An efficient method for the synthesis of 3-arylpyrroles

Full text of DOI:10.1021/jo961981u

J . Org. Chem. 1997, 62, 2649-2651
2649
Sch em e 1
An Efficien t Meth od for th e Syn th esis of
3-Ar ylp yr r oles
Neville P. Pavri and Mark L. Trudell*,†
Department of Chemistry, University of New Orleans,
New Orleans, Louisiana 70148
Received October 22, 1996
The introduction of substituents in the 3â-position of
pyrroles is of great importance as intermediates in the
synthesis of natural products and conducting polymers.1,2
It is well-known that pyrroles have a propensity to
undergo kinetic electrophilic substitution reactions pre-
dominantly at the 2-position.3 However, the 3-substi-
tuted pyrroles are less accessible. The 3-substituted
pyrroles have been previously prepared by (a) ring closure
reactions,4,5 (b) metal-catalyzed reactions,6,7 (c) utilization
of a removable deactivating substituent at the 2-position
(usually acyl) to direct entry of an electrophile to the 4â-
position,8 (d) acid-mediated isomerization of 2-substituted
isomers,9 (e) Lewis acid-catalyzed reactions of acylating
agents with 1-(benzenesulfonyl)pyrrole,10 and (f) use of
a sterically bulky N-substituent to obstruct electrophilic
attack at the 2-position.11 However, some of these
methods are somewhat limited to the electrophilic sub-
stitution of an acyl group. Herein we report an expedi-
tious method for the synthesis of a series of 3-aryl-
substituted pyrroles in good overall yields.
As illustrated in Scheme 1, the 3-arylpyrroles were
prepared in a short reaction sequence from the readily
available aryl aldehydes 1. The aldehydes 1 were
converted into the corresponding methyl 3-arylacrylate
esters 2 using a Masamune-Rousch or a Wadsworth-
Emmons (2f and 2h ) olefination procedure.12,13 Under
both of these reaction conditions, 3-indolecarboxaldehyde
was unreactive. However, the N-benzyl derivative 1h
reacted smoothly under Wadsworth-Emmons reaction
conditions to afford 2h in 80% yield.
with TosMIC afforded the 4-aryl-3-(methoxycarbonyl)-
pyrroles 3 in good yields (Scheme 1, Table 1). Electron
neutral or electron-deactivated aryl vinyl esters could be
successfully employed in the cyclization reaction. How-
ever, the TosMIC addition reaction with 2 which pos-
sessed electron-rich substituents on the aryl ring (i.e.,
Ar ) p-CH3OC6H5) did not yield the desired pyrroles, but
rather gave intractable mixtures. The disubstituted
pyrrole derivatives 3 were found to be air-stable easily
handled solids.
Initially, attempts were made to remove the 3-meth-
oxycarbonyl ester moiety in a single step. However,
treatment of the 3,4-disubstituted pyrroles under strong
acidic conditions (H2SO4, PTSA, CF3CO2H) at elevated
temperatures resulted in the decomposition of many of
the heteroaromatic substituents and incomplete conver-
sion.15 Therefore as an alternative approach the ester
moieties were hydrolyzed to the carboxylic acids with
excess KOH in 50% MeOH. The acid derivatives were
then decarboxylated by heating in 2-ethanolamine to give
the 3-substituted pyrroles 4 in good yield (Table 1).16
Several of the pyrrole derivatives (4c-e, g) were found
to decompose slowly in the presence of air. As a result,
these analogs were protected immediately upon isolation
as the corresponding methyl carbamates 5c,d ,g. The
chloropyridyl derivative 4e was protected as the tert-butyl
carbamate 5e. This afforded air-stable solid compounds
which were easily characterized and could be stored over
extended periods.
The method described above extends the methodology
developed by van Leusen et al.14 and is believed to be a
very facile approach for the preparation of 3-arylpyrrole
derivatives not readily available by other synthetic
methods. In addition, this methodology has the advan-
tage that it employs readily available precursors and is
tolerant of a wide variety of aryl and heteroaryl systems.
