Pyridinium N-(2′-azinyl)aminides: Regioselective synthesis of N-(2-pyridyl) substituted polyamines

Article abstract of DOI:10.1016/S0040-4020(02)00901-8

The regioselective alkylation of pyridinium-N-(2′-pyridyl)aminide with alkyl dihalides under mild conditions, followed by N-N bond reduction of the corresponding bis-salts, allowed an easy preparation of N,N′-bis(2-pyridyl)diamines. The same methodology h

Full text of DOI:10.1016/S0040-4020(02)00901-8

Tetrahedron 58 (2002) 8573–8579
Pyridinium N-(20-azinyl)aminides: regioselective synthesis
of N-(2-pyridyl) substituted polyamines
*
´
M. Jose Reyes, Francisca Delgado, M. Luisa Izquierdo and Julio Alvarez-Builla
´ ´ ´ ´
Departamento de Quımica Organica, Universidad de Alcala, Alcala de Henares, 28871 Madrid, Spain
Received 16 May 2002; accepted 24 July 2002
Abstract—The regioselective alkylation of pyridinium-N-(20-pyridyl)aminide with alkyl dihalides under mild conditions, followed by N–N
bond reduction of the corresponding bis-salts, allowed an easy preparation of N,N0-bis(2-pyridyl)diamines. The same methodology has been
applied to the synthesis of N,N0,N00-tris(2-pyridyl)triamines. q 2002 Elsevier Science Ltd. All rights reserved.
The role of polyamines in biological systems is well
recognized and, over the last two decades, many functions
of prokaryotic and eukaryotic cells have been shown to be
polyamine dependent.1–3 Natural and synthetic polyamines
are potent cation-channel blockers and templates for the
design of synthetic vectors with potential application in
gene therapy.3 A number of polyamine analogues have
shown promise as anticancer agents4,5 and a platinum
complex linked by a bridging diamine showed biological
activity against various human cancer cell lines.6,7
achieved using cesium hydroxide.9 In the last years, we have
been interested in heteroaryl-stabilized cycloiminium ylides
1, as building blocks for the synthesis of heterocyclic
derivatives10–15 and, more recently, we are exploring the
synthetic utility of pyridinium N-(20-azinyl)aminides 2
(Scheme 1).16–21 Some of our work in this field has been
concerned with alkylation processes and in a preceding21
paper we reported the regioselective synthesis of 2-alkyl-
aminoazines 4 in a two-step method. As it is well known, the
direct alkylation of heterocyclic amidines 5 is unsatisfactory
as a preparative method, because mixtures of N-endo-
substituted 6 and N-exosubstituted 7 derivatives are
obtained and, usually, alkylation mainly occurs at the
most basic endocyclic nitrogen22,23 (Scheme 1). However,
when permanent nitride species, such as the pyridinium
N-(20azinyl)aminides 2, are used, regioselective alkylation
takes place at the exocyclic nitrogen, and the salts 3 are
The synthetic approaches to polyamine chemistry have been
recently reviewed, being the N-alkylation of amines the
most widely used reaction in polyamine synthesis.8 To
avoid polyalkylation, excess of amine or a suitable
protecting group have to be used but, in the field of
diamines and polyamines, mono N-alkylation has been
Scheme 1.
Keywords: polyamines; pyridinium bis-salts; aminides; alkylation; ylids.
*
Corresponding author. Tel.: þ34-91-885-4606; fax: þ34-91-885-4686; e-mail: julio.alvarez@uah.es
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00901-8

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M. J. Reyes et al. / Tetrahedron 58 (2002) 8573–8579
Scheme 2.
obtained. Two factors can explain the observed regioselec-
tivity, the stabilizing effect of the pyridinium moiety over
the exocyclic N-aminide anion, and the existence of an
intramolecular hydrogen bond blocking the a-nuclear
nitrogen.17 The final N–N bond reduction of the pyridinium
salts affords the corresponding 2-alkylaminoazines 4.
1. Results and discussion
Different dihaloderivatives 8 were reacted at room tem-
perature with the N-(20-pyridyl)aminide 2a to produce the
bis-pyridinium salts 9 as the main products (Scheme 2).
Reduction with formic acid/triethylamine in the presence
of Pt/C,18 afforded the corresponding diamines 11 (Table 1).
The alkylation process employing 0a benzylic dihaloderiva-
tive, as a,a0-dibromoxylenes, 2,2 -bis(bromomethyl)-1,10-
biphenyl or 2,5-bis(bromomethyl)pyridine, afforded a
quantitative yield of the bis-salts 9i–m (Table 1), in a
highly regioselective process, where no traces of the
regioisomers 10 were detected in the reaction mixture.
This paper presents the results obtained in the synthesis of
some N,N0-bis(2-pyridyl)diamines 11 from N-(20-pyridyl)-
aminide 2a (Het¼2-pyridyl) and the corresponding dihalo-
derivatives (molar ratio 2:1), by applying the two-step
method previously descri0bed. The same methodology
allows the synthesis of N,N ,N00-tris(2-pyridyl)triamines 15.
Preparation of the starting pyridinium N-aminides 2 has
been previously described.17,18
The same process, when applied to the less reactive
Table 1. Compounds 9a–m and 11a–m obtained
Compound 9
W
X
Reaction time (days)
Yield (%)
Compound 11
Yield (%)
a
b
c
d
e
f
(CH2)4
(CH2)5
(CH2)6
(CH2)7
(CH2)8
(CH2)9
I
I
I
Br
Br
Br
Br
I
3
3
3
5
5
9
7
7
50
58
54
40
40
55
50
46
a
b
c
d
e
f
45
49
42
64
43
70
40
51
g
h
(CH2)2O(CH2)2
(CH2)2O(CH2)2O(CH2)2
g
h
i
Br
Br
Br
Br
2
2
2
2
96
97
95
90
i
j
60
50
55
47
j
k
l
k
l
m
Br
1
97
m
85

M. J. Reyes et al. / Tetrahedron 58 (2002) 8573–8579
8575
Scheme 3.
Scheme 4.
aliphatic dihaloderivatives took place in the same way,
yielding the bis-salts 9a–h as the main products, but also
the corresponding ring alkylated derivatives 10 in a rough
10–15% yield, detected by 1H NMR. As chain length
increases, longer time was necessary to obtain a similar
conversion, and in compounds 9a–f about a 15% of starting
aminide 2a was always detected. On the contrary, with short
dialkylating agents, like in the synthesis of 12 (Scheme 3)
from 1,2-diiodoethane or 1,3-diiodopropane, no bis-alkyl-
ation was observed on 2a, probably due to electronic
repulsion in the intermediate salt. With diiodoethane, 2a
was recovered as hydroiodide, indicating a predominance of
the elimination process, while compound 13 was obtained
from 1,3-diiodopropane.
