146.3, 140.4, 137.7,
137.6, 137.5, 134.8, 130.7, 130.4, 130.1, 130.0, 129.7, 129.5 (two
overlapped signals), 128.5, 128.2, 127.6, 126.4, 60.8. MS (EI, m/z):
420 (2, MþꢀBr), 339 (53), 338 (100), 337 (92), 309 (16), 263 (31),
261 (35) 169 (20), 168 (15), 91 (49); HRMS (ESI-TOF, CH3OH): calcd
for C27H22N3S: [MꢀBr]þ 420.1534, found 420.1528. Anal. Calcd for
C27H22BrN3S$3/2H2O: C, 61.48; H, 4.78; N, 7.97; S, 6.08. Found: C,
61.60; H, 4.39; N, 7.92; S, 5.70.
NMR (300 MHz, CD3OD):
d
8.76 (2H, dd, J¼6.9 and 1.3 Hz, H2(6)),
8.71 (1H, d, J¼2.3 Hz, H60), 8.47 (1H, tt, J¼7.7 and 1.3 Hz, H4), 7.96
(1H, d, J¼2.3 Hz, H40), 7.88 (2H, dd, J¼7.7 and 6.9 Hz, H3(5)), 7.43 (2H,
d, J¼8.9 Hz, H2000(6000)), 7.33 (2H, br s, H200(600)), 7.11 (5H, m , H400,
H20000(60000) and H30000(50000)), 7.04 (2H, d, J¼8.9 Hz, H3000(5000)), 5.03 (2H,
s, CH2), 3.87 (3H, s, OCH3), 2.41 (6H, s, CH3), 2.28 (3H, s, CH3); 13C NMR
(75 MHz, CD3OD):d161.6,154.5,147.9,147.8,145.9,140.4,140.1,137.8,
4.5.2. 1-{N-Benzyl-N-[3-phenyl-5-(thiophen-3-yl)pyridin-2-yl]ami-
no}pyridinium bromide (13b). White solid (300 mg, 60%, ethanol–
ethyl acetate), mp 193–195 ꢁC; IR (KBr) nmax (cmꢀ1): 1615, 1488,
1466, 1452, 1434, 1413, 1366, 913, 818, 721, 701, 685; 1H NMR
137.5, 131.9, 131.8, 131.3 (three overlapped signals), 131.2, 130.6,
129.8, 129.4, 125.9, 115.7, 60.4, 55.9, 21.4, 21.1. MS (EI, m/z): 486 (<2,
MþꢀBr), 406 (17), 405 (15), 315 (34), 82 (31), 81 (16), 80 (54), 79
(100), 52 (51), 51 (27); HRMS (ESI-TOF, CH3OH): calcd for C33H32N3O:

M. Co´rdoba et al. / Tetrahedron 66 (2010) 2624–2632
2631
[MꢀBr]þ 486.2545, found 486.2532. Anal. Calcd for C33H32BrN3O: C,
126.7, 126.2 (two overlapped signals), 123.4, 117.2, 45.7. MS (EI, m/
z): 342 (72, Mþ), 251 (19), 237 (24), 236 (24), 132 (12), 106 (100), 91
(63), 77 (14), 65 (19), 57 (11); HRMS (ESI-TOF, CH3OH): calcd for
C22H19N2S: [MþH]þ 343.1269, found 343.1260. Anal. Calcd for
C22H18N2S$1/5H2O (%): C, 76.36; H, 5.36; N, 8.09; S, 9.27. Found: C,
76.58; H, 5.62; N, 7.78; S, 9.18.
68.51; H, 5.81; N, 7.26. Found: C, 68.33; H, 5.70; N, 7.20.
