Visible-Light Photoredox-Catalyzed Sulfonyl Lactonization of Alkenoic Acids with Sulfonyl Chlorides for Sulfonyl Lactone Synthesis

Article abstract of DOI:10.1021/acs.joc.1c01378

A visible-light photoredox-catalyzed sulfonyl lactonization of unsaturated carboxylic acids with sulfonyl chlorides is described. This reaction features good functional group tolerance and a broad substrate scope, providing a simple and efficient protocol to access a wide range of sulfonyl lactones in high to excellent yields. Preliminary mechanistic investigations suggested that a free-radical pathway should be involved in the process.

Full text of DOI:10.1021/acs.joc.1c01378

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Article
Visible-Light Photoredox-Catalyzed Sulfonyl Lactonization of
Alkenoic Acids with Sulfonyl Chlorides for Sulfonyl Lactone
Synthesis
Wei-Hao Rao,* Qi Li, Fang-Yuan Chen, Li-Li Jiang, Pan Xu, Xue-Wan Deng, Ming Li, Guo-Dong Zou,
and Xinhua Cao
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ABSTRACT: A visible-light photoredox-catalyzed sulfonyl lactonization
of unsaturated carboxylic acids with sulfonyl chlorides is described. This
reaction features good functional group tolerance and a broad substrate
scope, providing a simple and efficient protocol to access a wide range of
sulfonyl lactones in high to excellent yields. Preliminary mechanistic
investigations suggested that a free-radical pathway should be involved in
the process.
interest in the catalytic synthesis of sulfone,4d we herein report
the first photoredox-catalyzed sulfonyl lactonization of alkenoic
acids with sulfonyl chlorides (Scheme 1d).
INTRODUCTION
■
Sulfone constitutes an important class of structural motifs that
are ubiquitous in biologically active molecules1 and play a key
role in forging the carbon−carbon double bond via Julia
olefination in organic synthesis.2 Among the considerable
efforts toward the efficient synthesis of sulfones, direct
sulfonylation of C−H bonds emerges as an attractive tool for
efficient incorporation of a sulfonyl group in molecules from
the viewpoint of step-economy and rapid diverse synthesis.3 As
an alternative approach, vicinal sulfonyl functionalization of
alkenes exhibits excellent performance in assembling molecule
complexity, which enables the simultaneous introduction of a
sulfonyl group and other useful groups.4
γ-Lactones are valuable structural motifs widely found in a
large number of biologically active molecules and are versatile
synthetic intermediates en route to many related architec-
tures.5 Recently, catalytic sulfonyl lactonization of unsaturated
acids boosted the synthesis of sulfonyl γ-lactones in virtue of
the significance of sulfones and γ-lactones. In this area, Wu6
and Han7 independently reported a photoredox- or copper-
catalyzed three-component sulfonyl lactonization of 2-vinyl-
benzoic acids with the combination of aryl diazonium
tetrafluoroborates and DABSO as arylsulfonyl donors (Scheme
1a). However, these reactions suffer from explosive diazonium
salts and fail in the introduction of alkylsulfonyl groups.
Although Lu and co-workers later developed a copper-
catalyzed sulfonyl lactonization of 2-vinylbenzoic acids with
sodium sulfinates,8 additional one-step reduction of sulfonyl
chlorides into sodium sulfinates is required (Scheme 1b). Early
in 2015, the Buchwald group reported an elegant copper-
catalyzed sulfonyl lactonization of 4-phenylpent-4-enoic acid
with TsCl (Scheme 1c).9 However, expensive silver carbonate
is essential for good catalytic efficiency. With our continuous
RESULTS AND DISCUSSION
■
Recently, advances in visible-light photoredox activation of
sulfonyl chlorides have been gained.10 Inspired by these
seminal works, we hypothesized that visible-light photo-
catalysis11 could be used to form sulfur-centered radical
intermediates under mild conditions from readily available
sulfonyl chlorides. We anticipated that sulfur-centered radical
intermediates could be further captured by alkenes via radical
addition across the double bond. With these considerations, we
commenced our study by the reaction of 2-vinylbenzoic acid 1
with 1.5 equiv of tosyl chloride at room temperature as the
model reaction (Table 1). After an extensive screening of
solvents (entries 1−5), the reaction with MeCN as the solvent
afforded the desired product 1a in 45% yield by nuclear
magnetic resonance (NMR) analysis (entry 4). To our delight,
1a could be obtained in 78% isolated yield using Ir(ppy)3 (1
mol %) as the catalyst and Na2CO3 (2 equiv) as the base in
dichloromethane (DCM) (entry 5). Further evaluation of
bases (entries 6−13) showed that 1a could be produced in the
presence of the tested bases, including inorganic bases and
organic bases, revealing that Na2CO3 was superior to the tested
Received: June 10, 2021
https://doi.org/10.1021/acs.joc.1c01378
J. Org. Chem. XXXX, XXX, XXX−XXX
© XXXX American Chemical Society
A

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Scheme 1. Construction of Sulfonyl Lactones via Sulfonyl Lactonization of Alkenoic Acids with Different Sulfonyl Donors
a
ppy)2(dtbbpy)]PF6 did not give a higher yield of 1a (entries
14−16). Control experiment shows that Ir(ppy)3 and visible
light were essential to the reaction since 1a was not detected
under the same conditions in the absence of Ir(ppy)3 or light
(entry 17 and 18). Finally, the reaction of 1, tosyl chloride, and
Na2CO3 under Ir(ppy)3 catalysis in DCM irradiated with blue
light-emitting diodes (LEDs) (20 W, λmax = 455 nm) at room
temperature was identified as the optimized conditions (entry
5).
Table 1. Screening of Reaction Conditions
b
entry
base
solvent
yield (%)
1
2
3
4
5
6
7
8
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Li2CO3
DMAc
DMF
DMSO
MeCN
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
0
0
0
With the optimized conditions in hand, we next explored the
scope of unsaturated carboxylic acids (Scheme 2). A wide
variety of 2-vinylbenzoic acids were compatible with the
protocol, and the corresponding products (1a−12a) were
obtained in high to excellent yields. Methoxyl (2a), fluoro
(3a), and methyl (4a) groups on the aryl ring were well
tolerated. Substrates with alkyl-substituted 2-vinyl groups also
worked well to afford the corresponding lactones (5a−7a) in
85−88% yields. Moreover, reactions of substrates with aryl-
substituted 2-vinyl groups proceeded well to afford the desired
lactones (8a−12a) in excellent yields. Notably, both electron-
donating methyl (8a), methoxyl (9a), and chloro (11a) groups
and the electron-withdrawing fluoro (10a) group were well
tolerated. 4-Aryl pent-4-enoic acids, including primary,
secondary, and tertiary types, were decent substrates, which
underwent the transformation smoothly to generate the
corresponding products (13a−20a and 22a−24a) in 85−
92% yields, though poor dr selectivity was obtained for 20a
and 22a. As expected, 21a was obtained in poor yield, which
was likely caused by the poor stability of the alkyl radical
generated by the addition of tosyl radical across the C−C
double bond. Interestingly, with the protocol, α-spirocyclic
lactones (23a−24a) could be obtained in high yields.
45
c
82(78)
10
58
15
60
28
15
78
36
68
56
0
K2CO3
Cs2CO3
NaHCO3
Et3N
9
10
11
12
13
14
15
16
17
18
DIPEA
2,6-lutidine
DABCO
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
d
e
f
g
0
0
h
a
Reaction conditions: 1 (0.2 mmol), Ir(ppy)3 (1 mol %) and TsCl
(0.3 mmol, 1.5 equiv) in solvent (2 mL) irradiated by blue LEDs (20
b
W, λmax = 455 nm) at rt for 24 h under N2. 1H NMR yields using
c
CH2Br2 as the internal standard. Isolated yields in the parentheses.
Ru(bpy)3Cl2 (1 mol %) instead of Ir(ppy)3 was used. Ru-
(bpy)3(PF6)2 (1 mol %) instead of Ir(ppy)3 was used. [Ir(dF(CF3)-
ppy)2(dtbbpy)]PF6 (1 mol %) instead of Ir(ppy)3 was used. Without
d
e
f
g
h
Subsequently, we focused on the study of the sulfonyl
chloride scope. As shown in Scheme 3, a range of arylsulfonyl
chlorides bearing substituents on the aryl ring reacted well and
gave the desired lactones 8b−8p in high to excellent yields,
regardless of their electronic properties. Notably, strong
Ir(ppy)3. Performed in the dark.
bases. Replacement of Ir(ppy)3 with other photocatalysts,
including Ru(bpy)3Cl2, Ru(bpy)3(PF6)2, or [Ir(dF(CF3)-
B
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a
Scheme 2. Scope of Unsaturated Carboxylic Acids
a
Reaction conditions: 1−24 (0.3 mmol), Ir(ppy)3 (1 mol %), TsCl (0.45 mmol, 1.5 equiv), and Na2CO3 (0.6 mmol, 2 equiv) in DCM (3 mL) at rt
for 24 h under N2. Isolated yields.
electron-withdrawing cyano (8f) and trifluoromethyl (8h)
groups were compatible with this protocol. Fluoro (8g, 8j, 8n),
chloro (8k), and bromo (8l, 8m) groups could survive,
providing the opportunity for further elaboration. Both 1-
naphthyl and 2-naphthyl sulfonyl chlorides were suitable
substrates and gave the corresponding lactones (8o−8p) in
high yields. Furthermore, the incorporation of alkylsulfonyl
groups into lactones could also be realized with the protocol, as
evidenced by the formation of 8q and 8r in high yields.
