Rhodium-catalyzed transannulation of 1,2,3-triazoles to polysubstituted pyrroles

Article abstract of DOI:10.1021/jo501043h

Rhodium-catalyzed transannulation of N-sulfonyl-1,2,3-triazoles with vinyl ether has been accomplished for the synthesis of various polysubstituted pyrroles. The present method allows the synthesis of mono-, di-, and trisubstituted pyrroles with appropriate substitutions. Furthermore, the developed methodology was applied in the formal synthesis of neolamellarin A, an antitumor agent.

Full text of DOI:10.1021/jo501043h

Note
pubs.acs.org/joc
Rhodium-Catalyzed Transannulation of 1,2,3-Triazoles to
Polysubstituted Pyrroles
Shanmugam Rajasekar and Pazhamalai Anbarasan*
Department of Chemistry, Indian Institute of Technology Madras, Chennai - 600036, India
S
* Supporting Information
ABSTRACT: Rhodium-catalyzed transannulation of N-sulfonyl-1,2,3-triazoles with vinyl ether has been accomplished for the
synthesis of various polysubstituted pyrroles. The present method allows the synthesis of mono-, di-, and trisubstituted pyrroles
with appropriate substitutions. Furthermore, the developed methodology was applied in the formal synthesis of neolamellarin A,
an antitumor agent.
yrroles are ubiquitous subunits present in various bioactive
natural products and pharmaceutically important mole-
α-diazoimines,10 were employed as starting material for the
synthesis of pyrroles11 using Rh and Ni catalysts and various
coupling partners, such as alkynes,12 allenes,13 and furans14
(Scheme 1).
Most of these reactions often produce the mixture of
regioisomers, presumably due to the lack of directing ability in
the coupling partners, and also have limitations on the kind of
substitution that can be introduced on the pyrrole motif. Thus,
the development of highly amenable and efficient synthesis of
P
cules.1 They exhibit a wide range of bioactivities such as
antitumor, anti-inflammatory, and antibiotic activities (Figure
1). Furthermore, pyrroles also serves as vital intermediates in
Scheme 1. Transition-Metal-Catalyzed Transannulation of
1,2,3-Triazoles to Pyrroles
Figure 1. Representative examples of pyrrole-containing natural
products and pharmaceuticals.
the synthesis of flavoring components,2 dyes,3 and organic
functional materials.4 Having mentioned these potentials, the
synthesis of polysubstituted pyrroles has been an attractive field
in organic synthesis and medicinal chemistry.
Typically, pyrroles are synthesized through classical Paal−
Knorr,5 Huisgen,6 and Hantzsch7 processes. During the last
decades, various approaches have been documented for the
synthesis of pyrrole through both metal-catalyzed inter-8 and
intramolecular9 cyclization strategies. However, these strategies
require multiple steps and prefunctionalized substrates. Most
recently, readily accessible 1,2,3-triazoles, an efficient source of
Received: May 13, 2014
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo501043h | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
polysubstituted pyrroles with appropriate coupling partners is
highly desirable.15 Continuing our constant efforts in the
functionalization of 1,2,3-triazoles16 and inspired by the
potential of polysubstituted pyrroles, we herein disclose the
rhodium-catalyzed transannulation of 1,2,3-triazoles to pyrroles
with substituted vinyl ethers.
Scheme 3. Rhodium-Catalyzed Synthesis of 1,3-
Disubstituted Pyrroles from Triazole 6 and 8a
Initially, we focused on the optimization of suitable reaction
conditions for the rhodium-catalyzed transannulation of 1,2,3-
triazole 6a to pyrrole 7aa with ethylvinyl ether 8a. Reaction of
6a with 2 equiv of 8a with 2 mol % of Rh2(OAc)4 in CHCl3 at
70 °C in 8.5 h afforded 78% of unaromatized product A along
with a detectable amount of pyrrole 7aa (Scheme 2). The
product A can be converted to pyrrole 7aa in 87% yield
utilizing acid-mediated elimination of ethanol.
Scheme 2. Rhodium-Catalyzed Transannulation of Triazole
6a with 8a
Interestingly, prolonging the reaction time (20 h) also
afforded the pyrrole 7aa in 82% yield (Table 1, entry 1).
Table 1. Rhodium-Catalyzed Transannulation of 6a with 8a:
Optimization
a
annulation conditions. Replacement of the p-toluenesulfonyl
moiety with mesyl and phenylsulfonyl gave the pyrroles 7ba
and 7ca in comparable yield. Simple alkyl substituted aryl-
containing pyrroles (7da, 7ea, 7fa, and 7ia) were achieved in
good yield from the corresponding 1,2,3-triazoles. Sterically
hindered, naphthalene substituted triazole under the rhodium-
catalyzed transannulation conditions afforded the pyrrole in
63% yield. Electron-poor, halogen and trifluoromethyl sub-
stituted aryl-containing triazoles furnished the pyrroles (7ja−
7pa) in moderate to good yield. Interestingly, electron-rich, p-
anisyl substituted triazole also underwent smooth reaction and
pyrrole 7ga was isolated in 78% yield. Thiophene, heteroarene
substituted pyrrole (7ra), and cyclohexenyl substituted pyrrole
(7qa) were also synthesized in good yield. Next, reaction of
1,4,5-trisubstituted triazoles and ethylvinyl ether 8a gave the
1,2,3-trisubstituted pyrrole 7sa in 51% yield.
b
entry
Rh(II) cat.
solvent
temp (°C) time (h) yield (%)
1
2
3
4
5
6
7
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(Oct)4
Rh2(Oct)4
CHCl3
DCE
70
90
45
70
70
90
70
20
16
22
20
22
16
20
82
80
0
DCM
DCM
C6H5Cl
DCE
63
80
92
91
CHCl3
a
Reaction conditions: 6a (1 equiv), 8a (2 equiv), Rh(II) cat. (2 mol
b
%), solvent (2 mL for 0.16 mmol), temp, time. All are isolated yields.
Subsequently, the potential of the methodology was
extended to the synthesis of tri- and tetrasubstituted pyrroles
employing different triazoles and substituted enol ethers
(Scheme 4). Reaction of β-aryl substituted enol ethers (8b−
8j) with 6a afforded the 1,3,4-trisubstituted pyrroles (7ab−7ai)
in moderate to good yield. Interestingly, both sterically and
electronically different aryl substituted enol ethers were
tolerated under the optimized conditions. However, the
reaction of a highly electron-withdrawing nitro group
substituted β-arylenol ether with 6a afforded the corresponding
dihydropyrrole as the major product, even at a prolonged
reaction time. Consequently, the corresponding pyrrole 7aj was
obtained in 48% yield after the treatment of dihydropyrrole
with TMSOTf. Similarly, reaction of α-aryl substituted enol
ethers (8k−8m) with triazoles (6b and 6c) furnished the 1,2,4-
trisubstituted pyrroles (7bk, 7bi, and 7cm) in good yield. The
α-methyl substituted enol ether also underwent a smooth
reaction to afford the pyrrole 7an in 75% yield. Furthermore,
the present strategy also allows the synthesis of 1,2,3,5-
Changing the solvent to 1,2-dichloroethane (DCE) along with
an increase in temperature (90 °C) showed the similar result in
16 h (Table 1, entry 2). However, no formation of pyrrole was
observed at decreased temperature (45 °C) in dichloromethane
(DCM) (Table 1, entry 3). Screening solvents (DCM and
chlorobenzene) at 70 °C gave the product 7aa in 63% and 80%
yield (Table 1, entries 4 and 5). Best results were observed
when the catalyst was changed to Rh2(Oct)4 (Table 1, entries 6
and 7). However, due to the ready availability of Rh2(OAc)4
compared to Rh2(Oct)4, we used Rh2(OAc)4 as catalyst for the
substrate studies. Similarly, chloroform at 70 °C and DCE at 90
°C gave the similar result, but the latter was opted since the
latter gave the best result in substrate scope.
