Iron-Catalyzed Thiolation and Selenylation of Cycloalkyl Hydroperoxides via C-C Bond Cleavage

Article abstract of DOI:10.1021/acs.joc.1c01366

A cheap iron-catalyzed C-C bond cleavage/thiolation and selenylation of cycloalkyl hydroperoxides are presented. This redox-neutral protocol provides efficient access to diverse distal keto-functionalized thioethers and selenium compounds. Remarkably, only some amounts of disulfides are required for this transformation.

Full text of DOI:10.1021/acs.joc.1c01366

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Iron-Catalyzed Thiolation and Selenylation of Cycloalkyl
Hydroperoxides via C−C Bond Cleavage
Qing-Xin Sun, He Chen, Shuai Liu, Xiao-Qiang Wang, Xin-Hua Duan, and Li-Na Guo*
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ABSTRACT: A cheap iron-catalyzed C−C bond cleavage/
thiolation and selenylation of cycloalkyl hydroperoxides are
presented. This redox-neutral protocol provides efficient access to
diverse distal keto-functionalized thioethers and selenium com-
pounds. Remarkably, only some amounts of disulfides are required
for this transformation.
selenoether with a distal carbonyl group.7 However, there
still exists some shortages in this protocol, including the
requirement of (over) stoichiometric amounts of oxidant (BI-
OH) and disulfides as well as the limitation of substrate scope
(limited to cyclobutanols). In fact, besides single-electron
oxidation of cycloalkanols, homolysis and single-electron
reduction of cycloalkyl peroxides could offer an alternative to
the reactive alkoxy radical intermediates, which play a key role
in the C−C bond cleavage. In this regard, our group and
Maruoka’s group reported a series of cheap Cu, Fe, or Ni-
catalyzed C−C bond cleavage reactions of alkylsilyl peroxides
under mild conditions.8 Therein, the redox neutral reactions
were developed and the unstrained substrates were well
compatible. These features encouraged us to develop a simple
catalytic system for the C−C bond cleavage/C−S bond
formation.
INTRODUCTION
■
The thioether motifs are widespread in natural products,
pharmaceuticals, and functional materials (Scheme 1).1
Scheme 1. Pharmaceutical Molecules Containing Thioether
Motifs
Results and Discussion. Disulfides are well-known
radical-trapping agents, which are widely employed for the
C−S bond formation.9 Initially, we examined the reaction of
cyclopentyl silyl peroxide and diphenyl disulfide 2a under iron
catalysis. After several attempts, we found that the reaction
worked well in the presence of 5 mol % Fe(OTf)2 in MeOH
under argon, giving the desired thioether 3a in 85% yield. In
view of step- and atom-economy, the corresponding hydro-
peroxide 1a was examined instead of cyclopentyl silyl peroxide.
To our delight, the reaction of 1a and 2a proceeded smoothly
to afford 3a in 70% yield (Table 1, entry 1). Solvent screening
revealed that MeOH is the most suitable solvent (entries 2−6).
Then, a series of iron salts were tested as the catalyst. Both
Fe(OTf)3 and Fe(OTs)3 showed slightly better catalytic
Moreover, thioethers are versatile synthetic intermediates for
the synthesis of sulfoxide, sulfone, and other organosulfur
compounds.2 Thus, the construction of C−S bonds has
received great attention from chemists, and significant progress
has been made in this field.3 Especially, the radical addition,
substitution, and coupling reactions of sulfur-centered radicals
have inarguably brought chemists a new platform for the
construction of diverse C−S bonds.4 In recent years, radical-
mediated ring-opening C−C bond cleavage has emerged as an
efficient strategy for the C−C and C-heteroatom bond
formation.5 For instance, the alkoxy radical-initiated C−C
bond cleavage has become a powerful tool for the C−C, C−N,
C−B, and C−Si bond formation.6 In 2016 and 2017, Zhu et al.
reported the Mn-catalyzed C−S and C−Se bond formation
reaction through C−C bond cleavage of cycloalkanols, which
provided an efficient approach to the thioethers and
Received: June 9, 2021
https://doi.org/10.1021/acs.joc.1c01366
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© XXXX American Chemical Society
A

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Article
a
a
Table 1. Optimized Reaction Conditions of 1a and 2a
Scheme 2. Scope of Alkyl Hydroperoxides
entry
catalyst (mol %)
solvent
MeOH
EtOH
NMP
CH3CN
DMF
1,4-dioxane
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
yield
b
1
2
3
4
5
6
7
8
Fe(OTf)2 (5)
Fe(OTf)2 (5)
Fe(OTf)2 (5)
Fe(OTf)2 (5)
Fe(OTf)2 (5)
Fe(OTf)2 (5)
Fe(OAc)2 (5)
FeCl2 (5)
Fe(OTf)3 (5)
Fe(OTs)3 (5)
CuI (5)
Cu(OTf) (5)
Fe(OTs)3 (5)
Fe(OTs)3 (3)
70 (85)
53
63
51
26
9
d
n.r.
17
72
75
trace
5
9
10
11
12
13
14
15
c
75
c
74
d
n.r.
a
Reaction conditions: catalyst (5 mol %), 1a (0.2 mmol, 1.0 equiv),
2a (0.22 mmol, 1.1 equiv), and solvent (2.0 mL), at room
b
temperature, under N2, for 12 h, isolated yield. Cyclopentyl silyl
c
d
peroxide was used. 0.16 mmol of 2a was used. No reaction.
activity than Fe(OTf)2, giving 3a in 72 and 75% yields,
respectively, while Fe(OAc)2 and FeCl2 were less effective
(entries 7−10). Switching from iron catalysts to copper
catalysts such as CuI and Cu(OTf) led to poor yields of 3a
(entries 11 and 12). Therefore, the cheaper Fe(OTs)3 was
chosen as the catalyst. Satisfactorily, reducing the amount of
diphenyl disulfide 2a from 1.1 equiv to 0.8 equiv did not affect
the yield of 3a (entry 13), while further reduction of 2a led to
3a in lower yield. Finally, the catalyst loading could be reduced
to 3 mol % without an obvious decrease in yield, but the
catalyst is essential to this reaction (entries 14 and 15). When
the reaction was carried out in the air, only a trace of 3a was
observed and 1a was decomposed to the corresponding
alcohol (not shown).
Having established the optimized reaction conditions, we set
out to explore the scope of this reaction. As shown in Scheme
2, a variety of alkyl hydroperoxides 1 reacted successfully with
2a to afford the target thioethers 3 in moderate to good yields.
Both 1-aryl- and 1-alkyl-substituted cyclopentyl hydroper-
oxides were engaged efficiently in this C−C bond cleavage/C−
S bond formation process to give the distal keto-functionalized
thioethers 3a−3g in good yields. 1-Alkoxyl substrate was also
compatible, delivering the ester-functionalized thioether 3h in
28% yield. Notably, this protocol was also reliable for less
strained substrates with six-, seven-, eight-, and even twelve-
membered rings, furnishing the corresponding desired
products 3i−3l in reasonable yields. 1,2-Disubstituted
substrates could undergo the C−C bond cleavage regiose-
lectively to provide the secondary alkylaryl sulfides 3m−3o in
41−78% yields. Hydroperoxide 1p derived from norcamphor
was also an amenable substrate, producing 3p in 70% yield.
The thiophene substituted-cyclopentyl hydroperoxide deliv-
ered the product 3q in a moderate yield.
a
Reaction conditions: Fe(OTs)3 (3 mol %), 1 (0.2 mmol, 1.0 equiv),
2a (0.16 mmol, 0.8 equiv), and MeOH (2.0 mL), at room
temperature, under N2, for 12 h, isolated yield.
thioethers 4a−4r in moderate to good yields. Diaryl disulfides
with electron-donating groups or electron-withdrawing groups
on the aromatic ring both were efficient substrates. Syntheti-
cally useful functional groups including OMe (4c), OH (4d),
NH2 (4e), and Br (4h, 4i, and 4m) were well tolerated, which
provide opportunities for further synthetic transformations.
Notably, heteroaryl disulfides such as di(2-thienyl) disulfide,
bis(2-methyl-3-furyl) disulfide, 2,2′-dipyridyl disulfide, and
4,4′-dipyridyl disulfide were compatible with the reactions,
providing the corresponding products 4o−4r in moderate to
good yields. Unfortunately, by using dialkyl disulfides, such as
dibenzyl disulfide and di-tert-butyl disulfide as substrates, only
a trace amount of the expected products was observed, along
with some amount of valerophenone obtained as major
byproducts, which were formed through the C−C bond
cleavage/H-atom transfer process (not shown). When the
unsymmetrical disulfide, 1-(tert-butyl)-2-(4-methoxyphenyl)-
disulfane 2t, was subjected to the reaction system, only 11% of
thioether 4c was obtained and no dialkyl thioether 4s was
detected.
To extend the application of this protocol, diselenides were
also examined for the C−C bond cleavage/C−Se bond
formation reaction (Scheme 4). The reaction of hydroperoxide
1a and diphenyl diselenides 5a still worked to afford the keto-
functionalized selenium compound 6a in 51% yield. Unfortu-
nately, increasing the amount of diselenide 5a to 1.5 equiv
could not improve the yield of product 6a. Other cycloalkyl
hydroperoxides were also applicable for the C−Se bond
Next, a wide range of disulfides were evaluated with 1a
under the optimal conditions (Scheme 3). Diverse symmetrical
diaryl disulfides reacted with 1a smoothly to afford the target
B
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a
Scheme 3. Scope of Disulfides
Scheme 5. Large Scale Reaction and Oxidation of
Compound 3a
Finally, several control experiments were performed to verify
the mechanism of this reaction (Scheme 6). When 2.0 equiv of
TEMPO, a well-known radical-trapping agent, was added into
the reaction of 1a and 2a, no desired product 3a was observed.
Meanwhile, the alkyl-TEMPO adduct 8a was isolated in 79%
yield. These results suggest that a radical intermediate might be
involved in this reaction (eq 1). Additionally, the presence of
BHT led to a decreased yield of 3a, which also supports a
radical pathway for this transformation (eq 2). Interestingly,
when the ratio of 1a and 2a was adjusted to 3:1, 61% yield of
3a was still isolated, which indicated that disulfide could serve
as a double “S” source in this transformation (eq 3). Notably,
when unsymmetrical diaryl disulfide 2u was treated with 1a,
both thioethers 4c and 4f were obtained. At the same time, a
certain amount of symmetrical diaryl disulfides 2d and 2g was
also isolated (eq 4).
a
Reaction conditions: Fe(OTs)3 (3 mol %), 1a (0.2 mmol, 1.0 equiv),
Base on the abovementioned results and literature,9
a
2 (0.16 mmol, 0.8 equiv), and MeOH (2.0 mL), at room temperature,
under N2, for 12 h, isolated yield. Cyclopentyl silyl peroxide was
used.
b
plausible mechanism is proposed in Scheme 7. Single-electron
reduction of alkyl hydroperoxide 1a by Fe(II) generates the
alkoxy radical I and hydroxide anion. The alkoxy radical
subsequently triggers β-carbon scission to afford the C-
centered radical II. Then, the radical II is captured by disulfide
2a to give product 3a and sulfur-centered radical III, which can
undergo single-electron oxidation by Fe(III) to furnish the
sulfide ion IV. Then, the hydroxide anion bonds with IV to
form sulfenic acid V. Sulfenic acid is an unstable species that
could convert into disulfide 2a.10 In addition, a radical chain
propagation process cannot be ruled out at present.
formation, producing 6b−6f in moderate yields. It is worth
mentioning that some amount of benzeneseleninic acid was
isolated as the byproduct in most of these reactions; this is due
to the further oxidation of selenoether with peroxide.
