Tert-Butyl Nitrite Promoted Oxidative Intermolecular Sulfonamination of Alkynes to Synthesize Substituted Sulfonyl Pyrroles from the Alkynylamines and Sulfinic Acids

Article abstract of DOI:10.1021/acs.joc.8b00741

tert-Butyl nitrite promoted oxidative intermolecular sulfonamination of alkynes to synthesize substituted sulfonyl pyrroles from the alkynylamines and sulfinic acids via tandem addition/cyclization was developed. This reaction is performed well by employing tert-butyl nitrite as the oxidant, and various substituted sulfonyl pyrroles are formed in moderate to good yields with no requirement of metal catalysis.

Full text of DOI:10.1021/acs.joc.8b00741

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Note
tert-Butyl Nitrite Promoted Oxidative Intermolecular
Sulfonamination of Alkynes to Synthesize Substituted
Sulfonyl Pyrroles from the Alkynylamines and Sulfinic Acids
Zhenjie Qi, Yong Jiang, Yanyan Wang, and Rulong Yan
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00741 • Publication Date (Web): 06 Jun 2018
Downloaded from http://pubs.acs.org on June 6, 2018
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tert-Butyl
Nitrite
Promoted
Oxidative
Intermolecular
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Sulfonamination of Alkynes to Synthesize Substituted Sulfonyl
Pyrroles from the Alkynylamines and Sulfinic Acids
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Zhenjie Qi,a Yong Jiang,b Yanyan Wang,c Rulong Yan*a
a State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering,
Lanzhou University, Gansu, China.
b School of Chemistry and Chemical Engineering, Yangtze Normal University, Chongqing, China.
c Jinchuan Advanced Materials Technology Co., Ltd. Lanzhou, Gansu, China.
yanrl@lzu.edu.cn
Fax: +86 931 8912596; Tel: +86 931 8912586
Abstract: tertꢀButyl nitrite (TBN) promoted oxidative intermolecular
sulfonamination of alkynes to synthesize substituted sulfonyl pyrroles
from the alkynylamines and sulfinic acids via tandem addition/cyclization
has been developed. This reaction is performed well by employing
tertꢀbutyl nitrite as the oxidant, and various substituted sulfonyl pyrroles
are formed in moderate to good yields with no requirement of metal
catalysis.
The reaction of radicalꢀbased tandem cyclization offers a strategic
platform for the construction of polysubstituted heterocyclic structures in
convergent manners through orchestrated multiple C−C/C−X bonds
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formation. Sulfonyl radical, as intriguing sulfurꢀcentered radical, which
can be initiated from the common sulfinic acid, has received tremendous
attentions in radicalꢀbased reactions due to its greater synthetic value.1 In
recent years, the pioneering studies about sulfonylation reactions using
sulfinic acids as sulfonylating agents, mainly focus on direct
sulfonylation of olefins or alkynes and decarboxylative sulfonylation of
α,βꢀunsaturated carboxylic acids.2 Despite the reactions of direct
sulfonylation have been well exploited so far, the sulfonylation and
cyclization to generate heterocyclic compound with benzenesulfinic acid
through radical tandem reaction are very rare. Efforts from the Han3 and
Zhu4 groups have demonstrated sulfonamination of alkynes to construct
3ꢀsulfonylindoles and sulfoneꢀcontaining 4ꢀquinolones with sulfinic acids
through radical tandem cyclization. Recently, the group of Wang provides
a direct method for the preparation of 3ꢀsulfonated coumarins with
sulfinic acids and phenyl propiolates by visibleꢀlight initiated oxidative
cyclization under metalꢀfree conditions.5 Notwithstanding the impressive
advances, the obvious drawback of these approaches is only generation
the sulfonyl benzoꢀheterocyclic compounds. Therefore, the formation of
sulfonyl pyrroles from sulfinic acid in facial and mild strategy manner is
still highly desirable.
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The substituted pyrroles are privileged heterocyclic scaffold prevalent
in many different fields, incorporating smart materials, pharmaceuticals,
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Scheme 1. Reactions for the Synthesis of Sulfonyl Pyrroles
and natural products.6 Moreover, the sulfonyl substituted pyrroles play
significant influence in organic synthesis and medicinal chemistry.7 While
the research on the synthesis of sulfonyl substituted pyrroles is limited to
only a few reports.8 These methods for the synthesis sulfonyl pyrroles are
mainly based on sulfonyl migration. The group of Chan develops
gold(I)ꢀcatalyzed
cycloisomerization
of
Nꢀsubstituted
Nꢀsulfonylꢀaminobutꢀ3ꢀynꢀ2ꢀols through regioselectivity migration of the
sulfonyl group to synthesize 3ꢀsulfonylꢀ[NH]ꢀpyrroles.9 Recently, a
oneꢀpot synthesis of sulfonyl pyrroles is reported by Laha's group via
sulfonyl migration and oxidative arylation.10 But these methods still
suffer from harsh reaction conditions, multiꢀstep synthesis of precursors,
expensive transition metal catalysts.11 Inspired by recent studies in
construction heterocyclic scaffolds and CꢀS bond formation,12 herein, we
disclose a direct method to synthesize 3ꢀsulfonyl pyrroles from
alkynylamines and sulfinic acids via sulfonamination of alkyne and
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Table 1. Optimization of Reaction Conditiona
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Yield
(%)b
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Entry
Solvent
Oxidant
Acid (%)
1
2
THF
DCE
DMSO
DMF
MeCN
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
TBN
-
54
62
0
-
3
-
4
-
trace
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57
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67
21
45
0
5
-
6c
7d
8
-
-
-
9
K2S2O8
TBHP
BQ
-
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11
12
13
14
15
16
17
18
19
-
-
DDQ
PIDA
TBN
-
0
-
33
60
65
57
73
88
64
CF3SO3H
CF3COOH
BF3·OEt2
AcOH
TBN
TBN
TBN
TBN
AcOH (20)
AcOH (40)
TBN
a All reactions were carried out in argon atmosphere using 1a (0.30
mmol), 2a (0.60 mmol), oxidant (2.2 equiv.), acid (10 mol %) at 100
oC in 2 mL solvent for 10 h. b Isolated yield. c80 oC. d120 oC.
tandem oxidation/cyclization. (Scheme 1).
Initially, the substrates Nꢀ(4ꢀphenylbutꢀ3ꢀynꢀ1ꢀyl) aniline (1a) and
benzenesulfinic acid (2a) were selected as the model for this reaction.
Treating the substrate 1a and 2a with DTBP (diꢀtertꢀbutyl peroxide) in
THF
at
100
oC
under
argon,
the
desired
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1,2ꢀdiphenylꢀ3ꢀ(phenylsulfonyl)ꢀ1Hꢀpyrrole (3aa) was obtained in 54%
yield (Table 1, entry 1). The absolute stereochemistries of the product
was determined by Xꢀray analysis of a single crystal of 3ab13 (in the
Supporting Information). The DCE (1,2ꢀdichloroethane) as solvent gave a
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higher
yield
than
DMSO
(dimethyl
sulfoxide),
DMF
(dimethylformamide), MeCN and THF (entries 1ꢀ5). Changing the
reaction temperature did not increase the yield of product 3aa (entries
6ꢀ7). Then various oxidants were examined for this reaction, TBN
(tertꢀbutyl nitrite) showed better efficiency for this process and gave the
desired product 3aa in 67% (entry 2, entries 8ꢀ13). Meanwhile, it was
found that the acid significantly influenced the reaction and the yield was
increased to 73% when 10 mmol % AcOH was introduced (Table 1,
entries 14ꢀ17). Luckily, increasing the AcOH loading to 20 mol %, the
yield was improved to 88%. (Table 1, entries 17ꢀ19). So the optimized
reaction system was established as Table 1, entry 18.
With the optimized conditions in hand, the scope and generality of this
reaction were investigated, and the results were illustrated in Scheme 2.
