Synthesis of 2-Sulfenylindenones via One-Pot Tandem Meyer-Schuster Rearrangement and Radical Cyclization of Arylpropynols with Disulfides

Article abstract of DOI:10.1021/acs.joc.6b00762

A tandem annulation of arylpropynols with disulfides has been developed for the synthesis of 2-sulfenylindenone derivatives. The reaction pathway involves one-pot tandem Meyer-Schuster rearrangement of arylpropynols and successive radical cyclization with disulfides. Various arylpropynols and disulfides with a number of functional groups are compatible in this reaction that affords the corresponding 2-sulfenylindenones in moderate to good yields.

Full text of DOI:10.1021/acs.joc.6b00762

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Note
Synthesis of 2-Sulfenylindenones via One–Pot Tandem Meyer-Schuster
Rearrangement and Radical Cyclization of Arylpropynols with Disulfides
Xing-Song Zhang, Jun-Ying Jiao, Xiao-Hong Zhang, Bo-Lun Hu, and Xing-Guo Zhang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00762 • Publication Date (Web): 27 May 2016
Downloaded from http://pubs.acs.org on May 29, 2016
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The Journal of Organic Chemistry
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Synthesis of 2-Sulfenylindenones via One–Pot
Tandem Meyer-Schuster Rearrangement and
Radical Cyclization of Arylpropynols with Disulfides
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XingꢀSong Zhang; JunꢀYing Jiao; XiaoꢀHong Zhang;* BoꢀLun Hu and XingꢀGuo Zhang*
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, China
kamenzxh@wzu.edu.cn; zxg@wzu.edu.cn
RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required
according to the journal that you are submitting your paper to)
ABSTRACT
A tandem annulation of arylpropynols with disulfides has been developed for the synthesis of 2ꢀ
sulfenylindenone derivatives. The reaction pathway involves one–pot tandem MeyerꢀSchuster
rearrangement of arylpropynols and successive radical cyclization with disulfides. Various
arylpropynols and disulfides with a number of functional groups are compatible in this reaction to afford
the corresponding 2ꢀsulfenylindenones in moderate to good yields.
Indenones are important structural scaffolds in a great number of pharmaceuticals and biologically
active molecules,1 including alcoholic fermentation activators,2 fungicides,3 potential estrogen binding
receptors4 and anticancer agents (indotecan and indimitecan).5 Moreover, they are also versatile
6
intermediates in the synthesis of some natural products such as steroids
and gibberellins.7
Consequently, the synthesis of indenones received much attention and a variety of synthetic strategies
have been developed for the construction of these carboncycles. Traditionally, indenone derivatives
were prepared from the intramolecular FriedelꢀCraftsꢀtype cyclizations or the addition of Grignard
reagents to indandiones.8 Palladium or rhodiumꢀ catalyzed annulations of internal alkynes with 2ꢀ
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halophenyl carbonyl compounds or their equivalents
provided other powerful methods for the
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synthesis of substituted indenones (Scheme 1, eq 1). Recently, the intramolecular cyclization of 1, 3ꢀ
diarylpropynones triggered by superacids 11 or radicals 12 has been proven as an efficient method for the
synthesis of indenones. For example, Zou and coꢀworkers reported a manganeseꢀmediated addition of
thiophenol to 1, 3ꢀdiarylpropynones for the synthesis of thiolated indenones (eq 2).12a While significant
progress has been made in the construction of indenone skeletons, the development of new practical and
general protocol for the synthesis of diverse multiꢀsubstituted indenones is still highly desired. As part
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of our continuing interest in synthesis of sulfenylated aromatic cyclics, we wish to report an iodineꢀ
mediated oneꢀpot tandem MeyerꢀSchuster rearrangement and radical cyclization reaction of
arylpropynols with disulfides. This reaction was conducted in oneꢀpot twoꢀstep process and had greatly
simplified synthetic strategies, 14 leading to 2ꢀsulfenylindenones in moderate to good yields (eq 3).
Scheme 1. Synthesis of indenones
15
We chose the model reaction between 1, 3ꢀdiphenylpropꢀ2ꢀynꢀ1ꢀol 1a and diphenyl disulfide 2a to
optimize the reaction conditions, and the results were listed in Table 1. Initially, the reaction of substrate
1a with diphenyl disulfide 2a, 30 mol % benzoyl peroxide (BPO) and 2 equiv K2S2O8 was carried out in
acetic acid at 120 oC under N2 atmosphere, but only trace amount of the desired product 3ꢀphenylꢀ
2(phenylthio)ꢀ1Hꢀindenꢀ1ꢀone 3 was observed (entry 1). Considering that iodine source could promote
disulfide to yield in situ the free radical RS· or the active RSI,13d we subsequently investigated the
reaction in the presence of 2 equiv ICl. As expected, the product yield was dramatically increased to
61% (entry 2). Encouraged by these results, various iodine sources such as PhI(OAc)2, NIS and I2 were
tested (entries 3ꢀ5), the results showed that I2 provided the best results and the product 3 could be
isolated in 82% yield (entry 5). However, lower yields of product 3 were obtained in the absence of
BPO or when
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Table 1. Screening Conditions a
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Entry [I] source Additive Oxidant
Solvent
Yield (%)b
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7
ꢀꢀ
BPO
BPO
BPO
BPO
BPO
ꢀꢀ
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
trace
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ICl
PhI(OAc)2
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NIS
I2
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82
I2
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I2
AIBN
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I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
TBHP
BPO
BPO
BPO
BPO
BPO
BPO
BPO
BPO
BPO
K2S2O8
H2O2
AcOH
AcOH
AcOH
AcOH
AcOH
Dioxane
DMF
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35
8
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AgOTf
Ag2CO3
Cu(OAc)2
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
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17 d
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67
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21
MeNO2
MeCN
AcOH
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52, 60 c
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a Reaction conditions: 1a (0.2 mmol), 2a (0.2 mmol), I2 (2 equiv), BPO
(30 mol %), K2S2O8 (2 equiv) in HOAc (2 mL) under an N2 atmosphere
o
b
c
d
at 120 C for 24 h; Isolated yield; 5 mol% TfOH was added; at 100
oC.
