1,4-Carbonylative addition of arylboronic acids to methyl vinyl ketone: a new synthetic tool for rapid furan and pyrrole synthesis

Article abstract of DOI:10.1016/j.tet.2006.09.035

The rhodium catalysed 1,4-carbonylative addition of arylboronic acids to methyl vinyl ketone under carbon monoxide pressure was studied. High yields of 1,4-diketones were obtained using a catalytic system formed from Rh(COD)₂BF₄ (COD=1,5-cyclooctadiene) and triphenylphosphine even at very low catalyst loading (0.02 mol %). A short synthetic procedure combining this carbonylation reaction with a subsequent cyclisation step affords pyrroles or furans.

Full text of DOI:10.1016/j.tet.2006.09.035

Tetrahedron 62 (2006) 11740–11746
1,4-Carbonylative addition of arylboronic acids
to methyl vinyl ketone: a new synthetic tool
for rapid furan and pyrrole synthesis
*
Helene Chochois, Mathieu Sauthier, Eddy Maerten, Yves Castanet and Andre Mortreux
ꢀ ꢁ
ꢀ
´
Unite de Catalyse et Chimie du Solide, UMR CNRS 8181, USTL, ENSCL, BP 90108, 59652 Villeneuve d’Ascq, France
Received 21 July 2006; revised 7 September 2006; accepted 12 September 2006
Available online 17 October 2006
Abstract—The rhodium catalysed 1,4-carbonylative addition of arylboronic acids to methyl vinyl ketone under carbon monoxide pressure
was studied. High yields of 1,4-diketones were obtained using a catalytic system formed from Rh(COD)2BF4 (COD¼1,5-cyclooctadiene) and
triphenylphosphine even at very low catalyst loading (0.02 mol %). A short synthetic procedure combining this carbonylation reaction with
a subsequent cyclisation step affords pyrroles or furans.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
of acyl reagent. In view of the wide availability and low
cost of carbon monoxide, another interesting approach
would be the development of a catalysed acylating reaction
through in situ generation of the metal–acyl reagent via an
environmentally clean carbonylation step and using simple
reagents. Despite important developments of carbonylation
reactions, acylation reactions of enones involving carbon
monoxide source are rare.13
Five membered heterocyclic compounds such as pyrroles,
furans or thiophenes and their derivatives are important
products in organic chemistry since their structures can be
found in many natural or therapeutic compounds.1 Classical
methods to access this class of compounds involve cyclisa-
tion reactions of 1,4-dicarbonyl reagents.2 In this context
a straightforward synthesis of 1,4-diketones is a significant
objective in synthetic chemistry.
In this context, the reaction of 1,4-addition of arylboronic
acids to a,b-enones attracted our attention.14 Actually this re-
action is catalysed by rhodium salts and involves a rhodium–
carbon bond containing intermediate.15 Since rhodium
complexes are suitable for carbonylation reactions, it was
anticipated that a molecule of CO would readily insert into
the metal–carbon bond to afford a metal–acyl derivative
suitable for a subsequent acylation reaction (see Scheme 1).
This hypothesis was confirmed experimentally and we
recently reported the rhodium catalysed carbonylative
1,4-addition of arylboronic acids to methyl vinyl ketone.16
The Stetter reaction of substituted benzaldehydes with
enones catalysed by thiazolium salts leads to 1,4-diketones
and has already been applied for synthetic purposes but
has the disadvantage of requiring high catalytic loadings.3
Alternatively, several stoichiometric acyl–metal reagents
such as acyl cobaltate,4 ferrate,5 cuprate,6 nickelate,7 molyb-
date8 or chromate9 were also used efficiently. The acyl
moiety stabilised by the metal formally acts as a nucleophile
with the enones playing the role of Michael acceptors.
Unfortunately, the toxicity of the metal salt as well as the
cost of their stoichiometric use is a strong limitation to their
further development. Further improvements in the use of
acyl–transition metal intermediates were dedicated to their
production in the course of a catalytic cycle. Oxidative addi-
tion of aldehydes at a rhodium centre usually at high reaction
temperatures,10 or transmetallation of the acyl moiety from
a acylzirconocene11 or acylstannyl12 derivative to a palla-
dium metal centre allowed the use of catalytic amounts of
noble metal but needed again the stoichiometric amounts
O
O
O
R
+
Ar
O
R
1% RhH(CO)(PPh3)3
CO, 15 h
R
Ar
+
Ar B(OH)2
+
Ar
O
Ar
1
2
3
4
5
Scheme 1. Rhodium catalysed aroylation of enones with arylboronic acids
and carbon monoxide.
Under CO pressure, the reaction allows the conversion of an
arylboronic acid 1 and an unsubstituted enone 2 to a 1,4-
diketone 3 (Scheme 1). The product 4, which is selectively
obtained when the reaction was carried out in the absence
* Corresponding author. Tel.: +33 320 434 927; fax: +33 320 436 585;
e-mail: yves.castanet@ensc-lille.fr
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.09.035

H. Chochois et al. / Tetrahedron 62 (2006) 11740–11746
H2O
11741
of CO and diarylketone 5 are usually obtained as side prod-
O
O
ucts in low quantities depending on the reaction conditions.