The optimized conditions were proved to be effective for the generation
of sunfonyl pyrroles and various alkynylarylamines with
electronꢀdonating or withdrawing groups on benzene rings reacted with
substrate 2a smoothly, giving the desired sulfonyl pyrroles in moderate to
excellent yields. Therefore, the results demonstrated that the reaction was
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Scheme 2. Scope of Aminoalkynesa
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a
Reaction conditions: 1 (0.30 mmol), 2a (0.60 mmol), AcOH (20
mol %) and TBN (0.66 mmol ) in DCE (2.0 mL) at 100 oC under Ar.
sensitive to the steric effect of the orthoꢀposition and the products 3ea
and 3la were obtained only in 58% and 65% yields. The
Nꢀ(4ꢀ(thiophenꢀ2ꢀyl)butꢀ3ꢀynꢀ1ꢀyl)aniline 1g was also tolerated in this
reaction, producing the desired pyrrole 3ga in 65% yield. The substrate 1s
of Nꢀ(butꢀ3ꢀynꢀ1ꢀyl)aniline genenrated the corresponding product 3sa in
46% yield under the standard conditions. Furthermore, homopropargylic
amines with Nꢀsubstituent as alkyl substituents also performed well and
the desired products were isolated in ideal yields (3ta-3wa). In addition
the alkynylarylamines with groups at 4ꢀposition or alkyl group at
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Scheme 3. Scope of Sulfinic Acidsa
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a Reaction conditions: 1a (0.30 mmol), 2 (0.60 mmol), AcOH (20
mol %) and TBN (0.66 mmol) in DCE (2.0 mL) at 100 oC under Ar.
1ꢀposition performed unsuccessfully in this process and no products were
detected (3xaꢀ3za).
Having successfully achieved the cascade sequence with
homopropargylic amines, we shifted our attention to explore the scope of
sulfinic acids 2. The reactions of a variety of sulfinic acids with 1a were
tested, and the results were illustrated in Scheme 3. Arylsulfinic acids
bearing substituents such as pꢀMe, pꢀOMe, pꢀCF3, pꢀOCF3, pꢀCl, pꢀF,
pꢀCN (2cꢀ2i) on the phenyl ring gave the corresponding sulfonyl
substituted pyrroles in high yields. Obviously, 2ꢀmethylbenzenesulfinic
acid reacted with 1a to afford 3ab in 67% yield, suggesting that the
Scheme 4. Scalable Experiment of Substituted Sulfonyl Pyrroles
O
O
S
Ph
Ph
AcOH (20 mol %)
TBN (2.2 equiv)
H
O
S
OH
N
Ph
+
Ph
N
DCE, Ar, 10 h
Ph
Ph
2a
1a
(5mmol, 1.10g)
3aa
(68%)
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reaction was influenced by the steric effect. More challenging substrate 2j
was also tolerated well, generating the desired product in 79% yield. The
methanesulfinic acid 2l performed unsuccessfully in this process and only
trace desired product was detected.
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It was worth mention that scalable experiment of substituted sulfonyl
pyrroles had been performed with optimized conditions and the desired
product 3aa was obtained in 68% when the amount of substrate 1a was
increased to 5mmol (1.10g) (Scheme 4).
In order to gain further insight into this reaction and verify the reaction
mechanism, 3.0 equiv the radical scavenge of 2,2,6,6ꢀtetramethylꢀ1ꢀpiperi
dinylꢀoxy (TEMPO) was added to the standard reaction system and no
desired product 3aa was detected. The result demonstrated that the
reaction underwent radical pathway (Scheme 5, entry 1). When the
radical scavenger of 2,6ꢀdiꢀtertꢀbutylꢀ4ꢀmethylꢀphenol (BHT) was used
for this reaction, the product 3aa was almost not detected and a product
414 (in the Supporting Information), which was confirmed by NMR,
HMRS and XRD spectroscopy, was isolated in 52% yield (Scheme 5,
entry 2). This result suggested that sulfonyl radical should be the
important radical intermediate for this transformation.
Based on the above control experiment and the literature,2ꢀ5 a plausible
mechanism is proposed in Scheme 6. Initially, sulfinic acids 2a reacts
with TBN to generate the corresponding radical A, which could
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Scheme 5. Control Experiments
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equilibrates to intermediate B under optimized conditions. Subsequently,
the sulfonyl radical adds to the alkynyl moiety of substrate 1a to afford
the vinyl radical intermediate C under acidic and oxidative conditions.
The intermediate D is easily gained from C via intramolecular radical
addition and cyclization process. Finally, D is oxidized to give the desired
product 3aa.
In summary, we have demonstrated a metalꢀfree and direct annulation
method for the synthesis of 3ꢀsubstituted pyrrole sulfones from
Scheme 6. Proposed Mechanism
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alkynylarylamines and sulfinic acids via radical cascade
sulfonation/cyclization process. This protocol not only provides a novel
method for the efficient CꢀS bond formation but also provides a general
approach for the synthesis of 3ꢀsulfonylpyrrole frameworks. In addition,
various substituted homopropargylic amines proceed smoothly with
sulfinic acids and the desired products are obtained in moderate to good
yields.
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Experimental Section
1
General remarks. H NMR and 13C NMR spectra of materials and
products were respectively recorded on 300MHz and 75MHz (VARIAN
300M), 400MHz and 100MHz (BRUKER 400M or JNMꢀECS 400M) in
CDCl3. All chemical shifts are given as δ value (ppm) with reference to
tetramethylsilane (TMS) as an internal standard. All compounds were
further characterized by HRMS; HRMS was performed on an FTꢀICRMS
mass instrument and measured with electrospray ionization (ESI). Copies
1
of their H NMR and 13C NMR spectra are provided in Supporting
Information. Products were purified by flash chromatography on 200ꢀ300
mesh silica gels. All melting points were determined without correction.
Unless otherwise noted, commercially available reagents and solvents
were used without further purification. In addition, it is important to note
that tertꢀbutyl nitrite (TBN) is toxic and easily to decompose.
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General procedure for the synthesis of aminoalkynes 1a-1w and
1z15ꢀ17. For the reaction scheme, see Scheme S1 in the Supporting
Information.
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To a suspension of Pd(PPh3)2Cl2 (21 mg, 0.03 mmol), CuI (5.7 mg,
0.03 mmol) in Et3N (1.5 mL) was added a solution of R2I (1.2 eq) and
butꢀ3ꢀynꢀ1ꢀol (210 mg, 3.0 mmol, 1.0 eq) in Et3N (15 mL). The mixture
was stirred at room temperature for 12 h and then was diluted with
EtOAc (20 mL), filtered off and evaporated under reduced pressure. The
residue was purified through column chromatography on silica gel
(petroleum ether/EtOAc = 15/1 to 5/1) to afford substituted S1 in 90%
yields as yellow oil.
To a solution of S1 (3 mmol), triethylamine (0.52 mL, 3.6 mmol), and
4ꢀ(dimethylamino)pyridine (7.8 mg, 0.05 mmol) in DCM (18 mL) at 0 oC
was added pꢀtoluenesulfonyl chloride (0.6 g, 3.1 mmol) in three portions.
The reaction mixture was brought to room temperature and stirred for 15
h. Aq. NaOH (1 N, 5.7 mL) was added, and the mixture was vigorously
stirred for 15 min at rt. The usual workup (DCM, brine) gave
pꢀtoluenesulfonate derivatives S2 in 80% yields as yellowish oil.
To a solution of R1NH2 (3.0 mmol, 1.5 eq), the above obtained S2 (2.0
mmol, 1 eq) and KI (0.2 mmol, 0.1 eq) in DMF (4 mL) was added K2CO3
(6.0 mmol, 3 eq). The mixture was heated to 90 °C. After the complete
consumption of S2 (TLC), the reaction mixture was cooled to room
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temperature, quenched with a saturated solution of NH4Cl, extracted with
AcOEt three times (3×20 mL), washed with small amounts of water (100
mL). The combined organic layers were dried with anhydrous Na2SO4
and the solvent was removed in vacuo to afford a residue. The residue
was purified by column chromatography on silica gel using petroleum
ether/EtOAc (40:1) as eluent to provide the desired compounds 1a-1w in
35%ꢀ80% yields as a yellow oil.