To demonstrate the potential application of the protocol in
large-scale synthesis, a gram-scale synthesis was performed. As
shown in Scheme 4, 8a was obtained in a 92% yield under the
standard reaction conditions.
TsCl with Ir(III)* released a tosyl radical, which was then
attacked by the double bond of 1 to form benzyl radical
intermediate A. A would undergo a single electron transfer
facilitated by Ir(IV) to give cation intermediate B, accom-
panied by the regeneration of the Ir(III) catalyst. Subsequent
intermolecular nucleophilic substitution of B in the presence of
Na2CO3 as a base would furnish the desired lactone 1a.
In conclusion, we have developed a visible-light photoredox-
catalyzed sulfonyl lactonization of unsaturated carboxylic acids
with sulfonyl chlorides. With this simple and mild protocol, a
wide range of sulfonyl lactones were synthesized in high to
excellent yields with good functional group tolerance.
Preliminary mechanistic investigations suggested that a free-
radical pathway would be involved in the process.
To gain mechanistic insights into the sulfonyl lactonization
of alkenes, a preliminary mechanistic investigation was
conducted (Scheme 5). With the addition of TEMPO as a
radical scavenger, the transformation was completely sup-
pressed since 8a was not detected. Moreover, 1,1-dipheny-
ethylene as a radical scavenger also suppressed the reaction, in
which only a trace of 8a was detected and the radical trapping
product 8aa was isolated in 28% yield based on the amount of
TsCl. Based on these results, we supposed that a radical
pathway with sulfonyl radical species would be involved in the
transformation.
EXPERIMENTAL SECTION
■
General Information. NMR spectra were recorded on JNM-
ECZ600R/S3 600 MHz (for 1H NMR) and 150 MHz (for 13C
NMR) using TMS as an internal standard. Chemical shifts are given
1
relative to the residual solvents of CDCl3 (7.26 ppm for H NMR,
77.16 ppm for 13C{1H} NMR) unless otherwise noted. HRMS for
new compounds were recorded on a MicroMass Waters Xevo G2-XS
QTof, Xinyang Normal University. Melting points were measured on
an SGW X-4A melting point apparatus and are uncorrected. Blue
LED columnar tubes (450−455 nm, 20 W, 132 lamp beads, size of 11
cm diameter × 10 cm height, materials of aluminum and PC) were
purchased from Huacai LED Lighting Manufacturer Co., Ltd. on the
Taobao shopping platform. The irradiation container is a Schlenk
tube made of borosilicate glass, and the distance from the light source
Based on our observations above and related precedents,6,10
a plausible mechanism was proposed to elucidate the process
(Scheme 6). It was well documented that the Ir(III) catalyst
was excited with visible light into Ir(III)*. The reaction of
C
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a
Scheme 3. Scope of Sulfonyl Chlorides
a
Reaction conditions: 8 (0.3 mmol), Ir(ppy)3 (1 mol %), RSO2Cl (0.45 mmol, 1.5 equiv), and Na2CO3 (0.6 mmol, 2 equiv) in DCM (3 mL) at rt
for 24 h under N2. Isolated yields.
Scheme 4. Scalable Synthesis of 8a
Scheme 5. Mechanistic Investigation
to the Schlenk tube is about 5 mm. For column chromatography,
silica gel (300−400 mesh) was used as the stationary phase. Unless
otherwise noted, all commercial materials were used without further
purification. Solvents were used after purification directed by
Purification of Laboratory Chemicals, 6th Ed.
cap were added alkenoic acids (0.3 mmol, 1 equiv), Ir(ppy)3 (0.003
mmol, 1 mol %), sulfonyl chlorides (0.45 mmol, 1.5 equiv), Na2CO3
(64 mg, 0.6 mmol, 2 equiv), and dry DCM (3.0 mL). The flask was
then charged with N2 via twice N2-vacuum exchanges, and the mixture
was irradiated under stirring with a blue LED ribbon (20 W) at rt
(cooling with two mini-fans) for 24 h. The reaction mixture was then
diluted with DCM (20 mL) and transferred into a separatory funnel.
The organic phase was sequentially washed with water (2 mL × 20
mL) and brine (20 mL) and dried over anhydrous Na2SO4, then
concentrated under reduced pressure on a rotary evaporator. The
Preparation of Starting Materials. Substrates 1−24 are prepared
according to the reported literature studies.4d,12
General procedure for the Sulfonyl Lactonization of
Alkenoic Acids with Sulfonyl Chlorides. To a 30 mL Schlenk
flask equipped with a magnetic stirring bar and a Teflon-lined screw
D
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Scheme 6. Proposed Mechanism
residue was further purified by silica gel column chromatography
(eluent: petroleum ether/EtOAc) to afford the desired product.
Structural Characterization of Compounds. 3-(Tosylmethyl)-
isobenzofuran-1(3H)-one (1a). The titled compound 1a was
prepared according to the GP and purified by silica column
chromatography in petroleum ether/ethyl acetate = 3:1. 1a was
obtained as a white solid (70 mg, 78%). Melting point: 138−140 °C.
1H NMR (600 MHz, chloroform-d) δ 7.86 (d, J = 8.4 Hz, 2H), 7.72
(d, J = 7.8 Hz, 1H), 7.67−7.64 (m, 1H), 7.57 (t, J = 7.8 Hz, 1H), 7.39
(d, J = 8.0 Hz, 2H), 5.94 (dd, J = 7.8, 4.2 Hz, 1H), 3.67 (dd, J = 15.0,
4.2 Hz, 1H), 3.58 (dd, J = 15.0, 7.8 Hz, 1H), 2.47 (s, 3H). 13C{1H}
NMR (150 MHz, chloroform-d) δ 169.2, 147.2, 145.7, 136.1, 134.8,
130.2, 130.2, 128.5, 126.1, 125.6, 122.7, 75.0, 60.6, 21.9. HRMS (ESI/
QTOF) m/z: [M + Na]+ calcd for C16H14NaO4S 325.0505; found
325.0503.
128.2, 123.1, 119.5, 81.9, 63.4, 27.2, 21.8, 17.5. HRMS (ESI/QTOF)
m/z: calcd for [M + Na]+ C18H18NaO4S 353.0818; found 353.0823.
3-Methyl-3-(tosylmethyl)isobenzofuran-1(3H)-one (5a). The ti-
tled compound 5a was prepared according to the GP and purified by
silica column chromatography in petroleum ether/ethyl acetate = 3:1.
5a was obtained as a white solid (80 mg, 85%). Melting point: 156−
1
158 °C. H NMR (600 MHz, chloroform-d) δ 7.84 (d, J = 7.8 Hz,
1H), 7.62 (d, J = 7.8 Hz, 1H), 7.58 (d, J = 8.4 Hz, 2H), 7.53 (t, J = 7.8
Hz, 1H), 7.48 (d, J = 7.8 Hz, 1H), 7.27 (d, J = 8.4 Hz, 2H), 3.83 (d, J
= 15.0 Hz, 1H), 3.74 (d, J = 15.0 Hz, 1H), 2.41 (s, 3H), 1.78 (s, 3H).
13C{1H} NMR (150 MHz, chloroform-d) δ 168.6, 150.8, 145.1,
137.1, 134.4, 123.0, 129.8, 128.0, 125.8, 125.6, 122.2, 83.1, 62.9, 27.0,
21.8. HRMS (ESI/QTOF) m/z: calcd for [M + H]+ C17H17O4S
317.0842; found 317.0838.
3-Ethyl-3-(tosylmethyl)isobenzofuran-1(3H)-one (6a). The titled
compound 6a was prepared according to the GP and purified by silica
column chromatography in petroleum ether/ethyl acetate = 3:1. 6a
was obtained as a white solid (85 mg, 86%). The titled compound is
known.6 Melting point: 122−124 °C. 1H NMR (600 MHz,
chloroform-d) δ 7.85 (d, J = 7.8 Hz, 1H), 7.63 (t, J = 7.8 Hz, 1H),
7.55 (d, J = 8.4 Hz, 2H), 7.54 (t, J = 7.8 Hz, 1H), 7.43 (d, J = 7.8 Hz,
1H), 7.27 (d, J = 7.8 Hz, 2H), 3.87 (d, J = 13.8 Hz, 1H), 3.76 (d, J =
13.8 Hz, 1H), 2.42 (s, 3H), 2.23 (dd, J = 14.4, 7.2 Hz, 1H), 2.02 (dd,
J = 13.8, 6.6 Hz, 1H), 0.66 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (150
MHz, chloroform-d) δ 168.9, 148.8, 145.1, 137.2, 134.3, 130.0, 129.8,
128.0, 126.9, 125.7, 122.4, 85.7, 62.1, 32.7, 21.8, 7.1. HRMS (ESI/
QTOF) m/z: calcd for [M + H]+ C18H19O4S 331.0999; found
331.0996.
6-Methoxy-3-(tosylmethyl)isobenzofuran-1(3H)-one (2a). The
titled compound 2a was prepared according to the GP and purified
by silica column chromatography in petroleum ether/ethyl acetate =
3:1. 2a was obtained as a white solid (85 mg, 85%). Melting point:
1
136−138 °C. H NMR (600 MHz, chloroform-d) δ 7.92−7.72 (m,
2H), 7.53 (d, J = 8.4 Hz, 1H), 7.38 (d, J = 8.4 Hz, 2H), 7.30−7.11
(m, 2H), 5.87 (dd, J = 7.2, 4.8 Hz, 1H), 3.85 (s, 3H), 3.63 (dd, J =
15.0, 4.8 Hz, 1H), 3.55 (dd, J = 15.0, 7.2 Hz, 1H), 2.46 (s, 3H).