We now wish to report complementary catalytic data to our
preliminary communication as well as the direct application
of this new reaction in a carbonylation–cyclisation short syn-
thetic procedure for furan or pyrrole heterocycle synthesis.
R
R
Ar
Path A
2. Results and discussion
ArB(OH)2
[Rh] Ar
[Rh] OH
2.1. Catalytic carbonylation reactions
Reactions performed with phenylboronic acid 1a and
2 equiv of methyl vinyl ketone 2a at 80 ꢀC under 20 bar
CO showed strongly differing results depending on the
nature of the solvent (Table 1). The reaction is completely
ineffective in dioxane (entry 3) and only partially occurring
in dry THF or in THF/water solvents (entries 1 and 2). Best
results were indeed obtained with MeOH as a polar and
protic solvent. Dried methanol led to very similar results
to those obtained if methanol is combined with 10% H2O
(entries 4 and 8). This observation is rather unexpected since
in the parent reaction of rhodium catalysed 1,4-addition of
arylboronic acids to enones without CO, it is commonly
observed that organic solvent/water solutions are preferred
to water free solvents. Water is thought to be involved in
a protonolysis step of a rhodium–carbon bond containing
intermediate leading to ketone liberation (see Scheme 2).
In the case of the carbonylation reaction, water is not
necessary for high conversion and it is likely that the proton
comes from the boronic acid itself. Actually, the reaction
worked in dry THF in which the only source of proton was
the boronic acid. The possible role of MeOH as a proton
donor cannot be completely discarded. However, the high
efficiency observed with this solvent could also arise from
its high polarity. Less polar alcoholic solvents gave lower
yield of 3 without noticeable changes in the selectivity of
the reaction. Moreover, the reaction was completely ineffec-
tive in isopropanol.
CO
O
O
Path B
R
[Rh]
Ar
O
O
Ar
R
H2O
Scheme 2. Mechanism proposed for the 1,4-addition of arylboronic acids to
a,b-unsaturated ketones.
from 78 to 52%. On the other hand, above 20 bar, the effect
of the pressure on the selectivity of the reaction was rather
limited (compare entries 4 and 10).
The selectivity in benzophenone 5 was strongly dependent
on the temperature of the reaction. If reaction temperatures
higher than 80 ꢀC were used, the quantities of 5 increased
at the cost of the yields of ketones 3 and 4. At 100 ꢀC, the
yield of 5 reached 18% and the yield of diketone 3 dropped
from 78% at 80 ꢀC to 44% at 100 ꢀC.
In order to get better insight into the reaction, the evolution
over time of the quantities of products 3–5 was checked. The
reaction was carried out with a methyl vinyl ketone to phe-
nylboronic acid ratio of 2, using RhH(CO)(PPh3)3 (0.5% vs
phenylboronic acid) as a well defined catalyst precursor, at
80 ꢀC and under 20 bar CO. Aliquot samples were taken at
regular time intervals and analysed by GC with the help of
an internal standard. In order to allow the analysis of enough
samples the reaction medium was five times diluted com-
pared to a typical run.
As expected with carbonylation reactions, the CO pressure
has a strong effect on the selectivity of the process.17 For ex-
ample, when the CO pressure dropped from 20 bar to 1 bar,
the yield of by-product 4 increased from 9 to 21% and in the
mean time, the yield of carbonylated derivative 3 decreased
First of all, it should be noticed that the reaction performed
under diluted conditions (50 mL MeOH) did not reach such
high yields as in a normal catalytic run (10 mL MeOH). The
yield of 3 is only 63% compared to the 78% obtained with
the more concentrated catalytic run. The yields of 4 and 5
remained, on the other hand, practically unchanged. Never-
theless, Figure 1 shows that after a short activation period of
approximately 30 min, the three products 3, 4 and 5 are
simultaneously formed with a diketone to ketone ratio or a
diketone to diphenylketone ratio that remains unchanged
during the course of the reaction. This strongly supports
the hypothesis of closely related catalytic cycles explaining
the formation of these three products. Based on the catalytic
cycle proposed by Hayashi15 for the direct 1,4-addition of
arylboronic acids to a,b-enones, we suggested a related
catalytic cycle combining the non-carbonylative and the
carbonylative processes and using common catalytic inter-
mediates (Scheme 2).
