Platinum-catalyzed regioselective hydration of 1-(2-propynyl)-2- formylpyrroles

Article abstract of DOI:10.3987/COM-12-S(N)55

The hydration reaction of 1-(2-propynyl)-2-formylpyrroles with a platinum catalyst in aqueous media is described. Various 1-(2-oxopropyl)-2-formylpyrroles were regioselectively synthesized Via the platinum-promoted intramolecular 6-exo-dig cyclization pathway.

Full text of DOI:10.3987/COM-12-S(N)55

HETEROCYCLES, Vol. 86, No. 1, 2012
599
HETEROCYCLES, Vol. 86, No. 1, 2012, pp. 599 - 609. © 2012 The Japan Institute of Heterocyclic Chemistry
Received, 25th June, 2012, Accepted, 13th July, 2012, Published online, 19th July, 2012
DOI: 10.3987/COM-12-S(N)55
PLATINUM-CATALYZED REGIOSELECTIVE HYDRATION OF
1-(2-PROPYNYL)-2-FORMYLPYRROLES
Masahiro Yoshida* and Shota Yodokawa
Graduate School of Pharmaceutical Sciences, The University of Tokushima,
1-78-1 Sho-machi, Tokushima 770-8505, Japan
E-mail: yoshi@tokushima-u.ac.jp
Abstract – The hydration reaction of 1-(2-propynyl)-2-formylpyrroles with a
platinum
catalyst
in
aqueous
media
is
described.
Various
1-(2-oxopropyl)-2-formylpyrroles were regioselectively synthesized via the
platinum-promoted intramolecular 6-exo-dig cyclization pathway.
INTRODUCTION
Hydration of alkynes is a useful protocol for introduction of carbonyl component within the molecules,
and various methodologies for the application in organic synthesis have been reported.1,2 Among them,
transition metal-catalyzed hydration of alkynes utilizing neighboring group participation is one of the
useful protocol to obtain the desired product in high regioselectivity.3 For example, Sahoo recently
reported a gold-catalyzed hydration of propargyl acetates, in which -acyloxy methyl ketones were
regioselectively produced by assisting a neighboring carbonyl group.3d During the course of our studies
on the platinum-catalyzed reactions using alkynyl compounds,4 we focused on a regioselective hydration
of 1-(2-propynyl)pyrroles utilizing neighboring group participation. We report herein a
platinum-catalyzed
hydration
of
1-(2-propynyl)-2-formylpyrroles,
in
which
various
1-(2-oxopropyl)-2-formylpyrroles can be synthesized in a regioselective manner.
RESULTS AND DISCUSSION
The initial attempts were carried out using 1-(2-propynyl)-2-formylpyrrole (1a) (Scheme 1). When the
substrate 1a was treated with 10 mol % of PtCl2 in dioxane/H2O (2/1) at 100 ºC for 10 min,4a,b the
reaction successfully proceeded to afford 1-(2-oxopropyl)-2-formylpyrrole (2a) in 77% yield.5 The
reaction also proceeded when 10 mol % AuCl3 was used as the catalyst, but the reaction time was
prolonged to 10 h and the yield was decreased to 65%.
‡ This paper is dedicated to Prof. Ei-ichi Negishi on the occasion of his 77th birthday.

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HETEROCYCLES, Vol. 86, No. 1, 2012
H
H
10 mol % catalyst
dioxane/H2O (2/1)
N
N
O
O
O
1a
2a
2a
catalyst
PtCl2
time
10 min
10 h
yield of
77%
AuCl3
65%
Scheme 1
We next attempted the reactions using various substrates 1b–1i having an aryl group at the alkynyl
position (Scheme 2). When phenyl-substituted substrate 1b was subjected to the reaction with PtCl2, the
hydrated product 2b was obtained in 82% yield together with the regioisomer 3b in 12% yield (Table 1,
entry 1). The tolyl- and p-methoxyphenyl-substituted substrates 1c and 1d were transformed to the
ketones 2c and 2d, but considerable amount of the regioisomers 3c and 3d were also produced,
respectively (entries 2 and 3). The reactions of 1e and 1f, having a fluoro and a chloro group on the
aromatic ring, afforded the corresponding products 2e and 2f in moderate yields with good
regioselectivity (entries 4 and 5). When the substrates 1g and 1h having an electron-withdrawing group
were subjected to the reactions, the corresponding products 2g and 2h were obtained in low yields (entries
6 and 7). On the other hand, the reaction of the substrate 1i which contains an ester moiety on the phenyl
group successfully afforded the corresponding ketone 2i and the regioisomer 3i in 63% and 11% yields,
respectively (entry 8). Interestingly, the observed regioselectivity for the production of 2 was contrary to
the literature reports that p-Lewis acid-promoted hydrations of aryl-substituted alkynes prefer to add
water at the RC≡CAr carbon atom (R = alkyl).6 These results imply that the reactions proceed by
assisting a neighboring formyl group.
H
H
H
10 mol % PtCl2
N
N
N
O
+
O
O
dioxane/H2O (2/1)
100 ºC, 0.5–5 h
O
O
R
R
R
1b–i
2b–i
3b–i
Scheme 2

HETEROCYCLES, Vol. 86, No. 1, 2012
601
Table 1. Platinum-catalyzed hydration of aryl-substituted substrates 1b–i.
