Stille reaction on pyridinium cations

Article abstract of DOI:10.1055/s-2002-34903

A novel unit based on pyridinium cations has been synthesized by the Stille reaction and represents a model for development of molecular electronic devices.

Full text of DOI:10.1055/s-2002-34903

1904
LETTER
Stille Reaction on Pyridinium Cations
Stille
Reactionon
o
Pyridinium
C
m
ations ingo García-Cuadrado, Ana M. Cuadro, Julio Alvarez-Builla, Juan J. Vaquero*
Departamento de Química Orgánica, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain
Fax +34(91)8854686; E-mail: juanjose.vaquero@uah.es
Received 5 September 2002
(Scheme 1) as a model for the preparation of the novel
systems 2.
Abstract: A novel unit based on pyridinium cations has been syn-
thesized by the Stille reaction and represents a model for develop-
ment of molecular electronic devices.
Key words: heteroaromatic cations, Stille reaction, molecular elec-
tronic devices
The preparation of organic molecules with extended
-
conjugation has attracted considerable attention because
such materials exhibit interesting properties and can serve
as models for the construction of nanoarchitectures. Mo-
lecular wires, electron-conducting devices and molecular
machines are all fields of active investigation, to name a
few examples.1 Recent studies have shown that oligo(phe-
nyleneethynylene)s containing nitro groups 1 (Figure 1)
are good candidates for electronic switching and memory
devices,2 and attachment of terminal groups to one or both
ends of the molecule could make them function as so-
called molecular alligator clips.3
Scheme 1
3-Bromo-N-methylpyridinium iodide 3a was treated with
tributylvinylstannane in the presence of 5 mmol%
Pd(PPh3)4 in DMF at room temperature with 10 mmol%
copper(I) iodide as co-catalyst (Method A).10 In this case,
however, only traces of the desired derivative were ob-
tained. Repeated attempts at 80 ºC gave the 3-vinyl deriv-
ative 4a in only 20% yield. In contrast, coupling of 3a
with donor11 units such as phenylethynyl-, phenyl-, 2-
thienyl-, 2-furanyl- and N-methyl-2-pyrrolyl tributylstan-
nane gave moderate yields, even after heating (80 ºC) in
some cases.
In this context, we considered that the presence of het-
eroaromatic cations in a -conjugated system, such as 2
(Figure 1), could lead to a new class of compounds with
potentially interesting properties such as electronic con-
ductivity, electrochromism, and optical non-linearity,
among others.4
After considering alternatives to prepare the desired vinyl
derivative 4a, coupling of 3a with tributylvinyltin was
tested in the presence of tri-ortho-tolylphosphine (5
mmol%) and tris(dibenzylideneacetone)dipalladium (5
mmol%) [P(o-Tol)3/Pd2(dba)3] at 80 ºC for 1.5 hours in
DMF. This reaction gave 4a in 63% yield. These new re-
action conditions (Method B)12 were successfully applied
to the coupling of 3a with phenyl- and 2-furanyl tributyl-
stannane as representative examples. The results summa-
rized in Table 1 show the most satisfactory yields under
the conditions used for 3a.
With this target in mind, azinium cations were chosen as
key building blocks and palladium coupling processes as
methods to create the core units. Palladium-catalyzed re-
actions have emerged as powerful tools for C–C bond
formation5 and have been applied to a variety of heterocy-
clic substrates.6 However, a coupling route involving het-
eroaromatic cations is a field that has received little
attention. To our knowledge, only one example has been
reported by Zoltewicz7 from N-functionalized pyridyl-
stannanes. More recently we described the first example8
of Stille reaction9 involving quinolizinium cations. In the
present paper, we wish to report our results using the Stille
reaction for the successful substitution of pyridinium salts
On the basis of these results, we focused our attention on
coupling with -deficient stannanes, which would pro-
duce units with linkers for subsequent coordination
(Table 1, entries 7–9). Initially, 2- and 4-pyridinylstan-
nanes were tested, yielding the coupled products as a com-
Figure 1
Synlett 2002, No. 11, Print: 29 10 2002.
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© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

