Synthesis and photophysical properties of oligoarylenes with a pyrrolo[2,3-d]pyrimidine core

Article abstract of DOI:10.1016/j.tetlet.2010.05.093

The palladium-catalyzed Suzuki-Miyaura reaction of 2,4-dichloropyrrolo[2,3-d]pyrimidine with aryl boronic acids has been studied. Pd(OAc)₂/dicyclohexyl(2-biphenyl)phosphine/K₃PO₄ was found to be an efficient catalyst system to prepare 4-aryl-2-chloro- and 2,4-diarylpyrrolo[2,3-d]pyrimidines. Novel non-linear molecules consisting of a pyrrolo[2,3-d]pyrimidine core and aryl branches have been elucidated as blue light-emitters with fluorescence quantum yields ranging from 4% to 67% in THF solution. The impact of an electron-withdrawing t-BuOCO group attached to the pyrrole ring of pyrrolopyrimidine derivatives on optical properties is discussed.

Full text of DOI:10.1016/j.tetlet.2010.05.093

Tetrahedron Letters 51 (2010) 3902–3906
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis and photophysical properties of oligoarylenes
with a pyrrolo[2,3-d]pyrimidine core
a
b
a
b
Sigitas Tumkevicius a, , Jelena Dodonova , Karolis Kazlauskas , Viktoras Masevicius , Lina Skardziute ,
*
Saulius Jursenas b
a Department of Organic Chemistry, Vilnius University, Naugarduko 24, LT-03225 Vilnius, Lithuania
b Institute of Applied Research, Vilnius University, Sauletekio 9-III, LT-10222 Vilnius, Lithuania
a r t i c l e i n f o
a b s t r a c t
Article history:
The palladium-catalyzed Suzuki–Miyaura reaction of 2,4-dichloropyrrolo[2,3-d]pyrimidine with aryl
boronic acids has been studied. Pd(OAc)2/dicyclohexyl(2-biphenyl)phosphine/K3PO4 was found to be
an efficient catalyst system to prepare 4-aryl-2-chloro- and 2,4-diarylpyrrolo[2,3-d]pyrimidines. Novel
non-linear molecules consisting of a pyrrolo[2,3-d]pyrimidine core and aryl branches have been eluci-
dated as blue light-emitters with fluorescence quantum yields ranging from 4% to 67% in THF solution.
The impact of an electron-withdrawing t-BuOCO group attached to the pyrrole ring of pyrrolopyrimidine
derivatives on optical properties is discussed.
Received 22 March 2010
Revised 30 April 2010
Accepted 21 May 2010
Available online 27 May 2010
Keywords:
Pyrrolopyrimidines
Suzuki–Miyaura reaction
Oligoarylenes
Ó 2010 Elsevier Ltd. All rights reserved.
Cross-coupling
Fluorescence
Organic molecules with a
p
-conjugated backbone have attracted
formation in the construction of biaryl skeletons.13 However, a liter-
ature survey on arylpyrrolo[2,3-d]pyrimidines revealed that the Su-
zuki–Miyaura reaction on pyrrolo[2,3-d]pyrimidines has not been
explored in detail. To the best of our knowledge, only a few examples
have been reported on the application of palladium-catalyzed cross-
coupling for the arylation of the pyrrole ring of a pyrrolo[2,3-
d]pyrimidine,14 and no work on functionalization of the pyrimidine
moiety in pyrrolo[2,3-d]pyrimidines has been published.
Initially, we conducted a brief screen of common palladium cata-
lysts and ligands using 4-tert-butylphenylboronic acid and 2,4-
dichloropyrrolo[2,3-d]pyrimidine (1) as coupling partners in the
Suzuki–Miyaura cross-coupling. The catalystsand ligandsemployed
were PdCl2(PPh3)2, PdCl2(dppf), Pd(OAc)2 and PCy2(2-biphenyl),
PCy2(20,60-(MeO)2-2-biphenyl), P(t-Bu)2(2-biphenyl), P(i-Pr)2(2-
biphenyl) and dppf, respectively. The reaction of 1 with 2.16 equiv
of 4-tert-butylphenylboronic acid in the presence of PdCl2(PPh3)2/
K3PO4, which was previously found to be an efficient catalyst system
for the synthesis of densely substituted 4,6-diarylpyrimidines,15 re-
sulted in the formation of only mono-coupled product 2b in 41%
yield. Analogous results were obtained employing Pd(OAc)2/dppf/
K3PO4 or Pd(OAc)2/PCy2(20,60-(MeO)2-2-biphenyl)/K3PO4 as catalyst
systems. The yields of 2b were 29% and 35%, respectively. The use of
Pd(OAc)2 with P(t-Bu)2(2-biphenyl) or P(i-Pr)2(2-biphenyl) as a
ligand led to the formation of a complex mixture of products. Only
PdCl2(dppf) or Pd(OAc)2/PCy2(2-biphenyl) gave the double cross-
coupling product 3b in 28% and 48% yields, respectively. Performing
the reaction of 1 with 1.2 equiv of 4-tert-butylphenylboronic acid in
growing interest over recent years owing to their applications in a
wide range of electronic and optoelectronic devices.1 Non-linear
(so-called star-shaped and banana-shaped) molecules are of inter-
est in materials science owing to their light-emitting,2 self-assem-
bling3 and complex forming properties with metal ions or organic
molecules.3,4 New synthetic methods and novel structures are con-
tinuously being introduced into this field. Incorporation of azahet-
erocycles such as pyridine,2e,5 pyrazine,2b pyrimidine,2f,6 s-triazine7
or quinoxaline8 at the centre of the backbone of such molecules
leads to a strong enhancement of physical and photophysical prop-
erties. It is worth mentioning that pyrrolo[2,3-d]pyrimidine deriva-
tives constitute a very important class of compounds exhibiting
antiviral9 and antitumor10 activities. Owing to the site-specific
incorporation of fluorescent pyrrolo[2,3-d]pyrimidine derivatives
into oligonucleotides, they have been demonstrated to be ideally
suitable for probing the structure of DNA.11 In view of the growing
importance of highly efficient light-emitting materials in biological,
chemical and materials science, we report herein our results on the
synthesis and light-emitting properties of non-linear oligoarylenes
containing a pyrrolo[2,3-d]pyrimidine moiety.