After identifying the suitable reaction conditions for the
transannulation of triazole to pyrrole, the generality of the
method was investigated. As shown in Scheme 3, various 1,3-
disubstituted pyrroles were achieved from triazoles 6 and
ethylvinyl ether 8a employing the rhodium-catalyzed trans-
B
dx.doi.org/10.1021/jo501043h | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Scheme 4. Rhodium-Catalyzed Synthesis of Tri- and
Tetrasubstituted Pyrroles
Scheme 6. Synthesis of Polysubstituted Pyrroles
be synthesized with high regioselectivity employing the present
strategy.
After demonstrating the potential of the present strategy for
the synthesis of pyrroles, we were interested in the application
of the developed method in the formal synthesis of neo-
lamellarin A (4). Neolamellarin A was isolated from a crude
extract of the sponge Dendrilla nigra17 and exhibits antitumor
activity. The key intermediate 3,4-dianisylpyrrole 9g18 for the
synthesis of 4 could be readily accessible through the present
protocol (Scheme 7). Thus, the rhodium-catalyzed trans-
Scheme 7. Formal Synthesis of Neolamellarin A
tetrasubstituted pyrroles in good yield. Reaction of 4,5-
disubstituted triazoles (7s and 7t) with α-aryl enol ethers (8k
and 8m) and α-alkyl enol ether 8n gave the tetrasubstituted
pyrroles (7tk, 7sm, 7tm, 7sn, and 7tn) in good to excellent
yield.
Next, transannulation of triazole 6a with cyclic enol ether 8o
under the optimized conditions afforded the bicyclic compound
A′ in 77% yield, a potential motif present in a number of
bioactive molecules, along with a detectable amount of pyrrole
7ao (Scheme 5). Since prolonging the reaction time did not
improve the pyrrole yield, the bicyclic compound A′ was
treated with a catalytic amount of TMSOTf to give pyrrole 7ao
in good yield.
Next, the conversion of synthesized N-sulfonyl pyrrole
derivatives 7 to the polysubstituted pyrroles 9 were
investigated. Treatment of N-sulfonyl pyrrole with KOH in
methanol/THF afforded the free pyrroles (9a−9f) in excellent
yield (Scheme 6). It is interesting to know that various mono-,
di- (2,3-, 2,4-, and 3,4-), and tri (2,3,5)-substituted pyrroles can
annulation of triazole 6g′ with enol ether 8d under the
optimized conditions afforded the pyrrole, which, on
subsequent reaction with KOH, furnished the key intermediate
9g in two steps.
We postulate the following mechanism for the formation of
pyrrole 7 from triazole 6 and enol ether 8 (Scheme 8). The
reactive rhodium carbenoid II could be generated from 6
through the formation of α-diazoimine I. Reaction of II with 8
through a nucleophilic addition pathway would form zwitter
ion III, which, on cyclization, would afford the intermediate A
and reactive rhodium species. On the other hand, formation of
A could be achieved from II and 8 via the cyclopropanated
product IV and subsequent Cloke rearrangement.19 Finally,
aromatization of A through elimination of alcohol would
furnish the pyrrole 7.
Scheme 5. Rhodium-Catalyzed Transannulation of 6a with
8o
C
dx.doi.org/10.1021/jo501043h | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
ether 8a (0.028−0.032 mL, 0.28−0.34 mmol) in DCE (2 mL) was
introduced through a syringe. The reaction tube was sealed and stirred
at 90 °C for 16−20 h. After the TLC analysis, the reaction mixture was
cooled to room temperature and purified by column chromatography
using a hexanes/ethyl acetate mixture as eluent to furnish the pyrroles
(7aa−7sa).
Scheme 8. Plausible Mechanism
7ba: 37 mg, 74% yield; colorless gummy solid; 1H NMR (400
MHz, CDCl3, 24 °C): δ 7.52 (d, 2H, J = 7.4 Hz), 7.40−7.36 (m, 3H),
7.29 (d, 1H, J = 7.3 Hz), 7.18−7.16 (m, 1H), 6.69 (m, 1H), 3.18 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ 133.4, 129.8, 129.0,
127.4, 125.8, 121.6, 116.2, 112.3, 43.0; HRMS: calcd. for C11H11NO2S
+ H: 222.0589; found: 222.0587.
1
7ca: 40 mg, 79% yield; brown gummy solid; H NMR (400 MHz,
CDCl3, 24 °C): δ 7.85 (m, 2H), 7.57−7.53 (m, 1H), 7.48−7.42 (m,
4H), 7.39 (t, 1H, J = 2 Hz), 7.31−7.28 (m, 2H), 7.21−7.19 (m, 1H),
7.17−7.16 (m, 1H), 6.6 (dd, 1H, J = 3.3, 1.7 Hz); 13C{1H} NMR (100
MHz, CDCl3, 24 °C): δ 139.1, 134.1, 133.5, 129.9, 129.6, 128.9, 127.6,
126.9, 125.7, 121.8, 116.5, 112.5; HRMS: calcd. for C16H13NO2S + H:
284.0745; found: 284.0743.
1
7da: 38 mg, 76% yield; white solid; mp: 109 °C; H NMR (400
MHz, CDCl3, 24 °C): δ 7.77 (d, 2H, J = 8.4 Hz), 7.38−7.37 (d, 3H),
7.28 (d, 2H, J = 8.1 Hz), 7.18−7.17 (m, 1H), 7.14 (d, 2H, J = 8.0),
6.58 (dd, 1H, J = 3.3, 1.7 Hz), 2.39 (s, 3H), 2.34 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3, 24 °C): δ 145.1, 136.9, 136.2, 135.7, 130.1,
129.7, 129.6, 127.0, 125.6, 121.7, 116.1, 112.2, 21.7, 21.3; HRMS:
calcd. for C18H17NO2S + Na: 334.0878; found: 334.0880.
In conclusion, we developed a highly efficient and amenable
strategy for the synthesis of polysubstituted pyrroles from
readily accessible triazoles and enol ethers. Employing the
developed methodology, mono-, di-, and trisubstituted pyrroles
can be achieved with high regioselectivity. Furthermore, the
utility of the present method was demonstrated in the synthesis
of the key intermediate for the synthesis of an antitumor agent,
neolamellarin A.
7ea: 34 mg, 68% yield; gummy solid; 1H NMR (500 MHz, CDCl3,
24 °C): δ 7.77 (d, 2H, J = 8.4 Hz), 7.39−7.38 (m, 3H), 7.28 (d, 2H, J
= 8.1 Hz), 7.18−7.16 (m, 3H), 6.58 (dd, 1H, J = 3.2, 1.6 Hz), 2.64 (q,
2H, J = 7.6 Hz), 2.39 (s, 3H), 1.23 (t, 3H, J = 7.6 Hz); 13C{1H} NMR
(125 MHz, CDCl3, 24 °C): δ 145.2, 143.4, 136.2, 130.9, 130.1, 129.7,
128.4, 127.0, 125.7, 121.7, 116.1, 112.4, 28.7, 21.8, 15.7; HRMS: calcd.
for C19H19NO2S + H: 326.1215; found: 326.1218.
EXPERIMENTAL SECTION
■
1
7fa: 32 mg, 65% yield; white solid; mp: 135 °C; H NMR (500
Synthesis of 2-Ethoxy-4-phenyl-1-tosyl-2,3-dihydro-1H-pyr-
role (A). 1,2,3-Triazoles 6a (50 mg, 0.17 mmol) and Rh2(OAc)4 (1.4
mg, 0.003 mmol, 2 mol %) were added under a nitrogen atmosphere
to an over-dried 5 mL reaction tube equipped with a stir bar.