The yields obtained by this method are superior to those
reported by previous methods.5 For example, a recent
report describes the synthesis of 4a from benzaldehyde
in five steps and 37% overall yield, while the new method
described above afforded 4a in four steps and 52% overall
yield. In summary, this new synthetic method allows for
the efficient preapartion of 3-arylpyrroles in good overal
yield and represents a dramatic improvement over exist-
ing methodology.
The pyrrole ring system was generated by the proce-
dure developed by van Leusen et al.14 Treatment of 2
† Address correspondence to this author at Department of Chem-
istry, University of New Orleans, New Orleans, LA 70148. Tel: (504)
280-7337. FAX: (504) 280-6860. E-mail: MLTCM@UNO.EDU.
(1) Sundberg, R. J . In Comprehensive Heterocyclic Chemstry; Bird,
C. W., Cheesman, G. W. H., Eds.; Pergamon Press: Oxford, 1984; Vol.
4, p 313 and references cited therein.
(2) (a) Collard, D. M.; Fox, M. A. J . Am. Chem. Soc. 1991, 113, 9415.
(b) Andrieux, C. P.; Audebert, P.; Hapiot, P.; Saveant, J . M. J . Am.
Chem. Soc. 1990, 112, 2439.
(3) J ones, R. A.; Bean, G. P. In The Chemistry of Pyrroles; Academic
Press: London, 1977; references cited therein.
(4) Babler, J . H.; Spina, K. P. Tetrahedron Lett. 1984, 25, 1659.
(5) Me´ndez, J . M.; Flores, B.; Leo´n, F.; Mart´ınez, M. E.; Va´zquez,
A.; Garcia, G. A.; Salmo´n, M. Tetrahedron Lett. 1996, 37, 4099.
(6) Campi, E. M.; J ackson, R.; Nilsson, Y. Tetrahedron Lett. 1991,
32, 1093.
(7) Dragisich, V.; Murray, C. K.; Klarner, B. P.; Wulff, W. D.; Yang,
D. C. J . Am. Chem. Soc. 1990, 112, 1251.
(8) Loader, C. E.; Anderson, H. J . Can. J . Chem. 1981, 59, 2673.
(9) DeSales, J .; Greenhouse, R.; Muchowski, J . M. J . Org. Chem.
1982, 47, 3668.
(10) Kakushimi, M.; Hamel, P.; Frenette, R.; Rokach, J . J . Org.
Chem. 1983, 48, 3214.
(11) Bray, B. L.; Matheis, P. H.; Naef, R.; Solas, D. R.; Tidwell, T.
T.; Artis, D. R.; Muchowski, J . M. J . Org. Chem. 1990, 55, 6317.
(12) Blanchette, M. A.; Choy, W.; Davis, J . T.; Essenfeld, A. P.;
Masamune, S.; Rousch, W. R.; Sakai, T. Tetrahedron Lett. 1984, 25,
2183.
(13) For a recent review of phosphoryl-stabilized olefination reac-
tions, see: Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863.
(14) van Leusen, A. M.; Siderius, H.; Hoogenboom, B. E.; van
Leusen, D. Tetrahedron Lett. 1972, 5337.
(15) J ackson, A. H. In Pyrroles; J ones, R. A., Ed.; J ohn Wiley and
Sons: New York, 1990; p 305 and references cited therein.
(16) Cue, B. W., J r.; Chamberlain, N. J . Heterocycl. Chem. 1981,
18, 667.
S0022-3263(96)01981-0 CCC: $14.00 © 1997 American Chemical Society

2650 J . Org. Chem., Vol. 62, No. 8, 1997
Notes
Ta ble 1. Syn th esis of 3-Ar ylp yr r ole Der iva tives
and then the methyl chloroformate (1 mmol) was added. The
mixture was stirred overnight, diluted with water, and extracted
with ether (3 × 50 mL) or CH2Cl2 (3 × 50 mL). The solvent
was dried (Na2SO4) and concentrated under reduced pressure.
The residue was purified by column chromatography.
