Palladium-Catalyzed Intermolecular Oxidative Cyclization of Allyltosylamides with AcOH: Assembly of 3-Pyrrolin-2-ones

Article abstract of DOI:10.1021/acs.joc.7b00804

The first example of Pd-catalyzed oxidative cyclization of allyltosylamides with acetic acid is reported. This transformation involved C-N/C-C bond formation and provided 3-pyrrolin-2-ones in a one-pot manner with easy-operation, excellent atom economy and good yields. Mechanistic studies indicate that the reaction proceeds through intermolecular aminopalladation, migratory insertion, reinsertion and β-hydride elimination processes.

Full text of DOI:10.1021/acs.joc.7b00804

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Note
Palladium-Catalyzed Intermolecular Oxidative Cyclization of
Allyltosylamides with AcOH: Assembly of 3-Pyrrolin-2-ones
Jiuzhong Huang, Jia Zheng, Wanqing Wu, Jianxiao Li, Zhiqiang Ma, Yanwei Ren, and Huanfeng Jiang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b00804 • Publication Date (Web): 07 Jul 2017
Downloaded from http://pubs.acs.org on July 7, 2017
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Palladium-Catalyzed Intermolecular Oxidative
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Cyclization of Allyltosylamides with AcOH: Assembly
of 3-Pyrrolin-2-ones
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Jiuzhong Huang, Jia Zheng, Wanqing Wu, Jianxiao Li, Zhiqiang Ma*, Yanwei Ren,
and Huanfeng Jiang*
Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of
Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640,
P. R. China
Fax: (+86) 20ꢀ87112906; Eꢀmail: cezqma@scut.edu.cn, jianghf@scut.edu.cn
ABSTRACT: The first example of Pdꢀcatalyzed oxidative cyclization of
allyltosylamides with acetic acid is reported. This transformation involved CꢀN/CꢀC
bond formation and provided 3ꢀpyrrolinꢀ2ꢀones in a oneꢀpot manner with
easyꢀoperation, excellent atom economy and good yields. Mechanistic studies indicate
that the reaction proceeds through intermolecular aminopalladation, migratory
insertion, reinsertion and βꢀhydride elimination processes.
Transition metalꢀcatalyzed oxidative coupling reactions have drawn increasing
attention as powerful synthetic strategy for the formation of C–C/C–X (X=O, N, S…)
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bonds over the past decade.1 Especially, Pdꢀcatalyzed oxidative cyclizations of
alkenes to construct functionalized molecules have been well explored.2 In this regard,
as commercial materials, carboxylic acids/anhydrides have been extensively explored
in alkenyl C–H bond functionalization for the synthesis of heterocycles, in which they
are generally used as synthons by offering one or two bonding sites.3 For instance,
Ackermann reported the Ruꢀcatalyzed C–H bond alkenylation between benzoic acids
and active alkenes with the formation of C–O bond (Scheme 1, I).3a Recently, Wei and
colleagues have successfully constructed CꢀC1/NꢀC1 bonds at C1 position via
Pdꢀcatalyzed C−H functionalization of acrylamides (Scheme 1, II).3c In the aspect of
C2 position as bonding site, our group utilized the anhydrides to construct CꢀO/CꢀC1
bonds in Cuꢀcatalyzed3d and Mnꢀpromoted3e carboesterification of alkenes (Scheme 1,
III). Considering our interests in Pdꢀcatalyzed oxidation cyclization reactions4 and
expanding the scope of synthetic applications of carboxylic acids/anhydrides, we are
the first to disclose AcOH as a C2 synthon to enable rapid assembly of various
3ꢀpyrrolinꢀ2ꢀones.
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Scheme 1. Transition Metal Catalyzed Intermolecular Cyclization Reactions
involving Carboxylic Acids/Anhydrides
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3ꢀPyrrolinꢀ2ꢀone skeleton is an important moiety in natural products and
pharmaceuticals. For example, NMDA receptor glycine antagonist5a and NK1
receptor antagonist5b are the potential therapeutic drugs of chronic pain and CNS
diseases (Figure 1). As synthons,6 3ꢀpyrrolinꢀ2ꢀone skeleton has been modified to
diverse functionalized molecules. However, examples of oneꢀstep approaches from
readily available starting materials are still rare.7 Generally, 3ꢀpyrrolinꢀ2ꢀones could
be obtained by the reduction of maleimide8 and the oxidation of pyrrole.9 More
convenient and versatile methods for constructing functionalized 3ꢀpyrrolinꢀ2ꢀones
are still reckoned as a challenging task.
Figure 1. Selected Biological Active Molecules Containing 3-Pyrrolin-2-one
Motifs
At the outset of this investigation, we employed cinnamyltosylamides as
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available substrates. In the presence of 10 mol % Pd(OAc)2 and 2.0 equiv of
Cu(OAc)2 at 95 oC, 63% yield of 2a was obtained in the reaction of
cinnamyltosylamide with AcOH/Ac2O (Table 1, entry 1). The catalyst screening
showed that other palladium salts such as PdCl2, Pd(CH3CN)2Cl2 and Pd(TFA)2 were
less effective (Table 1, entries 2–4). Further examinations of different additives
revealed that Ag salts promoted this reaction efficiently (Table 1, entries 11–14). To
our delight, the yield increased to 89% when using 2.0 equiv of AgOAc (Table 1,
entry 14). The reaction was totally inhibited when 20 mol % of 1,10ꢀphenanthroline
was added as ligand (Table 1, entry 15). Increasing or decreasing the reaction
temperature showed no obvious beneficial effect (Table 1, entries 16 and 17). It is
noteworthy that the Nꢀacetylation of substrate 1a was observed when decreasing the
amount of AgOAc to 1.2 equiv (entry 19). Without AcOH or Ac2O, product 2a could
be obtained in low yields (Table 1, entries 20 and 21). On the basis of above
investigations, the optimal reaction conditions for this transformation is Pd(OAc)2 (10
mol %), AgOAc (2.0 equiv) in AcOH/Ac2O (1/1, v/v) at 95 oC for 24h.
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Table 1. Optimization of Reaction Conditionsa
catalyst
(10 mol %)
additive
(2.0 equiv)
entry
AcOH:Ac2O
T (oC)
95
yield (%)b
1
2
3
Pd(OAc)2
PdCl2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
1:1
1:1
1:1
68 (63)
95
8
Pd(CH3CN)2Cl2
95
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Pd(TFA)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Cu(OAc)2
CuCl2
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
0:1
1:0
95
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95
115
65
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95
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CuCl
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7
Cu(OTf)2
Fe(NO3)3
Fe(acac)3
Fe(OAc)2
AgNO3
AgNO2
Ag2O
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15c
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18d
19e
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n.d.
61
72
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
Ag(OAc)2
Ag(OAc)2
89 (85)
n.r.
68
32
45
acetylation
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a Reaction conditions: 1a (0.1 mmol), catalyst (10 mol %), additive (2.0 equiv), Ac2O (0.6 mL),
b
1
AcOH (0.6 mL) under air for 24 h; Yield determined by H NMR with CH2BrCl as internal
standard; Isolated yield is in the parentheses. n.d. = not detected; n.r. = not reaction. c 20 mol% of
1,10ꢀphenanthroline was added; d 2.0 equiv of KOAc was added; e 1.2 equiv of AgOAc was added;
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Ts = pꢀTosyl, acac = acetylacetonato.
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With the optimized conditions in hand, various Nꢀcinnamyltosylamides were
examined (Table 2). It was found that most substrates with electronꢀdeficient and
electronꢀrich functional groups including isopropyl, methoxy, nitro, fluoro, chloro,
ethylthio, acetyl and phenyl were successfully transformed to the desired
3ꢀpyrrolinꢀ2ꢀones in moderate yields (2a–2f, 2h–2m). However, the nitrile group
could not be tolerated but hydrolyzed into the corresponding amide group under the
standard conditions (2g). The reaction rate of substrate with electronꢀdonating group
was faster than that with electronꢀwithdrawing group, but they transformed into the
corresponding products in similar yields at last (2c, 2d), which might be attributed to
the slight decomposition of products with EDG under the standard conditions.