Subsequently, a solution of ethylvinyl ether 8a (21.6 mg, 0.032 mL,
0.34 mmol) in CHCl3 (2 mL) was introduced through a syringe. The
reaction tube was sealed and kept at 90 °C for 8.5 h. After the TLC
analysis, the reaction mixture was cooled to room temperature and
purified by column chromatography using a hexanes/ethyl acetate
mixture as eluent to afford the 2-ethoxy-4-phenyl-1-tosyl-2,3-dihydro-
MHz, CDCl3, 24 °C): 7.76 (d, 2H, J = 8.4 Hz), 7.41−7.35 (m, 5H),
7.27 (d, 2H, J = 8.1 Hz), 7.18 (dd, 1H, J = 3.5, 2.6 Hz), 6.58 (dd, 1H, J
= 1.6, 3.3 Hz), 2.39 (s, 3H), 1.31 (s, 9H); 13C{1H} NMR (125 MHz,
CDCl3, 24 °C): δ 150.3, 145.1, 136.2, 130.7, 130.1, 129.6, 127.0, 125.8,
125.4, 121.7, 116.2, 112.4, 34.6, 31.4, 21.7; HRMS: calcd. for
C21H23NO2S + H: 354.1528; found: 354.1516.
1
7ga: 38 mg, 78% yield; brown solid; mp: 113 °C; H NMR (400
MHz, CDCl3, 24 °C): δ 7.77 (d, 2H, J = 8.3 Hz), 7.39 (d, 2H, J = 8.8
Hz), 7.33−7.32 (m, 1H), 7.28 (d, 2H, J = 8.3 Hz), 7.18−7.17 (m,
1H,), 6.88 (d, 2H, J = 8.8 Hz), 6.54 (dd, 1H, J = 3.12, 1.6 Hz), 3.8 (s,
3H), 2.39 (s, 3H); 13C {1H} NMR (100 MHz, CDCl3, 24 °C): δ
158.9, 145.1, 136.1, 130.1, 129.4, 127.0, 126.8, 126.3, 121.7, 115.5,
114.3, 112.2, 55.5, 21.7; HRMS: calcd. for C18H17NO3S + Na:
350.0827; found: 350.0842.
1
1H-pyrrole A (45 mg, 78% yield) as a colorless viscous liquid. H
NMR (400 MHz, CDCl3, 24 °C): 7.70 (d, 2H, J = 8.3 Hz), 7.30−7.20
(m, 7H), 6.79 (d, 1H, J = 2.5 Hz), 5.34 (d, 1H, J = 6.7 Hz), 3.93 (dq,
1H, J = 9.5, 7.0 Hz), 3.62 (dq, 1H, J = 9.5, 7.0 Hz), 2.77 (ddd, 1H, J =
16.8, 7.1, 2.7 Hz), 2.68−2.63 (m, 1H), 2.38 (s, 3H), 1.19 (t, 3H, J =
7.0 Hz); 13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ 144.0, 135.8,
133.4, 129.9, 128.7, 127.5, 127.2, 126.1, 125.1, 123.4, 89.9, 63.0, 38.7,
21.6, 15.0.
Synthesis of 3-Phenyl-1-tosyl-1H-pyrrole (7aa). Dihydropyr-
role A (44 mg, 0.13 mmol) and 3 mL of THF were added in a 10 mL
round-bottom flask equipped with a stir bar. Subsequently, 1 M HCl
(0.1 mL) was added, and the mixture was stirred at room temperature
for 6 h. After the TLC analysis, it was cooled to room temperature and
purified by column chromatography using hexanes/ethyl acetate as
eluent to afford the pyrrole 7aa (34 mg, 87% yield) as a white solid.
mp: 119 °C; 1H NMR (400 MHz, CDCl3, 24 °C): δ 7.77 (d, 2H, J =
7.6 Hz), 7.47 (d, 2H, J = 7.6 Hz), 7.41 (m, 1H), 7.34 (t, 2H, J = 7.3
Hz), 7.26−7.19 (m, 4H), 6.59 (m, 1H), 2.39 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3, 24 °C): δ 145.2, 136.2, 133.6, 130.2, 129.7, 128.9,
127.2, 127.1, 125.7, 121.8, 116.4, 112.2, 21.7; HRMS: calcd. for
C17H15NO2S+H: 298.0902; found: 298.0901.
7ha: 33 mg, 66% yield; gummy liquid; 1H NMR (400 MHz, CDCl3,
24 °C): δ 8.08 (d, 1H, J = 8.0 Hz), 7.88−7.79 (m, 4H), 7.50−7.43 (m,
4 H), 7.37 (t, 1H, J = 1.8 Hz), 7.32 (d, 2H, J = 8.2 Hz), 7.29 (t,1H, J =
3.0 Hz), 6.58 (dd, 1H, J = 3.14, 1.6 Hz), 2.42 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3, 24 °C): δ 145.2, 136.2, 134.0, 132.2, 131.6, 130.2,
128.5, 128.3, 127.9, 127.1, 126.9, 126.3, 125.9, 125.6, 125.5, 120.9,
119.1, 115.8, 21.8; HRMS: calcd. for C21H17NO2S + Na: 370.0878;
found: 370.0869.
1
7ia: 37 mg, 75% yield; gummy solid; H NMR (400 MHz, CDCl3,
24 °C): δ 7.77 (2H, d, J = 6.7 Hz), 7.39−7.4 (m, 1H), 7.29−7.27 (m,
4H), 7.23 (t, 1H, J = 5.9 Hz), 7.19−7.18 (m, 1H), 7.05 (d, 1H, J = 5.8
Hz), 6.59 (dd, 1H, J = 2.12, 1.3 Hz), 2.39 (s, 3H), 2.35 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ 145.1, 138.5, 136.1,
133.5, 130.2, 129.8, 128.8, 127.9, 127.0, 126.5, 122.8, 121.7, 116.4,
112.3, 21.7, 21.6; HRMS: calcd. for C18H17NO2S + K: 350.0617;
found: 350.0625.
1
7ja: 29 mg, 58% yield; gummy solid; H NMR (400 MHz, CDCl3,
General Procedure for the Synthesis of Substituted Pyrrole
from 4-Substituted-N-sulfonyl-1,2,3-triazole 6 and Ethylvinyl
Ether 8a. 4-Substituted-N-sulfonyl-1,2,3-triazoles 6 (50 mg, 0.14−
0.17 mmol) and Rh2(OAc)4 (1.4 mg, 0.003 mmol, 2 mol %) were
added under a nitrogen atmosphere to an over-dried 5 mL reaction
tube equipped with a stir bar. Subsequently, a solution of ethyl vinyl
24 °C): δ 7.78 (d, 2H, J = 8.4 Hz), 7.43−7.40 (m, 2H), 7.35 (t, 1H, J =
1.88 Hz), 7.30 (d, 2H, J = 8.08 Hz), 7.19 (dd, 1H, J = 3.2, 2.2 Hz),
7.02 (t, 2H, J = 8.7 Hz), 6.54 (dd, 1H, J = 3.2, 1.6 Hz), 2.39 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ 162.2 (d, J = 244.4 Hz),
145.3, 136.1, 130.2, 129.8 (d, J = 2.4 Hz), 128.8, 127.3 (d, J = 7.9 Hz),
D
dx.doi.org/10.1021/jo501043h | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
127.1, 121.9, 116.2, 115.8 (d, J = 21.4 Hz), 112.2, 21.7; HRMS: calcd.
for C17H14NO2FS + H: 316.0808; found: 316.0816.
General Procedure for the Synthesis of 3,4-Diaryl-1-tosyl-
1H-pyrroles (7ab−7aj). 4-Phenyl-N-sulfonyl-1,2,3-triazoles 6a (50
mg, 0.17 mmol) and Rh2(OAc)4 (1.4 mg, 0.003 mmol, 2 mol %) were
added under a nitrogen atmosphere to an over-dried 10 mL reaction
tube equipped with a stir bar. Subsequently, a solution of vinyl ether
8b−8j (44−64 mg, 0.33 mmol) in cyclohexane (2 mL) was introduced
through a syringe. The reaction tube was sealed and stirred at 90 °C
for 48 h. After the TLC analysis, it was cooled to room temperature
and purified by column chromatography using a hexanes/ethyl acetate
mixture as eluent to afford pyrroles 7ab−7aj.