4.5.6. 1-{N-[3-(4-Bromo-3,5-dimethylphenyl)-5-(4-methoxy-
phenyl)pyridin-2-yl]-N-[(4-methyl)benzyl]-amino}pyridinium
bromide (13f). Beige solid (532 mg, 94%, ethanol–ethyl acetate), mp
165–167 ꢁC; IR (KBr) nmax (cmꢀ1): 1609, 1516, 1468, 1247, 1184, 833,
1
709; H NMR (300 MHz, CD3OD):
d
8.72 (1H, d, J¼2.4 Hz, H60), 8.70
4.6.2. N-Benzyl-N-[3-phenyl-5-(thiophen-3-yl)pyridin-2-yl]amine
(14b). White solid (164 mg, 48%, ethyl acetate–hexane), mp 101–
103 ꢁC; IR (KBr) nmax (cmꢀ1): 3427, 1606, 1487, 1468, 784, 757, 700;
(2H, dd, J¼6.9 and 1.3 H0z, H2(6)), 8.49 (1H, tt, J¼7.9 and 1.3 Hz, H4),
7.95 (1H, d, J¼2.4 Hz, H4 ), 7.88 (2H, dd, J¼7.9 and 6.9 Hz, H3(5)), 7.68
(2H, d, J¼8.9 Hz, H200(600)), 7.10 (9H, m, H300(500), H2000(6000), H4000,
H20000(60000) and H30000(50000)), 5.03 (2H, s, CH2), 3.87 (3H, s, OCH3), 2.37
1H NMR (300 MHz, CD3OD):
d
8.41 (1H, d, J¼2.3 Hz, H6), 7.52 (1H, d,
J¼2.3 Hz, H4), 7.44 (3H, m, H200(600) and H400), 7.37 (2H, m, H300(500)),
7.32 (5H, m, H2000(6000), H3000(5000) and H4000), 7.24 (3H, m, H20, H40 and
H50), 4.94 (1H, d, J¼5.5 Hz, NH), 4.69 (2H, d, J¼5.5 Hz, CH2); 13C NMR
(6H, s,CH3), 2.28 (3H, s, CH3); 13CNMR(75 MHz,CD3OD):
d161.7, 153.9,
148.1, 147.6, 145.6, 140.2, 140.1, 139.6, 137.8, 137.0, 132.2, 131.8, 131.1,
130.6,130.5,129.7,129.4,129.2,127.6,115.8, 60.2, 55.8,21.3, 21.1. MS(EI,
m/z): 486 (<2,MþꢀBr), 406 (15), 315 (30), 274 (13), 105 (15), 82 (40), 80
(44), 79 (100), 52 (42); HRMS (ESI-TOF, CH3OH): calcd for C33H32N3O:
[MꢀBr]þ 486.2545, found 486.2538. Anal. Calcd for C33H32BrN3O: C,
69.96; H, 5.69; N, 7.42. Found: C, 69.86; H, 5.59; N, 7.78.
(75 MHz, CD3OD):
d 155.9, 144.8, 141.4, 140.4, 138.9, 136.8, 130.3,
130.1, 129.4, 129.1, 128.2, 127.8, 127.4, 126.4, 124.4, 122.9, 119.5, 46.1.
MS (EI, m/z): 342 (51, Mþ), 237 (18), 236 (18), 149 (24), 106 (100), 91
(48), 57 (26); HRMS (ESI-TOF, CH3OH): calcd for C22H19N2S:
[MþH]þ 343.1269, found 343.1260. Anal. Calcd for C22H18N2S: C,
77.16; H, 5.30; N, 8.18; S, 9.36. Found: C, 77.55; H, 5.68; N, 7.93; S,
9.09.