LETTER
Stille Reaction on Pyridinium Cations
Yield (%)
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Table 1 Palladium-Catalyzed Cross-Coupling Reaction between 3 and Stannanes
Entry
Stannane
Coupling product
1
2
4a (63)b
4b (80)a
–
–
5b (79)a,b
6b (69)b
3
4
4c (79)b
4d (91)b
5c (54)b
5d (75)b
6c (64)b
6d (65)b
5
6
7
4e (78)a
4f (51)a
4g (44)c
5e (68)b
5f (59)b
5ge (59)a
6e (86)b
6f (66)b
8
9
4h (44)c
4e (20)c
a Method A: Bu3Sn-R, Pd(PPh3)4 (5 mmol%) CuI (10 mmol%), DMF, r.t. or heating at 80 ºC.
b Method B: Bu3Sn-R, Pd2(dba)3/P(o-Tol)3 (5 mmol%), DMF. r.t. or heating at 80 ºC.
c Method C: Bu3Sn-R, Pd2(dba)3/P(o-Tol)3 (5 mmol%), KF (1.3 equiv), DMF, 80 ºC.
d 4g Isolated as iodide.
e 5g Isolated as tosylate.
plex mixture. However, the use of KF13 (Method C)14 to room temperature (Table 1, entry 2). Alternatively, the re-
avoid homocoupling, gave compounds 4g and 4h in 44% action of 3b with stannanes by Method B produced the
yield. The reaction of 3a with 2-pyrazinylstannane afford- corresponding derivatives 5 (Table 1, entries 2–6) in good
ed 4i (20%) along with the homocoupled product (38%).
yields, either at room temperature or by heating at 80 ºC.
By contrast, the same procedure with 3b in the presence
of 2-tributyl stannylpyridine, by either Methods A or B,
gave the dehalogenated pyridinium salt as the main prod-
uct. In an attempt to overcome the competing dehalogena-
tion process, the counterion was changed from iodide to
tosylate.7 Thus, N-methylpyridinium 3b, as the tosylate,
was coupled with 2-tributylstannylpyridine to give 5g in
59% yield (Table 1, entry 7). Under identical conditions,
Application of the Methods A and B, to the preparation of
2-vinyl derivative 5a from 3b and tributylvinylstannane
proved unsuccessful, giving only the dehalogenated N-
methylpyridinium iodide. Similarly, coupling with fura-
nyl- and thienylstannane by method A failed to produce
the heteroaryl derivatives. However, the same reaction
with phenylethynylstannane was complete in 15 hours at
Synlett 2002, No. 11, 1904–1906 ISSN 0936-5214 © Thieme Stuttgart · New York