For the synthesis of novel pyrrolo[2,3-d]pyrimidine derivatives,
2,4-dichloro[2,3-d]pyrimidine (1)12 was used as the starting mate-
rial. The Suzuki–Miyaura reaction is a powerful tool for C–C bond
* Corresponding author. Tel.: +370 610 06920; fax: +370 5 2330987.
E-mail address: sigitas.tumkevicius@chf.vu.lt (S. Tumkevicius).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.05.093

S. Tumkevicius et al. / Tetrahedron Letters 51 (2010) 3902–3906
3903
the presence of Pd(OAc)2/PCy2(2-biphenyl)/K3PO4 as the catalyst
Ar
N
Ar
N
Cl
N
system at 50–60 °C led to compound 2b in 66% yield (Table 1, entry
3). Among the catalyst systems studied, only Pd(OAc)2/PCy2(2-
biphenyl)/K3PO4 resulted in clean conversions and enabled mono-
and double cross-coupling reactions and, therefore, it was selected
as the most suitable catalyst system for further development. Using
the reaction conditionspresented in Scheme1 and Table 1, a series of
4-aryl-2-chloro- (2a–e)16 and 2,4-diarylpyrrolo[2,3-d]pyrimidines
(3a–e)17 were synthesized. Formation of the corresponding 2-aryl-
4-chloropyrrolo[2,3-d]pyrimidines was not observed. Assignment
of the structures 2a–e was based on NOE 1H NMR experiments. An
increase in the signal intensities of the 5-H and 20-H protons was
observed to be 7–12% (Fig. 1). This indicated that the 4-Cl group in
thepyrrolopyrimidine 1reactedfirstin theSuzuki–Miyaura reaction
to yield the corresponding 4-aryl derivatives 2a–e.
ii
N
i
N
N
N
N
N
Cl
Ar
Cl
H
H
H
1
3a-e
2a
-e
Scheme 1. Reagents and conditions: (i) 2 mol % Pd(OAc)2, 4 mol % PCy2(2-biphe-
nyl), 1.2 equiv ArB(OH)2, 2.4 equiv K3PO4, 1,4-dioxane, 50–60 °C, Ar; (ii) 2 mol %
Pd(OAc)2, 4 mol % PCy2(2-biphenyl), 2.4 equiv ArB(OH)2, 4.8 equiv K3PO4, 1,4-
dioxane,
D, Ar.
Bu-t
Bu-t
9%
7%
Cl
11%
Cl
12%
t-Bu
H
H
H
H
H
H
H
H
N
N
N
N
Although the Suzuki–Miyaura reaction of 1 with arylboronic
acids enabled the synthesis of arylpyrrolopyrimidines with suffi-
cient site-selectivity, the yields of compounds 2 and 3 were low
or moderate.
N
H
N
N
H
N
H
N
H
N
Cl
N
N
2c
2a
2b
3b
Figure 1. NOE experiments on 2a–c and 3b.
We suppose that the reason for this is an interaction between
the pyrrole aza-group in the anion form under basic conditions
with the boronic acid or palladium catalyst, similar to that ob-
served for 4-amino-2-chloropyrimidine.18 Therefore, we studied
the Suzuki–Miyaura reaction of N7-protected pyrrolo[2,3-d]pyrim-
idine 419 under analogous conditions. It was found that using
2.4 equiv of the corresponding boronic acid enabled the double
cross-coupling reaction to give compounds 5a–e20 in good to
excellent yields (Scheme 2, Table 2).
However, the presence of a 7-tert-butoxycarbonyl group in-
creased the reactivity of the 2-chlorine group in 4 and all attempts
to obtain 4-aryl-2-chloro-7-tert-butoxycarbonylpyrrolo[2,3-d]pyr-
imidines failed. Formation of the diarylpyrrolopyrimidines 5a–e
was observed even when only 1 equiv amount of boronic acid was
used in the reaction.
Cl
Ar
N
Cl
N
N
N
i
N
ii
N
N
H
N
Cl
N
Ar
Cl
O-tBu
O-tBu
O
O
1
4
5a-e
Scheme 2. Reagents and conditions: (i) Boc2O, DMAP, DIPEA, CH2Cl2, Ar; (ii)
2 mol % Pd(OAc)2, 4 mol % PCy2(2-biphenyl), 2.4 equiv ArB(OH)2, 4.8 equiv K3PO4,
1,4-dioxane,
D, Ar.