Table 1. Rhodium catalysed aroylation reaction of methyl vinyl ketone 2
with phenylboronic acid 1 under CO pressurea
Entry Solvent
P (CO) (atm) T (ꢀC) 3 (%)b 4 (%)b 5 (%)b
1
2
3
4
5
6
7
8
THF
20
20
20
20
20
20
20
80
80
80
80
80
80
80
80
80
80
100
42
46
0
78
60
59
0
75
52
76
44
<2
3
0
9
8
8
0
8
21
5
7
9
0
7
6
6
0
6
7
THF/H2O (9/1)
1,4-Dioxane
MeOH
n-PrOH
n-BuOH
i-PrOH
MeOH/H2O (9/1) 20
9
10
11
MeOH
MeOH
MeOH
1
40
20
4
18
7
a
The reaction was carried out using phenylboronic acid (1.5 mmol), methyl
vinyl ketone (3.2 mmol), 1% RhH(CO)(PPh3)3 and 10 mL solvent for
18 h.
b
Yields determined by GC based on the arylboronic acid.

11742
H. Chochois et al. / Tetrahedron 62 (2006) 11740–11746
Table 2. Influence of the catalyst precursor on the aroylation reaction of
methyl vinyl ketone 2 with phenylboronic acid 1a
1
3
0,9
0,8
0,7
0,6
0,5
0,4
0,3
0,2
0,1
0
Entry Rhodium catalyst Catalyst (%) 3 (%) 4 (%) 5 (%)
1
2
3
4
5
6
7
8
Rh(COD)2BF4+3PPh3 0.5
Rh(COD)2BF4+3PPh3 0.02
74
80
35
60
74
70
42
39
33
45
9
7
3
5
7
8
5
5
4
5
5
1
<1
<1
1
<1
<1
<1
<1
<1
Rh(COD)2BF4
Rh(COD)Cl
0.01
0.01
Rh(COD)2BF4+3PPh3 0.01
Rh(COD)Cl+3PPh3 0.01
Rh(COD)2BF4+3PPh3 0.005
Rh(COD)2BF4+6PPh3 0.005
Rh(COD)2BF4+1dppb 0.005
Rh(COD)2BF4+2dppb 0.005
4
5
9
10
1400
0
200
400
600
time (min)
800
1000
1200
a
Reactions were carried out using phenylboronic acid (1.5 mmol) and
methyl vinyl ketone (3.2 mmol) in 10 mL MeOH under 20 bar CO at
80 ꢀC for 18 h.
Figure 1. Formation profiles of the products 3–5 in the catalytic reaction
(Scheme 1) versus time. The reaction was run at 70 ꢀC with methyl vinyl
ketone (3 mmol), PhB(OH)2 (1.5 mmol), RhH(CO)(PPh3)3 (0.015 mmol)
and CO (20 bar) in MeOH (50 mL).
yields of 3 and the selectivity of the reaction for 3 versus
the non-carbonylated derivative 4 remained rather un-
changed. On the other hand, it is noteworthy that the use
of low catalyst amounts afforded a better selectivity into
the 1,4-diketone product 3. Experiments carried out with
less than 0.02% of rhodium showed the formation of much
lower quantities of diphenylketone compared to the standard
experiments made with 0.5% catalyst. Actually the use of
higher reaction temperatures with high catalyst concen-
tration induced the formation of much higher quantities of
the undesired diphenylketone. This drawback can be par-
tially avoided with a lower amount of Rh.
The arylrhodium catalytic species is obtained in both cases
by a transmetallation step of the phenyl from the boron to
the rhodium centre. This intermediate can readily insert
the olefin leading to the ketone formation. Alternatively,
arylrhodium complexes are known to easily insert a CO
molecule to give an aroylrhodium intermediate.18 Insertion
of the olefin into the aroylrhodium bond followed by a hydro-
lysis step gives the 1,4-diketone. It is noteworthy that
under CO pressure, very low amounts of benzene are ob-
tained by hydrololytic B–C bond cleavage of phenylboronic
acid. Catalytic experiments with p-tolylboronic acid and
m-chlorophenylboronic acid showed similar results. This is
in marked contrast to the usually large excesses of organo-
boronic acids required for the direct 1,4-addition of arylbor-
onic acids to a,b-enones. Such starting material degradation
can be explained by a competitive Rh–C bond protonolysis.
Low protonolysis of the arylboronic acid under our condi-
tions can be explained by a fast insertion of the olefin into
the arylrhodium or aroylrhodium bond compared to the
hydrolysis step. Another explanation can arise from the
higher stability of the aroylrhodium complex compared to
the arylrhodium complex towards protonolysis. This is
supported by the fact that proton NMR and GC analysis of
the crude reaction mixture did not show the presence of
significant amounts of benzoic acid or methylbenzoic ester
as the respective products of hydrolysis and methanolysis
of an aroylrhodium intermediate.
Using optimised reactions conditions, high yields of dike-
tones that can be easily isolated by column chromatography
and fully characterised before further use, are obtained from
variously substituted arylboronic acids (Table 3, entries 1
and 5–9).