2. Experimental
All melting points were determined in open capillary tubes,
on a Gallenkamp MFB-595-010M and are uncorrected. IR
spectra were obtained on a Perkin–Elmer FTIR 1725X
spectrometer. 1H and 13C NMR (300 and 75 MHz,
respectively) spectra were recorded on a Varian Unity
300 MHz spectrometer at room temperature. Chemical
shifts are given in ppm (d) relative to TMS. Coupling
constants (J) are in hertz (Hz), and signals are described as
follows: s, singlet; d, doublet; t, triplet; br., broad; m,
multiplet; ap., apparent; etc. Mass spectra (m/z, I%) were
recorded on a VG AutoSpec (Micromass Instrument).
Elemental analyses were carried out on a Heraeus Rapid
CHN analyzer and are within 0.4% of the theoretical values
for all the new compounds described. All reagents were
obtained from commercial sources and used without further
purification. All solvents were purified, dried and finally
distilled before use following reported procedures.25 TLC
analyses were performed on silica gel 60 plates F254
(Macherey–Nagel) and flash purifications were carried out
on silica gel 60 (40–63 mm, Merck) and/or employing
Biotage columns, using the solvent eluting reported for each
case. Spots were visualized under UV light. Ylides 2a,b
have been previously described.17,18
When 1-bromo-2-(2-bromoethoxy)ethane or 1-iodo-2-[2-
(2-iodoethoxy)ethoxy]ethane were used as alkylating
agents, the bis-salts 9g and 9h were obtained with similar
yields than analogous compounds 9b and 9e. Monoalkyl-
ation product was detected in the synthesis of 9g and, when
the reaction mixture was reduced, 4-pyridin-2-yl morpho-
line24 was obtained together with the diamine 11g.
When the process was applied to the synthesis of tris-salts
14, (Scheme 4) the process occurred with high regioselec-
tivity and yield. In this case, a mixture of acetonitrile and
N,N-dimethylformamide was used as solvent, to avoid
precipitation of the intermediates bis-salts, insolubles in
acetone, the usual solvent. Then, the usual reduction with
formic acid/triethylamine–Pd/C produced the triamines 15.
2.1. Preparation of pyridinium salts 9a–m and 14a,b
General method. To a solution of the pyridinium N-(20-
pyridyl)aminide 2a (514 mg, 3 mmol) in acetone (15 mL),
the corresponding dihalide (1.4 mmol) was added, and the
mixture was stirred at room temperature until no progress
was observed by TLC. The salts were obtained either as
solids, which were filtered, washed with acetone and
recrystallized or as oils, which were washed with diethyl
ether and used in the next step without further purification.
As a conclusion, the use of pyridinium N-aminides like
2a,b, can be a good way to produce di- or polialkylamino
derivatives bearing 2-aminoheterocyclic fragments, where
properties like basicity, or coordinating ability, can be easily
modulated.

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M. J. Reyes et al. / Tetrahedron 58 (2002) 8573–8579
To obtain 9g and 9h, THF (15 mL) was used as solvent. The
salts0 14 were obtained in the same way from pyridinium
N-(2 -pyridyl)aminide 2a0 (770 mg, 0 4.5 mmol) for 14a or
from pyridinium N-(5 -bromo-2 -pyridyl)aminide 2b
(1.13 g, 4.5 mmol) for 14b, and 2,4,6-tris(bromomethyl)-
mesitylene26 (500 mg, 1.4 mmol) in a mixture of aceto-
nitrile (13.5 mL) and N,N-dimethylformamide (1.5 mL).
CH2–N); 1.61 (4H, m, CH2b); 1.37 (8H, m, CH2g, CH2d
and CH21).
2.1.6. 1-{[9-(Pyridin-1-ium-pyridin-2-ylamino)nonyl]-
pyridin-2-ylamino}pyridinium dibromide (9f). Brown
oil (484 mg, 55%, total yield, 35% for 9f); dH (300 MHz,
CD3OD) 9.23 (4H, dd, J¼6.8, 1.2 Hz, H2(6)); 8.82 (2H, tt,
J¼7.7, 1.2 Hz, H4); 8.31 (4H, dd, J¼7.7, 6.8 Hz, H3(5));
8.10 (2H, dd, J¼5.0, 1.8 Hz, H60); 7.84 (2H, ddd, J¼8.6,
7.3, 1.8 Hz, H40); 7.12 (2H, d, J¼8.6 Hz, H30); 7.07 (2H, dd,
J¼7.3, 5.0 Hz, H50); 4.15 (4H, t, J¼7.5 Hz, CH2–N); 1.61
(4H, m, CH2b); 1.37 (10H, m, CH2g, CH2d and CH21).
2.1.1. 1-{4-[(Pyridin-1-ium-pyridin-2-ylamino)butyl]-
pyridin-2-ylamino}pyridinium diiodide (9a). Yellow
solid (456 mg, 50%, methanol), mp 233–2348C; [Found:
C, 44.21; H, 4.04; N, 12.76. C24H26I2N6 requires C,
44.19; H, 4.02; N, 12.88%]; nmax (KBr) 3008, 1917,
1473, 1429 cm21; dH (300 MHz, CD3OD) 9.24 (4H, dd,
J¼5.2, 1.2 Hz, H2(6)); 8.82 (2H, tt, J¼7.6, 1.2 Hz, H4);
8.31 (4H, dd, J¼7.6, 5.2 Hz, H3(5)); 8.12 (2H, dd, 0J¼4.8,
1.6 Hz, H60)0; 70.83 (2H, ddd, J¼8.7, 7.3, 1.6 Hz, H4 ); 7.08
(4H, m, H3 (5 )); 4.26 (4H, br.t, CH2–N); 1.89 (4H, m,
CH2–C).
2.1.7. 1-{[3-Oxa-5-(pyridin-1-ium-pyridin-2-ylamino)-
pentyl]pyridin-2-ylamino}pyridinium dibromide (9g).