AIBN or TBHP was used as additive (entries 6ꢀ8). We next examined various oxidants, including H2O2,
AgOTf, Ag2CO3 and Cu(OAc)2, but all were less effective than K2S2O8 (entries 9ꢀ12). During the
screening of solvent, dioxane, DMF, MeNO2 and MeCN were found to provide lower yields (entries 5,
13ꢀ16). Meanwhile, a 74% yield of product 3 was obtained when MeNO2 was used as the solvent (entry
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15). In view of the results that strong acid could promote the MS rearrangement of the alkynol,16 5 mol %
TfOH was employed in MeCN, but only 60 % yield of product 3 was obtained (entry 16). The yield was
reduced to 56% when the reaction was carried out at 100 oC (entry 17).
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With the optimal conditions in hand, we next investigated the substrate scope of various arylpropynols
and disulfides (Table 2). Initially, a wide variety of disulfides were tested and the results demonstrated
that aryl disulfides with both electronꢀdonating and electronꢀwithdrawing groups underwent the
cyclization reaction smoothly. In general, aryl disulfides with electronꢀdonating groups gave the
products in higher yields than those bearing electronꢀwithdrawing groups, and MeNO2 was found to be
more suitable solvent than HOAc for some substrates with electronꢀwithdrawing groups. For example,
pꢀtolyl disulfide provided product 4 in 88% yield. While fluoride disulfides in MeNO2 provided
products 6, 7 and 8 in 61%, 63% and 65% yields, respectively. Similarly, chlorophenyl disulfides
afforded their corresponding products 9ꢀ12 in 55ꢀ71 % yields. Furthermore, products 13 and 14, with
the strong electronꢀwithdrawing nitro group were isolated in 60% and 67% yields, respectively.
Gratifyingly, the alkyl disulfides such as diethyl disulfide underwent the cyclization reaction
successfully to give product 15 in a 54% yield.
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In order to verify which phenyl ring was attacked in the radical cyclization, 3ꢀphenylꢀ1ꢀ(pꢀtolyl)propꢀ
2ꢀynꢀ1ꢀol 1b was reacted with diphenyl disulfide 2a under standard conditions. Phenyl cyclized product
16 was isolated in 72% yield, and tolyl cyclized product 23 could not be detected. Moreover, structure
of product 16 was confirmed by Xꢀray crystallography (Scheme 2). These results suggested that
arylpropynols underwent a MeyerꢀSchuster rearrangement, and then radical cyclization occurred.
Subsequently, other substituent on R2 was investigated. oꢀTolyl provided product 17 in 55% yields, and
4ꢀethylphenyl afforded product 18 61% yield. Fluoride and chloride products 19, 20 and 21 were
obtained in 63ꢀ80% yields. It was notable that an acceptable 32% yield of 22 can be obtained when R2
was an aliphatic cyclohexyl group. Finally, some R1 groups on paraꢀ position of phenyl were obtained
Scheme 2. Selective cyclization and XꢀRay of compound 16.
O
O
OH
Me
SPh
SPh
PhSSPh
Standard
Conditions
+
Me
1b
23, 0 %
16, 72%
Me
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Table 2.Tandem annulation of arylpropynols with disulfides a
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a Reaction conditions: 1 (0.2 mmol), 2 (0.2 mmol), I2 (2 equiv), BPO (30
mol %), K2S2O8 (2 equiv) in HOAc (2 mL) under an N2 atmosphere at
120 oC for 24 h; b MeNO2 was used as solvent.
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in 63ꢀ80% yields. It was notable that an acceptable 32% yield of 22 could be obtained when R2 was an
aliphatic cyclohexyl group. Finally, some R1 groups on paraꢀ position of phenyl were investigated.
Electronꢀdonating groups such as methyl, ethyl and nꢀbutyl, provided products 23 – 25 in 63ꢀ70%
yields. Electronꢀpoor fluoride, chloride and bromide phenyl gave products 26 – 28 in slightly lower
yields (51ꢀ65%). The regioselectivity was observed when metaꢀchloro substituted arylpropynol was
reacted with diphenyl disulfide 2a, and the 6ꢀposition cyclized product 29a was isolated in 62% yield
along with the 2ꢀposition cyclized 29b in 21% yield.
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To further understand this transformation, the reaction of 1, 3ꢀdiphenylpropꢀ2ꢀynꢀ1ꢀone 30 with
diphenyl disulfide 2a was carried out under the optimal reaction conditions, only trace amount of
product 3 was observed (Scheme 3, eq.4). These results suggested that this reaction did not proceed via
the oxidation of 1a to 1, 3ꢀdiarylpropynones and its subsequent intramolecular cyclization. Moreover,
the reaction of substrate 1a and diphenyl disulfide 2a was conducted in the presence of 2.5 equiv of
2,2,6,6ꢀtetramethylꢀ1ꢀpiperidinyloxy (TEMPO), a radical scavenger, but the reaction was completely
restrained and most of substrate 1a was recovered (Scheme 3, eq.5). All of the above results disclosed
that this tandem reaction might be involved in a radical process.
Scheme 3. Control Experiment
On the basis of the obtained experimental results and previous reports,12b, 13d a plausible mechanism
is proposed for this reaction (Scheme 4). Propargyl alcohol is firstly transformed to active allenol
intermediate A via the acidꢀcatalyzed MeyerꢀSchuster rearrangement under acidic reaction conditions.