Additional experiments made with some other well-known
transmetalling reagents using the same reaction conditions
showed low efficiencies. No reaction was observed
19
with ArSi(OEt)3 or another boron derivative such as
NaB(Ar)4 and only moderate yields was obtained with
20
ArSn(Bu)3 (Table 3, entries 2–4). Boronic acids are thus
the best reactant for this carbonylation reaction. Unfortu-
nately, attempts to change the Michael acceptor, using the
same reaction conditions and catalyst, have been up until
Table 3. Rhodium catalysed aroylation reaction of methyl vinyl ketone un-
der CO pressure with various boronic acids and transmetallation reagentsa
As a high loading of expensive rhodium is usually used in the
corresponding non-carbonylative reaction, it was important
to determine the extent to which it was possible to decrease
the amount of catalyst without a dramatic loss of the yields
of 3.
Entry
Transmetallation reagent
Ar
3 (%)b
1
2
3
4
5
6
7
8
9
ArB(OH)2
ArSn(Bu)3
NaB(Ar)4
ArSi(OEt)3
ArB(OH)2
ArB(OH)2
ArB(OH)2
ArB(OH)2
ArB(OH)2
C6H5
C6H5
C6H5
C6H5
4-MeC6H4
4-MeOC6H4
3-ClC6H4
4-ClC6H4
4-FC6H4
76
53
0c
0
Table 2 shows that as little as 0.01% of the rhodium precur-
sor is enough to complete the reaction within one night at
80 ꢀC using Rh(COD)Cl as the catalyst precursor combined
with triphenylphosphine. Phosphine free catalytic systems
showed much lower reactivity although they remained effi-
cient if used with a higher amount of rhodium (0.5%). Using
the same reaction conditions, experiments carried out with
0.005% of rhodium afforded much lower yields of 1,4-di-
ketone 3. The combination of different phosphorous based
ligands with Rh(COD)2BF4 did not further improve the
78
72
65
68
65
a
Reactions were carried out using the corresponding transmetallation
reagent (1.5 mmol), methyl vinyl ketone (3.2 mmol) and 0.5%
RhH(CO)(PPh3)3 in 10 mL MeOH with 40 bar CO pressure at 80 ꢀC for
18 h.
Isolated yields.
PhCOPh is the only formed product.
b
c

H. Chochois et al. / Tetrahedron 62 (2006) 11740–11746
11743
Table 4. Carbonylation–cyclisation sequences for pyrroles and furans
now unsuccessful. In particular, substituted enones such
as cyclohexenone failed to react even at higher reaction
temperatures. The reaction does not proceed with non-
activated olefins either, for example, no product was
detected with 1-hexene except the diphenylketone.
synthesisa
Entry
Ar
X¼NPhb (%)
X¼Oc (%)
49
1
2
3
4
5
6
C6H5
56
51
45
53
59
44
4-MeC6H4
4-MeOC6H4
4-ClC6H4
3-ClC6H4
4-FC6H4
50 (54)d
66
49
2.2. Procedure for pyrroles and furans synthesis
44
42
For economical and environmental reasons, it is of interest to
use the diketones without any previous purification for a fur-
ther organic transformation. We thus evaluated the possibil-
ity to combine, in a short procedure, the diketone formation
through carbonylation with a cyclisation step giving pyrrole
or furan derivatives (Scheme 3). This procedure would allow
simple and fast access to the pyrrole and furan heterocycles
in a short catalytic multicomponent synthetic procedure.21
The Paal–Knorr cyclisation with an amine is a common
synthetic pathway to access pyrroles.22 The procedure com-
monly requires high temperature reactions and an acidic
media. In our case, starting from our crude catalytic mixtures
the reaction remained only partially successful. Indeed, pyr-
roles formation proceeded more efficiently via the iodine
catalysed Paal–Knorr cyclisation even though the yield for
this step was not quantitative. Better results were obtained
when the amount of iodine used was increased compared
to the literature procedure from 3 to 40% and the reaction
time at 40 ꢀC (instead of room temperature) from 4 h to
16 h.23
a
The carbonylation reactions were carried out using the corresponding
arylboronic reagent (1.5 mmol) and 0.5% RhH(CO)(PPh3)3 in 10 mL
MeOH for 18 h, 20 bar CO and 80 ꢀC.
The crude mixture obtained after carbonylation was stirred overnight with
aniline and iodine in dichloromethane.
The crude mixture obtained after carbonylation was refluxed overnight in
toluene with 1 equiv p-toluenesulfonic acid.
The carbonylation reaction was run in a biphasic toluene (5 mL)/water
(5 mL) system and the cyclisation step was run with the organic phase
dried with MgSO4.
b
c
d
the carbonylation reaction could be directly performed in
a toluene/water (1/1) mixture with similar yields. The water
layer was then extracted and the organic layer dried with
magnesium sulfate. After filtration, the toluene solution
was refluxed in the presence of p-toluenesulfonic acid to
generate the furan. This procedure performed with p-tolyl-
boronic acid allowed the isolation of the corresponding furan
in a similar yield. It has the main advantage of shortening the
procedure by avoiding the tedious methanol evaporation
step.