4.5.7. 1-(N-{5-(4-Methoxyphenyl)-3-[N-(4-methylbenzyl)pyridin-3-
ium]pyridin-2-yl}-N-[(4-methyl)benzyl]amino)pyridinium dibromide
(13g). Yellow solid (695 mg, 96%, ethanol), mp 176–178 ꢁC; IR (KBr)
nmax (cmꢀ1): 1609, 1517, 1428, 1250, 1183, 1120, 684; 1H NMR
4.6.3. N-[3-(Benzo[b]thiophen-3-yl)-5-phenylpyridin-2-yl]-N-ben-
zylamine (14c). Beige solid (235 mg, 60%, ethyl acetate–hexane),
mp 78–80 ꢁC; IR (KBr) nmax (cmꢀ1): 2919, 1602, 1508, 1486, 1451,
(300 MHz, CD3OD):
d
9.48 (1H, m, H2000), 9.21 (1H, dt, J¼6.4 and
1.3 Hz, H6000), 9.15 (2H, dd, J¼6.9 and 1.3 Hz, H2(6)), 8.97 (1H, dt,
J¼8.0 and 1.6 Hz, H4000), 8.92 (1H, d, J¼2.4 Hz, H60), 8.57 (1H, tt, J¼7.7
and 1.3 Hz, H4), 8.33 (1H, d, J¼2.4 Hz, H40), 8.32 (1H, dd, J¼8.1 and
6.4 Hz, H5000), 8.04 (2H, dd, J¼7.7 and 6.9 Hz, H3(5)), 7.76 (2H, d,
J¼8.9 Hz, H200(600)), 7.53 (2H, d, J¼8.1 Hz, H20000(60000)), 7.33 (2H, d,
J¼8.1 Hz, H30000(50000)), 7.12 (2H, d, J¼8.9 Hz, H300(500)), 7.04 (2H, d,
J¼7.9 Hz, H200000(600000)), 6.86 (2H, d, J¼7.9 Hz, H300000(500000)), 5.94 (2H, s,
CH2), 4.93 (2H, s, CH2), 3.89 (3H, s, OCH3), 2.39 (3H, s, CH3), 2.28 (3H,
1427, 762, 734, 696; 1H NMR (500 MHz, CDCl3):
d 8.49 (1H, d,
J¼2.3 Hz, H6), 7.91 (1H, br d, J¼7.9 Hz, H700), 7.68 (1H, d,
J¼2.3 Hz, H4), 7.63 (1H, br d, J¼7.2 Hz, H400), 7.54 (2H, dd, J¼8.1
and 1.2 Hz, H20(60)), 7.50 (1H, s, H200), 7.38 (4H, m, H30(50), H500
and H600), 7.29 (1H, tt, J¼7.4 and 1.1 Hz, H40), 7.26 (4H, m,
H2000(6000) and H3000(5000)), 7.21 (1H, m, H4000), 4.80 (1H, t, J¼5.6 Hz,
NH), 4.68 (2H, d, J¼5.6 Hz, CH2); 13C NMR (75 MHz, CDCl3):
s, CH3); 13C NMR (75 MHz, CD3OD):
d 162.2, 153.2, 148.6, 148.0,
d
155.4, 145.9, 140.5, 139.7, 138.2, 137.7, 136.9, 132.8, 128.9, 128.4,
127.4, 127.0, 126.7, 126.1, 125.9, 125.7, 124.9, 124.5, 123.1, 122.9,
115.7, 45.4. MS (EI, m/z): 392 (13, Mþ), 91 (100), 77 (22), 65
(27); HRMS (ESI-TOF, CH3OH): calcd for C26H21N2S: [MþH]þ
393.14200, found 393.14307. Anal. Calcd for C26H20N2S$1/2H2O
(%): C, 78.36; H, 5.23; N, 7.03; S, 8.05. Found: C, 78.65; H, 5.18;
N, 7.32; S, 8.05.
147.9, 145.7, 145.6, 141.7, 140.4, 140.3, 138.8, 138.4, 131.6, 131.5, 130.9,
130.8, 130.5, 130.4, 129.9, 129.7, 129.6, 128.8, 126.0, 115.9,115.5, 66.0,
62.2, 55.9, 21.3, 21.1. MS (EI, m/z): 645/643 (<2/<2, MþꢀBr), 288
(17), 82 (49), 81 (44), 80 (87), 79 (100), 78 (15), 53 (27), 52 (57), 51
(36), 50 (22); HRMS (ESI-TOF, CH3OH): calcd for C38H3679BrN4O:
[MꢀBr]þ 643.2072, found 643.2035. Anal. Calcd for
C38H36Br2N4O$2/5H2O (%): C, 59.31; H, 5.37; N, 7.28; S, 9.52. Found:
C, 59.34; H, 4.98; N, 7.57.