7ka: 40 mg, 81% yield; white solid; 1H NMR (400 MHz, CDCl3, 24
°C): δ 7.78 (d, 2H, J = 8.4 Hz), 7.39−7.37 (m, 3H), 7.3 (d, 4H, J = 8.5
Hz), 7.2−7.19 (m, 1H), 6.55 (dd, 1H, J = 3.2, 1.6 Hz), 2.4 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ 145.4, 135.9, 132.8,
132.2, 130.2, 129.1, 128.5, 127.1, 126.9, 121.9, 116.5, 112.0, 21.8;
HRMS: calcd. for C17H14ClNO2S + H: 332.0512; found: 332.0511.
1
7la: 33 mg, 65% yield; white solid; mp: 125 °C; H NMR (400
MHz, CDCl3, 24 °C): δ 7.78 (d, 2H, J = 8.4 Hz), 7.46−7.44 (m, 2H),
7.39 (t, 1H, J = 1.96 Hz), 7.33−7.28 (m, 4H), 7.20−7.18 (m, 1H),
6.55 (dd, 1H, J = 3.1, 1.7 Hz), 2.39 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3, 24 °C): δ 145.4, 136.0, 132.6, 132.0, 130.2, 128.5, 127.3, 127.1,
121.9, 120.8, 116.5, 111.9, 21.8; HRMS: calcd. for C17H14NO2S79Br +
H: 376.0007; found: 376.0005.
1
7ab: 33 mg, 52% yield; white solid; mp: 125 °C; H NMR (400
MHz, CDCl3, 24 °C): δ 7.77 (d, 2H, J = 8.4 Hz), 7.25 (d, 2H, J = 8.2
Hz), 7.18−7.16 (m, 8H), 7.11−7.09 (m, 4H), 2.35 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3, 24 °C): δ 145.3, 136.1, 133.7, 130.3, 128.7,
128.6, 128.4, 127.2, 127.1, 119.0, 21.8; HRMS: calcd. for C23H19NO2S
+ H: 374.1215; found: 374.1231.
1
7ma: 37 mg, 73% yield; white solid; mp: 126 °C; H NMR (400
7ac: 27 mg, 42% yield; white solid; 1H NMR (500 MHz, CDCl3, 24
°C): δ 7.82 (d, 2H, J = 8.3 Hz), 7.32 (d, 2H, J = 8.3 Hz), 7.25−7.21
(m, 6H), 7.19−7.17 (m, 2H), 7.06 (m, 4H), 2.41 (s, 3H), 2.32 (s,
3H); 13C{1H} NMR (125 MHz, CDCl3, 24 °C): δ 145.3, 136.8, 136.1,
133.8, 130.7, 130.2, 129.2, 128.7, 128.5, 128.4, 127.2, 127.0, 119.0,
118.8, 21.8, 21.3; HRMS: calcd. for C24H21NO2S + H: 388.1371;
found: 388.1375.
MHz, CDCl3, 24 °C): δ 7.78 (d, 2H, J = 8.4 Hz), 7.41 (t, 1H, J = 3.8
Hz), 7.32−7.29(m, 1H), 7.15 (td, 1H, J = 10.1, 2.3 Hz), 6.99−6.95 (m,
1H), 6.57 (dd, 1H, J = 3.2, 1.7 Hz), 2.4 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3, 24 °C): δ 163.3 (d, J = 243.7 Hz), 145.4, 135.9 (d, J =
4.2 Hz), 135.4, 130.4 (d, J = 34.4 Hz), 130.2, 128.5, 127.1, 121.9, 121.3
(d, J = 3.0 Hz), 116.9, 113.9 (d, J = 21.2 Hz), 112.5 (d, J = 22.1 Hz),
112.0, 21.8; HRMS: calcd. for C17H14NO2FS + H: 316.0808; found:
316.0817.
1
7ad: 46 mg, 69% yield; yellow gummy solid; H NMR (400 MHz,
1
CDCl3, 24 °C): δ 7.75 (d, 2H, J = 8.0 Hz), 7.24 (d, 2H, J = 8.0 Hz),
7.17−7.09 (m, 7H), 7.02 (d, 2H, J = 8.4 Hz), 6.71 (d, 2H, J = 8.5 Hz),
3.7 (s, 3H), 2.34 (s, 3H); 13C {1H} NMR (100 MHz, CDCl3, 24 °C):
δ 158.8, 145.3, 136.1, 133.8, 130.2, 129.8, 128.7, 128.6, 128.4, 127.2,
126, 118.9, 118.5, 113.9, 55.3, 21.8; HRMS: calcd. for C24H21NO3S +
H: 404.1320; found: 404.1305.
7na: 29 mg, 58% yield; brown gummy solid; H NMR (400 MHz,
CDCl3, 24 °C): δ 7.79 (d, 2H, J = 8.4 Hz), 7.61 (dd, 1H, J = 7.8, 1
Hz), 7.48 (t, 1H, J = 2.12 Hz), 7.35−7.28 (m, 4H), 7.18−7.17 (m,
1H), 7.11 (td, 1H, J = 7.7, 1.7 Hz), 6.57 (dd, 1H, J = 3.2, 1.6 Hz), 2.4
(s, 3H); 13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ 145.3, 136.1,
134.8, 133.7, 130.9, 130.2, 128.6, 128.2, 127.6, 127.1, 122.4, 120.3,
119.7, 115.1, 21.8; HRMS: calcd. for C17H14NO2S79Br + H: 376.0007;
found: 375.9995.
1
7ae: 37 mg, 57% yield; brown gummy solid; H NMR (400 MHz,
CDCl3, 24 °C): δ 7.76 (d, 2H, J = 8.4 Hz), 7.24 (d, 2H, J = 8.0 Hz),
7.17−7.15 (m, 5H), 7.11−7.09 (m, 2H), 7.06−7.02 (m, 1H), 6.97−
6.95 (m, 2H), 6.87 (d, 2H, J = 7.04 Hz), 2.34 (s, 3H), 2.2 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ 145.3, 138.0, 136.1,
133.7, 133.5, 130.2, 129.3, 128.8, 128.7, 128.6, 128.4, 128.2, 127.8,
127.2, 127.0, 125.8, 119.0, 118.9, 21.8, 21.5; HRMS: calcd. for
C24H21NO2S + H: 388.1371; found: 388.1363.
1
7oa: 35 mg, 70% yield; white solid; mp: 123 °C; H NMR (500
MHz, CDCl3, 24 °C): δ 7.79 (d, 2H, J = 8.4 Hz), 7.60−7.55 (m, 4H),
7.48 (t, 1H, J = 1.9 Hz), 7.31 (d, 2H, J = 8.2 Hz), 7.23−7.22 (m, 1H),
6.61 (dd, 1H, J = 3.2, 1.7 Hz), 2.40 (s, 3H); 13C{1H} NMR (125 MHz,
CDCl3, 24 °C): δ 145.4, 137.1, 135.7, 130.2, 128.9 (q, J = 32 Hz),
128.1, 127.0, 125.8 (q, J = 3.6 Hz), 125.7, 124.2 (q, J = 269.9 Hz),
121.1, 117.2, 111.8, 21.7; HRMS: calcd. for C18H14NO2SF3 + Na:
388.0595; found: 388.0608.