In the presence of BPO and I2, diphenyl sulfide is decomposed to yield free radical PhS·, which
selectively attack the double bond of the intermediate A to give alkyl radical B. Subsequently,
intermediate B undergoes ketoꢀenol tautomerism and intramolecular radical cyclization to generate
cyclohexadienyl radical C. Single electron transfer and deprotonation of cyclohexadienyl radical C in
the presence of K2S2O8 give dihydroindenone D, 17 which can be oxidized to the desired product 3.
In conclusion, we have developed an effective method for the synthesis of 2ꢀsulfenylindenone
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derivatives from the iodineꢀmediated oneꢀpot tandem cyclization of arylpropynols and disulfides. The
reaction proceeded via a Meyer-Schuster rearrangement of arylpropynols, followed by sulfenyl radical
addition to allenol and final cyclization. A variety of arylpropynols and disulfides bearing aryl or alkyl
groups underwent the tandem reaction smoothly to give the corresponding 2ꢀsulfenylindenones in
moderate to good yields. The present protocol would serve as a new optional route for the synthesis of
2ꢀsulfenylindenone derivatives.
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Scheme 4. Possible Mechanism
S
Ph
2a
Ph
S
BPO/I2
OH
Ph
HO
H
HO
SPh
Ph
.
PhS
H+
Ph
Meyer-Schuster
rearrangement
A
B
1a
O
O
O
K2S2O8/I2
K2S2O8
SPh
SPh
SPh
H+
H
Ph
Ph
Ph
3
D
C
Experimental Section
General Information:
1
13
Chemicals were either purchased or purified by standard techniques. H NMR and C NMR spectra
13
were measured on a 500 MHz spectrometer (1H at 500 MHz, C at 125 MHz), using CDCl3 as the
solvent with tetramethylsilane (TMS) as an internal standard at room temperature. Chemical shifts are
given in δ relative to TMS, and the coupling constants J are given in hertz. Highꢀresolution mass spectra
were recorded on an ESIꢀQꢀTOF mass spectrometer. All reactions under nitrogen atmosphere were
conducted using standard Schlenk techniques. Melting point data are uncorrected. Column
chromatography was performed using EM silica gel 60 (300ꢀ400 mesh).
Typical experimental procedure for the synthesis of arylpropynol 15
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To a solution of alkyne (13 mmol) in anhydrous THF (30 mL) at ꢀ78 oC under N2 atmosphere was
added nꢀBuLi (1.6 mol in hexanes, 6.9 mL, 11 mmol). The reaction was stirred at this temperature for
20 min then at room temperature for 1 h. After cooling to ꢀ78 oC, aldehyde (10 mmol) was added to the
mixture and was allowed to warm to room temperature gradually and stirred for an additional hour
before quenched with aqueous NH4Cl. The mixture was extracted with EtOAc (3 × 10 mL), and the
combined oganic phases were washed with water and brine, dried with anhydrous MgSO4, and filtered.
The filtrate was concentrated under pressure and the residue was purified by flash chromatography on
silica gel (hexanes/ethyl acetal, V/V, 15:1) to produce the desired alcohol as yellow oil.
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General procedure for the synthesis of thiolated indenones:
Under N2 atmosphere, an ovenꢀdried reaction vessel was charged with 1,3ꢀdiarylpropynones 1 (0.2
mmol), disulfides 2 (0.2 mmol), K2S2O8 (0.4 mmol), I2 (0.4 mmol), BPO (0.06 mmol) and AcOH (2
mL). The vessel was sealed and heated at 120 °C for 24 h and then cooled to room temperature. The
mixture was cleaned with Na2S2O4 saturated solution three times and extracted with ethyl acetate three
times, and the combined organic layer was dried over anhydrous MgSO4. After removal of the solvent
under reduced pressure, the residue was purified by silica gel column chromatography [petroleum ether
(bp. 60ꢀ90 oC)ꢀEtOAc gradients, V/V, 50:1] to give the products 3-29.
12a
o
1
3-phenyl-2-(phenylthio)-1H-inden-1-one (3):
red solid (51.6 mg, 82% yield), mp 125ꢀ127 C. H
NMR (500 MHz, CDCl3) δ 7.59ꢀ7.57 (m, 2H), 7.52 (d, J = 7.0 Hz, 1H), 7.50ꢀ7.46 (m, 3H), 7.39ꢀ7.36
(m, 1H), 7.29ꢀ7.24 (m, 3H), 7.20ꢀ7.17 (m, 3H), 7.14ꢀ7.11 (m, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ
193.2, 162.0, 144.5, 134.8, 133.8, 131.8, 131.1, 130.3, 129.5, 129.3, 129.0, 128.7, 128.6, 127.4, 126.5,
123.5, 121.8; LRMS (EI, 70 eV) m/z (%): 314 (M+, 100), 165 (43), 313, 221 (29), 237 (27).
o
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3-phenyl-2-(p-tolylthio)-1H-inden-1-one (4): red solid (57.8 mg, 88% yield), mp 154ꢀ156 C. H NMR
(500 MHz, CDCl3) δ 7.58 (d, J = 7.0 Hz, 2H), 7.50ꢀ7.46 (m, 4H), 7.38ꢀ7.35 (m, 1H), 7.28ꢀ7.25 (m, 1H),
13
7.20ꢀ7.17 (m, 3H), 7.01 (d, J = 7.5 Hz, 2H), 2.26 (s, 3H); C{1H} NMR (125 MHz, CDCl3) δ 193.3,
161.0, 144.6, 136.7, 133.7, 131.9, 131.1, 130.8, 130.2, 129.9, 129.8, 129.3, 128.63, 128.62, 128.0,
123.5, 121.6, 21.2; LRMS (EI, 70 eV) m/z (%): 328 (M+, 100), 165 (30), 300 (29), 327 (27), 329 (26);
HRMS (ESI) calcd for C22H17OS+ ([M + H]+): 329.0995, Found: 329.0989.
