Polypyrrole-supported graphite felt for acetylene coupling reaction in solid phase

Article abstract of DOI:10.1055/s-2004-834835

Substrate immobilization on graphite felt for solid-phase acetylene coupling reaction was achieved by electrochemical polymerization of the substrate precursor containing a pyrrole side chain, where the amount of substrate on the electrode surface was easily controlled by the number of repeated cyclic voltammetric scannings. Couplings between terminal acetylenes and the iodobenzene-modified graphite felt electrode or aromatic iodides and the terminal acetylene-modified graphite felt electrode in the presence of palladium catalyst proceeded smoothly in satisfactory yields.

Full text of DOI:10.1055/s-2004-834835

LETTER
2513
Polypyrrole-Supported Graphite Felt for Acetylene Coupling Reaction in
Solid Phase
A
Y
cetylene Couplin
o
g
R
eaction
i
s
n
S
olid Ph
h
ase itomo Kashiwagi,* Shinya Chiba, Hiroshi Ikezoe, Jun-ichi Anzai
Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578, Japan
Fax +81(22)2176840; E-mail: kashi@mail.pharm.tohoku.ac.jp
Received 10 August 2004
investigated the Sonogashira reaction on a GF electrode as
a solid support.
Abstract: Substrate immobilization on graphite felt for solid-phase
acetylene coupling reaction was achieved by electrochemical poly-
2
merization of the substrate precursor containing a pyrrole side A GF electrode has a much lager surface area (0.7 m /g)
chain, where the amount of substrate on the electrode surface was
in comparison with polystylene resin, the Pt and Au elec-
easily controlled by the number of repeated cyclic voltammetric
trodes are commercially available at low price. We were
scannings. Couplings between terminal acetylenes and the iodoben-
intrigued by the possibility of using electrochemistry to
zene-modified graphite felt electrode or aromatic iodides and the
generate a polymer film support on a GF electrode surface
terminal acetylene-modified graphite felt electrode in the presence
with the substrate site attached to the polymer chain.
Thus, we prepared a substrate-modified GF electrode by
electrochemical polymerization of substrate precursors
containing a pyrrole side chain and used for palladium
of palladium catalyst proceeded smoothly in satisfactory yields.
Key words: Sonogashira reaction, solid-phase synthesis, poly-
pyrrole, electrochemical polymerization, modified electrode
(
Pd) catalyst reactions, which are widely researched using
7
polystyrene resin.
Solid-phase synthesis has attracted much interest in or-
1
ganic synthesis because it can improve the reaction yield The preparation of substrate-modified GF electrodes for
by using an excessive reagent and the used reagent can Sonogashira reaction as one of the Pd catalyst reactions is
easily be removed by washing. The solid supports used for shown in Scheme 1. The substrate precursors containing a
solid-phase synthesis are usually polymer resins such as pyrrole side chain were synthesized from 3-(pyrrol-1-
8
polystyrene. Electrochemistry is at the interface of solu- yl)propionic acid and 4-iodobenzyl alcohol. This pyr-
tion and solid-phase chemistry, as reactions occur in the role-based monomer 1 was modified on a GF electrode
2
9
diffusion layer formed at an electrode surface. The possi- by electrochemical polymerization at repeated cyclic
bility of using electrochemistry in solid-phase synthesis voltammetric scans between 0 and +1.5 V vs Ag/AgCl.10
has recently been reported. Pilard et al. demonstrated The amount of substrate on the GF electrode surface was
solid-phase chemistry with a modified electrode prepared determined by the amount of recovered 4-iodobenzyl al-
3
,4
by electrochemical polymerization of substrate precursors cohol that was yielded by the treatment of iodobenzene-
3
containing a thiophene side chain. Pickett and co-work- modified GF electrode with NaOCH
. The relationship
3
ers developed polypyrrole-supported solid-phase chemis- between the amount of substrate and the number of re-
4
try on an electrode surface. More recently, Kwon and peated cyclic voltammetric scannings is shown Figure 1.
Mrksich reported a study that used as a model reaction the The amount of substrate on the GF electrode surface in-
cycloaddition of cyclopentadiene with a self-assembled creased with the increasing number of repeated cyclic
monolayer (SAM) on an electrode surface by hydroquino- voltammetric scannings. The loading of substrate on the
5
ne-terminated alkanethiol. However, they used a plati- GF electrode of 20-times scanning was ca. 80 mmol/g. The
num (Pt) or a gold (Au) electrode as a solid support. Here surface of this modified electrode was stable even if it
we report the first efficient, solid-phase chemistry with a leaves it for several months.
graphite felt (GF) electrode as a solid support.
Preparative Sonogashira reaction was performed on the
6
The Sonogashira reaction is a very useful process for pre- iodobenzene-modified GF electrode (3.0 × 1.0 × 0.5 cm)
paring disubstituted acetylenes that commonly exist in or- in DMF (10 mL) containing Et
N (10 mmol), terminal
ganic compounds. The reaction involves palladium- acetylene (5 mmol), Pd(PPh ) (0.25 mmol) and CuI (0.5
3 4
3
11
catalyzed carbon-carbon bond formation between an aryl mmol, Scheme 1). The result using 1-octyne as terminal
halide and a terminal acetylene. The Sonogashira reaction acetylene is shown in Figure 2. The coupling product
is generally very mild, and does not require strict anhy- yield was 90% when the substrate-modified GF electrode
drous or inert atmosphere conditions, which makes it eas- of 5-times scanning (loading 15 mmolg ) was used. In ad-
ily amenable to automation. Intrigued by the potential use dition, the homogeneous Sonogashira reaction using 1 and
of Sonogashira reaction in combinational chemistry, we 1-octyne was carried out with lower yield (30%) than the
solid-phase system using the substrate-modified GF elec-
–1
trode. We also tried under standard polymerization and re-
action conditions on a Pt plate electrode instead of a GF
electrode, however, the generated polymer film was not
SYNLETT 2004, No. 14, pp 2513–2516
Advanced online publication: 20.10.2004
DOI: 10.1055/s-2004-834835; Art ID: U22504ST
2
2
.1
1
.2
0
0
4
©
Georg Thieme Verlag Stuttgart · New York