Moreover, orthoꢀsubstituted cinnamyltosylamides (2n–2q) were transferred to the
target products in similar yields with paraꢀ and metaꢀsubstituted ones. Gratifyingly,
most of disubstituted substrates exhibited good compatibility in this reaction (2s, 2s,
2u), but 3ꢀmethylꢀ4ꢀmethoxy substrate afforded the product in lower yield (2t).
Unfortunately, dihydrobenzofuran moiety was not tolerated under the current
conditions. The electronic effects may still be a major reason. In addition, the
structure of 2a was confirmed by Xꢀray crystallographic analysis.
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Table
2.
Pd-Catalyzed
Intermolecular Oxidative
Cyclizations
of
Cinnamyltosylamides with AcOHa, b
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a
Reaction conditions: 1 (0.10 mmol), Pd(OAc)2 (10 mol %), AgOAc (0.20 mmol), AcOH (0.6
mL), Ac2O (0.6 mL) at 95 oC for 24 h; b Yields referred to isolated yield.
To our delight, the reactions of allyltosylamide 3a also proceeded smoothly to
provide the corresponding 5ꢀmemberred ring product 4a (Table 3, See Xꢀray of 4a
in SI) 9 Due to low conversion rate under the standard conditions (95 oC),
.
crotyltosylamide 3b and 4ꢀbutenyl tosylamide 3c transformed into 6ꢀmemberred ring
product 4b at 110 oC via 6ꢀendo cyclization, in which 3b should undergo
isomerization of olefin before cyclization. Meanwhile, (E)ꢀ3ꢀpentenyl tosylamide 3d
and 3ꢀmethylꢀ3ꢀbutenyl tosylamide 3e gave 2ꢀpyrrolidone derivates containing
exocyclic double bond 4c and 4d at higher temperature, respectively. On the basis of
the current results, it is difficult to control the formation of 5ꢀ or 6ꢀmembered ring for
the nature of substrates.
Table
3.
Pd-Catalyzed
Intermolecular
Oxidative
Cyclization
of
(Homo)Allyltosylamides with AcOHa, b
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a Reaction conditions: 3 (0.10 mmol), Pd(OAc)2 (10 mol %), AgOAc (0.20 mmol), AcOH (0.6
mL), Ac2O (0.6 mL) for 24 h; b Yields referred to isolated yield.
To gain further insights into this reaction, firstly, we subjected the Nꢀacetylation
byꢀproduct 5 (Table 1, entry 21) to the standard reaction conditions, which failed to
provide the corresponding product (Scheme 2, eq 1). Next, a series of deuterium
labeling experiments were carried out. When the reaction was used AcOH/d6ꢀAc2O as
solvent, no deuterated product was provided (eq 2). However, in the case of 1a in
d4ꢀAcOD/dry Ac2O, product [D]-2a was obtained with 72% D (eq 3). The low level of
deuterium incorporation was caused by Pd(OAc)2, AgOAc. Furthermore, [D]-2a with
75% D was afforded in d6ꢀAc2O/d4ꢀAcOD, which is near to the result of eq 3 (eq 4). It
is noteworthy that the deuterated product [D]-2a (75% deuterium) was stable under
the standard conditions10 (eq 5), which indicated H/D exchange is impossible after
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formation of 2a. Hence, it is supposed that AcOH was the only source of product 2a.
Nevertheless, the role of anhydride as solvent was still not very clear. And when
propionic acid instead of AcOH was used in the reaction, the desired product couldn’t
be detected.
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Scheme 2. Control Experiments
On the basis of the above results and previous works,11 a tentative mechanism for
the Pdꢀcatalyzed oxidative cyclization between allyltosylamides and AcOH is
proposed in Scheme 3. Firstly, intermediate A is formed by the reaction of Pd(OAc)2
and Nꢀtosylamide.2c, 4b, 12 Then the NꢀPd species A inserts to the alkene isomer of
AcOH,13 followed by the intermolecular aminopalladation to generate the
intermediate B.14 Subsequent 1,2ꢀmigratory insertion offers intermediate C (path a). A
sequence of βꢀhydride elimination and reinsertion provides the intermediate E.15
Finally, βꢀhydride elimination of complex E releases product 2a and Pd(0). The
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catalyst is regenerated by oxidation of AgOAc.16 Additionally, the intermediate B can
undergo βꢀoxygen elimination to afford the Nꢀacetylation byꢀproduct 5. 17
Scheme 3. Proposed Mechanism
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In conclusion, this method affords the desired 3ꢀpyrrolinꢀ2ꢀones with good yields
and group tolerance. The reaction mechanism consists of intermolecular
aminopalladation, migratory insertion, reinsertion and βꢀhydride elimination
processes. Furthermore, we have developed
a
new and convenient
palladiumꢀcatalyzed oxidative cyclization of allyltosylamides and acid as C2 synthon.
EXPERIMENTAL SECTION
1
General Method: H and 13C NMR spectra were recorded on BRUKER DRXꢀ400
spectrometer using CDCl3 as solvent and TMS as an internal standard. The chemical
shifts are referenced to signals at 7.26 and 77.0 ppm, respectively. The data of HRMS
was carried out on a highꢀresolution mass spectrometer (LCMSꢀITꢀTOF). IR spectra
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were obtained either as potassium bromide pellets or as liquid films between two
potassium bromide pellets with a BRUKER TENSOR 27 spectrometer. Melting
points were determined with Büchi Melting Point Bꢀ545 instrument. Unless otherwise
stated, all reagents and solvents were purchased from commercial suppliers and used
without further purification.
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Synthesis of (E)-N-(3-chloroallyl)-4-methylbenzenesulfonamide20: TsNH2 (10.0
mmol), K2CO3 (6.0 mmol), CH3CN (40 mL) and (E)ꢀ1,3ꢀdichloropropꢀ1ꢀene (5.0
mmol) were successively added to 100 mL roundꢀbottomed flask with magnetic stirrer
bar. The mixture was stirred at 60 oC (oil bath temperature) for 16 h. The reaction was
quenched with saturated NH4Cl aq. and extracted with EtOAc (3 × 50 mL), washed
with brine (10 mL). The combined organic layers were dried over anhydrous Na2SO4
and the solvent was removed under vacuum. The crude product was purified via
column chromatography (EtOAc/hexanes = 1/3) on silica gel to afford the product as
white solid (759 mg, 62% yield).
A representative procedure for N-cinnamyltosylamides derivatives (1a-1w):
(E)ꢀNꢀ(3ꢀchloroallyl)ꢀ4ꢀmethylbenzenesulfonamide (1.0 mmol), Aryl boric acid (1.2
mmol), K2CO3 (2.5 mmol), Pd(dppf)Cl2 (0.1 mmol), EtOH (3 mL) and toluene (3 mL)
were successively added to 25 mL seal tube, then was evacuated and filled with N2 for
o
three times. The mixture was stirred at 60 C (oil bath temperature) overnight. The
reaction was quenched with saturated NH4Cl aq. and extracted with EtOAc (3 × 20
mL), washed with brine (10 mL). The combined organic layers were dried over
anhydrous Na2SO4 and the solvent was removed under vacuum. The crude product
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was purified via column chromatography (EtOAc/hexanes = 1/3ꢀ1/2) on silica gel.
The characterization data of 1a21a, 1c21b, 1e21b, 1f21b, 1p21a were consistent with the
reported literatures.