To illustrate the utilization of this simple protocol, the scale-
up reaction of 1a (5 mmol) with 2a (4 mmol) was conducted.
As shown in Scheme 5, the desired keto-functionalized
thioether 3a was still obtained in 70% yield. In addition,
product 3a could be oxidized by m-CPBA to afford sulfone 7a
in 97% isolated yield.
In conclusion, we have developed an efficient iron-catalyzed
thiolation and selenylation of cycloalkyl hydroperoxides via C−
a
Scheme 4. Scope of Selenylation
a
Reaction conditions: Fe(OTs)3 (3 mol %), 1 (0.2 mmol, 1.0 equiv), 5a (0.16 mmol, 0.8 equiv), and MeOH (2.0 mL), at room temperature, under
b
N2, for 12 h, isolated yield. Fe(OTf)2 was used as the catalyst.
C
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Scheme 6. Mechanism Studies
Scheme 7. Plausible Mechanism
shift (δ = ppm), multiplicity (s = singlet, d = doublet, t = triplet, m =
multiplet, dd = double doublet, td = triple doublets etc.), integration,
coupling constant (Hz), and assignment. High-resolution mass
spectrometry (HRMS) was obtained on WATERS I-Class VION
IMS Q-Tof. The melting points were measured using open glass
capillaries in an SGW X-4A apparatus. IR spectra were recorded on a
Bruker Tensor 27 spectrometer, and only major peaks are reported
(cm−1).
Starting Materials. All of the cycloalkyl hydroperoxides were
prepared from the corresponding cycloalkyl alcohols according to the
literature on a 3 mmol scale.8 All symmetrical and unsymmetrical
disulfides were purchased from commercial resources or synthesized
according to the literature.11
C bond cleavage. A variety of distal keto-functionalized
thioethers and selenium compounds could be synthesized
with moderate to good yields. Remarkably, no external oxidant
and only some amounts of disulfides were required for this
transformation. Based on the control experiments, a probably
radical pathway was proposed.
EXPERIMENTAL SECTION
■
General Methods. All commercially available reagents and
solvents were used without further purification. All catalytic reactions
were conducted in oven-dried Schlenk tubes. The reactions were
monitored by TLC and visualized using UV light. Column
chromatography was carried out on 200−300 mesh silica gel. 1H
NMR and 13C{1H} NMR spectra were recorded on Bruker Advance
Characterization of Unknown Starting Materials 1. (1-
Hydroperoxycyclopentyl)benzene (1a). Colorless oil (380 mg,
71%). Rf 0.30 (petroleum ether/ethyl acetate = 30:1). 1H NMR
(400 MHz, CDCl3): δ = 7.56−7.01 (m, 6H), 2.20−2.19 (m, 2H),
1.86−1.81 (m, 4H), 1.67−1.66 (m, 2H). 13C{1H} NMR (100 MHz,
III-400 in CDCl3 at room temperature. The H and 13C{1H} NMR
1
chemical shifts are reported in ppm relative to either the CDCl3 peak
(13C) (δ = 77.16 ppm) or tetramethylsilane (1H) (δ = 0 ppm) as an
internal standard. Data of 1H NMR are reported as follows: chemical
D
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CDCl3): δ = 141.7, 127.3, 126.5, 125.5, 94.4, 34.6, 22.7. Spectral data
matched literature values.8
84.5, 34.1, 25.6, 22.0. IR (neat): υmax (cm−1) 3189, 2821, 1678, 754.
HRMS (ESI) m/z: [M + Na]+ calcd for C12H16O2Na, 215.1043;
found, 215.1046.
1-(1-Hydroperoxycyclopentyl)-4-(trifluoromethyl)benzene (1b).
Colorless oil (501 mg, 68%). Rf 0.3 (petroleum ether/ethyl acetate
= 30:1). 1H NMR (400 MHz, CDCl3): δ = 7.64−7.56 (m, 4H), 7.43
(s, 1H), 2.34−2.28 (m, 2H), 2.00−1.89 (m, 4H), 1.84−1.79 (m, 2H).
13C{1H} NMR (100 MHz, CDCl3): δ = 147.1, 129.7 (q, J = 32.2 Hz),
126.7, 125.3 (q, J = 3.7 Hz), 124.1 (q, J = 270.3 Hz), 95.1, 36.0, 23.9.
IR (neat): υmax (cm−1) 3431, 2897, 1651, 1399, 776. HRMS (ESI) m/
z: [M + Na]+ calcd for C12H13F3O2Na, 269.0760; found, 269.0760.
1-Fluoro-3-(1-hydroperoxycyclopentyl)benzene (1c). Colorless
oil (400 mg, 68%). Rf 0.30 (petroleum ether/ethyl acetate = 30:1).
1H NMR (400 MHz, CDCl3): δ = 7.37 (s, 1H), 7.32 (t, J = 6.0 Hz,
1H), 7.25 (d, J = 8.0 Hz, 1H), 7.19−7.16 (m, 1H), 7.03−6.95 (m,
1H), 2.36−2.22 (m, 2H), 1.98−1.85 (m, 4H), 1.83−1.73 (m, 2H).
13C{1H} NMR (100 MHz, CDCl3): δ = 163.0 (d, J = 244.2 Hz),
145.7 (d, J = 6.6 Hz), 129.9 (d, J = 8.1 Hz), 121.9 (d, J = 2.8 Hz),
114.4 (d, J = 21.0 Hz), 113.6 (d J = 21.8 Hz), 95.1 (d, J = 1.7 Hz),
35.9, 23.8. IR (neat): υmax (cm−1) 3257, 2751, 1701, 1394, 796.
HRMS (ESI) m/z: [M + Na]+ calcd for C11H13FO2Na, 219.0792;
found, 219.0793.
1-(1-Hydroperoxycyclopentyl)-2-methylbenzene (1d). White
solid (420 mg, 73%). m.p. 31−32 °C, Rf 0.30 (petroleum ether/
ethyl acetate = 30:1). 1H NMR (400 MHz, CDCl3): δ = 7.42 (d, J =
7.6 Hz, 1H), 7.23−7.14 (m, 3H), 7.06 (s, 1H), 2.53 (s, 3H), 2.47−
2.38 (m, 2H), 2.11−2.00 (m, 2H), 1.87−1.84 (m, 2H), 1.73−1.69
(m, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ = 139.6, 137.5, 132.4,
128.2, 127.9, 125.4, 96.4, 35.4, 23.9, 21.5. IR (neat): υmax (cm−1)
3257, 2692, 1683, 1298, 767. HRMS (ESI) m/z: [M + Na]+ calcd for
C12H16O2Na, 215.1043; found, 215.1041.
2-(1-Hydroperoxycyclopentyl)naphthalene (1e). White solid (445
mg, 65%). m.p. 55−57 °C, Rf 0.30 (petroleum ether/ethyl acetate =
20:1). 1H NMR (400 MHz, CDCl3): δ = 7.92 (s, 1H), 7.90−7.82 (m,
3H), 7.61 (dd, J = 8.4, 1.6 Hz, 1H), 7.55−7.45 (m, 2H), 7.37 (s, 1H),
2.48−2.35 (m, 2H), 2.12−2.07 (m, 2H), 2.01−1.93 (m, 2H), 1.87−
1.82 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ = 140.1, 133.1,
132.8, 128.3, 128.2, 127.6, 126.3, 126.1, 125.3, 124.8, 95.7, 35.8, 24.0.
IR (neat): υmax(cm−1) 3389, 2733, 1701, 1414, 750, 732. HRMS
(ESI) m/z: [M + Na]+ calcd for C15H16O2Na, 251.1043; found,
251.1045.
1-Hydroperoxy-1-pentylcyclopentane (1f). Colorless oil (305 mg,
59%). Rf 0.20 (petroleum ether/ethyl acetate = 20:1). 1H NMR (400
MHz, CDCl3): δ = 7.32 (s, 1H), 1.84−1.80 (m, 2H), 1.72−1.65 (m,
4H), 1.58−1.54 (m, 2H), 1.51−1.44 (m, 2H), 1.39−1.25 (m, 6H),
0.89 (t, J = 6.8 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 94.9,
36.3, 34.9, 32.4, 24.6, 24.2, 22.7, 14.1. HRMS (ESI) m/z: [M + K]+
calcd for C10H20O2K, 211.1095; found, 211.1092.
1-Hydroperoxy-1-phenylcycloheptane (1j). Colorless oil (340 mg,
55%). Rf 0.30 (petroleum ether/ethyl acetate = 30:1). 1H NMR (400
MHz, CDCl3): δ = 7.46 (dd, J = 8.0, 1.2 Hz, 2H), 7.36 (t, J = 8.4 Hz,
2H), 7.27 (t, J = 8.0 Hz, 1H), 7.23 (s, 1H), 2.18−1.99 (m, 4H),
1.84−1.74 (m, 2H), 1.70−1.63 (m, 2H), 1.60−1.52 (m, 4H).
13C{1H} NMR (100 MHz, CDCl3): δ = 145.9, 128.6, 127.3, 125.6,
89.2, 37.7, 30.1, 22.7. IR (neat): υmax (cm−1) 3409, 2922, 1445, 1009,
753, 699. HRMS (ESI) m/z: [M + Na]+ calcd for C13H18O2Na,
229.1199; found, 229.1204.
1-Hydroperoxy-1-phenylcyclooctane (1k). Colorless oil (343 mg,
52%). Rf 0.30 (petroleum ether/ethyl acetate = 30:1). 1H NMR (400
MHz, CDCl3): δ = 7.52−7.47 (m, 2 H), 7.42−7.31 (m, 2H), 7.30−
7.21 (m, 1H), 7.16 (s, 1H), 2.25−2.17 (m, 1H), 2.09−1.91 (m, 3H),
1.74−1.63 (m, 5H), 1.59−1.47 (m, 5H). 13C{1H} NMR (100 MHz,
CDCl3): δ = 143.5, 127.6, 126.4, 125.1, 88.1, 30.5, 27.4, 24.1, 20.8. IR
(neat): υmax (cm−1) 3362, 2920, 1683, 1445, 756, 699. HRMS (ESI)
m/z: [M + Na]+ calcd for C14H20O2Na, 243.1356; found, 243.1355.