Brown oil (442 mg, 55%, total yield, 50% for 9g); dH
(300 MHz, CD3OD) 9.20 (4H, dd, J¼6.7, 1.4 Hz, H2(6));
8.75 (2H, tt, J¼7.8, 1.4 Hz, H4); 8.24 (4H, dd, J¼7.8,
6.7 Hz, H3(5)); 8.11 (2H, ddd, J¼4.9, 1.8, 0.9 Hz, H60);
7.80 (2H, ddd, J¼8.7, 7.0, 1.8 Hz, H40); 7.06 (2H, dd,
J¼7.0, 4.9 Hz, H50); 6.97 (2H, d, J¼8.7 Hz, H30); 4.31 (4H,
t, J¼4.9 Hz, CH2O); 3.79 (4H, t, CH2N).
2.1.2. 1-{5-[(Pyridin-1-ium-pyridin-2-ylamino)pentyl]-
pyridin-2-ylamino}pyridinium diiodide (9b). Brown oil
(500 mg, 50% for 11b); dH (300 MHz, CD3OD) 9.27 (4H,
dd, J¼5.9, 1.3 Hz, H2(6)); 8.81 (2H, tt, J¼7.0, 1.3 Hz, H4);
8.32 (4H, dd, J¼7.0, 5.9 Hz, H3(5)); 8.10 (2H, dd, 0J¼5.3,
1.8 Hz, H60); 7.83 (2H, ddd, J¼8.7, 7.3, 1.8 Hz, H4 ); 7.13
(2H, d, J¼8.7 Hz, H30); 7.06 (2H, dd, J¼7.3, 5.3 Hz, H50);
4.21 (4H, br.t, CH2–N); 1.72 (6H, m, CH2–C).
2.1.8. 1-{[3,6-Dioxa-8-(pyridin-1-ium-pyridin-2-ylamino)-
octyl]pyridin-2-ylamino} pyridinium diiodide (9h).
Brown oil (748 mg, 75%, total yield, 46% for 9h); dH
(300 MHz, CD3OD) 9.26 (4H, dd, J¼6.8, 1.3 Hz, H2(6));
8.82 (2H, tt, J¼7.8, 1.3 Hz, H4); 8.31 (4H, dd, J¼7.8,
6.8 Hz, H3(5)); 8.11 (2H, ddd, J¼4.9, 1.8, 0.9 Hz, H60);
7.83 (02H, ddd, J¼8.6, 7.3, 1.8 Hz, H40); 7.06 (4H, m, H30
and 5 ); 4.41 (4H, t, J¼4.7 Hz, CH2O); 3.78 (4H, t, J¼
4.7 Hz, CH2N); 3.38 (4H, s, (OCH2)2).
2.1.3. 1-{6-[(Pyridin-1-ium-pyridin-2-ylamino)hexyl]-
pyridin-2-ylamino}pyridinium diiodide (9c). Yellow
solid (514 mg, 54%, ethanol), mp 210–2128C; [Found: C,
46.14; H, 4.35; N, 12.45. C26H30I2N6 requires C, 45.90;
H, 4.44; N, 12.35%]; nmax (KBr) 3012, 1619, 1468,
1432 cm21; dH (300 MHz, CD3OD) 9.25 (4H, dd, J¼5.8,
1.4 Hz, H2(6)); 8.83 (2H, tt, J¼7.3, 1.4 Hz, H4); 8.33 (4H,
dd,0 J¼7.3, 5.8 Hz, H3(5)); 8.09 (2H, dd, J¼5.0, 1.9 Hz,
H6 ); 7.84 (2H, ddd, J¼8.7, 7.3, 1.9 Hz, H40); 7.16 0(2H, d,
J¼8.7 Hz, H30); 7.07 (2H, dd, J¼7.3, 5.0 Hz, H5 ); 4.21
(4H, t, J¼7.6 Hz, CH2–N); 1.67 (4H, m, CH2b); 1.55 (4H,
m, CH2g).
2.1.9. 1-{[2-(Pyridin-1-ium-pyridin-2-ylaminomethyl)-
benzyl]pyridin-2-ylamino}pyridinium dibromide (9i).
Pale yellow solid (815 mg, 96%, ethanol/ethyl acetate),
mp 218–2198C; [Found: C, 55.41; H, 4.61; N, 13.61.
C28H26Br2N6 requires C, 55.46; H, 4.32; N, 13.86%]; nmax
(KBr) 2995, 1586, 1470, 1428, 775, 691 cm21; dH
(300 MHz, CD3OD) 9.27 (4H, dd, J¼6.8, 1.6 Hz, H2(6));
8.700 (2H, tt, J¼7.7, 1.6 Hz, H4); 8.20 (6H0, m, H3(5) and
H6 ); 7.83 (2H, ddd, J¼8.7, 7.5, 1.6 Hz, H4 ); 7.16 (6H, m,
H–Ar and H50); 7.05 (2H, d, J¼7.5 Hz, H30); 5.68 (4H, s,
CH2).
2.1.4. 1-{7-[(Pyridin-1-ium-pyridin-2-ylamino)heptyl]-
pyridin-2-ylamino}pyridinium dibromide (9d). Brown
oil (420 mg, 50% total yield, 42% for 2d); dH (300 MHz,
CD3OD) 9.21 (4H, dd, J¼5.8, 1.2 Hz, H2(6)); 8.80 (2H, tt,
J¼7.2, 1.2 Hz, H4); 8.31 (4H, dd, J¼7.2, 5.8 Hz, H3(5));
8.10 (2H, dd, J¼4.8, 1.9 Hz, H60); 7.81 (2H, ddd, J¼8.7,
7.3, 1.9 Hz, H40); 7.12 (2H, d, J¼8.7 Hz, H30); 7.07 (2H, dd,
J¼7.3, 4.8 Hz, H50); 4.20 (4H, t, J¼7.5 Hz, CH2–N); 1.65
(4H, m, CH2b); 1.45 (6H, m, CH2g and CH2d).
2.1.10. 1-{[3-(Pyridin-1-ium-pyridin-2-ylaminomethyl)-
benzyl]pyridin-2-ylamino}pyridinium dibromide (9j).
White solid (823 mg, 96%, ethanol/ethyl acetate), mp
227–2288C; [Found: C, 55.76; H, 4.40; N, 14.10.
C28H26Br2N6 requires C, 55.46; H, 4.32; N, 13.86%]; nmax
(KBr) 3012, 1574, 1468, 1427, 773, 682 cm21; dH
(300 MHz, CD3OD) 9.17 (4H, dd, J¼6.8, 1.2 Hz, H2(6));
8.608 (2H, tt, J¼7.6, 1.2 Hz, H4); 8.16 (6H, m, H3(5) and
H6 ); 7.86 (2H, ddd, J¼080 .5, 8.0, 1.6 0H0 z, H40); 7.62 (1H,0br.s,
H-200); 7.34 (3H, m, H4 (600) and H5 ); 7.15 (4H, m, H3 and
50); 5.37 (4H, s, CH2).
