Visible-Light-Promoted (Phenylsulfonyl)methylation of Electron-Rich Heteroarenes and N-Arylacrylamides

Article abstract of DOI:10.1021/acs.joc.6b00689

Visible-light-promoted radical (phenylsulfonyl)methylation reactions of electron-rich heteroarenes and N-arylacrylamides have been developed starting from bromomethyl phenyl sulfone derivatives. This method provides a mild and efficient access to various (phenylsulfonyl)methylated compounds.

Full text of DOI:10.1021/acs.joc.6b00689

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Featured Article
Visible-Light-Promoted (Phenylsulfonyl)methylation
of Electron-Rich Heteroarenes and N-Arylacrylamides
Fei Liu, and Pixu Li
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00689 • Publication Date (Web): 27 May 2016
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Visible-Light-Promoted (Phenylsulfonyl)methylation of
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Electron-Rich Heteroarenes and N-Arylacrylamides
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Fei Liu and Pixu Li*
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Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry,
Chemical Engineering, and Materials Science, Soochow University
199 RenAi Road, Suzhou, Jiangsu 215123, China
Tel: +86ꢀ512ꢀ65880826; Eꢀmail: lipixu@suda.edu.cn
Abstract: Visibleꢀlightꢀpromoted radical (phenylsulfonyl)methylation reactions of electronꢀrich
heteroarenes and Nꢀarylacrylamides have been developed starting from bromomethyl phenyl
sulfone derivatives. This method provides
(phenylsulfonyl)methylated compounds.
a mild and efficient access to various
Introduction:
Methylation is a fundamental and ubiquitous reaction in organic synthesis and biological
processes.1ꢀ3 Traditional widelyꢀused methylating reagents in organic synthesis include
electrophilic iodomethane, dimethyl sulfate, dimethylcarbonate, and diazomethane. Recently,
transitionꢀmetal catalyzed methylation reactions have attracted much attention.4,5 Another
important type of methylation reaction is the methyl radical addition to heteroarene.6,7 Minisci
reaction, in which the reactive species is the protonated heteroarene base, is a useful radical
methylation reaction.8,9 Recently, several interesting radical methylation of aromatic rings
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using methyl radical derived from peroxide were reported.10ꢀ13 While direct methylation of
heteroarene is straightꢀforward and efficient, its major drawback is that the methylated
product often is very difficult to be purified from the unreacted starting material because their
structure and properties are so similar. Indirect methylation of heteroarene becomes one of the
effective alternative methods to circumvent this problem. 2014, Baran group reported an
elegant CꢀH methylation of heteroarenes.14 Zinc bis(phenylsulfonylmethanelsulfinate) (PSMS)
was prepared from the commercially available bromomethyl phenyl sulfone. PSMS reacted
with heteroarene to afford (phenylsulfonyl)methylated heteroarene, which could be easily
separated from the unreacted starting material and desulfonylated to give methylated
heteroarene product. The reaction was reported to go through a phenylsulfonyl methyl radical
addition pathway (Figure 1, equation 1).
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Figure 1. Radical benzenesulfonyl methylation reacitons
To the best of our knowledge, three reports on photoredox direct radical methylation reactions
have been reported in the literature.15ꢀ17 No indirect methylation by visibleꢀlightꢀpromoted
reaction has been disclosed. In continuation of our interest on the development of new
visibleꢀlightꢀpromoted CꢀH bond functionalization of arenes and heteroarenes,18ꢀ21 we
envisioned that the (phenylsulfonyl)methyl radical could be generated directly from
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bromomethyl phenyl sulfone under photoredox conditions.22 The resulting
(phenylsulfonyl)methyl radical would react with electronꢀrich heteroarenes via electrophillic
radical addition.23 As shown in the proposed transformation (Scheme 1), the
visibleꢀlightꢀexited photocatalyst reacts with bromomethyl phenyl sulfone via single electron
transfer (SET) to generate a (phenylsulfonyl)methyl radical A. Radical addition of A to an
electronꢀrich heteroarene would afford a radical species B. Oxidation of the radical
intermediate B by the photocatalyst at high oxidation state completes the photocatalytic cycle
and generates cation C. Upon giving up a proton, cation C rearomatizes and leads to the
(phenylsulfonyl)methylated product 3a (Scheme 1). Alternatively, radical B could be
deprotonated to generate a radical anion species, followed by an oxidation to afford the
product 3a.
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Scheme 1. Proposed Transformation
Results and Discussion:
Based on the above postulation, we started our investigation of this reaction using
bromomethyl phenyl sulfone (1a) and ethyl 1Hꢀpyrroleꢀ2ꢀcarboxylate (2a) as the starting
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materials and Ir(ppy)3 as the photocatalyst. Because the reaction requires a base in the
proposed mechanism, we screened several bases using DMSO as solvent. To our delight, the
desired (phenylsulfonyl)methylated product 3a was obtained (Table 1, entries 1ꢀ5). Among all
of the bases screened, Li2CO3 was the most effective base (80%, Table 1, entries 5). Next, a
series of photocatalysts, including other Ru or Irꢀbased polybipyridyl complexes and organic
dyes, were screened. The highest yield was obtained in the reaction using Ir(ppy)3 as the
catalyst (Table 1, entries 5ꢀ11). The solvent effect was also checked. Commonly used
solvents such as toluene, DMF, MeCN, MeOH, and THF were tested. However, none of the
above solvents afforded higher yield than DMSO (Table 1, entries 12ꢀ16). When the reaction
time was extended to 48 h, the yield of the desired product 3a was boosted to 96% (Table 1,
entry 17). To this end, a set of control experiments were carried out. No product 3a was
observed in the absence of either catalyst or visibleꢀlight irradiation (Table 1, entries 17−18).
The results indicated that the catalyst and light irradiation were both critical to the reaction.
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Table 1. Optimization of reaction conditions a
Entry
Catalyst
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Solvent
DMSO
DMSO
DMSO
DMSO
DMSO
Base
NEt3
LC Yield
20 %
1
2
3
4
5
DIEA
K2CO3
KOH
11 %
63 %
trace
Li2CO3
80 %
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.
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Ru(bpy)3Cl2 6H2O
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
PhMe
DMF
Li2CO3
Li2CO3
Li2CO3
Li2CO3
Li2CO3
Li2CO3
Li2CO3
Li2CO3
Li2CO3
Li2CO3
Li2CO3
25 %
11 %
16 %
trace
N.R.
trace
42 %
43 %
75 %
54 %
20 %
7
FIrpic
8
Ir(dF(CF3)ppy)(dtbbpy)PF6
Ir(ppy)2(dtbbpy)PF6
Rose Bengal
Eosin Yellowish
Ir(ppy)3
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Ir(ppy)3
Ir(ppy)3
MeCN
EtOH
Ir(ppy)3
Ir(ppy)3
THF
96 %
(83 %)c
17b
Ir(ppy)3
—
DMSO
Li2CO3
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19
DMSO
DMSO
Li2CO3
Li2CO3
N.R.