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N-(3-phenylprop-2-yn-1-yl)aniline (1a). Yellow oil (397.8 mg, 60%
1
yield). H NMR (300 MHz, CDCl3, ppm): δ = 7.42ꢀ7.39 (m, 2 H),
7.30ꢀ7.28 (m, 3 H), 7.22ꢀ7.18 (m, 2 H), 6.75ꢀ6.72 (m, 1 H), 6.68ꢀ6.66 (m,
2 H), 3.99 (s, 1 H), 3.42ꢀ3.38 (m, 2 H), 2.75ꢀ2.71 (m, 2 H); 13C NMR (75
MHz, CDCl3, ppm): δ = 147.7, 131.6, 129.3, 128.3, 127.9, 123.4, 117.8,
113.2, 87.2, 82.3, 42.8, 20.2.
N-(4-(p-tolyl)but-3-yn-1-yl)aniline (1b). Yellow oil (458.2 mg, 65%
1
yield). H NMR (300 MHz, CDCl3, ppm): δ = 7.31ꢀ7.28 (m, 2 H),
7.19ꢀ7.15 (m, 2 H), 7.07ꢀ7.06 (m, 2 H), 6.73ꢀ7.69 (m, 1 H), 6.62ꢀ6.60 (m,
2 H), 3.92 (s, 1 H), 3.34ꢀ3.30 (m, 2 H), 2.67ꢀ2.63 (m, 2 H), 2.30 (s, 3 H);
13C NMR (75 MHz, CDCl3, ppm): δ = 147.5, 137.8, 131.4, 129.2, 128.9,
120.2, 117.6, 113.0, 86.4, 82.2, 42.6, 21.3, 20.0.
N-(4-(3,4-dimethylphenyl)but-3-yn-1-yl)aniline (1c). Yellow oil (410.9
1
mg, 55% yield). H NMR (300 MHz, CDCl3, ppm): δ = 7.20ꢀ7.13 (m, 4
H), 7.05ꢀ7.03 (m, 1 H), 6.74ꢀ6.70 (m, 1 H), 6.65ꢀ6.63 (m, 2 H), 3.96 (s, 1
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H), 3.37ꢀ3.34 (m, 2 H), 2.70ꢀ2.67 (m, 2 H), 2.23 (s, 3 H), 2.21 (s, 3 H);
13C NMR (75 MHz, CDCl3, ppm): δ = 147.7, 136.7, 136.5, 132.6, 129.5,
129.3, 129.0, 120.6, 117.7, 113.1, 86.1, 82.3, 42.7, 20.1, 19.6, 19.5.
N-(4-(3,5-dimethylphenyl)but-3-yn-1-yl)aniline (1d). Yellow oil (433.3
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mg, 58% yield). H NMR (300 MHz, CDCl3, ppm): δ = 7.21ꢀ7.16 (m, 2
H), 7.04 (s, 2 H), 6.92 (s, 1 H), 6.75ꢀ6.71 (m, 1 H), 6.66ꢀ6.64 (d, J = 6.0
Hz, 2 H), 3.96 (s, 1 H), 3.37ꢀ3.34 (m, 2 H), 2.70ꢀ2.67 (m, 2 H), 2.27 (s, 6
13
H); C NMR (75 MHz, CDCl3, ppm): δ = 147.7, 137.8, 129.8, 129.3,
123.0, 117.7, 113.1, 86.4, 82.5, 42.7, 21.1, 20.1.
N-(4-(2-fluorophenyl)but-3-yn-1-yl)aniline (1e). Yellow oil (487.7 mg,
1
68% yield). H NMR (400 MHz, CDCl3, ppm): δ = 7.40ꢀ7.36 (m, 1 H),
7.26ꢀ7.17 (m, 3 H), 7.07ꢀ7.02 (m, 2 H), 6.75ꢀ6.70 (m, 1 H), 6.67ꢀ6.65 (m,
13
2 H), 4.02 (s, 1 H), 3.40ꢀ3.37 (m, 2 H), 2.75ꢀ2.72 (m, 2 H); C NMR
(100 MHz, CDCl3, ppm): δ = 162.9 (d, J = 249.0 Hz, 1 C), 147.6, 133.4,
129.5 (d, J = 8.0 Hz, 1 C), 129.3, 123.8 (d, J = 4.0 Hz, 1 C), 117.7, 115.3
(d, J = 19.0 Hz, 1 C), 113.1, 111.9 (d, J = 16.0 Hz, 1 C), 92.7, 75.6, 42.5,
20.2.
N-(4-(3-fluorophenyl)but-3-yn-1-yl)aniline (1f). Yellow oil (430.2 mg,
1
60% yield). H NMR (400 MHz, CDCl3, ppm): δ = 7.25ꢀ7.16 (m, 4 H),
7.11ꢀ7.07 (m, 1 H), 7.01ꢀ6.96 (m, 1 H), 6.75ꢀ6.72 (m, 1 H), 6.66ꢀ6.64 (m,
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2 H), 3.93 (s, 1 H), 3.39ꢀ3.36 (m, 2 H), 2.71ꢀ2.68 (m, 2 H); C NMR
(100 MHz, CDCl3, ppm): δ = 162.3 (d, J = 245.0 Hz, 1 C), 147.5, 129.8,
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129.3, 127.8, 125.3 (d, J = 10.0 Hz, 1 C), 118.5 (d, J = 30.0 Hz, 1 C),
117.8, 115.2 (d, J = 22.0 Hz, 1 C), 113.1, 88.4, 81.1, 42.5, 20.1.
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N-(4-(thiophen-2-yl)but-3-yn-1-yl)aniline (1g). Yellow oil (306.5 mg,
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45% yield). H NMR (300 MHz, CDCl3, ppm): δ = 7.23ꢀ7.16 (m, 4 H),
7.01 (m, 1 H), 6.77ꢀ6.58 (m, 3 H), 4.32ꢀ4.30 (m, 2 H), 3.93 (s, 1 H),
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2.26ꢀ2.23 (m, 2 H); C NMR (75 MHz, CDCl3, ppm): δ = 147.6, 132.0,
129.5, 127.8, 127.2, 122.5, 120.9, 113.6, 96.3, 84.0, 50.3, 18.9.
3-methyl-N-(4-phenylbut-3-yn-1-yl)aniline (1h). Yellow oil (444.2 mg,
1
63% yield). H NMR (300 MHz, CDCl3, ppm): δ = 7.42ꢀ7.39 (m, 2 H),
7.30ꢀ7.24 (m, 3 H), 7.11ꢀ7.06 (m, 1 H), 6.58ꢀ6.56 (d, J = 6.0 Hz, 1 H),
6.49ꢀ6.47 (d, J = 6.0 Hz, 2 H), 3.93 (s, 1 H), 3.41ꢀ3.36 (m, 2 H),
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2.74ꢀ2.69 (m, 2 H), 2.29 (s, 3 H); C NMR (75 MHz, CDCl3, ppm): δ =
147.7, 139.1, 131.6, 129.2, 128.2, 127.9, 123.4, 118.7, 113.9, 110.2, 87.2,
82.2, 42.7, 21.6, 20.2.