2.1.5. 1-{8-[(Pyridin-1-ium-pyridin-2-ylamino)octyl]pyri-
din-2-ylamino}pyridinium dibromide (9e). Yellow solid
(344 mg, 40%, ethanol/ethyl acetate), mp 202–2038C;
[Found: C, 54.95; H, 5.59; N, 13.45. C28H34Br2N6 requires
C, 54.74; H, 5.58; N, 13.68%]; nmax (KBr) 3005, 2932,
1617, 1472, 1433 cm21; dH (300 MHz, CD3OD) 9.22
(4H, dd, J¼5.2, 1.2 Hz, H2(6)); 8.80 (2H, tt, J¼7.3,
1.2 Hz, H4); 8.30 (4H, dd, J¼0 7.3, 5.2 Hz, H3(5)); 8.10
(2H, dd, J¼4.8, 1.7 Hz, H6 ); 7.82 (2H, ddd, 0 J¼8.5,
7.2, 1.7 Hz, H40); 7.10 (2H, d, J¼8.5 Hz, H3 ); 7.07
(2H, dd, J¼7.2, 4.8 Hz, H50); 4.15 (4H, t, J¼7.5 Hz,
2.1.11. 1-{[4-(Pyridin-1-ium-pyridin-2-ylaminomethyl)-
benzyl]pyridin-2-ylamino}pyridinium dibromide (9k).
White solid (806 mg, 95%, ethanol), mp .2908C; [Found:
C, 55.34; H, 4.34; N, 13.63. C28H26Br2N6 requires C, 55.46;
H, 4.32; N, 13.86%]; nmax (KBr) 3009, 2934, 1621, 1468,
1427, 643 cm21; dH (300 MHz, CD3OD) 9.15 (4H, dd,

M. J. Reyes et al. / Tetrahedron 58 (2002) 8573–8579
8577
J¼6.8, 1.2 Hz, H2(6)); 8.73 (2H, tt, J¼7.8, 1.2 Hz, H4);
8.17 (6H, m, H3(5) and H60); 7.86 (2H, ddd, J¼08.8, 7.5,
1.8 Hz, H40); 7.41 (4H, s, H–Ar); 7.17 (4H, m, H3 and 50);
5.35 (4H, s, CH2).
ethanol/ethyl acetate), mp .1708C (dec.); [Found: C,
41.98; H, 3.28, N, 11.07. C39H33Br6N9 requires C, 42.31;
H, 3.00; N, 11.39]; nmax (KBr) 3024, 1618, 1577, 1465,
1372, 1001, 678 cm21; dH (300 MHz, CD3OD) 9.30 (6H,
dd, J¼6.7, 1.3 Hz, H2(6)); 8.75 (3H, tt, J¼7.8, 1.3 Hz, H4);
8.27 (3H, br. d, J¼2.2 Hz, H60); 8.25 (6H, 0 dd, J¼7.8,
6.7 Hz, H3(5)); 8.02 (3H, dd, J¼8.9, 2.2 Hz, H4 ); 7.65 (3H,
s, H–Ar); 7.09 (3H, d, J¼8.9 Hz, H30); 5.45 (6H, s, CH2).
2.1.12. 1-{[6-(Pyridin-1-ium-pyridin-2-ylaminomethyl)-
pyridin-2-ylmethyl]pyridin-2-ylamino}pyridinium
dibromide (9l). White solid (765 mg, 90%, ethanol), mp
182–1838C; [Found: C, 53.23; H, 4.37; N, 15.91.
C27H25Br2N7 requires C, 53.40; H, 4.15; N, 16.14%]; nmax
(KBr) 3010, 1588, 1471, 1430, 780, 685 cm21; dH
(300 MHz, CD3OD) 9.28 (4H, dd, J¼6.8, 1.5 Hz, H2(6));
8.73 (2H, tt, J¼7.9, 1.5 Hz, H4); 8.21 (4H, dd, J¼7.9,
6.8 Hz, H3(5)); 8.10 (2H, ddd, J¼4.8, 2.0, 0.8 Hz, H60);
7.90 (1H, t, J¼7.9 Hz, H400); 7.74 (2H, ddd, J¼8.9, 7.3,
2.0 Hz, H40); 7.59 0(2H, d, J¼7.9 Hz, H300(500)); 7.05 (2H, dd,
J¼7.3, 4.8 Hz, H5 ); 6.90 (2H, d, J¼8.9 Hz, H30); 5.56 (4H,
s, CH2).
2.2. Reduction of pyridinium salts
General method. Platinum on charcoal (5%) (260 mg) was
suspended into a solution of the pyridinium bis-salts
(0.6 mmol) in CH3CN (9 mL) and cooled in an ice bath
with stirring. Formic acid (98%, 2.6 mL) in CH3CN
(4.5 mL) and then triethylamine (6.2 mL) in the same
solvent (9 mL) were added dropwise. The reaction mixture
was refluxed for 4 h. The resulting suspension was filtered
through Celite, the filtrate was evaporated, made basic with
saturated aq. solution of potassium carbonate and extracted
with ethyl acetate (3£25 mL). The combined organic phases
were dried over MgSO4, filtered and evaporated to dryness.
The residue was purified by flash chromatography (ethyl
acetate) and finally, recrystallized and identified. Reduction
of pyridinium tris-salts 14 was accomplished in the same
way, using platinum on charcoal (5%) (390 mg) in CH3CN
(13.5 mL), formic acid (3.9 mL) in CH3CN (6.6 mL) and
triethylamine (9.3 mL) in the same solvent (13.5 mL).