1-Hydroperoxy-1-phenylcyclododecane (1l). White solid (410
mg, 49%). m.p. 101−102 °C, Rf 0.30 (petroleum ether/ethyl acetate =
30:1).1H NMR (400 MHz, CDCl3): δ = 7.36 (dd, J = 8.2, 1.0 Hz,
2H), 7.30 (t, J = 7.6 Hz, 2H), 7.24−7.18 (m, 1H), 7.07 (s, 1H),
2.03−1.88 (m, 2H), 1.63−1.57 (m, 2H), 1.30 (s, 16H), 1.11 (s, 2H).
13C{1H} NMR (100 MHz, CDCl3): δ = 144.2, 128.5, 127.3, 125.8,
88.6, 30.3, 26.3, 26.2, 22.3, 22.0, 19.4. IR (neat): υmax (cm−1) 3332,
2897, 1632, 1396, 765, 700, 685. HRMS (ESI) m/z: [M + Na]+ calcd
for C18H28O2Na, 299.1982; found, 299.1983.
(1-Hydroperoxy-2-methylcyclopentyl)benzene (1m). Colorless oil
1
(375 mg, 65%). Rf 0.30 (petroleum ether/ethyl acetate = 30:1). H
NMR (400 MHz, CDCl3): δ = 7.45−7.35 (m, 4H), 7.34−7.27 (m,
1H), 7.22 (s, 1H), 2.48−2.42 (m, 1H), 2.30−2.09 (m, 3H), 1.98−
1.81 (m, 2H), 1.40−1.33 (m, 1H), 0.55 (d, J = 7.2 Hz, 3H). 13C{1H}
NMR (100 MHz, CDCl3): δ = 140.5, 128.4, 127.6, 127.2, 98.7, 41.5,
32.3, 30.0, 21.2, 18.7. IR (neat): υmax (cm−1) 3398, 2965, 1603, 1456,
788. HRMS (ESI) m/z: [M + Na]+ calcd for C12H16O2Na, 215.1043;
found, 215.1045.
(2-Heptyl-1-hydroperoxycyclopentyl)benzene (1n). Colorless oil
1
(447 mg, 54%). Rf 0.30 (petroleum ether/ethyl acetate = 30:1). H
NMR (400 MHz, CDCl3): δ = 7.44−7.35 (m, 4H), 7.34−7.28 (m,
1H), 7.21 (s, 1H), 2.50−2.41 (m, 1H), 2.23−2.17 (m, 1H), 2.11−
2.01 (m, 1H), 2.00−1.78 (m, 3H), 1.47−1.39 (m, 1H), 1.28−1.19
(m, 4H), 1.17−1.01 (m, 7H), 0.84 (t, J = 7.2 Hz, 3H), 0.68−0.58 (m,
1H). 13C{1H} NMR (100 MHz, CDCl3): δ = 140.7, 128.5, 127.6,
127.2, 98.6, 47.1, 32.3, 31.9, 31.2, 29.7, 29.5, 29.3, 27.9, 22.7, 21.5,
14.2. IR (neat): υmax (cm−1) 3396, 2955, 1719, 1449, 760, 700.
HRMS (ESI) m/z: [M + Na]+ calcd for C18H28O2Na, 299.1982;
found, 299.1979.
(3-(1-Hydroperoxycyclopentyl)propyl)benzene (1g). Colorless oil
1
(363 mg, 55%). Rf 0.30 (petroleum ether/ethyl acetate = 30:1). H
(1-Hydroperoxy-2-methylcyclohexyl)benzene (1o). Colorless oil
1
NMR (400 MHz, CDCl3): δ = 7.21 (t, J = 7.2 Hz, 2H), 7.14−7.09
(m, 4H), 2.58−2.55 (m, 2H), 1.82−1.71 (m, 2H), 1.67−1.59 (m,
6H), 1.52−1.45 (m, 2H), 1.42−1.34 (m, 2H). 13C{1H} NMR (100
MHz, CDCl3): δ = 142.5, 128.4, 128.3, 125.8, 94.7, 36.2, 35.7, 34.9,
26.2, 24.5. IR (neat): υmax (cm−1) 3410, 2902, 1703, 1284, 749.
HRMS (ESI) m/z: [M + Na]+ calcd for C14H20O2Na, 243.1356;
found, 243.1351.
(321 mg, 52%). Rf 0.30 (petroleum ether/ethyl acetate = 30:1). H
NMR (400 MHz, CDCl3): δ = 7.43−7.37 (m, 4H), 7.3−7.27 (m,
1H), 6.92 (s, 1H), 2.31−2.27 (m, 1H), 2.10−2.0 (m, 3H), 1.84−1.77
(m, 1H), 1.73−1.68 (m, 1H), 1.54−1.63 (m, 2H), 1.39−1.34 (m,
1H), 0.65 (d, J = 7.2 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ
= 144.1, 128.7, 127.6, 126.1, 87.8, 37.1, 28.4, 25.1, 21.5, 19.7, 15.9. IR
(neat): υmax (cm−1) 3424, 2936, 1691, 1446, 755. HRMS (ESI) m/z:
[M + Na]+ calcd for C13H18O2Na, 229.1199; found, 229.1205.
(1S,2R,4R)-2-Hydroperoxy-2-phenylbicyclo[2.2.1]heptane (1p).
Colorless oil (422 mg, 69%) Rf 0.3 (petroleum ether/ethyl acetate
= 30:1). 1H NMR (400 MHz, CDCl3): δ = 7.46 (d, J = 7.6 Hz, 2H),
7.40−7.35 (m, 2H), 7.32−7.29 (m, 1H), 6.98 (br, 1H), 2.73 (s, 1H),
2.42 (s, 1H), 2.10−2.01 (m, 2H), 1.91 (d, J = 14 Hz, 1H), 1.55−1.43
(m, 2H), 1.31 (d, J = 9.6 Hz, 1H), 1.17−1.00 (m, 2H). 13C{1H}
NMR (100 MHz, CDCl3): δ = 140.2, 128.6, 128.2, 127.8, 94.8, 44.3,
40.0, 36.9, 36.6, 29.0, 23.8. IR (neat): υmax (cm−1) 3449, 2958, 1449,
1324, 758, 700. HRMS (ESI) m/z: [M + Na]+ calcd for C13H16O2Na,
227.1043; found, 227.1046.
1-Hydroperoxy-1-methoxycyclopentane (1h). Colorless oil (257
1
mg, 65%). Rf 0.30 (petroleum ether/ethyl acetate = 30:1). H NMR
(400 MHz, CDCl3): δ = 8.27 (br, 1H), 3.32 (s, 3H), 2.01−1.90 (m,
2H), 1.81−1.71 (m, 2H), 1.71−1.64 (m, 4H). 13C{1H} NMR (100
MHz, CDCl3): δ = 117.6, 50.5, 33.4, 23.8. IR (neat): υmax (cm−1)
3420, 2957, 1711, 1172, 751. HRMS (ESI) m/z: [M + H]+ calcd for
C6H13O3, 133.0859; found, 133.0858.
(1-Hydroperoxycyclohexyl)benzene (1i). Colorless oil (351 mg,
61%). Rf 0.30 (petroleum ether/ethyl acetate = 30:1). 1H NMR (400
MHz, CDCl3): δ = 7.50 (dd, J = 7.2, 0.4 Hz, 2H), 7.40 (t, J = 7.6 Hz,
2H), 7.30 (t, J = 7.2 Hz, 1H), 7.13 (s, 1H), 2.18−2.15 (m, 2H),
1.86−1.72 (m, 5H), 1.62−1.59 (m, 2H), 1.38−1.26 (m, 1H).
13C{1H} NMR (100 MHz, CDCl3): δ = 144.8, 128.6, 127.5, 125.7,
2-(1-Hydroperoxycyclopentyl)thiophene (1q). Colorless oil (331
1
mg, 65%). Rf 0.3 (petroleum ether/ethyl acetate = 30:1). H NMR
E
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(400 MHz, CDCl3): δ = 7.51 (s, 1H), 7.18 (d, J = 5.2 Hz, 1H), 6.96
(d, J = 3.6 Hz, 1H), 6.89 (t, J = 4.8 Hz, 1H), 2.31−2.20 (m, 2H),
1.99−1.88 (m, 2H), 1.85−1.76 (m, 2H), 1.73−1.68 (m, 2H).
13C{1H} NMR (100 MHz, CDCl3): δ = 146.1, 125.7, 124.1, 123.9,
peroxide 1a (0.2 mmol, 1.0 equiv) in MeOH (2 mL) was added with
a syringe under nitrogen. The tube was then sealed, and the mixture
was stirred at room temperature for 12 h. After that, the resulting
mixture was concentrated in vacuo to remove solvents. The crude
product was purified by flash column chromatography on silica gel
(EtOAc/petroleum ether = 1:50) to give product 3a in 31% yield.
Characterization of Products 3, 4, 6, and 7. 1-Phenyl-5-
(phenylthio)pentan-1-one (3a). White solid (39.7 mg, 74%); m.p.
92.0, 36.0, 22.8. IR (neat): υmax (cm−1) 3128, 2697, 1414, 750. HRMS
(ESI) m/z: [M + Na]+ calcd for C9H12O2SNa, 207.0450; found,
207.0452.
General Procedure for the Reaction of Cycloalkyl Hydro-
peroxides 1 with Disulfide 2. A 10 mL oven-dried Schlenk tube
equipped with a magnetic stir bar was charged with Fe(OTs)3 (3 mol
%) and disulfide 2 (0.16 mmol, 0.8 equiv). Then, the tube was
evacuated and backfilled with nitrogen three times. Subsequently,
solution of cycloalkyl hydroperoxide 1 (0.2 mmol, 1.0 equiv) in
MeOH (2 mL) was added with a syringe under nitrogen. The tube
was then sealed, and the mixture was stirred at a specified temperature
for 12 h. After that, the resulting mixture was concentrated in vacuo to
remove solvents. The crude product was purified by flash column
chromatography on silica gel (EtOAc/petroleum ether = 1:50) to give
products 3 and 4 in yields listed in Schemes 2 and 3, respectively.
General Procedure for the Reaction of Cycloalkyl Hydro-
peroxides 1 with Diselenide 5. A 10 mL oven-dried Schlenk tube
equipped with a magnetic stir bar was charged with a catalyst (3 mol
%) and diselenide 5 (0.16 mmol, 0.8 equiv). Then, the tube was
evacuated and backfilled with nitrogen three times. Subsequently,
solution of cycloalkyl hydroperoxide 1 (0.2 mmol, 1.0 equiv) in
MeOH (2 mL) was added with a syringe under nitrogen. The tube
was then sealed, and the mixture was stirred at a specified temperature
for 12 h. After that, the resulting mixture was concentrated in vacuo to
remove solvents. The crude product was purified by flash column
chromatography on silica gel (EtOAc/petroleum ether = 1:50) to give
product 6 in yields listed in Scheme 4.