4-methyl-N-(4-phenylbut-3-yn-1-yl)aniline (1i). Yellow oil (472.4 mg,
1
67% yield). H NMR (300 MHz, CDCl3, ppm): δ = 7.42ꢀ7.39 (m, 2 H),
7.29ꢀ7.26 (m, 3 H), 7.01ꢀ6.99 (d, J = 6.0 Hz, 2 H), 6.60ꢀ6.57 (m, 2 H),
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3.84 (s, 1 H), 3.37ꢀ3.33 (m, 2 H), 2.71ꢀ2.67 (m, 2 H), 2.24 (s, 3 H); C
NMR (75 MHz, CDCl3, ppm): δ = 145.3, 131.6, 129.8, 128.2, 127.8,
127.0, 123.4, 113.5, 87.3, 82.1, 43.0, 20.4, 20.1.
4-ethyl-N-(4-phenylbut-3-yn-1-yl)aniline (1j). Yellow oil (470.6 mg,
1
63% yield). H NMR (300 MHz, CDCl3, ppm): δ = 7.42ꢀ7.39 (m, 2 H),
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7.29ꢀ7.26 (m, 3 H), 7.04ꢀ7.02 (m, 2 H), 6.61ꢀ6.59 (m, 2 H), 3.85 (s, 1 H),
3.37ꢀ3.33 (m, 2 H), 2.71ꢀ2.66 (m, 2 H), 2.58ꢀ2.50 (m, 2 H ), 1.22ꢀ1.16 (m,
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3 H); C NMR (75 MHz, CDCl3, ppm): δ = 145.5, 133.6, 131.6, 128.6,
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128.2, 127.8, 123.4, 113.3, 87.3, 82.1, 43.0, 27.9, 20.1, 16.0.
3,5-dimethyl-N-(4-phenylbut-3-yn-1-yl)aniline (1k). Yellow oil (515.4
1
mg, 69% yield). H NMR (300 MHz, CDCl3, ppm): δ = 7.42ꢀ7.39 (m, 2
H), 7.30ꢀ7.28 (m, 3 H), 6.40 (s, 1 H), 6.30 (s, 2 H), 3.87 (s, 1 H),
3.39ꢀ3.35 (m, 2 H), 2.73ꢀ2.68 (m, 2 H), 2.22 (s, 6 H); 13C NMR (75 MHz,
CDCl3, ppm): δ = 147.7, 139.0, 131.6, 128.2, 127.8, 123.4, 119.8, 111.1,
87.3, 82.1, 42.7, 21.5, 20.2.
2-fluoro-N-(4-phenylbut-3-yn-1-yl)aniline (1l). Yellow oil (351.3 mg,
1
49% yield). H NMR (300 MHz, CDCl3, ppm): δ = 7.42ꢀ7.40 (m, 2 H),
7.30ꢀ7.28 (m, 3 H), 7.01ꢀ6.96 (m, 2 H), 6.78ꢀ6.73 (m, 1 H), 6.67ꢀ6.62 (m,
1 H), 4.27 (s, 1 H), 3.45ꢀ3.41 (m, 2 H), 2.76ꢀ2.73 (m, 2 H); 13C NMR (75
MHz, CDCl3, ppm): δ = 153.3 (J = 178.5 Hz, 1 C), 137.8 (d，J = 9.0 Hz, 1
C), 133.2, 129.8, 129.5, 126.1, 124.9, 118.6 (d, J = 6.8 Hz, 1 C), 116.2 (d,
J = 13.5 Hz, 1 C), 113.9 (d, J = 3.0 Hz, 1 C), 88.3, 84.0, 43.9, 21.7.
4-chloro-N-(4-phenylbut-3-yn-1-yl)aniline (1m). Yellow oil (382.5 mg,
1
50% yield). H NMR (300 MHz, CDCl3, ppm): δ = 7.42ꢀ7.38 (m, 2 H),
7.31ꢀ7.28 (m, 3 H), 7.15ꢀ7.12 (m, 2 H), 6.60ꢀ6.55 (m, 2 H), 3.40 (s, 1 H),
3.37ꢀ3.33 (m, 2 H), 2.73ꢀ2.68 (m, 2 H); 13C NMR (75 MHz, CDCl3, ppm):
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δ = 146.2, 131.6, 129.1, 128.3, 128.0, 123.3, 122.3, 114.2, 86.8, 82.4,
42.7, 20.0.
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N-(4-phenylbut-3-yn-1-yl)-[1,1'-biphenyl]-4-amine (1n). Yellow oil
(356.4 mg, 40% yield). 1H NMR (300 MHz, CDCl3, ppm): δ = 7.54ꢀ7.52
(d, J = 6.0 Hz, 2 H), 7.46ꢀ7.36 (m, 6 H), 7.28ꢀ7.22 (m, 4 H), 6.71ꢀ6.69 (d,
J = 6.0 Hz, 2 H), 4.03 (s, 1 H), 3.41ꢀ3.37 (m, 2 H), 2.72ꢀ2.69 (m, 2 H);
13C NMR (75 MHz, CDCl3, ppm): δ = 147.1, 141.1, 131.6, 130.6, 128.6,
128.2, 127.9, 127.9, 126.2, 126.1, 123.4, 113.3, 87.1, 82.3, 42.7, 20.2.
3-chloro-4-methyl-N-(4-phenylbut-3-yn-1-yl)aniline (1o). Yellow oil
(339.3 mg, 43% yield). 1H NMR (300 MHz, CDCl3, ppm): δ = 7.41ꢀ7.39
(m, 2 H), 7.30ꢀ7.28 (m, 3 H), 7.02ꢀ7.00 (d, J = 6.0 Hz, 1 H), 6.67 (d, J =
0.5 Hz, 1 H), 6.49ꢀ6.46 (m, 1 H), 3.91 (s, 1 H), 3.36ꢀ3.32 (m, 2 H),
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2.72ꢀ2.68 (m, 2 H), 2.25 (s, 3 H); C NMR (75 MHz, CDCl3, ppm): δ =
146.8, 134.9, 131.6, 131.3, 128.3, 127.9, 124.6, 123.3, 113.4, 112.0, 86.9,
82.3, 42.8, 20.1, 18.9.
2-methoxy-N-(4-(p-tolyl)but-3-yn-1-yl)aniline (1p). Yellow oil (349.8
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mg, 44% yield). H NMR (300 MHz, CDCl3, ppm): δ = 7.31ꢀ7.29 (m, 2
H), 7.09ꢀ7.07 (d, J = 6.0 Hz, 2 H), 6.90ꢀ6.86 (m, 1 H), 6.77ꢀ6.75 (m, 1 H),
6.70ꢀ6.64 (m, 2 H), 4.57 (s, 1 H), 3.81 (s, 3 H), 3.40ꢀ3.37 (m, 2 H),
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2.73ꢀ2.69 (m, 2 H), 2.32 (s, 3 H); C NMR (75 MHz, CDCl3, ppm): δ =
146.9, 137.7, 137.6, 131.4, 128.9, 121.2, 120.4, 116.7, 109.9, 109.5, 86.5,
82.1, 55.3, 42.5, 21.3, 20.1.
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N-(4-(3,5-dimethylphenyl)but-3-yn-1-yl)-2-methoxyaniline
(1q).
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Yellow oil (334.8 mg, 40% yield). 1H NMR (300 MHz, CDCl3, ppm): δ =
7.04 (s, 2 H), 6.90ꢀ6.86 (m, 2 H), 6.77ꢀ6.76 (d, J = 3.0 Hz, 1 H),
6.70ꢀ6.64 (m, 2 H), 4.57 (s, 1 H), 3.82 (s, 3 H), 3.40ꢀ3.37 (m, 2 H),
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2.72ꢀ2.69 (m, 2 H), 2.26 (s, 6 H); C NMR (75 MHz, CDCl3, ppm): δ =
146.9, 137.6, 137.6, 129.6, 129.2, 123.1, 121.2, 116.7, 109.9, 109.5, 86.5,
82.3, 55.3, 42.5, 21.0, 20.1.