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D. García-Cuadrado et al.
LETTER
(4) Nerenz, H.; Meier, M.; Grahn, W.; Reisner, A.; Schmälzlin,
E.; Standler, S.; Meerholz, K.; Bräuchle, C.; Jones, P. G. J.
Chem. Soc., Perkin Trans. 2 1998, 437.
the reaction of 3b with 2-tributylstannylpyrazine also
gave the coupled compound, as evidenced by NMR spec-
troscopy. In this case, however, isolation of the product
has proved difficult so far.
(5) (a) Tsuji, J. Palladium Reagents and Catalysts: Innovations
in Organic Synthesis; John Wiley and Sons: Chichester,
1995, Chap. 4, 125. (b) Farina, F. Comprehensive
Organometallic Chemistry II, Vol. 12; Abel, E. W.; Stone, F.
G. A.; Wilkinson, G., Eds.; Pergamon Press: Oxford, 1995,
Chap. 3.4, 161. (c) Metal-Catalyzed Cross-Coupling
Reactions; Diederich, F.; Stang, P. J., Eds.; Wiley-VCH:
Weinheim, 1998. (d) Perspectives in Organopalladium
Chemistry for the XXI Century; Tsuji, J., Ed.; Elsevier Press:
Lausanne, Switzerland, 1999.
Finally, 3c was treated with different stannanes under the
conditions of Method B. Table 1 shows the results ob-
tained in the coupling of 3c with representative alkenyl,
alkynyl and heteroaryl organotin compounds. Unfortun-
ately, coupling with tributylvinylstannane led to extensive
decomposition (Table 1, entry 1) either on using Method
A or B. A number of modifications such as changes in sol-
vents, amount of alkene, or use of cosolvents were tried
but the coupling was unsuccessful. An explanation for this
result with 3b and 3c could be related with the activation
of pyridinium - and -positions, which bear a partial
positive charge that favours nucleophilic attack and even
polymerization of the final product.15
(6) (a) Undheim, K.; Benneche, T. Adv. Heterocycl. Chem.
1995, 62, 330. (b) Kalinin, V. N. Synthesis 1992, 413.
(c) Li, J. J.; Gribble, G. W. Palladium in Heterocyclic
Chemistry; Pergamon Press: Oxford, 2000.
(7) Zoltewicz, J. A.; Cruskie, M. P. J. Org. Chem. 1995, 60,
3487.
(8) Barchín, B. M.; Valenciano, J.; Cuadro, A. M.; Alvarez-
Builla, J.; Vaquero, J. J. Org. Lett. 1999, 1, 545.
It is anticipated that the methodology described here will
be useful for the preparation of highly conjugated systems
such as 7 (Scheme 2) by a double Stille reaction.
(9) (a) Mitchell, T. N. In Metal-Catalyzed Cross-Coupling
Reactions; Diederich, F.; Stang, P. J., Eds.; Wiley-VCH:
New York, 1998, Chap. 4. (b) Farina, V.; Krishnamurthy,
V.; Scott, W. J. Org. React. 1997, 50, 1. (c) Farina, V.;
Roth, G. P. Advances in Metal-Organic Chemistry, Vol. 5;
Liebeskind, L. S., Ed.; JAI Press, Inc.: Greenwich, 1996, 1.
(d) Mitchell, T. N. Synthesis 1992, 803. (e) Ritter, K.
Synthesis 1993, 735. (f) Stille, J. K. Angew. Chem., Int. Ed.
Engl. 1986, 25, 508.
(10) Representative Procedure A: A flame-dried two-necked
flask was charged under argon with the pyridinium salt
(100 mg, 0.333 mmol) in dry DMF (5 mL). Then, 10 mol%
CuI (0.033 mmol, 6.3 mg) and the corresponding stannane
(1.3 equiv, 0.429 mmol) were slowly added followed by
5 mol% Pd(PPh3)4 (0.0165 mmol, 15.1 mg). The reaction
mixture was heated at 80 ºC or stirred at r.t. (as indicated)
and then filtered through a small pad of celite and washed
with methanol. The solvent was removed and the residue
was triturated with EtOAc. Purification of the crude product
by column chromatography on silica gel (reverse phase),
using water as the eluent yielded the coupling product.
(11) Devasagayaraj, A.; Tour, J. M. Macromolecules 1999, 32,
6425.
(12) Representative Procedure B: A flame-dried two-necked
flask was charged under argon with the pyridinium salt (100
mg, 0.333 mmol) in dry DMF (5 mL). Then, 5 mol%
Pd2(dba)3 (0.0165 mmol, 15.1 mg) and 5 mol% P(o-Tol)3
(0.0165 mmol, 5 mg) were slowly added followed by the
corresponding stannane (1.3 equiv, 0.429 mmol). The
mixture was stirred at r.t. and the work-up procedure, which
was similar to Method A, yielded the coupling product.
(13) (a) Littke, A. F.; Fu, G. C. Angew. Chem. Int. Ed. 1999, 38,
2411. (b) Majeed, A. J.; Antonsen, O.; Beneche, T.;
Undheim, K. Tetrahedron 1989, 45, 993.
(14) Representative Procedure C: A flame-dried two-necked
flask was charged under argon with the pyridinium salt (100
mg, 0.333 mmol) in dry DMF (5 mL). Then, 5 mol%
Pd2(dba)3 (0.0165 mmol, 15.1 mg), 5 mol% P(o-Tol)3
(0.0165 mmol, 5 mg) and 1.3 equiv KF (0.429 mmol, 24.9
mg) were slowly added followed by 1.3 equiv of the
corresponding stannane (0.429 mmol). The reaction mixture
was heated at 80 ºC (as indicated), the residue was triturated
with acetonitrile and the liquid was purified by column
chromatography on silica gel (reverse phase) using water as
the eluent.
Scheme 2
In summary, we have developed an efficient and mild pro-
tocol for the synthesis of substituted azinium cations using
vinyl-, alkynyl-, aryl-, and heteroaryl stannanes and bro-
mopyridinium salts. Further work is currently underway,
aimed at the preparation of more complex systems from
other dihaloheteroaromatic cations and the construction
of systems with alternating donor/acceptor repeated units.
Acknowledgement
The authors thank the Comisión Interministerial de Ciencia y Tec-
nología (CICYT, Project SAF98-0093) for financial support, and
the Ministerio de Educación y Cultura for a research grant (D.G-C.)
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Synlett 2002, No. 11, 1904–1906 ISSN 0936-5214 © Thieme Stuttgart · New York