Superbase-promoted direct N-carbonylation of pyrrole with carbonic acid diesters

Article abstract of DOI:10.1016/j.tetlet.2008.03.129

Carbonic acid diesters have been investigated as carbonylating agents in the direct reaction with pyrrole (HetNH). In the presence of superbases (DBU, P₁-t-Bu, BTPP) as catalysts, the heteroaromatic substrate can be N-carbonylated by direct reaction with carbonic acid diesters under not-severe experimental conditions. The carbonylation reaction makes accessible pyrrole N-carbonyl derivatives (HetNC(O)OR, (HetN)₂CO) selectively through a simple straightforward way, which offers a safe eco-friendly alternative to the traditional synthetic methods based on hazardous phosgene or phosgene-derivatives.

Full text of DOI:10.1016/j.tetlet.2008.03.129

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3691–3696
Superbase-promoted direct N-carbonylation of pyrrole
with carbonic acid diesters
Marianna Carafa, Monica Distaso, Valentina Mele, Francesca Trani, Eugenio Quaranta *
Dipartimento di Chimica, Universit a` di Bari, Campus Universitario, Via E. Orabona, 4, 70126 Bari, Italy
Received 22 November 2007; revised 20 March 2008; accepted 25 March 2008
Available online 29 March 2008
Abstract
Carbonic acid diesters have been investigated as carbonylating agents in the direct reaction with pyrrole (HetNH). In the presence of
superbases (DBU, P -t-Bu, BTPP) as catalysts, the heteroaromatic substrate can be N-carbonylated by direct reaction with carbonic acid
1
diesters under not-severe experimental conditions. The carbonylation reaction makes accessible pyrrole N-carbonyl derivatives (Het-
NC(O)OR, (HetN) CO) selectively through a simple straightforward way, which offers a safe eco-friendly alternative to the traditional
2
synthetic methods based on hazardous phosgene or phosgene-derivatives.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Organic carbonates; Catalysis; Pyrrole; Carbonylation; Phosgene substitution
The development of environmentally improved new
synthetic routes, which are as much direct as possible
and resort to the use of safe and nontoxic starting
materials, is a major target of modern chemistry of syn-
thesis. Due to worldwide awareness of environmental
hazards of phosgene and governmental policies for
environment protection, a series of efforts are cur-
rently being focussed on replacing COCl2 in organic
synthesis.
the synthesis of pyrrole N-carbonyl derivatives, Het-
NC(O)Z (HetNH = pyrrole; Z = OR, OAr, HetN), well-
known compounds widely
HetNH þ ðROÞ CO ! HetNCðOÞOR þ ROH
ð1Þ
ð2Þ
2
2
HetNH þ ðROÞ CO ! ðHetNÞ CðOÞ þ 2ROH
2
2
Organic carbonates are nowadays obtainable through
used as intermediates or starting materials in the synthesis
of a variety of fine chemicals, drugs and biologically
1
a
phosgene-free routes even on industrial scale and are
receiving growing attention as eco-friendly safe and non-
toxic phosgene substitutes in carbonylation reactions of
amines for the synthesis of carbamates, isocyanates, and
active substances (epibatidine and derivatives, tropane
3–6
alkaloids, etc.).
Such compounds are traditionally
5
synthesized from toxic and harmful phosgene or
COCl -derivatives (dicarbonates, alkyl-azidoformates,
,1 -carbonyldiimidazole,
1
ureas. However, much less is known on their use for direct
7
8
2
2
carbonylation of N-heteroaromatic compounds. In princi-
0
6,9
10
1
chloroformates ) through
ple, this approach (Eqs. 1 and 2) is an attractive route to
procedures which, often, require the preliminary conver-
sion of pyrrole into a more nucleophilic metal pyrryl
5
,8,10
salt.
A more recent and complex synthetic approach,
requiring two moles of pyrrole per mole of HetNC(O)Z
product, is based on the activation of pyrrole-1-carboxylic
acid.
*
Corresponding author. Tel./fax: +39 0805442083.
E-mail address: quaranta@chimica.uniba.it (E. Quaranta).
1
1
0
040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.03.129

3692
M. Carafa et al. / Tetrahedron Letters 49 (2008) 3691–3696
So far, the direct reaction of pyrrole with carbonic acid
(
a)
2
.5
2
diesters has received very poor attention. In this work
organic carbonates, including industrially relevant
dimethyl carbonate (DMC), methyl phenyl carbonate
(b)
(c)
(
MPC) and diphenyl carbonate (DPC), have been investi-
1
.5
1
gated as carbonylating agents in the direct reaction with
pyrrole to obtain HetNC(O)Z derivatives. This reaction
requires a suitable catalyst and, herein, we also show that
superbases, such as 1,8-diazabicyclo[5.4.0]undec-7-ene
0.5
0
(
DBU) or phosphazenes, are effective catalysts for the
relevant carbonylation process.