Table 2
Preparation of compounds 5a–e
Entry
Arylboronic acid
Reaction time (h)
Product (Yield,a %)
The pyrrolo[2,3-d]pyrimidine derivatives (3a–e and 5a–e) were
subjected to optical absorption and fluorescence studies. The de-
tails of their photophysical properties are summarized in Table 3.
All the compounds in dilute THF solution exhibited strong absorp-
tion with their absorption maxima positioned in the range 263–
342 nm and emission maxima located in the range 382–436 nm
(Fig. 2). For compounds 3a–e the following spectral features can
be highlighted. The shape and maxima of the absorption and
fluorescence spectra of compounds 3a,b,d resemble those of pyr-
rolo[2,3-d]pyrimidine.21 Slight modifications of the spectra might
be induced by the aryl substituents attached to the pyrimidine.
Similar fluorescence quantum yields (Uf = 41–43%) estimated for
the solutions of these compounds obviously indicate similar exten-
1
2
3
3.5
2
5a (78)
5b (76)
5c (94)
B(OH)2
B(OH)2
t-Bu
1
B(OH)2
B(OH)2
MeO
4
5
5
3
5d (42)
B(OH)2
5e (86)b
N
a
Yield after isolation and purification by column chromatography.
4.8 equiv of 4-(9-carbazolyl)phenylboronic acid and 9.6 equiv of K3PO4 were
b
used.
Table 1
Preparation of compounds 2a–e and 3a–e
sion of
p-conjugation governing the optical transitions. The simi-
Entry Arylboronic acid
Equiv Temp (°C)/
Product (Yield,a
%)
larities in the absorption and fluorescence spectra and quantum
yields of 3a and 3d possessing additional phenyl groups at the
meta-position of the benzene ring attached to the pyrrolopyrimi-
dine core can be justified by the out-of-plane twisting of the phe-
time
1
2
1.2
2.4
50–60/3 h
/9 h
50–60/2 h
/15 min
50–60/2 h
/2 h
70/1.5 h
2a (13)
3a (24)
B(OH)2
D
3
4
1.2
2.4
2b (66)
3b (48)
B(OH)2
t-Bu
D
nyl end-groups of compound 3d resulting in broken p-conjugation.
5
6
1.2
2.4
2c (46)
3c (29)
Such twisted molecular conformations are well-known and were
observed in 4,6-di(heteroaryl)pyrimidines.3a As opposed to this,
introduction of additional phenyl end-groups to the para-position
of the phenyl groups of the pyrrolopyrimidine (compound 3c) re-
sults in extended conjugation, and thus, in a red shift of the spec-
tral bands (Fig. 2c). The extension of the conjugation length in 3c
also manifests in a dramatically increased absorbance of the low-
est-energy optical transitions, as well as in an enhanced fluores-
cence quantum yield (up to 53%, see Table 3).
B(OH)2
B(OH)2
D
7
8
1.2
2.4
2d (68)
3d (49)
D
/2 h
9
1.2
2.4
D
D
/2.5 h
/3 h
2e (47)
3e (63)
10
B(OH)2
N
a
Yield after isolation and purification by column chromatography.

3904
S. Tumkevicius et al. / Tetrahedron Letters 51 (2010) 3902–3906
Table 3
UV–Vis absorption and fluorescence data for compounds 3a–e and 5a–e in 10ꢀ5 M THF solution
a
Compound
kabs (nm)
e
(l molꢀ1 cmꢀ1
)
kem (nm)
Ufb (%)
Stokes shift (cmꢀ1
)
sc (ns)
3a
3b
3c
3d
3e
5a
5b
5c
5d
5e
216, 264, 318
215, 270, 321
217, 299
215, 258, 325
265, 282, 293, 331, 341
213, 263, 303
213, 274, 307
215, 294
27,208, 39,969, 12,185
28,665, 42,810, 11,721
55,035, 74,472
44,226, 68,076, 12,302
19,693, 22,984, 29,529, 35,003, 37,219
37,454, 36,692, 20,357
37,623, 38,480, 23,346, 17,005
44,437, 50,131, 23,801
63,463, 19,802
403
401
421
415
415
386
382
387
391
436
42
41
53
43
50
3.6
5.7
15
13
67
6633
6215
9692
6673
5229
7097
6395
8174
7211
6304
3.6
2.9
3.0
3.5
2.75
<0.1
<0.1
1.5
2.6
4.1
256, 305
236, 255, 293, 342
72,903, 44,475, 24,940, 29,822
a
b
c
Excited at 320 nm.
Fluorescence quantum yield determined using two methods, that is, the integrating sphere method and by comparison with a standard (quinine sulfate in 0.1 M H2SO4).
Fluorescence lifetime estimated at kem
.
1
an almost twofold increase in absorbance (from 12,000 l mol
ꢀ1 cmꢀ1 to 20,000 l molꢀ1 cmꢀ1) and a blue shift by ꢁ20 nm of
the lowest absorption bands for compounds 5a,b,d as compared
to 3a,b,d.
5a
The changes in absorption are accompanied by a similar blue
shift of the fluorescence spectra and a remarkable drop in the fluo-
rescence quantum yield. In the limiting case of compound 5a,
reduction of the quantum yield amounts to one order of magni-
tude, that is, from 42% to 3.6%. The reduction is not so significant
(only 3.5 times) for compounds possessing more bulky end-groups
such as methoxy (5c) and phenyl (5d). It is likely that bulky end-
groups inhibit twisting of intermediate phenyl groups, thus
enhancing the probability of radiative decay from an excited state.