Under these conditions, GC analysis at the end of the reac-
tion indicated the complete disappearance of the starting
diketone along with pyrrole formation. The side products,
i.e., ketones 4 and 5 remained unaffected. The analytically
pure pyrroles were finally isolated by alumina gel column
chromatography with overall 45–60% yields from the start-
ing boronic acid.
3. Conclusion
We have shown that the carbonylative 1,4-addition of aryl-
boronic acids to enones affords the corresponding diketones
with high selectivity even at low catalyst loadings. The reac-
tion allows an efficient access to 1,4-diketones. Interestingly,
this reaction can be coupled with a cyclisation without
previous purification giving pyrrole or furan derivatives.
Thus, the whole process constitutes an efficient way to
access these last classes of compounds.
The 1,4-diketones can also be reacted without previous pu-
rification to form furans. After a carbonylation reaction,
the solvent was evaporated. The cyclisation was promoted
by p-toluenesulfonic acid monohydrate in refluxing toluene
for one night.24 The complete conversion of the reaction
product was then confirmed by GC analysis. The furans
were finally purified by alumina gel column chromatography
and isolated with similar yields to the corresponding pyr-
roles. Following those procedures, it was possible to synthe-
sise a series of furan and pyrrole heterocycles with good
overall yields (Table 4).
4. Experimental
4.1. General
All experiments were carried out with solvents, rhodium
complexes, phosphines, arylboronic acids, amines, APTS
and methyl vinyl ketone purchased from Aldrich or Acros
and used as received.
To avoid any change of solvent between the catalytic and
cyclisation step for furan synthesis, it is noteworthy that
2) p-TsOH
toluene
Ar
Ar
O
6
O
1) 0.5 % RhH(CO)(PPh3)3
R
Ar B(OH)2
+
CO; MeOH
2) PhNH2; I2
toluene
N
1
2
7
Scheme 3. Pyrrole and furan synthesis via a rhodium catalysed aroylation of enones with arylboronic acids and carbon monoxide followed by a cyclisation step.

11744
H. Chochois et al. / Tetrahedron 62 (2006) 11740–11746
GLC analyses were performed on a Chrompack CP 9001 ap-
paratus equipped with a flame ionisation detector and a CPSil
126.71 (s, 1C, CH aromatic); 36.93 (s, 1C, CH2); 32.44 (s,
1C, CH2); 29.99 (s, 1C, CH3).
5CB (25 mꢁ0.32 mm, Chrompack) column. 1H, 19F and 13
C
NMR spectra were recorded on a AC-300 Bruker spectro-
meter at 23 ꢀC; chemical shifts are reported in parts per
million downfield from TMS.
1-(4-Fluorophenyl)pentane-1,4-dione: yellow liquid, 62%
yield. H NMR: (200 MHz, CDCl3) d¼7.94 (m, 2H, CH
1
aromatic); 7.36 (m, 2H, CH aromatic); 3.21 (t, 2H,
3
3JH–H¼5.9 Hz, CH2); 2.84 (t, 2H, JH–H¼5.9 Hz, CH2);
4.1.1. General procedure for carbonylation reactions and
enones isolation. A 100 mL stainless steel autoclave equip-
ped with a magnetic stirrer was charged with arylboronic
acid (1.5 mmol) and the required amount of rhodium cata-
lyst. MeOH (10 mL) was thus added followed by methyl
vinyl ketone (0.25 mL, 3 mmol). The autoclave was pressur-
ised to 20 bar and the mixture was warmed at 80 ꢀC for 18 h.
After cooling to room temperature, the reactor was vented
and the orange-yellow methanol solution was evaporated
to dryness. The diketones were finally purified by silica
gel column chromatography using petroleum/ether (9/1) as
eluent.
2.20 (s, 3H, COCH3). 13C NMR: (CDCl3, 75 MHz)
d¼206.65 (s, 1C, CH3CO); 196.38 (s, 1C, ArCO); 165.24
(d, 1C, 1JF–C¼254.4 Hz, FC); 132.62 (s, 1C, CCO); 131.42
2
(d, 2C, JF–C¼117.1 Hz, CH aromatic); 115.1 (s, 2C,
3JF–C¼21.6 Hz, CH aromatic); 36.48 (s, 1C, CH2); 31.75
(s, 1C, CH2); 29.48 (s, 1C, CH3).
4.1.2. General procedure for pyrroles synthesis. In the
first part of the synthesis, the carbonylation reaction was
run according to the procedure used for the enones synthesis
(vide supra). The mixture obtained was evaporated and
the residue dissolved in a solution of iodine (0.183 g,
0.72 mmol) and aniline (0.194 mL, 2.1 mmol) in THF
(10 mL). The resulting solution was then heated at 40 ꢀC
for one night. The reaction was monitored by GC and ended
once the GC peak corresponding to the starting enone has
disappeared. The solvent was evaporated and the pyrrole
purified by alumina gel column chromatography using
petroleum/ether (9/1) as eluent.