4.6.4. N-[5-(Benzo[b]thiophen-3-yl)-3-phenylpyridin-2-yl]-N-ben-
zylamine (14d). Yellow oil (275 mg, 70%); IR (NaCl) nmax (cmꢀ1):
3436, 2922, 1676, 1605, 1524, 1489, 1394, 1346, 1258, 1243, 783,
4.6. Preparation of unsymmetrical benzyl (3,5-diarylpyridin-
2-yl)amines (14)
759, 733, 699; 1H NMR (500 MHz, CDCl3):
d 8.39 (1H, d,
J¼2.3 Hz, H6), 7.90 (2H, m, H70 and H40), 7.56 (1H, d, J¼2.3 Hz,
H4), 7.47 (4H, m, H200(600) and H300(500)), 7.37 (3H, m, H50, H60 and
H400), 7.35 (1H, s, H20), 7.32 (4H, m, H2000(6000) and H3000(5000)), 7.24
(1H, m, H4000), 5.03 (1H, t, J¼5.6 Hz, NH), 4.72 (2H, d, J¼5.6 Hz,
General method: Zinc dust (10 mmol) was added to a solution of
the corresponding pyridinium salt 13 (1 mmol) in glacial acetic acid
(15 mL) and the mixture was stirred at room temperature for the
time indicated in Table 3, until the starting pyridinium salt was no
longer detected by TLC. Once the reaction had finished, the solvent
was evaporated to dryness. The residue was purified by column
chromatography on silica gel, using hexane:ethyl acetate as eluent,
and the corresponding N-benzyl(3,5-diarylpyridin-2-yl)amine 14
was crystallized from a suitable solvent.
CH2); 13C NMR (125 MHz, CDCl3):
d 154.7, 146.5, 140.6, 139.7,
138.0, 137.5, 137.4, 135.0, 129.3, 128.9, 128.5, 128.0, 127.5, 127.1,
124.4, 124.3, 123.0, 122.7, 122.4, 122.1, 121.3, 45.6. MS (EI, m/z):
392 (65, Mþ), 391 (29), 286 (25), 106 (100), 91 (56), 65 (18);
HRMS (ESI-TOF, CH3OH): calcd for C26H21N2S: [MþH]þ 393.1425,
found 393.1424.
4.6.5. N-[5-(3,5-Dimethylphenyl)-3-(4-methoxyphenyl)pyridin-2-
yl]-N-[(4-methyl)benzyl]amine (14e). \Colourless oil (302 mg, 74%);
IR (NaCl) nmax (cmꢀ1): 3435, 2922, 1602, 1513, 1246, 1176, 1030; 1H
4.6.1. N-Benzyl-N-[5-phenyl-3-(thiophen-3-yl)pyridin-2-yl]amine
(14a). White solid (215 mg, 63%, ethyl acetate–hexane), mp 130–
132 ꢁC; IR (KBr) nmax (cmꢀ1): 1602, 1485, 1350, 1227, 800, 774, 765,
734, 694, 674; 1H NMR (500 MHz, CDCl3):
d
8.38 (1H, d, J¼2.4 Hz,
NMR (300 MHz, CD3OD):
d
8.18 (1H, d, J¼2.3 Hz, H6), 7.53 (1H, d,
J¼2.3 Hz, H4), 7.38 (2H, d, J¼8.6 Hz, H200(600)), 7.19 (2H, d, J¼8.1 Hz,
H2000(6000)), 7.15 (2H, ap s, H20(60)), 7.11 (2H, d, J¼8.1 Hz, H3000(5000)), 7.04
(2H, d, J¼8.6 Hz, H300(500)), 6.95 (1H, ap s, H40), 4.55 (2H, s, CH2), 3.83
(3H, s, OCH3), 2.34 (6H, s, CH3), 2.30 (3H, s, CH3); 13C NMR (75 MHz,
H6), 7.62 (1H, d, J¼2.4 Hz, H4), 7.53 (2H, dd, J¼8.1 and 1.2 Hz,
H20(60)), 7.44 (1H, dd, J¼5.0 and 2.9 Hz, H500), 7.40 (3H, m, H30(50)
and H200), 7.31 (5H, m, H2000(6000), H3000(5000) and H40), 7.24 (2H, m,
H4000 and H400), 5.07 (1H, d, J¼5.5 Hz, NH), 4.70 (2H, d, J¼5.5 Hz,
CH2); 13C NMR (125 MHz, CDCl3):
d 154.9, 145.2, 139.8, 138.4, 138.0,
CD3OD):
d 161.0, 156.2, 144.6, 139.5, 139.3, 138.1, 137.5, 137.4, 131.2,
130.8,130.0,129.4,128.2,127.6,124.8,124.2,115.7, 55.7, 46.0, 21.5, 21.1.