2
514
Y. Kashiwagi et al.
LETTER
O
O
i
iii
iv
NH
N
OH
N
O
ii
I
1
O
O
v
vi
N
O
N
O
C
C
R
vii
HO
I
C
n
n
C
R
GF
GF
Scheme 1 Reagents and conditions: i, Acrylonitrile (1.0 equiv), n-Bu NOH (0.1 equiv), –78 °C: ii, KOH, H O, D; iii, 4-iodobenzyl alcohol
4
2
(
(
1.0 equiv), 4-dimethylaminopyridine (5 mol%), DCC (1.5 equiv), CH Cl , 0 °C; iv, electrochemical polymerization; v, terminal acetylene
2 2
5 mmol), Et N (10 mmol), Pd(PPh ) (0.1 mmol), CuI (0.2 mmol), DMF; vi, THF, NaOCH ; vii, HCl.
3
3 4
3
1
00
100
80
80
60
40
60
40
2
0
20
0
0
5
10
15
20
20
40
60
80
100 120
140
the number of scanning
loading (µmol/g)
Figure 1
Figure 2
The results from the Sonogashira reaction of various ter-
minal acetylenes using the iodobenzene-modified GF
electrode of 5-times scanning are shown in Table 1. The
reaction with acetylenic hydrocarbons was obtained to the
corresponding coupling products in high yield (entries 1,
strongly attached to the Pt electrode surface and solid-
phase synthesis could not be used. The coupling product
yield decreased with the increasing immobilized substrate
on the GF electrode surface. This observation suggests
that a thick polymer film was formed on the GF electrode
surface with the increasing repeated cyclic voltammetric
scanning and did not infiltrate the terminal acetylene and
catalyst into a polymer layer.
2
, and 4). Couplings between acetylenic alcohols and the
substrate-modified GF electrode also proceeded smoothly
entries 5 and 6). All terminal acetylenes were converted
to the corresponding coupling products in adequate yield
72–94%).
(
(
Table 1 Results from the Sonogashira Reaction of Various Terminal Acetyles Using the Iodobenzene-Modified GF Electrode of 5-Times
Scanning
Entry
1
Substrate
Product
Yield (%)
90
HC
C
6 13
C H
C
C
C
C
C6H13
HO
HO
2
3
HC
C
86
94
C
CH
C
C
HO
Synlett 2004, No. 14, 2513–2516 © Thieme Stuttgart · New York