Entry
Substrate 1
R = H (1b)
Time (h)
2 (Yield /%)a
2b (82)
2c (52)
3 (Yield /%)a
3b (12)
3c (25)
3d (26)
3e (11)
3f (13)
1
2
3
4
5
6
7
8
0.5
2.5
5
R = Me (1c)
R = OMe (1d)
R = F (1e)
2d (33)
2e (66)
1
R = Cl (1f)
2
2f (51)
R = Ac (1g)
R = CN (1h)
R = CO2Me (1i)
1
2g (28)
2h (28)
2i (63)
3g (9)
5
3h (6)
1
3i (11)
aIsolated yields.
A plausible mechanism for the hydration of the 1-(2-propynyl)-2-formylpyrroles 1 is shown in Scheme 3.
The platinum catalyst activates the carbon-carbon triple bond in 1 by coordination as shown in 4.
Intramolecular 6-exo-dig cyclization of the internal formyl oxygen occurs to form the cyclized
intermediate 5, which produces a ketone 2 upon hydrolysis followed by proto-demetallation process. It is
expected that the regioisomers 3 are produced via the intermediate 5’, derived from intramolecular
7-endo-dig cyclization of 4.
H
O H
H
H
N
PtX2
N
N
O
R
O
O
R
– H
– X
R
X2Pt
XPt
5
1
4
H
H
OH
N
N
N
HX
O
O
O
R
O
_
PtX2
R
O
XPt
O
XPt
R
2
H
N
N
O
O
R
R
XPt
5'
3
Scheme 3

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HETEROCYCLES, Vol. 86, No. 1, 2012
Information on the reaction mechanism was gained by carrying out the reaction using formyl-free
substrates (Scheme 4). When the 1-(2-propynyl)pyrrole (6) was subjected to the reaction, the yield of the
hydrated product 7 was dramatically decreased to 4%. Furthermore, the reaction of vinyl-substituted
substrate 8 did not give the corresponding product 9. These results support the hypothesis that the
reaction proceeds via the intramolecular 6-exo-dig cyclization pathway by assisting a neighboring formyl
group.
10 mol % PtCl2
N
N
dioxane/H2O (2/1)
100 ºC, 6 h
O
6
7
4%
10 mol % PtCl2
N
N
N.R.
dioxane/H2O (2/1)
100 ºC, 10 h
O
8
9
not obtained
Scheme 4
In conclusion, we have developed a methodology for the synthesis of 1-(2-oxopropyl)-2-formylpyrroles
by platinum-catalyzed hydration reactions. By introducing a formyl group on the pyrrole ring,
regioselective hydration has been accomplished via the intramolecular 6-exo-dig cyclization pathway.
Functionalization of pyrroles is an important research area of heterocyclic chemistry for synthesizing a
variety of biologically active natural products and industrially useful compounds in an efficient and
selective manner.7 Our reaction would provide a useful methodology for the selective functionalization of
1-(2-oxopropyl) pyrroles. Efforts to extend the scope of these reactions and their subsequent application
to the syntheses of biologically active heterocyclic molecules are currently in progress.
EXPERIMENTAL
Solvents were dried and distilled according to standard protocols. The phrase ‘residue upon workup’
refers to the residue obtained when the organic layer was separated and dried over anhydrous MgSO4 and
the solvent was evaporated under reduced pressure.
Starting Materials. 1-(2-Propynyl)-2-formylpyrroles 1a–1i were prepared according to the procedures
described in the literature.8

HETEROCYCLES, Vol. 86, No. 1, 2012
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Typical Procedure for the Preparation of 1-(2-Propynyl)-2-formylpyrrole 1.
Synthesis of 1d: To a stirred solution of NaH (44.0 mg, 1.10 mmol) in DMF (20 mL) was added
dropwise 2-formylpyrrole (95.1 mg, 1.00 mmol) in DMF (2 mL) at 0 °C and stirring was continued for 30
min at the same temperature. Then 1-(3-bromo-1-propyl)-4-methoxybenzene (247 mg, 1.10 mmol) in
DMF (2 mL) was added to the solution at 0 °C. After stirring was continued for 20 min at the same
temperature, the reaction mixture was quenched with water and extracted with Et2O. The combined
extracts were washed with 0.5 N HCl, and the residue upon workup was chromatographed on silica gel
with hexane-AcOEt (90/10 v/v) as eluent to give 1-[3-(4-Methoxyphenyl)-2-propynyl]-2-formylpyrrole
1d (218 mg, 91%) as a colorless solid.
1-(3-Phenyl-2-propynyl)-2-formylpyrrole (1b): Colorless plates; mp 54.2–56.3 °C (recrystallized from
AcOEt-hexane); IR (KBr) 2977, 2808, 1660, 788, 754 cm–1; 1H-NMR (400 MHz, CDCl3) δ 5.43 (2H, s),
6.30 (1H, dd, J = 2.4 and 4.0 Hz), 6.98 (1H, dd, J = 1.6 and 4.0 Hz), 7.30–7.34 (3H, m), 7.36–7.38 (1H,
13
m), 7.44–7.47 (2H, m), 9.59 (1H, s); C-NMR (100MHz, CDCl3) δ 39.0 (CH2), 82.7 (Cq), 86.1 (Cq),
110.0 (CH), 122.2 (Cq), 124.9 (CH), 128.3 (CH), 128.7 (CH), 130.4 (CH), 131.2 (Cq), 131.8 (CH), 179.5
(CH); HRMS (ESI) m/z calcd for C14H11NNaO [M+Na]+ 232.0738, found 232.0740.