4-chloro-N-(4-(3,5-dimethylphenyl)but-3-yn-1-yl)aniline (1r). Yellow
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oil (297.2 mg, 35% yield). H NMR (300 MHz, CDCl3, ppm): δ =
7.13ꢀ7.11 (m, 2 H), 7.03 (s, 2 H), 6.92 (s, 1 H), 6.56ꢀ6.54 (m, 2 H), 4.52
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(s, 1 H), 3.33ꢀ3.29 (m, 2 H), 2.69ꢀ2.65 (m, 2 H), 2.27 (s, 6 H); C NMR
(75 MHz, CDCl3, ppm): δ = 146.3, 137.8, 129.8, 129.3, 129.0, 122.8,
122.1, 114.1, 86.1, 52.6, 42.7, 21.0, 20.0.
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N-(but-3-yn-1-yl)aniline (1s). Yellow oil (355.2 mg, 80% yield). H
NMR (300 MHz, CDCl3, ppm): δ = 7.18ꢀ7.14 (m, 2 H) , 6.73ꢀ6.69 (m, 1
H), 6.60ꢀ6.58 (m, 2 H), 3.88 (s, l H), 3.27 (m, 1 H), 2.45ꢀ2.41 (m, 2 H),
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2.05ꢀ2.00 (m, 2 H); C NMR (75 MHz, CDCl3, ppm): δ = 147.4, 129.2,
117.7, 113.0, 81.7, 70.0, 42.3, 19.0.
N-benzyl-4-phenylbut-3-yn-1-amine (1t). Yellow oil (493.5 mg, 70%
1
yield). H NMR (300 MHz, CDCl3, ppm): δ = 7.40ꢀ7.38 (m, 2 H),
7.36ꢀ7.31(m, 4 H), 7.29ꢀ7.25 (m, 4 H), 3.86 (s, 2 H), 2.89ꢀ2.86 (m, 2 H),
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2.66ꢀ2.62 (m, 2 H), 2.09 (s, 1 H); C NMR (75 MHz, CDCl3, ppm): δ =
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140.0, 131.7, 131.4, 128.6, 128.3, 127.9, 127.5, 123.6, 87.8, 81.8, 53.3,
47.5, 20.5.
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N-butyl-4-phenylbut-3-yn-1-amine (1u). Yellow oil (434.2 mg, 72%
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yield). H NMR (400 MHz, CDCl3, ppm): δ = 7.41ꢀ7.39 (m, 2 H),
7.28ꢀ7.27 (m, 3 H), 2.87ꢀ2.84 (m, 2 H), 2.66ꢀ2.60 (m, 4 H), 1.71 (s, 1 H),
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1.52ꢀ1.48 (m, 2 H), 1.39ꢀ1.35 (m, 2 H), 0.94ꢀ0.91 (m, 3 H); C NMR
(100 MHz, CDCl3, ppm): δ = 131.8, 128.5, 127.6, 123.8, 88.1, 81.8, 49.2,
48.7, 47.9, 32.3, 20.6, 14.1.
N-(4-phenylbut-3-yn-1-yl)cyclohexanamine (1v). Yellow oil (469.9 mg,
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69% yield). H NMR (400 MHz, CDCl3, ppm): δ = 7.41ꢀ7.38 (m, 2 H),
7.30ꢀ7.27 (m, 3 H), 2.90ꢀ2.85 (m, 2 H), 2.62ꢀ2.58 (m, 2 H), 2.53ꢀ2.46 (m,
1 H), 1.92ꢀ1.88 (d, J = 16.0 Hz, 2 H), 1.76ꢀ1.61 (m, 4 H), 1.33ꢀ1.07 (m, 5
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H); C NMR (100 MHz, CDCl3, ppm): δ = 131.5, 128.2, 127.6, 123.6,
88.0, 81.7, 56.2, 45.2, 33.56, 26.1, 25.0, 20.8.
N-(4-phenylbut-3-yn-1-yl)octadecan-1-amine (1w). Yellow oil (547.9
1
mg, 46% yield). H NMR (400 MHz, CDCl3, ppm): δ = 7.42ꢀ7.38 (m, 2
H), 7.29ꢀ7.26 (m, 3 H), 2.88ꢀ2.83 (m, 2 H), 2.68ꢀ2.60 (m, 4 H), 1.67 (s, 1
13
H), 1.51ꢀ1.49 (m, 2 H), 1.25 (m, 30 H), 0.89ꢀ0.88 (m, 3 H); C NMR
(100 MHz, CDCl3, ppm): δ = 131.6, 128.2, 127.7, 123.6, 87.9, 81.7, 49.4,
48.2, 31.9, 30.1, 29.7, 29.6, 29.4, 27.3, 22.7, 20.5, 14.1.
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N-(hept-3-yn-1-yl)aniline (1z). Yellow oil (415.1 mg, 74% yield). H
NMR (400 MHz, CDCl3, ppm): δ = 7.19ꢀ7.14 (m, 2 H), 6.72ꢀ6.68 (m, 1
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H), 6.62ꢀ6.60 (m, 2 H), 3.91 (s, 1 H), 3.32ꢀ3.20 (m, 2 H), 2.47ꢀ2.42 (m, 2
H), 2.16ꢀ2.11 (m, 2 H), 1.55ꢀ1.46 (m, 2 H), 0.99ꢀ0.95 (m, 3 H); 13C NMR
(100 MHz, CDCl3, ppm): δ = 147.8, 129.2, 117.5, 113.0, 82.0, 77.2, 42.9,
22.3, 20.7, 19.4, 13.4.
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General procedure for the synthesis of 1x-1y18ꢀ19. For the reaction
scheme, see Scheme S2 in the Supporting Information.
A dried roundꢀbottom flask was charged with benzaldehyde (8.0
mmol), the aniline (8.0 mmol), molecular sieves 4Å (1mg /1.0 mmol
aldehyde) and dichloromethane. The reaction mixture was stirred at room
temperature and traced by TLC until the reaction finished. Then the
mixture was filtered and the filtrate was concentrated under reduced
pressure, gave the pure imines without additional purification.
An aluminum amalgam was prepared from aluminum powder (0.5 g,
18.0 mmol) and a catalytic amount of mercuric chloride (10 mg) in 7.5
mL anhydrous THF by vigorously stirring at room temperature for 1 h
under a N2 atmosphere. A solution of propargyl bromide (18.0 mmol ) in
12.5 mL of anhydrous THF was then slowly added to the suspension at
such a rate as to maintain the temperature between 30ꢀ40℃. After the
addition, the reaction mixture was continued to stir until a dark grey
solution was obtained. The generated propargyl aluminum sesquibromide
solution was added to a solution of imine (6.0 mmol) in 20.0 mL of
anhydrous THF at ꢀ78℃ under N2 atmosphere. The reaction mixture was
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stirred at ꢀ78℃ for about 1 h, then warmed to room temperature and
continue to stir for additional 3ꢀ4 h (monitored by TLC). The mixture was
quenched by adding saturated NH4Cl (aq), and extracted with EtOAc (3
×20 mL), and washed with brine, combined organic extracts, dried over
MgSO4, and concentrated in vacuo to give the residue. The residue was
purified by flash chromatography over silica gel (gradient elution of
EtOAc /petroleum ether, PE : EA = 50 : 1).
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N-(1-(4-chlorophenyl)-4-phenylbut-3-yn-1-yl)aniline (1x). Yellow oil
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(506.4mg, 51% yield). H NMR (400 MHz, CDCl3, ppm): δ = 7.41ꢀ7.25
(m, 8 H), 7.14ꢀ7.08 (m, 2 H), 6.72ꢀ6.67 (m, 2 H), 6.55ꢀ6.52 (d, J = 12.0
Hz, 2 H), 4.61ꢀ4.55 (m, 1 H), 4.48 (s, 1 H), 3.00ꢀ2.81 (m, 2 H); 13C NMR
(100 MHz, CDCl3, ppm): δ = 146.8, 140.9, 133.1, 131.6, 129.2, 128.8,
128.3, 128.1, 127.8, 123.0, 118.0, 113.7, 85.1, 56.2, 29.2.
