New acyclic Pd-diaminocarbene catalyst for Suzuki arylation of meso-chlorosubstituted tricarboindocyanine dyes

Article abstract of DOI:10.1016/j.tetlet.2012.12.060

Acyclic Pd-diaminocarbene complex showed high catalytic activity in Suzuki arylation of meso-chlorine-substituted tricarboindocyanine dyes. Arylated dyes were obtained in 57-83% yields in the presence of 5 × 10^-4 equiv of catalyst.

Full text of DOI:10.1016/j.tetlet.2012.12.060

Tetrahedron Letters 54 (2013) 1202–1204
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
New acyclic Pd–diaminocarbene catalyst for Suzuki arylation of
meso-chlorosubstituted tricarboindocyanine dyes
Sergey Miltsov a, Vladimir Karavan a, Vadim Boyarsky a, Sara Gómez-de Pedro b, Julian Alonso-Chamarro b,
Mar Puyol b,
⇑
a Department of Chemistry, St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Petrodvorets, Russian Federation
b Grup de Sensors i Biosensors, Unitat de Quimica Analítica, Facultat de Ciències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Acyclic Pd–diaminocarbene complex showed high catalytic activity in Suzuki arylation of meso-chlorine-
substituted tricarboindocyanine dyes. Arylated dyes were obtained in 57–83% yields in the presence of
5 Â 10À4 equiv of catalyst.
Received 7 August 2012
Revised 13 December 2012
Accepted 14 December 2012
Available online 22 December 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Suzuki arylation
Pd-catalyst
N-Heterocyclic carbenes
Cyanine dyes
Pd-complexes with N-heterocyclic carbenes (NHCs) are widely
used as highly efficient catalysts of cross-coupling reactions, such
as in Suzuki, Heck, or Sonogashira reactions, among others.1 The
catalytic activity of Pd-complexes with acyclic diaminocarbenes
(ADCs) in the corresponding reactions2 has been recently proved,
surpassing in some cases the activity of NHC-based catalysts.3
These catalysts have became even more attractive, since a simple
procedure for their preparation has been developed, which consists
of the addition of nitrogen nucleophiles (benzophenone hydra-
zone,3 1,3-diiminoisoindolin-1-one,4 3-iminoisoindolin-1-one,5
and aniline6) to palladium-coordinated isonitriles.
plasticized PVC membranes. Therefore, new NIR plasticized-PVC
soluble indicators are needed. Moreover, such molecules can be ap-
plied to other research fields as for example, the bis-aminosubsti-
tuted derivative of IR-780 (R = Et, R1 = H, R2 = NH2),8 which has
been recently successfully incorporated in the main chain of polya-
mides that exhibited promising electro optical properties.9
In the course of our studies on the synthesis of absorbing NIR
cyanine dyes, some limitations have been found. The first is the
failure of enhancing their stability and the second, the introduction
of functional groups in the basic structure of meso-chlorosubstitut-
ed dyes and their analogues (Fig. 1).
Trends in the optical sensor field are directed to make possible
the combination of traditional bulk optodes (activated PVC mem-
branes) with miniaturized optical components and microsystems.
The design, formulation, and integration of the membranes are still
key factors for modulating sensitivity, selectivity, response time,
and dynamic range of the sensor. A proper selection of the main
compounds involved in the recognition/signaling process is essen-
tial. In this sense, pH indicators have been widely used. Their
absorption bands should match the wavelengths of the cheap light
sources, being the near-infrared region of special interest.7 This re-
gion is clean of chemical interferences since only scarce groups of
molecules are spectroscopically active and hence, a considerable
specificity can be achieved. Most of the commercially available
dyes with absorption bands in the NIR region are not soluble in
Palladium-catalyzed Suzuki arylation in meso-position of the
dyes allows not only the substitution of the highly reactive chlo-
rine atom by inert fragments, but also the modification of their
structure as desired. The alternative route to meso-arylated dyes
requires the preparation of meso-arylated pentamethine salts
formed by Vilsmeier–Haack formylation of 1-arylcyclohexenes,10
which are not readily available, especially with functional substitu-
tion (COOH, NH2, OH). IR-780 and their related dyes slowly decom-
R1
R1
R2
R2
Cl
N
R
N
R
X
n
⇑
Corresponding author.