1-[3-(4-Methylphenyl)-2-propynyl]-2-formylpyrrole (1c): Colorless needles; mp 44.7–45.6 °C
(recrystallized from AcOEt-hexane); IR (KBr) 3133, 3039, 2933, 2812, 1660, 1509, 1405, 817, 744 cm–1;
1H-NMR (400 MHz, CDCl3) δ 2.35 (3H, s), 5.42 (2H, s), 6.29 (1H, dd, J = 2.8 and 4.0 Hz), 6.98 (1H, dd,
J = 2.0 and 4.0 Hz), 7.11–7.13 (2H, m), 7.32–7.35 (2H, m), 7.36–7.38 (1H, m), 9.58 (1H, d, J = 1.2 Hz);
13C-NMR (100MHz, CDCl3) δ 21.4 (CH3), 39.0 (CH2), 81.9 (Cq), 86.3 (Cq), 109.9 (CH), 119.1 (Cq),
124.8 (CH), 129.1 (CH), 130.4 (CH), 131.1 (Cq), 131.7 (CH), 138.9 (CH), 179.5 (CH); HRMS (ESI) m/z
calcd for C15H13NNaO [M+Na]+ 246.0895, found 246.0883.
1-[3-(4-Methoxyphenyl)-2-propynyl]-2-formylpyrrole (1d): Colorless needles; mp 42.4–44.6 °C
1
(recrystallized from AcOEt-hexane); IR (KBr) 2963, 2845, 2228, 1662, 1249, 832 cm–1; H-NMR (400
MHz, CDCl3) δ 3.81 (3H, s), 5.41 (2H, s), 6.29 (1H, dd, J = 2.4 and 3.6 Hz), 6.82–6.86 (2H, m), 6.97 (1H,
dd, J = 2.0 and 3.6 Hz), 7.37–7.40 (3H, m), 9.58 (1H, d, J = 0.4 Hz); 13C-NMR (100MHz, CDCl3) δ 39.1
(CH2), 55.3 (CH3), 81.3 (Cq), 86.1 (Cq), 109.9 (CH), 114.0 (CH), 114.3 (Cq), 124.9 (CH), 130.4 (CH),
131.2 (Cq), 133.3 (CH), 159.9 (Cq), 179.5 (CH); HRMS (ESI) m/z calcd for C15H13NNaO2 [M+Na]+
262.0844, found 262.0844.
1-[3-(4-Fluorophenyl)-2-propynyl]-2-formylpyrrole (1e): Colorless needles; mp 62.4–64.1 °C
1
(recrystallized from AcOEt-hexane); IR (KBr) 1661, 1507, 1406, 1220, 837, 746 cm–1; H-NMR (400
MHz, CDCl3) δ 5.41 (2H, s), 6.30 (1H, dd, J = 2.4 and 4.0 Hz), 6.98 (1H, dd, J = 1.6 and 4.0 Hz),
6.99–7.04 (2H, m), 7.32–7.34 (1H, m), 7.40-7.45 (2H, m), 9.59 (1H, d, J = 1.2 Hz); 13C-NMR (100MHz,
CDCl3) δ 38.8 (CH2), 82.5 (Cq), 84.8 (Cq), 110.0 (CH), 115.5 (CH, d, J = 21.4 Hz), 118.2 (Cq, d, J = 3.3

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HETEROCYCLES, Vol. 86, No. 1, 2012
Hz), 124.8 (CH), 130.3 (CH), 131.1 (Cq), 133.7 (CH, d, J = 8.3 Hz), 162.6 (Cq, d, J = 248.7 Hz), 179.4
(CH); HRMS (ESI) m/z calcd for C14H10FNNaO [M+Na]+ 250.0644, found 250.0639.
1-[3-(4-Chlorophenyl)-2-propynyl]-2-formylpyrrole (1f): Colorless needles; mp 90.3–91.0 °C
(recrystallized from AcOEt-hexane); IR (KBr) 3099, 2813, 2362, 1651, 1335, 1037, 792, 750 cm–1;
1H-NMR (400 MHz, CDCl3) δ 5.42 (2H, s), 6.30 (1H, dd, J = 2.4 and 4.0 Hz), 6.98 (1H, dd, J = 1.6 and
4.0 Hz), 7.28–7.32 (3H, m), 7.35–7.38 (2H, m), 9.59 (1H, d, J = 0.8 Hz); 13C-NMR (100MHz, CDCl3) δ
38.9 (CH2), 83.8 (Cq), 84.8 (Cq), 110.1 (CH), 120.7 (Cq), 124.9 (CH), 128.7 (CH), 130.4 (CH), 131.2
(Cq), 133.0 (CH), 134.8 (Cq), 179.6 (CH); HRMS (ESI) m/z calcd for C14H10ClNNaO [M+Na]+ 266.0349,
found 266.0355.