, no light
Ir(ppy)3
N.R.
a Reaction conditions: 1a (1.0 mmol), 2a (0.5 mmol), photocatalyst (0.01 mmol, 2 mol %), base (1.0
mmol), solvent (1.25 mL) under N2 atmosphere and a 14 W CFL irradiation. b reacted for 48 h.
c
Isolated yield.
To verify the reaction was initiated by the formation of (phenylsulfonyl)methyl radical, a
luminescence quenching reaction was carried out. The result clearly showed that bromomethyl
phenyl sulfone was an effective quencher of excited Ir(ppy)3. Moreover, the reaction was
completely inhibited by the addition of 2 equivalents of TEMPO. And the adduct of
(phenylsulfonyl)methyl radical and TEMPO was detected by LCMS.
With the optimized reaction conditions in hand, we then turned our attention to the generality of
the reaction. The scope of bromomethyl aryl sulfone 1 and heteroarene 2 was investigated (Table
2). First, we investigated the scope of heteroarene. When substitution group on the pyrrole
nitrogen was changed to methyl, ethyl, propyl, and Boc, the reactions afford 80%, 91%, 79%,
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and 62% yields of the corresponding products, respectively (Table 2, 3bꢀ3e). Switching the ethyl
ester group of 2a to methyl ester (2f) or acyl group (2g) afforded the desired products in good
yields too (75% and 65% respectively, Table 2, 3fꢀg). Next, other 5ꢀmembered heteroarenes,
such as furan and thiophene derivatives, were screened. The reactions of 2ꢀhydroxymethylfuran
(2h), 2ꢀmethylthiophene (2i), and 2ꢀchlorothiophene (2j) proceeded smoothly and afforded the
desired products in 45%, 98%, and 50% respectively (Table 2, 3hꢀj). Particularly,
2ꢀmethylꢀ4ꢀbenzenesulfonylmethylthiophene (3i) was obtained in near quantitative isolated yield.
Indoles are very important compounds both in pharmaceuticals and natural products. So we also
investigated the reaction of indole derivatives. It was found that indoles also underwent the
(phenylsulfonyl)methylation reaction regardless of the nitrogen was substituted or not (Table 2,
3kꢀ3m). However, they typically gave lower yields than those of pyrrole derivatives. Other
bicyclic arenes, such as benzofuran and 5ꢀbromo benzofuran, were examined as well. Good yield
was obtained with benzofuran as the substrate (88%, Table 2, 3n). On the contrary,
5ꢀbromobenzofuran only afforded 25% yield of the corresponding product (Table 2, 3o),
suggesting that the substituent could significantly affect the radical addition reaction. To our
surprise, caffeine only afforded the corresponding product in 24% under our conditions (Table 2,
3p). It is much lower than the 75% yield using Baran’s conditions. It indicated that other factors
in the reaction might have compound influence on the radical addition. We also investigated
various substituents on the phenyl ring of the bromomethyl phenyl sulfone. Bromomethyl phenyl
sulfones with electronꢀdonating groups, such as methyl or methoxyl group, on the phenyl group
afforded the corresponding products in good yields (66% and 76% respectively, Table 2, 3q and
3r). However, bromomethyl phenyl sulfone with an electronꢀwithdrawing nitro group only gave
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moderate yield of product (40%, Table 2, 3s). When unsubstituted pyrrole, furan, and thiophene
were employed as the substrates, bis(phenylsulfonyl)methylation occurred. Pyrrole gave 57%
yield of the bis(phenylsulfonyl)methylated product, while furan and thiophene afforded 28% and
25% yields of the corresponding products, respectively (Table 2, 3t-3v).
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Table 2. Scope of substrates a
a
Reaction conditions: 1 (1.0 mmol), 2 (0.5 mmol), Ir(ppy)3 (0.01 mmol, 2 mol %), Li2CO3 (1.0 mmol), DMSO
(1.25 mL) for 48 h under N2 atmosphere and a 14 W CFL irradiation.
In addition to the (phenylsulfonyl)methylation of heteroarenes, we have also found that
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(phenylsulfonyl)methyl radical reacted with Nꢀarylacrylamide derivatives 4.24
A
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visibleꢀlightꢀpromoted free radical addition/cyclization cascade reaction17,25ꢀ27 occurred to
produce a series of (phenylsulfonyl)methylated oxindoles 5. The results were shown in Table
3. The reaction of bromomethyl phenyl sulfone (1a) and NꢀmethylꢀNꢀphenylmethacrylamide
(4a) under our photoredox reaction conditions afforded oxindole 5a in 94% yield (Table 3,
5a). When the substituents on the phenyl ring of the bromomethyl phenyl sulfone were
electronꢀdonating groups, such as methyl and methoxy groups, the reactions proceeded
smoothly and gave the corresponding products in good yields (81% and 75% respectively,
Table 3, 5b and 5c). The bromomethyl phenyl sulfone bearing an electronꢀwithdrawing nitro
group only afforded 15% yield of the desired product (Table 3, 5d). When substituent on the
phenyl ring of Nꢀarylacrylamide 4 was electronꢀdonating methoxy group, good yield was
obtained (67%, Table 3, 5e). However, no desired product was formed when an
electronꢀwithdrawing nitro group was on the phenyl ring of Nꢀarylacrylamide 4 (Table 3, 5f).
When NꢀmethylꢀNꢀphenylacrylamide (4g) was used as the reactant, only trace amount of 5g
was formed (Table 3, 5g).
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Table 3. (Phenylsulfonyl)methyl radical addition to N-arylacrylamide derivatives a
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a
Reaction conditions: 1 (1.0 mmol), 4 (0.5 mmol), Ir(ppy)3 (0.01 mmol, 2 mol %), Li2CO3 (1.0 mmol), DMSO
(1.25 mL) for 24 h under an atmosphere of N2 and a 14 W CFL irradiation.
In summary, we have developed a mild visibleꢀlightꢀpromoted (phenylsulfonyl)methylation of
electronꢀrich heteroarenes. In the reaction, (phenylsulfonyl)methyl radical was generated from
bromomethyl phenyl sulfone via SET with photo sensitizer under visible light irradiation. It
reacted with heteroarenes intermolecularly to afford various (phenylsulfonyl)methylated
heteroarenes, which could be further desulfonylated to methylated heteroarenes. Inexpensive
and easily accessible bromomethyl phenyl sulfone derivatives were used as the reagent. In
addition, this (phenylsulfonyl)methylation reaction is applicable to the reaction with
Nꢀarylacrylamide derivatives to afford oxindoles.