3-(Meth oxyca r bon yl)-4-p h en ylp yr r ole (3a ). Method A
with 2a afforded pale yellow crystals (0.71 g, 70%): mp 181-
182 °C (MeOH) [lit.14 mp 182-183 °C]; 1H NMR (CDCl3) δ 8.45
(br s, 1H), 7.50-7.26 (m, 6H), 6.79 (s, 1H), 3.73 (s, 3H); 13C NMR
(CDCl3) δ 164.1, 134.7, 129.2, 129.0, 127.3, 126.9, 125.8, 119.3,
117.5, 51.6.
3-(Meth oxycar bon yl)-4-(2-n aph th yl)pyr r ole (3b). Method
A with 2b after column chromatography (SiO2, Et2O/hexane, 1:1)
1
afforded a white solid (0.76 g, 60%): mp 199-202 °C; H NMR
(acetone-d6) δ 10.75 (br s, 1H), 8.01 (s, 1H), 7.88-7.81 (m, 3H),
7.69 (d, J ) 3.0 Hz, 1H), 7.59 (s, 1H), 7.47-7.44 (m, 2H), 7.08
(s, 1H), 3.68 (s, 3H); 13C NMR (acetone-d6) δ 165.4, 134.3, 134.0,
133.1, 129.3, 128.6, 128.2, 127.6, 127.4, 126.8, 126.7, 126.5, 126.0,
120.1, 113.6, 50.8. Anal. Calcd for C16H13NO2: C, 76.41; H, 5.21;
N, 5.57. Found: C, 76.08; H, 5.35; N, 5.63.
3-(Met h oxyca r b on yl)-4-(4-m et h ylp h en yl)p yr r ole (3c).
Method A with 2c after column chromatography (SiO2, Et2O/
hexane, 2:1) afforded white crystals (0.69 g, 64%): mp 156-159
°C; 1H NMR (acetone-d6) δ 10.67 (br s, 1H), 7.50 (s, 1H), 7.39 (d,
J ) 7.5 Hz, 2H), 7.11 (d, J ) 7.8 Hz, 2H), 6.89 (s, 1H), 3.64 (s,
3H), 2.31 (s, 3H); 13C NMR (acetone-d6) δ 165.2, 135.8, 133.2,
129.6, 128.8, 126.7, 126.4, 119.3, 113.2, 50.7, 20.9. Anal. Calcd
for C13H13NO2: C, 72.53; H, 6.08; N, 6.52. Found: C, 72.53; H,
6.07; N, 6.49.
4-(4-Ch lor op h en yl)-3-(m et h oxyca r b on yl)p yr r ole (3d ).
Method A with 2d after column chromatography (SiO2, EtOAc/
hexane, 1:3) afforded white crystals (0.7 g, 60%): mp 171-173
°C. 1H NMR (acetone-d6) δ 10.81 (br s, 1H), 7.57-7.54 (m, 3H),
7.35 (d, J ) 6.0 Hz, 2H), 7.03 (s, 1H), 3.71 (s, 3H); 13C NMR
(acetone-d6) δ 165.3, 135.1, 132.0, 131.5, 128.3, 126.9, 125.5,
120.0, 113.3, 50.9. Anal. Calcd for C12H10ClNO2: C, 61.14; H,
4.27; N, 5.95. Found: C, 61.29; H, 4.33; N, 5.89.
4-[5-(2-Ch lor opyr idyl)]-3-(m eth oxycar bon yl)pyr r ole (3e).
Method A with 2e after column chromatography (SiO2, Et2O/
hexane, 6:1) afforded a white solid (0.81 g, 68%): mp 179-181
°C; 1H NMR (acetone-d6) δ 10.91 (br s, 1H), 8.53 (s, 1H), 8.01 (d,
J ) 8.0 Hz, 1H), 7.64 (s, 1H), 7.41 (d, J ) 8.0 Hz, 1H), 7.16 (s,
1H), 3.73 (s, 3H); 13C NMR (acetone-d6) δ 165.8, 150.7, 149.8,
141.1, 132.0, 127.9, 124.3, 122.3, 121.2, 114.1, 51.5. Anal. Calcd
for C11H9ClN2O2: C, 55.83; H, 3.83; N, 11.84. Found: C, 55.79;
H, 3.85; N, 11.77.