The direct reaction of pyrrole with DPC has never been
studied in the past. No significant reaction has been
observed when pyrrole and DPC (1:3.9 mol/mol) were
heated at 393 K for 8 h. However, addition of DBU mod-
ified the reactivity of the system. In fact, under very mild
conditions, DBU can promote effectively the direct carbon-
ylation of pyrrole with DPC to give both HetNC(O)OPh
0
2
4
6
8
10 12 14 16 18 20 22 24
time (h)
Fig. 1. Reaction of pyrrole (9.51 mmol) with DPC (4.72 mmol) in the
presence of DBU (9.37 mmol) at 293 K. (a): 1; (b): 2; (c) pyrrole.
Table 1
Carbonylation of HetNH (pyrrole, indole, carbazole) to HetNC(O)OPh
with DPC (HetNH/DPC ꢀ 1:4 mol/mol) in the presence of DBU
(
1) and (HetN) CO (2) (Eqs. 1 and 2, R = Ph) in relative
2
a
yields, which depend on the working conditions. Figure 1
illustrates the results obtained, at 293 K, using a homoge-
neous 2:2:1 (mol/mol) mixture of pyrrole, DBU and
DPC. The conversion of pyrrole was not complete even
after a long time (ꢀ50% after 24 h) and 1 was obtained
as main product. Figure 1 also suggests that an equilibrium
state is likely reached under the used conditions. Accord-
ingly, the use of a great excess of pyrrole versus DPC
increased the formation of 2 with respect to 1. For instance,
after 24 h at 293 K, 1 and 2 were obtained in approximately
equimolar amounts, when pyrrole (14.41 mmol), DBU
b
Entry HetNH
mmol of
T
t
HetNH GC-
c
(
K) (h) conversion (%)
HetNH DPC DBU
1
2
3
4
5
Pyrrole
Pyrrole
Pyrrole
Indole
3.60
3.60
3.60
3.69
14.12 3.68
14.00 0.335 343 24
14.04 0.335 393 24
14.07 3.68
14.03 3.68
333
3
97
62
98
333
333
3
3
100
100
Carbazole 3.59
a
Selectivity to HetNC(O)OPh was P99% in all the runs. (HetN)
any, formed in trace amounts.
2
CO, if
b
The reaction mixture was homogeneous at the working temperature.
n-Dodecane was used as internal standard.
c
(
2.95 mmol) and DPC (1.45 mmol) were allowed to react
in a 10:2:1 molar ratio. Under the working conditions,
the conversion of DPC was practically quantitative in less
than 6 h. Work-up of reaction mixture afforded 2 in 48%
yield. To date, this is the sole example of synthesis of 2
amounts. Table 1 (entries 2 and 3) shows clearly that the
carbonylation process is promoted also by catalytic
amounts (10 mol %) of the amidine base. Under the latter
conditions, however, quantitative conversion to 1 required
longer reaction times and higher temperatures. Product 1
has been isolated in high yield (ꢀ90%). Moreover, most
of the excess of DPC (up to 90%) can be recovered.
5
through a route that avoids the use of phosgene or a phos-
0
6,9
gene derivative such as 1,1 -carbonyldiimidazole.
The reactivity of system was directed towards the selec-
tive formation of 1 by modifying suitably the experimental
conditions. At 333 K, a 1:1:3.9 (mol/mol) mixture of pyr-
role, DBU and DPC afforded 1 in high yield and selectively
Also indole and carbazole were easily converted in high
yield into the corresponding N-phenoxycarbonyl deriva-
tives by reaction with DPC, under conditions analogous
to those employed for pyrrole. Entries 4 and 5 in Table 1
summarize the results obtained when DBU has been used
in equimolar ratio with respect to the heteroaromatic sub-
strate HetNH (indole, carbazole). Both 1-phenoxycarbonyl
indole (3) and 9-phenoxycarbonyl carbazole (4) have been
à
0
(
P99%) within short times (3 h; Table 1, entry 1). 1,1 -
carbonyldipyrrole, (HetN) CO, formed only in trace
2
A few early works have dealt with the reaction of HetNM salts
1
2a
10c,12a
t
(
M = K, Na, Li, MgBr) with DMC
or (EtO)
2
CO
or BuO-
1
2b
C(O)OPh.