Experimental Section:
General Information: All reactions were carried out in glassware under N2 atmosphere.
Starting materials, bromomethyl aryl sulfones and Nꢀarylacrylamide derivatives, were
synthesized according to the literature methods.28,29 Chemicals without special descriptions
were obtained from commercial sources, and were used without further purification. Column
chromatography was generally performed on silica gel (300ꢀ400 mesh). Thinꢀlayer
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chromatography (TLC) was visualized using UV light. NMR spectra were recorded in CDCl3
or DMSOꢀd6 on a 400 MHz spectrometer. Chemical shifts were reported in parts per million
(δ) relative to TMS (0.00 ppm) for 1H NMR data and CDCl3 (77.16 ppm) or DMSOꢀd6 (39.52
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13
ppm) for C NMR data. The abbreviations are used: s = singlet, d = doublet, t = triplet, q =
quartet, dd = double doublet, m = multiplet, br.s = broad singlet, and br = broad signal.
HRMS spectra were measured on a TOF mass spectrometer with electrospray ionization (ESI)
as the ionization source. Melting points are uncorrected.
General procedure:
(Phenylsulfonyl)methylation of heteroarenes: To a solution of bromomethyl aryl sulfone 1
(1.0 mmol), heteroarene 2 (0.5 mmol), and Li2CO3 (74.0 mg, 1.0 mmol) in DMSO (1.25 mL)
was added Ir(ppy)3 (6.5 mg, 0.01 mmol, 2 mol %) under nitrogen atmosphere. The reaction
mixture were placed at a distance of 5 cm from a 14 W compact fluorescent lamp and stirred
at room temperature. After 48 h, the reaction mixture was poured into H2O (15 mL) and
extracted with EtOAc (3×15 mL). The combined organic layers were washed with water
(2×30 mL) and brine (30 mL) and dried over anhydrous MgSO4. The mixture was filtered and
the filtrate was concentrated under reduced pressure. The crude material was purified by silica
gel flash chromatography to give the desired product.
Radical cascade reactions of N-arylacrylamide derivatives: To a solution of bromomethyl
aryl sulfone 1 (1.0 mmol), Nꢀarylacrylamide 4 (0.5 mmol), and Li2CO3 (74 mg, 1.0 mmol) in
DMSO (1.25 mL) was added Ir(ppy)3 (6.5 mg, 0.01 mmol, 2 mol %) under nitrogen
atmosphere. The reaction mixture were placed at a distance of 5 cm from a 14 W compact
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fluorescent lamp and stirred at room temperature. After 24 h, the reaction mixture was poured
into H2O (15 mL) and extracted with EtOAc (3×15 mL). The combined organic layers were
washed with water (2×30 mL) and brine (30 mL) and dried over anhydrous MgSO4. The
mixture was filtered and the filtrate was concentrated under reduced pressure. The crude
material was purified by silica gel flash chromatography to give the desired product.
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Ethyl 5-((phenylsulfonyl)methyl)-1H-pyrrole-2-carboxylate (3a)14: The general procedure
was followed using bromomethyl phenyl sulfone 1a (234.0 mg, 1.0 mmol) and ethyl
1Hꢀpyrroleꢀ2ꢀcarboxylate 2a (69.5 mg, 0.5 mmol) as the starting materials. Purification by
column chromatography using EtOAc/PE (1:2) as the eluent afforded 3a (121.8 mg, 83%) as
a white solid. mp = 144−146 °C (lit 105−107 °C). 1H NMR (400 MHz, CDCl3) δ 9.46 (s, 1H),
7.71 – 7.58 (m, 3H), 7.53 – 7.43 (m, 2H), 6.80 – 6.68 (m, 1H), 5.89 – 5.81 (m, 1H), 4.40 –
4.29 (m, 4H), 1.37 (t, J = 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 161.0, 137.6, 134.2,
129.2, 128.5, 124.8, 123.2, 115.6, 113.1, 60.8, 55.7, 14.5. IR (neat): 3282, 3140, 2989, 2922,
1679, 1488, 1228, 764 cm−1. HRMS (ESI) m/z: calcd for C14H16NO4S+ [M+H]+ 294.0795,
found 294.0808.
Ethyl 1-methyl-5-((phenylsulfonyl)methyl)-1H-pyrrole-2-carboxylate (3b): The general
procedure was followed using bromomethyl phenyl sulfone 1a (234.0 mg, 1.0 mmol) and
ethyl 1ꢀmethylꢀ1Hꢀpyrroleꢀ2ꢀcarboxylate 2b (76.5 mg, 0.5 mmol) as the starting materials.
Purification by column chromatography using EtOAc/PE (1:4) as the eluent afforded 3b
(123.0 mg, 80%) as a white solid. mp = 58−60 °C. 1H NMR (400 MHz, CDCl3) δ 7.71 – 7.62
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(m, 3H), 7.54 – 7.46 (m, 2H), 6.83 (d, J = 4.0 Hz, 1H), 5.80 (d, J = 4.0 Hz, 1H), 4.40 (s, 2H),
4.27 (q, J = 7.2 Hz, 2H), 3.77 (s, 3H), 1.34 (t, J = 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ
161.1, 137.8, 134.2, 129.2, 128.7, 126.3, 124.9, 117.1, 112.4, 60.1, 54.6, 32.9, 14.5. IR (neat):
3071, 2980, 2934, 2908, 1698, 1317, 1246, 1149, 743 cm−1. HRMS (ESI) m/z: calcd for
C15H18NO4S+ [M+H]+ 308.0951, found 308.0948.
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Ethyl 1-ethyl-5-((phenylsulfonyl)methyl)-1H-pyrrole-2-carboxylate (3c): The general
procedure was followed using bromomethyl phenyl sulfone 1a (234.0 mg, 1.0 mmol) and
ethyl 1ꢀethylꢀ1Hꢀpyrroleꢀ2ꢀcarboxylate 2c (83.5 mg, 0.5 mmol) as the starting materials.
Purification by column chromatography using EtOAc/PE (1:4) as the eluent afforded 3c
(142.6 mg, 91%) as a white solid. mp = 65−67 °C. 1H NMR (400 MHz, CDCl3) δ 7.73 – 7.67
(m, 2H), 7.67 – 7.61 (m, 1H), 7.53 – 7.46 (m, 2H), 6.83 (d, J = 4.0 Hz, 1H), 5.79 (d, J = 4.0
Hz, 1H), 4.40 (s, 2H), 4.35 – 4.23 (m, 4H), 1.34 (t, J = 7.1 Hz, 3H), 1.23 (t, J = 7.1 Hz, 3H).