2-((4-methoxyphenyl)thio)-3-phenyl-1H-inden-1-one (5): red solid (52.4 mg, 76% yield), mp 136ꢀ137
1
oC. H NMR (500 MHz, CDCl3) δ 7.58ꢀ7.56 (m, 2H), 7.51ꢀ7.47 (m, 4H), 7.36ꢀ7.34 (m, 1H), 7.28ꢀ7.23
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(m, 3H), 7.15 (d, J = 7.5 Hz, 1H), 6.75 (d, J = 8.5 Hz, 2H), 3.75 (s, 3H); C{1H} NMR (125 MHz,
CDCl3) δ 193.5, 159.7, 159.2, 144.7, 133.7, 132.7, 131.9, 131.0, 130.1, 129.2, 128.9, 128.7, 128.6,
124.3, 123.4, 121.4, 114.7, 55.4; LRMS (EI, 70 eV) m/z (%): 344 (M+, 100), 345 (24), 151 (23), 343
(22), 165 (20); HRMS (ESI) calcd for C22H17O2S+ ([M + H]+): 345.0944, Found: 345.0963.
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2-((2-fluorophenyl)thio)-3-phenyl-1H-inden-1-one (6): red solid (40.6 mg, 61% yield), mp 106ꢀ107 C.
1H NMR (500 MHz, CDCl3) δ 7.59ꢀ7.58 (m, 2H), 7.50ꢀ7.44 (m, 4H), 7.36ꢀ7.35 (m, 1H), 7.29ꢀ7.25 (m,
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2H), 7.17ꢀ7.12 (m, 2H), 7.00ꢀ6.94 (m, 2H); C{1H} NMR (125 MHz, CDCl3) δ 192.8, 160.9 (d, JCF =
245.0 Hz), 160.7, 144.5, 133.8, 132.3, 131.6, 131.1, 130.2, 129.3, 128.8 (d, 3JCF = 8.8 Hz), 128.6, 128.5,
126.3, 124.5 (d, 4JCF =3.8 Hz), 123.5, 121.6, 121.1 (d, 2JCF = 16.3 Hz), 115.8 (d, 2JCF = 21.3 Hz); LRMS
(EI, 70 eV) m/z (%): 332 (M+, 100), 221 (44), 165 (41), 176 (26), 333 (24); HRMS (ESI) calcd for
C21H14FOS+ ([M + H]+): 333.0744, Found: 333.0756.
o
2-((3-fluorophenyl)thio)-3-phenyl-1H-inden-1-one (7): red solid (41.9 mg, 63% yield), mp 112ꢀ114 C.
1H NMR (500 MHz, CDCl3) δ 7.60ꢀ7.58 (m, 2H), 7.56 (d, J = 7.5 Hz, 1H), 7.53ꢀ7.49 (m, 3H), 7.43ꢀ7.40
(m, 1H), 7.34ꢀ7.31 (m, 1H), 7.23 (d, J = 7.0 Hz, 1H), 7.19ꢀ7.15 (m, 1H), 7.06ꢀ7.05 (m, 1H), 6.98ꢀ6.95
(m, 1H), 6.85ꢀ6.81 (m, 1H); C{1H} NMR (125 MHz, CDCl3) δ 192.9, 162.9 (d, JCF = 246.3 Hz),
163.0, 144.3, 137.3 (d, 3JCF = 7.5 Hz), 133.9, 131.6, 131.1, 130.5, 130.2 (d, JCF = 8.8 Hz), 129.8, 128.7,
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128.6, 126.3, 124.6, 123.7, 122.0, 115.9 (d, JCF = 23.8 Hz), 113.5 (d, JCF = 21.3 Hz); LRMS (EI, 70
eV) m/z (%): 332 (M+, 60), 207 (100), 331 (70), 281 (45), 73 (42); HRMS (ESI) calcd for C21H14FOS+
([M + H]+): 333.0744, Found: 333.0753.
o
2-((4-fluorophenyl)thio)-3-phenyl-1H-inden-1-one (8): red solid (43.3 mg, 65% yield), mp 172ꢀ174 C.
1H NMR (500 MHz, CDCl3) δ 7.57ꢀ7.55 (m, 2H), 7.52ꢀ7.48 (m, 4H), 7.38ꢀ7.35 (m, 1H), 7.29ꢀ7.25 (m,
3H), 7.17 (d, J = 7.5 Hz, 1H), 6.92ꢀ6.87 (m, 2H); C{1H} NMR (125 MHz, CDCl3) δ 193.2, 162.1 (d,
1JCF = 245.0 Hz), 161.0, 144.5, 133.8, 132.2 (d, JCF = 7.5 Hz), 131.8, 131.0, 130.3, 129.5, 129.3, 128.7,
128.6, 127.9, 123.5, 121.7, 116.1 (d, JCF = 22.5 Hz); LRMS (EI, 70 eV) m/z (%): 332 (M+, 100), 165
(44), 304 (34), 139 (31), 333 (30); HRMS (ESI) calcd for C21H14FOS+ ([M + H]+): 333.0744, Found:
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333.0755.
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2-((2-chlorophenyl)thio)-3-phenyl-1H-inden-1-one (9): red solid (41.9 mg, 60% yield), mp 156ꢀ158 C.
1H NMR (500 MHz, CDCl3) δ 7.53ꢀ7.48 (m, 3H), 7.45ꢀ7.40 (m, 3H), 7.36ꢀ7.33 (m, 1H), 7.27ꢀ7.22 (m,
2H), 7.16 (d, J = 7.5Hz, 1H), 7.10ꢀ7.08 (m, 1H), 7.03ꢀ6.99 (m, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ
192.7, 162.8, 144.4, 134.2, 133.8, 133.3, 131.6, 131.1, 130.4, 130.1, 129.9, 129.6, 128.7, 128.5, 127.3,
127.1, 126.0, 123.6, 121.9; LRMS (EI, 70 eV) m/z (%): 348 (M+, 33), 313 (100), 207 (36), 165 (25),
314 (24); HRMS (ESI) calcd for C21H14ClOS+ ([M + H]+): 349.0448, Found: 349.0454.