3-(Meth oxyca r bon yl)-4-(3-p yr id yl)p yr r ole (3f). Method
A with 2f after column chromatography (SiO2, EtOAc/hexane,
5:1) afforded a white solid (0.64 g, 64%): mp 154-157 °C; 1H
NMR (acetone-d6) δ 10.89 (br s, 1H), 8.69 (s, 1H), 8.43 (d, J )
4.7 Hz, 1H), 7.89 (d, J ) 7.5 Hz, 1H), 7.60 (s, 1H), 7.33-7.30
(m, 1H), 7.07 (s, 1H), 3.68 (s, 3H); 13C NMR (acetone-d6) 165.6,
149.6, 149.1, 141.4, 131.9, 127.2, 125.1, 121.9, 121.1, 113.8, 51.2.
Anal. Calcd for C11H10N2O2: C, 65.34; H, 4.98; N, 13.85.
Found: C, 65.30; H, 5.03; N, 13.75.
3-(Meth oxyca r bon yl)-4-(3-th ien yl)p yr r ole (3g). Method
A with 2g after column chromatography (SiO2, EtOAc/hexane,
1:2) afforded a pale yellow solid (0.62 g, 60%): mp 167-168 °C;
1H NMR (acetone-d6) δ 10.71 (br s, 1H), 7.81 (s, 1H), 7.54 (s,
1H), 7.41-7.36 (m, 2H), 7.13 (s, 1H), 3.72 (s, 3H); 13C NMR
(acetone-d6) δ 165.4, 136.1, 129.4, 126.8, 124.4, 121.6, 121.3,
119.5, 113.0, 50.7. Anal. Calcd for C10H9NO2S: C, 57.96; H,
4.38; N, 6.76. Found: C, 57.84; H, 4.38; N, 6.66.
Exp er im en ta l Section
All chemicals were purchased from Aldrich Chemical Co.,
Milwaukee, WI, unless otherwise noted. Ether (E. M. Science)
and THF were dried by distillation from Na/benzophenone.
Dimethyl sulfoxide was dried by vacuum distillation over CaH2.
Acetonitrile was dried by distillation over P2O5. Chromatogra-
phy refers to flash chromatography on silica gel (silica gel 60,
230-400 mesh, E. M. Science) and petroleum ether refers to
pentanes with a boiling point range of 30-60 °C. Reported
melting points are uncorrected. Elemental analyses were
obtained from Atlantic Microlab, Inc., Norcross, GA.
Meth od A. P r ep a r a tion of 3,4-Disu bstitu ted P yr r oles
3a -h . A solution of TosMIC (5.1 mmol) and R,â-unsaturated
ester (5.0 mmol) in a dry ether/DMSO (2:1) solution was added
dropwise under an N2 atmosphere to a stirred solution of NaH
(6.4 mmol) in ether. The mixture started to reflux due to the
exothermic reaction. After 1 h, water was carefully added to
the mixture and the aqueous phase was extracted with ether (1
× 50 mL) and CH2Cl2 (2 × 75 mL). The combined organic
extracts were dried (Na2SO4) and then concentrated under
reduced pressure. The residue was purified by column chro-
matography.
4-[3-(1-Ben zylin dolyl)]-3-(m eth oxycar bon yl)pyr r ole (3h ).
Method A with 2h after column chromatography (EtOAc/hexane,
1:2.5) afforded a tan solid (0.77 g, 48%): mp 117-119 °C; 1H
NMR (acetone-d6) δ 10.79 (br s, 1H), 7.89 (s, 1H), 7.77 (d, J )
3.0 Hz, 1H), 7.62 (s, 1H), 7.44-7.01 (m, 9H), 5.51 (s, 2H), 3.70
(s, 3H); 13C NMR (acetone-d6) δ 165.8, 139.7, 137.4, 130.1, 129.7,
129.2, 128.4, 128.2, 126.6, 122.2, 121.1, 120.2, 119.3, 114.0, 111.0,
110.2, 50.97, 50.68. Anal. Calcd for C21H18N2O2: C, 76.34; H,
5.49; N, 8.48. Found: C, 75.98; H, 5.61; N, 8.38.