13C NMR (101 MHz, CDCl3) δ 160.6, 137.7, 134.1, 129.1, 128.7, 125.3, 123.6, 117.4, 112.5,
60.0, 54.3, 40.1, 16.4, 14.3. IR (neat): 3064, 2989, 2938, 2873, 1706, 1249, 1148, 741 cm−1.
HRMS (ESI) m/z: calcd for C16H20NO4S+ [M+H]+ 322.1108, found 322.1110.
Ethyl 5-((phenylsulfonyl)methyl)-1-propyl-1H-pyrrole-2-carboxylate (3d): The general
procedure was followed using bromomethyl phenyl sulfone 1a (234.0 mg, 1.0 mmol) and
ethyl 1ꢀpropylꢀ1Hꢀpyrroleꢀ2ꢀcarboxylate 2d (90.5 mg, 0.5 mmol) as the starting materials.
Purification by column chromatography using EtOAc/PE (1:5) as the eluent afforded 3d
(132.5 mg, 79%) as a white solid. mp = 77−80 °C. 1H NMR (400 MHz, CDCl3) δ 7.72 – 7.60
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(m, 3H), 7.55 – 7.46 (m, 2H), 6.83 (d, J = 4.0 Hz, 1H), 5.79 (d, J = 4.0 Hz, 1H), 4.39 (s, 2H),
4.27 (q, J = 7.1 Hz, 2H), 4.22 – 4.14 (m, 2H), 1.66 – 1.55 (m, 2H), 1.34 (t, J = 7.1 Hz, 3H),
0.87 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 160.8, 137.8, 134.2, 129.2, 128.8,
125.8, 124.1, 117.5, 112.5, 60.1, 54.7, 46.7, 24.8, 14.5, 11.2. IR (neat): 3020, 2985, 2960,
2876, 1703, 1319, 1144, 1082, 739 cm−1. HRMS (ESI) m/z: calcd for C17H22NO4S+ [M+H]+
336.1264, found 336.1270.
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1-(tert-Butyl) 2-ethyl 5-((phenylsulfonyl)methyl)-1H-pyrrole-1,2-dicarboxylate (3e): The
general procedure was followed using bromomethyl phenyl sulfone 1a (234.0 mg, 1.0 mmol)
and 1ꢀ(tertꢀbutyl) 2ꢀethyl 1Hꢀpyrroleꢀ1,2ꢀdicarboxylate 2e (119.5 mg, 0.5 mmol) as the
starting materials. Purification by column chromatography using DCM/PE (5:2) as the eluent
afforded 3e (122.3 mg, 62%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ7.76 – 7.71 (m,
2H), 7.66 – 7.60 (m, 1H), 7.55 – 7.47 (m, 2H), 6.69 (d, J = 3.6 Hz, 1H), 5.94 (d, J = 3.6 Hz,
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1H), 4.75 (s, 2H), 4.29 (q, J = 7.2 Hz, 2H), 1.58 (s, 9H), 1.35 (t, J = 7.2 Hz, 3H). C NMR
(101 MHz, CDCl3) δ 160.5, 148.7, 138.3, 134.0, 129.1, 128.6, 127.9, 125.8, 118.0, 114.5,
86.0, 61.0, 54.4, 27.5, 14.4. IR (neat): 3065, 2982, 2937, 2907, 1717, 1307, 1221, 1135, 745
cm−1. HRMS (ESI) m/z: calcd for C19H23NO6SNa+ [M+Na]+ 416.1138, found 416.1152.
Methyl 5-((phenylsulfonyl)methyl)-1H-pyrrole-2-carboxylate (3f): The general procedure
was followed using bromomethyl phenyl sulfone 1a (234.0 mg, 1.0 mmol) and methyl
1Hꢀpyrroleꢀ2ꢀcarboxylate 2f (62.5 mg, 0.5 mmol) as the starting materials. Purification by
column chromatography using EtOAc/PE (1:2.5) as the eluent afforded 3f (105.0 mg, 75%) as
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a white solid. mp = 144−146 °C. 1H NMR (400 MHz, CDCl3) δ 10.06 (s, 1H), 7.70 – 7.64 (m,
2H), 7.63 – 7.55 (m, 1H), 7.50 – 7.42 (m, 2H), 6.80 – 6.73 (m, 1H), 5.92 – 5.86 (m, 1H), 4.44
(s, 2H), 3.85 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 161.5, 137.5, 134.1, 129.1, 128.5, 124.2,
123.6, 115.8, 113.0, 55.7, 51.8. IR (neat): 3278, 3144, 2985, 2950, 2920, 2844, 1686, 1490,
1229, 1124, 753 cm−1. HRMS (ESI) m/z: calcd for C13H14NO4S+ [M+H]+ 280.0638, found
280.0639.
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1-(5-((Phenylsulfonyl)methyl)-1H-pyrrol-2-yl)ethan-1-one (3g): The general procedure
was followed using bromomethyl phenyl sulfone 1a (234.0 mg, 1.0 mmol) and
1ꢀ(1Hꢀpyrrolꢀ2ꢀyl)ethanꢀ1ꢀone 2g (54.5 mg, 0.5 mmol) as the starting materials. Purification
by column chromatography using EtOAc/PE (1:3) as the eluent afforded 3g (85.8 mg, 65%)
as a white solid. mp = 161−163 °C. 1H NMR (400 MHz, CDCl3) δ 10.49 (s, 1H), 7.73 – 7.66
(m, 2H), 7.61 – 7.53 (m, 1H), 7.50 – 7.40 (m, 2H), 6.84 – 6.75 (m, 1H), 6.09 – 5.98 (m, 1H),
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4.49 (s, 2H), 2.42 (s, 3H). C NMR (101 MHz, CDCl3) δ 188.3, 137.8, 134.1, 133.2, 129.1,
128.5, 125.8, 117.5, 113.2, 55.6, 25.6. IR (neat): 3235, 3127, 2982, 2916, 1638, 1488, 1153,
796 cm−1. HRMS (ESI) m/z: calcd for C13H14NO3S+ [M+H]+ 264.0689, found 264.0686.
(5-((Phenylsulfonyl)methyl)furan-2-yl)methanol (3h): The general procedure was followed
using bromomethyl phenyl sulfone 1a (234.0 mg, 1.0 mmol) and furanꢀ2ꢀylmethanol 2h (49.0
mg, 0.5 mmol) as the starting materials. Purification by column chromatography using
EtOAc/PE (1:2.5) as the eluent afforded 3h (57.0 mg, 45%) as a white solid. mp = 73−75 °C.