13C{1H} NMR (150 MHz, chloroform-d) δ 169.2, 161.4, 145.6,
139.4, 136.2, 130.2, 128.4, 127.1, 123.6, 123.5, 107.9, 74.8, 60.7, 56.0,
21.8. HRMS (ESI/QTOF) m/z: calcd for [M + Na]+ C17H16NaO5S
355.0611; found 355.0612.
6-Fluoro-3-(tosylmethyl)isobenzofuran-1(3H)-one (3a). The ti-
tled compound 3a was prepared according to the GP and purified by
silica column chromatography in petroleum ether/ethyl acetate = 3:1.
3a was obtained as a white solid (79 mg, 82%). Melting point: 170−
3-Butyl-3-(tosylmethyl)isobenzofuran-1(3H)-one (7a). The titled
compound 7a was prepared according to the GP and purified by silica
column chromatography in petroleum ether/ethyl acetate = 3:1. 7a
was obtained as a white solid (95 mg, 88%). Melting point: 159−160
1
172 °C. H NMR (600 MHz, chloroform-d) δ 7.85 (d, J = 8.4 Hz,
1
2H), 7.70 (dd, J = 8.4, 4.2 Hz, 1H), 7.52 (dd, J = 7.2, 2.4 Hz, 1H),
7.43 (td, J = 8.4, 2.4 Hz, 1H), 7.40 (d, J = 8.4 Hz, 2H), 5.93 (t, J = 6.6
Hz, 1H), 3.64 (dd, J = 14.4, 4.8 Hz, 1H), 3.64 (dd, J = 14.4, 6.6 Hz,
1H), 2.47 (s, 3H). 13C{1H} NMR (150 MHz, chloroform-d) δ 167.9,
164.5, 162.9, 145.8, 142.7, 136.9, 130.3, 128.4, 127.9, 127.8, 124.9,
124.8, 122.9, 122.7, 112.5, 112.4, 74.9, 60.4, 21.9. 19F NMR (565
MHz, chloroform-d) δ -109.6 (d, J = 2.3 Hz, 1F). HRMS (ESI/
QTOF) m/z: calcd for [M + H]+ C16H14FO4S 321.0591; found
321.0602.
°C. H NMR (600 MHz, chloroform-d) δ 7.86 (dt, J = 7.8, 1.2 Hz,
1H), 7.65 (td, J = 7.8, 1.2 Hz, 1H), 7.59−7.53 (m, 3H), 7.49−7.44
(m, 1H), 7.33−7.27 (m, 2H), 3.85 (d, J = 15.0 Hz, 1H), 3.75 (d, J =
15.0 Hz, 1H), 2.43 (s, 3H), 2.18 (ddd, J = 14.4, 12.0, 4.2 Hz, 1H),
1.96 (ddd, J = 14.4, 12.0, 4.2 Hz, 1H), 1.31−1.05 (m, 3H), 0.82−0.77
(m, 4H). 13C{1H} NMR (150 MHz, chloroform-d) δ 169.0, 149.2,
145.2, 137.2, 134.3, 130.0, 129.8, 128.0, 126.7, 125.8, 122.5, 85.4,
62.4, 39.3, 24.7, 22.5, 21.8, 13.9. HRMS (ESI/QTOF) m/z: calcd for
[M + Na]+ C20H22NaO4S 381.1131; found 381.1144.
3,7-Dimethyl-3-(tosylmethyl)isobenzofuran-1(3H)-one (4a). The
titled compound 4a was prepared according to the GP and purified by
silica column chromatography in petroleum ether/ethyl acetate = 3:1.
4a was obtained as a white solid (87 mg, 88%). The titled compound
is known.6 Melting point: 115−117 °C. 1H NMR (600 MHz,
chloroform-d) δ 7.64−7.56 (m, 2H), 7.50 (t, J = 7.8 Hz, 1H), 7.33−
7.24 (m, 4H), 3.80 (d, J = 15.0 Hz, 1H), 3.68 (d, J = 15.0 Hz, 1H),
2.65 (s, 3H), 2.43 (s, 3H), 1.77 (s, 3H). 13C{1H} NMR (150 MHz,
chloroform-d) δ 168.7, 151.4, 145.1, 140.0, 137.1, 134.1, 131.4, 130.0,
3-Phenyl-3-(tosylmethyl)isobenzofuran-1(3H)-one (8a). The ti-
tled compound 8a was prepared according to the GP and purified by
silica column chromatography in petroleum ether/ethyl acetate = 3:1.
8a was obtained as a white solid (102 mg, 90%). The titled compound
is known.8 Melting point: 159−161 °C. 1H NMR (600 MHz,
chloroform-d) δ 7.89 (dd, J = 7.8, 1.2 Hz, 1H), 7.68−7.63 (m, 1H),
7.61 (d, J = 7.8 Hz, 1H), 7.58−7.54 (m, 1H), 7.54−7.50 (m, 2H),
7.45−7.41 (m, 2H), 7.35−7.31 (m, 2H), 7.31−7.28 (m, 1H), 7.28−
7.23 (m, 2H), 4.28 (d, J = 15.0 Hz, 1H), 4.19 (d, J = 15.0 Hz, 1H),
E
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2.43 (s, 3H). 13C{1H} NMR (150 MHz, chloroform-d) δ 168.7,
149.2, 145.1, 139.1, 137.2, 134.4, 123.0, 129.2, 129.0, 128.1, 126.1,
125.8, 124.7, 123.4, 85.1, 63.3, 21.8. HRMS (ESI/QTOF) m/z: calcd
for [M + H]+ C22H19O4S 379.0999; found 379.0995.
21.8. HRMS (ESI/QTOF) m/z: [M + H]+ calcd for C18H19O4S
331.0999; found 331.0996.
5-(p-Tolyl)-5-(tosylmethyl)dihydrofuran-2(3H)-one (14a). The
titled compound 14a was prepared according to the GP and purified
by silica column chromatography in petroleum ether/ethyl acetate =
3:1. 14a was obtained as a white solid (90 mg, 87%). The titled
3-Phenyl-3-(tosylmethyl)isobenzofuran-1(3H)-one (9a). The ti-
tled compound 9a was prepared according to the GP and purified by
silica column chromatography in petroleum ether/ethyl acetate = 3:1.
9a was obtained as a white solid (108 mg, 92%). The titled compound
is known.7 Melting point: 152−154 °C. 13C{1H} NMR (600 MHz,
chloroform-d) δ 7.87 (d, J = 7.8 Hz, 1H), 7.61 (t, J = 7.8 Hz, 1H),
7.57 (t, J = 7.2 Hz, 1H), 7.53 (t, J = 7.2 Hz, 1H), 7.52 (d, J = 7.8 Hz,
1H), 7.30 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 8.4 Hz, 2H), 7.11 (d, J =
8.4 Hz, 2H), 4.27 (d, J = 15.6 Hz, 1H), 4.19 (d, J = 15.6 Hz, 1H),
2.41 (s, 3H), 2.28 (s, 3H). 13C NMR (150 MHz, chloroform-d) δ
168.7, 149.3, 144.9, 138.9, 137.2, 136.1, 134.3, 129.8, 129.8, 129.7,
128.0, 125.9, 125.7, 124.6, 123.4, 85.1, 63.1, 21.7, 21.0. HRMS (ESI/
QTOF) m/z: [M + H]+ calcd for C23H21O4S 393.1155; found
393.1152.
7
1
compound is known. Melting point: 153−154 °C. H NMR (600
MHz, chloroform-d) δ 7.68 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz,
2H), 7.21−7.15 (m, 2H), 7.12 (d, J = 8.4 Hz, 2H), 3.73 (d, J = 15.0
Hz, 1H), 3.70 (d, J = 15.0 Hz, 1H), 3.32 (ddd, J = 13.2, 9.6, 8.4 Hz,
1H), 2.81 (ddd, J = 18.0, 9.6, 4.8 Hz, 1H), 2.62 (ddd, J = 13.2, 9.6, 4.8
Hz, 1H), 2.48 (ddd, J = 18.0, 9.6, 8.4 Hz, 1H), 2.42 (s, 3H), 2.31 (s,
3H). 13C{1H} NMR (150 MHz, chloroform-d) δ 175.5, 145.0, 138.9,
138.6, 137.6, 129.9, 129.6, 128.0, 124.6, 84.9, 65.2, 32.5, 28.4, 21.8,
21.1. HRMS (ESI/QTOF) m/z: [M + H]+ calcd for C19H21O4S
345.1155; found 345.1152.
5-(4-Methoxyphenyl)-5-(tosylmethyl)dihydrofuran-2(3H)-one
(15a). The titled compound 15a was prepared according to the GP
and purified by silica column chromatography in petroleum ether/
ethyl acetate = 3:1. 15a was obtained as a white solid (92 mg, 85%).
3-(4-Methoxyphenyl)-3-(tosylmethyl)isobenzofuran-1(3H)-one
(10a). The titled compound 10a was prepared according to the GP
and purified by silica column chromatography in petroleum ether/
ethyl acetate = 3:1. 10a was obtained as a white solid (116 mg, 95%).