1
86−87 °C, Rf 0.21 (petroleum ether/ethyl acetate = 50:1). H NMR
(400 MHz, CDCl3): δ = 7.87−7.85 (m, 2H), 7.49−7.45 (m, 1H),
7.39−7.35 (m, 2H), 7.29−7.15 (m, 4H), 7.12−7.04 (m, 1H), 2.92−
2.87 (m, 4H), 1.82−1.77 (m, 2H), 1.70−1.63 (m, 2H). 13C{1H}
NMR (100 MHz, CDCl3): δ = 199.9, 137.0, 136.7, 133.1, 129.2,
129.0, 128.7, 128.1, 125.9, 38.1, 33.5, 28.9, 23.4 ppm; IR (neat): υmax
2929, 2857, 1684, 1579, 1275, 1179, 1095, 1021, 763, 749, 687 cm−1.
HRMS (ESI) m/z: [M + Na]+ calcd for C17H18OSNa, 293.0971;
found, 293.0964.
5-(Phenylthio)-1-(4-(trifluoromethyl)phenyl)pentan-1-one (3b).
White solid (43.3 mg, 64%); m.p. 106−107 °C, Rf 0.17 (petroleum
1
ether/ethyl acetate = 50:1). H NMR (400 MHz, CDCl3): δ = 7.96
(d, J = 8.0 Hz, 2H), 7.65 (d, J = 8.2 Hz, 2H), 7.26−7.19 (m, 4H),
7.11−7.08 (m, 1H), 2.95−2.88 (m, 4H), 1.87−1.79 (m, 2H), 1.70−
1.63 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ = 198.9, 139.6,
136.6, 134.4 (q, J = 32.8 Hz), 129.3, 129.0, 128.5, 126.4 (q, J = 271
Hz), 126.1, 125.8 (q, J = 3.7 Hz), 38.4, 33.6, 28.8, 23.2 ppm; IR
(neat): υmax 3057, 2950, 1685, 1409, 1329, 1228, 1123, 838, 740, 690
cm−1 HRMS (ESI) m/z: [M + Na]+ calcd for C18H17F3OSNa,
361.0844; found, 361.0850.
1-(3-Fluorophenyl)-5-(phenylthio)pentan-1-one (3c). White solid
(45.6 mg, 79%); m.p. 70−71 °C, Rf 0.18 (petroleum ether/ethyl
1
acetate = 50:1). H NMR (400 MHz, CDCl3): δ = 7.65−7.63 (m,
1H), 7.56−7.53 (m, 1H), 7.38−7.33 (m, 1H), 7.26−7.18 (m, 5H),
7.11−7.08 (m, 1H), 2.89 (t, J = 7.2 Hz, 2H), 2.88 (t, J = 7.2 Hz, 2H),
1.85−1.78 (m, 2H), 1.69−1.63 (m, 2H). 13C{1H} NMR (100 MHz,
CDCl3): δ = 198.6 (d, J = 2.0 Hz), 163.0 (d, J = 247.9 Hz), 139.1 (d,
J = 6.1 Hz), 136.6, 130.4 (d, J = 7.6 Hz), 129.3, 129.0, 126.0, 123.9
(d, J = 3.0 Hz), 120.1 (d, J = 21.5 Hz), 114.9 (d, J = 22.2 Hz), 38.3,
33.5, 28.8, 23.3 ppm; IR (neat): υmax 3067, 2949, 2866, 1685, 1586,
1480, 1440, 1244, 874, 749, 684 cm−1 HRMS (ESI) m/z: [M + Na]+
calcd for C17H17FOSNa, 311.0876; found, 311.0871.
Large Scale Reaction of Cycloalkyl Hydroperoxide 1a with
Disulfide 2a. To an oven-dried 200 mL Schlenk tube containing a
magnetic stir bar were added Fe(OTs)3 (3 mol %) and diphenyl
disulfide 2a (4 mmol, 0.8 equiv). Then, the tube was evacuated and
backfilled with nitrogen three times. Subsequently, solution of
cycloalkanol hydroperoxide 1a (5 mmol, 1.0 equiv) in MeOH (50
mL) was added with a syringe under nitrogen. The tube was then
sealed, and the mixture was stirred at room temperature for 12 h.
After that, the resulting mixture was concentrated in vacuo to remove
solvents. The crude product was purified by flash column
chromatography on silica gel (EtOAc/petroleum ether = 1:50) to
give product 3a as a white solid (0.95 g, 70%).
Oxidation of Compound 3a. The following procedure was
adapted from the literature.7 To a solution of 3a (54.1 mg, 0.2 mmol)
in DCM (15 mL), m-CPBA was added dropwise (85wt %, 122 mg,
0.6 mmol) at 0 °C. Then, the mixture was stirred at room temperature
for 2 h. After the reaction was completed, saturated NaHCO3 aqueous
solution (10 mL) was slowly added. The mixture was extracted with
DCM (10 mL × 3). The combined organic layers were washed with
brine (20 mL) and dried and concentrated to give a crude residue,
which was purified by flash chromatography on silica gel (EtOAc/
petroleum ether = 1:5) to afford product 7a (58.0 mg, 97%).
Radical Trapping Experiment. A 10 mL oven-dried Schlenk
tube equipped with a magnetic stir bar was charged with Fe(OTs)3 (3
mol %), diphenyl disulfide 2a (0.16 mmol, 0.8 equiv), and TEMPO
(0.4 mmol, 2 equiv). Then, the tube was evacuated and backfilled
with nitrogen three times. Subsequently, solution of cyclopentyl
hydroperoxide 1a (0.2 mmol, 1.0 equiv) in MeOH (2 mL) was added
with a syringe under nitrogen. The tube was then sealed, and the
mixture was stirred at room temperature for 12 h. After that, the
resulting mixture was concentrated in vacuo to remove solvents. The
crude product was purified by flash column chromatography on silica
gel (EtOAc/petroleum ether = 1:50) to give product 8a in 79% yield,
and no 3a was observed.
5-(Phenylthio)-1-(o-tolyl)pentan-1-one (3d). Colorless oil (39.2
1
mg, 69%); Rf 0.16 (petroleum ether/ethyl acetate = 50:1). H NMR
(400 MHz, CDCl3): δ = 7.52 (d, J = 7.4 Hz, 1H), 7.30−7.15 (m, 7H),
7.09 (t, J = 7.2 Hz, 1H), 2.88 (t, J = 7.2 Hz, 2H), 2.83 (t, J = 7.2 Hz,
2H), 2.39 (s, 3H), 1.81−1.74 (m, 2H), 1.67−1.60 (m, 2H). 13C{1H}
NMR (100 MHz, CDCl3): δ = 204.2, 138.10, 138.05, 136.7, 132.1,
131.3, 129.2, 129.0, 128.4, 126.0, 125.8, 41.1, 33.6, 28.9, 23.6, 21.4
ppm; IR (neat): υmax 3059, 2927, 1682, 1480, 1263, 1217, 1091, 1025,
747, 691 cm−1 HRMS (ESI) m/z: [M + Na]+ calcd for C18H20OSNa,
307.1127; found, 307.1130.
1-(Naphthalen-2-yl)-5-(phenylthio)pentan-1-one (3e). White
solid (34 mg, 53%); m.p. 82−83 °C, Rf 0.12 (petroleum ether/
ethyl acetate = 50:1). 1H NMR (400 MHz, CDCl3): δ = 8.39 (s, 1H),
7.96−7.80 (m, 4H), 7.54−7.48 (m, 2H), 7.28−7.17 (m, 4H), 7.14−
7.10 (m, 1H), 3.06 (t, J = 7.2 Hz, 2H), 2.93 (t, J = 7.2 Hz, 2H), 1.90−
1.86 (m, 2H), 1.74−1.70 (m, 2H). 13C{1H} NMR (100 MHz,
CDCl3): δ = 200.0 136.7, 135.7, 134.4, 132.7, 129.8, 129.7, 129.3,
129.0, 128.60, 128.56, 127.9, 126.9, 126.0, 124.0, 38.2, 33.6, 28.9,
23.7. ppm; IR (neat): υmax 3054, 2945, 2706, 1682, 1437, 1276, 750,
689 cm−1 HRMS (ESI) m/z: [M + Na]+ calcd for C21H20OSNa,
343.1127; found, 343.1118.
1-(Phenylthio)decan-5-one (3f). Colorless oil (36.4 mg, 69%); Rf
1
0.40 (petroleum ether/ethyl acetate = 50:1). H NMR (400 MHz,
CDCl3): δ = 7.26−7.18 (m, 4H), 7.12−7.10 (m, 1H), 2.84 (t, J = 7.2
Hz, 2H), 2.35−2.28 (m, 4H), 1.64−1.46 (m, 6H), 1.24−1.18 (m,
4H), 0.81 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ =
211.1, 136.7, 129.1, 129.0, 125.9, 42.9, 42.2, 33.5, 31.5, 28.8, 23.7,
23.0, 22.6, 14.1 ppm; IR (neat): υmax 3058, 2929, 2857, 1711, 1584,
1439, 1261, 1091, 1023, 799, 749, 691 cm−1 HRMS (ESI) m/z: [M +
Na]+ calcd for C16H24OSNa, 287.1440; found, 287.1440.
Radical Inhibition Experiment. A 10 mL oven-dried Schlenk
tube equipped with a magnetic stir bar was charged with Fe(OTs)3 (3
mol %), diphenyl disulfide 2a (0.16 mmol, 0.8 equiv), and BHT (0.4
mmol, 2 equiv). Then, the tube was evacuated and backfilled with
nitrogen three times. Subsequently, solution of cyclopentyl hydro-
F
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1-Phenyl-8-(phenylthio)octan-4-one (3g). Colorless oil (42.0 mg,
67%); Rf 0.13 (petroleum ether/ethyl acetate = 50:1). 1H NMR (400
MHz, CDCl3): δ = 7.32−7.25 (m, 5H), 7.21−7.15 (m, 4H), 2.90 (t, J
= 7.2 Hz, 2H), 2.60 (t, J = 7.6 Hz, 2H), 2.40−2.36 (m, 4H), 1.93−
1.85 (m, 2H), 1.71−1.60 (m, 4H). 13C{1H} NMR (100 MHz,
CDCl3): δ = 210.5, 141.7, 136.7, 129.1, 129.0, 128.6, 128.5, 126.1,
125.9, 42.3, 42.0, 35.2, 33.5, 28.8, 25.3, 23.0 ppm; IR (neat): υmax
3059, 2933, 2859, 1709, 1583, 1495, 1479, 1093, 1025, 740, 694 cm−1
HRMS (ESI) m/z: [M + Na]+ calcd for C20H24OSNa, 335.1440;
found, 335.1441.