1H NMR (400 MHz, CDCl3) δ 7.76 – 7.70 (m, 2H), 7.67 – 7.61 (m, 1H), 7.54 – 7.47 (m, 2H),
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6.22 (s, 2H), 4.44 (s, 2H), 4.40 (s, 2H), 2.40 (s, 1H). 13C NMR (101 MHz, CDCl3) δ 155.7,
142.1, 138.2, 134.1, 129.2, 128.6, 113.1, 109.2, 57.2, 56.1. IR (neat): 3494, 3134 2975, 2923,
2855, 1445, 1150, 1020, 765 cm−1. HRMS (ESI) m/z: calcd for C12H12O4SNa+ [M+Na]+
275.0349, found 275.0362.
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2-Methyl-5-((phenylsulfonyl)methyl)thiophene (3i)30: The general procedure was followed
using bromomethyl phenyl sulfone 1a (234.0 mg, 1.0 mmol) and 2ꢀmethylthiophene 2i (49.0
mg, 0.5 mmol) as the starting materials. Purification by column chromatography using
DCM/PE (2:1) as the eluent afforded 3i (123.5 mg, 98%) as a white solid. mp = 132−134 °C.
1H NMR (400 MHz, CDCl3) δ7.78 – 7.71 (m, 2H), 7.66 – 7.60 (m, 1H), 7.53 – 7.46 (m, 2H),
6.61 – 6.54 (m, 2H), 4.43 (s, 2H), 2.42 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 142.5, 137.7,
133.9, 130.4, 129.1, 128.8, 125.9, 125.5, 57.6, 15.4. IR (neat): 3092, 3059, 2965, 2920, 1445,
1301, 1141, 728 cm−1. HRMS (ESI) m/z: calcd for C12H12O2S2Na+ [M+Na]+ 275.0171, found
275.0178.
2-Chloro-5-((phenylsulfonyl)methyl)thiophene (3j): The general procedure was followed
using bromomethyl phenyl sulfone 1a (234.0 mg, 1.0 mmol) and 2ꢀchlorothiophene 2j (59.0
mg, 0.5 mmol) as the starting materials. Purification by column chromatography using
DCM/PE (3:1) as the eluent afforded 3j (68.3mg, 50%) as a white solid. mp = 131−134 °C.
1H NMR (400 MHz, CDCl3) δ 7.78 – 7.72 (m, 2H), 7.69 – 7.63 (m, 1H), 7.56 – 7.49 (m, 2H),
6.74 (d, J = 4.0 Hz, 1H), 6.60 (d, J = 4.0 Hz, 1H), 4.40 (s, 2H). 13C NMR (101 MHz, CDCl3)
δ 137.4, 134.3, 132.1, 129.9, 129.3, 128.8, 127.4, 126.4, 57.6. IR (neat): 3054, 2990, 2966,
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2920, 1476, 1299, 1143, 728 cm−1. HRMS (ESI) m/z: calcd for C11H9ClO2S2Na+ [M+Na]+
294.9625, found 294.9624.
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1-Methyl-2-((phenylsulfonyl)methyl)-1H-indole (3k)31: The general procedure was
followed using bromomethyl phenyl sulfone 1a (234.0 mg, 1.0 mmol) and
1ꢀmethylꢀ1Hꢀindole 2k (65.5 mg, 0.5 mmol) as the starting materials. Purification by column
chromatography using DCM/PE (2:1) as the eluent afforded 3k (92.9 mg, 65%) as a white
solid. mp = 177−179 °C (lit 177 °C). 1H NMR (400 MHz, CDCl3) δ 7.70 – 7.59 (m, 3H), 7.51
– 7.41 (m, 3H), 7.32 – 7.21 (m, 2H), 7.12 – 7.05 (m, 1H), 6.11 (s, 1H), 4.55 (s, 2H), 3.67 (s,
3H). 13C NMR (101 MHz, CDCl3) δ 138.2, 137.8, 134.1, 129.1, 128.8, 127.1, 126.4, 122.6,
120.9, 120.0, 109.7, 105.7, 55.1, 30.2. IR (neat): 3023, 2946, 2896, 2839, 1592, 1496, 1260,
1150, 833, 759 cm−1. HRMS (ESI) m/z: calcd for C16H15NO2SNa+ [M+Na]+ 308.0716, found
308.0726.
3-Methyl-2-((phenylsulfonyl)methyl)-1H-indole (3l)32: The general procedure was followed
using bromomethyl phenyl sulfone 1a (234.0 mg, 1.0 mmol) and 3ꢀmethylꢀ1Hꢀindole 2l (65.5
mg, 0.5 mmol) as the starting materials. Purification by column chromatography using
EtOAc/PE (1:4) as the eluent afforded 3l (85.5 mg, 60%) as a colorless solid. mp =
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176−178 °C (lit 183−185 °C). H NMR (400 MHz, CDCl3) δ 8.52 (s, 1H), 7.62 – 7.56 (m,
3H), 7.44 – 7.33 (m, 4H), 7.24 – 7.19 (m, 1H), 7.12 – 7.06 (m, 1H), 4.49 (s, 2H), 1.68 (s, 3H).
13C NMR (101 MHz, CDCl3) δ 137.5, 136.6, 134.1, 129.2, 128.4, 128.1, 123.2, 121.1, 119.6,
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119.1, 113.4, 111.2, 54.5, 7.8. IR (neat): 3363, 2954, 2924, 2854, 1450, 1288, 1139, 1082,
738 cm−1. HRMS (ESI) m/z: calcd for C16H16NO2S+ [M+H]+ 286.0896, found 286.0888.
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2-((Phenylsulfonyl)methyl)-1H-indole (3m)31: The general procedure was followed using
bromomethyl phenyl sulfone 1a (234.0 mg, 1.0 mmol) and 1Hꢀindole 2n (58.5 mg, 0.5 mmol)
as the starting materials. Purification by column chromatography using DCM/PE (5:2) as the
eluent afforded 3n (39.6 mg, 29%) as a white solid. mp = 189−190 °C (lit 190 °C). 1H NMR
(400 MHz, DMSO) δ 11.13 (s, 1H), 7.81 – 7.68 (m, 3H), 7.66 – 7.55 (m, 2H), 7.45 – 7.40 (m,
1H), 7.40 – 7.34 (m, 1H), 7.12 – 7.01 (m, 1H), 7.00 – 6.90 (m, 1H), 6.11 (s, 1H), 4.83 (s, 2H).