Recently, as a part of a study on the use of DMC as
methylating agent of N-heterocyclic compounds, it has been briefly
reported that (Bu N)Br (8 mol %) catalyzes the reaction of pyrrole with
13
§
isolated in good yield (76% and 80%, respectively). The
4
DMC to give 1-methylpyrrole (HetNMe) and HetNC(O)OMe as major
products. After 24 h at 393 K total conversion of pyrrole was attained, but
the reaction was not selective (HetNC(O)OMe: 51%; HetNMe: 36%). At
§
3
4
83 K, the process was more selective (HetNC(O)OMe: 92%; HetNMe:
%), but the conversion rate of pyrrole was divided by two.
1-Phenoxycarbonyl indole is a well-known compound, which is
1
4a,d
traditionally synthesized by reaction with phenyl chloroformate,
or
à
0
DPC has been used as reagent and reaction medium: the reaction
by reaction of indole with 1,1 -carbonyldiimidazole and phenol in the
presence of DMAP, or by coupling of PhONa with indole-1-carboxylic
acid anhydride according to the method developed by Patel. To the best
of our knowledge, the carbazole derivative 4 is a new compound which has
been fully characterized by spectroscopic methods (IR, NMR, MS).
1
4c
mixture, heterogeneous at 293 K, became rapidly homogeneous at 333 K.
In the present study, solvent-free conditions have been employed
deliberately in view of the current widespread attention for solventless
processes.
1
4b

M. Carafa et al. / Tetrahedron Letters 49 (2008) 3691–3696
3693
Table 2
Carbonylation of pyrrole (HetNH) to HetNC(O)OR with carbonic acid diesters in the presence of superbases
a
Entry
Carbonate
Base
mmol of
Base
Molar ratio (mol/mol)
T (K)
t (h)
Yield (%)
HetNH
Carbonate
HetNH
Base
Carbonate
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
a
DMC
DMC
DMC
DMC
DMC
DBzC
DBzC
DBzC
MPC
MPC
MPC
MPC
MPC
t-BuPC
t-BuPC
t-BuPC
t-BuPC
t-BuPC
t-BuPC
t-BuPC
DBU
DBU
3.60
3.68
11.88
2.38
11.88
11.88
11.88
6.37
6.00
5.82
3.15
3.15
3.15
3.15
3.15
3.15
3.15
3.15
3.15
1.57
1.57
1.57
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
3.3
3.4
16.8
16.8
16.8
9.0
16.7
16.2
4.5
4.5
4.5
4.5
4.5
4.4
4.4
4.4
4.4
4.4
4.4
4.4
293
393
393
393
393
393
393
393
293
333
333
363
393
293
333
363
393
293
363
393
27
1.5
3
15
30
60
66
68
32
42
65
75
88
23
40
47
61
7
35
Traces
21
0.706
0.706
0.706
0.706
0.706
0.360
0.360
0.706
0.706
0.706
0.706
0.706
0.706
0.706
0.706
0.706
0.360
0.360
0.360
0.709
0.071
0.072
0.072
0.072
0.036
0.036
0.736
0.736
0.074
0.074
0.074
0.736
0.736
0.736
0.736
0.327
0.327
0.327
P
1
-t-Bu
0.1
0.1
0.1
0.1
0.1
0.1
1
BTPP
BTPP
BTPP
BTPP
BTPP
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
BTPP
BTPP
BTPP
3
6.5
5.5
7
24
28.5
5
24
24
24
93
24
44
25
41
25
12
b,c
c
1
1
1
1
1
1
1
1
1
1
2
1
c
0.1
0.1
0.1
1
1
1
1
1
1
1
d
e
b
f
g
b
78
h
2
HetNC(O)OR GC-yield (internal standard: n-dodecane).
Under comparable conditions, but in the absence of any catalyst, no reaction was observed.
Yield of 1: <1%.
Yield of 1: 2%.
Yield of 1: 12%.
After 24 h, 8 yield was 26%.
b
c
d
e
f
g
Pyrrole conversion was equal to 35%. After 1 h at 393 K, minor amounts of 8 were clearly evident in the reaction mixture.
Pyrrole conversion was 6%. After 3 h at 393 K, the yield of 8 was equal to 41%.
h
studies in progress are turned to make possible both the
quantitative recovery and the recycling of catalysts.