N-(1-phenyloct-1-yn-4-yl)aniline (1y). Yellow solid (482.0 mg, 58%
1
yield). H NMR (400 MHz, CDCl3, ppm): δ = 7.40ꢀ7.37 (m, 2 H),
7.28ꢀ7.25 (m, 3 H), 7.19ꢀ7.15 (m, 2 H), 6.71ꢀ6.67 (m, 1 H), 6.63ꢀ6.61 (m,
2 H), 3.71 (s, 1 H), 3.60ꢀ3.57 (m, 1 H), 1.81ꢀ1.77 (m, 1 H), 1.66ꢀ1.34 (m,
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1 H), 1.46ꢀ1.34 (m, 4 H), 0.97ꢀ0.90 (m, 3 H); C NMR (100 MHz,
CDCl3, ppm): δ = 147.3, 131.6, 129.3, 128.2, 127.7, 123.6, 117.3, 113.4,
86.6, 82.7, 51.7, 34.0, 28.4, 24.7, 22.6, 14.0
General procedure for the synthesis of sulfinic acids20
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Benzenesulfinic acid and pꢀtoluenesulfinic acid were obtained by
acidification of the commercially available sodium benzenesulfinate and
sodium pꢀtoluenesulfinate, then the mixture was extracted by Et2O. After
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dried by Na2SO4, the solvent was removed under vacuum at 0 C to
provide pure product. Other arylsulfinic acids, heteroaromatic and
aliphatic sulfinic acids were prepared by the following procedures:
arylsulfonyl chloride (10 mmol) and anhydrous sodium sulfite (30 mmol)
were added into 20 mL of water. The reaction mixture was kept at 70ꢀ80
oC for 5 h. After the reaction was complete, the mixture was washed with
chloroform. The water phase was acidified with excess concentrated HCl
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solution at 0 C, then extracted by Et2O. After dried by Na2SO4, the
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organic solvent was removed under vacuum at 0 C to provide pure
products.
General procedure for synthesis of substituted sulfonyl pyrroles from
alkynylanilines and sulfinic acids:
The alkynylamines 1 (1 equiv, 0.3 mmol), sulfinic acids 2 (2 equiv, 0.6
mmol), TBN (2.2 equiv, 0.66 mmol) (TBN is very toxic and dangerous.
Caution!), AcOH (20 mol %, 0.06 mmol) were mixed in DCE (2 mL)
were stirred at 100 oC under argon atmosphere for 10 h (TLC monitored).
Then the reaction mixture was cooled to room temperature and the
solvent was evaporated in vacuo, the crude product was purified by
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column chromatography, eluting with petroleum ether/EtOAc (10:1) to
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1,2-diphenyl-3-(phenylsulfonyl)-1H-pyrrole (3aa).
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Yellow solid (94.8 mg, 88% yield), melting point: 94ꢀ96 C. H NMR
(400 MHz, CDCl3, ppm): δ 7.52ꢀ7.50 (d, J = 8.0 Hz, 2 H), 7.41ꢀ7.38 (m,
1 H), 7.29ꢀ7.17 (m, 8 H), 7.09ꢀ7.07 (m, 2 H), 7.02ꢀ7.00 (m, 2 H),
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6.91ꢀ6.89 (m, 2 H); C NMR (100 MHz, CDCl3, ppm): δ 143.1, 138.6,
135.5, 132.1, 131.4, 129.1, 129.0, 128.6, 128.4, 127.7, 127.6, 127.0,
125.8, 124.1, 122.4, 110.4; HRMS(ESI)m/z calcd for C22H18NO2S
[M+H]+ 360.1053; found: 360.1046.
1-phenyl-3-(phenylsulfonyl)-2-(p-tolyl)-1H-pyrrole (3ba).
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Yellow solid (76.1 mg, 68% yield), melting point: 106ꢀ108 C. H NMR
(300 MHz, CDCl3, ppm): δ 7.55ꢀ7.53 (d, J = 6.0 Hz, 2 H), 7.43ꢀ7.38 (m,
1 H), 7.30ꢀ7.21 (m, 6 H), 7.03ꢀ6.97 (m, 5 H), 6.87 (s, 2 H), 2.31 (s, 3 H);
13C NMR (75 MHz, CDCl3, ppm): δ 143.2, 138.7, 138.4, 135.7, 132.0,
131.4, 131.2, 128.9, 128.4, 127.6, 127.5, 126.9, 125.8, 123.7, 122.3,
110.4, 21.3; HRMS(ESI)m/z calcd for C23H20NO2S [M+H]+ 374.1209;
found: 374.1217.
2-(3,4-dimethylphenyl)-1-phenyl-3-(phenylsulfonyl)-1H-pyrrole (3ca).
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Yellow solid (84.8 mg, 73% yield), melting point: 120ꢀ122 C. H NMR
(300 MHz, CDCl3, ppm): δ 7.58ꢀ7.55 (m, 2 H), 7.45ꢀ7.40 (m, 1 H),
7.32ꢀ7.22 (m, 6 H), 7.04ꢀ7.01 (m, 1 H), 6.95ꢀ6.92 (m, 1 H), 6.89ꢀ6.86 (m,
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2 H), 6.80 (s, 1 H), 6.76ꢀ6.73 (d, J = 9.0 Hz, 1 H), 2.21 (s, 3 H), 2.11 (s, 3
H); 13C NMR (75 MHz, CDCl3, ppm): δ 143.3, 138.8, 137.1, 136.0, 135.7,
132.4, 132.0, 128.9, 128.7, 128.3, 127.6, 127.5, 127.1, 126.4, 125.9,
123.7, 122.1, 110.4, 19.6, 19.6; HRMS(ESI)m/z calcd for C24H22NO2S
[M+H]+ 388.1366; found: 388.1376.
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2-(3,5-dimethylphenyl)-1-phenyl-3-(phenylsulfonyl)-1H-pyrrole (3da).
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Yellow solid (90.6 mg, 78% yield), melting point: 123ꢀ125 C. H NMR
(300 MHz, CDCl3, ppm): δ 7.57ꢀ7.54 (m, 2 H), 7.45ꢀ7.40 (m, 1 H),
7.32ꢀ7.22 (m, 6 H), 7.04ꢀ7.01 (m, 2 H), 6.91ꢀ6.86 (m, 3 H), 6.60 (s, 2 H),
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2.15 (s, 6 H); C NMR (75 MHz, CDCl3, ppm): δ 143.2, 138.8, 137.0,
135.9, 132.0, 130.2, 129.0, 128.9, 128.3, 127.9, 127.5, 127.2, 125.8,
123.8, 122.0, 110.4, 21.1; HRMS(ESI)m/z calcd for C24H22NO2S [M+H]+
388.1366; found: 388.1360.
2-(2-fluorophenyl)-1-phenyl-3-(phenylsulfonyl)-1H-pyrrole (3ea).
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Yellow solid (65.6 mg, 58% yield), melting point: 115ꢀ116 C. H NMR
(400 MHz, CDCl3, ppm): δ 7.59ꢀ7.56 (m, 2 H), 7.46ꢀ7.44 (m, 1 H),
7.42ꢀ7.34 (m, 3 H), 7.31ꢀ7.23 (m, 4 H), 7.15ꢀ7.12 (m, 3 H), 7.10ꢀ7.05 (m,
2 H), 6.95ꢀ6.76 (m, 1 H); 13C NMR (100 MHz, CDCl3, ppm): δ 160.2 (d,
J = 247.0 Hz, 1 C), 142.9, 138.5, 134.1, 132.3, 131.4 (d, J = 8.0 Hz, 1 C),
129.4, 129.0, 128.5, 128.0, 126.9, 125.4, 125.0, 123.6 (d, J = 3.0 Hz, 1 C),
123.1, 117.3 (d, J = 16.0 Hz, 1 C), 115.1 (d, J = 20.0 Hz, 1 C), 110.4;
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HRMS(ESI)m/z calcd for C22H17FNO2S [M+H]+ 378.0959; found:
378.0950.