1
7af: 42 mg, 58 yield; yellow solid; mp: 142 °C; H NMR (500
MHz, CDCl3, 24 °C): δ 7.82 (d, 2H, J = 8.4 Hz), 7.31 (d, 2H, J = 8.1
Hz), 7.23−7.20 (m, 5H), 7.18−7.16 (m, 2H), 6.75 (m, 2H), 6.59 (s,
1H), 3.83 (s, 3H), 3.58 (s, 3H), 2.40 (s, 3H); 13C{1H} NMR (125
MHz, CDCl3, 24 °C): δ 148.6, 148.2, 145.3, 136.1, 133.8, 130.3, 128.8,
128.7, 128.5, 128.4, 127.2, 127.1, 126.3, 120.7, 118.9, 112.1, 111.2,
55.9, 55.7, 21.8; HRMS: calcd. for C25H23NO4S + H: 434.1426; found:
434.1415.
7pa: 41 mg, 83% yield; viscous liquid; 1H NMR (400 MHz, CDCl3,
24 °C): δ 7.80 (d, 2H, J = 8.4 Hz), 7.69 (s, 1H), 7.64−7.62 (m, 1H),
7.47−7.45 (m, 3H), 7.32 (d, 2H, J = 8.2 Hz), 7.24−7.22 (m, 1H), 6.61
(dd, 1H, J = 1.7, 3.2 Hz), 2.40 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3, 24 °C): δ 145.5, 135.9, 134.5, 131.3 (q, J = 31.9 Hz), 130.3,
129.3, 128.9, 128.3, 127.1, 123.7 (q, J = 3.7 Hz,), 122.8, 122.4 (q, J =
3.8 Hz), 116.9, 111.9, 21.8; HRMS: calcd. for C18H14F3NO2S + H:
366.0776; found: 366.0783.
7ag: 48 mg, 70% yield; gummy solid; 1H NMR (400 MHz, CDCl3,
24 °C): δ 7.83 (d, 2H, J = 8.4 Hz), 7.32(d, 2H, J = 8.1 Hz), 7.24 (m,
5H), 7.20 (d, 2H, J = 8.5 Hz), 7.16−7.14 (m, 2H), 7.09 (2H, J = 8.5
Hz), 2.41 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ 145.5,
136.1, 133.4, 133.1, 132.2, 130.9, 130.3, 129.9, 128.7, 128.6, 127.5,
127.3, 119.2, 119.1, 21.8; HRMS: calcd. for C23H18NO2ClS + H:
408.0825; found: 408.0824.
1
7qa: 26 mg, 53% yield; white solid; mp: 151 °C; H NMR (400
MHz, CDCl3, 24 °C): δ 7.72 (d, 2H, J = 8.4 Hz), 7.27 (d, 2H, J = 7.3
Hz), 7.09−7.07 (m, 1H), 7.02 (m, 1H), 7.02 (m, 1H), 6.42 (dd, 1H, J
= 3.3, 1.6 Hz), 2.39 (s, 3H), 2.23−2.20 (m, 2H), 2.15−2.12 (m, 2H),
1.73−1.67 (m, 2H), 1.64−1.59 (m, 2H); 13C{1H} NMR (100 MHz,
CDCl3, 24 °C): δ 144.9, 136.3, 131.5, 130.0, 129.6, 126.9, 123.2, 121.4,
115.3,110.8, 26.7, 25.6, 22.7, 22.4, 21.7; HRMS: calcd. for
C17H19NO2S + H: 302.1215; found: 302.1205.
7ah: 33 mg, 49% yield; yellow viscous liquid; 1H NMR (400 MHz,
CDCl3, 24 °C): δ 7.83 (d, 2H, J = 8.4 Hz), 7.32−7.29 (m, 3H), 7.26−
7.24 (m, 2H), 7.22−7.16 (m, 3H), 7.13−7.10 (m, 3H), 6.87 (td, 1H, J
= 7.4, 1.0 Hz), 6.80 (d, 1H, J = 8.2 Hz), 3.38 (s, 3H), 2.41 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ 156.9, 145.1, 136.3,
134.9, 131.4, 130.2, 129.8, 128.9, 128.2, 127.5, 127.2, 126.7, 124.8,
122.8, 120.6, 120.3, 120.3, 118.0, 111.3, 55.1, 21.8; HRMS: calcd. for
C24H21NO3S + H: 404.1320; found: 404.1312.
1
7ra: 38 mg, 77% yield; brown solid; H NMR (400 MHz, CDCl3,
24 °C):δ 7.77 (d, 2H J = 8.4 Hz), 7.32−7.27 (m, 5H), 7.19 (dd, 1H, J
= 5.0 1.2 Hz), 7.16−7.15 (m, 1H), 6.51 (dd, 1H, J = 3.2, 1.6 Hz), 2.4
(s, 3H); 13C {1H} NMR (125 MHz, CDCl3, 24 °C): δ 145.2, 136.1,
134.9, 130.2, 127.0, 126.3, 125.9, 125.1, 121.7, 119.4, 116.4, 112.7,
21.8; HRMS: calcd. for C15H13NO2S2 + Na: 326.0285; found:
326.0284.
1
7ai: 34 mg, 48% yield; brown gummy solid; H NMR (400 MHz,
CDCl3, 24 °C): δ 7.87 (d, 2H, J = 8.2 Hz), 7.81 (t, 2H, J = 7.8 Hz),
7.68 (d, 1H, J = 8.4 Hz), 7.44−7.34 (m, 5H), 7.29−7.25 (m, 3H), 7.03
(m, 5H), 2.40 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ
145.4, 136.1, 133.8, 133.5, 132.4, 131.7, 130.3, 128.3, 128.29, 128.2,
128.1, 127.5, 126.8, 126.7, 126.2, 126.0, 125.8, 125.4, 121.0, 118.1,
21.8; HRMS: calcd. for C27H21NO2S + H: 424.1371; found: 424.1388.
7sa: 25 mg, 51% yield; gummy solid; 1H NMR (400 MHz, CDCl3,
24 °C): δ 7.63 (d, 2H, J = 8.3 Hz), 7.23−7.18 (m, 4H), 7.12−6.98 (m,
3H), 6.5 (d, 1H, J = 3.4 Hz), 2.92 (t, 2H, J = 6.8 Hz), 2.86 (t, 2H, J =
6.8 Hz), 2.32 (s, 3H); 13C {1H} NMR (100 MHz, CDCl3, 24 °C): δ
145.1, 136.3, 133.3, 131.3, 130.2, 130.1, 128.0, 126.9, 126.8, 126.3,
124.2, 122.3, 122.2, 107.9, 29.2, 21.7, 21.4; HRMS: calcd. for
C19H17NO2S + H: 324.1058; found: 324.1072.
1
7aj: 27 mg, 46% yield; white gummy liquid; H NMR (400 MHz,
CDCl3, 24 °C): δ 8.08−8.06 (m, 2H), 7.87 (d, 2H, J = 8.4 Hz), 7.43−
E
dx.doi.org/10.1021/jo501043h | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
7.35 (m, 5H), 7.28−7.26 (m, 4H), 7.15−7.13 (m, 2H), 2.44 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ 148.5, 145.7, 135.8,
135.6, 134.7, 132.9, 130.5, 129.3, 128.75, 128.70, 128.5, 127.6, 127.4,
126.3, 123.1, 121.9, 119.6, 119.5, 21.8; HRMS: calcd. for C23H18N2O4S
+ H: 419.1066; found: 419.1062.
21.7, 15.4; HRMS: calcd. for C20H19NO2S + H: 338.1215; found:
338.1211.
7tn: 38 mg, 74% yield; white gummy solid; H NMR (400 MHz,
CDCl3, 24 °C): δ 7.22−7.16 (m, 2H), 7.13−7.08 (m, 1H), 6.33 (s,
1H), 3.11 (t, 2H, J = 7.6 Hz), 3.09 (s, 3H), 3.00 (t, 2H, J = 7.6 Hz),
2.47 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ 133.6,
132.5, 131.1, 130.4, 127.9, 123.9, 126.3, 122.6, 122.3, 108.7, 42.7, 29.5,
22.7, 15.3; HRMS: calcd. for C14H15NO2S + H: 262.0902; found:
262.0903.