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2-((3-chlorophenyl)thio)-3-phenyl-1H-inden-1-one (10): red solid (43.3 mg, 62% yield), mp 135ꢀ137
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oC. H NMR (500 MHz, CDCl3) δ 7.59ꢀ7.55 (m, 3H), 7.51ꢀ7.50 (m, 3H), 7.42ꢀ7.39 (m, 1H), 7.33ꢀ7.31
(m, 1H), 7.26ꢀ7.23 (m, 2H), 7.17ꢀ7.09 (m, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 192.9, 162.7,
144.3, 136.9, 134.8, 133.9, 131.6, 131.0, 130.5, 130.0, 129.7, 128.7, 128.5, 127.7, 127.2, 126.7, 126.3,
123.7, 122.0; LRMS (EI, 70 eV) m/z (%):348 (M+, 100), 165 (64), 221 (40), 350 (39), 284 (34); HRMS
(ESI) calcd for C21H14ClOS+ ([M + H]+): 349.0448, Found: 349.0444.
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2-((4-chlorophenyl)thio)-3-phenyl-1H-inden-1-one (11): red solid (49.5 mg, 71% yield), mp 135ꢀ136
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oC. H NMR (500 MHz, CDCl3) δ 7.59ꢀ7.57 (m, 2H), 7.54ꢀ7.49 (m, 4H), 7.41ꢀ7.38 (m, 1H), 7.32ꢀ7.29
(m, 1H), 7.22ꢀ7.20 (m, 3H), 7.18ꢀ7.16 (m, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 193.0, 162.0, 144.4
, 133.8, 133.2, 132.7, 131.7, 131.0, 130.8, 130.4, 129.6, 129.1, 128.7, 128.6, 127.0, 123.6, 121.8; LRMS
(EI, 70 eV) m/z (%): 348 (M+, 24), 207 (100), 281 (43), 208 (26), 341 (20); HRMS (ESI) calcd for
C21H14ClOS+ ([M + H]+): 349.0448, Found: 349.0448.
2-((3,5-dichlorophenyl)thio)-3-phenyl-1H-inden-1-one (12): red oil (42.2 mg, 55% yield). 1H NMR (500
MHz, CDCl3) δ 7.58ꢀ7.56 (m, 3H), 7.52ꢀ7.49 (m, 3H), 7.44ꢀ7.41 (m, 1H), 7.36ꢀ7.33 (m, 1H), 7.26ꢀ7.23
13
(m, 1H), 7.10 (s, 3H); C{1H} NMR (125 MHz, CDCl3) δ 192.6, 163.5, 144.2 , 138.5, 135.3, 134.0,
131.4, 131.0, 130.7, 130.0, 128.8, 128.5, 126.9, 126.7, 125.3, 123.8, 122.2; LRMS (EI, 70 eV) m/z (%):
382 (M+, 100), 165 (99), 384 (71), 221 (59), 176 (41); HRMS (ESI) calcd for C21H13Cl2OS+ ([M + H]+):
383.0059, Found: 383.0053.
o
2-((3-nitrophenyl)thio)-3-phenyl-1H-inden-1-one (13): red solid (43.1 mg, 60% yield), mp 124ꢀ126 C.
1H NMR (500 MHz, CDCl3) δ 8.05 (s, 1H), 7.97ꢀ7.95 (m, 1H), 7.60ꢀ7.57 (m, 3H), 7.55 (d, J = 7.0 Hz,
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1H), 7.52ꢀ7.49 (m, 3H), 7.44ꢀ7.41 (m, 1H), 7.39ꢀ7.32 (m, 2H), 7.25ꢀ7.24 (m, 1H); C{1H} NMR (125
MHz, CDCl3) δ 192.7, 163.3, 148.6, 144.2 , 137.7, 134.6, 134.1, 131.4, 130.9, 130.7, 130.0, 129.6,
128.8, 128.5, 125.3, 123.8, 123.6, 122.2, 121.3; LRMS (EI, 70 eV) m/z (%): 359 (M+, 100), 165 (64),
221 (42), 284 (25), 360 (24); HRMS (ESI) calcd for C21H14NO3S+ ([M + H]+): 360.0689, Found:
360.0697.
2-((4-nitrophenyl)thio)-3-phenyl-1H-inden-1-one (14): yellow solid (48.2 mg, 67% yield), mp 187ꢀ189
oC. 1H NMR (500 MHz, CDCl3) δ 7.99 (d, J = 8.5Hz, 2H), 7.52ꢀ7.45 (m, 6H), 7.40ꢀ7.29 (m, 2H), 7.26ꢀ
13
7.21 (m, 3H); C{1H} NMR (125 MHz, CDCl3) δ 192.4, 165.0, 146.0, 145.4 , 144.0, 134.1, 131.3,
131.0, 130.3, 128.9, 128.5, 127.8, 126.7, 124.6, 124.1, 123.9, 122.5; LRMS (EI, 70 eV) m/z (%): 359
(M+, 100), 165 (53), 221 (40), 360 (24), 284 (21); HRMS (ESI) calcd for C21H14NO3S+ ([M + H]+):
360.0689, Found: 360.0695.
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2-(ethylthio)-3-phenyl-1H-inden-1-one (15): red solid (28.8 mg, 54% yield), mp 92ꢀ94 C. H NMR
(500 MHz, CDCl3) δ 7.58ꢀ7.55 (m, 2H), 7.54ꢀ7.47 (m, 4H), 7.34ꢀ7.31 (m, 1H), 7.23ꢀ7.20 (m, 1H), 7.08
(d, J = 7.5 Hz, 1H), 3.02 (q, J = 7.5 Hz, 2H); 1.20 (t, J = 7.5 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3)
δ 194.4, 157.2, 145.1, 133.8, 132.4, 131.4, 129.8, 129.4, 128.7, 128.6, 128.5, 123.2, 120.7, 26.6, 15.5;
LRMS (EI, 70 eV) m/z (%): 266 (M+, 59), 233 (100), 165 (82), 215 (33), 237 (27); HRMS (ESI) calcd
for C17H15OS+ ([M + H]+): 267.0838, Found: 267.0845.