Fluorescence decay time measurements support the latter consid-
eration indicating short decay times (<0.1 ns) for compounds 5a,b
and prolonged decay times (1.5–2.6 ns) for compounds 5c,d. The
general influence of the t-BuOCO group is that the blue shift of
the absorption and fluorescence spectra, the reduction of fluores-
cence quantum yields and the decay times observed for com-
pounds 5a–d strongly contrast with the influence observed for
compound 5e. The attachment of the electron-withdrawing t-BuO-
CO group to 3e results in a red shift of the fluorescence spectrum
from 415 to 436 nm, an enhancement of the quantum yield from
50% to 67%, and an increase of the decay time from 2.75 to 4.1 ns
(see Table 3 and Fig. 2e). This exceptional behaviour induced by
the presence of the polar t-BuOCO group might be explained by
the forced planarization of the phenyl groups, which increases
3a
(a)
0
5b
3b
(b)
0
3c
5c
5c
MeO
3c
(c)
(d)
(e)
0
0
0
5d
3d
5e
N
the extent of p-conjugation in the excited state. A close similarity
in the absorption spectra of compounds 3e and 5e, and also simi-
larities in the lowest absorption bands of the spectra with those
of ethylcarbazole22 are evidences of orthogonal-like orientation
of the phenyl and carbazolyl groups in the ground state, and thus,
poor conjugation between the carbazolyl end-groups and the
remaining fragments. However, in the excited state, charge redis-
tribution induced by the presence of the polar t-BuOCO group in
compound 5e results in a more planar conformation of the mole-
cule than in the case of compound 3e, which does not possess this
group.
3e
300
400
500
600
Wavelength (nm)
Figure 2. Normalized absorption and fluorescence spectra of compounds (a) 3a and
5a, (b) 3b and 5b, (c) 3c and 5c, (d) 3d and 5d, (e) 3e and 5e in 10ꢀ5 M THF solution.
Solid lines correspond to compounds 3a–e, dashed lines to compounds 5a–e.
Interestingly, the maxima of the absorption spectrum of com-
pound 3e possessing carbazolyl end-groups were similar to those
of ethylcarbazole.22 Attachment of carbazolyl end-groups (3e) to
the para-position of the phenyl groups of the pyrrolopyrimidine
derivatives also results in an enhancement of quantum yield up
to 50%. The fluorescence lifetimes estimated for the pyrrolopyrim-
idines 3a–e span the range from 2.75 to 3.6 ns, which is typical for
fluorescent organic molecules featuring significant radiative
relaxation probability. Attachment of an additional electron-with-
drawing t-BuOCO group to the pyrrole ring of the pyrrolo[2,3-
d]pyrimidine core (5a–e) invokes the following spectral changes:
In conclusion, this investigation provides access to novel fluo-
rescent molecules consisting of a pyrrolo[2,3-d]pyrimidine core
and various peripheral chromophoric units. The pyrrolo[2,3-
d]pyrimidine derivatives were found to exhibit blue-UV fluores-
cence ranging from 380 nm to 440 nm with emission quantum
yields in the range of 4–67%. Introduction of a polar t-BuOCO group
was found to have a dramatic impact on the fluorescence proper-
ties of the pyrrolopyrimidine derivatives. With derivatives 5a–d,
where the pyrrolo[2,3-d]pyrimidine core acts as a fluorophore,
intramolecular charge transfer results in a significant quenching
of fluorescence (down to 3.6%), whereas for 5e, where a carbazolyl

S. Tumkevicius et al. / Tetrahedron Letters 51 (2010) 3902–3906
3905
15. Tumkevicius, S.; Dodonova, J.; Baskirova, I.; Voitechovicius, A. J. Heterocycl.
Chem. 2009, 46, 960.
moiety is invoked in formation of the lowest excited states, intra-
molecular charge transfer facilitates a significant increase in the
emission quantum yield up to 67%. A more detailed study of the
photophysical properties of the synthesized compounds and a fur-
ther modification of the pyrrolo[2,3-d]pyrimidine skeleton to cre-
ate more efficient light-emitting materials are currently being
carried out and the results will be reported in due course.
16. Typical procedure for the preparation of 4-aryl-2-chloro-7H-pyrrolo[2,3-
d]pyrimidines (2a–e). A solution of compound 1 (1.06 mmol) in anhydrous
1,4-dioxane (5 mL) was degassed with argon, and K3PO4 (0.54 g, 2.55 mmol),
arylboronic acid (1.28 mmol), 2.0 mol % Pd(OAc)2 and 4.0 mol %
dicyclohexyl(2-biphenyl)phoshine were added with stirring under argon. The
mixture was stirred at 40–50 °C for 1.5–3 h until compound 1 had been
consumed (TLC). The solvent was evaporated under reduced pressure and H2O
(5 mL) was added to dissolve inorganic salts. The obtained solution was
extracted with CHCl3 (3 ꢂ 25 mL), and the combined organic layer was dried
over Na2SO4, and evaporated under reduced pressure. The resulting solid was
purified by column chromatography using CHCl3 as an eluent. Data for selected
Acknowledgment
compounds. Compound 2b: yield 66%; mp 165 °C. IR (KBr): 3434 cmꢀ1 (NH). 1
NMR (300 MHz, CDCl3): 1.44 (s, 9H, CMe3), 6.93 (dd, 1H,
3 = 3.6 Hz,
H
K. Kazlauskas acknowledges EU Structural Funds project ‘‘Post-
doctoral Fellowship Implementation in Lithuania” for funding his
postdoctoral fellowship.