Synthesis of 7ao. 4-Phenyl-N-tosyl-1,2,3-triazoles 6a (75 mg, 0.25
mmol) and Rh2(OAc)4 (2.2 mg, 0.005 mmol, 2 mol %) were added
under a nitrogen atmosphere to an over-dried 10 mL reaction tube
equipped with a stir bar. Subsequently, a solution of cyclic vinyl ether
8o (35 mg, 0.5 mmol) in dichloroethane (3 mL) was introduced
through a syringe. The reaction tube was sealed and stirred at 90 °C
for 6 h. After the TLC analysis, it was cooled to room temperature and
purified by column chromatography using a hexanes/ethyl acetate
mixture (3:17) as eluent to afford dihydropyrrole A′ (65 mg, 77%
yield) as a white gummy solid. 1H NMR (400 MHz, CDCl3, 24 °C): δ
7.78 (d, 2H, J = 8.4 Hz), 7.33−7.26 (m, 6H), 7.23−7.18 (m, 1H), 6.91
(d, 1H, J = 1.2 Hz), 3.96−3.92 (m, 1H), 3.87−3.83 (m, 1H), 3.49−
3.42 (m, 1H), 3.87−3.83 (m, 1H), 2.41 (s, 3H), 2.16−2.01 (m, 1H),
1.77 (dd, 1H, J = 12.3, 5.2 Hz); 13C{1H} NMR (100 MHz, CDCl3, 24
°C): δ 144.0, 136.3, 132.9, 129.9, 128.9, 127.4, 127.2, 125.1, 122.9,
94.7, 66.6, 48.6, 30.9, 21.7; HRMS: calcd. for C19H19NO3S + H:
342.1164; found: 342.1158.
1
Typical Procedure for the Synthesis of 1,2,4-Tri- and 1,2,3,5-
Tetrasubstituted Pyrrole. 1,2,3-Triazoles (50 mg, 0.15−0.2 mmol)
and Rh2(OAc)4 (1.4−1.8 mg, 0.003−0.004 mmol, 2 mol %) were
added under a nitrogen atmosphere to an over-dried 5 mL reaction
tube equipped with a stir bar. Subsequently, a solution of vinyl ether
(22−73 mg, 0.32−0.51 mmol) in DCE (2 mL) was introduced
through a syringe. The reaction tube was sealed and stirred at 90 °C
for 24 h. After the TLC analysis, it was cooled to room temperature
and purified by column chromatography using hexanes/ethyl acetate
mixture as eluent to afford the pyrrole.
7bk: 41 mg, 63% yield; gummy solid; 1H NMR (400 MHz, CDCl3,
24 °C): δ 7.58−7.54 (m, 5H), 7.43−7.36 (m, 5H), 7.29−7.24 (m,
1H), 6.65 (d, 1H, J = 2.0 Hz), 2.89 (s, 3H); 13C {1H} NMR (100
MHz, CDCl3, 24 °C): δ 136.5, 133.3, 131.1, 130.9, 129.0, 128.0, 127.5,
127.3, 125.7, 119.3, 114.5, 42.4; HRMS: calcd. for C17H15NO2S + H:
298.0902; found: 298.0890.
1
7bl: 44 mg, 61 yield; white viscous liquid; H NMR (500 MHz,
CDCl3, 24 °C): δ 7.58 (d, 1H, J = 2.0 Hz), 7.54 (d, 2H, J = 7.8 Hz),
7.5 (d, 2H, J = 8.6 Hz), 7.40−7.37 (m, 4H), 7.30−7.25 (m, 1H), 6.65
(d, 1H, J = 2.0 Hz), 2.89 (s, 3H); 13C {1H} NMR (125 MHz, CDCl3,
24 °C): δ 135.3, 135.2, 133.0, 132.1, 129.4, 129.0, 128.4, 127.9, 127.5,
119.8, 115.0, 42.5; HRMS: calcd. for C17H14ClNO2S + H: 332.0512;
found: 332.0523.
Dihydropyrrole A′ (65 mg, 0.19 mmol) and 4 mL of DCE were
added in a 10 mL round-bottom flask equipped with a stir bar.
Subsequently, TMSOTf (2 mg, 5 mol %) was added, and the mixture
was stirred at room temperature for 1 h. After the TLC analysis, the
reaction mixture was quenched with water, extracted with dichloro-
methane (2 × 10 mL), and dried over Na2SO4. Evaporation of solvent,
followed by purification of the crude by column chromatography using
hexanes/ethyl acetate as eluent, afforded the pyrrole 7ao (45 mg, 70%
1
7cm: 25 mg, 58% yield; yellow solid; H NMR (400 MHz, CDCl3,
24 °C): δ 8.21 (d, 2H, J = 9.1 Hz), 7.78 (d, 1H, J = 2.0 Hz), 7.56−7.49
(m, 5H), 7.42−7.25 (m, 7H), 6.61 (d, 1H, J = 1.6 Hz); 13C{1H} NMR
(100 MHz, CDCl3, 24 °C): δ 147.7, 138.2, 137.8, 134.9, 134.3, 132.7,
131.4, 129.3, 129.1, 128.8, 127.7, 126.9, 125.7, 122.9, 121.9, 116.6;
HRMS: calcd. for C22H16N2O4S + H: 405.0909; found: 405.0901.
1
1
7an: 39 mg, 75% yield; white solid; mp: 113 °C; H NMR (400
yield) as a white gummy solid. H NMR (400 MHz, CDCl3, 24 °C):
MHz, CDCl3, 24 °C): δ 7.70 (d, 2H, J = 8.4 Hz), 7.55 (d, 1H, J = 1.9
Hz), 7.48−7.46 (m, 2H), 7.35 (t, 2H, J = 7.4 Hz), 7.3 (d, 2H, J = 8.0
Hz), 7.44−7.20 (m, 1H), 6.28−6.27 (m, 1H), 2.4 (s, 3H), 2.33 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ 145.0, 136.4, 133.8,
131.9, 130.2, 128.9, 127.0, 126.9, 125.5, 117.7, 111.9, 21.7, 13.9;
HRMS: calcd. for C18H17NO2S + H: 312.1058; found: 312.1059.
7tk: 45 mg, 69% yield; white solid; 1H NMR (400 MHz, CDCl3, 24
°C): 7.54−7.51 (m, 2H), 7.44−7.38 (m, 4H), 7.20−7.18 (m, 1H), 6.6
(s, 3H), 3.25 (t, 2H, J = 7.8 Hz), 3.11 (t, 2H, J = 7.6 Hz), 2.92 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ 137.8, 133.9, 133.8,
132.5, 130.8, 130.6, 128.6, 128.1, 127.8, 126.9, 126.7, 124.0, 122.5,
111.9, 42.2, 29.5, 23.1; HRMS: calcd. for C19H17NO2S + H: 324.1058;
found: 324.1073.
7.78 (d, 2H, J = 8.4 Hz), 7.37−7.25 (m, 7H), 7.18 (d, 1H, J = 1.2 Hz),
7.09−7.08 (m, 1H), 3.68 (t, 3H, J = 6.6 Hz), 2.77 (t, 2H, J = 6.6 Hz),
2.41 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ 145.2,
136.2, 133.9, 130.2, 128.7, 128.4, 127.3, 127.1, 124.0, 119.1, 118.6,
62.3, 29.2, 21.8; HRMS: calcd. for C19H19NO3S + H: 342.1164; found:
342.1172.
Typical Procedure for the Synthesis of Polysubstituted
Pyrroles. In a 25 mL round-bottom flask equipped with a stir bar, 1-
tosyl-1H-pyrrole 7 (0.07−0.1 mmol) and KOH (11−16 mg, 0.21−0.3
mmol) were added. Subsequently, 4 mL (1:1 ratio) of THF and
methanol was added, and the mixture was kept at 70 °C for 4 h. After
the TLC analysis, it was cooled to room temperature and purified by
column chromatography using a hexanes/ethyl acetate mixture as
eluent to furnish the polysubstituted pyrroles.