LETTER
Acetylene Coupling Reaction in Solid Phase
2515
Table 1 Results from the Sonogashira Reaction of Various Terminal Acetyles Using the Iodobenzene-Modified GF Electrode of 5-Times
Scanning (continued)
Entry
4
Substrate
Product
Yield (%)
88
CH CH C CH
2
2
C
C
HO
5
6
HC
HC
C
C
82
85
C
C
C
C
OH
HO
HO
OH
OH
OH
7
8
O
O
80
84
HC
C
C
C
C
C
HO
HO
O
O
O
O
HC
HC
C
C
O
O
9
75
Cl
C
C
HO
Cl
1
1
0
1
Cl
Cl
72
92
HC
C
C
C
C
C
HO
HO
C
CH
N
N
1
2
CH
78
C
N
N
C
C
HO
We also attempted the use of a pyrrole-based monomer 2 trode or aromatic iodides and the terminal acetylene-
possessing terminal acetylene instead of iodobenzene. modified GF electrode in the presence of a Pd catalyst
The substrate precursors containing a pyrrole side chain proceeded smoothly in satisfactory yields. We are now
were synthesized from 3-(pyrrol-1-yl)propionic acid and exploring Heck reactions of the iodobenzene-modified
1
-butyne-3-ol. The preparation of the terminal acetylene- GF electrode with olefins.
modified GF electrode for Sonogashira reaction is shown
in Scheme 2. The same tendency is shown as when using
the iodobenzene-modified GF electrode for the amount of
Acknowledgment
terminal acetylene on the GF electrode surface by repeat- This work was supported in part by Grants-in-Aid (No. 15590035)
from Japan Society for the Promotion of Science. The Sumitomo
ed cyclic voltammetric scans. The results from the Sono-
Foundation and the Takeda Science Foundation are also acknow-
ledged for financial support.
gashira reaction of various aromatic iodides using the
terminal acetylene-modified GF electrode of 5-times
scanning are shown in Table 2. All aromatic iodides were
converted to the corresponding coupling products in ade- References
quate yield (73–95%).
(
1) Ley, S. V.; Baxendal, I. R.; Bream, R. N.; Jackson, P. S.;
Leach, A. G.; Longbottom, D. A.; Nesi, M.; Scott, J. S.;
Storer, R. I.; Taylor, S. J. J. Chem. Soc., Perkin Trans. 1
In conclusion, we have reported here the first efficient,
immobilization of substrate on a GF electrode by electro-
chemical polymerization of substrate precursors contain-
ing a pyrrole side chain and use for solid-phase synthesis
in place of a polystyrene resin. Couplings between termi-
nal acetylenes and the iodobenzene-modified GF elec-
2
000, 3815.
(
2) Bard, A. J.; Faulkner, L. R. Electrochemical Methods:
Fundamentals and Applications; John Wiley and Sons: New
York, 1980.
Synlett 2004, No. 14, 2513–2516 © Thieme Stuttgart · New York