13C NMR (101 MHz, DMSO) δ 138.5, 136.6, 134.0, 129.3, 128.0, 127.6, 125.7, 121.6, 120.0,
119.2, 111.5, 103.8, 55.0. IR (neat): 3324, 3056, 2992, 2918, 2849, 1734, 1292, 1082, 801,
710 cm−1. HRMS (ESI) m/z: calcd for C15H13NO2SNa+ [M+Na]+ 294.0559, found 294.0557.
2-((Phenylsulfonyl)methyl)benzofuran (3n)33: The general procedure was followed using
bromomethyl phenyl sulfone 1a (234.0 mg, 1.0 mmol) and benzofuran 2o (59.0 mg, 0.5 mmol)
as the starting materials. Purification by column chromatography using DCM/PE (2:1) as the
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eluent afforded 3o (120.0 mg, 88%) as a white solid. mp = 166−168 °C (lit 166−168 °C). H
NMR (400 MHz, CDCl3) δ7.86 – 7.71 (m, 2H), 7.68 – 7.59 (m, 1H), 7.56 – 7.42 (m, 3H),
7.39 – 7.31 (m, 1H), 7.30 – 7.18 (m, 2H), 6.67 (s, 1H), 4.55 (s, 2H). 13C NMR (101 MHz,
CDCl3) δ 155.4, 145.2, 138.3, 134.2, 129.3, 128.6, 128.0, 125.1, 123.3, 121.4, 111.4, 109.1,
56.6. IR (neat): 3120, 3064, 2991, 2937, 1445, 1306, 1146, 740 cm−1. HRMS (ESI) m/z: calcd
for C15H12O3SNa+ [M+Na]+ 295.0399, found 295.0397.
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5-Bromo-2-((phenylsulfonyl)methyl)benzofuran (3o): The general procedure was followed
using bromomethyl phenyl sulfone 1a (234.0 mg, 1.0 mmol) and 5ꢀbromobenzofuran 2p
(98.0 mg, 0.5 mmol) as the starting materials. Purification by column chromatography using
DCM/PE (3:2) as the eluent afforded 3p. (43.9 mg, 25%) as a white solid. mp = 193−195 °C.
1H NMR (400 MHz, CDCl3) δ7.83 – 7.71 (m, 2H), 7.69 – 7.61 (m, 2H), 7.54 – 7.45 (m, 2H),
7.42 – 7.33 (m, 1H), 7.24 – 7.18 (m, 1H), 6.61 (s, 1H), 4.54 (s, 2H). 13C NMR (101 MHz,
CDCl3) δ 154.1, 146.7, 138.1, 134.3, 129.9, 129.4, 128.6, 128.2, 124.0, 116.4, 112.9, 108.5,
56.5. IR (neat): 3109, 2989, 2962, 2920, 2849, 1719, 1443, 1152, 805 cm−1. HRMS (ESI) m/z:
calcd for C15H11BrO3SNa+ [M+Na]+ 372.9504, found 372.9501.
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1,3,7-Trimethyl-8-((phenylsulfonyl)methyl)-3,7-dihydro-1H-purine-2,6-dione (3p)14: The
general procedure was followed using bromomethyl phenyl sulfone 1a (234.0 mg, 1.0 mmol)
and 1,3,7ꢀtrimethylꢀ3,7ꢀdihydroꢀ1Hꢀpurineꢀ2,6ꢀdione 2q (97.0 mg, 0.5 mmol) as the starting
materials. Purification by column chromatography using EtOAc/PE (2:1) as the eluent
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afforded 3q. (42.0 mg, 24%) as a white solid. mp = 244−245 °C (lit 243−245 °C). H NMR
(400 MHz, CDCl3) δ 7.80 – 7.74 (m, 2H), 7.74 – 7.67 (m, 1H), 7.60 – 7.52 (m, 2H), 4.56 (s,
2H), 4.06 (s, 3H), 3.40 (s, 3H), 3.36 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 155.4, 151.6,
147.7, 141.3, 137.9, 134.7, 129.4, 128.8, 109.1, 54.8, 33.0, 29.7, 28.2. IR (neat): 3356, 2971,
2918, 2849, 1703, 1661, 1149, 755 cm−1. HRMS (ESI) m/z: calcd for C15H17N4O4S+ [M+H]+
349.0965, found 349.0964.
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Ethyl 5-(tosylmethyl)-1H-pyrrole-2-carboxylate (3q): The general procedure was followed
using 1ꢀ((bromomethyl)sulfonyl)ꢀ4ꢀmethylbenzene 1b (248.0 mg, 1.0 mmol) and ethyl
1Hꢀpyrroleꢀ2ꢀcarboxylate 2a (69.5 mg, 0.5 mmol) as the starting materials. Purification by
column chromatography using EtOAc/PE (1:2) as the eluent afforded 3r (101.5 mg, 66%) as a
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white solid. mp = 177−179 °C. H NMR (400 MHz, CDCl3) δ 9.74 (s, 1H), 7.56 – 7.50 (m,
2H), 7.29 – 7.23 (m, 2H), 6.78 – 6.74 (m, 1H), 5.90 – 5.86 (m, 1H), 4.38 (s, 2H), 4.33 (q, J =
7.2 Hz, 2H), 2.40 (s, 3H), 1.37 (t, J = 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 160.9,
145.3, 134.7, 129.8, 128.5, 124.7, 123.5, 115.6, 113.1, 60.7, 55.7, 21.8, 14.5. IR (neat): 3269,
3141, 3004, 2986, 1683, 1489, 1279, 767 cm−1. HRMS (ESI) m/z: calcd for C15H17NO4SNa+
[M+Na]+ 330.0770, found 330.0773.
Ethyl 5-(((4-methoxyphenyl)sulfonyl)methyl)-1H-pyrrole-2-carboxylate (3r): The general
procedure was followed using 1ꢀ((bromomethyl)sulfonyl)ꢀ4ꢀmethoxybenzene 1c (264.0 mg,
1.0 mmol) and ethyl 1Hꢀpyrroleꢀ2ꢀcarboxylate 2a (69.5 mg, 0.5 mmol) as the starting
materials. Purification by column chromatography using EtOAc/PE (1:3) as the eluent
afforded 3s (123.1 mg, 76%) as a white solid. mp = 168−169 °C. 1H NMR (400 MHz, CDCl3)
δ 9.79 (s, 1H), 7.64 – 7.49 (m, 2H), 7.00 – 6.85 (m, 2H), 6.82 – 6.71 (m, 1H), 5.93 – 5.82 (m,
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1H), 4.37 (s, 2H), 4.33 (q, J = 7.2 Hz, 2H), 3.85 (s, 3H), 1.37 (t, J = 7.2 Hz, 3H). C NMR
(101 MHz, CDCl3) δ 164.1, 160.9, 130.7, 129.0, 124.6, 123.7, 115.6, 114.3, 113.0, 60.7, 55.9,
55.8, 14.5. IR (neat): 3270, 3021, 2970, 2881, 1680, 1488, 1298, 765 cm−1. HRMS (ESI) m/z:
calcd for C15H17NO5SNa+ [M+Na]+ 346.0720, found 346.0726.