2.1.13. 1-{[20-(Pyridin-1-ium-pyridin-2-ylaminomethyl)-
biphenyl-2-ylmethyl]pyridin-2-ylamino}pyridinium
dibromide (9m). Beige solid (930 mg, 97%, ethanol/ethyl
acetate), mp 221–2238C; [Found: C, 59.21; H, 4.47; N,
12.14. C34H30Br2N6 requires C, 59.29; H, 4.71; N, 12.28];
nmax (KBr) 3011, 1617, 1588, 1468, 1427, 773, 687 cm21
;
dH (300 MHz CD3OD) 9.02 (4H, dd, J¼6.8, 1.4 Hz, H2(6));
8.81 (2H, tt, J¼7.8, 1.4 Hz, H4); 8.24 (4H, 0 dd, J¼7.8,
6.8 Hz, H3(5)); 8.11 (2H, dd, J¼4.9, 1.8 Hz, H6 ); 7.72 (2H,
ddd, J¼8.5, 7.3, 1.8 Hz, H40); 7.52 (2H, dd, J¼7.2, 1.9 Hz,
H–Ar); 7.44 (2H, td, J¼7.2, 1.9 Hz, H–Ar); 7.40 (2H, td,
J¼7.2, 1.9 Hz, H–Ar); 7.15 (2H, 0dd, J¼7.2, 1.9 Hz, H–Ar);
7.008 (2H, dd, J¼7.3, 4.9 Hz, H5 ); 6.66 (2H, d, J¼8.5 Hz,
H3 ); 5.37 (2H, d, J¼14.8 Hz, CH2); 5.12 (2H, d, J¼
14.8 Hz, CH2).
2.2.1. N,N0-Dipyridin-2-yl-butane-1,4-diamine (11a).
White solid (65 mg, 45%, ethyl acetate/hexane), mp 151–
1528C; [Found: C, 69.23; H, 7.53; N, 22.82. C14H18N4
requires C, 69.39; H, 7.49; N, 23.12%]; nmax (KBr) 3241,
2937, 2867, 1604, 1440 cm21; dH (300 MHz, CDCl3) 8.06
(2H, ddd, J¼5.0, 2.0, 0.8 Hz, H6); 7.39 (2H, ddd, J¼8.4,
6.5, 2.0 Hz, H4); 6.54 (2H, ddd, J¼6.5, 5.0, 2.0 Hz, H5);
6.36 (2H, br.d, J¼8.4 Hz, H3); 4.62 (2H, br.s, HN); 3.31
(4H, m, CH2N); 1.72 (4H, m, CH2). dC (75 MHz, CDCl3)
158.4 (C2), 147.7 (C6), 137.1 (C4), 112.4 (C5), 106.4 (C3),
41.5 (CH2N), 26.7 (CH2).
2.1.14. 1-[3-Iodoethyl(pyridin-2-yl)amino]pyridinium
iodide (13). White solid (666 mg, 95%, ethanol/ethyl
acetate), mp 181–1828C; [Found: C, 33.36; H, 3.22; N,
9.08 C13H15I2 N3 requires C, 33.43; H, 3.24; N, 9.00%];
nmax (KBr) 3003, 1637, 1617, 1513 cm21; dH (300 MHz,
CD3OD) 9.74 (2H, dd, J¼6.7, 1.4 Hz, H2(6)); 9.07 (1H, tt,
J¼7.9, 1.4 Hz, H4); 8.58 (2H, dd, J¼7.9, 6.7 Hz, H3(5));
8.53 (1H, dd, J¼6.4, 1.6 Hz, H60); 8.21 (1H, ddd, J¼9.0,
7.6, 1.6 Hz, H40); 7.50 (1H, ddd, J¼7.6, 6.4, 1.3 Hz, H50);
6.88 (1H, d, J¼9.0 Hz, H30); 4.85 (2H, ap.t, J¼5.7 Hz,
CH2–N); 4.46 (2H, t, J¼6.0 Hz, CH2–I); 2.78 (2H, m,
CH2).
2.2.2. N,N0-Dipyridin-2-yl-pentane-1,5-diamine (11b).
Creamy solid (75 mg, 49%, ethyl acetate/hexane), mp
148–1498C; [Found: C, 69.90; H, 7.91; N, 21.72.
C15H20N4 requires C, 70.28; H, 7.86; N, 21.86%]; nmax
(KBr) 3312, 2933, 2857, 1614, 1468 cm21; dH (300 MHz,
CDCl3) 8.06 (2H, ddd, J¼5.0, 1.9, 0.9 Hz, H6); 7.40 (2H,
ddd, J¼8.5, 6.5, 1.9 Hz, H4); 6.55 (2H, ddd, J¼6.5, 5.0,
0.9 Hz, H5); 6.35 (2H, dt, J¼8.5, 0.9 Hz, H3); 4.50 (2H,
br.s, HN); 3.26 (4H, ap.q, J¼6.7 Hz, CH2N); 1.67 (4H, m,
CH2b), 1.51 (2H, m, CH2g). dC (75 MHz, CDCl3) 158.8
(C2), 148.1 (C6), 137.4 (C4), 112.7 (C5), 106.5 (C3), 42.0
(CH2N), 29.4 (CH2b), 24.5 (CH2g).
2.1.15. 1-{[3,5-Bis(pyridin-1-ium-pyridin-2-ylamino-
methyl)benzyl]pyridin-2-ylamino}pyridinium tribromide
(14a). Yellow solid (914 mg, 75%, ethanol), mp .2908C;
[Found: C, 53.54; H, 4.27; N, 14.25. C39H36Br3N9 requires
C, 53.81; H, 4.17; N, 14.48%]; nmax (KBr) 3008, 1619,
1467, 1432, 779, 686 cm21; dH (300 MHz, CD3OD) 9.21
(6H, dd, J¼6.0, 1.4 Hz, H2(6)); 8.068 (3H, tt, J¼8.1, 1.4 Hz,
H4); 8.18 (9H,0 m, H3(5) and H6 ); 7.83 (3H, ddd, J¼8.4,
7.3, 2.1 Hz, H4 ); 7.61 (3H, s, H–Ar); 7.150(3H, dd, J¼7.3,
4.8 Hz, H50); 7.03 (3H, d, J¼8.4 Hz, H3 ); 5.38 (6H, s,
CH2).
2.2.3. N,N0-Dipyridin-2-yl-hexane-1,6-diamine (11c).
White solid (68 mg, 42%, ethyl acetate/hexane), mp 151–
1528C (lit.27 151–1538C); [Found: C, 70.70; H, 8.16; N,
20.37. C16H22N4 requires C, 71.08; H, 8.20; N, 20.72%];
nmax (KBr) 3285, 2933, 2850, 1610, 1457 cm21; dH
(300 MHz, CDCl3) 8.06 (2H, dd, J¼4.9, 1.8 Hz, H6); 7.40
(2H, ddd, J¼8.5, 7.1, 1.8 Hz, H4); 6.54 (2H, ddd, J¼7.1,
4.9, 0.8 Hz, H5); 6.36 (2H, br.d, J¼8.5 Hz, H3); 4.50 (2H,
br.s, HN); 3.25 (4H, ap.q, J¼7.0 Hz, CH2N); 1.64 (4H, m,
2.1.16. 1-{[3,5-Bis(pyridin-1-ium-5-bromopyridin-2-yl-
aminomethyl)benzyl]-5-bromopyridin-2-ylamino}pyri-
dinium tribromide (14b). White solid (1.2 g, 77%,

8578
M. J. Reyes et al. / Tetrahedron 58 (2002) 8573–8579
CH2b), 1.45 (4H, m, CH2g). dC (75 MHz, CDCl3) 158.5
(C2), 147.8 (C6), 137.1 (C4), 112.3 (C5), 106.1 (C3), 41.8
(CH2N), 29.2 (CH2b), 26.5 (CH2g).