Methyl 5-(phenylthio)pentanoate (3h). Colorless oil (12.5 mg,
28%); Rf 0.15 (petroleum ether/ethyl acetate = 50:1). 1H NMR (400
MHz, CDCl3): δ = 7.26−7.19 (m, 4H), 7.10 (t, J = 7.2 Hz, 1H), 3.59
(s, 3H), 2.86 (t, J = 7.2 Hz, 2H), 2.26 (t, J = 7.2 Hz, 2H), 1.72−1.58
(m, 4H). 13C{1H} NMR (100 MHz, CDCl3): δ = 173.9, 136.6, 129.3,
129.0, 126.0, 51.7, 33.7, 33.4, 28.7, 24.2 ppm; spectral data match
those previously reported.9c
1-Phenyl-6-(phenylthio)hexan-1-one (3i). Colorless oil (16.0 mg,
28%); Rf 0.28 (petroleum ether/ethyl acetate = 30:1). 1H NMR (400
MHz, CDCl3): δ = 7.88−7.86 (m, 2H), 7.50−7.46 (m, 1H), 7.41−
7.37 (m, 2H), 7.26−7.18 (m, 4H), 7.10−7.07 (m, 1H), 2.89 (t, J =
7.2 Hz, 2H), 2.87 (t, J = 7.2 Hz, 2H), 1.73−1.60 (m, 4H), 1.49−1.42
(m, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ = 200.3, 137.1, 136.9,
133.1, 129.1, 129.0, 128.7, 128.2, 125.9, 38.5, 33.6, 29.1, 28.6, 23.9
ppm; IR (neat): υmax 3059, 2931, 1684, 1282, 749, 690, 656 cm−1
HRMS (ESI) m/z: [M + Na]+ calcd for C18H20OSNa, 307.1127;
found, 307.1122.
1-Phenyl-7-(phenylthio)heptan-1-one (3j). White solid (38.8 mg,
65%); m.p. 87−88 °C, Rf 0.31 (petroleum ether/ethyl acetate = 30:1).
1H NMR (400 MHz, CDCl3): δ = 7.89−7.86 (m, 2H), 7.51−7.45 (m,
1H), 7.42−7.36 (m, 2H), 7.25−7.18 (m, 4H), 7.10−7.07 (m, 1H),
2.89 (t, J = 7.2 Hz, 2H), 2.85 (t, J = 7.2 Hz, 2H), 1.70−1.56 (m, 4H),
1.45−1.32 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3): δ = 200.5,
137.1, 137.0, 133.1, 128.99, 128.96, 128.7, 128.2, 125.8, 38.6, 33.6,
29.1, 29.0, 28.8, 24.3 ppm; IR (neat): υmax 3054, 2931, 1685, 752,
729, 687 cm−1 HRMS (ESI) m/z: [M + Na]+ calcd for C19H22OSNa,
321.1284; found, 321.1278.
(400 MHz, CDCl3): δ = 7.87−7.85 (m, 2H), 7.50−7.46 (m, 1H),
7.40−7.30 (m, 4H), 7.21−7.11 (m, 3H), 3.05−3.00 (m, 1H), 2.90−
2.86 (m, 2H), 1.87−1.83 (m, 2H), 1.59−1.53 (m, 4H), 1.39−1.38
(m, 2H), 1.23−1.19 (m, 8H), 0.80 (t, J = 7.2Hz, 3H). 13C{1H} NMR
(100 MHz, CDCl3): δ = 200.1, 137.1, 135.7, 133.1, 132.1, 128.9,
128.7, 128.2, 126.7, 49.2, 38.5, 34.6, 34.2, 32.0, 29.6, 29.3, 26.9, 22.8,
21.6, 14.3 ppm; IR (neat): υmax S3059, 2925, 2853, 1685, 1582, 1449,
1221, 1090, 1023, 799, 748, 690 cm−1 HRMS (ESI) m/z: [M + Na]+
calcd for C24H32OSNa, 391.2066; found, 391.2065.
1-Phenyl-6-(phenylthio)heptan-1-one (3o). Colorless oil (41.8
1
mg, 70%); Rf 0.20 (petroleum ether/ethyl acetate = 80:1). H NMR
(400 MHz, CDCl3): δ = 7.88−7.86 (m, 2H), 7.50−7.46 (m, 1H),
7.40−7.36 (m, 2H), 7.32−7.30 (m, 2H), 7.22−7.12 (m, 3H), 3.18−
3.13 (m, 1H), 2.89 (t, J = 7.2 Hz, 2H), 1.68−1.48 (m, 6H), 1.20 (d, J
= 6.8 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 200.3, 137.1,
135.3, 133.1, 132.1, 128.9, 128.7, 128.1, 126.8, 43.3, 38.5, 36.5, 26.8,
24.1, 21.3 ppm; IR (neat): υmax 3058, 2928, 2859, 1683, 1581, 1447,
1260, 1091, 1023, 799, 748, 690 cm−1 HRMS (ESI) m/z: [M + Na]+
calcd for C19H22OSNa, 321.1284; found, 321.1286.
1-Phenyl-2-(3-(phenylthio)cyclopentyl)ethan-1-one (3p). Color-
less oil (41.6 mg, 70% d.r. = 1.82:1); Rf 0.14 (petroleum ether/ethyl
1
acetate = 30:1). H NMR (400 MHz, CDCl3): δ = 7.88−7.85 (m,
2H), 7.48 (t, J = 7.4 Hz, 1H), 7.38 (t, J = 7.6 Hz, 2H), 7.28−7.26 (m,
2H), 7.21−7.17 (m, 2H), 7.10 (t, J = 7.2 Hz, 1H), 3.65−3.62 (m,
1H), 3.01 (d, J = 6.8 Hz, 0.71H), 2.94 (d, J = 7.2 Hz, 1.29H), 2.72−
2.60 (m, 0.63H), 2.51−2.36 (m, 0.73H), 2.17−1.87 (m, 2.74H),
1.71−1.58 (m, 1.30H), 1.47−1.36 (m, 0.41H), 1.28−1.17 (m,
1.45H). 13C{1H} NMR (100 MHz, CDCl3): δ = 198.6, 198.5,
135.97, 135.93, 135.9, 135.8, 131.98, 131.97, 129.0, 128.9, 127.8,
127.7, 127.6, 127.02, 127.00, 124.98, 124.97, 44.1, 43.7, 43.3, 39.4,
38.9, 34.3, 33.4, 32.1, 32.0, 31.1, 30.4 ppm; IR (neat): υmax 3057,
2950, 2860, 1682, 1582, 1479, 1445, 1211, 1092, 1024, 798, 749, 690
cm−1 HRMS (ESI) m/z: [M + Na]+ calcd for C19H20OSNa,
319.1127; found, 319.1133.
5-(Phenylthio)-1-(thiophen-2-yl)pentan-1-one (3q). Colorless oil
1
(24.3 mg, 44%) Rf 0.18 (petroleum ether/ethyl acetate = 30:1). H
NMR (400 MHz, CDCl3): δ = 7.62 (dd, J = 4.0, 1.2 Hz, 1H), 7.55
(dd, J = 4.8, 1.2 Hz, 1H), 7.26−7.19 (m, 4H), 7.12−7.04 (m, 2H),
2.89 (t, J = 7.2 Hz, 2H), 2.84 (t, J = 7.2 Hz, 2H), 1.86−1.78 (m, 2H),
1.70−1.63 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ = 191.8,
143.2, 135.5, 132.5, 130.7, 128.1, 127.9, 127.1, 124.8, 37.7, 32.4, 27.7,
22.7 ppm; IR (neat): υmax 3065, 2935, 1686, 1448, 1191, 801, 750,
692 cm−1 HRMS (ESI) m/z: [M + Na]+ calcd for C15H16OS2Na,
299.0535; found, 299.0534.
1-Phenyl-5-(p-tolylthio)pentan-1-one (4a). White solid (40.3 mg,
71%); m.p. 63−64 °C, Rf 0.22 (petroleum ether/ethyl acetate = 50:1).
1H NMR (400 MHz, CDCl3): δ = 7.87−7.84 (m, 2H), 7.49−7.45 (m,
1H), 7.39−7.35 (m, 2H), 7.18−7.16 (m, 2H), 7.02−7.00 (m, 2H),
2.89 (t, J = 7.2 Hz, 2H), 2.84 (t, J = 7.2 Hz, 2H), 2.23 (s, 3H), 1.81−
1.75 (m, 2H), 1.66−1.60 (m, 2H). 13C{1H} NMR (100 MHz,
CDCl3): δ = 200.0, 137.0, 136.2, 133.1, 132.8, 130.1, 129.8, 128.7,
128.1, 38.1, 34.3, 29.0, 23.4, 21.1 ppm; IR (neat): υmax 3055, 2914,
1683, 1491, 1280, 1241, 798, 688 cm−1 HRMS (ESI) m/z: [M + Na]+
calcd for C18H20OSNa, 307.1127; found, 307.1122.
1-Phenyl-8-(phenylthio)octan-1-one (3k). Colorless oil (33 mg,
49%); Rf 0.21 (petroleum ether/ethyl acetate = 30:1). 1H NMR (400
MHz, CDCl3): δ = 7.90−7.87 (m, 2H), 7.48−7.40 (m, 1H), 7.38−
7.37 (m, 2H), 7.26−7.18 (m, 4H), 7.10−7.08 (m, 1H), 2.88 (t, J =
7.2 Hz, 2H), 2.84 (t, J = 7.2 Hz, 2H), 1.68−1.53 (m, 4H), 1.39−1.28
(m, 6H). 13C{1H} NMR (100 MHz, CDCl3): δ = 200.6, 137.13,
137.05, 133.0, 129.0, 128.9, 128.7, 128.2, 125.8, 38.7, 33.6, 29.3,
29.19, 29.15, 28.8, 24.4. ppm; IR (neat): υmax 3058, 2928, 1684, 1409,
1261, 1091, 1023, 745, 690, 657 cm−1 HRMS (ESI) m/z: [M + Na]+
calcd for C20H24OSNa, 335.1440; found, 335.1442.