1-[3-(4-Acetylphenyl)-2-propynyl]-2-formylpyrrole (1g): Thin yellow needles; mp 69.6–70.8 °C
(recrystallized from AcOEt-hexane); IR (KBr) 3010, 2824, 2387, 2359, 1683, 1661, 1404, 838, 748 cm–1;
1H-NMR (400 MHz, CDCl3) δ 2.60 (3H, s), 5.46 (2H, s), 6.32 (1H, dd, J = 2.0 and 4.0 Hz), 6.99 (1H, dd,
J = 1.6 and 4.0 Hz), 7.30–7.32 (1H, m), 7.51–7.54 (2H, m), 7.89–7.92 (2H, m), 9.60 (1H, d, J = 1.2 Hz);
13C-NMR (100MHz, CDCl3) δ 26.6 (CH3), 38.8 (CH2), 85.0 (Cq), 86.1 (Cq), 110.2 (CH), 124.9 (CH),
127.0 (Cq), 128.2 (CH), 130.4 (CH), 131.1 (Cq), 131.9 (CH), 136.7 (Cq), 179.6 (CH), 197.2 (Cq); HRMS
(ESI) m/z calcd for C16H13NNaO2 [M+Na]+ 274.0844, found 274.0844.
1-[3-(4-Cyanophenyl)-2-propynyl]-2-formylpyrrole (1h): Colorless needles; mp 126.3–128.6 °C
1
(recrystallized from AcOEt-hexane); IR (KBr) 2816, 2225, 1651, 1335, 840 cm–1; H-NMR (400 MHz,
CDCl3) δ 5.46 (2H, s), 6.32 (1H, dd, J = 2.4 and 4.0 Hz), 6.99 (1H, dd, J = 2.0 and 4.0 Hz), 7.25–7.27
(1H, m), 7.51–7.53 (2H, m), 7.60–7.62 (2H, m), 9.59 (1H, d, J = 0.8 Hz); 13C-NMR (100MHz, CDCl3) δ
38.7 (CH2), 84.0 (Cq), 87.4 (Cq), 110.3 (CH), 112.2 (Cq), 118.2 (Cq), 124.9 (CH), 127.1 (Cq), 130.4
(CH),131.1 (Cq), 132.0 (CH), 132.3 (CH), 179.6 (CH); HRMS (ESI) m/z calcd for C15H11N2O [M+H]+
235.0871, found 235.0865.
1-[3-(4-Methoxycarbonylphenyl)-2-propynyl]-2-formylpyrrole (1i): Colorless needles; mp
102.4–103.5 °C (recrystallized from AcOEt-hexane); IR (KBr) 2952, 2360, 1721, 1661, 1405, 1277, 1108,
1
786 cm–1; H-NMR (400 MHz, CDCl3) δ 3.92 (3H, s), 5.46 (2H, s), 6.31 (1H, dd, J = 2.8 and 4.0 Hz),
6.99 (1H, dd, J = 2.0 and 4.0 Hz), 7.31–7.33 (1H, m), 7.49–7.52 (2H, m), 7.97–8.00 (2H, m), 9.59 (1H, d,
13
J = 0.8 Hz); C-NMR (100MHz, CDCl3) δ 38.8 (CH2), 52.1 (CH3), 85.0 (Cq), 85.8 (Cq), 110.1 (CH),
124.8 (CH), 126.7 (Cq), 129.4 (CH), 129.9 (Cq), 130.3 (CH), 131.1 (Cq), 131.6 (CH), 166.2 (Cq), 179.5
(CH); HRMS (ESI) m/z calcd for C16H13NNaO3 [M+Na]+ 290.0793, found 290.0800.
General Procedure for Platinum–Catalyzed Hydration of 1: To a stirred solution of 1b (50.0mg, 0.24
mmol) in dioxane/H2O (2:1, 2 mL) was added PtCl2 (6.4 mg, 0.024 mmol) at rt. After stirring was
continued for 30 min at 100 °C, the resulting mixture was cooled to rt and diluted with minimum amount
of Et2O. The solution was dried over anhydrous MgSO4 and filtered through a small amount of silica gel.

HETEROCYCLES, Vol. 86, No. 1, 2012
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Concentration at reduced pressure gave the residue, which was chromatographed on silica gel with
hexane-AcOEt (90/10 v/v) as eluent to give 2b (44.5 mg, 82%) as a colorless solid and 3b (6.7 mg, 12%)
as a colorless solid.
1-(2-Oxopropyl)-2-formylpyrrole (2a): Yield 77%; colorless needles; mp 59.0–61.0 °C (recrystallized
1
from AcOEt-hexane); IR (KBr) 1731, 1659, 1482, 1406, 762 cm–1; H-NMR (400 MHz, CDCl3) δ 2.23
(3H, s), 5.10 (2H, s), 6.32 (1H, dd, J = 2.4 and 4.4 Hz), 6.85–6.87 (1H, m), 7.00 (1H, dd, J = 2.0 and 4.4
Hz), 9.50 (1H, d, J = 1.2 Hz); 13C-NMR (100MHz, CDCl3) δ 26.9 (CH3), 57.9 (CH2), 110.2 (CH), 124.6
(CH), 131.4 (Cq), 132.1 (CH), 179.7 (CH), 201.6 (Cq); HRMS (ESI) m/z calcd for C8H9NNaO2 [M+Na]+
174.0531, found 174.0526.
1-(3-Phenyl-2-oxopropyl)-2-formylpyrrole (2b): Yield 82%; colorless needles; mp 66.6–69.4 °C
1
(recrystallized from AcOEt-hexane); IR (KBr) 2929, 2807, 1734, 1659, 1405, 759 cm–1; H-NMR (400
MHz, CDCl3) δ 3.85 (2H, s), 5.09 (2H, s), 6.28 (1H, dd, J = 2.4 and 4.4 Hz), 6.77–6.79 (1H, m), 6.99 (1H,
13
dd, J = 2.0 and 4.4 Hz), 7.25–7.31 (3H, m), 7.34–7.38 (2H, m), 9.49 (1H, d, J = 1.2 Hz); C-NMR
(100MHz, CDCl3) δ 47.4 (CH2), 57.0 (CH2), 110.2 (CH), 124.6 (CH), 127.3 (CH), 128.8 (CH), 129.6
(CH), 131.4 (Cq), 132.2 (CH), 133.0 (Cq), 179.7 (CH), 201.3 (Cq); HRMS (ESI) m/z calcd for
C14H14NO2 [M+H]+ 228.1025, found 228.1026.