The titled compound is known.7 Melting point: 143−145 °C. H
1
NMR (600 MHz, chloroform-d) δ 7.65 (d, J = 8.4 Hz, 2H), 7.27 (d, J
= 8.4 Hz, 2H), 7.23−7.15 (d, J = 9.0 Hz, 2H), 6.81 (d, J = 9.0 Hz,
2H), 3.77 (s, 3H), 3.73 (d, J = 15 Hz, 1H), 3.70 (d, J = 15 Hz, 1H),
3.38−3.19 (m, 1H), 2.80 (ddd, J = 18.0, 9.6, 4.8 Hz, 1H), 2.63 (ddd, J
= 13.2, 9.6, 4.8 Hz, 1H), 2.48 (ddd, J = 18.0, 9.6, 9.0 Hz, 1H), 2.41 (s,
3H). 13C{1H} NMR (150 MHz, chloroform-d) δ 175.5, 159.7, 144.9,
137.5, 133.5, 129.9, 128.0, 126.1, 114.2, 84.8, 65.3, 55.4, 32.5, 28.4,
21.7. HRMS (ESI/QTOF) m/z: calcd for [M + H]+ C19H21O5S
361.1104; found 361.1088.
1
Melting point: 169−170 °C. H NMR (600 MHz, chloroform-d) δ
7.92−7.80 (m, 1H), 7.68−7.62 (m, 1H), 7.59 (d, J = 7.8 Hz, 1H),
7.57−7.53 (m, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 9.0 Hz,
2H), 7.28−7.21 (m, 2H), 6.82 (d, J = 9.0 Hz, 2H), 4.26 (d, J = 15.6
Hz, 1H), 4.14 (d, J = 15.6 Hz, 1H), 3.76 (s, 3H), 2.43 (s, 3H).
13C{1H} NMR (150 MHz, chloroform-d) δ 168.7, 160.0, 149.3,
145.0, 137.2, 134.3, 131.0, 129.9, 129.9, 128.1, 126.4, 126.0, 126.0,
123.5, 114.4, 85.2, 63.4, 55.5, 21.8. HRMS: calcd for C23H21O5S [M +
H]+ 409.1104, found 409.1100.
5-(4-Fluorophenyl)-5-(tosylmethyl)dihydrofuran-2(3H)-one
(16a). The titled compound 16a was prepared according to the GP
and purified by silica column chromatography in petroleum ether/
ethyl acetate = 3:1. 16a was obtained as a white solid (93 mg, 89%).
3-(4-Fluorophenyl)-3-(tosylmethyl)isobenzofuran-1(3H)-one
(11a). The titled compound 11a was prepared according to the GP
and purified by silica column chromatography in petroleum ether/
ethyl acetate = 3:1. 11a was obtained as a white solid (109 mg, 92%).
The titled compound is known.7 Melting point: 144−145 °C. H
1
1
NMR (600 MHz, chloroform-d) δ 7.64 (d, J = 8.4 Hz, 2H), 7.31−
7.26 (m, 4H), 7.00−6.97 (m, 2H), 3.72 (s, 2H), 3.36−3.15 (m, 1H),
2.82 (ddd, J = 18.0, 10.2, 5.4 Hz, 1H), 2.61 (ddd, J = 13.2, 10.2, 5.4
Hz, 1H), 2.48 (ddd, J = 18.0, 10.2, 8.4 Hz, 1H), 2.41 (s, 3H).
13C{1H} NMR (150 MHz, chloroform-d) δ 175.2, 163.4, 161.7,
Melting point: 176−177 °C. H NMR (600 MHz, chloroform-d) δ
7.89 (dd, J = 7.8, 1.2 Hz, 1H), 7.71−7.64 (m, 1H), 7.64−7.60 (m,
1H), 7.57 (td, J = 7.8, 1.2 Hz, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.45−
7.38 (m, 2H), 7.31−7.24 (m, 2H), 7.01 (dd, J = 9.6, 7.2 Hz, 2H), 4.24
(d, J = 15.6 Hz, 1H), 4.14 (d, J = 15.6 Hz, 1H), 2.43 (s, 3H). 13C{1H}
NMR (150 MHz, chloroform-d) δ 168.4, 162.8 (d, J = 247.8 Hz, 1C),
149.1, 145.2, 137.1, 134.9, 134.5, 130.1, 130.0, 128.1, 127.0 (d, J = 8.4
Hz, 2C), 126.2, 125.7, 123.5, 116.1 (d, J = 21.8 Hz, 2C), 84.8, 63.4,
21.8. 19F NMR (565 MHz, chloroform-d) δ -112.1. HRMS (ESI/
QTOF) m/z: calcd for [M + H]+ C22H18FO4S 397.0904; found
397.0919.
145.1, 137.4, 130.0, 127.9, 126.8, 126.8, 115.9, 115.7, 84.5, 65.2, 32.8,
28.2, 21.7. 19F NMR (565 MHz, chloroform-d) δ −112.9 (ddt, J =
12.7, 7.5, 4.7 Hz, 1F). HRMS (ESI/QTOF) m/z: calcd for [M + H]+
C18H18FO4S 349.0904; found 349.0900.
5-(4-Chlorophenyl)-5-(tosylmethyl)dihydrofuran-2(3H)-one
(17a). The titled compound 17a was prepared according to the GP
and purified by silica column chromatography in petroleum ether/
ethyl acetate = 3:1. 17a was obtained as a white solid (98 mg, 90%).
3-(4-Chlorophenyl)-3-(tosylmethyl)isobenzofuran-1(3H)-one
(12a). The titled compound 12a was prepared according to the GP
and purified by silica column chromatography in petroleum ether/
ethyl acetate = 3:1. 12a was obtained as a white solid (106 mg, 86%).
The titled compound is known.7 Melting point: 150−152 °C. H
1
NMR (600 MHz, chloroform-d) δ 7.64 (d, J = 8.4 Hz, 1H), 7.35−
7.17 (m, 6H), 3.71 (s, 2H), 3.28 (ddd, J = 13.2, 9.6, 8.4 Hz, 1H), 2.83
(ddd, J = 18.0, 9.6, 5.4 Hz, 1H), 2.60 (ddd, J = 13.2, 9.6, 5.4 Hz, 1H),
2.48 (ddd, J = 18.0, 9.6, 8.4 Hz, 1H), 2.42 (s, 3H). 13C{1H} NMR
(150 MHz, chloroform-d) δ 175.1, 145.2, 140.0, 137.3, 134.7, 130.0,
129.1, 128.0, 126.4, 84.4, 65.0, 32.7, 28.2, 21.8. HRMS (ESI/QTOF)
m/z: [M + H]+ calcd for C18H18ClO4S 365.0609; found 365.0621.
3,3,5-Triphenyl-5-(tosylmethyl)dihydrofuran-2(3H)-one (18a).
The titled compound 18a was prepared according to the GP and
purified by silica column chromatography in petroleum ether/ethyl
acetate = 3:1. 18a was obtained as a white solid (130 mg, 90%).
The titled compound is known.7 Melting point: 214−215 °C. H
1
NMR (600 MHz, chloroform-d) δ 7.90 (dd, J = 7.8, 0.6 Hz, 1H),
7.70−7.65 (m, 1H), 7.64−7.60 (m, 1H), 7.60−7.56 (m, 1H), 7.54−
7.50 (m, 2H), 7.37 (d, J = 8.8 Hz, 2H), 7.31−7.25 (m, 4H), 4.23 (d, J
= 15.6 Hz, 1H), 4.12 (d, J = 15.6 Hz, 1H), 2.44 (s, 3H). 13C{1H}
NMR (150 MHz, chloroform-d) δ 168.3, 148.9, 145.3, 137.4, 137.0,
135.2, 134.6, 130.2, 123.0, 129.3, 128.1, 126.3, 126.2, 125.6, 123.3,
84.7, 63.2, 21.8. HRMS (ESI/QTOF) m/z: [M + H]+ calcd for
C22H18ClO4S 413.0609; found 413.0605.
5-Phenyl-5-(tosylmethyl)dihydrofuran-2(3H)-one (13a). The ti-
tled compound 13a was prepared according to the GP and purified by
silica column chromatography in petroleum ether/ethyl acetate = 3:1.
13a was obtained as a white solid (85 mg, 86%). The titled compound
is known.7,9 Melting point: 120−122 °C. 1H NMR (600 MHz,
chloroform-d) δ 7.69 (d, J = 8.3 Hz, 2H), 7.36−7.22 (m, 7H), 3.75
(d, J = 15.6 Hz, 1H), 3.71 (d, J = 15.6 Hz, 1H), 3.37 (ddd, J = 13.2,
10.2, 8.4 Hz, 1H), 2.85 (ddd, J = 18.0, 10.2, 4.8 Hz, 1H), 2.63 (ddd, J
= 13.2, 10.2, 4.8 Hz, 1H), 2.49 (ddd, J = 18.0, 10.2, 8.4 Hz, 1H), 2.42
(s, 3H). 13C{1H} NMR (150 MHz, chloroform-d) δ 175.5, 145.1,
142.0, 137.6, 130.0, 129.0, 128.6, 128.0, 124.6, 84.8, 65.1, 32.6, 28.3,
1
Melting point: 178−179 °C. H NMR (600 MHz, chloroform-d) δ
7.57 (d, J = 8.4 Hz, 2H), 7.43 (dd, J = 8.4, 1.2 Hz, 2H), 7.40−7.35
(m, 2H), 7.33−7.28 (m, 1H), 7.24 (d, J = 8.4 Hz, 2H), 7.22−7.19 (m,
2H), 7.16 (dd, J = 5.0, 1.9 Hz, 3H), 7.09−7.03 (m, 5H), 4.32 (d, J =
13.8 Hz, 1H), 3.66 (s, 2H), 3.55 (d, J = 13.8 Hz, 1H), 2.41 (s, 3H).
13C{1H} NMR (150 MHz, chloroform-d) δ 175.9, 144.9, 141.5,
141.0, 140.1, 137.6, 129.8, 129.0, 128.5, 128.4, 128.2, 128.1, 128.0,
127.7, 127.5, 127.3, 125.0, 82.4, 64.5, 57.9, 46.2, 21.8. HRMS (ESI/
QTOF) m/z: calcd for [M + Na]+ C30H26NaO4S 505.1444; found
505.1443.