DBU also promoted the carbonylation of pyrrole with
DMC to HetNC(O)OMe (5). At 293 K, the methoxycarb-
onylation was very selective (100%) but proceeded
slowly in low yield (Table 2, entry 1). At more elevated
temperatures (Table 2, entry 2) 5 formed in higher yield,
but less selectively (83%) because of significant side-pro-
duction of 1-methylpyrrole (6) since the beginning of the
run.
BTPP is both a stronger base and a more powerful nucleo-
1
5
phile than P -t-Bu.
1
The selectivity of N-methoxycarbonylation diminished
–
with time because of the progressive formation of 6. For
instance, entry 5 in Table 2 shows that, after 6.5 h at
393 K, in the presence of BTPP as the catalyst, the yield
of 5 was only slightly higher (68%), but selectivity was less
satisfactory (95%). The phosphazene catalyst deactivated
by converting into OP(NR ) (NR = NMe or NC H ),
2
3
2
2
4
8
without any catalytic activity. At 393 K (Table 2, entries
3 and 4), the deactivation of phosphazene was still modest
for short reaction times. In fact, after 2–3 h, most of the
catalyst was still active and, after stopping the catalytic
run, can be separated from the reaction mixture to be
We have focussed, therefore, on base catalysts other
than DBU. We have found that, in the temperature range
explored
tBuN = P(NMe2)3 (P -t-Bu) and tBuN = P(NC H )
8 3
(293–393 K),
phosphazenes,
such
as
1
4
k
(
BTPP), are effective and selective catalysts for the direct
reused.
methoxycarbonylation of pyrrole with DMC. Entries 3
and 4 (Table 2) summarize the results obtained at 393 K
in the presence of a catalytic amount (10 mol %) of phos-
phazene and using DMC both as a reagent and solvent
–
The reaction of pyrrole with DMC, used as methylating substrate in
3
place of harmful conventional methylating agents such as CH I or
dimethyl sulfate, is currently under study as eco-friendly way to the
synthesis of 6. For instance, we have found that, after 23 h at 393 K, a
1
6
(
DMC/pyrrole = 17 mol/mol). Besides 5, HetNMe also
formed as the side-product, but in very low amounts as
long as reaction times were short. At 393 K (Table 2,
entries 3 and 4), 5 can be obtained in good yields (60–
1
mixture of pyrrole (0.708 mmol), DMC (11.87 mmol) and P -t-Bu
(0.708 mmol) gave 6 in 97% yield.
k
1
The recovery of BTPP, which is less volatile than P -t-Bu, was easily
achieved by distilling in vacuo, at 293 K, the reaction mixture. The
distillate contained 5, with unreacted pyrrole and DMC as main
components, but not BTPP (by GC), which, together with minor amounts
6
6%) and with high selectivity (P98%) within ꢀ3 h. To
our knowledge, these results do not find any better prece-
dent in the literature. BTPP was found to be a more effec-
of OP(NC
4 8 3
H ) , was the major component of the poorly volatile
tive catalyst than P -t-Bu, in accordance with the fact that
distillation residue.
1

3694
M. Carafa et al. / Tetrahedron Letters 49 (2008) 3691–3696
BTPP, in catalytic amount (10 mol %), also promoted
O
O
the N-benzyloxycarbonylation of pyrrole with dibenzyl
carbonate. At 393 K, depending on the working conditions
N
+ ROH
OPh
N
+ PhOH (3)
OR
(
Table 2, entries 6–8), 1-benzyloxycarbonyl pyrrole (7) has
been obtained in 32–65% yield. Remarkably, 1-benzylpyr-
role did not form under the employed conditions.
(a)
(b)
ROH
We have also investigated the reaction of pyrrole with a
few alkyl aryl carbonates. In the presence of an equimolar
amount of DBU, pyrrole reacted with an excess of MPC
O
O
ROH
+
+
(c)
RO
OPh
RO
OR
N
H
N
H
(
(
MPC/pyrrole = 4.5 mol/mol), under very mild conditions
293–333 K), to give HetNC(O)OMe (5) in good yield (75–
Scheme 1.
8
8%) within reasonable times (Table 2, entries 9 and 10).
The formation of 5 was also promoted by catalytic
amounts of DBU versus pyrrole (Table 2, entries 11–13).