1-(3-Phenyl-3-oxopropyl)-2-formylpyrrole (3b): Yield 12%; colorless plates; mp 55.7–57.4 °C
1
(recrystallized from AcOEt-hexane); IR (KBr) 2923, 2360, 1684, 1660, 1404, 743 cm–1; H-NMR (400
MHz, CDCl3) δ 3.50 (2H, t, J = 6.4 Hz), 4.73 (2H, t, J = 6.4 Hz), 6.19 (1H, dd, J = 2.4 and 4.0 Hz), 6.94
(1H, dd, J = 2.0 and 4.0 Hz), 7.14–7.16 (1H, m), 7.42–7.46 (2H, m), 7.54–7.58 (1H, m), 7.92–7.95 (2H,
13
m), 9.54 (1H, d, J = 1.2 Hz); C-NMR (100MHz, CDCl3) δ 39.7 (CH2), 44.2 (CH2), 109.6 (CH), 125.3
(CH), 128.1 (CH), 128.6 (CH), 131.1 (Cq), 132.9 (CH), 133.4 (CH), 136.5 (Cq), 179.2 (CH), 197.7 (Cq);
HRMS (ESI) m/z calcd for C14H13NNaO2 [M+Na]+ 250.0844, found 250.0833.
1-[3-(4-Methylphenyl)-2-oxopropyl]-2-formylpyrrole (2c): Yield 52%; colorless needles; mp
69.9–70.8 °C (recrystallized from AcOEt-hexane); IR (KBr) 2929, 2820, 1733, 1659, 1405, 764 cm–1;
1H-NMR (400 MHz, CDCl3) δ 2.34 (3H, s), 3.80 (2H, s), 5.08 (2H, s), 6.27 (1H, dd, J = 2.4 and 4.0 Hz),
6.76–6.78 (1H, m), 6.98 (1H, dd, J = 1.6 and 4.0 Hz), 7.13–7.16 (4H, m), 9.49 (1H, d, J = 0.8 Hz);
13C-NMR (100MHz, CDCl3) δ 21.0 (CH3), 47.0 (CH2), 56.9 (CH2), 110.1 (CH), 124.6 (CH), 129.4 (CH),
129.5 (CH), 129.9 (Cq), 131.4 (Cq), 132.2 (CH), 137.0 (Cq), 179.7 (CH), 201.6 (Cq); HRMS (ESI) m/z
calcd for C15H15NNaO2 [M+Na]+ 264.1000, found 264.0996.
1-[3-(4-Methylphenyl)-3-oxopropyl]-2-formylpyrrole (3c): Yield 25%; colorless needles; mp
1
40.5–42.7 °C (recrystallized from AcOEt-hexane); IR (KBr) 2922, 1660, 1404, 815, 759 cm–1; H-NMR
(400 MHz, CDCl3) δ 2.39 (3H, s), 3.46 (2H, t, J = 6.4 Hz), 4.71 (2H, t, J = 6.4 Hz), 6.19 (1H, dd, J = 2.4
and 4.0 Hz), 6.93 (1H, dd, J = 2.0 and 4.0 Hz), 7.13–7.15 (1H, m), 7.22–7.24 (2H, m), 7.82–7.84 (2H, m),

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9.54 (1H, d, J = 1.2 Hz); 13C-NMR (100MHz, CDCl3) δ 21.6 (CH3), 39.6 (CH2), 44.3 (CH2), 109.5 (CH),
125.3 (CH), 128.2 (CH), 129.3 (CH), 131.1 (Cq), 132.9 (CH), 134.1 (Cq), 144.2 (Cq), 179.2 (CH), 197.3
(Cq); HRMS (ESI) m/z calcd for C15H16NO2 [M+H]+ 242.1181, found 242.1180.
1-[3-(4-Methoxyphenyl)-2-oxopropyl]-2-formylpyrrole (2d): Yield 33%; colorless needles; mp
72.6–73.7 °C (recrystallized from AcOEt-hexane); IR (KBr) 2930, 2845, 1732, 1653, 1246, 1030, 831,
1
763 cm–1; H-NMR (400 MHz, CDCl3) δ 3.78 (2H, s), 3.80 (3H, s), 5.08 (2H, s), 6.28 (1H, dd, J = 2.4
and 4.0 Hz), 6.77–6.79 (1H, m), 6.87–6.90 (2H, m), 6.98 (1H, dd, J = 1.6 and 4.0 Hz), 7.15–7.18 (2H, m),
9.49 (1H, d, J = 1.2 Hz); 13C-NMR (100MHz, CDCl3) δ 46.5 (CH2), 55.3 (CH3), 56.9 (CH2), 110.2 (CH),
114.3 (CH), 124.6 (CH), 125.0 (Cq), 130.6 (CH), 131.4 (Cq), 132.2 (CH), 158.9 (Cq), 179.7 (CH), 201.7
(Cq); HRMS (ESI) m/z calcd for C15H15NNaO3 [M+Na]+ 280.0950, found 280.0951.