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Ethyl 5-(((4-nitrophenyl)sulfonyl)methyl)-1H-pyrrole-2-carboxylate (3s): The general
procedure was followed using 1ꢀ((bromomethyl)sulfonyl)ꢀ4ꢀnitrobenzene 1d (279.0 mg, 1.0
mmol) and ethyl 1Hꢀpyrroleꢀ2ꢀcarboxylate 2a (69.5 mg, 0.5 mmol) as the starting materials.
Purification by column chromatography using EtOAc/PE (1:2.5) as the eluent afforded 3t
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(67.9 mg, 40%) as a white solid. mp = 184−186 °C. H NMR (400 MHz, CDCl3) δ 9.75 (s,
1H), 8.35 – 8.25 (m, 2H), 7.89 – 7.77 (m, 2H), 6.79 – 6.71 (m, 1H), 5.88 – 5.82 (m, 1H), 4.47
(s, 2H), 4.35 (q, J = 7.1 Hz, 2H), 1.39 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ
160.9, 151.1, 143.0, 130.1, 125.4, 124.3, 122.1, 115.6, 113.5, 61.1, 55.8, 14.5. IR (neat): 3273,
3124, 2917, 2849, 1673, 1521, 1275, 765 cm−1. HRMS (ESI) m/z: calcd for C14H14N2O6SNa+
[M+Na]+ 361.0465, found 361.0466.
2,5-Bis((phenylsulfonyl)methyl)-1H-pyrrole (3t): The general procedure was followed
using bromomethyl phenyl sulfone 1a (234.0 mg, 1.0 mmol) and ethyl 1Hꢀpyrrole 2r (69.5
mg, 0.5 mmol) as the starting materials. Purification by column chromatography using
EtOAc/PE (2:3) as the eluent afforded 3u (107.0 mg, 57%) as a white solid. mp =
154−156 °C. 1H NMR (400 MHz, CDCl3) δ 9.34 (s, 1H), 7.78 – 7.68 (m, 4H), 7.67 – 7.58 (m,
13
2H), 7.54 – 7.44 (m, 4H), 5.76 – 5.66 (m, 2H), 4.38 (s, 4H) . C NMR (101 MHz, CDCl3) δ
137.8, 134.0, 129.1, 128.6, 120.1, 112.1, 55.9. IR (neat): 3357, 3187, 2958, 2849, 1646, 1289,
1147, 800, 686 cm−1. HRMS (ESI) m/z: calcd for C18H17NO4S2Na+ [M+Na]+ 398.0491, found
398.0487.
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2,5-Bis((phenylsulfonyl)methyl)furan (3u): The general procedure was followed using
bromomethyl phenyl sulfone 1a (234.0 mg, 1.0 mmol) and furan 2s (34.0 mg, 0.5 mmol) as
the starting materials. Purification by column chromatography using EtOAc/PE (2:3) as the
eluent afforded 3v (52.7 mg, 28%) as a white solid. mp = 125−126 °C. 1H NMR (400 MHz,
CDCl3) δ 7.77 – 7.71 (m, 4H), 7.69 – 7.63 (m, 2H), 7.56 – 7.49 (m, 4H), 6.21 (s, 2H), 4.30 (s,
4H). 13C NMR (101 MHz, CDCl3) δ 143.9, 138.2, 134.2, 129.3, 128.6, 113.7, 55.8. IR (neat):
3061, 2976, 2930, 2849, 1304, 1143, 1083, 810, 685 cm−1. HRMS (ESI) m/z: calcd for
C18H16O5S2Na+ [M+Na]+ 399.0331, found 399.0343.
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2,5-Bis((phenylsulfonyl)methyl)thiophene (3v): The general procedure was followed using
bromomethyl phenyl sulfone 1a (234.0 mg, 1.0 mmol) and thiophene 2t (42.0 mg, 0.5 mmol)
as the starting materials. Purification by column chromatography using DCM as the eluent
afforded 3w (49.3 mg, 25%) as a white solid. mp = 209−211 °C. 1H NMR (400 MHz, DMSO)
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δ 7.78 – 7.69 (m, 6H), 7.65 – 7.55 (m, 4H), 6.63 (s, 2H), 4.93 (s, 4H). C NMR (101 MHz,
DMSO) δ 137.9, 134.1, 131.2, 130.0, 129.2, 128.1, 55.6. IR (neat): 3068, 2978, 2922, 2850,
1300, 1144, 756, 683 cm−1. HRMS (ESI) m/z: calcd for C18H16O4S3Na+ [M+Na]+ 415.0103,
found 415.0103.
1,3-Dimethyl-3-(2-(phenylsulfonyl)ethyl)indolin-2-one (5a): The general procedure was
followed using bromomethyl phenyl sulfone 1a (234.0 mg, 1.0 mmol) and
NꢀmethylꢀNꢀphenylmethacrylamide 4a (87.5 mg, 0.5 mmol) as the starting materials.
Purification by column chromatography using EtOAc/PE (2:3) as the eluent afforded 5a
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(155.1 mg, 94%) as a white solid. mp = 112−114 °C. H NMR (400 MHz, CDCl3) δ 7.86 –
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6
7
8
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7.78 (m, 2H), 7.68 – 7.61 (m, 1H), 7.59 – 7.51 (m, 2H), 7.32 – 7.25 (m, 1H), 7.12 – 7.02 (m,
2H), 6.88 – 6.81 (m, 1H), 3.17 (s, 3H), 2.97 – 2.87 (m, 1H), 2.79– 2.69 (m, 1H), 2.23 (td, J =
13.0, 4.8 Hz, 1H), 2.11 (td, J = 13.1, 3.6 Hz, 1H), 1.34 (s, 3H). 13C NMR (101 MHz, CDCl3)
δ 178.9, 143.0, 138.7, 133.9, 132.1, 129.4, 128.6, 128.1, 123.2, 122.6, 108.5, 51.8, 46.8, 30.7,
26.4, 23.4. IR (neat): 3065, 2989, 2943, 2917, 1702, 1608, 1492, 1146, 750 cm−1. HRMS (ESI)
m/z: calcd for C18H20NO3S+ [M+H]+ 330.1158, found 330.1161.
