A palladium-catalyzed synthesis of 2-alkylidene-pyrrolo[c]-1,4-dioxanes: Synthesis of 3,4-(cis-1,2-dimethyl)ethylenedioxypyrrole

Article abstract of DOI:10.1016/j.tetlet.2004.04.042

Palladium-catalyzed cyclization of ethyl-1-benzyl-3,4-dihydroxypyrrole-2,5- dicarboxylate with various propargylic carbonates rendered 2- alkylidenepyrrolo[c]-1,4-dioxane derivatives with excellent yields. Further chemical manipulations of a selected compound led to 3,4-(cis-1,2-dimethyl) ethylenedioxypyrrole in good yield.

Full text of DOI:10.1016/j.tetlet.2004.04.042

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 4973–4975
A palladium-catalyzed synthesis of 2-alkylidene-pyrrolo[c]-1,4-
dioxanes: synthesis of 3,4-(cis-1,2-dimethyl)ethylenedioxypyrrole
Kyukwan Zong,b Khalil A. Abbouda and John R. Reynoldsa,*
aDepartment of Chemistry, Center for Macromolecular Science and Engineering, University of Florida,
PO Box 117200, Gainesville, FL 32611-7200, USA
bDivision of Science Education, Chonbuk National University, Jeonju, Jeonbuk, South Korea 561-756
Received 25 February 2004; accepted 9 April 2004
Available online 10 May 2004
Abstract—Palladium-catalyzed cyclization of ethyl-1-benzyl-3,4-dihydroxypyrrole-2,5-dicarboxylate with various propargylic car-
bonates rendered 2-alkylidenepyrrolo[c]-1,4-dioxane derivatives with excellent yields. Further chemical manipulations of a selected
compound led to 3,4-(cis-1,2-dimethyl)ethylenedioxypyrrole in good yield.
ꢀ 2004 Elsevier Ltd. All rights reserved.
Heterocycle-based conjugated polymers, such as poly-
pyrrole, polythiophene, polyfuran, and others, have
received significant attention due to the wide range of
electrical, electrochemical, and optical properties they
display. The heteroatoms within a ring play an impor-
tant role in controlling the properties of the polymers
due to their intrinsic electron-donating or electron-
withdrawing capabilities, along with other properties,
which include hydrogen bonding and polarizability.1
These polymers have been utilized in the applications as
semiconductors for field-effect transistors2;3 and
LEDs,4;5 as conductors for electrostatic charge dissipa-
tion and EMI shielding, and redox active materials for
energy storage (batteries and supercapacitors) and
electrochromic devices.6 Appending an alkylenedioxy
bridge across the 3- and 4-positions of pyrrole yields
poly(3,4-alkylenedioxypyrrole) (PEDOP), which adds
electron density to the aromatic ring, reducing both the
monomer and polymer oxidation potentials and results
in the formation of highly stable conducting states.
Despite the importance of poly(alkylenedioxypyrroles),
the routes for monomer synthesis are limited due to the
intrinsic electron-rich property of pyrrole rendering the
chemistry more difficult than the thiophene equivalent.
Merz et al. first reported the synthesis of 3,4-ethylendi-
oxypyrrole (EDOP, 1), which included examples of
noncyclic dialkoxyprroles.7 The chemistry used was
similar to many dioxythiophene syntheses where the ring
formation is completed via Williamson etherification.
Subsequently, our group has reported the synthesis of a
range of 3,4-alkylenedioxypyrroles, their derivatives,
and their electrochemical studies.8–10 As reported, this
route is practical for the synthesis of 3,4-alkylene-
dioxypyrroles equipped with less hindered substituents
on the alkylenedioxy bridge. Investigating the tailored
properties of the polymers lead to a search for a route to
produce a variety of derivatives that may have bulky or
functionalized substituents. It is difficult to place sub-
stituents on the ethylenedioxy ring using the Williamson
etherification method and low yields result.
O
O
O
O
N
H
1
N
H
2
EDOP
ProDOP
Here we report an efficient route for the synthesis of
substituted 3,4-ethylenedioxypyrroles via palladium-
catalyzed cyclization of a dihydroxypyrrole derivative
with various propargylic carbonates as well as the syn-
thesis of 3,4-[cis-1,2-dimethyl]ethylenedioxypyrrole. It is
well known that palladium reacts with propargylic car-
bonate to form an allenylic palladium complex in situ,
which subsequently reacts with a heteroatomic nucleo-
phile to give carbon–heteroatom bond formation.11–14
Sinou et al. published a series of papers on the synthesis
Keywords: Dioxyheterocycle; Dioxypyrrole.
* Corresponding author. Tel.: +1-3523929151; fax: +1-3523929741;
e-mail: reynolds@chem.ufl.edu
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.04.042