135.8, 128.9, 128.6, 127.8, 127.5, 127.1 (two overlapped signals),

2632
M. Co´rdoba et al. / Tetrahedron 66 (2010) 2624–2632
MS (EI, m/z): 408 (76, Mþ), 407 (37), 289 (27), 120 (100), 105 (87), 77
(24), 57 (15); HRMS (ESI-TOF, CH3OH): calcd for C28H29N2O: [MþH]þ
409.2280, found 409.2419.
10895; (q) Cho, S.-D.; Kim, H.-K.; Yim, H.-S.; Kim, M.-R.; Lee, J.-K.; Kim, J.-J.;
Yoon, Y.-J. Tetrahedron 2007, 63, 1345–1352; (r) Guram, A. S.; Wang, X.;
Brunel, E. E.; Faul, M. M.; Larsen, R. D.; Martinelli, M. J. J. Org. Chem. 2007,
72, 5104–5112; (s) Yang, D. X.; Colletti, S. L.; Wu, K.; Song, M.; Li, G. Y.; Shen,
H. C. Org. Lett. 2009, 11, 381–384.
4. Molander, G. A.; Ellis, N. Acc. Chem. Res. 2007, 40, 275–286 and references
therein.
5. (a) Prieto, M.; Zurita, E.; Rosa, E.; Mun˜oz, L.; Lloyd-Williams, P.; Giralt, E. J. Org.
Chem. 2004, 69, 6812–6820; (b) Billingsley, K.; Buchwald, S. L. J. Am. Chem. Soc.
2007, 129, 3358–3366; (c) Nichele, T. Z.; Favero, C.; Monteiro, A. L. Catal.
Commun. 2009, 10, 693–696.
4.6.6. N-[3-(3,5-Dimethylphenyl)-5-(4-methoxyphenyl)pyridin-2-
yl]-N-[(4-methyl)benzyl]amine (14f). White solid (290 mg, 71%,
ethyl acetate–hexane), mp 140–142 ꢁC; IR (KBr) nmax (cmꢀ1): 3408,
1608, 1569, 1493, 1460, 1339, 1280, 1248, 1181, 1130, 827; 1H NMR
(300 MHz, CDCl3):
d
8.32 (1H, d, J¼2.3 Hz, H6), 7.48 (1H, d, J¼2.3 Hz,
6. (a) Leadbeater, N. E. Chem. Commun. 2005, 2881–2902; (b) Silva, A. C.; Souza, A.