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A representative procedure for (homo)allyltosylamides derivatives (3a-3e):
TsNH2 (2.0 mmol), K2CO3 (2.4 mmol), CH3CN (8 mL) and (homo)allyl bromide (2.0
mmol) were successively added to 25 mL roundꢀbottomed flask with magnetic stirrer
bar. The mixture was stirred at 60 oC (oil bath temperature) for 16 h. The reaction was
quenched with saturated NH4Cl (aq.) and extracted with EtOAc (3 × 15 mL), washed
with brine (10 mL). The combined organic layers were dried over anhydrous Na2SO4
and the solvent was removed under vacuum. The crude product was purified via
column chromatography (EtOAc/hexanes = 1/4) on silica gel. The characterization
data of 3a22a, 3b22a, 3c22b, 3d22c, 3e20d were consistent with the reported literatures.
A representative procedure for 3-pyrrolin-2-ones derivatives: Allyltosylamide
(0.10 mmol), Pd(OAc)2 (0.01 mmol), AgOAc (0.20 mmol) in AcOH (0.6 mL), Ac2O
(0.6 mL) were added to a 20 mL tube with magnetic stirrer bar. The mixture was
o
stirred at 90
–
130 C (oil bath temperature) for 24 h under open air. After the reaction
was finished (monitored by TLC), the mixture was cooled to room temperature. The
reaction was neutralized with saturated NaHCO3 aq. and extracted with EtOAc (3 ×
15 mL), washed with brine (10 mL). The combined organic layers were dried over
anhydrous Na2SO4 and the solvent was removed under vacuum. The crude product
was purified via column chromatography (EtOAc/hexanes = 1/3) on silica gel.
Analytical Characterization Data of Substrates and Products
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(E)-N-(3-(4-isopropylphenyl)allyl)-4-methylbenzenesulfonamide (1b): Purified via
flash column chromatography with 25% ethyl acetate/petroleum ether, yielding 65%
(213 mg). 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 7.8 Hz,
2H), 7.16 (q, J = 8.3 Hz, 4H), 6.41 (d, J = 15.8 Hz, 1H), 5.96 (dt, J = 15.7, 6.4 Hz,
1H), 4.54 (s, 1H), 3.74 (t, J = 5.8 Hz, 2H), 2.87 (dt, J = 13.8, 6.9 Hz, 1H), 1.23 (d, J =
6.9 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 148.9, 143.5, 137.1, 133.7, 133.1, 129.7,
127.2, 126.6, 126.4, 123.1, 45.6, 33.8, 23.9, 21.5. HRMS (ESIꢀTOF) m/z: [M + Na]+
Calcd for C19H23NO2SNa 352.1342; found 352.1344.
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(E)-4-methyl-N-(3-(4-nitrophenyl)allyl)benzenesulfonamide (1d): Purified via
flash column chromatography with 40% ethyl acetate/petroleum ether, yielding 83%
(275 mg). 1H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 8.7 Hz, 2H), 7.80 (d, J = 8.2 Hz,
2H), 7.39 (d, J = 8.7 Hz, 2H), 7.33 (d, J = 8.1 Hz, 2H), 6.56 (d, J = 15.9 Hz, 1H), 6.26
(dd, J = 13.9, 8.0 Hz, 1H), 4.86 (t, J = 6.1 Hz, 1H), 3.83 (t, J = 5.6 Hz, 2H), 2.44 (s,
3H). 13C NMR (101 MHz, CDCl3) δ 147.1, 143.8, 142.6, 137.0, 130.5, 129.8, 129.4,
127.2, 126.9, 123.9, 45.1, 21.5. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C16H16N2O4SNa 355.0723; found 355.0720.
(E)-N-(3-(4-cyanophenyl)allyl)-4-methylbenzenesulfonamide (1g): Purified via
flash column chromatography with 45% ethyl acetate/petroleum ether, yielding 43%
(148 mg). 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.3 Hz, 2H), 7.58 (d, J = 8.3 Hz,
2H), 7.33 (dd, J = 7.9, 6.9 Hz, 4H), 6.50 (d, J = 15.9 Hz, 1H), 6.19 (dt, J = 15.9, 6.0
Hz, 1H), 4.84 (s, 1H), 3.81 (t, J = 5.2 Hz, 2H), 2.44 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ 143.7, 140.6, 137.0, 132.4, 131.0, 129.8, 128.5, 127.2, 126.9, 118.7, 111.2,
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45.1, 21.5. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C17H16N2O2SNa 335.0825;
found 335.0833.
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(E)-N-(3-(4-(ethylthio)phenyl)allyl)-4-methylbenzenesulfonamide (1h): Purified
via flash column chromatography with 33% ethyl acetate/petroleum ether, yielding
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73% (253 mg). H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.2 Hz, 2H), 7.30 (d, J =
8.0 Hz, 2H), 7.22 (d, J = 8.3 Hz, 2H), 7.15 (d, J = 8.3 Hz, 2H), 6.39 (d, J = 15.8 Hz,
1H), 6.05 – 5.91 (m, 1H), 4.61 (s, 1H), 3.74 (d, J = 5.0 Hz, 2H), 2.93 (q, J = 7.3 Hz,
2H), 2.41 (s, 3H), 1.31 (t, J = 7.3 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 143.7,
137.1, 136.6, 133.6, 132.5, 129.7, 128.7, 127.2, 126.8, 123.7, 45.5, 27.4, 21.5, 14.3.
HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C18H21NO2S2Na 370.0906; found
370.0910.
(E)-N-(3-([1,1'-biphenyl]-4-yl)allyl)-4-methylbenzenesulfonamide (1i): Purified
via flash column chromatography with 30% ethyl acetate/petroleum ether, yielding
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81% (294 mg). H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.2 Hz, 2H), 7.60 (d, J =
7.3 Hz, 2H), 7.55 (d, J = 8.2 Hz, 2H), 7.46 (t, J = 7.6 Hz, 2H), 7.36 (dd, J = 16.7, 7.7
Hz, 5H), 6.50 (d, J = 15.8 Hz, 1H), 6.09 (dd, J = 14.3, 7.9 Hz, 1H), 4.71 (s, 1H), 3.81
(s, 2H), 2.44 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 143.6, 140.7, 140.5, 137.2, 135.1,
132.6, 129.8, 128.8, 127.4, 127.2, 126.9, 126.8, 124.2, 45.5, 21.5. HRMS (ESIꢀTOF)
m/z: [M + Na]+ Calcd for C22H21NO2SNa 386.1185; found 386.1182.
(E)-4-methyl-N-(3-(m-tolyl)allyl)benzenesulfonamide (1j): Purified via flash
column chromatography with 30% ethyl acetate/petroleum ether, yielding 68% (204
mg). 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.2 Hz, 2H), 7.27 (d, J = 8.1 Hz, 2H),
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7.15 (t, J = 7.7 Hz, 1H), 7.02 (t, J = 6.5 Hz, 3H), 6.38 (d, J = 15.8 Hz, 1H), 5.97 (dt, J
= 15.8, 6.4 Hz, 1H), 4.92 (t, J = 6.0 Hz, 1H), 3.72 (t, J = 5.9 Hz, 2H), 2.39 (s, 3H),
2.30 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 143.5, 138.1, 137.2, 136.1, 133.1, 129.7,
128.7, 128.4, 127.2, 127.1, 123.9, 123.6, 45.5, 21.5, 21.3. HRMS (ESIꢀTOF) m/z: [M
+ Na]+ Calcd for C17H19NO2SNa 324.1029; found 324.1034.