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K. Zong et al. / Tetrahedron Letters 45 (2004) 4973–4975
of 2-alkylidene-1,4-benzodioxanes via palladium-cata-
lyzed cyclization of a catechol and a propargylic
carbonate.11–13 In our work, we predicted that the 3,4-
dihydroxypyrrole derivative 3 may be used as a catechol
equivalent to produce methylidene-1,4-pyrrolo[c]diox-
ane as shown in Scheme 1.
One pot hydrogenation of the exo-vinylidene unit and
catalytic hydrogen transfer debenzylation of 5c was
carried out in the presence of a palladium catalyst as
shown in Scheme 2 at 90 ꢁC. The reaction smoothly
afforded both saturated and debenzylated 7 and 8 with 7
in 95% yield. As expected, hydrogenation took place
predominantly on the less hindered side of the exo-
vinylidene group to give the cis-product in a 95:5 ratio.
The major product 7 was easily purified by recrystalli-
zation from a mixture of ethyl acetate diluted with
hexane. The X-ray crystal structure of 7 confirmed the
cis orientation of the two methyl groups on the dioxane
ring where one methyl group (C7) was highly distorted
from the dioxane plane as shown in Figure 1. It should
also be noted that the pyrrole ring and two neighboring
ester groups are in the same plane due to hydrogen
bonding between the NH of the pyrrole and the car-
bonyl group.17
Indeed the reaction of the dihydroxypyrrole 3 with
methyl propargylic carbonate 4a in the presence of
Pd(PPh3)4/dppb (1,4-bis(diphenylphosphino)butane), in
THF at room temperature, gave the cyclized product
methylidene-1,4-pyrrolo[c]dioxane 5a, in 85% yield in
36 h. The use of another catalyst, Pd2(dba)3, under the
similar reaction conditions brought comparable reaction
times and yields. We observed a lower reactivity of 3 in
comparison with catechol as explained by less nucleo-
philicity of the diol of 3 as the two neighboring ester
groups withdraw electrons from the oxygen of the diol.
When the system was heated to reflux (66 ꢁC), the
reaction proceeded much faster and was complete in
12 h.15 In order to evaluate substituent effects on the
reaction rate, two substrates, 1-methylethynyl methyl
carbonate (4b) and 3-methylethynyl methyl carbonate
(4c), were prepared for comparison. The two com-
pounds are structural isomers by location of a methyl
group. When 4b was employed in the reaction, it gave 6b
in excellent yield (98%) with trace amounts of 5b. The
reaction of 4c gave 5c in 95% yield with 6c in trace
amounts. Note, with these methyl substituents, 5c and
6b are the same compound. The size of the substituent
was increased from methyl to ethyl using 3-ethylethynyl
methyl carbonate (4d) and 1-ethylethnyl-methyl car-
bonate (4e). Again, the reaction with 4d gave 5d as a
major product in 95% yield with 6d as a minor product
while the reaction of 4e gave 6e as a major product in
96% yield and 5e as a minor product.
Hydrolysis and decarboxylation of 7 (Scheme 2) gave
3,4-[cis-1,2-dimethyl]ethylenedioxypyrrole
9 in 70%
yield.10 Compound 9 was a pale yellow oil sensitive to
decomposition by oxygen as with other alkylenedioxy-
pyrroles. All compounds were fully characterized and
spectroscopic data for selected compounds is given.16
Me
O
O
EtO2C
CO2Et
N
Ph
5c
H2 (Pd/C)
AcOH, 90 oC
12 h
Me
Me
O
Me
O
Me
O
However, the regioselectivity was somewhat decreased
to around 85:15 and no significant reaction rate differ-
ence between the two reactants was observed. To dem-
onstrate the usefulness of the methodology developed
here, compound 5c was selected for further chemical
manipulation.
O
+
EtO2C
EtO2C
CO2Et
CO2Et
N
H
8
N
H
7
5%
95%
recrystallization
ethyl acetate/hexane
HO
EtO2C
OH
CO2Et
Me
O
Me
R2
+
R1
O
OCO2Me
N
4
Ph
EtO2C
a R1 = H, R2 = H
b R1 = H, R2 = Me
c R1 = Me, R2 = H
d R1 = Et, R2 = H
e R1 = H, R2 = Et
CO2Et
N
3
H
7
Pd(PPh3)4
1) 3M NaOH, 70 oC
6 h, then HCl
dppb, THF
reflux, 12 h
2) triethanolamine
180 oC, 5-10 min
Me
R1
R2
R2
R1
Me
O
O
O
O
O
O
+
EtO2C
CO2Et
EtO2C
CO2Et
N
N
N
H
9
Ph
Ph
6
5
Scheme 1.
Scheme 2.