1-[3-(4-Methoxyphenyl)-3-oxopropyl]-2-formylpyrrole (3d): Yield 26%; colorless needles; mp
71.1–72.6 °C (recrystallized from AcOEt-hexane); IR (KBr) 2966, 2926, 2852, 2816, 1660, 1600, 1256,
1170, 836, 761 cm–1; 1H-NMR (400 MHz, CDCl3) δ 3.43 (2H, t, J = 6.4 Hz), 3.86 (3H, s), 4.71 (2H, t, J =
6.4 Hz), 6.19 (1H, dd, J = 2.4 and 4.0 Hz), 6.89–6.92 (2H, m), 6.93 (1H, dd, J = 2.0 and 4.0 Hz),
13
7.13–7.15 (1H, m), 7.90–7.93 (2H, m), 9.54 (1H, d, J = 0.8 Hz); C-NMR (100MHz, CDCl3) δ 39.4
(CH2), 44.4 (CH2), 55.4 (CH3), 109.5 (CH), 113.8 (CH), 125.3 (CH), 129.7 (Cq), 130.4 (CH), 131.1 (Cq),
132.9 (CH), 163.7 (Cq), 179.2 (CH), 196.2 (Cq); HRMS (ESI) m/z calcd for C15H15NNaO3 [M+Na]+
280.0950, found 280.0950.
1-[3-(4-Fluorophenyl)-2-oxopropyl]-2-formylpyrrole (2e): Yield 66%: colorless needles; mp
63.8–65.6 °C (recrystallized from AcOEt-hexane); IR (KBr) 2931, 2809, 1735, 1659, 1407, 1223, 836,
1
765 cm–1; H-NMR (400 MHz, CDCl3) δ 3.82 (2H, s), 5.09 (2H, s), 6.29 (1H, dd, J = 2.4 and 4.0 Hz),
6.80–6.82 (1H, m), 7.00 (1H, dd, J = 1.6 and 4.0 Hz), 7.01–7.06 (2H, m), 7.19–7.23 (2H, m), 9.49 (1H, d,
13
J = 0.8 Hz); C-NMR (100MHz, CDCl3) δ 46.1 (CH2), 57.1 (CH2), 110.2 (CH), 115.6 (CH, d, J = 21.5
Hz), 124.6 (CH), 128.6 (Cq, d, J = 3.3 Hz), 131.2 (CH, d, J = 7.4 Hz), 131.3 (Cq), 132.2 (CH), 162.1 (Cq,
d, J = 244.6 Hz), 179.7 (CH), 201.1 (Cq); HRMS (ESI) m/z calcd for C14H13FNO2 [M+H]+ 246.0930,
found 246.0922.
1-[3-(4-Fluorophenyl)-3-oxopropyl]-2-formylpyrrole (3e): Yield 11%; colorless needles; mp
125.7–126.8 °C (recrystallized from AcOEt-hexane); IR (KBr) 2893, 2849, 1677, 1656, 1404, 1373, 852,
764 cm–1; 1H-NMR (400 MHz, CDCl3) δ 3.46 (2H, t, J = 6.4 Hz), 4.71 (2H, t, J = 6.4 Hz), 6.20 (1H, dd, J
= 2.4 and 3.6 Hz), 6.94 (1H, dd, J = 2.0 and 3.6 Hz), 7.09–7.13 (3H, m), 7.95–7.98 (2H, m), 9.54 (1H, d,
13
J = 0.8 Hz); C-NMR (100MHz, CDCl3) δ 39.7 (CH2), 44.3 (CH2), 109.6 (CH), 115.8 (CH, d, J = 22.3
Hz), 125.4 (CH), 130.7 (CH, d, J = 9.0 Hz), 131.1 (Cq), 132.9 (CH), 133.0 (Cq, d, J = 3.3 Hz), 165.9 (Cq,
d, J = 254.4 Hz), 179.3 (CH), 196.1 (Cq); HRMS (ESI) m/z calcd for C14H13FNO2 [M+H]+ 246.0930,
found 246.0930.

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1-[3-(4-Chlorophenyl)-2-oxopropyl]-2-formylpyrrole (2f): Yield 51%; colorless needles; mp
84.5–87.3 °C (recrystallized from AcOEt-hexane); IR (KBr) 2927, 2807, 1734, 1656, 1492, 1481, 1323,
1
1092, 1066, 801, 760 cm–1; H-NMR (400 MHz, CDCl3) δ 3.81 (2H, s), 5.09 (2H, s), 6.30 (1H, dd, J =
2.8 and 4.4 Hz), 6.80–6.82 (1H, m), 7.00 (1H, dd, J = 2.0 and 4.4 Hz), 7.16–7.19 (2H, m), 7.31–7.33 (2H,
13
m), 9.49 (1H, d, J = 0.8 Hz); C-NMR (100MHz, CDCl3) δ 46.3 (CH2), 57.1 (CH2), 110.3 (CH), 124.7
(CH), 128.9 (CH), 131.0 (CH), 131.3 (Cq), 131.4 (Cq), 132.2 (CH), 133.3 (Cq), 179.8 (CH), 200.8 (Cq);
HRMS (ESI) m/z calcd for C14H13ClNO2 [M+H]+ 262.0635, found 262.0623.