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2-(phenylthio)-3-(p-tolyl)-1H-inden-1-one (16): red solid (47.3 mg, 72% yield), mp 84ꢀ86 C. H NMR
(500 MHz, CDCl3) δ 7.52ꢀ7.50 (m, 3H), 7.39ꢀ7.36 (m, 1H), 7.31ꢀ7.28 (m, 4H), 7.24ꢀ7.18 (m, 4H), 7.14ꢀ
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7.11 (m, 1H), 2.42 (s, 3H); C{1H} NMR (125 MHz, CDCl3) δ 193.3, 162.5, 144.5, 140.8, 135.2,
133.7, 131.3, 129.5, 129.4, 129.2, 129.0, 128.9, 128.7, 126.7, 126.4, 123.4, 121.8, 21.7; LRMS (EI, 70
eV) m/z (%): 328 (M+, 100), 313 (29), 329, 327 (27), 121 (25); HRMS (ESI) calcd for C22H17OS+ ([M +
H]+): 329.0995, Found: 329.1010.
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2-(phenylthio)-3-(o-tolyl)-1H-inden-1-one (17): red solid (36.1 mg, 55% yield), mp 125ꢀ127 C. H
NMR (500 MHz, CDCl3) δ 7.52ꢀ7.50 (m, 1H), 7.32ꢀ7.30 (m, 2H), 7.27ꢀ7.23 (m, 5H), 7.19ꢀ7.11 (m,
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4H), 6.77 (d, J = 7.0 Hz, 1H), 2.26 (s, 3H); C{1H} NMR (125 MHz, CDCl3) δ 193.2, 162.4, 145.4,
135.9, 134.1, 133.7, 131.8, 130.7, 130.5, 130.4, 129.6, 129.4, 129.3, 128.9, 128.0, 126.9, 126.0, 123.3,
121.4, 20.3; LRMS (EI, 70 eV) m/z (%): 328 (M+, 100), 219 (78), 189 (31), 191 (28), 329 (26) HRMS
(ESI) calcd for C22H17OS+ ([M + H]+): 329.0995, Found: 329.0990.
o
3-(4-ethylphenyl)-2-(phenylthio)-1H-inden-1-one (18): 12a red solid (41.8 mg, 61% yield), mp 91ꢀ93 C.
1H NMR (500 MHz, CDCl3) δ 7.54ꢀ7.51 (m, 3H), 7.39ꢀ7.36 (m, 1H), 7.32 (d, J = 7.5 Hz, 2H), 7.30ꢀ7.23
(m, 4H), 7.21ꢀ7.18 (m, 2H), 7.14ꢀ7.11 (m 1H), 2.72 (q, J = 7.5 Hz, 2H), 1.28 (t, J = 7.5 Hz, 3H);
13C{1H} NMR (125 MHz, CDCl3) δ 193.3, 162.3, 147.0, 144.6, 135.1, 133.6, 131.3, 129.5, 129.2,
129.0, 128.8, 128.2, 127.9, 126.7, 126.4, 123.4, 121.9, 29.1, 15.4; LRMS (EI, 70 eV) m/z (%): 342 (M+,
100), 313 (75), 314 (29), 343 (26), 121 (25).
3-(2-fluorophenyl)-2-(phenylthio)-1H-inden-1-one (19): red solid (53.2 mg, 80% yield), mp 132ꢀ134 oC.
1H NMR (500 MHz, CDCl3) δ 7.50 (d, J = 7.0 Hz, 1H), 7.43ꢀ7.39 (m, 2H), 7.36ꢀ7.33 (m, 1H), 7.29 (d, J
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= 7.5 Hz, 2H), 7.25ꢀ7.20 (m, 2H), 7.18ꢀ7.11 (m, 4H), 6.96 (d, J = 7.5 Hz, 1H); C{1H} NMR (125
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MHz, CDCl3) δ 192.7, 159.9 (d, JCF = 248.8 Hz), 155.6, 144.6, 134.1, 133.6, 131.7 (d, JCF = 7.5 Hz),
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130.9, 130.4, 130.3, 130.2, 129.3, 128.9, 128.0, 126.9, 124.3, 123.4, 121.4, 116.4 (d, JCF =21.3 Hz),;
LRMS (EI, 70 eV) m/z (%): 332 (M+, 100), 183 (36), 333 (23), 237, 331 (18); HRMS (ESI) calcd for
C21H14FOS+ ([M + H]+): 333.0744, Found: 333.0740.
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3-(4-fluorophenyl)-2-(phenylthio)-1H-inden-1-one (20): red solid (41.9 mg, 63% yield), mp 131ꢀ133 oC.
1H NMR (500 MHz, CDCl3) δ 7.59ꢀ7.57 (m, 2H), 7.52 (d, J = 7.0 Hz, 1H), 7.40ꢀ7.37 (m, 1H), 7.30ꢀ7.24
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(m, 3H), 7.20ꢀ7.16 (m, 4H), 7.15ꢀ7.11 (m, 2H); C{1H} NMR (125 MHz, CDCl3) δ 193.0, 163.8 (d,
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1JCF = 250 Hz), 160.6, 144.4, 136.7, 134.5, 133.8, 131.1, 130.8 (d, JCF = 8.8 Hz), 129.6, 129.5, 129.4,
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129.1, 126.7, 123.6, 121.5, 115.9 (d, JCF =21.3 Hz); LRMS (EI, 70 eV) m/z (%): 332 (M+, 100), 183
(31), 239 (30), 331 (27), 255 (26); HRMS (ESI) calcd for C21H14FOS+ ([M + H]+): 333.0744, Found:
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333.0750.