1-p-Tolylpentane-1,4-dione: white solid, 78% yield. 1H
3
NMR: (300 MHz, CDCl3) d¼7.85 (d, 2H, JH–H¼8 Hz,
3
CH aromatic); 7.21 (d, 2H, JH–H¼8 Hz, CH aromatic);
3.21 (t, 2H, 3JH–H¼6.3 Hz, CH2); 2.83 (t, 2H, 3JH–H¼6.3 Hz,
CH2); 2.36 (s, 3H, ArCH3); 2.21 (s, 3H, COCH3). 13C NMR:
(CDCl3, 75 MHz) d¼207.41 (s, 1C, CH3CO); 198.10 (s, 1C,
ArCO); 143.90 (s, 1C, CH3C); 134.13 (s, 1C, CCO); 129.22
(s, 2C, CH aromatic); 128.13 (s, 2C, CH aromatic); 37.05 (s,
1C, CH2); 32.29 (s, 1C, CH2); 30.09 (s, 1C, CH3); 21.61 (s,
1C, ArCH3).
2-p-Tolyl-5-methyl-1-phenyl-1H-pyrrole:
yellow-orange
1
solid, 51% yield. H NMR: (300 MHz, CDCl3) d¼7.2–7.3
(m, 3H, CH aromatic); 7.06 (m, 2H, CH aromatic); 6.86
(m, 4H, CH aromatic); 6.45 (d, 1H, 3JH–H¼1.9 Hz, CHPyrr);
6.21 (d, 1H, 3JH–H¼1.9 Hz, CHPyrr); 2.35 (s, 3H, CH3); 2.25
(s, 3H, CH3). 13C NMR: (CDCl3, 50 MHz) d¼139.15 (s, 1C,
NCipso); 134.83 (s, 1C, Cq); 133.84 (s, 1C, Cq); 130.88 (s,
1C, Cq); 130.36 (s, 1C, Cq); 128.54 (s, 2C, CH aromatic);
128.31 (s, 2C, CH aromatic); 128.12 (s, 2C, CH aromatic);
127.32 (s, 2C, CH aromatic); 126.92 (s, 1C, CH aromatic);
107.87 (s, 1C, CHPyrr); 107.09 (s, 1C, CHPyrr); 20.65 (s,
1C, CH3); 12.95 (s, 1C, CH3).
1-(4-Methoxyphenyl)pentane-1,4-dione: white solid, 72%
yield. 1H NMR: (300 MHz, CDCl3) d¼7.92 (d, 2H,
3
3JH–H¼9 Hz, CH aromatic); 6.89 (d, 2H, JH–H¼9 Hz, CH
3
aromatic); 3.83 (s, 3H, OCH3); 3.19 (t, 2H, JH–H¼6.5 Hz,
3
CH2); 2.85 (t, 2H, JH–H¼6.5 Hz, CH2); 2.23 (s, 3H,
COCH3). 13C NMR: (CDCl3, 75 MHz) d¼207.54 (s, 1C,
CH3CO); 197.01 (s, 1C, ArCO); 163.51 (s, 1C, CH3OC);
130.29 (s, 2C, CH aromatic); 129.12 (s, 1C, CCO); 113.69
(s, 2C, CH aromatic); 55.45 (s, 1C, OCH3); 37.13 (s, 1C,
CH2); 32.05 (s, 1C, CH2); 30.12 (s, 1C, CH3).
2-(4-Methoxyphenyl)-5-methyl-1-phenyl-1H-pyrrole: red-
orange solid, 45% yield. 1H NMR: (300 MHz, CDCl3)
d¼7.42 (m, 3H, CH aromatic); 7.22 (d, 2H, 3JH–H¼6.4 Hz,
1-(4-Chlorophenyl)pentane-1,4-dione: white solid, 68%
yield. 1H NMR: (200 MHz, CDCl3) d¼7.83 (d, 2H,
3
CH aromatic); 7.06 (d, 2H, JH–H¼8.8 Hz, CH aromatic);
3
3
3JH–H¼8 Hz, CH aromatic); 7.36 (d, 2H, JH–H¼8 Hz, CH
6.75 (d, 2H, JH–H¼8.8 Hz, CH aromatic); 6.36 (d, 1H,
3
aromatic); 3.20 (t, 2H, JH–H¼6.3 Hz, CH2); 2.80 (t, 2H,
3JH–H¼2.9 Hz, CHPyrr); 6.15 (d, 1H, 3JH–H¼2.9 Hz, CHPyrr);
3.77 (s, 3H, OCH3); 2.21 (s, 3H, CH3). 13C NMR: (CDCl3,
75 MHz) d¼157.84 (s, 1C, OCq); 139.53 (s, 1C, NCipso);
134.05 (s, 1C, Cq); 130.99 (s, 1C, Cq); 129.18 (s, 2C, CH
aromatic); 128.99 (s, 2C, CH aromatic); 128.60 (s, 2C, CH
aromatic); 127.37 (s, 1C, CH aromatic); 126.42 (s, 1C,
Cq); 113.52 (s, 2C, CH aromatic); 107.81 (s, 1C, CHPyrr);
107.38 (s, 1C, CHPyrr); 55.15 (s, 1C, OCH3); 13.42 (s, 1C,
CH3).