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2-(3-fluorophenyl)-1-phenyl-3-(phenylsulfonyl)-1H-pyrrole (3fa).
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Yellow solid (75.8 mg, 67% yield), melting point: 99ꢀ101 C. H NMR
(400 MHz, CDCl3, ppm): δ 7.58ꢀ7.55 (m, 2 H), 7.46ꢀ7.40 (m, 1 H),
7.33ꢀ7.20 (m, 5 H), 7.18ꢀ7.13 (m, 1 H), 7.03ꢀ6.94 (m, 3 H), 6.91ꢀ6.88 (m,
3 H), 6.79ꢀ6.75 (m, 1 H); 13C NMR (100 MHz, CDCl3, ppm): δ 163.3 (d,
J = 327.0 Hz, 1 C), 142.8, 138.3, 133.6, 132.3, 131.1 (d, J = 11.0 Hz, 1
C), 129.2 (d, J = 5.0 Hz, 1 C), 128.5, 127.9, 127.4 (d, J = 4.0 Hz, 1 C),
126.9, 125.7, 124.5, 122.8, 118.5, 118.2, 115.6 (d, J = 7.0 Hz, 1 C), 110.5;
HRMS(ESI)m/z calcd for C22H17FNO2S [M+H]+ 378.0959; found:
378.0966.
1-phenyl-3-(phenylsulfonyl)-2-(thiophen-2-yl)-1H-pyrrole (3ga).
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Yellow solid (71.2 mg, 65% yield), melting point: 114ꢀ116 C. H NMR
(400 MHz, CDCl3, ppm): δ 7.60ꢀ7.57 (m, 2 H), 7.46ꢀ7.41 (m, 1 H),
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7.33ꢀ7.27 (m, 6 H), 7.16ꢀ7.09 (m, 3 H), 7.00ꢀ6.91 (m, 3 H); C NMR
(100 MHz, CDCl3, ppm): δ 142.6, 138.5, 132.4, 132.3, 129.9, 129.0,
129.0, 128.8, 128.5, 128.1, 127.1, 126.6, 126.0, 125.8, 123.2, 110.7;
HRMS(ESI)m/z calcd for C20H16NO2S2 [M+H]+ 366.0617; found:
366.0623.
2-phenyl-3-(phenylsulfonyl)-1-(m-tolyl)-1H-pyrrole (3ha).
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Yellow solid (95.1 mg, 85% yield), melting point: 114ꢀ116 C. H NMR
(300 MHz, CDCl3, ppm): δ 7.52ꢀ7.49 (d, J = 9.0 Hz, 2 H), 7.42ꢀ7.27 (m,
1 H), 7.23ꢀ7.17 (m, 5 H), 7.09ꢀ7.00 (m, 4 H), 6.90ꢀ6.86 (m, 3 H),
6.77ꢀ6.75 (d, J = 6.0 Hz, 1 H); 13C NMR (75 MHz, CDCl3, ppm): δ 143.1,
139.1, 138.5, 135.5, 132.1, 131.4, 129.2, 128.7, 128.5, 128.4, 127.9,
127.6, 127.0, 126.4, 123.9, 122.9, 122.3, 110.3, 21.1; HRMS(ESI)m/z
calcd for C23H20NO2S [M+H]+ 374.1209; found: 374.1213.
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2-phenyl-3-(phenylsulfonyl)-1-(p-tolyl)-1H-pyrrole (3ia).
Yellow solid (100.7 mg, 90% yield), melting point: 116ꢀ118 oC. 1H NMR
(300 MHz, CDCl3, ppm): δ 7.52ꢀ7.49 (m, 2 H), 7.42ꢀ7.37 (m, 1 H),
7.29ꢀ7.17 (m, 5 H), 7.09ꢀ7.06 (m, 2 H), 7.03ꢀ7.00 (d, J = 9.0 Hz, 2 H) ,
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6.90ꢀ6.85 (m, 4 H), 2.27 (s, 3 H); C NMR (75 MHz, CDCl3, ppm): δ
142.9, 137.2, 135.5, 133.6, 132.2, 131.4, 129.2, 128.8, 128.4, 127.9,
127.0, 126.8, 124.6, 122.2, 110.7; HRMS(ESI)m/z calcd for C23H20NO2S
[M+H]+ 374.1209; found: 374.1206.
1-(4-ethylphenyl)-2-phenyl-3-(phenylsulfonyl)-1H-pyrrole (3ja).
Yellow solid (106.8 mg, 92% yield), melting point: 123ꢀ125 oC. 1H NMR
(400 MHz, CDCl3, ppm): δ 7.52ꢀ7.50 (d, J = 8.0 Hz, 2 H), 7.42ꢀ7.39 (m,
1 H), 7.29ꢀ7.17 (m, 6 H), 7.09ꢀ7.02 (m, 4 H), 6.93ꢀ6.86 (m, 4 H),
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2.61ꢀ2.53 (m, 2 H), 1.19ꢀ1.14 (m, 3 H); C NMR (100 MHz, CDCl3,
ppm): δ 143.8, 143.1, 136.3, 135.5, 132.1, 131.5, 129.3, 128.5, 128.4,
128.3, 127.6, 127.0, 125.7, 123.8, 122.4, 110.3, 28.2, 15.2;
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HRMS(ESI)m/z calcd for C24H22NO2S [M+H]+ 388.1366; found:
388.1375.
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1-(3,5-dimethylphenyl)-2-phenyl-3-(phenylsulfonyl)-1H-pyrrole (3ka).
Yellow solid (101.0 mg, 87% yield), melting point: 131ꢀ133 oC. 1H NMR
(300 MHz, CDCl3, ppm): δ 7.52ꢀ7.49 (m, 2 H), 7.41ꢀ7.36 (m, 1 H),
7.30ꢀ7.17 (m, 5 H), 7.09ꢀ7.06 (m, 2 H), 6.88ꢀ6.83 (m, 3 H), 6.61 (s, 2 H),
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2.15 (s, 6 H); C NMR (75 MHz, CDCl3, ppm): δ 143.2, 138.7, 138.5,
135.5, 132.0, 131.4, 128.5, 128.3, 127.5, 127.0, 123.7, 123.6, 122.3,
110.2, 21.0; HRMS(ESI)m/z calcd for C24H22NO2S [M+H]+ 388.1366;
found: 388.1373.
1-(2-fluorophenyl)-2-phenyl-3-(phenylsulfonyl)-1H-pyrrole (3la).
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Yellow solid (73.5 mg, 65% yield), melting point: 119ꢀ121 C. H NMR
(300 MHz, CDCl3, ppm): δ 8.01ꢀ7.98 (m, 2 H), 7.92ꢀ7.90 (m, 4 H),
7.78ꢀ7.68 (m, 3 H), 7.62ꢀ7.58 (m, 2 H), 7.55ꢀ7.51 (m, 4 H); 13C NMR (75
MHz, CDCl3, ppm): δ 160.2 (d, J = 186.0 Hz, 1 C), 142.9, 138.5, 134.1,
132.3, 131.4 (d, J = 6.8 Hz, 1 C), 129.4, 129.0, 128.5, 128.0, 126.9, 125.5,
125.0, 123.6 (d, J = 3.0 Hz, 1 C), 123.1, 117.3 (d, J = 11.3 Hz, 1 C),
115.1 (d, J = 16.5 Hz, 1 C), 110.4; HRMS(ESI)m/z calcd for
C22H17FNO2S [M+H]+ 378.0959; found: 378.0950.
1-(4-chlorophenyl)-2-phenyl-3-(phenylsulfonyl)-1H-pyrrole (3ma).