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3-(4-chlorophenyl)-2-(phenylthio)-1H-inden-1-one (21): red solid (52.3 mg, 75% yield), mp 85ꢀ87 C.
1H NMR (500 MHz, CDCl3) δ 7.54ꢀ7.53 (m, 3H), 7.47ꢀ7.46 (m, 2H), 7.41ꢀ7.38 (m, 1H), 7.31ꢀ7.27 (m,
3H), 7.22ꢀ7.19 (m, 2H), 7.17ꢀ7.14 (m, 2H); C{1H} NMR (125 MHz, CDCl3) δ 192.8, 160.2, 144.2,
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136.7, 136.3, 134.3, 133.9, 131.0, 130.2, 130.0, 129.6, 129.1, 129.0, 128.1, 126.8, 123.7, 121.4; LRMS
(EI, 70 eV) m/z (%): 348 (M+, 100), 350 (41), 320, 284 (38), 163 (32); HRMS (ESI) calcd for
C21H14ClOS+ ([M + H]+): 349.0448, Found: 349.0452.
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3-cyclohexyl-2-(phenylthio)-1H-inden-1-one (22): yellow solid (20.5 mg, 32% yield), mp 90ꢀ92 C. H
NMR (500 MHz, CDCl3) δ 7.46 (d, J = 7.0 Hz, 1H), 7.41ꢀ7.38 (m, 2H), 7.29ꢀ7.26 (m, 3H), 7.25ꢀ7.22
(m, 2H), 7.16ꢀ7.13 (m, 1H), 3.22ꢀ3.16 (m, 1H), 1.97ꢀ1.86 (m, 4H), 1.82ꢀ1.75 (m, 3H), 1.43ꢀ1.34 (m,
3H); 13C{1H} NMR (125 MHz, CDCl3) δ 193.7, 172.3, 143.6, 135.9, 133.6, 131.5, 129.4, 129.1, 128.6,
126.2, 126.1, 123.1, 121.7, 39.9, 30.0, 26.3, 26.1; LRMS (EI, 70 eV) m/z (%): 320 (M+, 100), 143 (32),
115 (29), 321, 211 (24); HRMS (ESI) calcd for C21H21OS+ ([M + H]+): 321.1308, Found: 321.1308.
5-methyl-3-phenyl-2-(phenylthio)-1H-inden-1-one (23): red solid (46.0 mg, 70% yield), mp 130ꢀ132 oC.
1H NMR (500 MHz, CDCl3) δ 7.59ꢀ7.57 (m, 2H), 7.52ꢀ7.48 (m, 3H), 7.43 (d, J = 7.5 Hz, 1H), 7.28ꢀ7.26
(m, 2H), 7.22ꢀ7.18 (m, 2H), 7.15ꢀ7.12 (m, 1H), 7.10ꢀ7.08 (m, 1H), 7.01 (s, 1H), 2.36 (s, 3H); C{1H}
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NMR (125 MHz, CDCl3) δ 192.9, 161.8, 145.0, 144.8, 135.0, 132.0, 130.2, 129.5, 129.2, 129.0, 128.7,
128.6, 128.5, 127.7, 126.5, 123.7, 123.0, 22.2; LRMS (EI, 70 eV) m/z (%):328 (M+, 100), 300 (39), 329
(26), 327, 251 (23). HRMS (ESI) calcd for C22H17OS+ ([M + H]+): 329.0995, Found: 329.0993.
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5-ethyl-3-phenyl-2-(phenylthio)-1H-inden-1-one (24): red solid (43.1 mg, 63% yield), mp 119ꢀ121 C.
1H NMR (500 MHz, CDCl3) δ 7.59ꢀ7.58 (m, 2H), 7.53ꢀ7.48 (m, 3H), 7.46 (d, J = 7.5 Hz, 1H), 7.28ꢀ7.26
(m, 2H), 7.21ꢀ7.18 (m, 2H), 7.15ꢀ7.11 (m, 2H), 7.03 (s, 1H), 2.65 (q, J = 8.0 Hz, 2H), 1.23 (t, J = 8.0
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Hz, 3H); C{1H} NMR (125 MHz, CDCl3) δ 192.9, 161.9, 151.2, 145.0, 135.0, 132.0, 130.2, 129.2,
129.0, 128.9, 128.8, 128.6, 128.4, 127.7, 126.4, 123.8, 122.0, 26.9, 15.4; LRMS (EI, 70 eV) m/z (%):
342 (M+, 100), 314 (38), 313 (31), 343 (27), 299 (23); HRMS (ESI) calcd for C23H19OS+ ([M + H]+):
343.1151, Found: 343.1160.
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5-butyl-3-phenyl-2-(phenylthio)-1H-inden-1-one (25): red solid (48.2 mg, 65% yield), mp 73ꢀ75 C. H
NMR (500 MHz, CDCl3) δ 7.59ꢀ7.57 (m, 2H), 7.52ꢀ7.47 (m, 3H), 7.44 (d, J = 7.5 Hz, 1H), 7.28ꢀ7.25
(m, 2H), 7.21ꢀ7.18 (m, 2H), 7.14ꢀ7.08 (m, 2H), 7.00 (s, 1H), 2.60 (t, J = 8.0 Hz, 2H), 1.59ꢀ1.55 (m, 2H),
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1.38ꢀ1.33 (m, 2H), 0.92 (t, J = 7.5 Hz, 3H); C{1H} NMR (125 MHz, CDCl3) δ 192.9, 161.9, 149.9,
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144.9, 135.0, 132.0, 130.1, 129.3, 129.0, 128.9, 128.8, 128.7, 128.6, 127.7, 126.5, 123.7, 122.4, 36.3,
33.4, 22.5, 14.0; LRMS (EI, 70 eV) m/z (%): 370 (M+, 100), 313 (34), 371 (33), 299, 207 (25); HRMS
(ESI) calcd for C25H23OS+ ([M + H]+): 371.1464, Found: 371.1467.