3JH–H¼6.3 Hz, CH2); 2.20 (s, 3H, COCH3). 13C NMR:
(CDCl3, 50 MHz) d¼206.65 (s, 1C, CH3CO); 196.78 (s,
1C, ArCO); 138.94 (s, 1C, ClC or CCO); 134.13 (s, 1C,
ClC or CCO); 128.94 (s, 2C, CH aromatic); 128.33 (s, 2C,
CH aromatic); 36.44 (s, 1C, CH2); 31.81 (s, 1C, CH2);
29.46 (s, 1C, CH3).
1-(3-Chlorophenyl)pentane-1,4-dione: yellow liquid, 65%
yield. 1H NMR: (300 MHz, CDCl3) d¼7.89 (s, 1H, CH aro-
3
matic); 7.80 (d, 1H, JH–H¼7.7 Hz, CH aromatic); 7.47 (d,
2-(4-Chlorophenyl)-5-methyl-1-phenyl-1H-pyrrole: orange
3
3
1
1H, JH–H¼7.7 Hz, CH aromatic); 7.36 (t, 1H, JH–H
¼
solid, 53% yield. H NMR: (300 MHz, CDCl3) d¼7.8–6.8
3
7.7 Hz, CH aromatic); 3.19 (t, 2H, JH–H¼5.8 Hz, CH2);
(m, 9H, CH aromatic); 6.41 (br s, 1H, CHPyrr); 6.15 (br s,
1H, CHPyrr); 2.18 (s, 3H, CH3). 13C NMR: (CDCl3,
75 MHz) d¼138.71 (s, 1C, NCipso); 132.45 (s, 1C, Cq);
131.69 (s, 1C, Cq); 131.57 (s, 1C, Cq); 130.95 (s, 1C, Cq);
128.65 (s, 2C, CH aromatic); 128.34 (s, 2C, CH aromatic);
127.96 (s, 2C, CH aromatic); 127.69 (s, 2C, CH aromatic);
3
2.85 (t, 2H, JH–H¼5.8 Hz, CH2); 2.21 (s, 3H, COCH3).
13C NMR: (CDCl3, 75 MHz) d¼207.01 (s, 1C, CH3CO);
197.24 (s, 1C, ArCO); 138.12 (s, 1C, ClC or CCO);
134.85 (s, 1C, ClC or CCO); 133.03 (s, 1C, CH aromatic);
129.93 (s, 1C, CH aromatic); 128.12 (s, 1C, CH aromatic);

H. Chochois et al. / Tetrahedron 62 (2006) 11740–11746
11745
127.16 (s, 1C, CH aromatic); 108.61 (s, 1C, CHPyrr); 107.29
(s, 1C, CHPyrr); 13.91 (s, 1C, CH3).
75 MHz) d¼158.69 (s, 1C, Cq); 152.40 (s, 1C, Cq);
151.18 (s, 1C, Cq); 124.78 (s, 2C, CH aromatic); 124.70
(s, 1C, Cq); 114.11 (s, 2C, CH aromatic); 107.60 (s, 1C,
CHFur); 104.28 (s, 1C, CHFur); 55.23 (s, 1C, OCH3); 13.68
(s, 1C, CH3).
2-(3-Chlorophenyl)-5-methyl-1-phenyl-1H-pyrrole: orange
1
solid, 59% yield. H NMR: (300 MHz, CDCl3) d¼7.40–
7.30 (m, 3H, CH aromatic); 7.00–7.23 (m, 5H, CH aro-
matic); 6.88 (m, 1H, CH aromatic); 6.41 (d, 1H,
3JH–H¼2.9 Hz, CHPyrr); 6.13 (d, 1H, 3JH–H¼2.9 Hz, CHPyrr);
2.16 (s, 3H, CH3). 13C NMR: (CDCl3, 75 MHz) d¼139.07
(s, 1C, NCipso); 135.27 (s, 1C, Cq); 133.81 (s, 1C, Cq);
132.63 (s, 1C, Cq); 132.49 (s, 1C, Cq); 129.16 (s, 2C, CH
aromatic); 129.12 (s, 1C, CH aromatic); 128.41 (s, 2C,
CH aromatic); 127.73 (s, 1C, CH aromatic); 127.50 (s, 1C,
CH aromatic); 125.57 (s, 2C, CH aromatic); 109.51 (s,
1C, CHPyrr); 107.81 (s, 1C, CHPyrr); 13.32 (s, 1C, CH3).
2-(4-Chlorophenyl)-5-methylfuran: orange solid, 53% yield.