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(E)-N-(3-(3-methoxyphenyl)allyl)-4-methylbenzenesulfonamide (1k): Purified via
flash column chromatography with 40% ethyl acetate/petroleum ether, yielding 55%
(174 mg). 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.2 Hz, 2H), 7.31 (d, J = 8.1 Hz,
2H), 7.21 (t, J = 7.8 Hz, 1H), 6.89 – 6.75 (m, 3H), 6.42 (d, J = 15.8 Hz, 1H), 6.01 (dt,
J = 15.8, 6.3 Hz, 1H), 4.87 (t, J = 6.1 Hz, 1H), 3.80 (s, 3H), 3.78 – 3.72 (m, 2H), 2.42
(s, 3H). 13C NMR (101 MHz, CDCl3) δ 159.7, 143.5, 137.6, 137.1, 132.9, 129.8,
129.5, 127.2, 124.5, 119.1, 113.5, 111.7, 55.2, 45.4, 21.5. HRMS (ESIꢀTOF) m/z: [M
+ Na]+ Calcd for C17H19NO3SNa 340.0978; found 340.0980.
(E)-N-(3-(3-chlorophenyl)allyl)-4-methylbenzenesulfonamide (1l): Purified via
flash column chromatography with 30% ethyl acetate/petroleum ether, yielding 72%
(231 mg).1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.2 Hz, 2H), 7.33 (d, J = 8.1 Hz,
2H), 7.26 – 7.18 (m, 3H), 7.15 – 7.08 (m, 1H), 6.39 (d, J = 15.8 Hz, 1H), 6.02 (dt, J =
15.8, 6.2 Hz, 1H), 4.72 (t, J = 5.9 Hz, 1H), 3.84 – 3.74 (m, 2H), 2.44 (s, 3H). 13C
NMR (101 MHz, CDCl3) δ 143.7, 138.0, 137.2, 134.5, 131.6, 129.8, 127.8, 127.2,
126.3, 125.8, 124.6, 45.2, 21.5. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C16H16ClNO2SNa 344.0482; found 344.0487.
(E)-N-(3-(3-acetylphenyl)allyl)-4-methylbenzenesulfonamide (1m): Purified via
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flash column chromatography with 40% ethyl acetate/petroleum ether, yielding 51%
(167 mg). 1H NMR (400 MHz, CDCl3) δ 7.80 (dd, J = 11.0, 6.6 Hz, 4H), 7.44 (d, J =
7.8 Hz, 1H), 7.38 (dd, J = 10.5, 5.3 Hz, 1H), 7.32 – 7.28 (m, 2H), 6.49 (d, J = 15.9 Hz,
1H), 6.11 (dt, J = 15.8, 6.2 Hz, 1H), 5.09 (s, 1H), 3.78 (t, J = 5.7 Hz, 2H), 2.59 (s, 3H),
2.41 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 198.1, 143.6, 137.4, 137.1, 136.7, 131.8,
130.8, 129.7, 128.8, 127.7, 127.2, 126.2, 125.8, 45.2, 26.6, 21.5. HRMS (ESIꢀTOF)
m/z: [M + Na]+ Calcd for C18H19NO3SNa 352.0978; found 352.0970.
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(E)-4-methyl-N-(3-(o-tolyl)allyl)benzenesulfonamide (1n): Purified via flash
column chromatography with 30% ethyl acetate/petroleum ether, yielding 75% (225
mg). 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.1 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H),
7.26 – 7.19 (m, 1H), 7.12 (dt, J = 11.4, 5.7 Hz, 3H), 6.65 (d, J = 15.7 Hz, 1H), 5.88
(dt, J = 15.6, 6.3 Hz, 1H), 4.85 (t, J = 5.9 Hz, 1H), 3.76 (t, J = 6.2 Hz, 2H), 2.40 (s,
4H), 2.24 (s, 4H). 13C NMR (101 MHz, CDCl3) δ 143.5, 137.2, 135.4, 135.2, 130.9,
130.3, 129.8, 127.8, 127.2, 126.1, 125.7, 125.5, 45.7, 21.5, 19.7. HRMS (ESIꢀTOF)
m/z: [M + Na]+ Calcd for C17H19NO3SNa 324.1029; found 324.1033.
(E)-N-(3-(2-fluorophenyl)allyl)-4-methylbenzenesulfonamide (1o): Purified via
flash column chromatography with 33% ethyl acetate/petroleum ether, yielding 77%
(234 mg). 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.0 Hz, 2H), 7.27 (t, J = 8.3 Hz,
3H), 7.19 (dd, J = 13.5, 6.7 Hz, 1H), 7.10 – 6.93 (m, 2H), 6.57 (d, J = 16.0 Hz, 1H),
6.10 (dt, J = 15.9, 6.3 Hz, 1H), 4.91 (s, 1H), 3.76 (t, J = 6.1 Hz, 2H), 2.39 (s, 3H). 13C
NMR (101 MHz, CDCl3) δ 161.4, 158.9, 143.6, 137.0, 129.7, 129.2 (d, J = 8.5 Hz),
127.5 (d, J = 3.6 Hz), 127.2, 126.9 (d, J = 4.9 Hz), 125.4 (d, J = 3.5 Hz), 124.1 (d, J =
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3.5 Hz), 115.7 (d, J = 22 Hz), 45.7, 21.5. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C16H16FNO2SNa 328.0778; found 328.0775.
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(E)-4-methyl-N-(3-(2-nitrophenyl)allyl)benzenesulfonamide (1q): Purified via
flash column chromatography with 50% ethyl acetate/petroleum ether, yielding 74%
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(235 mg). H NMR (400 MHz, CDCl3) δ 8.12 – 8.02 (m, 2H), 7.81 (d, J = 8.3 Hz,
2H), 7.57 (d, J = 7.7 Hz, 1H), 7.47 (t, J = 7.9 Hz, 1H), 7.33 (d, J = 8.2 Hz, 2H), 6.53
(d, J = 15.9 Hz, 1H), 6.18 (dt, J = 15.9, 6.0 Hz, 1H), 4.91 (s, 1H), 3.93 – 3.68 (m, 2H),
2.43 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 148.5, 143.8, 137.9, 137.1, 132.2, 130.4,
129.8, 129.5, 127.8, 127.2, 122.4, 120.9, 45.0, 21.5. HRMS (ESIꢀTOF) m/z: [M +
Na]+ Calcd for C16H16N2O4SNa 355.0723; found 355.0721.
(E)-N-(3-(3-chloro-4-methylphenyl)allyl)-4-methylbenzenesulfonamide
(1r):
Purified via flash column chromatography with 40% ethyl acetate/petroleum ether,
yielding 83% (278 mg). 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.2 Hz, 2H), 7.31
(d, J = 8.1 Hz, 2H), 7.18 (d, J = 1.2 Hz, 1H), 7.14 (d, J = 7.8 Hz, 1H), 7.03 (dd, J =
7.8, 1.3 Hz, 1H), 6.35 (d, J = 15.8 Hz, 1H), 5.96 (dt, J = 15.8, 6.3 Hz, 1H), 4.87 (s,
1H), 3.76 (t, J = 5.8 Hz, 2H), 2.43 (s, 3H), 2.35 (s, 3H). 13C NMR (101 MHz, CDCl3)
δ 143.6, 137.2, 135.5, 134.5, 131.5, 131.0, 129.7, 127.2, 126.8, 124.7, 124.6, 45.3,
21.5, 19.7. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C17H18ClNO2SNa 358.0639;
found 358.0637.
(E)-N-(3-(3,4-dimethylphenyl)allyl)-4-methylbenzenesulfonamide (1s): Purified
via flash column chromatography with 30% ethyl acetate/petroleum ether, yielding
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63% (198 mg). H NMR (400 MHz, CDCl3) δ 7.79 (t, J = 8.7 Hz, 2H), 7.33 (d, J =
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8.0 Hz, 2H), 7.11 – 6.93 (m, 3H), 6.40 (d, J = 15.8 Hz, 1H), 5.97 (dt, J = 15.7, 6.4 Hz,
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1H), 4.61 (s, 1H), 3.75 (t, J = 5.9 Hz, 2H), 2.45 (s, 3H), 2.25 (s, 6H). C NMR (101
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MHz, CDCl3) δ 143.5, 137.2, 136.7, 136.6, 133.75, 133.2, 129.8, 129.7, 127.7, 127.2,
123.9, 122.8, 45.6, 21.5, 19.7, 19.5. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C18H21NO2SNa 338.1185; found 338.1191.