In principle, the reaction of pyrrole with MPC may
afford the methylation of heteroaromatic ring or also result
in the co-formation of 1. However, under the conditions
used in entries 9–13 (Table 2), we have never observed
the formation of methylated pyrroles. Moreover, the for-
mation of 1 is absolutely negligible at the lowest working
temperatures (Table 2, entries 9–11), but becomes more
important at 393 K (Table 2, entry 13). Elevated tempera-
tures (393 K) also promote the side-production of notice-
able amounts of anisole and the formation of DMC and
DPC. The incidence of these side-processes was negligible
at the lowest temperatures investigated (Table 2, entries
dence of formation of C-carbonylation products (2-pyrrole
esters, 1,2 -dipyrrylketone, etc.). This feature deserves
0
attention as such species may form in variable amounts
depending on the conditions employed, when HetNM salts
are reacted stoichiometrically with organic carbon-
1
0c,12a
10c
ates
or chloroformates.
The easy selective access to 1-phenoxycarbonyl pyrrole,
HetNC(O)OPh (Eq. 1, R = Ph), prompted us to explore
also the reactivity of 1 with alcohols (Eq. 3, Scheme 1).
In principle, reaction (3) offers another potential solution
for the synthesis of 1-alkoxycarbonyl pyrroles, which
may prove a useful synthetic route when the direct way
(Eq. 1) is less convenient or not at all practicable (for
instance, if the relevant organic carbonate is not readily
accessible). To date, we have found no examples of transe-
sterification reactions of HetNC(O)Z (HetNH = pyrrole;
Z = OR, OAr) compounds with alcohols. Herein, we focus
on the reactions of 1 with a few alcohols, such as MeOH,
9
–11). The formation of anisole implies the decarboxyl-
ation of the alkyl aryl carbonate, a well-known process
which may be promoted by guanidine bases or also Lewis
1
7
acids. In an ad-hoc experiment, we ascertained the forma-
tion of anisole when DBU and MPC (1:4.5 mol/mol) were
reacted at 393 K for 24 h.
PhCH OH and the more sterically crowded t-BuOH, which
2
t-Butyl phenyl carbonate (t-BuPC) was less reactive than
MPC (in Table 2, compare entries 14 and 15 with entries 9
and 10, respectively). At 363 K, in the presence of an equi-
molar amount of DBU versus pyrrole, the heteroaromatic
substrate reacted with t-BuPC to give 1-t-butyloxycarbonyl
pyrrole (8) in modest yield (Table 2, entry 16). Under com-
parable conditions, BTPP was more efficient than DBU (in
Table 2, compare entries 18 and 19 with entries 14 and 16,
respectively). In the temperature range 293–363 K (Table 2,
entries 14–16, 18 and 19), side-products such as t-BuOPh
or 1, if any, were formed only in traces or minor amounts.
Whatever catalyst (BTPP or DBU) was used, increasing
temperature to 393 K (Table 2, entries 17 and 20) caused
a drastic reduction of yield of 8, which, under the working
conditions, further reacted with time to give back pyrrole
or to produce other species (including trace amounts of
alkylation products of pyrrole (123 m/z)). The highest tem-
perature (393 K) also promoted the extended decarboxyl-
ation of the organic carbonate.
allow to emphasize different types of reactivity. Moreover,
the relevant –C(O)OR (R = Me, PhCH , t-Bu) groups are
2
often used to protect the N-atom of pyrrole in a variety
3
,4
of reactions.
At 293 K, in the absence of any catalyst, 1 reacted read-
ily with anhydrous MeOH (MeOH/1 = 500 mol/mol) to
give 5 selectively (100%). Under the working conditions,
the conversion of 1 was already as high as 96% after 7 h
and practically quantitative (ꢀ100%) within 22 h. The
absence of by-products, such as pyrrole and methyl phenyl
carbonate or DMC, is noteworthy as it indicates (see
Scheme 1) that (i) the attack of MeOH to 1 causes the selec-
tive expulsion of phenoxo- instead of pyrryl-group and (ii)
5 does not react with MeOH in the absence of any catalyst.
Also PhCH OH reacted selectively with 1 (ROH/
2
1 = 29 mol/mol) to give 1-benzyloxycarbonyl pyrrole, but
in poor yield (even after 17.5 h at 348 K). The high yield
conversion of 1 into 7 can be attained in the presence of
a base, like DBU. At 293 K, 1 (0.801 mmol) reacted readily
All the described carbonylation reactions (Eqs. 1 and 2)
were very regioselective. In no case we have found any evi-
with a modest excess (ꢀ10%) of PhCH OH in diethyl ether
2
(1 mL) containing DBU (0.802 mmol). The conversion of 1
was practically quantitative within 6 h and afforded 7 in
high yield (80%, isolated). However, the presence of
DBU promoted also the formation of other species, such
as pyrrole and dibenzyl carbonate. Scheme 1 (see a–c)
The GC–MS analysis of the reaction mixture showed the formation of
t-BuOPh (150m/z) and minor amounts of t-butyl phenol isomers
(150 m/z).