1H NMR: (300 MHz, CDCl3) d¼7.55 (d, 2H, 3JH–H¼8.6 Hz,
3
CH aromatic); 7.32 (d, 2H, JH–H¼8.6 Hz, CH aromatic);
6.53 (br s, 1H, CHFur); 6.07 (br s, 1H, CHFur); 2.38 (s, 3H,
CH3). 13C NMR: (CDCl3, 75 MHz) d¼151.80 (s, 1C, Cq);
150.76 (s, 1C, Cq); 131.78 (s, 1C, Cq); 129.21 (s, 1C, Cq);
128.51 (s, 2C, CH aromatic); 124.01 (s, 2C, CH aromatic);
107.41 (s, 1C, CHFur); 105.90 (s, 1C, CHFur); 13.19 (s, 1C,
CH3).
2-(4-Fluorophenyl)-5-methyl-1-phenyl-1H-pyrrole:
red-
2-(3-Chlorophenyl)-5-methylfuran: orange solid, 44% yield.
1H NMR: (300 MHz, CDCl3) d¼7.64 (s, 1H, CH aromatic);
orange solid, 44% yield. 1H NMR: (300 MHz, CDCl3)
d¼7.37 (m, 3H, CH aromatic); 7.16 (m, 2H, CH aromatic);
7.02 (m, 2H, CH aromatic); 6.84 (m, 2H, CH aromatic); 6.31
3
7.50 (d, 1H, JH–H¼7.8 Hz, CH aromatic); 7.28 (dd, 1H,
3
3JH–H¼7.8 Hz, CH aromatic); 7.18 (d, 1H, JH–H¼7.8 Hz,
3
3
3
(d, 1H, JH–H¼3.42 Hz, CHPyrr); 6.10 (d, 1H, JH–H
¼
CH aromatic); 6.57 (d, 1H, JH–H¼3.0 Hz, CH aromatic);
3.42 Hz, CHPyrr); 2.16 (s, 3H, CH3). 13C NMR: (CDCl3,
6.08 (d, 1H, JH–H¼2.8 Hz, CH aromatic); 2.38 (s, 3H,
3
1
75 MHz) d¼161.92 (d, 1C, JF–C¼245.1 Hz, FC); 139.20
CH3). 13C NMR: (CDCl3, 75 MHz) d¼152.63 (s, 1C, Cq);
150.84 (s, 1C, Cq); 134.66 (s, 1C, Cq); 132.85 (s, 1C, Cq);
129.89 (s, 1C, CH aromatic); 126.59 (s, 1C, CH aromatic);
123.26 (s, 1C, CH aromatic); 121.13 (s, 1C, CH aromatic);
107.98 (s, 1C, CHFur); 107.09 (s, 1C, CHFur); 13.70 (s, 1C,
CH3).
(s, 1C, NCipso); 138.15 (s, 1C, Cq); 132.77 (s, 1C, Cq);
3
131.13 (s, 1C, Cq); 128.90 (d, 2C, JF–C¼7.9 Hz, CH aro-
matic); 128.59 (s, 2C, CH aromatic); 128.09 (s, 2C, CH
aromatic); 127.08 (s, 1C, CH aromatic); 114.31 (d, 2C,
2JF–C¼21.6 Hz, CH aromatic); 108.22 (s, 1C, CHPyrr);
107.17 (s, 1C, CHPyrr); 13.13 (s, 1C, CH3).
2-(4-Fluorophenyl)-5-methylfuran: orange solid, 42% yield.
1H NMR: (300 MHz, CDCl3) d¼7.55 (dd, 2H,
4.1.3. General procedure for furans synthesis. In the first
part of the synthesis, the carbonylation reaction is run ac-
cording to the procedure used for the enones synthesis
(vide supra). The mixture obtained is evaporated and the
residue dissolved in a solution of p-toluenesulfonic acid
monohydrate (60 mg, 1.5 mmol) in toluene (10 mL). The re-
sulting solution is then refluxed overnight. After evaporation
of the solvent, the furan is purified by alumina gel column
chromatography using petroleum/ether (9/1) as eluent. Al-
ternatively, the carbonylation reaction can be run in a tolu-
ene/H2O biphasic system. After one night of reaction with
20 bar of CO at 80 ꢀC, the organic layer is then separated
from the aqueous phase, dried over MgSO4 and filtered.
Addition of p-toluenesulfonic acid monohydrate to the tolu-
ene solution followed by overnight refluxing allows the com-
plete transformation of the diketone in the corresponding
furan heterocycle.
3
3JH–H¼8.6 Hz, CH aromatic); 7.32 (d, 2H, JH–H¼8.6 Hz,
CH aromatic); 6.53 (br s, 1H, CHFur); 6.07 (br s, 1H, CHFur);
2.38 (s, 3H, CH3). 13C NMR: (CDCl3, 75 MHz) d¼151.80
(s, 1C, Cq); 150.76 (s, 1C, Cq); 131.78 (s, 1C, Cq); 129.21
(s, 1C, Cq); 128.51 (s, 2C, CH aromatic); 124.01 (s, 2C,
CH aromatic); 107.41 (s, 1C, CHFur); 105.90 (s, 1C, CHFur);
13.19 (s, 1C, CH3).
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4
3
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