d
J
J
4 = 1.8 Hz, 5-H), 7.45 (dd, 1H, J3 = 3.6 Hz, J4 = 2.4 Hz, 6-H), 7.60–7.63 (m, 2H,
30,50-H), 8.12–8.15 (m, 2H, 20,60-H), 10.35 (br s, 1H, NH). 13C NMR (75 MHz,
DMSO-d6): d 31.7, 35.4, 101.3, 114.2, 120.7, 126.5, 129.3, 134.5, 152.9, 154.3,
154.7, 158.3. Anal. Calcd for C16H16ClN3: C, 67.25; H, 5.64; N, 14.70. Found: C,
67.27; H, 6.05; N, 14.83. Compound 2c: yield 46%, mp 255 °C. IR (KBr):
References and notes
3452 cmꢀ1 (NH). 1H NMR (300 MHz, CDCl3):
d 7.03 (dd, 1H, J
3 = 3.6 Hz,
J4 = 1.2 Hz, 5-H), 7.45–7.57 (m, 3H, 300, 400, 500-H), 7.75 (dd, 1H, J3 = 3.45 Hz,
J4 = 2.1 Hz, 6-H), 7.79–7.81 (m, 2H, 200,600-H), 7.91–7.94 (m, 2H, 30,50-H), 8.28–
8.30 (m, 2H, 20,60-H), 12.53 (br s, 1H, NH). 13C NMR (75 MHz, DMSO-d6 + two
drops CF3COOD): d 101.0, 114.3, 120.7, 127.4, 127.7, 128.5, 128.9, 129.6, 129.9,
136.3, 139.9, 143.0, 152.9, 154.6, 157.8. Anal. Calcd for C18H12ClN3: C, 70.71; H,
3.96; N, 13.74. Found: C, 70.93; H, 4.11; N, 13.59.
1. (a) Burroughes, J. H.; Bradley, D. D. C.; Brown, A. R.; Marks, R. N.; Mackay, K.;
Friend, R. H.; Burns, P. L.; Holmes, A. B. Nature 1990, 347, 539; (b) Roncali, J.
Chem. Rev. 1992, 92, 711; (c) Gustafsson, G.; Cao, Y.; Treacy, G. M.; Klavetter, F.;
Colaneri, N.; Heeger, A. J. Nature 1992, 357, 477; (d) Hide, F.; Diaz-Garcia, M. A.;
Schwartz, B. J.; Heeger, A. J. Acc. Chem. Res. 1997, 30, 430; (e) Kraft, A.;
Grimsdale, A. C.; Holmes, A. B. Angew. Chem., Int. Ed. 1998, 37, 402; (f) Bernius,
M. T.; Inbasekaran, M.; O’Brien, J.; Wu, W. S. Adv. Mater. 2000, 12, 1737; (g) Ho,
P. K. H.; Kim, J. S.; Burroughes, J. H.; Becker, H.; Li, S. F. Y.; Brown, T. M.; Cacialli,
F.; Friend, R. H. Nature 2000, 404, 481; (h) Gross, M.; Muller, D. C.; Nothofer, H.-
G.; Scherf, U.; Neher, D.; Brauchle, C.; Meerholz, K. Nature 2000, 405, 661; (i)
Hughes, G.; Bryce, M. R. J. Mater. Chem. 2005, 15, 94–107.
2. (a) Zhang, W.-B.; Jin, W.-H.; Zhou, X.-H.; Pei, J. Tetrahedron 2007, 63, 2907; (b)
Cristiano, R.; Westphal, E.; Bechtold, I. H.; Bortoluzzia, A. J.; Gallardo, H.
Tetrahedron 2007, 63, 2851; (c) Diez-Barra, E.; Garcia-Martinez, J. C.; Merino, S.;
del Rey, R.; Rodriguez-Lopez, J.; Sanchez-Verdu, P.; Tejeda, J. J. Org. Chem. 2001,
66, 5664; (d) Wang, H.; Xu, W.; Dai, Y.; Zhang, B.; Wu, Q.; Wang, D.; Zhang, M.;
Tian, M.; Wu, H. J. Heterocycl. Chem. 2007, 44, 993; (e) Yamaguchi, Y.;
Kobayashi, S.; Wakamiya, T.; Matsubara, Y.; Yoshida, Z. Angew. Chem., Int. Ed.
2005, 44, 7040; (f) Achelle, S.; Ramondene, Y.; Dupas, G.; Ple, N. Tetrahedron
2008, 64, 2783.
3. (a) Petitjean, A.; Khoury, R. G.; Kyritsakas, N.; Lehn, J.-M. J. Am. Chem. Soc. 2004,
126, 6637; (b) Schull, G.; Douillard, L.; Fiorini-Debuisschert, C.; Charra, F.;
Mathevet, F.; Kreher, D.; Attias, A.-J. Adv. Mater. 2006, 18, 2954; (c) Leininger,
S.; Olenyuk, B.; Stang, P. J. Chem. Rev. 2000, 100, 853.