CH2N). dC (75 MHz, CDCl3) 158.3 (C2), 147.9 (C6), 137.3
(C4), 112.8 (C5), 107.6 (C3), 70.4 (CH2O), 70.0 (CH2O),
41.8 (CH2N). MS (EI 70 eV) m/z 78 (41), 94 (38), 107 (100),
121 (22), 183 (83), 302 (Mþ 4); exact mass calcd for
C16H22N4O2 302.1743, found 302.1743.
2.2.4. N,N0-Dipyridin-2-yl-heptane-1,7-diamine (11d).
White solid (109 mg, 64%, ethyl acetate/hexane), mp
100–1018C; [Found: C, 71.63; H, 8.44; N, 19.66.
C17H24N4 requires C, 71.79; H, 8.51; N, 19.70%]; nmax
(KBr) 3279, 2928, 2854, 1611, 1475 cm21; dH (300 MHz,
CDCl3) 8.03 (2H, ddd, J¼5.0, 1.8, 0.9 Hz, H6); 7.37 (2H,
ddd, J¼8.6, 6.9, 1.8 Hz, H4); 6.51 (2H, ddd, J¼6.9, 5.0,
0.9 Hz, H5); 6.33 (2H, dt, J¼8.6, 0.9 Hz, H3); 4.53 (2H,
br.s, HN); 3.20 (4H, ap.q, J¼7.0 Hz, CH2N); 1.59 (4H, m,
CH2b), 1.37 (6H, m, CH2g and CH2d). dC (75 MHz, CDCl3)
158.8 (C2), 148.1 (C6), 137.4 (C4), 112.5 (C5), 106.3 (C3),
42.2 (CH2N), 29.4 (CH2b), 29.1 (CH2g), 26.9 (CH2d).
2.2.9. 2-(Pyridin-2-ylaminomethyl)benzylpyridin-2-yl-
amine (11i). White solid (105 mg, 60%, ethyl acetate),
mp 154–1568C; [Found: C, 74.47; H, 6.47; N, 19.02.
C18H18N4 requires C, 74.46; H, 6.25; N, 19.29%]; nmax
(KBr) 3239, 1608, 1511, 1482, 776 cm21; dH (300 MHz,
CDCl3) 8.08 (2H, ddd, J¼5.6, 2.0, 0.8 Hz, H6); 7.38 (4H, m,
H4 and H–Ar); 7.26 (2H, m, H–Ar), 6.58 (2H, ddd, J¼5.6,
5.0, 0.8 Hz, H5); 6.38 (2H, br.d, J¼8.4 Hz, H3); 5.21 (2H,
br.s, HN); 4.60 (4H, br.s, CH2). dC (75 MHz, CDCl3) 157.9
(C2), 147.4 (C6), 137.8 (C–Ar), 137.1 (C4), 128.7 (C–Ar),
127.5 (C–Ar), 112.7 (C5), 107.3 (C3), 43.5 (CH2).
2.2.5. N,N0-Dipyridin-2-yl-octane-1,8-diamine (11e).
White solid (77 mg, 43%, ethyl acetate/hexane), mp 111–
1128C; [Found: C, 72.18; H, 8.83; N, 18.81. C18H26N4
requires C, 72.44; H, 8.78; N, 18.77%]; nmax (KBr) 3330,
2927, 2854, 1610, 1478 cm21; dH (300 MHz, CDCl3) 8.05
(2H, ddd, J¼5.6, 1.8, 0.8 Hz, H6); 7.41 (2H, ddd, J¼8.4,
6.0, 1.8 Hz, H4); 6.54 (2H, ddd, J¼6.0, 5.6, 0.8 Hz, H5);
6.37 (2H, br.d, J¼8.4 Hz, H3); 4.58 (2H, br.s, HN); 3.23
(4H, m, CH2N); 1.61 (4H, m, CH2b), 1.35 (8H, m, CH2g
and CH2d). dC (75 MHz, CDCl3) 158.4 (C2), 147.5 (C6),
137.2 (C4), 112.2 (C5), 106.1 (C3), 41.9 (CH2N), 29.2
(CH2b), 28.9 (CH2g), 26.6 (CH2d).
2.2.10. 3-(Pyridin-2-ylaminomethyl)benzylpyridin-2-
ylamine (11j). White solid (87 mg, 50%, ethyl acetate),
mp 129–1308C; [Found: C, 74.19; H, 6.33; N, 18.91.
C18H18N4 requires C, 74.46; H, 6.25; N, 19.29%]; nmax
(KBr) 3256, 1614, 1521, 1491, 771 cm21; dH (300 MHz,
CDCl3) 8.08 (2H, dd, J¼5.2, 1.8 Hz, H6); 7.38 (3H, m, H4
and H–Ar); 7.27 (3H, m, H–Ar), 6.58 (2H, ddd, J¼6.0, 5.2,
0.8 Hz, H5); 6.34 (2H, br.d, J¼8.4 Hz, H3); 4.96 (2H, br.t,
J¼5.6 Hz, HN); 4.48 (4H, d, J¼5.6 Hz, CH2). dC (75 MHz,
CDCl3) 158.2 (C2), 147.7 (C6), 139.3 (C–Ar), 137.2 (C4),
128.6 (C–Ar), 126.1 (C–Ar), 125.9 (C–Ar), 112.8 (C5),
106.5 (C3), 45.9 (CH2).
2.2.6. N,N0-Dipyridin-2-yl-nonane-1,9-diamine (11f).
White solid (131 mg, 70%, ethyl acetate/hexane), mp
141–1428C; [Found: C, 72.70; H, 9.21; N, 17.58.