F
https://doi.org/10.1021/acs.joc.1c01378
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
1
3,3-Dimethyl-5-phenyl-5-(tosylmethyl)dihydrofuran-2(3H)-one
(19a). The titled compound 19a was prepared according to the GP
and purified by silica column chromatography in petroleum ether/
ethyl acetate = 3:1. 19a was obtained as a white solid (99 mg, 92%).
111−112 °C. H NMR (600 MHz, chloroform-d) δ 7.71 (d, J = 8.4
Hz, 2H), 7.37−7.29 (m, 6H), 7.29−7.26 (m, 1H), 3.70 (s, 2H), 3.25
(d, J = 13.2 Hz, 1H), 2.77 (d, J = 13.2 Hz, 1H), 2.43 (s, 3H), 1.90−
1.74 (m, 3H), 1.62−1.56 (m, 1H), 1.49 (dt, J = 13.2, 3.6 Hz, 1H),
1.40−1.24 (m, 3H), 1.20−1.10 (m, 1H), 1.01 (d, J = 13.2 Hz, 1H).
13C{1H} NMR (150 MHz, chloroform-d) δ 180.2, 145.0, 143.5,
1
Melting point: 134−136 °C. H NMR (600 MHz, chloroform-d) δ
7.71 (d, J = 8.4 Hz, 2H), 7.36−7.21 (m, 7H), 3.70 (s, 2H), 3.37 (d, J
= 13.2 Hz, 1H), 2.58 (d, J = 13.2 Hz, 1H), 2.41 (s, 3H), 1.40 (s, 3H),
0.89 (s, 3H). 13C{1H} NMR (150 MHz, chloroform-d) δ 180.6,
144.9, 143.0, 138.0, 129.9, 129.0, 128.4, 128.0, 124.5, 81.5, 65.6, 46.4,
40.3, 26.3, 25.5, 21.7. HRMS (ESI/QTOF) m/z: calcd for [M + Na]+
C20H22NaO4S 381.1131; found 381.1144.
138.1, 129.9, 129.1, 128.4, 128.1, 124.5, 82.0, 65.9, 45.1, 42.7, 34.4,
33.1, 25.2, 22.4, 22.0, 21.8. HRMS (ESI/QTOF) m/z: calcd for [M +
H]+ C23H27O4S 399.1625; found 399.1622.
3-Phenyl-3-((phenylsulfonyl)methyl)isobenzofuran-1(3H)-one
(8b). The titled compound 8b was prepared according to the GP and
purified by silica column chromatography in petroleum ether/ethyl
acetate = 3:1. 8b was obtained as a white solid (104 mg, 95%). The
titled compound is known. Melting point: 137−138 °C. H NMR
(600 MHz, chloroform-d) δ 7.87 (d, J = 7.5 Hz, 1H), 7.63 (dd, J =
8.3, 1.0 Hz, 2H), 7.60−7.55 (m, 3H), 7.52 (ddd, J = 8.0, 6.7, 1.8 Hz,
1H), 7.47−7.38 (m, 4H), 7.34−7.23 (m, 3H), 4.32 (d, J = 15.6 Hz,
1H), 4.25 (d, J = 15.6 Hz, 1H). 13C{1H} NMR (150 MHz,
chloroform-d) δ 168.6, 149.0, 140.0, 138.9, 134.4, 133.9, 129.9, 129.3,
129.1, 129.0, 127.9, 125.9, 125.6, 124.7, 123.3, 85.0, 62.94. HRMS
(ESI/QTOF) m/z: calcd for [M + Na]+ C21H16NaO4S 387.0662;
found 387.0650.
3-(((4-Methoxyphenyl)sulfonyl)methyl)-3-phenylisobenzofuran-
1(3H)-one (8c). The titled compound 8c was prepared according to
the GP and purified by silica column chromatography in petroleum
ether/ethyl acetate = 3:1. 8c was obtained as a white solid (97 mg,
82%). The titled compound is known.8 Melting point: 147−149 °C.
1H NMR (600 MHz, chloroform-d) δ 7.88 (d, J = 7.8 Hz, 1H), 7.69−
7.59 (m, 2H), 7.58−7.51 (m, 3H), 7.47−7.38 (m, 2H), 7.35−7.27
(m, 3H), 6.91 (d, J = 8.4 Hz, 8H), 4.27 (d, J = 15.6 Hz, 1H), 4.19 (d,
J = 15.6 Hz, 1H), 3.86 (s, 3H). 13C{1H} NMR (150 MHz,
chloroform-d) δ 168.7, 163.9, 149.3, 139.1, 134.4, 131.6, 130.3, 129.9,
129.1, 129.0, 126.0, 125.7, 124.7, 123.4, 114.5, 85.2, 63.4, 55.8.
HRMS (ESI/QTOF) m/z: calcd for [M + H]+ C22H19O5S 395.0948;
found 395.0966.
3-(((4-(Tert-butyl)phenyl)sulfonyl)methyl)-3-phenylisobenzofur-
an-1(3H)-one (8d). The titled compound 8d was prepared according
to the GP and purified by silica column chromatography in petroleum
ether/ethyl acetate = 3:1. 8d was obtained as a white solid (112 mg,
89%). The titled compound is known.8 Melting point: 193−194 °C.
1H NMR (600 MHz, chloroform-d) δ 7.87 (d, J = 7.2 Hz, 1H), 7.61−
7.57 (m, 2H), 7.55−7.52 (m, 3H), 7.45−7.43 (m, 4H), 7.33−7.26
(m, 3H), 4.28 (d, J = 15.6 Hz, 1H), 4.21 (d, J = 15.6 Hz, 1H), 1.33 (s,
9H). 13C{1H} NMR (150 MHz, chloroform-d) δ 168.6, 157.9, 149.0,
139.1, 136.9, 134.3, 129.9, 129.1, 129.0, 128.0, 126.3, 126.0, 126.0,
124.8, 123.5, 85.1, 63.2, 35.3, 31.1. HRMS (ESI/QTOF) m/z: calcd
for [M + H]+ C25H25O4S 421.1468; Found 421.1463.
3-(([1,1′-Biphenyl]-4-ylsulfonyl)methyl)-3-phenylisobenzofuran-
1(3H)-one (8e). The titled compound 8e was prepared according to
the GP and purified by silica column chromatography in petroleum
ether/ethyl acetate = 3:1. 8e was obtained as a white solid (112 mg,
85%). Melting point: 199−200 °C. 1H NMR (600 MHz, chloroform-
d) δ 7.95−7.84 (m, 1H), 7.70 (d, J = 8.4 Hz, 2H), 7.67−7.54 (m,
7H), 7.53−7.47 (m, 2H), 7.45−7.42 (m, 3H), 7.37−7.28 (m, 3H),
4.33 (d, J = 15.6 Hz, 1H), 4.23 (d, J = 15.6 Hz, 1H). 13C{1H} NMR
(151 MHz, chloroform-d) δ 168.6, 149.2, 147.0, 139.2, 139.1, 138.5,
134.4, 130.1, 129.2, 129.1, 128.8, 128.6, 128.0, 127.6, 126.2, 125.9,
124.8, 123.4, 85.1, 63.4. HRMS (ESI/QTOF) m/z: calcd for [M +
H]+ C27H21O4S 441.1155; found 441.1151.
3-Ethyl-3-methyl-5-phenyl-5-(tosylmethyl)dihydrofuran-2(3H)-
one (20a). The titled compound 20a was prepared according to the
GP and purified by silica column chromatography in petroleum
ether/ethyl acetate = 3:1. 20a was obtained as a white solid (98 mg,
88%), 1.5:1 dr ratio. Melting point: 108−10 °C. For two inseparable
8
1
1
isomers, H NMR (600 MHz, chloroform-d) δ 7.68 (d, J = 8.4 Hz,
0.73H), 7.66 (d, J = 7.8 Hz, 0.73H), 7.35−7.17 (m, 7H), 3.76−3.59
(m, 2H), 3.33 (d, J = 13.2 Hz, 0.58H), 3.25 (d, J = 13.2 Hz, 0.36H),
2.64 (d, J = 13.2 Hz, 0.35H), 2.46 (d, J = 13.2 Hz, 0.63H), 2.39 (s,
3H), 1.77 (dt, J = 14.9, 7.4 Hz, 0.6H), 1.68 (dq, J = 14.4, 7.8 Hz,
0.6H), 1.25 (td, J = 14.4, 7.2 Hz, 0.58H), 1.13 (dq, J = 14.4, 7.8 Hz,
0.38H), 0.98 (t, J = 7.8 Hz, 1.87H), 0.63 (t, J = 7.8 Hz, 1.18H).
13C{1H} NMR (150 MHz, chloroform-d) δ 180.2, 180.2, 144.9,
144.8, 143.3, 142.9, 138.0, 137.9, 129.8, 128.9, 128.4, 128.3, 128.0,
124.6, 124.4, 81.8, 81.5, 65.9, 65.6, 44.3, 44.1, 43.9, 43.68, 31.2, 31.0,
23.1, 22.4, 21.7, 8.8, 8.5. HRMS (ESI/QTOF) m/z: calcd for [M +
Na]+ C21H24NaO4S 395.1288; found 395.1292.