7sm: 36 mg, 54% yield; yellow solid ; 1H NMR (400 MHz, CDCl3,
24 °C): δ 8.27 (d, 2H, J = 8.7 Hz), 7.64 (d, 2H, J = 8.8 HZ), 7.36 (d,
2H, J = 8.4 Hz), 7.31−7.28 (m, 1H), 7.24−7.16 (m, 5H), 6.63 (s, 1H),
3.28 (t, 2H, J = 7.8 Hz), 3.03 (t, 2H, J = 7.8 Hz), 2.39 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ 147.2, 145.2, 139.3,
136.0, 135.5, 135.4, 133.8, 130.7, 130.1, 129.8, 127.9, 126.9, 126.8,
126.4, 124.9, 122.8, 122.4, 114.4, 29.3, 23.1, 21.6; HRMS: calcd. for
C25H20N2O4S + H: 445.1222; found: 445.1237.
9a: 12 mg, 79% yield; colorless liquid; 1H NMR (400 MHz, CDCl3,
24 °C): 8.30 (brs, 1H), 7.55−7.53 (m, 2H), 7.38−7.30 (m, 2H), 7.2−
7.16 (m, 1H), 7.10−7.09 (m, 1H), 6.84−6.82 (m, 1H), 6.57−6.55 (m,
1H); 13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ 136.0, 128.7, 125.6,
125.4, 125.2, 119.0, 114.7, 106.7.
9b: 12 mg, 74% yield; colorless liquid; 1H NMR (400 MHz, CDCl3,
24 °C): δ 7.95 (brs, 1H), 7.37 (d, 1H, J = 7.4 Hz), 7.21−7.15 (m, 2H),
7.04−7.00 (m, 1H), 6.69 (t, 1H, J = 2.6 Hz), 6.48 (t, 1H, J = 2.6 Hz),
3.01 (t, 2H, J = 7.3 Hz), 2.8 (t, 2H, J = 7.3 Hz); 13C {1H} NMR (100
MHz, CDCl3, 24 °C): δ 133.3, 132.9, 129.1, 127.9, 126.7, 124.4, 121.6,
118.3, 116.9, 103.6, 29.7, 21.8.
1
7tm: 34 mg, 48% yield; white solid; H NMR (400 MHz, CDCl3,
24 °C): δ 8.27 (d, 2H, J = 8.9 Hz), 7.68 (d, 2H, J = 8.9 Hz), 7.42−7.39
(m, 1H), 7.30−7.19 (m, 3H), 6.77 (s, 1H), 3.25 (t, 2H, J = 7.8 Hz),
3.12 (t, 2H, J = 7.8 Hz), 2.93 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3, 24 °C): δ 147.5, 138.9, 135.8, 135.2, 133.8, 130.8, 130.1, 128.2,
127.3, 127.1, 125.1, 123.1, 122.6, 114.2, 42.0, 29.3, 23.0; HRMS: calcd.
for C19H16N2O4S + H: 369.0909; found: 369.0917.
1
9c: 13 mg, 81% yield; brown liquid; H NMR (400 MHz, CDCl3,
24 °C): 7.91 (brs, 1H), 7.51−7.48 (m, 2H), 7.32 (t, 2H, J = 7.5 Hz),
7.17−7.12 (m, 1H), 6.23−6.21 (m, 1H), 2.31 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3, 24 °C): δ 136.2, 128.9, 128.7, 128.6, 125.4, 125.2,
113.0, 104.5, 13.2.
7sn: 23 mg, 44% yield; gummy solid; 1H NMR (500 MHz, CDCl3,
24 °C): δ 7.6 (d, 2H, J = 6.7 Hz), 7.27−7.23 (m, 3H), 7.18−7.14 (m,
2H), 7.04 (td, 1H, J = 7.3, 1.3 Hz), 6.27 (d, 1H), 3.13 (t, 2H, J = 7.8
Hz). 2.96 (t, 2H, J = 7.8 Hz), 2.46 (s, 3H), 2.38 (s, 3H); 13C {1H}
NMR (125 MHz, CDCl3, 24 °C): δ 144.8, 137.2, 133.7, 132.9, 131.6,
131.3, 130.1, 127.8, 126.8, 126.4, 126.1, 122.4, 122.2, 108.7, 29.6, 22.8,
9d: 12 mg, 66% yield; brown solid; 1H NMR (400 MHz, CDCl3, 24
°C): δ 8.25 (brs, 1H), 7.28−7.22 (m, 5H), 7.19 (d, 2H, J = 8.8 Hz),
6.90 (t, 1H,J = 2.5 Hz), 6.85 (t, 1H, J = 2.5 Hz), 6.83−6.78 (m, 2H),
3.8 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ 158, 136.0,
F
dx.doi.org/10.1021/jo501043h | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
129.8, 128.6, 128.4, 128.3, 125.8, 123.6, 123.4, 117.4, 117.1, 113.8,
55.4.
9e: 18 mg, 79% yield; gummy solid; H NMR (400 MHz, CDCl3,
24 °C): δ 8.41 (brs, 1H), 7.56 (d, 2H, J = 7.16 Hz), 7.43 (d, 2H, J =
8.6 Hz), 7.38−7.34 (m, 4H), 7.25−7.18 (m, 1H), 7.16−7.12 (m, 1H),
6.81−6.80 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ
135.4, 132.2, 132.1, 131.2, 129.3, 128.8, 127.0, 126.0, 125.3, 125.2,
116.0, 104.6.
(3) (a) Lunak, S., Jr.; Vala, M.; Vynuchal, J.; Ouzzane, I.; Horakova,
P.; Moziskova, P.; Elias, Z.; Weiter, M. Dyes Pigm. 2011, 91, 269.
(b) Lunak, S., Jr.; Havel, L.; Vynuchal, J.; Horakova, P.; Kucerik, J.;
Weiter, M.; Hrdina, R. Dyes Pigm. 2010, 85, 27.
(4) (a) Blangy, V.; Heiss, C.; Khlebnikov, V.; Letondor, C.; Stoeckli-
Evans, H.; Neier, R. Angew. Chem., Int. Ed. 2009, 48, 1688. (b) Wienk,
M. M.; Turbiez, M.; Gilot, J.; Janssen, R. A. J. Adv. Mater. 2008, 20,
2556. (c) Wang, Y.; Sotzing, G. A.; Weiss, R. A. Chem. Mater. 2008,
1
9f: 13 mg, 78% yield; brown liquid; 1H NMR (400 MHz, CDCl3, 24
°C): δ 7.61 (brs, 1H), 7.32−7.29 (m, 1H), 7.20−7.14 (m, 2H), 7.03−
6.99 (m, 1H), 6.14 (m, 1H), 2.99 (t, 2H, J = 8.0 Hz), 2.76 (t, 2H, J =
8.0 Hz), 2.29 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ
133.5, 132.8, 127.8, 127.1, 126.6, 124.0, 121.3,118.5, 101.2, 29.8, 21.8,
13.1; HRMS: calcd. for C13H13N + H: 184.1126; found: 184.1121.