C19H28N4 requires C, 73.04; H, 9.03; N, 17.93%]; nmax
(KBr) 3288, 2928, 2849, 1614, 1517, 1475 cm21; dH
(300 MHz, CDCl3) 8.06 (2H, dd, J¼5.1, 2.1 Hz, H6); 7.40
(2H, ddd, J¼8.6, 7.1, 2.1 Hz, H4); 6.54 (2H, ddd, J¼7.1,
5.1, 0.7 Hz, H5); 6.37 (2H, br.d, J¼8.6 Hz, H3); 4.47 (2H,
br.s, HN); 3.23 (4H, m, CH2N); 1.61 (4H, m, CH2b), 1.36
(10H, m, CH2g, CH2d and CH21). dC (75 MHz, CDCl3)
158.6 (C2), 147.9 (C6), 137.8 (C4), 112.3 (C5), 106.0 (C3),
41.9 (CH2N), 29.2 (CH2b), 29.1 (CH2g), 28.9 (CH2d), 26.7
(CH21).
2.2.11. 4-(Pyridin-2-ylaminomethyl)benzylpyridin-2-
ylamine (11k). White solid (96 mg, 55%, ethyl acetate),
mp 191–1938C; [Found: C, 74.34; H, 6.35; N, 18.99.
C18H18N4 requires C, 74.46; H, 6.25; N, 19.29%]; nmax
(KBr) 3245, 1599, 1533, 1458, 770 cm21; dH (300 MHz,
CDCl3) 8.08 (2H, dd, J¼5.2, 1.8 Hz, H6); 7.40 (2H, ddd,
J¼8.6, 7.2, 1.8 Hz, H4); 7.33 (4H, s, H–Ar), 6.59 (2H, ddd,
J¼7.2, 5.2, 0.8 Hz, H5); 6.37 (2H, br.d, J¼8.6 Hz, H3); 4.96
(2H, br.t, J¼6.0 Hz, HN); 4.49 (4H, d, J¼6.0 Hz, CH2). dC
(75 MHz, CDCl3) 158.1 (C2), 147.6 (C6), 139.2 (C–Ar),
137.2 (C4), 127.4 (C–Ar), 112.8 (C5), 106.6 (C3), 37.6
(CH2).
2.2.7. N,N0-Di-piridin-2-yl-3-oxo-pentane-1,5-diamine
(11g). Yellowish oil (62 mg, 40%); nmax (KBr) 3350,
1606, 1515, 771 cm21; dH (300 MHz, CDCl3) 8.06 (2H, dd,
J¼5.1, 1.9 Hz, H6); 7.35 (2H, ddd, J¼8.3, 7.1, 1.9 Hz, H4);
6.53 (2H, ddd, J¼7.1, 5.1, 0.9 Hz, H5); 6.37 (2H, br.d, J¼
8.3 Hz, H3); 4.91 (2H, br.s, HN); 3.64 (4H, t, J¼5.3 Hz,
CH2O); 3.48 (4H, q, J¼5.3 Hz, CH2N). dC (75 MHz,
CDCl3) 158.3 (C2), 147.4 (C6), 136.8 (C4), 112.3 (C5),
107.2 (C3), 69.39 (CH2O), 41.3 (CH2N). MS (EI 70 eV) m/z
78 (51), 94 (55), 107 (93), 119 (33), 139 (100), 258 (Mþ 8);
exact mass calcd for C14H18N4O 258.1481, found 258.1470.
2.2.12. [6-(Pyridin-2-ylaminomethyl)pyridin-2-yl-
methyl]pyridin-2-ylamine (11l). White solid (82 mg,
47%, ethyl acetate/hexane), mp 153–1558C (lit.28 147–
149); [Found: C, 69.92; H, 6.02; N, 24.30. C17H17N5
requires C, 70.08; H, 5.88; N, 24.04%]; nmax (KBr) 3268,
1610, 1519, 772 cm21; dH (300 MHz, CDCl3) 8.10 (2H, dd,
J¼5.0, 1.8 Hz, H6); 7.58 (1H, t, J¼8.9 Hz, H40); 7.41 (2H,
ddd, J¼8.5, 7.2, 1.8 Hz, H4); 7.23 (2H, d, J¼8.9 Hz,
H30(50)); 6.59 (2H, dd, J¼7.2, 5.0 Hz, H5); 6.49 (2H, d,
J¼8.5 Hz, H3); 5.72 (2H, br.s, HN); 4.63 (4H, d, J¼4.1 Hz,
CH2). dC (75 MHz, CDCl3) 158.1 (C2), 157.2 (C20, 60),
147.6 (C6), 136.9 (C40), 137.1 (C4), 119.6 (C30,50), 112.7
(C5), 107.3 (C3), 46.8 (CH2).
2.2.8. N,N0-Di-piridin-2-yl-3,6-dioxo-octane-1,8-diamine
(11h). Yellowish oil (92 mg, 51%); nmax (KBr) 3360, 1606,
1516, 773 cm21; dH (300 MHz, CDCl3) 8.05 (2H, ddd,
J¼5.1, 1.9, 0.9 Hz, H6); 7.36 (2H, ddd, J¼8.5, 7.1, 1.9 Hz,
H4); 6.53 (2H, ddd, J¼7.1, 5.1, 0.9 Hz, H5); 6.38 (2H, br.d,
J¼8.5 Hz, H3); 5.25 (2H, br.s, HN); 3.69 (4H, t, J¼4.9 Hz,
CH2O); 3.64 (4H, s, CH2O); 3.50 (4H, br.q, J¼4.9 Hz,
2.2.13. [(20-Pyridin-2-ylaminomethyl)biphenyl-2-yl-
methyl]pyridin-2-ylamine (11m). White solid (187 mg,
85%, ethyl acetate/hexane), mp 151–1538C; [Found: C,
78.32; H, 6.13; N, 14.96. C24H22N4 requires C, 78.66; H,
6.05; N, 15.29%]; nmax (KBr) 3228, 1595, 1437, 772 cm21
;

M. J. Reyes et al. / Tetrahedron 58 (2002) 8573–8579
8579
5. Reddy, V. K.; Sarkar, A.; Valasinas, A.; Marton, L. J.; Basu,
H. S.; Frydman, B. J. Med. Chem. 2001, 44, 404–417, and
references cited therein.
dH (300 MHz, CDCl3) 8.00 (2H, dd, J¼5.0, 2.0 Hz, H6);
7.49 (2H, m, H–Ar); 7.30 (6H, H4 and H–Ar); 7.19 (2H, m,
H–Ar); 6.51 (2H, ddd, J¼7.2, 5.0, 0.9 Hz, H5); 6.23 (2H,
br. d, J¼8.5 Hz, H3); 5.1 (2H, br. t, J¼5.6 Hz, HN); 4.27
(4H, m, CH2). dC (75 MHz, CDCl3) 158.4 (C2), 147.9 (C6),
139.8 (C20), 137.2 (C4), 137.0 (C10), 129.6 (C–Ar), 128.2
(C–Ar), 127.8 (C–Ar), 127.0 (C–Ar), 112.8 (C5), 106.9
(C3), 43.9 (CH2).