5-Methyl-3,3-diphenyl-5-(tosylmethyl)dihydrofuran-2(3H)-one
(21a). The titled compound 21a was prepared according to the GP
and purified by silica column chromatography in petroleum ether/
ethyl acetate = 3:1. 21a was obtained as a white solid (45 mg, 36%).
The titled compound is known.7 Melting point: 115−117 °C. H
1
NMR (600 MHz, chloroform-d) δ 7.57 (d, J = 8.4 Hz, 2H), 7.46−
7.42 (m, 2H), 7.40−7.35 (m, 2H), 7.34−7.28 (m, 7H), 7.27−7.23
(m, 1H), 3.96 (d, J = 14.4 Hz, 1H), 3.28 (d, J = 14.4 Hz, 1H), 3.20
(d, J = 14.4 Hz, 1H), 3.05 (d, J = 14.4 Hz, 1H), 2.43 (s, 3H), 1.69 (s,
3H). 13C{1H} NMR (150 MHz, chloroform-d) δ 176.0, 145.3, 142.3,
141.2, 137.5, 130.1, 129.2, 128.9, 127.9, 127.7, 127.7, 127.6, 127.4,
80.7, 63.1, 58.1, 46.6, 27.8, 21.8. HRMS (ESI/QTOF) m/z: calcd for
[M + H]+ C25H25O4S 421.1468; found 421.1463.
3-Methyl-5-phenyl-5-(tosylmethyl)dihydrofuran-2(3H)-one
(22a). The titled compound 22a was prepared according to the GP
and purified by silica column chromatography in petroleum ether/
ethyl acetate = 3:1. 22a was obtained as a white solid (91 mg, 88%),
1:1 dr ratio. Melting point: 140−141 °C. For one of two isomers, 1H
NMR (600 MHz, chloroform-d) δ 7.66 (d, J = 8.4 Hz, 1H), 7.37−
7.21 (m, 7H), 3.76 (d, J = 1.8 Hz, 2H), 2.99 (t, J = 12.6 Hz, 1H), 2.86
(dd, J = 12.6, 9.0 Hz, 1H), 2.53−2.42 (m, 1H), 2.41 (s, 3H), 1.30 (d,
J = 7.2 Hz, 3H). 13C{1H} NMR (150 MHz, chloroform-d) δ 177.7,
145.0, 140.9, 137.7, 129.9, 128.9, 128.6, 128.1, 124.8, 82.4, 65.0, 40.7,
34.2, 21.8, 14.5. HRMS (ESI/QTOF) m/z: calcd for [M + H]+
C19H21O4S 345.1155; found 345.1156.
3-Phenyl-3-(tosylmethyl)-2-oxaspiro[4.4]nonan-1-one (23a).
The titled compound 23a was prepared according to the GP and
purified by silica column chromatography in petroleum ether/ethyl
acetate = 3:1. 23a was obtained as a white solid (103 mg, 89%).
1
Melting point: 152−154 °C. H NMR (600 MHz, chloroform-d) δ
7.68 (d, J = 8.4 Hz, 2H), 7.35−7.22 (m, 7H), 3.73 (d, J = 15.6 Hz,
1H), 3.71 (d, J = 15.6 Hz, 1H), 3.32 (d, J = 13.2 Hz, 1H), 2.61 (d, J =
13.2 Hz, 1H), 2.41 (s, 3H), 2.28−2.15 (m, 1H), 1.85−1.77 (m, 2H),
1.71−1.59 (m, 2H), 1.58−1.46 (m, 2H), 1.14−1.00 (m, 1H).
13C{1H} NMR (150 MHz, chloroform-d) δ 181.1, 144.9, 142.6,
137.8, 129.9, 128.9, 128.4, 128.1, 124.7, 82.0, 65.4, 49.7, 46.9, 39.2,
38.0, 25.6, 25.3, 21.7. HRMS (ESI/QTOF) m/z: [M + H]+ calcd for
C22H25O4S 385.1468; found 385.1473.
4-(((3-Oxo-1-phenyl-1,3-dihydroisobenzofuran-1-yl)methyl)-
sulfonyl)benzonitrile (8f). The titled compound 8f was prepared
according to the GP and purified by silica column chromatography in
petroleum ether/ethyl acetate = 3:1. 8f was obtained as a white solid
1
(85 mg, 73%). Melting point: 159−161 °C. H NMR (600 MHz,
chloroform-d) δ 7.94−7.87 (m, 1H), 7.84−7.74 (m, 4H), 7.72−7.65
(m, 1H), 7.63−7.52 (m, 2H), 7.43−7.36 (m, 2H), 7.36−7.27 (m,
3H), 4.36 (d, J = 15.6 Hz, 1H), 4.22 (d, J = 15.6 Hz, 1H). 13C{1H}
NMR (150 MHz, chloroform-d) δ 168.4, 149.4, 144.1, 138.5, 134.8,
133.1, 130.3, 129.3, 129.3, 129.0, 126.3, 125.4, 124.6, 123.1, 117.8,
3-Phenyl-3-(tosylmethyl)-2-oxaspiro[4.5]decan-1-one (24a). The
titled compound 24a was prepared according to the GP and purified
by silica column chromatography in petroleum ether/ethyl acetate =
3:1. 24a was obtained as a white solid (104 mg, 87%). Melting point:
G
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117.2, 84.7, 63.4. HRMS (ESI/QTOF) m/z: calcd for [M + H]+
C22H16NO4S 390.0795; found 390.0778.
125.6, 124.7, 123.3, 84.9, 63.1. HRMS (ESI/QTOF) m/z: calcd for
[M + Na]+ C21H15ClNaO4S 421.0272; found 421.0287.
3-(((4-Fluorophenyl)sulfonyl)methyl)-3-phenylisobenzofuran-
1(3H)-one (8g). The titled compound 8g was prepared according to
the GP and purified by silica column chromatography in petroleum
ether/ethyl acetate = 3:1. 8g was obtained as a white solid (101 mg,
88%). The titled compound is known.8 Melting point: 136−138 °C.
1H NMR (600 MHz, chloroform-d) δ 7.89 (d, J = 7.8 Hz, 1H), 7.72−
7.66 (m, 2H), 7.66−7.62 (m, 1H), 7.60 (d, J = 7.8 Hz, 1H), 7.58−
7.52 (m, 1H), 7.43 (dd, J = 8.4, 1.2 Hz, 2H), 7.36−7.28 (m, 3H), 7.14
(t, J = 8.4 Hz, 2H), 4.32 (d, J = 15.6 Hz, 1H), 4.22 (d, J = 15.6 Hz,
1H). 13C{1H} NMR (150 MHz, chloroform-d) δ 168.4, 166.0 (d, J =
225.5 Hz, 1C), 149.5, 139.1, 136.5, 134.4, 131.1 (d, J = 9.5 Hz, 2C),
130.0, 129.2, 129.1, 126.1, 125.8, 124.8, 123.4, 116.6 (d, J = 22.7 Hz,
2C), 85.0, 63.6. 19F NMR (565 MHz, chloroform-d) δ −102.7.
HRMS (ESI/QTOF) m/z: calcd for [M + H]+ C21H16FO4S
383.0748; found 383.0743.
3-Phenyl-3-(((4-(trifluoromethyl)phenyl)sulfonyl)methyl)-
isobenzofuran-1(3H)-one (8h). The titled compound 8h was
prepared according to the GP and purified by silica column
chromatography in petroleum ether/ethyl acetate = 3:1. 8h was
obtained as a white solid (109 mg, 84%). The titled compound is
known.8 Melting point: 178−180 °C. 1H NMR (600 MHz,
chloroform-d) δ 7.91 (d, J = 7.8 Hz, 1H), 7.81 (d, J = 8.4 Hz,
2H), 7.73 (d, J = 8.4 Hz, 2H), 7.66−7.61 (m, 1H), 7.59−7.54 (m,
2H), 7.45−7.37 (m, 2H), 7.35−7.27 (m, 3H), 4.35 (d, J = 15.6 Hz,
1H), 4.25 (d, J = 15.6 Hz, 1H). 13C{1H} NMR (150 MHz,
chloroform-d) δ 168.5, 149.2, 143.5, 138.6, 135.5 (q, J = 33.0 Hz,
1C), 134.6, 130.2, 129.3, 129.2, 128.8, 126.5 (d, J = 3.8 Hz, 2C),
126.3, 125.9, 125.6, 124.7, 124.1, 123.2 (q, J = 271.4 Hz, 1C), 123.1,
122.3, 120.5, 84.8, 63.3. 19F NMR (565 MHz, chloroform-d) δ −63.1.
HRMS (ESI/QTOF) m/z: calcd for [M + H]+ C22H16F3O4S
433.0716; found 433.0712.
3-(((3-Bromophenyl)sulfonyl)methyl)-3-phenylisobenzofuran-
1(3H)-one (8l). The titled compound 8l was prepared according to
the GP and purified by silica column chromatography in petroleum
ether/ethyl acetate = 3:1. 8l was obtained as a white solid (114 mg,
86%). Melting point: 119−121 °C. 1H NMR (600 MHz, chloroform-
d) δ 7.90 (d, J = 7.8 Hz, 1H), 7.69 (d, J = 8.4 Hz, 1H), 7.64 (d, J = 7.8
Hz, 1H), 7.60−7.57 (m, 2H), 7.56−7.52 (m, 2H), 7.43 (d, J = 7.8 Hz,
2H), 7.39−7.27 (m, 4H), 4.33 (d, J = 15.6 Hz, 1H), 4.25 (m, d, J =
15.6 Hz, 1H). 13C{1H} NMR (150 MHz, chloroform-d) δ 168.4,
148.7, 141.6, 138.6, 137.0, 134.4, 130.9, 130.9, 130.2, 129.1, 126.6,
126.0, 125.7, 124.7, 123.3, 123.2, 84.9, 63.1. HRMS (ESI/QTOF) m/
z: calcd for [M + H]+ C21H16BrO4S 442.9947; found 442.9943.