1-[3-(4-Chlorophenyl)-3-oxopropyl]-2-formylpyrrole (3f): Yield 13%; colorless needles; mp
110.9–113.5 °C (recrystallized from AcOEt-hexane); IR (KBr) 2961, 2915, 1687, 1660, 1588, 1259, 1089,
1
1029, 801, 756 cm–1; H-NMR (400 MHz, CDCl3) δ 3.46 (2H, t, J = 6.4 Hz), 4.70 (2H, t, J = 6.4 Hz),
6.20 (1H, dd, J = 2.8 and 4.0 Hz), 6.94 (1H, dd, J = 2.0 and 4.0 Hz), 7.12–7.14 (1H, m), 7.40–7.43 (2H,
m), 7.85–7.89 (2H, m), 9.54 (1H, d, J = 0.8 Hz); 13C-NMR (100MHz, CDCl3) δ 39.7 (CH2), 44.2 (CH2),
109.7 (CH), 125.4 (CH), 129.0 (CH), 129.5 (CH), 131.1 (Cq), 132.9 (CH), 134.9 (Cq), 139.9 (Cq), 179.3
(CH), 196.5 (Cq); HRMS (ESI) m/z calcd for C14H13ClNO2 [M+H]+ 262.0635, found 262.0624.
1-[3-(4-Acetylphenyl)-2-oxopropyl]-2-formylpyrrole (2g): Yield 28%; colorless needles; mp
90.3–93.0 °C (recrystallized from AcOEt-hexane); IR (KBr) 1735, 1681, 1656, 1407, 1268, 761 cm–1;
1H-NMR (400 MHz, CDCl3) δ 2.60 (3H, s), 3.91 (2H, s), 5.11 (2H, s), 6.30 (1H, dd, J = 2.4 and 4.0 Hz),
6.81–6.83 (1H, m), 7.01 (1H, dd, J = 2.0 and 4.0 Hz), 7.33–7.35 (2H, m), 7.92–7.95 (2H, m), 9.50 (1H, d,
J = 1.2 Hz); 13C-NMR (100MHz, CDCl3) δ 26.6 (CH3), 46.8 (CH2), 57.3 (CH2), 110.3 (CH), 124.7 (CH),
128.7 (CH), 129.9 (CH), 131.4 (Cq), 132.2 (CH), 136.2 (Cq), 138.3 (Cq), 179.8 (CH), 197.6 (Cq), 200.4
(Cq); HRMS (ESI) m/z calcd for C16H15NNaO3 [M+Na]+ 292.0950, found 292.0942.
1-[3-(4-Acetylphenyl)-3-oxopropyl]-2-formylpyrrole (3g): Yield 9%; colorless needles; mp
75.0–77.6 °C (recrystallized from AcOEt-hexane); IR (KBr) 1684, 1658, 1403, 1263, 792 cm–1; 1H-NMR
(400 MHz, CDCl3) δ 2.63 (3H, s), 3.52 (2H, t, J = 6.4 Hz), 4.72 (2H, t, J = 6.4 Hz), 6.21 (1H, dd, J = 2.4
and 4.0 Hz), 6.95 (1H, dd, J = 2.0 and 4.0 Hz), 7.13–7.15 (1H, m), 8.01 (4H, s), 9.54 (1H, d, J = 1.2 Hz);
13C-NMR (100MHz, CDCl3) δ 26.8 (CH3), 40.1 (CH2), 44.2 (CH2), 109.7 (CH), 125.4 (CH), 128.3 (CH),
128.5 (CH), 131.2 (Cq), 132.9 (CH), 139.6 (Cq), 140.4 (Cq), 179.3 (CH), 197.2 (Cq), 197.3 (Cq); HRMS
(ESI) m/z calcd for C16H15NNaO3 [M+Na]+ 292.0950, found 292.0950.
1-[3-(4-Cyanophenyl)-2-oxopropyl]-2-formylpyrrole (2h): Yield 28%; brown needles; mp
157.3–159.8 °C (recrystallized from AcOEt-hexane); IR (KBr) 2981, 2847, 2227, 1714, 1646, 1477, 839
1
cm–1; H-NMR (400 MHz, CDCl3) δ 3.92 (2H, s), 5.12 (2H, s), 6.32 (1H, dd, J = 2.4 and 4.0 Hz),
6.84–6.86 (1H, m), 7.02 (1H, dd, J = 2.0 and 4.0 Hz), 7.33–7.35 (2H, m), 7.62–7.64 (2H, m), 9.49 (1H, d,
J = 1.2 Hz); 13C-NMR (100MHz, CDCl3) δ 46.5 (CH2), 57.4 (CH2), 110.4 (CH), 111.3 (Cq), 118.6 (Cq),
124.8 (CH), 130.6 (CH), 131.3 (Cq), 132.2 (CH), 132.3 (CH), 138.3 (Cq), 179.8 (CH), 199.9 (Cq);

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HETEROCYCLES, Vol. 86, No. 1, 2012
HRMS (ESI) m/z calcd for C15H13N2O2 [M+H]+ 253.0977, found 253.0985.