E-mail address: mariadelmar.puyol@uab.es (M. Puyol).
Figure 1. Structure of diverse meso-chlorosubstituted dyes IR-780, where R = n-Pr,
R1 = R2 = H, X = I, n = 1.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.12.060

S. Miltsov et al. / Tetrahedron Letters 54 (2013) 1202–1204
1203
Scheme 1. Arylation of meso-chlorine-substituted tricarboindocyanine dyes.
Table 1
Synthesized dyes, maximum absorbance wavelengths, and yields
meso-Chlorosubstituted dye
Dye
R
R1
R2
H
n
kmax (nm)
Yield (%)
1a
1b
1c
1d
1e
1f
2a
2b
2c
2d
2e
2f
Et
Et
Et
Et
H
1
1
1
1
0
1
1
764
802
755
793
795
769
772
68
76
83
79
57
61
65
–(CH@CH)2–
H
H
H
H
H
COOH
NHCOCH3
H
H
SO3Na
Et
NaO3S(CH2)4
Et
1g
2g
N
N
I
Cl
B(OH)2
Cl
Pd-cat (5x10-2 eq),
4
N
N
K2CO3
Br
I
3
N
N
H
I
(< 30 %)
5
Scheme 2. Arylation of meso-bromo-substituted dicarboindocyanine dyes.
pose under Suzuki coupling conditions, since addition of basic
nucleophiles to C@N bonds is not completely reversible. The nucle-
ophilic substitution of meso-chlorine atoms is another undesired
by-reaction. In order to avoid these side reactions, it is necessary
to perform arylations as fast as possible. However, the reported
procedures require long reaction times even at rather high loadings
of catalysts (0.03 equiv PEPPSI-IPr, 12 h, room temperature, yield
44%;11 0.15 equiv Pd(PPh3)4, 24 h, 100 °C, yield 62%12). Lee et al.13
reported an example of arylation in neutral aqueous media
(0.065 equiv Pd(PPh3)4, 20 h, 100 °C, yields 61–92%). However, this
procedure can only be applied for water-soluble dyes.
plex PdCl2(CyN„C)2.14 Arylhydrazine with powerful electron-
withdrawing substituent was chosen to diminish the basicity of
the anilinic nitrogen and prevent its addition to the second isoni-
trile ligand, which was previously observed with unsubstituted
phenylhydrazine.15 The new catalyst appeared to be highly effec-
tive in the arylation of target dyes (Scheme 1).
When reaction with 1a was carried out in methanol, consider-
able amounts of meso-methoxysubstituted derivative (ꢀ20%) were
detected by NMR analysis of the reaction mixture. The formation of
the by-product (meso-ethoxy dye) diminished to 8–10% by chang-
ing the solvent to ethanol. Finally, the side process was totally
ceased when the reaction was performed in 85% of aqueous i-pro-
panol. The complete conversion of dye 1a was obtained in 1 h with
5 Â 10À4 equiv of catalyst,16 while diminishing the catalyst loading
Thus, a newly synthesized palladium–ADC complex was used
for this purpose. The Pd-complex was prepared by the addition
of 4-nitrophenylhydrazine to palladium–cyclohexylisonitrile com-

1204
S. Miltsov et al. / Tetrahedron Letters 54 (2013) 1202–1204
Acc. Chem. Res. 2008, 41, 1440–1449; (d) Valente, C.; Calimsiz, S.; Hoi, K. H.;
Mallik, D.; Sayah, M.; Organ, G. Ang. Chem., Int. Ed. 2012, 51, 3314–3332; (e)
Organ, M. G.; Chass, G. A.; Fang, D.-C.; Hopkinson, A. C.; Valente, C. Synthesis
2008, 2776–2797; (f) Kantchev, E.; Assen, B.; O’Brien, C. J.; Organ, M. G. Ang.
Chem., Int. Ed. 2007, 46, 2768–2813.