4. (a) Bunzli, J.-C. G.; Piguet, C. Chem. Soc. Rev. 2005, 34, 1048; (b) Huang, J.-H.;
Wen, W.-H.; Sun, Y.-Y.; Chou, P.-T.; Fang, J.-M. J. Org. Chem. 2005, 70, 5827; (c)
Diring, S.; Retailleaub, P.; Ziessel, R. Tetrahedron Lett. 2007, 48, 8069.
5. Attias, A.-J.; Cavalli, C.; Donnio, B.; Guillon, D.; Hapiot, P.; Malthete, J. Chem.
Mater. 2002, 14, 375.
17. Preparation of 2,4-diaryl-7H-pyrrolo[2,3-d]pyrimidines (3a–e). Compounds 3a-e
were synthesized and isolated according to the procedure described for 2a–e
except that the reaction was carried out at reflux and double the amount of
K3PO4 and arylboronic acid were used. Data for selected compounds.
Compound 3b: yield 48%, mp 265 °C. IR (KBr): 3412 cmꢀ1 (NH). 1H NMR
(300 MHz, DMSO-d6): d 1.44 (s, 9H, CMe3), 1.45 (s, 9H, CMe3), 6.93 (dd, 1H,
J
3 = 3.6 Hz, J4 = 1.8 Hz, 5-H), 7.36 (dd, 1H, J3 = 3.3 Hz, J4 = 2.4 Hz, 6-H), 7.61 (dm,
2H, J = 8.7 Hz, 30,50-H), 7.65 (dm, 2H, J = 8.4 Hz, 30,50-H), 8.29 (dm, 2H, J = 8.7 Hz,
20,60-H), 8.55 (dm, 2H, J = 8.4 Hz, 20,60-H), 11.19 (br s, 1H, NH). 13C NMR
(75 MHz, DMSO-d6): d 31.74, 31.81, 35.19, 35.29, 100.9, 113.6, 125.9, 126.4,
127.9, 128.5, 129.1, 136.3, 136.8, 152.9, 153.5, 154.4, 156.2, 157.1. Anal. Calcd
for C26H29N3: C, 81.42; H, 7.62; N, 10.96. Found: C, 81.54; H, 7.78; N, 10.82.
Compound 3c: yield 29%, mp 281 °C. IR (KBr): 3435 cmꢀ1 (NH). 1H NMR
(300 MHz, CDCl3): d 7.02 (dd, 1H, J3 = 3.9 Hz, J4 = 1.8 Hz, 5-H), 7.46–7.55 (m,
7H, 6-H, 2 ꢂ 300,400,500-H), 7.74–7.77 (m, 4H, 2 ꢂ 200,600-H), 7.84 (dm, 2H,
J = 8.4 Hz, 30,50-H), 7.89 (dm, 2H, J = 8.4 Hz, 30,50-H), 8.45 (dm, 2H, J = 8.7 Hz,
20,60-H), 8.75 (dm, 2H, J = 8.7 Hz, 20,60-H), 10.14 (br s, 1H, NH). 13C NMR
(75 MHz, DMSO-d6 + two drops CF3COOD): d 101.4, 114.0, 127.4, 127.5, 127.8,
128.5, 128.7, 129.1, 129.6, 129.7, 129.8, 130.2, 136.6, 137.4, 140.1, 140.3, 142.3,
142.8, 154.1, 154.3, 155.2, 156.2. Anal. Calcd for C30H21N3: C, 85.08; H, 5.00; N,
9.92. Found: C, 85.29; H, 5.13; N, 9.87. Compound 3e: yield 63%, mp 310 °C
(dec.). IR (KBr): 3400 cmꢀ1 (NH). 1H NMR (300 MHz, DMSO-d6): d 7.14 (dd, 1H,
J
3 = 3.6 Hz, 4 = 1.8 Hz, 5-H), 7.33–7.39 (m, 4H, 30,50-H), 7.48–7.63 (m, 8H,
J
200,300,600,700-H), 7.82 (t, 1H, J = 2.7 Hz, 6-H), 7.87 (d, 2H, J = 8.4 Hz, 100,800-H), 7.95
(d, 2H, J = 8.4 Hz, 100,800-H), 8.29–8.34 (m, 4H, 400,500-H), 8.71 (d, 2H, J = 8.7 Hz,
20,60-H), 8.91 (d, 2H, J = 8.4 Hz, 20,60-H), 12.49 (br s, 1H, NH). 13C NMR (75 MHz,
DMSO-d6): d 101.1, 110.6, 114.1, 121.0, 121.1, 121.3, 121.4, 123.6, 123.7, 127.1,
127.2, 127.3, 127.5, 127.6, 129.5, 129.9, 131.2, 137.7, 138.3, 138.8, 139.3, 140.6,
140.7, 154.6, 155.3, 156.4. Anal. Calcd for C42H27N5: C, 83.84; H, 4.52; N, 11.64.
Found: C, 83.96; H, 4.59; N, 11.72.
6. (a) Itami, K.; Yamazaki, D.; Yoshida, J. J. Am. Chem. Soc. 2004, 126, 15396; (b)
Pascal, L.; Vanden Eynde, J. J.; Van Haverbeke, Y.; Dubois, P.; Michel, A.; Rant,
U.; Zojer, E.; Leising, G.; Van Dorn, L. O.; Gruhn, N. E.; Cornil, J.; Bredas, J. L. J.