3-(((2-Bromophenyl)sulfonyl)methyl)-3-phenylisobenzofuran-
1(3H)-one (8m). The titled compound 8m was prepared according to
the GP and purified by silica column chromatography in petroleum
ether/ethyl acetate = 3:1. 8m was obtained as a white solid (101 mg,
76%). Melting point: 183−184 °C. 1H NMR (600 MHz, chloroform-
d) δ 7.83 (d, J = 7.8 Hz, 1H), 7.73 (d, J = 7.2 Hz, 1H), 7.56 (t, J = 7.2
Hz, 2H), 7.53 (d, J = 7.2 Hz, 1H), 7.52−7.48 (m, 2H), 7.47−7.44 (m,
2H), 7.42 (td, J = 7.2, 1.8 Hz, 1H), 7.37−7.27 (m, 4H), 4.69 (d, J =
15.6 Hz, 1H), 4.55 (d, J = 15.6 Hz, 1H). 13C{1H} NMR (150 MHz,
chloroform-d) δ 168.3, 148.7, 138.9, 138.8, 135.4, 134.9, 134.2, 131.7,
130.1, 129.2, 128.2, 126.0, 125.8, 124.8, 123.4, 120.7, 85.0, 60.3.
HRMS (ESI/QTOF) m/z: calcd for [M + Na]+ C21H15BrNaO4S
464.9767; found 464.9753.
3-(((3,4-Difluorophenyl)sulfonyl)methyl)-3-phenylisobenzofur-
an-1(3H)-one (8n). The titled compound 8n was prepared according
to the GP and purified by silica column chromatography in petroleum
ether/ethyl acetate = 3:1. 8n was obtained as a white solid (101 mg,
84%). Melting point: 182−183 °C. 1H NMR (600 MHz, chloroform-
d) δ 7.91 (d, J = 7.8 Hz, 1H), 7.70−7.65 (m, 1H), 7.62 (d, J = 7.8 Hz,
1H), 7.59−7.54 (m, 1H), 7.51−7.49 (m, 1H), 7.47−7.40 (m, 2H),
7.37−7.23 (m, 4H), 4.31 (d, J = 15.6 Hz, 1H), 4.17 (d, J = 15.6 Hz,
1H). 13C{1H} NMR (150 MHz, chloroform-d) δ 168.3, 149.5, 138.9,
137.1, 134.5, 130.2, 129.3, 129.3, 126.3, 125.8, 124.8, 123.3, 118.5,
84.9, 63.9. 19F NMR (565 MHz, chloroform-d) δ −126.8, −132.8.
HRMS (ESI/QTOF) m/z: calcd for [M + H]+ C21H15F2O4S
401.0654; found 401.0650.
3-((Naphthalen-1-ylsulfonyl)methyl)-3-phenylisobenzofuran-
1(3H)-one (8o). The titled compound 8o was prepared according to
the GP and purified by silica column chromatography in petroleum
ether/ethyl acetate = 3:1. 8o was obtained as a white solid (98 mg,
79%). Melting point: 162−164 °C. 1H NMR (600 MHz, chloroform-
d) δ 8.65 (d, J = 8.4 Hz, 1H), 8.06 (d, J = 8.4 Hz, 1H), 7.96 (d, J = 8.4
Hz, 1H), 7.89−7.83 (m, 1H), 7.76 (dd, J = 7.8, 1.2 Hz, 1H), 7.75−
7.69 (m, 1H), 7.63 (t, J = 7.8 Hz, 1H), 7.50 (dd, J = 6.0, 3.0 Hz, 2H),
7.45−7.33 (m, 4H), 7.31−7.19 (m, 3H), 4.48 (d, J = 15.6 Hz, 1H),
4.39 (d, J = 15.6 Hz, 1H). 13C{1H} NMR (150 MHz, chloroform-d) δ
168.5, 148.6, 138.9, 135.5, 134.6, 134.2, 134.1, 130.8, 129.9, 129.6,
129.1, 129.1, 128.4, 127.2, 126.0, 125.9, 124.8, 124.6, 123.7, 123.3,
85.2, 62.3. HRMS (ESI/QTOF) m/z: calcd for [M + Na]+
C25H18NaO4S 437.0818; found 437.0820.
3-((Naphthalen-2-ylsulfonyl)methyl)-3-phenylisobenzofuran-
1(3H)-one (8p). The titled compound 8p was prepared according to
the GP and purified by silica column chromatography in petroleum
ether/ethyl acetate = 3:1. 8p was obtained as a white solid (102 mg,
82%). The titled compound is known.8 Melting point: 96−97 °C. 1H
NMR (600 MHz, chloroform-d) δ 8.06 (d, J = 1.6 Hz, 1H), 7.94 (d, J
= 9.0 Hz, 1H), 7.91 (d, J = 8.4 Hz, 1H), 7.88−7.81 (m, 2H), 7.71
(dd, J = 8.6, 1.9 Hz, 1H), 7.67 (ddd, J = 8.2, 6.9, 1.2 Hz, 1H), 7.61
(ddd, J = 8.0, 6.9, 1.1 Hz, 1H), 7.56−7.52 (m, 1H), 7.52−7.46 (m,
2H), 7.45−7.39 (m, 2H), 7.35−7.22 (m, 3H), 4.36 (d, J = 15.6 Hz,
1H), 4.27 (d, J = 15.6 Hz, 1H). 13C{1H} NMR (150 MHz,
chloroform-d) δ 168.6, 148.9, 139.0, 136.7, 135.4, 134.2, 132.1, 130.3,
130.0, 129.7, 129.7, 129.6, 129.1, 129.1, 128.1, 127.8, 126.0, 125.9,
124.8, 123.4, 122.4, 85.1, 63.1. HRMS (ESI/QTOF) m/z: calcd for
[M + Na]+ C25H18NaO4S 437.0818; found 437.0820.
3-Phenyl-3-((m-tolylsulfonyl)methyl)isobenzofuran-1(3H)-one
(8i). The titled compound 8i was prepared according to the GP and
purified by silica column chromatography in petroleum ether/ethyl
acetate = 3:1. 8i was obtained as a white solid (97 mg, 85%). Melting
1
point: 69−71 °C. H NMR (600 MHz, chloroform-d) δ 7.95−7.77
(m, 1H), 7.59−7.54 (m, 2H), 7.53−7.50 (m, 1H), 7.49−7.46 (m,
1H), 7.45−7.41 (m, 2H), 7.37 (d, J = 7.8 Hz, 1H), 7.34−7.25 (m,
5H), 4.30 (d, J = 15.6 Hz, 1H), 4.25 (d, J = 15.6 Hz, 1H), 2.33 (s,
3H). 13C{1H} NMR (150 MHz, chloroform-d) δ 168.6, 148.9, 139.7,
139.4, 139.0, 134.6, 134.2, 129.8, 129.1, 129.0, 128.9, 128.3, 125.8,
125.0, 124.7, 123.4, 85.0, 63.0, 21.2. HRMS (ESI/QTOF) m/z: calcd
for [M + H]+ C22H19O4S 379.0999; found 379.0996.
3-(((3-Fluorophenyl)sulfonyl)methyl)-3-phenylisobenzofuran-
1(3H)-one (8j). The titled compound 8j was prepared according to
the GP and purified by silica column chromatography in petroleum
ether/ethyl acetate = 3:1. 8j was obtained as a white solid (96 mg,
84%). Melting point: 159−160 °C. 1H NMR (600 MHz, chloroform-
d) δ 7.90 (d, J = 7.8 Hz, 1H), 7.68−7.61 (m, 1H), 7.60−7.54 (m,
2H), 7.51−7.40 (m, 4H), 7.36−7.28 (m, 4H), 7.28−7.23 (m, 1H),
4.33 (d, J = 15.6 Hz, 1H), 4.22 (d, J = 15.6 Hz, 1H). 13C{1H} NMR
(150 MHz, chloroform-d) δ 168.5, 162.3 (d, J = 251.1 Hz, 1C), 149.0,
142.0 (d, J = 6.2 Hz, 1C), 138.7, 134.5, 131.3 (d, J = 7.8 Hz, 1C),
130.2, 129.2, 129.2, 126.1, 125.7, 124.7, 123.9 (d, J = 2.6 Hz, 1C),
123.4, 121.3 (d, J = 21.2 Hz, 1C), 115.4 (d, J = 24.3 Hz, 1C), 84.9,
63.3. 19F NMR (565 MHz, chloroform-d) δ −108.8. HRMS (ESI/
QTOF) m/z: calcd for [M + H]+ C21H16FO4S 383.0748; found
383.0741.