10 times resulted in a domination of side products. On the other
hand, the catalyst stock solution in methanol (0.001 mmol/mL)
did not lose its activity within at least three months. Surprisingly,
the precursor complex PdCl2(CyN„C)2 was found to act also as a
catalyst of arylation. However, its activity was lower, since partial
reduction by alcohols to metallic palladium took place in alcoholic
solutions even at room temperature in few hours. In order to
achieve the same results for the synthesis of dye 2a, meaning the
complete conversion of the initial dye in 1 h and achieving a com-
parable yield, an increase of 100 times the molar amount of cata-
lyst was required. In this case, the catalytic species was probably
in situ generated by the addition of an alkoxide or an hydroxide an-
ion to the palladium–isonitrile complex, forming the aminoalkoxy-
or aminohydroxycarbene. The use of milder bases such as triethyl-
amine or sodium acetate was also tried; however, the attempts ap-
peared ineffective. It should be pointed out that in the case of dye
1c, two additional equivalents of K2CO3 were required for the neu-
tralization of carboxy groups. Otherwise, the arylation did not pro-
ceed. Results are summarized in Table 1, where the listed yields
correspond to purified products.
2. Boyarskiy, V. P.; Luzyanin, K. V.; Kukushkin, V. Yu. Coord. Chem. Rev. 2012, 256,
2029–2056.
3. Luzyanin, K. V.; Tskhovrebov, A. G.; Carias, M. C.; da Silva, M. F. C. G.; Pombeiro,
A. J. L.; Kukushkin, V. Yu. Organometallics 2009, 28, 6559–6566.
4. Chay, R. S.; Luzyanin, K. V.; Kukushkin, V. Yu.; da Silva, M. F. C. G.; Pombeiro, A.
J. L. Organometallics 2012, 31, 2379–2387.
5. Luzyanin, K. V.; Pombeiro, A. J. L.; Haukka, M.; Kukushkin, V. Yu.
Organometallics 2008, 27, 5379–5389.
´
´
6. Martınez-Martınez, A.-J.; Chicote, M.-T.; Bautista, D.; Vicente, J. Organometallics
2012, 31, 3711–3719.
7. (a) Miltsov, S.; Encinas, C.; Alonso, J. Tetrahedron Lett. 1999, 40, 4067–4068; (b)
Puyol, M.; Encinas, C.; Rivera, L.; Miltsov, S.; Alonso, J. J. Sens. Actuators, B 2007,
122, 53–59; (c) Rivera, L.; Puyol, M.; Miltsov, S.; Alonso, J. Anal. Bioanal. Chem.
2007, 387, 2111–2119; (d) Puyol, M.; Encinas, C.; Rivera, L.; Miltsov, S.; Alonso,
J. Dyes Pigm. 2007, 73, 383–389; (e) Miltsov, S.; Encinas, C.; Alonso, J.
Tetrahedron Lett. 2001, 42, 6129–6131.
8. Encinas, C.; Miltsov, S.; Rivera, L.; Encinas, C.; Alonso, J. Tetrahedron Lett. 2003,
44, 2301–2303.
9. Goikhman, M. Y.; Yevlampieva, N. P.; Kamanina, N. V.; Podeshvo, I. V.; Gofman,
I. V.; Miltsov, S. A. Polym. Sci., Ser. A 2011, 53, 457–468.
10. Salon, J.; Wolinska, E.; Raszkiewicz, A.; Patonay, G.; Strekowski, L. J. Heterocycl.
Chem. 2005, 42, 959–961.
11. Pinchuk, A.; Weichert, J. P.; Longino, M.; Kandela, I.; Clarke, W.; R. U.S. Patent
2012,01,28,596, 2012; Chem. Abstr. 2012, 156, 660169.
12. Port, M.; Rousseaux, O. WO Patent 200,90,53,596, 2009; Chem. Abstr. 2009, 150,
501154.
On the other hand, the attempted arylation of meso-bromosub-
stituted dicarboindocyanine 3 did not lead to the target product 4,
probably, due to steric hindrance in the reactive site. However, the
formation of the debrominated product 5 was observed at low con-
versions (<30%) (Scheme 2). In the absence of arylboronic acid the
reaction proceeded similarly. Moreover, attempts of completing
the process with increased amount of catalyst (5 Â 10À2 equiv) un-
der prolonged heating led to dye decomposition.