M. Carafa et al. / Tetrahedron Letters 49 (2008) 3691–3696
3695
describes a few plausible reaction pathways for the forma-
tion of these species. The GC analysis of the reaction solu-
4. (a) Pandey, G.; Tiwari, S. K.; Singh, R. S.; Mali, R. S. Tetrahedron
Lett. 2001, 42, 3947–3949; (b) Paparin, J.-L.; Cr e´ visy, C.; Gr e´ e, L.
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tion also showed the formation of PhOCH Ph. On the
2
whole, the incidence of these side-reactions was very mod-
est, as, under the working conditions (after 6 h, at 293 K),
pyrrole yield did not exceed 7%. By the same method 1-t-
butyloxycarbonyl pyrrole was also obtained (40% GC
yield), but under less mild reaction conditions (24 h at
6
. (a) Matsunaga, S.; Kinoshita, T.; Okada, S.; Harada, H.; Shibasaki,
M. J. Am. Chem. Soc. 2004, 126, 7559–7570; (b) Evans, D. A.; Borg,
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3
78 K; t-BuOH/DBU/1 = 147:1:1 mol/mol), as the system
7
t-BuOH/1 was less reactive, even in the presence of the
amidine base. The formation of 8 was accompanied by a
pronounced formation of pyrrole. These findings show that
reaction (3) is very sensitive to the structure of alcohol
used. Moreover, DBU can effectively promote the transe-
sterification reaction, but the amidine base may also open
other reaction pathways which may reduce the selectivity
of the transesterification process.
8. Carpino, L. A.; Barr, D. E. J. Org. Chem. 1966, 31, 764–767.
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123–1133.
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0. (a) Gabel, N. J. Org. Chem. 1962, 27, 301–303; (b) Acheson, R. M.;
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Wang, N. C.; Anderson, H. J. Can J. Chem. 1977, 55, 4103–4111.
11. Boger, D. L.; Patel, M. J. Org. Chem. 1987, 52, 2319–2323.
12. (a) Loader, C. E.; Anderson, H. J. Can J. Chem. 1971, 49, 45–48; (b)
Dhanak, D.; Reese, C. B. J. Chem. Soc., Perkin Trans. 1: Org. Bio-
Org. Chem. (1972–1999) 1986, 12, 2181–2186.
In summary, for the first time, the reactivity of pyrrole
towards carbonylating agents as carbonic acid diesters
1
3. Ouk, S.; Thi e´ baud, S.; Borredon, E.; Chabaud, B. Synth. Commun.
005, 35, 3021–3026.
2
has been explored. In the presence of superbases (P -t-
14. (a) Itahara, T. Heterocycles 1986, 24, 2557–2562; (b) Boger, D. L.;
Patel, M. J. Org. Chem. 1987, 52, 3934–3936; (c) Macor, J. E.; Cuff,
A.; Cornelius, L. Tetrahedron Lett. 1999, 40, 2733–2736; (d)
Jacquemard, U.; Ben e´ teau, V.; Lefoix, M.; Routier, S.; M e´ rour, J.-
Y.; Coudert, G. Tetrahedron Lett. 2004, 60, 10039–10047.
1
Bu, BTPP, DBU) as catalysts, pyrrole (HetNH) can be eas-
ily and selectively carbonylated at the N-atom by direct
reaction with organic carbonates. The carbonylation reac-
tion does not require severe experimental conditions and
makes accessible pyrrole N-carbonyl derivatives (Het-
1
5. Schwesinger, R.; Willaredt, J.; Schlemper, H.; Keller, M.; Schmitt, D.;
Fritz, H. . Chem. Ber. 1994, 127, 2435–2454.
16. Tundo, P.; Selva, M. Acc. Chem. Res. 2002, 35, 706–716.
1
8
NC(O)OR, (HetN) CO) through a simple straightfor-
2
1
7. (a) Barcelo, G.; Grenouillat, J.-P.; Sennyey, G. Tetrahedron 1990, 46,
ward way which avoids the traditional phosgene-based
methods involving stoichiometric steps and co-production
of wasted salts. We have also demonstrated that 1-phen-
oxycarbonyl pyrrole, easily obtainable from pyrrole and
DPC in high yield, is a suitable starting material for the
synthesis of alkoxycarbonyl pyrroles by transesterification
1
839–1848; (b) Braunstein, P.; Lakkis, M.; Matt, D. J. Mol. Catal.