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1,3-Dimethyl-3-(2-tosylethyl)indolin-2-one (5b): The general procedure was followed using
1ꢀ((bromomethyl)sulfonyl)ꢀ4ꢀmethylbenzene
1b
(248.0
mg,
1.0
mmol)
and
NꢀmethylꢀNꢀphenylmethacrylamide 4a (87.5 mg, 0.5 mmol) as the starting materials.
Purification by column chromatography using EtOAc/PE (1:2) as the eluent afforded 5b
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(139.6 mg, 81%) as a white solid. mp = 151−152 °C. H NMR (400 MHz, CDCl3) δ 7.76 –
7.63 (m, 2H), 7.37 – 7.31 (m, 2H), 7.31 – 7.25 (m, 1H), 7.15 – 7.01 (m, 2H), 6.88 – 6.80 (m,
1H), 3.17 (s, 3H), 2.88 (td, J = 13.2, 5.2 Hz, 1H), 2.71 (td, J = 13.2, 3.6 Hz, 1H), 2.44 (s, 3H),
13
2.20 (td, J = 13.0, 5.2 Hz, 1H), 2.10 (td, J = 13.0, 3.6 Hz, 1H), 1.34 (s, 3H). C NMR (101
MHz, CDCl3) δ 178.9, 144.8, 142.9, 135.6, 132.0, 130.0, 128.5, 128.0, 123.0, 122.5, 108.4,
51.8, 46.8, 30.7, 26.3, 23.3, 21.6. IR (neat): 3033, 2975, 2936, 2873, 1696, 1611, 1302, 1143,
757 cm−1. HRMS (ESI) m/z: calcd for C19H22NO3S+ [M+H]+ 344.1315, found 344.1322.
3-(2-((4-Methoxyphenyl)sulfonyl)ethyl)-1,3-dimethylindolin-2-one (5c): The general
procedure was followed using 1ꢀ((bromomethyl)sulfonyl)ꢀ4ꢀmethoxybenzene 1c (264.0 mg,
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1.0 mmol) and NꢀmethylꢀNꢀphenylmethacrylamide 4a (87.5 mg, 0.5 mmol) as the starting
materials. Purification by column chromatography using EtOAc/PE (1.15:1) as the eluent
afforded 5c (135.0 mg, 75%) as a white solid. mp = 142−144 °C. 1H NMR (400 MHz, CDCl3)
δ 7.68 – 7.62 (m, 2H), 7.22 – 7.16 (m, 1H), 7.05 – 6.94 (m, 2H), 6.93 – 6.88 (m, 2H), 6.79 –
6.73 (m, 1H), 3.78 (s, 3H), 3.08 (s, 3H), 2.79 (td, J = 13.0, 5.0 Hz, 1H), 2.66 – 2.56 (m, 1H),
2.12 (td, J = 13.0, 5.0 Hz, 1H), 2.01 (td, J = 13.0, 4.0 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ
178.9, 163.8, 142.9, 132.1, 130.2, 130.1, 128.5, 123.0, 122.5, 114.5, 108.4, 55.7, 51.9, 46.7,
30.8, 26.2, 23.3. IR (neat): 2981, 2929, 2872, 2840, 1693, 1593, 1493, 1139, 757 cm−1.
HRMS (ESI) m/z: calcd for C19H21NO4SNa+ [M+Na]+ 382.1083, found 382.1097.
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1,3-Dimethyl-3-(2-((4-nitrophenyl)sulfonyl)ethyl)indolin-2-one
(5d):
The
general
procedure was followed using 1ꢀ((bromomethyl)sulfonyl)ꢀ4ꢀnitrobenzene 1d (279.0 mg, 1.0
mmol) and NꢀmethylꢀNꢀphenylmethacrylamide 4a (87.5 mg, 0.5 mmol) as the starting
materials. Purification by column chromatography using EtOAc/PE (1:2) as the eluent
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afforded 5d (28.4 mg, 15%) as a light yellow solid. mp = 143−145 °C. H NMR (400 MHz,
CDCl3) δ 8.45 – 8.35 (m, 2H), 8.08 – 7.99 (m, 2H), 7.35 – 7.28 (m, 1H), 7.18 – 7.04 (m, 2H),
6.90 – 6.81 (m, 1H), 3.18 (s, 3H), 3.01 – 2.90 (m, 1H), 2.90 – 2.80 (m, 1H), 2.27 – 2.18 (m,
1H), 2.16 – 2.07 (m, 1H), 1.36 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 178.8, 151.1, 144.4,
143.0, 132.0, 129.7, 128.9, 124.7, 123.4, 122.6, 108.7, 51.8, 46.8, 30.5, 26.5, 23.5. IR (neat):
3099, 2957, 2919, 2849, 1692, 1492, 1149, 738 cm−1. HRMS (ESI) m/z: calcd for
C18H18N2O5SNa+ [M+Na]+ 397.0829, found 397.0833.
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5-Methoxy-1,3-dimethyl-3-(2-(phenylsulfonyl)ethyl)indolin-2-one (5e): The general
procedure was followed using bromomethyl phenyl sulfone 1a (234.0 mg, 1.0 mmol) and
Nꢀ(4ꢀmethoxyphenyl)ꢀNꢀmethylmethacrylamide 4b (102.5 mg, 0.5 mmol) as the starting
materials. Purification by column chromatography using EtOAc/PE (2:3) as the eluent
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afforded 5e (120.5 mg, 67%) as a colorless solid. mp = 109−111 °C. H NMR (400 MHz,
CDCl3) δ7.86 – 7.80 (m, 2H), 7.68 – 7.62 (m, 1H), 7.58 – 7.51 (m, 2H), 6.83 – 6.69 (m, 3H),
3.77 (s, 3H), 3.14 (s, 3H), 2.92 (td, J = 13.3, 4.8 Hz, 1H), 2.76 (td, J = 13.3, 4.8 Hz, 1H), 2.22
(td, J = 13.0, 4.8 Hz, 1H), 2.08 (td, J = 13.1, 4.8 Hz, 1H), 1.33 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ 178.4, 156.3, 138.5, 136.3, 133.8, 133.3, 129.3, 127.9, 112.6, 110.0, 108.7, 55.7,
51.6, 47.1, 30.6, 26.3, 23.3. IR (neat): 2996, 2967, 2934, 2832, 1694, 1594, 1490, 1149, 745
cm−1. HRMS (ESI) m/z: calcd for C19H22NO4S+ [M+H]+ 360.1264, found 360.1264.
Acknowledgements: Financial support is provided by the Scientific Research Foundation for
the Returned Overseas Chinese Scholars, State Education Ministry.
Supporting information: H and 13C NMR spectra of all products. Mechanistic experiments
1
and results. This material is available free of charge via the Internet at http://pubs.acs.org/.
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