K. Zong et al. / Tetrahedron Letters 45 (2004) 4973–4975
4975
11. Labrosse, J.-R.; Lhoste, P.; Sinou, D. J. Org. Chem. 2001,
66, 6634.
12. Labrosse, J.-R.; Lhoste, P.; Sinou, D. Org. Lett. 2000, 2,
527.
13. Labrosse, J.-R.; Lhoste, P.; Sinou, D. Tetrahedron Lett.
1999, 40, 9025.
14. Chowdhury, C.; Chaudhuri, G.; Guha, S.; Mukherjee,
A. K.; Kundu, N. G. J. Org. Chem. 1998, 63, 1863.
15. A typical procedure for palladium-catalyzed cyclization is
as follows. A mixture of the dihydroxypyrrole derivative 3
(0.5 g, 1.5 mmol) and the propargylic carbonate 4b (0.2 g,
1.65 mmol) in THF was deoxygenated by bubbling with
argon for 15 min. The solution prepared above was then
added to a deoxygenated solution of Pd(PPh3)4 (47 mg,
4.0 · 10ꢀ2 mmol) and dppb (71 mg, 0.16 mmol) in THF
under argon. The reaction mixture was stirred at reflux for
12 h. After cooling to room temperature, the solvent was
removed by rotary evaporation and the residue was
purified by column chromatography on silica gel using
hexane/ethyl acetate as the eluent.
Figure 1. X-ray crystal structure of 7.
In conclusion, we have demonstrated a highly efficient
route for synthesis of 2-alkylidenepyrrolo[c]-1,4-dioxane
derivatives via a palladium-catalyzed cyclization of a
dihydroxypyrrole derivative and propargylic carbon-
ates. A selected intermediate 5c was used to produce a
monomer, 3,4-(cis-1,2-dimethyl)ethylenedioxypyrrole,
potentially useful for producing an electroactive poly-
mer.6
16. Spectroscopic data of selected compounds; 7. A colorless
1
crystal; mp 132 ꢁC; H NMR (CDCl3, 300 MHz) d 8.60–
8.40 (br, 1H), 4.35 (m, 6H), 1.39–1.30 (m, 12H); 13C NMR
(CDCl3, 75 MHz) 160.0, 135.0, 108.3, 74.0, 61.1, 14.7,
14.5; HMRS (FAB) calcd for C18H19NO6 (MHþ)
298.1291, found 298.1291; Anal. Calcd for C18H19NO6:
C, 56.56; H, 6.44; N, 4.71. Found: C, 56.57; H, 6.50; N,
1
4.69. 9. A pale yellow oil; H NMR (CDCl3, 300 MHz) d
7.15–7.05 (br, 1H), 6.16 (d, J ¼ 3:0 Hz, 2H), 4.22 (q,
J ¼ 6:0 Hz, 2H), 1.28 (d, J ¼ 6:0 Hz, 6H); 13C NMR
(CDCl3, 75 MHz) 127.8, 98.4, 73.3, 14.2; HMRS (FAB)
calcd for C8H11NO2 (Mþ) 153.0790, found 153.0789;
Anal. Calcd for C8H11NO2: C, 62.73; H, 7.24; N, 9.14.
Found: C, 62.80; H, 7.20; N, 9.10.
Acknowledgements
K.A.A. wishes to acknowledge the National Science
Foundation and University of Florida for funding the
purchase of X-ray equipment.
17. Crystal data and structure refinement for 7. Empirical
formula, C14H19NO6; formula weight, 297.30; tem-
ꢀ
perature, 193(2) K; wavelength, 0.71073 A; crystal system,
orthorhombic; space group, Pca2(1); unit cell dimen-
ꢀ
ꢀ
ꢀ
sions, a ¼ 17:168ð2Þ A, b ¼ 10:0901ð7Þ A, c ¼ 17:348ð2Þ A,
3
ꢀ
References and notes
a ¼ 90ꢁ, b ¼ 90ꢁ, c ¼ 90ꢁ; volume, 3005.3(4) A ; Z, 8;
density (calculated), 1.314 Mg/m3; absorption coefficient,
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,
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paper, have been deposited with the Cambridge Crystal-
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obtained, free of charge, on application to CCDC, 12
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