1-Phenyl-12-(phenylthio)dodecan-1-one (3l). White solid (59.0
mg, 80%); m.p. 38−39 °C, Rf 0.27 (petroleum ether/ethyl acetate =
1
30:1). H NMR (400 MHz, CDCl3): δ = 7.89−7.87 (m, 2H), 7.49−
7.45 (m, 1H), 7.39−7.36 (m, 2H), 7.25−7.17 (m, 4H), 7.09−7.06
(m, 1H), 2.88 (t, J = 7.2 Hz, 2H), 2.83 (t, J = 7.2 Hz, 2H), 1.70−1.63
(m, 2H), 1.58−1.54 (m, 2H), 1.33−1.19 (m, 14H). 13C{1H} NMR
(100 MHz, CDCl3): δ = 200.7, 137.14, 137.12, 133.0, 128.9, 128.8,
128.7, 128.2, 125.7, 38.7, 33.6, 29.63, 29.58, 29.5, 29.3, 29.2, 29.0,
24.5. ppm; IR (neat): υmax 3056, 2918, 2849, 1680, 1466, 753, 688,
659 cm−1 HRMS (ESI) m/z: [M + H]+ calcd for C24H33OS,
369.2247; found, 369.2250.
5-((4-(tert-Butyl)phenyl)thio)-1-phenylpentan-1-one (4b). White
solid (48.9 mg, 75%); m.p. 68−69 °C, Rf 0.32 (petroleum ether/ethyl
1
acetate = 50:1). H NMR (400 MHz, CDCl3): δ = 7.95−7.93 (m,
2H), 7.58−7.54 (m, 1H), 7.48−7.44 (m, 2H), 7.32−7.26 (m, 4H),
2.99 (t, J = 7.2 Hz, 2H), 2.94 (t, J = 7.2 Hz, 2H), 1.92−1.85 (m, 2H),
1.77−1.70 (m, 2H), 1.30 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3):
δ = 200.0, 149.3, 137.1, 133.1, 133.0, 129.5, 128.7, 128.2, 126.1, 38.2,
34.6, 34.0, 31.4, 29.0, 23.5 ppm; IR (neat): υmax 3049, 2954, 1683,
1447, 1276, 750, 689, 657, 541 cm−1 HRMS (ESI) m/z: [M + Na]+
calcd for C21H26OSNa, 349.1597; found, 349.1593.
1-Phenyl-5-(phenylthio)hexan-1-one (3m). Colorless oil (44.4
1
mg, 78%); Rf 0.16 (petroleum ether/ethyl acetate = 50:1). H NMR
(400 MHz, CDCl3): δ = 7.88−7.85 (m, 2H), 7.48−7.46 (m, 1H),
7.40−7.31 (m, 4H), 7.23−7.14 (m, 3H), 3.18−3.17 (m, 1H), 2.89 (t,
J = 7.2 Hz, 2H), 1.87−1.81 (m, 2H), 1.61−1.55 (m, 2H), 1.23 (d, J =
6.8 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 200.0, 137.0,
135.2, 133.1, 132.2, 128.9, 128.7, 128.1, 126.9, 43.3, 38.4, 36.3, 21.9,
21.2 ppm; IR (neat): υmax 3058, 2957, 2925, 1684, 1408, 1222, 1024,
749, 691 cm−1 HRMS (ESI) m/z: [M + Na]+ calcd for C18H20OSNa,
307.1127; found, 307.1129.
5-((4-Methoxyphenyl)thio)-1-phenylpentan-1-one (4c). White
solid (37.2 mg, 62%); m.p. 72−73 °C, Rf 0.30 (petroleum ether/
1
ethyl acetate = 30:1). H NMR (400 MHz, CDCl3): δ = 7.87−7.85
(m, 2H), 7.49−7.46 (m, 1H), 7.39−7.35 (m, 2H), 7.26 (d, J = 8.8 Hz,
2H), 6.76 (d, J = 8.8 Hz, 2H), 3.71 (s, 3H), 2.88 (t, J = 7.2 Hz, 2H),
2.78 (t, J = 7.2 Hz, 2H), 1.82−1.74 (m, 2H), 1.60−1.55 (m, 2H).
1-Phenyl-5-(phenylthio)dodecan-1-one (3n). Colorless oil (30.3
mg, 41%); Rf 0.23 (petroleum ether/ethyl acetate = 100:1). 1H NMR
G
https://doi.org/10.1021/acs.joc.1c01366
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
13C{1H} NMR (100 MHz, CDCl3): δ = 200.0, 159.0, 137.0, 133.3,
133.1, 128.7, 128.1, 126.6, 114.6, 55.4, 38.1, 35.7, 29.0, 23.4 ppm; IR
(neat): υmax 3059, 3003, 1683, 1493, 1280, 1241, 808, 730, 690 cm−1
HRMS (ESI) m/z: [M + Na]+ calcd for C18H20O2SNa, 323.1076;
found, 323.1073.
5-((4-Hydroxyphenyl)thio)-1-phenylpentan-1-one (4d). White
solid (28.6 mg, 50%); m.p. 94−95 °C, Rf 0.20 (petroleum ether/
ethyl acetate = 5:1). 1H NMR (400 MHz, CDCl3): δ = 7.89−7.86 (m,
2H), 7.51−7.47 (m, 1H), 7.41−7.37 (m, 2H), 7.22−7.19 (m, 2H),
6.72−6.70 (m, 2H), 5.50 (s, 1H), 2.90 (t, J = 7.2 Hz, 2H), 2.77 (t, J =
7.2 Hz, 2H), 1.82−1.75 (m, 2H), 1.63−1.55 (m, 2H). 13C{1H} NMR
(100 MHz, CDCl3): δ = 200.7, 155.2, 136.9, 133.6, 133.3, 128.8,
128.2, 126.5, 116.2, 38.2, 35.8, 29.0, 23.4 ppm; IR (neat): υmax 3426,
3059, 2950, 1667, 1496, 1263, 817, 730, 683, 640, 505 cm−1 HRMS
(ESI) m/z: [M + Na]+ calcd for C17H18O2SNa, 309.0920; found,
309.0917.
5-((4-Aminophenyl)thio)-1-phenylpentan-1-one (4e). White solid
(25.7 mg, 45%); m.p. 72−73 °C, Rf 0.21 (petroleum ether/ethyl
acetate = 5:1). 1H NMR (400 MHz, CDCl3): δ = 7.87 (d, J = 7.2 Hz,
2H), 7.48 (t, J = 7.2 Hz, 1H), 7.38 (t, J = 7.2 Hz, 2H), 7.16 (d, J = 8.0
Hz, 2H), 6.54 (d, J = 8.4 Hz, 2H), 3.64 (s, 2H), 2.88 (t, J = 7.2 Hz,
2H), 2.73 (t, J = 7.2 Hz, 2H), 1.81−1.73 (m, 2H), 1.61−1.56 (m,
2H). 13C{1H} NMR (100 MHz, CDCl3): δ = 200.1, 146.0, 137.0,
134.1, 133.1, 128.7, 128.2, 123.4, 115.7, 38.2, 36.3, 29.1, 23.4 ppm; IR
(neat): υmax 3457, 3221, 3063, 2931, 2859, 1678, 596, 1494, 1448,
1276, 1219, 972, 821, 750, 690 cm−1 HRMS (ESI) m/z: [M + Na]+
calcd for C17H19NOSNa, 308.1080; found, 308.1082.
NMR (400 MHz, CDCl3): δ = 7.85 (d, J = 8.0 Hz, 2H), 7.47 (t, J =
6.8 Hz, 1H), 7.39−7.29 (m, 3H), 7.04 (t, J = 7.6 Hz, 1H), 6.71−6.51
(m, 2H), 4.65 (s, 2H), 2.87 (t, J = 7.0 Hz, 2H), 2.71 (t, J = 7.0 Hz,
2H), 1.79−1.73 (m, 2H), 1.61−1.55 (m, 2H). 13C{1H} NMR (100
MHz, CDCl3): δ = 200.1, 148.0, 137.0, 135.9, 133.1, 129.7, 128.7,
128.1, 118.8, 118.2, 115.2, 38.1, 34.7, 29.3, 23.3 ppm; IR (neat): υmax
3454, 3355, 3060, 2930, 1680, 1604, 1478, 1261, 1022, 799, 750, 690
cm−1 HRMS (ESI) m/z: [M + Na]+ calcd for C17H19NOSNa,
308.1080; found, 308.1084.
5-((2-Fluorophenyl)thio)-1-phenylpentan-1-one (4k). White solid
(51.9 mg, 90%); m.p. 42−43 °C, Rf 0.24 (petroleum ether/ethyl
1
acetate = 50:1). H NMR (400 MHz, CDCl3): δ = 7.86 (d, J = 7.8
Hz, 2H), 7.49−7.45 (m, 1H), 7.38−7.37 (m, 2H), 7.30−7.26 (m,
1H), 7.12−7.10 (m, 1H), 7.01−6.93 (m, 2H), 2.91−2.85 (m, 4H),
1.82−1.79 (m, 2H), 1.64−1.61 (m, 2H). 13C{1H} NMR (100 MHz,
CDCl3): δ = 199.9, 161.5 (d, J = 244.7 Hz), 136.9, 133.1, 132.0 (d, J
= 2.1 Hz), 128.7, 128.3 (d, J = 7.8 Hz), 128.1, 124.5 (d, J = 3.8 Hz),
123.3 (d, J = 17.7 Hz), 115.7 (d, J = 22.4 Hz), 38.0, 33.1, 28.9, 23.3
ppm; IR (neat): υmax 3084, 2936, 1677, 1468, 1449, 1281, 1214, 1071,
750, 727, 687 cm−1 HRMS (ESI) m/z: [M + Na]+ calcd for
C17H17FOSNa, 311.0876; found, 311.0881.
5-((2-Chlorophenyl)thio)-1-phenylpentan-1-one (4l). White solid
(48.9 mg, 69%); m.p. 55−56 °C, Rf 0.33 (petroleum ether/ethyl
1
acetate = 30:1). H NMR (400 MHz, CDCl3): δ = 7.88−7.86 (m,
2H), 7.48−7.46 (m, 1H), 7.40−7.36 (m, 2H), 7.29−7.26 (m, 1H),
7.20−7.12 (m, 2H), 7.04−7.02 (m, 1H), 2.93 (t, J = 7.2 Hz, 2H),
2.91 (t, J = 7.2 Hz, 2H), 1.87−1.83 (m, 2H), 1.73−1.69 (m, 2H).
13C{1H} NMR (100 MHz, CDCl3): δ = 199.8, 137.0, 136.2, 133.5,
133.2, 129.8, 128.7, 128.3, 128.1, 127.2, 126.4, 38.0, 32.4, 28.4, 23.6
ppm; IR (neat): υmax 3059, 2931, 1681, 1450, 1033, 745, 689 cm−1
HRMS (ESI) m/z: [M + Na]+ calcd for C17H17ClOSNa, 327.0581;
found, 327.0574.