3-P h en ylp yr r ole (4a ). Method B with 3a after column
chromatography (SiO2, Et2O/hexane, 1:1) afforded a pale yellow
oil (0.29 g, 82%) [lit.4 mp 41-42 °C]: 1H NMR (acetone-d6) δ
10.21 (br s, 1H), 7.55 (d, J ) 8.0 Hz, 1H), 7.30-7.08 (m, 5H),
6.83 (s, 1H), 6.49 (s, 1H); 13C NMR (acetone-d6) δ 137.5, 129.3,
125.7, 125.0, 119.7, 119.5, 115.5, 106.4.
Meth od B. P r ep a r a tion of 4a -h . The 3,4-disubstituted
pyrroles 3a -h (2.5 mmol) were refluxed for 2-3 h in a solution
of 50% MeOH containing an excess of KOH (25 mmol). Water
was added, and the mixture was acidified with 12 N HCl. The
precipitate was filtered. The filtrate was extracted with CH2-
Cl2 (2 × 25 mL) or Et2O (2 × 25 mL). The solvents were removed
under reduced pressure. The residue was then refluxed in
2-ethanolamine (freshly distilled) for 2 h. The reaction mixture
was cooled and poured into ice. The aqueous phase was
extracted with Et2O (3 × 50 mL) or CH2Cl2 (3 × 50 mL), dried
(Na2SO4), and concentrated under reduced pressure. The resi-
due was purified by column chromatography (SiO2).
Meth od C. P r ep a r a tion of Alk yl Ca r ba m a tes 5c,d ,g. To
a stirred solution of KH (2 mmol) in THF under N2 at 0 °C was
added the pyrrole (1 mmol). The solution was stirred for 45 min,

Notes
3-(2-Na p h th yl)p yr r ole (4b). Method B with 3b after col-
umn chromatography (SiO2, EtOAc/hexane, 1:1) afforded a white
solid (0.33 g, 67%): mp 92-94 °C; 1H NMR (acetone-d6) δ 10.24
(br s, 1H), 8.02 (s, 1H), 7.84-7.78 (m, 4H), 7.43-7.36 (m, 3H),
6.90 (s, 1H), 6.65 (s, 1H); 13C NMR (acetone-d6) δ 135.1, 135.0,
132.7, 132.6, 128.7, 128.3, 126.7, 125.3, 124.9, 122.5, 120.0, 116.2,
106.5. Anal. Calcd for C14H11N: C, 87.01; H, 5.74; N, 7.25.
Found: C, 86.77; H, 5.78; N, 7.22.
J . Org. Chem., Vol. 62, No. 8, 1997 2651
(acetone-d6) δ 10.12 (br s, 1H), 7.89 (d, J ) 3.0 Hz, 1H), 7.50 (s,
1H), 7.43-7.09 (m, 9H), 6.89 (s, 1H), 6.49 (s, 1H), 5.47 (s, 2H);
13C NMR (acetone-d6) δ 139.4, 137.7, 129.3, 128.1, 127.7, 125.1,
122.1, 120.9, 119.8, 118.7, 118.6, 114.8, 113.2, 110.6, 107.3, 50.2.
Anal. Calcd for C19H16N2: C, 83.79; H, 5.92; N, 10.29. Found:
C, 83.59; H, 6.08; N, 10.26.
1-(Met h oxyca r b on yl)-3-(4-m et h ylp h en yl)p yr r ole (5c).