6. Qu, Y.; Rauter, H.; Soares, A. P.; Bandarage, R.; Kelland,
L. R.; Farrel, N. J. Med. Chem. 2000, 43, 3189–3192.
7. Jansen, B. A. J.; van der Zwan, J.; den Dulk, H.; Brouwer, J.;
Reedijk, J. J. Med. Chem. 2001, 44, 245–249.
8. Kuksa, V.; Buchan, R.; Kong Thoo Lin, P. Synthesis 2000,
1189–1207.
9. Salvatore, R. N.; Schmidt, S. E.; Il Shin, S.; Nagle, A. S.;
Worrell, J. H.; Woon Jung, K. Tetrahedron Lett. 2000, 41,
9705–9708.
2.2.14. 3,5-Bis-(pyridin-2-ylaminomethyl)benzylpyridin-
2-ylamine (15a). White solid (178 mg, 75%, ethyl acetate/
hexane), mp 145–1468C; [Found: C, 72.69; H, 6.20; N,
20.97. C24H24N6 requires C, 72.70; H, 6.10; N, 21.20%];
nmax (KBr) 3239, 1599, 1458, 773 cm21; dH (300 MHz,
CDCl3) 8.05 (3H, dd, J¼4.8, 2.0 Hz, H6); 7.36 (3H, ddd,
J¼8.5, 7.2, 2.0 Hz, H4); 7.24 (3H, s, H–Ar); 6.56 (3H, dd,
J¼7.2, 4.8 Hz, H5); 6.32 (3H, d, J¼8.5 Hz, H3); 5.03 (3H,
br.s, HN); 4.45 (6H, br.s, CH2). dC (75 MHz, CDCl3) 158.1
(C2), 147.6 (C6), 139.8 (C10, 30, 50), 137.2 (C4), 124.9 (C20,
40, 60), 112.8 (C5), 106.7 (C3), 45.8 (CH2).
10. Cuadro, A. M.; Alvarez-Builla, J.; Vaquero, J. J. Heterocycles
1988, 27, 1233–1240.
11. Cuadro, A. M.; Alvarez-Builla, J.; Vaquero, J. J. Heterocycles
1989, 29, 57–65.
´
´
12. Carceller, R.; Garcıa-Navıo, J. L.; Izquierdo, M. L.; Alvarez-
Builla, J.; Sanz-Aparicio, J.; Florencio, F. Heterocycles 1989,
29, 1877–1889.
13. Molina, A.; Cuadro, A. M.; Alvarez-Builla, J.; Vaquero, J. J.;
´
´
Garcıa-Navıo, J. L. Heterocycles 1990, 31, 1451–1458.
14. Cuadro, A. M.; Novella, J. L.; Molina, A.; Alvarez-Builla, J.;
Vaquero, J. J. Tetrahedron 1990, 46, 6033–6046.
2.2.15. 3,5-Bis-(5-bromopyridin-2-ylaminomethyl)benzyl-
pyridin-5-bromo-2-ylamine (15b). Pale yellow solid
(266 mg, 70%, ethyl acetate/hexane), mp 170–1718C;
[Found: C, 45.87; H, 3.36; N, 13.03. C24H21Br3N6 requires
C, 45.53; H, 3.34; N, 13.27%]; nmax (KBr) 3234, 1590,
1455, 802 cm21; dH (300 MHz, CDCl3) 7.99 (3H, d, J¼
2.5 Hz, H6); 7.42 (3H, dd, J¼8.9, 2.5 Hz, H4); 7.19 (3H, s,
H–Ar); 6.22 (3H, d, J¼8.9 Hz, H3); 5.17 (3H, br. t, J¼
5.9 Hz, HN); 4.42 (6H, d, J¼5.9 Hz, CH2). dC (75 MHz,
CDCl3) 157.2 (C2), 148.9 (C6), 140.1 (C10, 30, 50), 140.0
(C4), 125.5 (C20, 40, 60), 108.5 (C3), 107.5 (C5), 46.2 (CH2).
15. Vaquero, J. J.; Alvarez-Builla, J. Adv. Nitrogen Heterocycl.
2000, 4, 159–249, and references cited therein.
´ ´
16. Carceller, R.; Garcıa-Navıo, J. L.; Izquierdo, M. L.; Alvarez-
Builla, J. Tetrahedron Lett. 1993, 34, 2019–2020.
´
17. Carceller, R.; Garcıa-Navıo, J. L.; Izquierdo, M. L.; Alvarez-
´
´
Builla, J.; Fajardo, M.; Gomez-Sal, P.; Gago, F. Tetrahedron
1994, 50, 4995–5012.
18. Burgos, C.; Delgado, F.; Garcıa-Navıo, J. L.; Izquierdo, M. L.;
Alvarez-Builla, J. Tetrahedron 1995, 51, 8649–8654.
´
´
´
19. De la Rosa, R.; Martınez-Barrasa, V.; Burgos, C.; Alvarez-
Builla, J. Tetrahedron Lett. 2000, 41, 5837–5840.
Acknowledgements
´
´
20. Garcıa de Viedma, A.; Martınez-Barrasa, V.; Burgos, C.;
Izquierdo, M. L.; Alvarez-Builla, J. J. Org. Chem. 1999, 64,
1007–1010.
´
The authors wish to thank the Comision Interministerial de
Ciencia y Tecnologıa (CICYT-2FD97-1248) for financial
´
´
´
´
21. Martınez-Barrasa, V.; Delgado, F.; Burgos, C.; Garcıa-Navıo,
J. L.; Izquierdo, M. L.; Alvarez-Builla, J. Tetrahedron 2000,
56, 2481–2490.
´
support, and the Ministerio de Educacion y Cultura (MEC)
for a studentship (M. J. R.).
22. Goerdeler, J.; Roth, W. Chem. Ber. 1963, 96, 534–549.
23. Fossey, J.; Loupy, A. Tetrahedron 1981, 37, 1935–1941.
24. Wagaw, S.; Buchwald, S. L. J. Org. Chem. 1996, 61,
7240–7241.
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