5-((4-Fluorophenyl)thio)-1-phenylpentan-1-one (4f). White solid
(48.4 mg, 84%); m.p. 91−92 °C, Rf 0.25 (petroleum ether/ethyl
1
acetate = 30:1). H NMR (400 MHz, CDCl3): δ = 7.95−7.93 (m,
2H), 7.56−7.53 (m, 1H), 7.47−7.43 (m, 2H), 7.35−7.31 (m, 2H),
7.00−6.96 (m, 2H), 2.98 (t, J = 7.2 Hz, 2H), 2.91 (t, J = 7.2 Hz, 2H),
1.89−1.83 (m, 2H), 1.72−1.67 (m, 2H). 13C{1H} NMR (100 MHz,
CDCl3): δ = 199.9, 161.8 (d, J = 246.1 Hz), 137.0, 133.1, 132.4 (d, J
= 8.0 Hz), 131.4 (d, J = 3.3 Hz), 127.7, 128.1, 116.1 (d, J = 21.9 Hz),
38.0, 35.0, 28.9, 23.3 ppm; IR (neat): υmax 3057, 2949, 1680, 1490,
1280, 819, 748, 690 cm−1 HRMS (ESI) m/z: [M + Na]+ calcd for
C17H17FOSNa, 311.0876; found, 311.0869.
5-((2-Bromophenyl)thio)-1-phenylpentan-1-one (4m). White
solid (33.5 mg, 48%); m.p. 51−52 °C, Rf 0.30 (petroleum ether/
1
ethyl acetate = 30:1). H NMR (400 MHz, CDCl3): δ = 7.89−7.86
(m, 2H), 7.48−7.44 (m, 2H), 7.40−7.36 (m, 2H), 7.19−7.15 (m,
2H), 6.96−6.92 (m, 1H), 2.96−2.89 (m, 4H), 1.88−1.82 (m, 2H),
1.76−1.70 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ = 199.9,
138.3, 137.0, 133.2, 133.1, 128.7, 128.1, 127.9, 127.8, 126.5, 123.5,
38.1, 32.8, 28.2, 23.6 ppm; IR (neat): υmax 3058, 2930, 1681, 1447,
1218, 1040, 745, 690 cm−1 HRMS (ESI) m/z: [M + Na]+ calcd for
C17H17BrOSNa, 371.0076; found, 371.0072.
5-((4-Chlorophenyl)thio)-1-phenylpentan-1-one (4g). White
solid (43.7 mg, 72%); m.p. 107−108 °C, Rf 0.25 (petroleum ether/
1
ethyl acetate = 50:1). H NMR (400 MHz, CDCl3): δ = 7.87−7.86
(m, 2H), 7.50−7.47 (m, 1H), 7.40−7.36 (m, 2H), 7.19−7.17 (m,
4H), 2.91 (t, J = 7.2 Hz, 2H), 2.86 (t, J = 7.2 Hz, 2H), 1.84−1.76 (m,
2H), 1.68−1.60 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ =
199.9, 137.0, 135.2, 133.2, 131.9, 130.6, 129.1, 128.7, 128.1, 38.0,
33.9, 28.7, 23.4 ppm; IR (neat): υmax 3060, 2948, 2863, 1680, 1477,
1277, 1098, 750, 688 cm−1 HRMS (ESI) m/z: [M + Na]+ calcd for
C17H17ClOSNa, 327.0581; found, 327.0585.
5-((3,5-Dichlorophenyl)thio)-1-phenylpentan-1-one (4n). White
solid (43.6 mg, 64%); m.p. 62−63 °C, Rf 0.27 (petroleum ether/ethyl
1
acetate = 50:1). H NMR (400 MHz, CDCl3): δ = 7.87 (d, J = 8.0
Hz, 2H), 7.50−7.47 (m, 1H), 7.38 (t, J = 7.2 Hz, 2H), 7.05 (s, 3H),
2.95−2.88 (m, 4H), 1.85−1.70 (m, 2H), 1.71−1.66 (m, 2H).
13C{1H} NMR (100 MHz, CDCl3): δ = 198.5, 139.7, 135.8, 134.1,
132.1, 127.6, 127.0, 124.8, 124.5, 36.8, 31.8, 27.2, 22.2 ppm; IR
(neat): υmax 3073, 2937, 1677, 1533, 1419, 1294, 1097, 830, 798, 754,
729, 689 cm−1 HRMS (ESI) m/z: [M + Na]+ calcd for
C17H16Cl2OSNa, 361.0191; found, 361.0196.
5-((4-Bromophenyl)thio)-1-phenylpentan-1-one (4h). White
solid (42.6 mg, 61%); m.p. 117−118 °C, Rf 0.26 (petroleum ether/
1
ethyl acetate = 30:1). H NMR (400 MHz, CDCl3): δ = 7.88−7.86
(m, 2H), 7.51−7.47 (m, 1H), 7.41−7.37 (m, 2H), 7.32−7.30 (m,
2H), 7.12−7.10 (m, 2H), 2.92 (t, J = 7.2 Hz, 2H), 2.87 (t, J = 7.2 Hz,
2H), 1.85−1.77 (m, 2H), 1.68−1.61 (m, 2H). 13C{1H} NMR (100
MHz, CDCl3): δ = 199.9, 137.0, 136.0, 133.2, 132.0, 130.7, 128.7,
128.1, 119.8, 38.0, 33.7, 28.7, 23.4 ppm; IR (neat): υmax 3058, 2936,
1680, 1276, 750, 689 cm−1 HRMS (ESI) m/z: [M + Na]+ calcd for
C17H17BrOSNa, 371.0076; found, 371.0066.
1-Phenyl-5-(thiophen-2-ylthio)pentan-1-one (4o). Colorless oil
1
(40.9 mg, 74%); Rf 0.25 (petroleum ether/ethyl acetate = 30:1). H
NMR (400 MHz, CDCl3): δ = 7.96−7.94 (m, 2H), 7.58−7.54 (m,
1H), 7.48−7.44 (m, 2H), 7.34−7.32 (m, 1H), 7.12−7.10 (m, 1H),
6.98−6.96 (m, 1H), 2.98 (t, J = 7.2 Hz, 2H), 2.83 (t, J = 7.2 Hz, 2H),
1.88−1.83 (m, 2H), 1.74−1.68 (m, 2H). 13C{1H} NMR (100 MHz,
CDCl3): δ = 200.0, 137.0, 134.6, 133.7, 133.1, 129.3, 128.7, 128.2,
127.6, 38.8, 38.1, 29.1, 23.1 ppm; IR (neat): υmax 3064, 2932, 1682,
1448, 1179, 750, 691 cm−1 HRMS (ESI) m/z: [M + Na]+ calcd for
C15H16OS2Na, 299.0535; found, 299.0529.
5-((2-Methylfuran-3-yl)thio)-1-phenylpentan-1-one (4p). Color-
less oil (35.1 mg, 64%); Rf 0.22 (petroleum ether/ethyl acetate =
30:1). 1H NMR (400 MHz, CDCl3): δ = 7.88−7.86 (m, 2H), 7.49 (t,
J = 7.2 Hz, 1H), 7.39 (t, J = 7.6 Hz, 2H), 7.19 (d, J = 2.0 Hz, 1H),
6.26 (d, J = 2.0 Hz, 1H), 2.89 (t, J = 7.2 Hz, 2H), 2.58 (t, J = 7.2 Hz,
2H), 2.25 (s, 3H), 1.81−1.73 (m, 2H), 1.58−1.51 (m, 2H). 13C{1H}
NMR (100 MHz, CDCl3): δ = 200.0, 154.8, 140.6, 137.0, 133.1,
128.7, 128.1, 115.1, 110.3, 38.2, 35.8, 29.3, 23.2, 12.0 ppm; IR (neat):
5-((3-Bromophenyl)thio)-1-phenylpentan-1-one (4i). White solid
(53.1 mg, 76%); m.p. 58−59 °C, Rf 0.24 (petroleum ether/ethyl
1
acetate = 30:1). H NMR (400 MHz, CDCl3): δ = 7.88−7.85 (m,
2H), 7.48−7.46 (m, 1H), 7.40−7.35 (m, 3H), 7.21−7.12 (m, 2H),
7.04 (t, J = 8.0 Hz, 1H), 2.93−2.87 (m, 4H), 1.83−1.79 (m, 2H),
1.69−1.64 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ = 199.8,
139.4, 137.0, 133.2, 131.1, 130.3, 128.8, 128.7, 128.1, 127.2, 122.9,
38.0, 33.3, 28.6, 23.4 ppm; IR (neat): υmax 3060, 2934, 1679, 1595,
1459, 1280, 1218, 750, 689 cm−1 HRMS (ESI) m/z: [M + Na]+ calcd
for C17H17BrOSNa, 371.0076; found, 371.0071.
5-((2-Aminophenyl)thio)-1-phenylpentan-1-one (4j). Dark oil
1
(31.9 mg, 56%); Rf 0.50 (petroleum ether/ethyl acetate = 5:1). H
H
https://doi.org/10.1021/acs.joc.1c01366
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
υmax 3060, 2920, 2857, 1682, 1956, 1512, 1447, 1269, 1088, 749, 690
cm−1 HRMS (ESI) m/z: [M + Na]+ calcd for C16H18O2SNa,
297.0920; found, 297.0922.
131.9, 128.4, 127.8, 127.5, 127.0, 126.3, 45.5, 37.3, 34.3, 34.0, 30.8,
28.4, 28.2, 26.6, 21.6, 21.4, 13.1 ppm; IR (neat): υmax 3059, 2926,
2854, 1687, 1448, 1261, 1022, 802, 750, 692 cm−1 HRMS (ESI) m/z:
[M + Na]+ calcd for C24H32OSeNa, 439.1511; found, 439.1511.
1-Phenyl-5-(phenylselanyl)dodecan-1-one (6f). Light yellow oil
1-Phenyl-5-(pyridin-2-ylthio)pentan-1-one (4q). Colorless oil
1
(23.0 mg, 43%); Rf 0.22 (petroleum ether/ethyl acetate = 20:1). H
1
(30.1 mg, 44%); Rf 0.29 (petroleum ether/ethyl acetate = 50:1). H
NMR (400 MHz, CDCl3): δ = 8.40 (d, J = 4.8 Hz, 1H), 7.96−7.94
(m, 2H), 7.55 (t, J = 7.4 Hz, 1H), 7.47−7.44 (m, 3H), 7.16 (d, J = 8.0
Hz, 1H), 6.97−6.94 (m, 1H), 3.22 (t, J = 7.2 Hz, 2H), 3.03 (t, J = 7.2
Hz, 2H), 1.93−1.88 (m, 2H), 1.85−1.79 (m, 2H). 13C{1H} NMR
(100 MHz, CDCl3): δ = 200.1, 159.3, 149.6, 137.1, 136.0, 133.1,
128.7, 128.2, 122.4, 119.4, 38.2, 29.8, 29.2, 23.6 ppm; IR (neat): υmax
3060, 2930, 2854, 1683, 1597, 1451, 1414, 1276, 1124, 751, 691 cm−1
HRMS (ESI) m/z: [M + H]+ calcd for C16H18NOS, 272.1104; found,
272.1106.