Yellow solid (100.2 mg, 85% yield), melting point: 135ꢀ137 oC. 1H NMR
(300 MHz, CDCl3, ppm): δ 7.51ꢀ7.48 (m, 2 H), 7.43ꢀ7.38 (m, 1 H),
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7.31ꢀ7.18 (m, 7 H), 7.08ꢀ7.05 (m, 2 H), 6.96ꢀ6.90 (m, 3 H), 6.87ꢀ6.86 (d,
J = 3.0 Hz, 1 H); 13C NMR (75 MHz, CDCl3, ppm): δ 142.9, 137.2, 135.5,
133.6, 132.2, 131.4, 129.2, 128.8, 128.4, 127.9, 127.0, 126.9, 126.8,
124.6, 122.2, 110.7; HRMS(ESI)m/z calcd for C22H17ClNO2S [M+H]+
394.0663; found: 394.0654.
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1-([1,1'-biphenyl]-4-yl)-2-phenyl-3-(phenylsulfonyl)-1H-pyrrole (3na).
Yellow solid (103.1 mg, 79% yield), melting point: 159ꢀ161 oC. 1H NMR
(400 MHz, CDCl3, ppm): δ 7.52ꢀ7.48 (m, 4 H), 7.45ꢀ7.38 (m, 5 H),
7.34ꢀ7.28 (m, 1 H), 7.27ꢀ7.19 (m, 5 H), 7.13ꢀ7.11 (m, 2 H), 7.07ꢀ7.05 (d,
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J = 8.0 Hz, 2 H), 6.93 (s, 2 H); C NMR (100 MHz, CDCl3, ppm): δ
143.0, 140.4, 139.5, 137.7, 135.4, 132.1, 131.5, 129.1, 128.8, 128.6,
128.4, 127.7, 127.5, 127.0, 126.9, 126.0, 124.2, 122.3, 110.5;
HRMS(ESI)m/z calcd for C28H22NO2S [M+H]+ 436.1366; found:
436.1374.
1-(3-chloro-4-methylphenyl)-2-phenyl-3-(phenylsulfonyl)-1H-pyrrole
(3oa).
Yellow solid (101.3 mg, 83% yield), melting point: 135ꢀ137 oC. 1H NMR
(400 MHz, CDCl3, ppm): δ 7.50ꢀ7.48 (m, 2 H), 7.42ꢀ7.38 (m, 1 H),
7.32ꢀ7.21 (m, 6 H), 7.09ꢀ7.07 (m, 3 H), 7.04ꢀ7.02 (d, J = 8.0 Hz, 1 H),
6.90ꢀ6.89 (m, 1 H), 6.86ꢀ6.85 (m, 1 H), 6.75ꢀ6.72 (m, 1 H), 2.28 (s, 3 H);
13C NMR (100 MHz, CDCl3, ppm): δ 143.0, 137.3, 135.8, 135.5, 134.5,
132.2, 131.4, 131.0, 128.8, 128.4, 127.8, 127.0, 126.2, 124.4, 124.1,
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122.2, 110.6, 19.6; HRMS(ESI)m/z calcd for C23H19ClNO2S [M+H]+
408.0820; found: 408.0811.
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1-(2-methoxyphenyl)-3-(phenylsulfonyl)-2-(p-tolyl)-1H-pyrrole (3pa).
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Yellow solid (75.0 mg, 62% yield), melting point: 160ꢀ162 C. H NMR
(300 MHz, CDCl3, ppm): δ 7.58ꢀ7.55 (m, 2 H), 7.42ꢀ7.39 (m, 1 H),
7.31ꢀ7.19 (m, 4 H), 7.06ꢀ7.03 (m, 1 H), 6.95 (s, 3 H), 6.85ꢀ6.82 (m, 2 H),
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6.80ꢀ6.73 (m, 2 H), 3.55 (s, 3 H), 2.27 (s, 3 H); C NMR (75 MHz,
CDCl3, ppm): δ 154.2, 143.5, 137.4, 136.4, 131.9, 129.9, 129.7, 129.2,
128.8, 128.6, 128.2, 127.6, 127.2, 122.6, 122.4, 120.2, 111.6, 109.8, 55.2,
21.1; HRMS(ESI)m/z calcd for C24H22NO3S [M+H]+ 404.1315; found:
404.1307.
2-(3,5-dimethylphenyl)-1-(2-methoxyphenyl)-3-(phenylsulfonyl)-1H-p
yrrole (3qa).
Yellow solid (82.6 mg, 66% yield), melting point: 168ꢀ169 oC. 1H NMR
(300 MHz, CDCl3, ppm): δ 7.61ꢀ7.58 (m, 2 H), 7.43ꢀ7.41 (m, 1 H),
7.37ꢀ7.24 (m, 2 H), 7.21ꢀ7.19 (d, J = 9.0 Hz, 1 H), 7.04ꢀ7.01 (d, J = 6.0
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Hz, 1 H), 6.88ꢀ6.81 (m, 5 H), 6.79ꢀ6.58 (m, 2 H); C NMR (75 MHz,
CDCl3, ppm): δ 154.2, 143.5, 137.4, 136.3, 131.9, 129.9, 129.7, 129.2,
128.8, 128.6, 128.2, 127.6, 127.2, 122.6, 122.4, 120.2, 111.6, 109.8, 55.2,
21.1; HRMS(ESI)m/z calcd for C25H24NO3S [M+H]+ 418.1472; found:
418.1478.
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Yellow solid (87.1 mg, 69% yield), melting point: 165ꢀ167 C. H NMR
(400 MHz, CDCl3, ppm): δ 7.55ꢀ7.52 (m, 2 H), 7.46ꢀ7.41 (m, 1 H),
7.32ꢀ7.30 (m, 2 H), 7.22ꢀ7.19 (m, 2 H), 6.98ꢀ6.95 (d, J = 12.0 Hz, 2 H),
6.91ꢀ6.90 (d, J = 4.0 Hz, 2 H), 6.84 (s, 1 H), 6.59 (s, 2 H), 2.17 (s, 6 H);
13C NMR (100 MHz, CDCl3, ppm): δ 143.1, 137.2, 135.9, 133.6, 132.1,
130.5, 130.2, 129.1, 129.0, 128.3, 127.2, 127.0, 124.3, 121.9, 116.5,
110.6, 21.1; HRMS(ESI)m/z calcd for C24H21ClNO2S [M+H]+ 422.0976;
found: 422.0981.
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1-phenyl-3-(phenylsulfonyl)-1H-pyrrole (3sa).
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Yellow solid (39.1 mg, 46% yield), melting point: 86ꢀ88 C. H NMR
(400 MHz, CDCl3, ppm): δ 7.52ꢀ7.50 (m, 2 H), 7.41ꢀ7.38 (m, 1 H),
7.29ꢀ7.24 (m, 1 H), 7.22ꢀ7.17 (m, 4 H), 7.09ꢀ7.07 (m, d, J = 8.0 Hz, 2 H),
13
7.02ꢀ7.00 (m, 1 H), 6.91ꢀ6.89 (m, 2 H); C NMR (100 MHz, CDCl3,
ppm): δ 143.1, 138.7, 132.1, 131.5, 129.0, 128.6, 128.4, 127.7, 127.0,
125.9, 124.2, 122.4, 110.5; HRMS(ESI)m/z calcd for C16H14NO2S
[M+H]+ 284.0740; found: 284.0736.
1-benzyl-2-phenyl-3-(phenylsulfonyl)-1H-pyrrole (3ta).
o
1
Yellow solid (98.5 mg, 88% yield), melting point: 92ꢀ94 C. H NMR
(300 MHz, CDCl3, ppm): δ 7.51ꢀ7.48 (d, J = 9.0 Hz, 2 H), 7.43ꢀ7.34 (m,
2 H), 7.32ꢀ7.24 (m, 8 H), 7.12ꢀ7.09 (d, J = 9.0 Hz, 2 H), 6.89ꢀ6.87 (m, 2
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