1-[3-(4-Cyanophenyl)-3-oxopropyl]-2-formylpyrrole (3h): Yield 6%; colorless needles; mp
123.9–125.8 °C (recrystallized from AcOEt-hexane); IR (KBr) 3095, 2922, 2225, 1687, 1650, 1402, 765
cm–1; 1H-NMR (400 MHz, CDCl3) δ 3.51 (2H, t, J = 6.4 Hz), 4.71 (2H, t, J = 6.4 Hz), 6.21 (1H, dd, J =
2.4 and 4.0 Hz), 6.96 (1H, dd, J = 2.0 and 4.0 Hz), 7.11–7.13 (1H, m), 7.74–7.76 (2H, m), 8.01–8.03 (2H,
13
m), 9.54 (1H, d, J = 1.2 Hz); C-NMR (100MHz, CDCl3) δ 40.1 (CH2), 44.1 (CH2), 109.8 (CH), 116.8
(Cq), 117.8 (Cq), 125.5 (CH), 128.5 (CH), 131.2 (Cq), 132.6 (CH), 132.9 (CH), 139.4 (Cq), 179.4 (CH),
196.5 (Cq); HRMS (ESI) m/z calcd for C15H13N2O2 [M+H]+ 253.0977, found 253.0981.
1-[3-(4-Methoxycarbonylphenyl)-2-oxopropyl]-2-formylpyrrole (2i): Yield 63%; colorless needles;
mp 117.6–118.4 °C (recrystallized from AcOEt-hexane); IR (KBr) 2942, 1722, 1656, 1285, 851, 761, 746
cm–1; 1H-NMR (400 MHz, CDCl3) δ 3.90 (2H, s), 3.91 (3H, s), 5.10 (2H, s), 6.29 (1H, dd, J = 2.4 and 4.0
Hz), 6.79–6.81 (1H, m), 7.00 (1H, dd, J = 1.6 and 4.0 Hz), 7.30–7.32 (2H, m), 8.00–8.02 (2H, m), 9.50
13
(1H, d, J = 1.2 Hz); C-NMR (100MHz, CDCl3) δ 46.9 (CH2), 52.0 (CH3), 57.2 (CH2), 110.3 (CH),
124.7 (CH), 129.2 (Cq), 129.7 (CH), 129.9 (CH), 131.3 (Cq), 132.2 (CH), 138.1 (Cq), 166.7 (Cq), 179.7
(CH), 200.3 (Cq); HRMS (ESI) m/z calcd for C16H16NO4 [M+H]+ 286.1079, found 286.1083.
1-[3-(4-Methoxycarbonylphenyl)-3-oxopropyl]-2-formylpyrrole (3i): Yield 11%; colorless needles;
mp 94.1–95.8 °C (recrystallized from AcOEt-hexane); IR (KBr) 1720, 1682, 1657, 1404, 1280, 749 cm–1;
1H-NMR (400 MHz, CDCl3) δ 3.52 (2H, t, J = 6.4 Hz), 3.94 (3H, s), 4.72 (2H, t, J = 6.4 Hz), 6.20 (1H,
dd, J = 2.0 and 4.0 Hz), 6.95 (1H, dd, J = 2.0 and 4.0 Hz), 7.12–7.14 (1H, m), 7.96–7.98 (2H, m),
8.08–8.11 (2H, m), 9.54 (1H, d, J = 0.8 Hz); 13C-NMR (100MHz, CDCl3) δ 40.1 (CH2), 44.1 (CH2), 52.4
(CH3), 109.7 (CH), 125.4 (CH), 128.0 (CH), 129.9 (CH), 131.1 (Cq), 132.9 (CH), 134.2 (Cq), 139.6 (Cq),
166.1 (Cq), 179.3 (CH), 197.3 (Cq); HRMS (ESI) m/z calcd for C16H16NO4 [M+H]+ 286.1079, found
286.1082.
1
1-(2-Oxopropyl)-1H-pyrrole (7): Brown oil; IR (neat) 2925, 2854, 1732, 1463, 1377 cm–1; H-NMR
(400 MHz, CDCl3) δ 2.06 (3H, s), 4.61 (2H, s), 6.24 (2H, t, J = 2.0 Hz), 6.61 (2H, t, J = 2.0 Hz);
13C-NMR (100MHz, CDCl3) δ 26.3 (CH3), 59.1 (CH2), 109.5 (CH), 121.6 (CH), 204.1 (Cq); HRMS
(ESI) m/z calcd for C7H9NONa [M+Na]+ 146.0582, found 146.0587.
1-(2-Propynyl)-2-vinyl-1H-pyrrole (8): According to the same procedure described for the synthesis of
1d, 8 was prepared from 2-vinylpyrrole with propargyl bromide. Yellow oil; IR (neat) 2925, 2853, 2360,
1457 cm–1; 1H-NMR (400 MHz, CDCl3) δ 2.40 (1H, t, J = 2.4 Hz), 4.67 (2H, d, J = 2.4 Hz), 5.10 (1H, dd,
J = 1.6 and 11.2 Hz), 5.52 (1H, dd, J = 1.2 and 17.2 Hz), 6.14 (1H, t, J = 3.2 Hz), 6.39 (1H, dd, J = 2.0
and 4.0 Hz), 6.64 (1H, dd, J = 11.2 and 17.2 Hz), 6.75–6.76 (1H, m); 13C-NMR (100MHz, CDCl3) δ 36.4
(CH2), 73.5 (Cq), 78.1 (CH), 107.3 (CH), 108.6 (CH), 112.0 (CH2), 122.0 (CH), 125.0 (CH), 131.6 (Cq);
HRMS (ESI) m/z calcd for C9H9NNa [M+Na]+ 154.0633, found 154.0629.

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ACKNOWLEDGEMENT
This study was supported in part by a Grant-in-Aid for the Encouragement of Young Scientists (B) from
the Japan Society for the Promotion of Science (JSPS).
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