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(E)-N-(3-(4-methoxy-3-methylphenyl)allyl)-4-methylbenzenesulfonamide
(1t):
Purified via flash column chromatography with 33% ethyl acetate/petroleum ether,
yielding 57% (188 mg). 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.3 Hz, 2H), 7.33
(d, J = 8.0 Hz, 2H), 7.06 (d, J = 4.6 Hz, 2H), 6.77 – 6.72 (m, 1H), 6.37 (d, J = 15.8 Hz,
1H), 5.87 (dt, J = 15.8, 6.5 Hz, 1H), 4.61 (s, 1H), 3.84 (d, J = 2.4 Hz, 3H), 3.74 (td, J
= 6.4, 1.2 Hz, 2H), 2.44 (s, 3H), 2.20 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 157.7,
143.4, 137.2, 132.9, 129.7, 128.5, 128.3, 127.2, 126.7, 125.3, 121.4, 109.8, 55.3, 45.7,
21.5, 16.2. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C18H21NO3SNa 354.1134;
found 354.1140.
(E)-N-(3-(5-fluoro-2-methoxyphenyl)allyl)-4-methylbenzenesulfonamide
(1u):
Purified via flash column chromatography with 40% ethyl acetate/petroleum ether,
yielding 73% (244 mg). 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.2 Hz, 2H), 7.31
(d, J = 7.1 Hz, 2H), 6.94 – 6.85 (m, 2H), 6.80 – 6.68 (m, 2H), 5.98 (dt, J = 15.8, 6.3
Hz, 1H), 4.87 (dd, J = 20.4, 14.5 Hz, 1H), 3.77 (dd, J = 9.0, 3.7 Hz, 5H), 2.42 (s, 3H).
13C NMR (101 MHz, CDCl3) δ 158.2, 155.8, 152.8, 143.5, 137.2, 129.7, 127.2, 127.0,
125.9, 114.8 (d, J = 23 Hz), 113.1 (d, J = 24 Hz), 111.91 (d, J = 8.2 Hz), 56.03 (d, J =
4.3 Hz), 45.7, 21.5. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C17H18FNO3SNa
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358.0884; found 358.0888.
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via flash column chromatography with 30% ethyl acetate/petroleum ether, yielding
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46% (163 mg). H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.0 Hz, 2H), 7.30 (d, J =
7.7 Hz, 2H), 7.20 (s, 1H), 7.05 (s, 2H), 6.30 (d, J = 15.8 Hz, 1H), 5.99 (dt, J = 15.5,
5.9 Hz, 1H), 4.83 (d, J = 49.0 Hz, 1H), 3.76 (s, 2H), 2.42 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ 143.7, 139.2, 137.2, 135.1, 130.2, 129.8, 127.6, 127.5, 127.2, 124.7, 45.0,
21.5. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C16H15Cl2NO2SNa 378.0093;
found 378.0098.
(E)-N-(3-(2,3-dihydrobenzofuran-5-yl)allyl)-4-methylbenzenesulfonamide (1w):
Purified via flash column chromatography with 40% ethyl acetate/petroleum ether,
yielding 56% (184 mg). 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.2 Hz, 2H), 7.29
(d, J = 8.2 Hz, 2H), 7.11 (s, 1H), 6.97 (d, J = 8.3 Hz, 1H), 6.68 (d, J = 8.2 Hz, 1H),
6.36 (d, J = 15.8 Hz, 1H), 5.84 (dt, J = 15.7, 6.5 Hz, 1H), 4.97 (d, J = 4.5 Hz, 1H),
4.56 (t, J = 8.7 Hz, 2H), 3.71 (dd, J = 9.1, 3.4 Hz, 2H), 3.16 (t, J = 8.7 Hz, 2H), 2.42
(s, 3H). 13C NMR (101 MHz, CDCl3) δ 160.0, 143.4, 137.2, 133.0, 129.7, 129.0,
127.5, 127.2, 126.9, 122.7, 121.2, 109.1, 71.4, 45.6, 29.5, 21.5. HRMS (ESIꢀTOF)
m/z: [M + Na]+ Calcd for C18H19NO3SNa 352.0978; found 352.0981.
4-Benzyl-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (2a): Purified via flash column
chromatography with 30% ethyl acetate/petroleum ether, yielding 85% (27.8 mg) as a
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white solid: m.p. = 168 – 169 °C. H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 7.9 Hz,
2H), 7.39 – 7.27 (m, 5H), 7.14 (d, J = 7.2 Hz, 2H), 5.71 (s, 1H), 4.32 (s, 2H), 3.67 (s,
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2H), 2.42 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 168.4, 162.7, 145.0, 135.6, 135.5,
129.7, 129.1, 128.80, 127.9, 127.5, 122.2, 53.5, 36.7, 21.7. HRMS (ESIꢀTOF) m/z: [M
+ Na]+ Calcd for C18H17NO3SNa 350.0821; found 350.0824. IR (KBr): 3489, 2960,
1723, 1264, 1164, 1028, 752 cm−1.
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4-(4-Isopropylbenzyl)-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (2b): Purified via flash
column chromatography with 30% ethyl acetate/petroleum ether, yielding 74% (27.3
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mg) as a yellow solid: m.p. = 139 – 140 °C. H NMR (400 MHz, CDCl3) δ 7.92 (d, J
= 8.1 Hz, 2H), 7.31 (d, J = 8.1 Hz, 2H), 7.19 (d, J = 7.9 Hz, 2H), 7.05 (d, J = 7.9 Hz,
2H), 5.72 (s, 1H), 4.32 (s, 2H), 3.64 (s, 2H), 2.89 (dd, J = 13.8, 6.9 Hz, 1H), 2.42 (s,
3H), 1.24 (d, J = 6.9 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 168.5, 163.1, 148.2,
145.0, 135.5, 132.9, 129.7, 128.7, 127.9, 127.1, 122.0, 53.5, 36.3, 33.8, 24.0, 21.6.
HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C21H23NO3SNa 392.1291; found
392.1294. IR (KBr): 2958, 1723, 1357, 1162, 660, 556 cm−1.
4-(4-Methoxybenzyl)-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (2c): Purified via flash
column chromatography with 44% ethyl acetate/petroleum ether, yielding 71% (25.3
mg) as a white solid: m.p. = 164 – 165 °C. 1H NMR (400 MHz, CDCl3) δ 7.92 (d, J =
8.2 Hz, 2H), 7.32 (d, J = 8.1 Hz, 2H), 7.05 (d, J = 8.4 Hz, 2H), 6.86 (d, J = 8.5 Hz,
2H), 5.70 (s, 1H), 4.30 (s, 2H), 3.80 (s, 3H), 3.62 (s, 2H), 2.42 (s, 3H);13C NMR (101
MHz, CDCl3) δ 168.5, 163.4, 158.9, 145.0, 135.5, 129.8, 129.7, 127.9, 127.5, 121.8,
114.5, 55.3, 53.4, 35.8, 21.6. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C19H19NO4SNa 380.0927; found 380.0934. IR (KBr): 2907, 1718, 1240, 1157, 1024,
657, 555 cm−1.
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1-Tosyl-4-(4-(trifluoromethyl)benzyl)-1,5-dihydro-2H-pyrrol-2-one (2d): Purified
via flash column chromatography with 45% ethyl acetate/petroleum ether, yielding
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75% (17.5 mg) as a white solid: m.p. = 183 – 185 °C. H NMR (400 MHz, CDCl3) δ
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8.21 (d, J = 7.8 Hz, 2H), 7.92 (d, J = 7.6 Hz, 2H), 7.34 (t, J = 6.8 Hz, 4H), 5.71 (s,
1H), 4.35 (s, 2H), 3.79 (s, 2H), 2.43 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 167.8,
160.3, 147.5, 145.3, 142.8, 135.3, 129.8, 129.7, 128.0, 124.3, 123.2, 53.4, 36.2, 21.7.
HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C18H16N2O5SNa 395.0672; found
395.0675. IR (KBr): 2923, 1721, 1515, 1349, 1164, 661, 552 cm−1.
4-(4-Fluorobenzyl)-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (2e): Purified via flash
column chromatography with 33% ethyl acetate/petroleum ether, yielding 86% (29.6
mg) as a light yellow solid: m.p. = 158 – 159 °C. 1H NMR (400 MHz, CDCl3) δ 7.92
(d, J = 8.2 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 7.11 (dd, J = 8.3, 5.4 Hz, 2H), 7.03 (t, J
= 8.5 Hz, 2H), 5.69 (s, 1H), 4.31 (s, 2H), 3.65 (s, 2H), 2.43 (s, 3H); 13C NMR (101
MHz, CDCl3) δ 168.2, 162.5, 145.1, 135.5, 131.3, 130.4 (d, J = 8.1 Hz), 129.7, 127.9,
122.2, 116.1, 115.9, 53.4, 35.8, 21.6. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C18H16FNO3SNa 368.0727; found 368.0731. IR (KBr): 2921, 1719, 1603, 1502, 1156,
823, 659, 552 cm−1.
4-(4-Chlorobenzyl)-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (2f): Purified via flash
column chromatography with 30% ethyl acetate/petroleum ether, yielding 68% (24.5
mg) as a White solid: m.p. = 178 – 180 °C. 1H NMR (400 MHz, CDCl3) δ 7.92 (d, J =
8.3 Hz, 2H), 7.31 (dd, J = 8.1, 4.6 Hz, 4H), 7.08 (d, J = 8.3 Hz, 2H), 5.69 (s, 1H),
4.31 (s, 2H), 3.65 (s, 2H), 2.42 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 168.1, 162.0,
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145.1, 135.4, 134.0, 133.5, 130.2, 129.7, 129.3, 128.0, 122.4, 53.6, 36.0, 21.6. HRMS
(ESIꢀTOF) m/z: [M + Na]+ Calcd for C18H16ClNO3SNa 384.0432; found 384.0435. IR
(KBr): 2926, 1723, 1355, 1162, 817, 662, 555 cm−1.
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4-((5-Oxo-1-tosyl-2,5-dihydro-1H-pyrrol-3-yl)methyl)benzamide (2g): Purified via
flash column chromatography with 50% ethyl acetate/petroleum ether, yielding 60%
(22.2 mg) as a light yellow solid: m.p. = 171 – 172 °C. 1H NMR (400 MHz, CDCl3) δ
7.92 (d, J = 8.2 Hz, 2H), 7.65 (d, J = 8.1 Hz, 2H), 7.33 (d, J = 8.1 Hz, 2H), 7.28 (d, J
= 8.2 Hz, 2H), 5.70 (s, 1H), 4.33 (s, 2H), 3.74 (s, 2H), 2.43 (s, 3H); 13C NMR (101
MHz, CDCl3) δ 167.8, 160.5, 145.3, 140.9, 135.3, 132.9, 129.8, 129.7, 128.0, 123.1,
118.3, 111.8, 53.4, 36.5, 21.7. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C19H18N2O4SNa 393.0879; found 393.0874. IR (KBr): 2923, 2228, 1723, 1355, 1163,
661, 554 cm−1.
4-(4-(Ethylthio)benzyl)-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (2h): Purified via
flash column chromatography with 40% ethyl acetate/petroleum ether, yielding 62%
(23.9 mg) as a white solid: m.p. = 169 – 170 °C. 1H NMR (400 MHz, CDCl3) δ 7.85
(d, J = 8.2 Hz, 2H), 7.21 (dd, J = 13.2, 5.1 Hz, 4H), 6.98 (d, J = 8.1 Hz, 2H), 5.64 (s,
1H), 4.24 (s, 2H), 3.56 (s, 2H), 2.87 (q, J = 7.3 Hz, 2H), 2.35 (s, 3H), 1.25 (t, J = 7.3
Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 167.3, 161.5, 144.0, 135.2, 134.4, 131.9,
128.7, 128.4, 128.2, 126.9, 121.2, 52.3, 35.1, 26.5, 20.6, 13.3. HRMS (ESIꢀTOF) m/z:
[M + Na]+ Calcd for C20H21NO3S2Na 410.0855; found 410.0857. IR (KBr): 2963,
1717, 1154, 1091, 1024, 753, 656 cm−1.
4-([1,1'-Biphenyl]-4-ylmethyl)-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (2i): Purified
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63% (25.3 mg) as a white solid: m.p. = 193 – 194 °C. H NMR (400 MHz, CDCl3) δ
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7.96 (d, J = 8.3 Hz, 2H), 7.64 – 7.56 (m, 4H), 7.47 (t, J = 7.5 Hz, 2H), 7.41 – 7.32 (m,
3H), 7.23 (d, J = 8.2 Hz, 2H), 5.84 – 5.75 (m, 1H), 4.38 (s, 2H), 3.74 (s, 2H), 2.45 (s,
3H); 13C NMR (101 MHz, CDCl3) δ 168.4, 162.6, 145.0, 140.5, 140.4, 135.5, 134.5,
129.7, 129.2, 128.8, 128.0,127.8, 127.5, 127.0, 122.2, 53.5, 36.3, 21.6. HRMS
(ESIꢀTOF) m/z: [M + Na]+ Calcd for C24H21NO3SNa 426.1134; found 426.1137. IR
(KBr): 2920, 1718, 1354, 1160, 753, 661, 555 cm−1.
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4-(3-Methylbenzyl)-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (2j): Purified via flash
column chromatography with 30% ethyl acetate/petroleum ether, yielding 69% (23.5
mg) as a white solid: m.p. = 130 – 131 °C. 1H NMR (400 MHz, CDCl3) δ 7.92 (d, J =
8.2 Hz, 2H), 7.32 (d, J = 8.1 Hz, 2H), 7.22 (t, J = 7.5 Hz, 1H), 7.09 (d, J = 7.6 Hz,
1H), 6.93 (d, J = 7.7 Hz, 2H), 5.73 (s, 1H), 4.31 (s, 2H), 3.63 (s, 2H), 2.42 (s, 3H),
2.33 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 168.5, 162.9, 145.0, 138.8, 135.5, 135.5,
129.7, 129.5, 128.9, 128.2, 127.9, 125.8, 122.0, 53.5, 36.6, 21.6, 21.3. HRMS
(ESIꢀTOF) m/z: [M + Na]+ Calcd for C19H19NO3SNa 364.0978; found 364.0985. IR
(KBr): 2922, 1722, 1355, 1162, 1026, 660, 556 cm−1.
4-(3-Methoxybenzyl)-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (2k): Purified via flash
column chromatography with 44% ethyl acetate/petroleum ether, yielding 48% (17.1
mg) as a light yellow solid: m.p. = 159 – 160 °C. 1H NMR (400 MHz, CDCl3) δ 7.92
(d, J = 8.3 Hz, 2H), 7.31 (d, J = 8.1 Hz, 2H), 7.25 (d, J = 6.6 Hz, 1H), 6.82 (dd, J =
8.1, 2.3 Hz, 1H), 6.71 (d, J = 7.5 Hz, 1H), 6.66 (d, J = 1.8 Hz, 1H), 5.81 – 5.70 (m,
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1H), 4.31 (s, 2H), 3.79 (s, 3H), 3.64 (s, 2H), 2.42 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 168.4, 162.6, 160.1, 145.0, 137.0, 135.5, 130.1, 129.7, 127.9, 122.1, 121.0,
114.7, 112.6, 55.2, 53.4, 36.7, 21.6. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C19H19NO4SNa 380.0927; found 380.0930. IR (KBr):2929, 1724, 1356, 1162, 1032,
662, 564 cm−1.