Method C with 4c after column chromatography (SiO2, EtOAc/
hexane, 1:3) afforded a white solid (0.19 g, 88%): mp 76-78 °C;
1H NMR (acetone-d6) δ 7.59 (s, 1H), 7.49 (d, J ) 7.8 Hz, 2H),
7.31 (d, J ) 2.3 Hz, 1H), 7.15 (d, J ) 7.5 Hz, 2H), 6.65 (d, J )
1.5 Hz, 1H), 3.96 (s, 3H), 2.30 (s, 3H); 13C NMR (acetone-d6) δ
151.5, 137.1, 132.2, 130.3, 129.1, 126.2, 121.9, 116.2, 111.7, 54.7,
21.2. Anal. Calcd for C13H13NO2: C, 72.54; H, 6.09; N, 6.51.
Found: C, 72.60; H, 6.08; N, 6.40.
3-(4-Meth ylp h en yl)p yr r ole (4c). Method B with 3c after
column chromatography (SiO2, Et2O/hexane, 1:1) afforded a pale
1
yellow solid (0.25 g, 63%): mp 85-87 °C; H NMR (acetone-d6)
δ 10.08 (br s, 1H), 7.52 (d, J ) 3.0 Hz, 2H), 7.14-7.07 (m, 3H),
6.87 (s, 1H), 6.61 (s, 1H); 13C NMR (acetone-d6) δ 134.8, 134.7,
129.9, 125.5, 125.0, 119.5, 115.1, 106.3, 21.07. The compound
was homogeneous by TLC (SiO2, Et2O/hexane, 1:2, Rf ) 0.85).
3-(4-Ch lor op h en yl)p yr r ole (4d ). Method B with 4c after
column chromatography (SiO2, Et2O/hexane, 1:1) afforded a
white solid (0.36 g, 81%): mp 116-117 °C; 1H NMR (acetone-
d6) δ 10.28 (br s, 1H), 7.54 (d, J ) 8.0 Hz, 2H), 7.28 (d, J ) 8.0
Hz, 2H), 7.23 (s, 1H), 6.84 (s, 1H), 6.47 (s, 1H); 13C NMR
(acetone-d6) δ 136.4, 130.5, 129.2, 127.0, 123.8, 120.0, 116.0,
106.4. The compound was homogeneous by TLC (SiO2, Et2O/
hexane, 1:2, Rf ) 0.5).
3-(4-Ch lor op h en yl)-1-(m et h oxyca r b on yl)p yr r ole (5d ).
Method C with 4d after column chromatography (SiO2, Et2O/
hexane, 1:2) afforded a white solid (0.19 g, 84%): mp 92-94 °C;
1H NMR (acetone-d6) δ 7.69-7.64 (m, 3H), 7.37 (d, J ) 7.8 Hz,
3H), 6.71 (s, 1H), 3.99 (s, 3H); 13C NMR (acetone-d6) δ 151.5,
134.1, 132.8, 129.8, 128.0, 122.3, 117.2, 111.6, 55.0. Anal. Calcd
for C12H10ClNO2: C, 61.16; H, 4.28; N, 5.96. Found: C, 61.19;
H, 4.32; N, 5.89.
3-[5-(2-Ch lor op yr id yl)]p yr r ole (4e). Method B with 3e
after column chromatography (SiO2, EtOAc/hexane, 2:1) afforded
a white solid (0.31 g, 70%): mp 141-143 °C; 1H NMR (acetone-
d6) δ 10.42 (br s, 1H), 8.60 (s, 1H), 7.92 (d, J ) 8.2 Hz, 1H), 7.35
(d, J ) 6.6 Hz, 1H), 7.31 (s, 1H), 6.91 (s, 1H), 6.55 (s, 1H); 13C
NMR (acetone-d6) δ 147.6, 146.5, 135.6, 132.5, 124.7, 120.5,
120.1, 116.7, 106.4. The compound was homogeneous by TLC
(SiO2, EtOAc/hexane, 1:1, Rf ) 0.41).