Synthesis of 9g. 4-(4-Methoxyphenyl)-1-(phenylsulfonyl)-1H-
1,2,3-triazole (50 mg, 0.16 mmol) and Rh2(OAc)4 (1.4 mg, 0.003
mmol, 2 mol %) were added under a nitrogen atmosphere to an over-
dried 5 mL reaction tube equipped with a stir bar. Subsequently, a
solution of 1-methoxy-4-(2-methoxyvinyl) benzene (53 mg, 0.32
mmol) in cyclohexane (2 mL) was introduced through a syringe. The
reaction tube was sealed and stirred at 90 °C for 24 h. After the TLC
analysis, it was cooled to room temperature and purified by column
chromatography using hexanes/ethyl acetate (17:3) as eluent to afford
the 3,4-bis(4-methoxyphenyl)-1-(phenylsulfonyl)-1H-pyrrole 7g′d (30
mg, 45% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3, 24 °C):
δ 7.94 (d, 2H, J = 7.2 Hz), 7.64−7.60 (m, 1H), 7.55−7.51 (m, 2H),
7.18 (s, 2H), 7.10 (d, 4H, J = 8.8 Hz), 6.79 (d, 4H, J = 8.5 Hz), 3.79
(s, 6H); 13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ 158.8, 139.2,
134.0, 129.8, 129.6, 128.63, 127.1, 126.1, 118.4, 113.9, 55.3; HRMS:
calcd. for C24H21NO4S + H: 420.1270; found: 420.1255. 3,4-Bis(4-
methoxyphenyl)-1-(phenylsulfonyl)-1H-pyrrole (30 mg, 0.1 mmol)
and KOH (16 mg, 0.3 mmol) were added in a round-bottom flask
equipped with a stir bar. Subsequently, 4 mL of a mixture of THF and
methanol in a 1:1 ratio was added, and it was kept at 70 °C for 4 h.
After the TLC analysis, it was cooled to room temperature and
purified by column chromatography using a hexanes/ethyl acetate
mixture as eluent to afford the 3,4-bis(4-methoxyphenyl)-1H-pyrrole
9g (22 mg, 77% yield) as a brown solid. 1H NMR (400 MHz, CDCl3,
24 °C): δ 8.24 (br. s, 1H), 7.19 (d, 4H, J = 8.8 Hz), 6.85 (d, 2H, J =
2.7 Hz), 6.82 (d, 4H, J = 8.8 Hz), 3.8 (s, 6H); 13C{1H} NMR (100
MHz, CDCl3, 24 °C): δ 158.0, 129.7, 128.6, 123.3, 116.9, 113.8, 55.4.
20, 2574. (d) Stępien
Ed. 2007, 46, 1431.
(5) (a) Paal, C. Ber. Dtsch. Chem. Ges. 1885, 18, 367. (b) Knorr, L.
Ber. Dtsch. Chem. Ges. 1884, 17, 1635.
(6) Huisgen, R.; Gotthardt, H.; Bayer, H. O.; Schaefer, F. C. Angew.
Chem., Int. Ed. Engl. 1964, 3, 136.
́
, M.; Donnio, B.; Sessler, J. L. Angew. Chem., Int.
(7) Hantzsch, A. Ber. Dtsch. Chem. Ges. 1890, 23, 1474.
(8) For selected pyrrole synthesis via intermolecular cyclization, see:
(a) Michlik, S.; Kempe, R. Nat. Chem. 2013, 5, 140. (b) Zhang, M.;
Neumann, H.; Beller, M. Angew. Chem., Int. Ed. 2013, 52, 597.
(c) Wang, L.; Ackermann, L. Org. Lett. 2013, 15, 176. (d) Huestis, M.
P.; Chan, L.; Stuart, D. R.; Fagnou, K. Angew. Chem., Int. Ed. 2011, 50,
1338. (e) Lourdusamy, E.; Yao, L.; Park, C.-M. Angew. Chem., Int. Ed.
2010, 49, 7963. (f) Rakshit, S.; Patureau, F. W.; Glorius, F. J. Am.
Chem. Soc. 2010, 132, 9585. (g) Mizuno, A.; Kusama, H.; Iwasawa, N.
Angew. Chem., Int. Ed. 2009, 48, 8318.
(9) For selected pyrrole synthesis via intramolecular cyclization, see:
(a) Jiang, Y.; Chan, W. C.; Park, C.-M. J. Am. Chem. Soc. 2012, 134,
4104. (b) Xin, X.; Wang, D.; Li, X.; Wan, B. Angew. Chem., Int. Ed.
2012, 51, 1693. (c) Egi, M.; Azechi, K.; Akai, S. Org. Lett. 2009, 11,
5002. (d) Kel’in, A. V.; Sromek, A. W.; Gevorgyan, V. J. Am. Chem. Soc.
2001, 123, 2074.
(10) For highlights on rhodium iminocarbenes, see: (a) Gulevich, A.
V.; Gevorgyan, V. Angew. Chem., Int. Ed. 2013, 52, 1371. For recent
literature on functionalization of triazole, see: (b) Kwok, S. W.; Zhang,
L.; Grimster, N. P.; Fokin, V. V. Angew. Chem., Int. Ed. 2014, 53, 3452.
(c) Parr, B. T.; Davies, H. M. L. Angew. Chem., Int. Ed. 2013, 52,
10044. (d) Miura, T.; Funakoshi, Y.; Murakami, M. J. Am. Chem. Soc.
2014, 136, 2272. (e) Miura, T.; Tanaka, T.; Hiraga, K.; Stewart, S. G.;
Murakami, M. J. Am. Chem. Soc. 2013, 135, 13652.
(11) Alford, J. S.; Spangler, J. E.; Davies, H. M. L. J. Am. Chem. Soc.
2013, 135, 11712.
(12) (a) Miura, T.; Yamauchi, M.; Murakami, M. Chem. Commun.
2009, 1470. (b) Chattopadhyay, B.; Gevorgyan, V. Org. Lett. 2011, 13,
3746. (c) Shi, Y.; Gevorgyan, V. Org. Lett. 2013, 15, 5394.
(13) (a) Schultz, E. E.; Sarpong, R. J. Am. Chem. Soc. 2013, 135,
4696. (b) Miura, T.; Hiraga, K.; Biyajima, T.; Nakamuro, T.;
Murakami, M. Org. Lett. 2013, 15, 3298.
ASSOCIATED CONTENT
■
S
* Supporting Information
Supporting Information containing 1H and 13C NMR spectra of
all the new compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
(14) Parr, B. T.; Green, S. A.; Davies, H. M. L. J. Am. Chem. Soc.
2013, 135, 4716.
(15) During the preparation of our manuscript, a similar pyrrole
synthesis from triazole was documented; see: Kim, C.-E.; Park, S.;
Eom, D.; Seo, B.; Lee, P. H. Org. Lett. 2014, 16, 1900.
(16) (a) Yadagiri, D.; Anbarasan, P. Chem.Eur. J. 2013, 19, 15115.
(b) Yadagiri, D.; Anbarasan, P. Org. Lett. 2014, 16, 2510.
(17) Liu, R.; Liu, Y.; Zhou, Y.-D.; Nagle, D. G. J. Nat. Prod. 2007, 70,
1741.
AUTHOR INFORMATION
Corresponding Author
*E-mail: anbarasansp@iitm.ac.in. Fax: +91-44-22574202.
Notes
■
The authors declare no competing financial interest.
(18) Arafeh, K. M.; Ullah, N. Nat. Prod. Commun. 2009, 4, 925.
(19) Cloke, J. B. J. Am. Chem. Soc. 1929, 51, 1174.
ACKNOWLEDGMENTS
■
We thank the Department of Science and Technology (DST),
New Delhi, for funding this work. S.R. thanks the Council of
Scientific & Industrial Research (CSIR) for a JRF fellowship.
REFERENCES
■
(1) (a) Gupton, J. In Heterocyclic Antitumor Antibiotics; Lee, M., Ed.;
Springer: Berlin, 2006; Vol. 2, p 53. (b) Mal, D.; Shome, B.; Dinda, B.
K. In Heterocycles in Natural Product Synthesis; Majumdar, K. C.,
Chattopadhyay, S. K., Eds.; Wiley-VCH Verlag GmbH & Co. KGaA:
Weinheim, Germany, 2011; p 187.
(2) Mason, M. E.; Johnson, B.; Hamming, M. J. Agric. Food Chem.
1966, 14, 454.
G
dx.doi.org/10.1021/jo501043h | J. Org. Chem. XXXX, XXX, XXX−XXX