13. Lee, H.; Mason, J. C.; Achilefu, S. J. Org. Chem. 2006, 71, 7862–7865.
14. Preparation of Pd-cat: 4-nitrophenylhydrazine (20 mg, 0.125 mmol) was added
to a solution of PdCl2(CyN„C)2 (50 mg, 0.125 mmol) in 5 mL of CHCl3 and kept
under reflux for 8 h. After filtration, the solution was concentrated in vacuo to
1 mL and diluted with 5 mL of ether. The crystals formed in 24 h were filtered
out, washed with ether and dried on air. Yield 71 mg (95%). 1H NMR (Bruker
DPX-300, 300 MHz) (DMSO-d6) d (ppm): 9.90 (br s, 1H), 8.10 (d, 2H, J = 8.7 Hz),
7.75 (br s, 1H), 7.05 (d, 1H, J = 10.2 Hz), 6.90 (d, 2H, J = 8.7 Hz), 4.44 (m, 1H),
With these results, the acyclic Pd–diaminocarbene complex
demonstrates high catalytic activity in Suzuki arylation of meso-
chlorine-substituted tricarboindocyanine dyes.
4.01 (m, 1H), 2.20–1.24 (m, 20H). IR (KBr, m
, cmÀ1): 2934–2856 (C–H); 2230
(C„N); 1330 (NO2). ES-MS+ (Bruker micrOTOF) [MÀCl]+: 512.0989 (calcd
512.1044 for C20H29ClN5O2Pd). ES-MSÀ: [MÀH]À:546.0646 (calcd 546.0655 for
C
20H28Cl2N5O2Pd). Anal. Calcd for C20H29Cl2N5O2Pd: C 43.77, H 5.33, N 12.76.
Acknowledgments
Found C 44.38, H 5.59, N 13.02.
15. (a) Moncada, A. I.; Khan, M. A.; Slaughter, L. M. Tetrahedron Lett. 2005, 46,
1399–1403; (b) Moncada, A. I.; Tanski, J. M.; Slaughter, L. M. J. Organomet.
Chem. 2005, 690, 6247–6251; (c) Moncada, A. I.; Manne, S.; Tanski, J. M.;
Slaughter, L. M. Organometallics 2006, 25, 491–505.
The authors thank Saint-Petersburg State University for a re-
search Grant, the FT Program (contract P676), RFBR (Grants 11-
03-00048-a, 11-03-12044-ofim, and 12-03-00076-a), and RAS Pre-
sidium Subprogram. This work has also been supported by the
Spanish Ministry of Science and Innovation (MICINN) through pro-
jects CTQ2009-12128 and the Consolider Ingenio 2010 project
CSD2006-12, and Catalonia Government through SGR 2009-0323.
We are grateful to E. Savicheva, B.Sc., for the preparation of the
catalyst.
16. Representative procedure for 2a: dye 1a (320 mg, 0.50 mmol), 4-
chlorophenylboronic acid (100 mg, 0.64 mmol), potassium carbonate
(100 mg, 0.72 mmol), and 0.25 mL of the stock solution of Pd-cat21
(0.001 mmol/mL) in 10 mL of 85% aqueous i-propanol were heated at reflux
for 1 h. After cooling and acidification with 1 mL of acetic acid, the volatiles
were evaporated in vacuo and the residue was recrystallized from methanol,
containing 100 mg/mL of NaI. Yield 242 mg (68%). 1H NMR (DMSO-d6) d (ppm)
1.16 (s, 12H), 1.23 (br t, J = 6,6 Hz, 6H), 1.95 (br s, 2H), 2.69 (br s, 4H), 4.15 (br s,
4H), 6.22 (d, J = 14.5 Hz, 2H), 7.06 (d, J = 14.5 Hz, 2H), 7.18 (br s, 2H), 7.29 (d,
J = 8.0 Hz, 2H),), 7.35 (br s, 4H), 7.53 (d, J = 7.3 Hz, 2H), 7.71 (d, J = 8.0 Hz, 2H).
ES-MS+ 587.3204 (calcd 587,3193). kmax (MeOH) 764 nm
mol cm).
(e
= 1.91 Â 105 l/
References and notes
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C.; Nolan, S. P. Chem. Soc. Rev. 2011, 40, 5151–5169; (c) Marion, N.; Nolan, S. P.