3-(((3-Chlorophenyl)sulfonyl)methyl)-3-phenylisobenzofuran-
1(3H)-one (8k). The titled compound 8k was prepared according to
the GP and purified by silica column chromatography in petroleum
ether/ethyl acetate = 3:1. 8k was obtained as a white solid (110 mg,
92%). Melting point: 103−105 °C. 1H NMR (600 MHz, chloroform-
d) δ 8.01−7.83 (m, 1H), 7.66−7.49 (m, 5H), 7.46−7.37 (m, 4H),
7.33−7.27 (m, 3H), 4.34 (d, J = 15.6 Hz, 1H), 4.26 (d, J = 15.6 Hz,
1H). 13C{1H} NMR (150 MHz, chloroform-d) δ 168.5, 148.8, 141.5,
138.6, 135.3, 134.4, 134.0, 130.7, 130.1, 129.1, 128.1, 126.2, 126.0,
H
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3-((Butylsulfonyl)methyl)-3-phenylisobenzofuran-1(3H)-one
(8q). The titled compound 8q was prepared according to the GP and
purified by silica column chromatography in petroleum ether/ethyl
acetate = 3:1. 8q was obtained as a white solid (89 mg, 86%). Melting
Further purification of the aqueous phase afforded a 33% recovery of
8 (22 mg)
(2-Tosylethene-1,1-diyl)dibenzene (8aa). The titled com-
pound 8aa was known.6 1H NMR (600 MHz, chloroform-d) δ 7.48
(d, J = 8.4 Hz, 2H), 7.41−7.33 (m, 2H), 7.32−7.27 (m, 4H), 7.23−
7.18 (m, 2H), 7.15 (d, J = 8.4 Hz, 2H), 7.10 (dd, J = 8.4, 1.2 Hz, 2H),
7.00 (s, 1H), 2.38 (s, 3H). 13C NMR (150 MHz, chloroform-d) δ
154.8, 143.9, 139.3, 138.7, 135.6, 130.3, 129.8, 129.4, 129.0, 128.9,
128.7, 128.3, 127.9, 127.8, 21.6.
1
point: 155−157 °C. H NMR (600 MHz, chloroform-d) δ 7.92 (d, J
= 7.8 Hz, 1H), 7.78−7.69 (m, 1H), 7.69−7.63 (m, 1H), 7.60−7.55
(m, 1H), 7.53 (dt, J = 9.0, 2.4 Hz, 2H), 7.41 (td, J = 7.2, 6.6, 1.8 Hz,
2H), 7.38−7.32 (m, 1H), 4.11 (d, J = 15.6 Hz, 1H), 3.93 (d, J = 15.6
Hz, 1H), 3.10−3.00 (m, 2H), 1.84−1.71 (m, 2H), 1.51−1.39 (m,
2H), 0.93 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (150 MHz, chloroform-
d) δ 168.9, 150.4, 138.9, 134.9, 130.1, 129.3, 129.2, 126.3, 125.0,
124.6, 122.9, 84.9, 60.0, 55.6, 23.9, 21.7, 13.6. HRMS (ESI/QTOF)
m/z: calcd for [M + H]+ C19H21O4S 345.1155; found 345.1156.
3-((Cyclopropylsulfonyl)methyl)-3-phenylisobenzofuran-1(3H)-
one (8r). The titled compound 8r was prepared according to the GP
and purified by silica column chromatography in petroleum ether/
ethyl acetate = 3:1. 8r was obtained as a white solid (77 mg, 78%).
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c01378.
Preparation and spectral characterization of starting
materials, spectral copies of all starting materials and
products (PDF)
The titled compound is known.8 Melting point: 164−165 °C. H
1
NMR (600 MHz, chloroform-d) δ 7.92 (d, J = 7.8 Hz, 1H), 7.75−
7.65 (m, 2H), 7.62−7.50 (m, 3H), 7.45−7.38 (m, 2H), 7.37−7.31
(m, 1H), 4.20 (d, J = 15.6 Hz, 1H), 4.02 (d, J = 15.6 Hz, 1H), 2.52
(tt, J = 7.8 4.8 Hz, 1H), 1.23−1.16 (m, 1H), 1.11 (dt, J = 10.2, 5.4 Hz,
1H), 1.05−0.95 (m, 2H). 13C{1H} NMR (150 MHz, chloroform-d) δ
169.0, 150.3, 139.0, 134.8, 130.1, 129.3, 129.1, 126.2, 125.3, 124.7,
123.1, 85.1, 61.3, 32.4, 5.8, 5.6. HRMS (ESI/QTOF) m/z: calcd for
[M + Na]+ C18H16NaO4S 351.0662; found 351.0668.
AUTHOR INFORMATION
Corresponding Author
■
Wei-Hao Rao − College of Chemistry and Chemical
Engineering, Xinyang Normal University, Xinyang 464000,
China; Ministry-of-Education Key Laboratory for the
Synthesis and Application of Organic Functional Molecules,
Hubei University, Wuhan 430062, China; orcid.org/
0000-0001-6197-0148; Email: whrao@xynu.edu.cn
Procedure for Gram-Scale Synthesis of 8a. To a 100 mL one-
necked, round-bottomed flask made of borosilicate glass equipped
with a magnetic stirring bar were added 8 (1.12 g, 5 mmol, 1 equiv),
Ir(ppy)3 (0.05 mmol, 1 mol %), tosyl chlorides (1.43 g, 7.5 mmol, 1.5
equiv), Na2CO3 (1.06 g, 10 mmol, 2 equiv), and dry DCM (50.0
mL). The flask was then charged with N2 via N2-vacuum exchanges
twice and capped with a rubber stopper. The mixture was irradiated
under stirring with a blue LED ribbon (20 W) at rt (cooling with two
mini-fans) for 24 h. The reaction mixture was then diluted with DCM
(20 mL) and transferred into a separatory funnel. The organic phase
was sequentially washed with water (2 × 30 mL) and brine (30 mL),
and dried over anhydrous Mg2SO4, then concentrated under reduced
Authors
Qi Li − College of Chemistry and Chemical Engineering,
Xinyang Normal University, Xinyang 464000, China
Fang-Yuan Chen − College of Chemistry and Chemical
Engineering, Xinyang Normal University, Xinyang 464000,
China
Li-Li Jiang − College of Chemistry and Chemical Engineering,
Xinyang Normal University, Xinyang 464000, China
Pan Xu − College of Chemistry and Chemical Engineering,
Xinyang Normal University, Xinyang 464000, China
Xue-Wan Deng − College of Chemistry and Chemical
Engineering, Xinyang Normal University, Xinyang 464000,
China
Ming Li − College of Chemistry and Chemical Engineering,
Xinyang Normal University, Xinyang 464000, China
Guo-Dong Zou − College of Chemistry and Chemical
Engineering, Xinyang Normal University, Xinyang 464000,
China
Xinhua Cao − College of Chemistry and Chemical Engineering,
Xinyang Normal University, Xinyang 464000, China;
orcid.org/0000-0001-6715-8433
1
pressure on a rotary evaporator to afford the residue. The direct H
NMR test of the residue without further purification showed that the
residual solvent is rather pure and could meet the purity standard as
8a (1.74 g) in 92% yield.
Mechanistic Investigation. With TEMPO as a Radical
Scavenger. To a 30 mL Schlenk flask equipped with a magnetic
stirring bar and a Teflon-lined screw cap were added 8 (0.3 mmol, 1
equiv), Ir(ppy)3 (0.003 mmol, 1 mol %), TsCl (0.45 mmol, 1.5
equiv), Na2CO3 (64 mg, 0.6 mmol, 2 equiv), TEMPO (0.6 mmol, 2
equiv), and dry DCM (3.0 mL). The flask was then charged with N2
via twice N2-vacuum exchanges, and the mixture was irradiated under
stirring with a blue LED ribbon (20 W) at rt (cooling with two mini-
fans) for 24 h. The reaction mixture was then diluted with DCM (5
mL), and 8a was not detected by TLC analysis. Further purification
afforded a 43% recovery of 8 (29 mg).
With 1,1-Diphenylethylene as a Radical Scavenger. To a 30 mL
Schlenk flask equipped with a magnetic stirring bar and a Teflon-lined
screw cap were added 8 (0.3 mmol, 1 equiv), Ir(ppy)3 (0.003 mmol, 1
mol %), TsCl (0.45 mmol, 1.5 equiv), Na2CO3 (64 mg, 0.6 mmol, 2
equiv), 1,1-diphenylethylene (0.6 mmol, 2 equiv), and dry DCM (3.0
mL). The flask was then charged with N2 via twice N2-vacuum
exchanges, and the mixture was irradiated under stirring with a blue
LED ribbon (20 W) at rt (cooling with two mini-fans) for 24 h. Trace
of 8a was detected by TLC analysis. The reaction mixture was then
diluted with DCM (20 mL) and transferred into a separatory funnel.
The organic phase was sequentially washed with water (2 mL × 20
mL) and brine (20 mL), and dried over anhydrous Na2SO4, then
concentrated under reduced pressure on a rotary evaporator. The
residue was further purified by silica gel column chromatography
(eluent: petroleum ether/EtOAc = 4:1) to afford the compound 8aa
(43 mg) as a white solid in 29% yield based on the amount of TsCl.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c01378
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors are grateful for the financial support from the
National Natural Science Foundation of China (Grant No.
21807091), Ministry-of-Education Key Laboratory for the
Synthesis and Application of Organic Functional Molecules
(Grant No. KLSAOFM2010), and Nanhu Scholars Program
for Young Scholars of XYNU. The authors also gratefully
acknowledge Dr. Qiu-Ju Zhou for NMR assistance.
I
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Article
(5) Wu, F.; Stewart, S.; Ariyarathna, J. P.; Li, W. Aerobic Copper-
Catalyzed Alkene Oxyamination for Amino Lactone Synthesis. ACS
Catal. 2018, 8, 1921−1925.
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