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5-fluoro-3-phenyl-2-(phenylthio)-1H-inden-1-one (26): red solid (43.2 mg, 65% yield), mp 159ꢀ161 C.
1H NMR (500 MHz, CDCl3) δ 7.57ꢀ7.55 (m, 2H), 7.52ꢀ7.48 (m, 4H), 7.30ꢀ7.28 (m, 2H), 7.22ꢀ7.19 (m,
2H), 7.17ꢀ7.14 (m, 1H), 6.94ꢀ6.91 (m, 2H); C{1H} NMR (125 MHz, CDCl3) δ 191.3, 166.6 (d, JCF =
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253.8 Hz), 158.7, 147.9, 134.0, 131.4, 130.4, 129.9, 129.5, 129.1, 128.8, 128.5, 127.0, 126.9, 125.4 (d,
3JCF = 10.0 Hz), 114.9 (d, JCF =22.5 Hz), 110.5 (d, JCF =26.3 Hz); LRMS (EI, 70 eV) m/z (%): 332
(M+, 100), 183 (31), 239 (30), 331 (27), 255 (26). HRMS (ESI) calcd for C21H14FOS+ ([M + H]+):
333.0744, Found: 333.0749.
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5-chloro-3-phenyl-2-(phenylthio)-1H-inden-1-one (27): red solid (42.6 mg, 61% yield), mp 151ꢀ153 C.
1H NMR (500 MHz, CDCl3) δ 7.56ꢀ7.55 (m, 2H), 7.52ꢀ7.48 (m, 3H), 7.44 (d, J = 8.0 Hz, 1H), 7.28ꢀ7.24
(m, 3H), 7.22ꢀ7.19 (m, 2H), 7.17ꢀ7.13 (m, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 191.7, 159.6,
146.4, 140.2, 134.0, 131.3, 130.5, 129.8, 129.3, 129.2, 129.1, 128.9, 128.8, 128.5, 126.9, 124.4, 122.3;
LRMS (EI, 70 eV) m/z (%): 348 (M+, 100), 350 (42), 284 (36), 255 (34), 349 (32). HRMS (ESI) calcd
for C21H14ClOS+ ([M + H]+): 349.0448, Found: 349.0444.
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5-bromo-3-phenyl-2-(phenylthio)-1H-inden-1-one (28): red solid (40.1 mg, 51% yield), mp 140ꢀ141 C.
1H NMR (500 MHz, CDCl3) δ 7.61ꢀ7.59 (m, 2H), 7.54 (d, J = 7.0 Hz, 1H), 7.50ꢀ7.49 (m, 2H), 7.41ꢀ7.38
(m, 1H), 7.31ꢀ7.27 (m, 3H), 7.22ꢀ7.19 (m, 3H), 7.15ꢀ7.13 (m, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ
193.2, 162.0, 144.6, 134.8, 133.8, 131.9, 131.1, 130.3, 129.5, 129.4, 129.0, 128.7, 128.6, 127.4, 126.6,
123.6, 121.8; LRMS (EI, 70 eV) m/z (%): 394/392 (M+, 100), 284 (60), 163 (59), 313 (52). HRMS
(ESI) calcd for C21H14BrOS+ ([M + H]+): 392.9943, Found: 392.9945.
6-chloro-3-phenyl-2-(phenylthio)-1H-inden-1-one (29a): red solid (43.3 mg, 62 % yield), mp 109ꢀ111
oC. H NMR (500 MHz, CDCl3) δ 7.58ꢀ7.56 (m, 2H), 7.52ꢀ7.49 (m, 3H), 7.47 (s, 1H), 7.35 (d, J = 8.0
Hz, 1H), 7.28ꢀ7.25 (m, 2H), 7.22ꢀ7.19 (m, 2H), 7.16ꢀ7.13 (m, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ
191.9, 161.3, 142.6, 135.8, 134.3, 133.0, 132.7, 131.4, 130.6, 129.6, 129.1, 128.8, 128.5, 127.7, 126.8,
124.1, 122.6; LRMS (EI, 70 eV) m/z (%): 348 (M+, 100), 255 (54), 284 (40), 350 (36), 176 (29). HRMS
(ESI) calcd for C21H14ClOS+ ([M + H]+): 349.0448, Found: 349.0471.
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4-chloro-3-phenyl-2-(phenylthio)-1H-inden-1-one (29b): red solid (14.7 mg, 21 % yield), mp 142ꢀ144
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oC. H NMR (500 MHz, CDCl3) δ 7.45ꢀ7.41 (m, 4H), 7.39ꢀ7.37 (m, 2H), 7.29ꢀ7.28 (m, 1H), 7.27ꢀ7.26
(m, 2H), 7.23ꢀ7.20 (m, 3H), 7.19ꢀ7.17 (m, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 191.7, 162.6,
139.9, 136.8, 133.9, 133.1, 132.9, 131.7, 130.7, 130.3, 129.4, 129.0, 128.7, 128.3, 128.2, 127.0, 121.9;
LRMS (EI, 70 eV) m/z (%): 348 (M+, 100), 350 (38), 284 (37), 349 (31), 121 (28). HRMS (ESI) calcd
for C21H14ClOS+ ([M + H]+): 349.0448, Found: 349.0468.
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Acknowledgment. We thank the National Natural Science Foundation of China (No. 21272177 and
21302144) and Zhejiang Provincial Natural Science Foundation of China (No. LR15B020002) for
financial support.
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Supporting Information Available: Copies of H and C NMR spectra for product 3ꢀ29, and Xꢀray
data for compound 16. This material is available free of charge via the Internet at http://pubs.acs.org.
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