1
987, 42, 353–355.
1
8. Experimental: Unless otherwise stated, all reactions and manipula-
tions were conducted under an inert gas atmosphere, by using vacuum
line techniques. All solvents were dried according to conventional
methods (P
dried over 5 A molecular sieves for 24 h, filtered, distilled, and stored
under N . Pyrrole was dried over CaH , filtered, distilled in vacuo
over fresh CaH and stored under N . The organic carbonates, except
2 5 2
O ; Na/benzophenone) and stored under N . DMC was
1
8
with alcohols. Further applications of these methods, as
well as the mechanistic features of the reported processes,
are under investigation.
2
2
2
2
1
9
for MPC, were commercial products (Fluka, Aldrich). DBU and the
phosphazene bases (Fluka, Aldrich) were used as received and stored
under an inert atmosphere.
Acknowledgements
Carbonylation of HetNH (pyrrole, indole, carbazole) with DPC in the
presence of DBU: The reaction mixture containing HetNH, DPC and
the base, after reacting at the working temperature, was cooled to
room temperature, if necessary, and dissolved in diethyl ether. The
We thank Universit a` di Bari (Fondi di Ateneo) and
MiUR (PRIN 2006031888_001) for funding.
4
ethereal solution was washed with water and dried over MgSO . The
product (1 or 2 or 3) was isolated by (flash)-chromatography on a
silica gel column using, as eluent, 20:1 (v/v) petroleum ether/ethyl
acetate for 1, 10:1 (v/v) petroleum ether/diethyl ether for 2 and 20:1
(v/v) petroleum ether/diethyl ether in the case of 3. The isolation of 4
required a different procedure. In this case the ethereal solution was
evaporated in vacuo. The carbazole derivative 4 was isolated from the
residue by washings with methanol, because of limited solubility of 4
in the alcohol solvent.
References and notes
1
. (a) Delledonne, D.; Rivetti, F.; Romano, U. Appl. Catal. A: Gen.
001, 221, 241–251; (b) Vauthey, I.; Valot, F.; Gozzi, C.; Fache, F.;
2
Lemaire, M. Tetrahedron Lett. 2000, 41, 6347–6350; (c) Distaso, M.;
Quaranta, E. J. Catal. 2004, 228, 36–42; (d) Distaso, M.; Quaranta, E.
Appl. Catal. B: Environ. 2006, 66, 72–80; (e) Distaso, M.; Quaranta,
E. J. Catal. 2008, 253, 278–288.
Carbonylation of pyrrole with dialkyl- or alkyl aryl carbonates in the
presence of superbases (DBU, P -t-Bu, BTPP). General procedure:
2
. Most of studies have focused on the use of dialkyl carbonates as
alkylating agents of indoles, benzimidazole and carbazole. See: (a)
Shieh, W.-C.; Dell, S.; Bach, A.; Repic, O.; Blacklock, T. J. Org.
Chem. 2003, 68, 1954–1957; (b) Shieh, W.-C.; Lozanov, M.; Loo, M.;
Repic, O.; Blacklock, T. Tetrahedron Lett. 2003, 44, 4563–4565; (c)
Shieh, W.-C.; Lozanov, M.; Repic, O. Tetrahedron Lett. 2003, 44,
1
Into a 30 mL Schlenk tube, containing pyrrole and the organic
carbonate (DMC or MPC, etc.), the catalyst (DBU or phosphazene)
and n-dodecane (internal standard) were added. The mixture was
allowed to react at the working temperature for a measured time and
analyzed by GC or GC–MS.
6
4
943–6945; (d) Shieh, W.-C.; Dell, S.; Repic, O. Org. Lett. 2001, 3,
279–4281; (e) Jiang, X.; Tiwari, A.; Thompson, M.; Chen, Z.;
Reaction of 1-phenoxycarbonyl pyrrole with alcohols. General proce-
dure: Into a 30 mL Schlenk tube, containing 1, the anhydrous alcohol
and, if used, DBU and diethyl ether, the internal standard (n-
dodecane) was added. The reaction mixture was allowed to react at
Cleary, T. P.; Lee, T. B. K. Org. Process Res. Dev. 2001, 5, 604–608.
. Natsume, M.; Muratake, H. Tetrahedron Lett. 1979, 36, 3477–3480.