3-(3-P yr id yl)p yr r ole (4f). Method B with 3f was used
except that the pH was adjusted to neutral with 12 N HCl and
concentrated under reduced pressure. The residue was then
heated in ethanolamine, followed by the usual workup and after
column chromatography (SiO2, ether) afforded a white solid (0.24
g, 65%): mp 136-137 °C; 1H NMR (acetone-d6) δ 10.52 (br s,
1H), 8.85 (s, 1H), 8.34 (d, J ) 4.5 Hz, 1H), 7.88 (d, J ) 7.5 Hz,
1H), 7.35 (s, 1H), 7.27 (d, J ) 6.0 Hz, 1H), 6.91 (s, 1H), 6.57 (s,
1H); 13C NMR (acetone-d6) δ 147.1, 146.8, 133.1, 132.3, 124.3,
121.5, 120.3, 116.3, 106.3. Anal. Calcd for C9H8N2: C, 74.98;
H, 5.59; N, 19.43. Found: C, 75.01; H, 5.59; N, 19.33.
3-(3-Th ien yl)p yr r ole (4g). Method B with 3g after column
chromatography (SiO2, Et2O/hexane, 1:1) afforded a white solid
(0.22 g, 60%): mp 74-76 °C; 1H NMR (acetone-d6) δ 10.11 (br s,
1H), 7.37-7.13 (m, 3H), 6.81 (s, 1H), 6.43 (s, 1H); 13C NMR
(acetone-d6) δ 138.9, 126.9, 126.0, 120.8, 119.4, 116.4, 115.6,
107.0. The compound was homogeneous by TLC (SiO2, Et2O/
hexane, 1:1, Rf ) 0.5).
1-(ter t-Bu t oxyca r b on yl)-3-[5-(2-ch lor op yr id yl)]p yr r ole
(5e). 4-(Dimethylamino)pyridine (DMAP, 0.1 mmol) and (Boc)2O
(1.2 mmol) were added to a stirred solution of pyrrole 4e (1
mmol) in dry CH3CN under nitrogen. The mixture was stirred
overnight, and excess (Boc)2O was destroyed by addition of
[2-(diethylamino)ethyl]amine (DEAEA, 0.3 mmol) with stirring
for 10 min. The crude product was obtained by partitioning
between Et2O and KHSO4 (1 M solution). The ether extract was
washed with H2O (25 mL) and NaHCO3 (1 M, 25 mL), dried with
Na2SO4, and concentrated under reduced pressure. The residue
was purified by column chromatography (SiO2, EtOAc/hexane,
1:3) to afford a white solid (0.24 g, 86%): mp 101-103 °C; 1H
NMR (acetone-d6) δ 8.69 (d, J ) 2.4 Hz, 1H), 8.06-8.03 (m, 1H),
7.81 (s, 1H), 7.44 (d, J ) 2.5 Hz, 1H), 7.36 (d, J ) 2.1 Hz, 1H),
6.75 (s, 1H), 1.64 (s, 9H); 13C NMR (acetone-d6) δ 149.4, 149.1,
147.3, 136.5, 130.3, 124.9, 123.9, 122.3, 117.8, 110.6, 84.9, 28.0.
Anal. Calcd for C14H15ClN2O2: C, 60.33; H, 5.42; N, 10.05.
Found: C, 60.26; H, 5.39; N, 10.04.
1-(Meth oxyca r bon yl)-3-(3-th ien yl)p yr r ole (5g). Method
C with 4g after column chromatography (SiO2, EtOAc/hexane,
1:4) afforded a pale yellow solid (0.16 g, 80%): mp 81-83 °C;
1H NMR (acetone-d6) δ 7.56 (d, J ) 5.7 Hz, 2H), 7.45-7.41 (m,
2H), 7.30 (d, J ) 1.8 Hz, 1H), 6.65 (s, 1H), 3.96 (s, 3H); 13C NMR
(acetone-d6) δ 152.4, 137.4, 127.9, 127.8, 125.7, 122.7, 120.8,
117.5, 113.2, 55.6. Anal. Calcd for C10H9NO2S: C, 57.96; H,
4.38; N, 6.76. Found: C, 58.13; H, 4.44; N, 6.59.
3′-(1-Ben zylin d olyl)p yr r ole (4h ). Method B with 3h after
column chromatography (SiO2, Et2O/hexane, 1.5:1) afforded a
pale yellow solid (0.47 g, 70%): mp 173-176 °C; 1H NMR
J O961981U