Phys. Chem. B 2002, 106, 6442; (c) Wong, K.-T.; Hsu, C. C. Org. Lett. 2001, 3, 173;
(d) Wong, K.-T.; Hung, T. S.; Lin, Y.; Wu, C.-C.; Lee, G.-H.; Peng, S.; Chou, C. H.;
Su, Y. O. Org. Lett. 2002, 4, 513; (e) Wu, C. C.; Lin, Y. T.; Chiang, H. H.; Cho, T. Y.;
Chen, C. W.; Wong, K. T.; Liao, Y. L.; Lee, G. H.; Peng, S. M. Appl. Phys. Lett. 2002,
81, 577; (f) Gompper, R.; Mair, H.; Polborn, K. Synthesis 1997, 696.
18. Itoh, T.; Mase, T. Tetrahedron Lett. 2005, 46, 3573.
19. 2,4-Dichloro-7-tert-butoxycarbonyl-7H-pyrrolo[2,3-d]pyrimidine (4). To
a
7. (a) Meier, H.; Karpuk, E.; Holst, H. C. Eur. J. Org. Chem. 2006, 2609; (b) Meier, H.;
Holst, H. C.; Oehlhof, A. Eur. J. Org. Chem. 2003, 4173; (c) Lee, S. J.; Chang, J. Y.
Tetrahedron Lett. 2003, 44, 7493; (d) Lee, H.; Kim, D.; Lee, H.; Qiu, W.; Oh, N.;
Zin, W.; Kima, K. Tetrahedron Lett. 2004, 45, 1019.
solution of compound (0.4 g, 2.13 mmol) in anhydrous CH2Cl2 (10 mL),
1
DIPEA (0.56 mL, 2.55 mmol), DMAP (0.052 g, 0.43 mmol) and Boc2O (0.7 g,
3.19 mmol) were added. The reaction mixture was stirred under reflux for
10 min. The solvent was evaporated under reduced pressure and the obtained
solid was purified by column chromatography (eluent—CHCl3) to give 0.41 g
(67%) of compound 4, mp 136–136.5 °C (from 2-propanol). IR (KBr): 1750 cmꢀ1
(CO). 1H NMR (300 MHz, CDCl3): d 1.72 (s, 9H, CMe3), 6.68 (d, 1H, J = 3.9 Hz, 5-
H), 7.73 (d, 1H, J = 3.9 Hz, 6-H). 13C NMR (75 MHz, DMSO-d6): d 28.2, 86.7,
102.9, 118.9, 128.4, 146.9, 153.1, 153.6, 154.6. Anal. Calcd for C11H11Cl2N3O2: C,
45.85; H, 3.85; N, 14.58. Found: C, 46.21; H, 3.94; N, 14.55.
8. Jaung, J.-Y. Dyes Pigments 2006, 71, 245.
9. Bennett, S. M.; Nghe, N. B.; Ogilvie, K. K. J. Med. Chem. 1990, 33, 2162.
10. Shih, C.; Chen, V. J.; Gossett, L. S.; Gates, S. B.; MacKellar, W. C.; Habeck, L. L.;
Shackelford, K. A.; Mendelsohn, L. G.; Soose, D. J.; Patel, V. F.; Andis, S. L.;
Bewley, J. R.; Rayl, E. A.; Moroson, B. A.; Beardsley, G. P.; Kohler, W.; Ratnam,
M.; Schultz, R. M. Cancer Res. 1997, 57, 1116.
11. Berry, D. A.; Jung, K.-Y.; Wise, D. S.; Sercel, A. D.; Pearson, W. H.; Mackie, H.;
Randolph, J. B.; Somers, R. L. Tetrahedron Lett. 2004, 45, 2457.
12. (a) Saxena, N. K.; Hagenow, B. M.; Genzlinger, G.; Turk, S. R.; Drach, J. C.;
Townsend, L. B. J. Med. Chem. 1988, 31, 1501; (b) Kazimierczuk, Z.; Cottam, H.
B.; Revankar, G. R.; Robins, R. K. J. Am. Chem. Soc. 1984, 106, 6379.
13. (a) Gholap, A. R.; Toti, K. S.; Shirazi, F.; Deshpande, M. V.; Srinivasan, K. V.
Tetrahedron 2008, 64, 10214; (b) Li, J.; Zhang, X.; Xie, Y. Synlett 2005, 1897; (c)
Yin, J.; Rainka, M. P.; Zhang, X.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124,
1163; (d) Kotha, S.; Lahiri, K.; Kashinath, D. Tetrahedron 2002, 58, 9633; (e)
Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457; (f) Suzuki, A. J. Organomet.
Chem. 1999, 576, 147; (g) Bellina, F.; Carpita, A.; Rossi, R. Synthesis 2004, 2419;
(h) Schroter, S.; Stock, C.; Bach, T. Tetrahedron 2005, 61, 2245; (i) Fairlamb, I. J.
S. Chem. Soc. Rev. 2007, 36, 1036.
14. (a) Sakamoto, T.; Kondo, Y.; Sato, S.; Yamanaka, H. Tetrahedron Lett. 1994, 35,
2919; (b) Calderwood, C. J.; Johnston, D. N.; Munschauer, R.; Rafferty, P. Bioorg.