3

3
696
M. Carafa et al. / Tetrahedron Letters 49 (2008) 3691–3696
br), 150.28 (slightly br), 151.42. MS (EI, 70 eV) m/z: 237 (M ), 193,
+
ꢀ
the working temperature and, at measured intervals of time, analyzed
ꢁ
1
by GC or GC–MS. The product 7 was isolated by fractionating the
reaction solution on a silica gel thin layer with petroleum ether/diethyl
ether (10:1 v/v).
144, 116, 89, 77, 65, 63, 51, 39. Compound 4: IR (Nujol, cm ): 3076,
3061, 3042, 3032 (w), 1736vs (C@O), 1599mw, 1485m, 1446s, 1366s,
1332m, 1304m, 1250m, 1219m, 1204s, 1157m, 1115mw, 1070m,
ꢁ1
1
1
Spectroscopic data. Compound 1: IR (Nujol, cm ): 1769vs (CO). H
NMR (acetone-d , 500 MHz): d 6.35 (t, 2H, H ), 7.32–7.39 (m, 3H,
para and Hortho), 7.42 (t, 2H, J = 2.3 Hz, H ), 7.46–7.52 (m, 2H,
, 125 MHz): d 113.75 (C ), 121.21(C ),
1022mw, 929w, 850w, 754s, 723ms, 692m. H NMR (CDCl
3
,
6
b
500 MHz): d 7.34–7.44 (m, 5H), 7.47–7.53 (m, 4H), 8.01 (d, 2H,
1
3
H
H
1
a
3
J = 7.6 Hz), 8.38 (d, 2H, J = 8.1 Hz). C NMR (CDCl , 125 MHz): d
1
3
meta). C NMR (acetone-d
6
b
a
116.49, 119.77, 121.76, 123.79, 126.22, 126.51, 127.43, 129.74, 138.12,
+ꢀ
22.36, 127.23 and 130.41 (Cortho, meta, para), 149.42 (C@O), 151.43
ipso). MS (EI, 70 eV) m/z: 187 (M ), 143, 115, 94, 77, 66, 51, 39.
150.11, 150.79. MS (EI, 70 eV) m/z: 287 (M ), 194, 166, 140, 115, 89,
+
ꢀ
ꢁ1
1
(
C
77, 65, 63, 51, 39. Compound 7: IR (neat, cm ): 1748vs (CO). H
ꢁ
1
1
Compound 2: IR (Nujol, cm ): 1734vs (CO). H NMR (CDCl
00 MHz) d: 6.36 (t, 4H, J = 2.2 Hz, H ), 7.30 (t, 4H, J = 2.2 Hz, H
, 100 MHz): d 113.24 (C ), 121.95 (C ), 148.01
C@O). MS (EI, 70 eV) m/z: 160 (M ), 94, 66, 39. Compound 3: IR
3
,
).
NMR (CDCl
J = 2 Hz, H
3
, 400 MHz): d 5.37 (s, 2H, OCH
), 7.31 (t, 2H, J = 2 Hz, H
a
2
), 6.25 (t, 2H,
), 7.36–7.46 (m, 5H,
), 112.46
4
1
b
a
b
13
3
C NMR (CDCl
3
b
a
H
aromatics). C NMR (CDCl
3
, 100 MHz): d 68.81 (OCH
2
+
ꢀ
(
(
(
(
(C
b
), 120.05 (C
a
), 128.35, 128.64, 128.67 (Cortho, meta, para), 134.85
+ꢀ
ꢁ1
1
3
Nujol, cm ): 1751vs (CO). H NMR (CD CN, 500 MHz): d 6.76
(Cipso), 150.23 (C(O)O). MS (EI, 70 eV) m/z: 201 (M ), 157, 123, 110,
91, 77, 65, 51, 39.
dd, 1H, J = 3.7 and 1 Hz, H3), 7.29 (td, 1H), 7.32–7.39 (m, 4H), 7.49
m, 2H, Hmeta), 7.65 (dt, 1H, J = 8 Hz, H4), 7.82 (d, 1H, J = 3.7 Hz,
19. Stratton, J.; Gatlin, B.; Venkatasubban, K. S. J. Org. Chem. 1992, 57,
3237–3240; See also Carpino, L. A.; Carpino, B. A.; Giza, C. A.;
Murray, R. W.; Santilli, A. A.; Terry, P. A. Org. Synth. 1964, 44, 22–
25.
1
3
H2), 8.20 (d, 1H, J = 8.4 Hz, H7). C NMR (CD
1
1
3
CN, 100 MHz): d
09.46, 115.75 and 116.02, 122.16, 122.72, 124.25, 125.53 and 125.59,
26.94 and 127.07, 127.39, 130.61 (slightly br), 131.59, 136.39 (slightly