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4-(3-Chlorobenzyl)-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (2l): Purified via flash
column chromatography with 30% ethyl acetate/petroleum ether, yielding 76% (27.4
1
mg) as a yellow solid: m.p. = 122 – 123 °C. H NMR (400 MHz, CDCl3) δ 7.84 (d, J
= 8.2 Hz, 2H), 7.24 (d, J = 8.1 Hz, 2H), 7.19 (d, J = 4.8 Hz, 2H), 7.05 (s, 1H), 6.96 (d,
J = 3.5 Hz, 1H), 5.62 (s, 1H), 4.24 (s, 2H), 3.57 (s, 2H), 2.34 (s, 3H); 13C NMR (101
MHz, CDCl3) δ 168.2, 161.8, 145.1, 137.5, 135.4, 134.8, 130.3, 129.8, 129.0, 127.9,
127.7, 127.1, 122.5, 53.4, 36.1, 21.7. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C18H16ClNO3SNa 384.0432; found, 384.0434. IR (KBr): 2929, 1723, 1355, 1162, 661,
557 cm−1.
4-(3-Acetylbenzyl)-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (2m): Purified via flash
column chromatography with 40% ethyl acetate/petroleum ether, yielding 52% (19.1
mg) as a light yellow solid: m.p. = 152 – 153 °C. 1H NMR (400 MHz, CDCl3) δ 7.92
(d, J = 8.3 Hz, 2H), 7.87 (d, J = 7.7 Hz, 1H), 7.75 (s, 1H), 7.46 (t, J = 7.7 Hz, 1H),
7.34 (t, J = 9.4 Hz, 3H), 5.70 (s, 1H), 4.32 (s, 2H), 3.74 (s, 2H), 2.60 (s, 3H), 2.43 (s,
3H); 13C NMR (101 MHz, CDCl3) δ 197.6, 168.1, 161.8, 145.1, 137.8, 136.2, 135.4,
133.4, 129.8, 129.4, 128.4, 128.0, 127.7, 122.6, 53.4, 36.4, 26.7, 21.7. HRMS
(ESIꢀTOF) m/z: [M + Na]+ Calcd for C20H19NO4SNa 392.0927; found 392.0928. IR
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(KBr): 2920, 1720, 1353, 1161, 662, 554 cm−1.
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4-(2-Methylbenzyl)-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (2n): Purified via flash
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column chromatography with 30% ethyl acetate/petroleum ether, yielding 79%
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(26.9mg) as a light yellow solid: m.p. = 91 – 92 °C. H NMR (400 MHz, CDCl3) δ
7.92 (d, J = 8.2 Hz, 2H), 7.32 (d, J = 8.2 Hz, 2H), 7.20 – 7.14 (m, 3H), 7.06 (d, J =
6.9 Hz, 1H), 5.59 (s, 1H), 4.32 (s, 2H), 3.66 (s, 2H), 2.42 (s, 3H), 2.22 (s, 3H); 13C
NMR (101 MHz, CDCl3) δ 168.4, 162.5, 145.0, 136.2, 135.5, 133.9, 130.8, 129.7,
129.6, 127.9, 127.8, 126.6, 122.1, 53.6, 34.4, 21.6, 19.3. HRMS (ESIꢀTOF) m/z: [M +
Na]+ Calcd for C19H19NO3SNa 364.0978; found, 364.0980. IR (KBr): 2927, 1725,
1358, 1027, 750, 661, 556 cm−1.
4-(2-Fluorobenzyl)-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (2o): Purified via flash
column chromatography with 30% ethyl acetate/petroleum ether, yielding 88% (30.3
mg) as a light yellow solid: m.p. = 142 – 143 °C. 1H NMR (400 MHz, CDCl3) δ 7.85
(d, J = 8.1 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 3.8 Hz, 1H), 7.02 (dd, J =
15.9, 8.5 Hz, 3H), 5.61 (s, 1H), 4.28 (s, 2H), 3.62 (s, 2H), 2.34 (s, 3H); 13C NMR (101
MHz, CDCl3) δ 168.3, 161.5, 160.7 (d, J = 45 Hz), 145.1, 135.4, 130.9 (d, J = 3.9 Hz),
129.7, 129.6 (d, J = 8.0 Hz), 127.9, 124.7 (d, J = 3.7 Hz), 122.8 (d, J = 15.9 Hz),
122.2, 115.8 (d, J = 21 Hz), 53.4, 29.8 (d, J = 3.3 Hz), 21.6. HRMSꢀESI (m/z): calcd
for C18H16FNO3SNa 368.0727; found, 368.0731. IR (KBr): 3637, 1725, 1356, 1164,
759, 662, 555 cm−1.
4-(2-Chlorobenzyl)-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (2p): Purified via flash
column chromatography with 30% ethyl acetate/petroleum ether, yielding 83% (29.9
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mg) as a light yellow solid: m.p. = 113 – 114 °C. 1H NMR (400 MHz, CDCl3) δ 7.93
(d, J = 8.3 Hz, 2H), 7.41 – 7.37 (m, 1H), 7.32 (d, J = 8.1 Hz, 2H), 7.27 – 7.23 (m, 2H),
7.19 (dd, J = 5.9, 3.5 Hz, 1H), 5.69 – 5.61 (m, 1H), 4.36 (s, 2H), 3.80 (s, 2H), 2.42 (s,
3H); 13C NMR (101 MHz, CDCl3) δ 168.3, 161.3, 145.0, 135.5, 134.1, 133.7, 130.9,
130.0, 129.7, 129.2, 127.9, 127.4, 122.5, 53.5, 34.3, 21.6. HRMS (ESIꢀTOF) m/z: [M
+ Na]+ Calcd for C18H16ClNO3SNa 384.0432; found 384.0433. IR (KBr): 2922, 1722,
1353, 1162, 752, 660, 553 cm−1.
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4-(2-Nitrobenzyl)-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (2q): Purified via flash
column chromatography with 45% ethyl acetate/petroleum ether, yielding 61% (22.6
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mg) as a brown solid: m.p. = 122 – 123 °C. H NMR (400 MHz, CDCl3) δ 8.16 (d, J
= 7.6 Hz, 1H), 8.04 (s, 1H), 7.92 (d, J = 8.2 Hz, 2H), 7.59 – 7.49 (m, 2H), 7.32 (d, J =
8.2 Hz, 2H), 5.69 (s, 1H), 4.37 (s, 2H), 3.81 (s, 2H), 2.42 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 167.8, 160.9, 148.6, 145.2, 137.6, 135.3, 135.0, 130.2, 129.8, 127.9, 123.8,
123.0, 122.7, 53.4, 36.0, 21.6. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C18H16N2O5SNa 395.0672; found 395.0678. IR (KBr): 2924, 1724, 1529, 1351, 1164,
663, 557 cm−1.
4-(3-Chloro-4-methylbenzyl)-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (2r): Purified
via flash column chromatography with 30% ethyl acetate/petroleum ether, yielding
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54% (20.2 mg) as a white solid: m.p. = 181 – 182 °C. H NMR (400 MHz, CDCl3) δ
7.92 (d, J = 8.2 Hz, 2H), 7.32 (d, J = 8.2 Hz, 2H), 7.19 (d, J = 7.7 Hz, 1H), 7.12 (s,
1H), 6.93 (d, J = 7.7 Hz, 1H), 5.72 (s, 1H), 4.31 (s, 2H), 3.61 (s, 2H), 2.43 (s, 3H),
2.36 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 168.2, 162.0, 145.0, 135.5, 135.3, 134.8,
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134.6, 131.5, 129.7, 129.3, 127.9, 127.0, 122.4, 53.3, 35.8, 21.6, 19.6. HRMS
(ESIꢀTOF) m/z: [M + Na]+ Calcd for C19H18ClNO3SNa 398.0588; found 398.0589. IR
(KBr): 2924, 1721, 1396, 1158, 756, 659, 558 cm−1.