2
516
Y. Kashiwagi et al.
LETTER
O
O
N
OH
i
N
O
C
ii
C
H
2
O
O
iii
iv
v
N
O
C
N
O
C
C
C
R
C
C
H
R
HO
n
n
GF
GF
Scheme 2 Reagents and conditions: i, 1-Butyn-3-ol (1.0 equiv), 4-dimethylaminopyridine (5 mol%), DCC (1.5 equiv), CH Cl , 0 °C, ii, elec-
2
2
trochemical polymerization; iii, iodide compound (5 mmol), Et N (10 mmol), Pd(PPh ) (0.1 mmol), CuI (0.2 mmol), DMF; iv, THF, NaOCH ;
3
3 4
3
v, HCl.
Table 2 Results from the Sonogashira Reaction of Various Aromat-
ic Iodides Using the Terminal Acetylene-Modified GF Electrode of 5-
Times Scanning
(6) (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron
Lett. 1975, 4467. (b) Sonogashira, K. Metal-Catalyzed
Cross-Coupling Reaction; Wiley-VCH: New York, 1998,
Chap. 5.
(7) Bräse, S.; Kirchohoff, J. H.; Köbberling, J. Tetrahedron
2003, 59, 885.
Entry Substrate
Product
Yield
%)
(
(
(
8) Blume, R. C.; Lindwall, H. G. J. Org. Chem. 1945, 10, 255.
1
2
I
OH
92
9) (a) Diaz, A. F.; Kanazawa, K. K. J. Chem. Soc., Chem.
Commun. 1979, 635. (b) Kanazawa, K. K.; Diaz, A. F.;
Geiss, R. H.; Gill, W. D.; Kwak, J. F.; Logau, J. A.; Robelt,
J. F.; Street, G. B. J. Chem. Soc., Chem. Commun. 1979, 854.
C
C
I
OH 90
H3CO
C
C
(10) General Procedure for Electrochemical Polymerization.
Electrochemical polymerization was performed in a one-
compartment cell with graphite felt (3.0 × 1.0 × 0.5 cm) as
the working electrode and a platinum wire as the counter
electrode, respectively. An Ag/AgCl electrode was used as
the reference electrode. All electrochemical polymerization
experiments were performed in MeCN solution with 0.01 M
monomer concentration and 0.1 M tetraethylammonium
perchlorate as the supporting electrolyte. Repeated cyclic
voltammetric scans between 0 and +1.5 V at 50 mV/s led to
the formation of a conducting polymer film at the GF
electrode.
H3CO
3
I
I
73
OH
OH
C
C
4
5
95
85
C
C
N
N
S
OH
C
C
(11) General Procedure for Sonogashira Reaction on the
Iodobenzene-Modified GF Electrode.
I
S
The iodobenzene-modified GF electrode (3.0 × 1.0 × 0.5
cm) was added to the dry DMF solution (10 mL) containing
Et N (10 mmol), terminal acetylene (5 mmol), Pd(PPh )
3
3 4
(
(
(
3) (a) Pilard, J. F.; Marchand, G.; Simonet, J. Tetrahedron
998, 54, 9401. (b) Marchand, G.; Pilard, J. F.; Berthelot, J.
R.; Simonet, J. New J. Chem. 1998, 23, 869. (c) Marchand,
G.; Pilard, J. F.; Simonet, J. Tetrahedron Lett. 2000, 41, 883.
4) (a) Passos, M. S.; Queiros, M. A.; Gall, T. L.; Ibrahim, S. K.;
Pickett, C. J. J. Electroanal. Chem. 1997, 435, 189.
(0.25 mmol) and CuI (0.5 mmol). The reaction mixture was
stirred for 12 h at r.t. At the end of the reaction, the GF
electrode was separated, and washed three times with THF.
Then, this GF electrode was added to THF (10 mL) and 28%
NaOMe in MeOH (5 mL). The reaction mixture was stirred
for 1 h at r.t. At the end of the reaction, this reaction mixture
1
(
b) Therias, S. M.; Passos, M. S.; Ibrahim, S. K.; Gall, T. L.;
was added to H O (10 mL) and 3 N HCl (10 mL), extracted
2
Queiros, M. A.; Pickett, C. J. Chem. Commun. 1998, 1175.
5) Kwon, Y.; Mrksich, M. J. Am. Chem. Soc. 2002, 124, 806.
three times with EtOAc (10 mL × 3), and filtered in vacuo.
This extracted solution was evaporated, and the product was
1
identified by H NMR spectroscopy.
Synlett 2004, No. 14, 2513–2516 © Thieme Stuttgart · New York