L. F.; Antunes, O. A. C. J. Organomet. Chem. 2007, 692, 3104–3107; (c) Lipshutz,
H4), 7.45 (2H, d, J¼8.6 Hz, H20(60)), 7.20 (2H, d, J¼8.0 Hz, H2000(6000)),
7.10 (2H, d, J¼8.0 Hz, H3000(5000)), 7.04 (2H, s, H200(600)), 6.98 (1H, s,
H400), 6.94 (2H, d, J¼8.6 Hz, H30(50)), 4.91 (1H, t, J¼5.7 Hz, NH), 4.62
(2H, d, J¼5.7 Hz, CH2), 3.82 (3H, s, OCH3), 2.32 (6H, s, CH3), 2.30 (3H,
´
B. H.; Ghorai, S. Aldrichim. Acta 2008, 41, 59–72; (d) Alacid, E.; Najera, C.
J. Organomet. Chem. 2009, 694, 1658–1665.
7. Li, J.-H.; Deng, C.-L.; Xie, Y.-X. Synth. Commun. 2007, 37, 2433–2448.
8. (a) Carceller, R.; Garcı´a-Navı´o, J. L.; Izquierdo, M. L.; Alvarez-Builla, J.; Fajardo,
M.; Go´ mez-Sal, P.; Gago, F. Tetrahedron 1994, 50, 4995–5012; (b) Martı´nez-
s, CH3); 13C NMR (75 MHz, CDCl3):
d 158.6, 154.4, 144.5, 138.8, 137.7,
´
´
Barrasa, V.; Delgado, F.; Burgos, C.; Garcıa-Navıo, J. L.; Izquierdo, M. L.; Alvarez-
Builla, J. Tetrahedron 2000, 56, 2481–2490; (c) Reyes, M. J.; Delgado, F.;
Izquierdo, M. L.; Alvarez-Builla, J. Tetrahedron 2002, 58, 8573–8579; (d) Castillo,
R.; Izquierdo, M. L.; Alvarez-Builla, J. Tetrahedron Lett. 2007, 48, 5899–5903; (e)
136.9, 136.5,135.5,131.1,129.5, 129.1,127.4,127.2,126.6, 125.7, 122.4,
114.3, 55.3, 45.4, 21.3, 21.1. MS (EI, m/z): 408 (100, Mþ), 407 (35),
289 (25), 120 (53), 105 (53), 79 (13), 77 (15); HRMS (ESI-TOF,
CH3OH): calcd for C28H29N2O: [MþH]þ 409.2280, found 409.2269.
Anal. Calcd for C28H28N2O$1/2H2O (%): C, 80.37; H, 6.74; N, 6.94.
Found: C, 80.24; H, 6.64; N, 6.54.
Castillo, R.; Co
´ rdoba, M.; Izquierdo, M. L.; Alvarez-Builla, J. Tetrahedron 2009, 65,
9782–9790.
9. (a) Reyes, M. J.; Izquierdo, M. L.; Alvarez-Builla, J. Tetrahedron Lett. 2004, 45,
8713–8715; (b) Reyes, M. J.; Castillo, R.; Izquierdo, M. L.; Alvarez-Builla, J. Tet-
rahedron Lett. 2006, 47, 6457–6460; (c) Castillo, R.; Reyes, M. J.; Izquierdo, M. L.;
Alvarez-Builla, J. Tetrahedron 2008, 64, 1351–1370.
10. (a) Muci, A. R.; Buchwald, S. L. Top. Curr. Chem. 2002, 219, 131–209; (b) Antilla, J.
C.; Baskin, J. M.; Barder, T. E.; Buchwald, S. L. J. Org. Chem. 2004, 69, 5578–5587;
(c) Urgaonkar, S.; Verkade, J. G. J. Org. Chem. 2004, 69, 9135–9142; (d) Sato, S.;
Sakamoto, T.; Miyazawa, E.; Kikugawa, Y. Tetrahedron 2004, 60, 7899–7906; (e)
Singh, O. M.; Singh, S. J.; Kim, S. N.; Lee, S.-G. Bull. Korean Chem. Soc. 2007, 28,
115–117; (f) Tu, S.; Jiang, B.; Zhang, Y.; Jia, R.; Zhang, J.; Yao, C.; Shi, F. Org.
Biomol. Chem. 2007, 5, 355–359; (g) Li, J. J.; Wang, Z.; Mitchell, L. H. J. Org. Chem.
2007, 72, 3606–3607; (h) Scho¨n, U.; Messenger, J.; Buckendahl, M.; Prabhu, M.
S.; Konda, A. Tetrahedron Lett. 2007, 48, 2519–2525; (i) Poola, B.; Choung, W.;
Nantz, M. H. Tetrahedron 2008, 64, 10798–10801; (j) Shah, H. C.; Shah, V. H.;
Desai, N. D. Arkivoc 2009, 76–87.
Acknowledgements
´
The authors wish to thank the Comision Interministerial de
´
Ciencia y Tecnologıa (CTQ2008-05027/BQU2) for financial support,
´
and the Ministerio de Educacion y Ciencia (MEC) and the Uni-
´
versidad de Alcala (UAH) for fellowships (R.R.C. and M.C.).
References and notes
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