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4-(3,4-Dimethylbenzyl)-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (2s): Purified via
flash column chromatography with 35% ethyl acetate/petroleum ether, yielding 59%
(20.9 mg) as a white solid: m.p. = 187 – 189 °C. 1H NMR (400 MHz, CDCl3) δ 7.94
(d, J = 8.0 Hz, 2H), 7.34 (d, J = 7.9 Hz, 2H), 7.10 (d, J = 7.5 Hz, 1H), 6.91 (s, 1H),
6.88 (d, J = 7.6 Hz, 1H), 5.75 (s, 1H), 4.32 (s, 2H), 3.63 (s, 2H), 2.45 (s, 3H), 2.26 (s,
6H). 13C NMR (101 MHz, CDCl3) δ 168.5, 163.2, 145.0, 137.4, 135.8, 135.5, 132.9,
130.2, 130.0, 129.7, 127.9, 126.1, 121.9, 53.4, 36.3, 21.7, 19.7, 19.4. HRMS
(ESIꢀTOF) m/z: [M + Na]+ Calcd for C20H21NO3SNa 378.1134; found 378.1132. IR
(KBr): 2925, 1743, 1548, 1369, 1230, 1053, 749, 697 cm−1.
4-(4-Methoxy-3-methylbenzyl)-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (2t): Purified
via flash column chromatography with 40% ethyl acetate/petroleum ether, yielding
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34% (12.6 mg) as a white solid: m.p. = 149 – 151 °C. H NMR (400 MHz, CDCl3) δ
7.95 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 7.9 Hz, 2H), 6.94 (d, J = 8.3 Hz, 1H), 6.90 (s,
1H), 6.78 (d, J = 8.2 Hz, 1H), 5.74 (s, 1H), 4.32 (s, 2H), 3.84 (s, 3H), 3.60 (s, 2H),
2.45 (s, 3H), 2.21 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 168.5, 163.5, 157.1, 145.0,
135.5, 131.0, 129.7, 127.9, 127.4, 127.1, 127.0, 121.7, 110.3, 55.4, 53.4, 35.9, 21.6,
16.2. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C20H21NO4SNa 394.1083; found
394.1085. IR (KBr): 2919, 2851, 1728, 1644, 1261, 1164, 753, 660 cm−1.
4-(5-Fluoro-2-methoxybenzyl)-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (2u): Purified
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via flash column chromatography with 45% ethyl acetate/petroleum ether, yielding
74% (27.7 mg) as a yellow solid: m.p. = 120 – 121 °C. 1H NMR (400 MHz, CDCl3) δ
7.93 (d, J = 8.2 Hz, 2H), 7.32 (d, J = 8.1 Hz, 2H), 6.95 (td, J = 8.5, 3.0 Hz, 1H), 6.84
– 6.78 (m, 2H), 5.66 (m, 1H), 4.33 (s, 2H), 3.78 (s, 3H), 3.64 (s, 2H), 2.42 (s, 3H); 13C
NMR (101 MHz, CDCl3) δ 168.6, 162.3, 157.9, 155.6, 153.3 (d, J = 2 Hz), 145.0,
135.5, 129.7, 127.9, 125.6 (d, J = 7.3 Hz), 121.8, 117.2 (d, J = 23 Hz), 114.7 (d, J =
23 Hz), 111.5 (d, J = 8.3 Hz), 55.9, 53.5, 31.0, 21.6. HRMS (ESIꢀTOF) m/z: [M +
Na]+ Calcd for C19H18FNO4SNa 398.0833; found 398.0837. IR (KBr): 2935, 1724,
1498, 1356, 1028, 662, 559 cm−1.
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4-(3,5-Dichlorobenzyl)-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (2v): Purified via
flash column chromatography with 30% ethyl acetate/petroleum ether, yielding 68%
(26.8 mg) as a white solid: m.p. = 134 – 135 °C. 1H NMR (400 MHz, CDCl3) δ 7.94
(d, J = 8.2 Hz, 2H), 7.37 – 7.30 (m, 3H), 7.04 (s, 2H), 5.74 (s, 1H), 4.32 (s, 2H), 3.63
(s, 2H), 2.43 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 167.9, 160.6, 145.2, 138.7, 135.6,
135.3, 129.8, 128.0, 127.9, 127.4, 123.0, 53.3, 35.8, 21.6. HRMS (ESIꢀTOF) m/z: [M
+ Na]+ Calcd for C18H15Cl2NO3SNa 418.0042; found 418.0042. IR (KBr): 2925, 1723,
1388, 1160, 755, 662, 561 cm−1.
4-Methyl-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (4a)18: Purified via flash column
chromatography with 25% ethyl acetate/petroleum ether, yielding 52% (13.0 mg) as a
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white solid: m.p. = 159 – 160 °C. H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 8.1 Hz,
2H), 7.34 (d, J = 8.0 Hz, 2H), 5.77 (s, 1H), 4.35 (s, 2H), 2.44 (s, 3H), 2.10 (s, 3H); 13C
NMR (101 MHz, CDCl3) δ 168.7, 159.7, 145.0, 135.6, 129.7, 127.9, 122.1, 54.8, 21.6,
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15.7. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C12H13NO3SNa 274.0508; found
274.0509. IR (KBr): 2923, 1714, 1351, 1163, 661, 556 cm−1.
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4-Methyl-1-tosyl-5,6-dihydropyridin-2(1H)-one (4b)19: Purified via flash column
chromatography with 25% ethyl acetate/petroleum ether, yielding 68% (18.0 mg) as a
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white solid: m.p. = 110 – 111 °C. H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 8.3 Hz,
2H), 7.30 (d, J = 8.1 Hz, 2H), 5.63 (d, J = 1.1 Hz, 1H), 4.03 (t, J = 6.5 Hz, 2H), 2.48 –
2.41 (m, 5H), 1.94 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 163.3, 156.9, 144.6, 136.0,
129.3, 128.4, 120.5, 43.8, 30.3, 22.9, 21.6. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd
for C13H15NO3SNa 288.0665; found 288.0666. IR (KBr): 2924, 1685, 1354, 1168,
952, 753, 661, 555 cm−1.
4-(Prop-1-en-1-yl)-1-tosylpyrrolidin-2-one (4c): Purified via flash column
chromatography with 30% ethyl acetate/petroleum ether, yielding 69% (19.2 mg) as a
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colorless liquid. H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 8.3 Hz, 2H), 7.35 (d, J =
8.1 Hz, 2H), 5.67 – 5.48 (m, 1H), 5.39 – 5.20 (m, 1H), 4.17 – 3.98 (m, 1H), 3.59 –
3.44 (m, 1H), 3.41 – 3.26 (m, 0.2 H), 3.05 – 2.90 (m, 0.8 H), 2.65 – 2.50 (m, 1H),
2.45 (s, 3H), 2.30 – 2.18 (m, 1H), 1.66 (d, J = 7.1 Hz, 3H); 13C NMR (101 MHz,
CDCl3) δ 172.5, 145.1, 135.2, 129.7, 129.2, 128.9, 128.2, 128.1, 128.0, 128.0, 127.9,
52.3, 39.1, 38.7, 35.1, 30.0, 21.6, 17.7, 13.1. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd
for C14H17NO3SNa 302.0821; found 302.0828. IR (KBr): 2923, 1740, 1357, 1171,
956, 662, 553 cm−1.
4-(Prop-1-en-2-yl)-1-tosylpyrrolidin-2-one (4d): Purified via flash column
chromatography with 30% ethyl acetate/petroleum ether, yielding 53% (14.7 mg) as a
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