NMR (400 MHz, CDCl3): δ = 7.88−7.86 (m, 2H), 7.50−7.37 (m,
5H), 7.19−7.17 (m, 3H), 3.27−3.19 (m, 1H), 2.89 (t, J = 7.2 Hz,
2H), 1.68−1.45 (m, 6H), 1.33 (d, J = 6.8 Hz, 3H). 13C{1H} NMR
(100 MHz, CDCl3): δ = 200.3, 137.1, 135.1, 133.1, 129.4, 129.0,
128.7, 128.2, 127.5, 39.7, 38.5, 37.4, 27.6, 24.0, 22.3 ppm; IR (neat):
υmax 3057, 2929, 2857, 1684, 1579, 1448, 1260, 1095, 1021, 799, 749,
690 cm−1 HRMS (ESI) m/z: [M + Na]+ calcd for C19H22OSeNa,
369.0728; found, 369.0731.
1-Phenyl-5-(phenylsulfonyl)pentan-1-one (7a). White solid (58.6
mg, 97%); m.p. 114−115 °C, Rf 0.21 (petroleum ether/ethyl acetate
= 5:1). 1H NMR (400 MHz, CDCl3): δ = 7.84−7.83 (m, 4H), 7.60−
7.57 (m, 1H), 7.51−7.47 (m, 3H), 7.40−7.36 (m, 2H), 3.08 (t, J =
7.2 Hz, 2H), 2.91 (t, J = 6.4 Hz, 2H), 1.76−1.74 (m, 4H). 13C{1H}
NMR (100 MHz, CDCl3): δ = 199.2, 139.1, 136.7, 133.8, 133.3,
129.4, 128.7, 128.12, 128.05, 56.2, 37.8, 22.7, 22.5. ppm; IR (neat):
υmax 3062, 2946, 1681, 1447, 1288, 1146, 1086, 750, 690 cm−1 HRMS
(ESI) m/z: [M + Na]+ calcd for C17H18O3SNa, 325.0869; found,
325.0871.
1-Phenyl-5-(pyridin-4-ylthio)pentan-1-one (4r). White solid (33.7
mg, 62%); m.p. 102−103 °C, Rf 0.11 (petroleum ether/ethyl acetate
= 10:1). 1H NMR (400 MHz, CDCl3): δ = 8.31 (d, J = 4.0 Hz, 2H),
7.88 (d, J = 7.4 Hz, 2H), 7.49 (t, J = 7.2 Hz, 1H), 7.39 (t, J = 7.6 Hz,
2H), 7.03 (d, J = 5.2 Hz, 2H), 2.97−2.93 (m, 4H), 1.89−1.70 (m,
4H). 13C{1H} NMR (100 MHz, CDCl3): δ = 199.6, 149.6, 149.1,
136.9, 133.2, 128.7, 128.1, 120.8, 37.9, 30.6, 28.2, 23.4 ppm; IR
(neat): υmax 3067, 2935, 2870, 1679, 1574, 1406, 1281, 799, 751, 732,
690 cm−1 HRMS (ESI) m/z: [M + H]+ calcd for C16H18OS,
272.1104; found, 272.1105.
1-Phenyl-5-(phenylselanyl)pentan-1-one (6a). Light yellow solid
(32.4 mg, 51%); Rf 0.24 (petroleum ether/ethyl acetate = 30:1). H
1
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c01366.
■
NMR (400 MHz, CDCl3): δ = 7.87−7.85 (m, 2H), 7.50−7.46 (m,
1H), 7.43−7.36 (m, 4H), 7.18−7.17 (m, 3H), 2.92−2.86 (m, 4H),
1.82−1.72 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3): δ = 200.0,
137.0, 133.1, 132.7, 130.4, 129.2, 128.7, 128.2, 126.9, 38.0, 29.9, 27.7,
24.5 ppm; spectral data match those previously reported.12
sı
Optimization of the reaction conditions and 1H and 13
spectra of all new compounds (PDF)
C
1-(3-Fluorophenyl)-5-(phenylselanyl)pentan-1-one (6b). Light
yellow solid (24.1 mg, 36%); m.p. 52−53 °C, Rf 0.20 (petroleum
1
ether/ethyl acetate = 30:1). H NMR (400 MHz, CDCl3): δ = 7.63
AUTHOR INFORMATION
Corresponding Author
(d, J = 7.8 Hz, 1H), 7.55−7.42 (m, 1H), 7.42−7.33 (m, 3H), 7.20−
7.16 (m, 4H), 2.89−2.85 (m, 4H), 1.81−1.69 (m, 4H). 13C{1H}
NMR (100 MHz, CDCl3): δ = 198.6 (d, J = 2.1 Hz), 163.0 (d, J =
247.9 Hz), 139.1 (d, J = 6.0 Hz), 132.7, 130.4 (d, J = 7.2 Hz), 129.2,
126.9, 123.9 (d, J = 3.0 Hz), 120.1 (d, J = 21.6 Hz), 114.9 (d, J = 22.2
Hz), 38.2, 29.8, 27.6, 24.3 ppm; IR (neat): υmax 3067, 2936, 1685,
1585, 1478, 1439, 1262, 1238, 1020, 873, 797, 761, 729, 683 cm−1
HRMS (ESI) m/z: [M + Na]+ calcd for C17H17FOSeNa, 359.0321;
found, 359.0325.
■
Li-Na Guo − Department of Chemistry, School of Chemistry,
Xi’an Key Laboratory of Sustainable Energy Material
Chemistry, and MOE Key Laboratory for Nonequilibrium
Synthesis and Modulation of Condensed Matter, Xi’an
Jiaotong University, Xi’an 710049, China; orcid.org/
0000-0002-9789-6952; Email: guoln81@xjtu.edu.cn
1-Phenyl-7-(phenylselanyl)heptan-1-one (6c). Light yellow solid
(28.3 mg, 41%); m.p. 68−69 °C, Rf 0.28 (petroleum ether/ethyl
Authors
1
Qing-Xin Sun − Department of Chemistry, School of
Chemistry, Xi’an Key Laboratory of Sustainable Energy
Material Chemistry, and MOE Key Laboratory for
Nonequilibrium Synthesis and Modulation of Condensed
Matter, Xi’an Jiaotong University, Xi’an 710049, China
He Chen − Department of Chemistry, School of Chemistry,
Xi’an Key Laboratory of Sustainable Energy Material
Chemistry, and MOE Key Laboratory for Nonequilibrium
Synthesis and Modulation of Condensed Matter, Xi’an
Jiaotong University, Xi’an 710049, China
Shuai Liu − Department of Chemistry, School of Chemistry,
Xi’an Key Laboratory of Sustainable Energy Material
Chemistry, and MOE Key Laboratory for Nonequilibrium
Synthesis and Modulation of Condensed Matter, Xi’an
Jiaotong University, Xi’an 710049, China
Xiao-Qiang Wang − Department of Chemistry, School of
Chemistry, Xi’an Key Laboratory of Sustainable Energy
Material Chemistry, and MOE Key Laboratory for
Nonequilibrium Synthesis and Modulation of Condensed
Matter, Xi’an Jiaotong University, Xi’an 710049, China
Xin-Hua Duan − Department of Chemistry, School of
Chemistry, Xi’an Key Laboratory of Sustainable Energy
Material Chemistry, and MOE Key Laboratory for
acetate = 30:1). H NMR (400 MHz, CDCl3): δ = 7.89−7.86 (m,
2H), 7.50−7.31 (m, 5H), 7.19−7.14 (m, 3H), 2.91−2.82 (m, 4H),
1.69−1.61 (m, 4H), 1.42−1.25 (m, 4H). 13C{1H} NMR (100 MHz,
CDCl3): δ = 200.5, 137.1, 133.0, 132.5, 130.7, 129.1, 128.7, 128.2,
126.8, 38.6, 30.1, 29.8, 28.9, 27.9, 24.3 ppm; IR (neat): υmax 3056,
2928, 2853, 1682, 1578, 1275, 1017, 907, 797, 750, 687 cm−1 HRMS
(ESI) m/z: [M + Na]+ calcd for C19H22OSeNa, 369.0728; found,
369.0730.
1-Phenyl-5-(phenylselanyl)hexan-1-one (6d). Light yellow oil
1
(39.1 mg, 59%); Rf 0.22 (petroleum ether/ethyl acetate = 30:1). H
NMR (400 MHz, CDCl3): δ = 7.88−7.85 (m, 2H), 7.50−7.37 (m,
5H), 7.20−7.19 (m, 3H), 3.29−3.20 (m, 1H), 2.89 (t, J = 7.2 Hz,
2H), 1.87−1.80 (m, 2H), 1.70−1.58 (m, 2H), 1.36 (d, J = 6.8 Hz,
3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 200.1, 137.1, 135.1,
133.1, 129.3, 129.0, 128.7, 128.2, 127.5, 39.6, 38.3, 37.3, 22.7, 22.3
ppm; IR (neat): υmax 3058, 2955, 2850, 1683, 1579, 1448, 1275, 1261,
1020, 797, 750, 690 cm−1 HRMS (ESI) m/z: [M + Na]+ calcd for
C18H20OSeNa, 355.0572; found, 355.0576.
1-Phenyl-6-(phenylselanyl)heptan-1-one (6e). Light yellow oil
1
(31 mg, 37%); Rf 0.39 (petroleum ether/ethyl acetate = 50:1). H
NMR (400 MHz, CDCl3): δ = 7.87−7.85 (m, 2H), 7.50−7.45 (m,
3H), 7.38 (t, J = 7.6 Hz, 2H), 7.19−7.17 (m, 3H), 3.14−3.07 (m,
1H), 2.87 (td, J = 7.2, 2.0 Hz, 2H), 1.90−1.79 (m, 2H), 1.64−1.52
(m, 4H), 1.42−1.35 (m, 2H), 1.18 (br s, 8H), 0.80 (t, J = 6.8 Hz,
3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 199.0, 135.9, 133.9,
I
https://doi.org/10.1021/acs.joc.1c01366
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
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Nonequilibrium Synthesis and Modulation of Condensed
Matter, Xi’an Jiaotong University, Xi’an 710049, China;
State Key Laboratory of Applied Organic Chemistry,
Lanzhou University, Lanzhou 730000, P. R. China;
orcid.org/0000-0002-1527-5934
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Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c01366
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from the National Natural Science
Foundation of China (21971201), Natural Science Basic
Research Plan in Shaanxi Province of China (2021JM-003),
and the China Postdoctoral Science Foundation Funded
Project (2019M663659) is greatly appreciated. We also
thank Zhang, Feng, and Bai of the Instrument Analysis Center
of Xi’an Jiaotong University for their assistance with NMR and
HRMS analyses.
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