Med. Chem. Lett. 2002, 12, 1683; (c) Wu, T. Y. H.; Schultz, P. G.; Ding, S. Org. Lett.
2003, 5, 3587; (d) Edstrom, E. D.; Wei, Y. J. Org. Chem. 1993, 58, 403; (e) Klecka,
M.; Pohl, R.; Klepetarova, B.; Hocek, M. Org. Biomol. Chem. 2009, 7, 866.
20. Preparation of 2,4-diaryl-7-tert-butoxycarbonyl-7H-pyrrolo[2,3-d]pyrimidines
(5a–e). Compounds 5a–e were synthesized and isolated according to the
procedure described for 3a–e but starting from compound 4 (0.1 g, 0.35 mmol),
and using the corresponding arylboronic acid (0.83 mmol), K3PO4 (0.35 g,
1.67 mmol), 2.0 mol % Pd(OAc)2, and 4.0 mol % dicyclohexyl(2-biphenyl)-
phosphine. Data for selected compounds. Compound 5b: yield 76%, mp 190–
192 °C. IR (KBr): 1736 cmꢀ1 (CO). 1H NMR (300 MHz, CDCl3): d 1.42 (s, 9H,
CMe3), 1.44 (s, 9H, CMe3), 1.82 (s, 9H, CMe3), 6.93 (d, 1H, J = 4.2 Hz, 5-H), 7.55
(dm, 2H, J = 8.7 Hz, 30,50-H), 7.64 (dm, 2H, J = 8.7 Hz, 30,50-H), 7.78 (d, 1H,
J = 4.2 Hz, 6-H), 8.17 (dm, 2H, J = 8.7 Hz, 20,60-H), 8.64 (dm, 2H, J = 8.7 Hz, 20,60-
H). 13C NMR (75 MHz, CDCl3): d 28.5, 31.5, 31.6, 35.1, 35.2, 85.0, 104.5, 116.1,
125.6, 126.1, 127.2, 128.3, 129.0, 135.6, 136.2, 148.8, 153.5, 153.8, 154.1, 158.1,
160.0. Anal. Calcd for C31H37N3O2: C, 76.98; H, 7.71; N, 8.69. Found: C, 76.52; H,
7.94; N, 8.88. Compound 5c: yield 94%, mp 129.5–130 °C. IR (KBr): 1735 cmꢀ1
(CO). 1H NMR (300 MHz, CDCl3): d 1.80 (s, 9H, CMe3), 3.93 (s, 3H, OMe), 3.95 (s,
3H, OMe), 6.89 (d, 1H, J = 4 Hz, 5-H), 7.05 (dm, 2H, J = 9 Hz, 30,50-H), 7.13 (dm,
2H, J = 9 Hz, 30,50-H), 7.74 (d, 1H, J = 4 Hz, 6-H), 8.20 (dm, 2H, J = 9 Hz, 20,60-H),

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S. Tumkevicius et al. / Tetrahedron Letters 51 (2010) 3902–3906
8.67 (dm, 2H, J = 9 Hz, 20,60-H). 13C NMR (75 MHz, CDCl3): d 28.5, 55.6, 55.7,
120.64, 120.7, 123.8, 124.0, 126.3, 126.4, 127.1, 127.5, 128.2, 130.2, 130.8,
137.0, 137.7, 139.7, 140.0, 140.9, 141.0, 148.4, 154.4, 157.4, 159.3. Anal. Calcd
for C47H35N5O2: C, 80.43; H, 5.03; N, 9.98. Found: C, 80.58; H, 5.17; N, 9.93.
21. (a) Seela, F.; Steker, H. Liebigs Ann. Chem. 1984, 1719; (b) Secrist, J. A.; Liu, P. S. J.
Org. Chem. 1978, 43, 3937.
22. Simokaitiene, J.; Grigalevicius, S.; Grazulevicius, J. V.; Rutkaite, R.; Kazlauskas,
K.; Jursenas, S.; Jankauskas, V.; Sidaravicius, J. J. Optoelectron. Adv. Mater. 2006,
8, 876.
84.9, 104.5, 113.9, 114.4, 115.4, 126.8, 130.1, 130.8, 131.0, 131.6, 148.7, 154.3,
157.7, 159.7, 161.6, 161.8. Anal. Calcd for C25H25N3O4: C, 69.59; H, 5.84; N,
9.74. Found: C, 69.91; H, 5.99; N, 9.71. Compound 5e: yield 86%, mp 230 °C
(dec.). IR (KBr): 1738 cmꢀ1 (CO). 1H NMR (300 MHz, DMSO-d6): d 1.87 (s, 9H,
CMe3), 7.07 (d, 1H, J = 4.2 Hz, 5-H), 7.34–7.63 (m, 12H, 2 ꢂ 30,50, 200,300,600,700-H),
7.81 (d, 2H, J = 8.4 Hz, 100,800-H), 7.87–7.92 (m, 3H, 6-H, 100,800-H), 8.21–8.23 (m,
4H, 2 ꢂ 400,500-H), 8.53 (d, 2H, J = 8.4 Hz, 20,60-H), 9.02 (d, 2H, J = 8.7 Hz, 20,60-H).
13C NMR (75 MHz, CDCl3): d 28.5, 85.4, 104.2, 110.1, 110.2, 116.6, 120.4, 120.6,