Catalytic Sulfur-Enabled Dehydrobicyclization of 1,6-Enynes toward Arylated Indeno[1,2-c]thiophenes

Article abstract of DOI:10.1021/acs.joc.6b00692

A new copper-catalyzed sulfur-enabled dehydrobicyclization of 1,6-enynes using potassium sulfide as a sulfurating reagent has been established, providing a straightforward access toward arylated indeno[1,2-c]thiophenes with moderate to good yields. This sulfur incorporation pathway involves Michael addition, 5-exo-dig/5-endo-trig bicyclization and dehydrogenation sequence, resulting in continuous multiple bond-forming events including C-S and C-C bonds to rapidly construct functional organic molecules.

Full text of DOI:10.1021/acs.joc.6b00692

Subscriber access provided by - Access paid by the | UCSB Libraries
Article
Catalytic Sulfur-Enabled Dehydrobicyclization of 1,6-
Enynes toward Arylated Indeno[1,2-c]thiophenes
Ya-Nan Wu, Rong Fu, Nan-Nan Wang, Wen-Juan Hao, Guigen Li, Shu-Jiang Tu, and Bo Jiang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00692 • Publication Date (Web): 13 May 2016
Downloaded from http://pubs.acs.org on May 16, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 28
The Journal of Organic Chemistry
1
2
3
4
5
Catalytic SulfurꢀEnabled Dehydrobicyclization of 1,6ꢀEnynes toward
6
7
8
9
Arylated Indeno[1,2ꢀc]thiophenes
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
YaꢀNan Wu,a Rong Fu,a NanꢀNan Wang,a WenꢀJuan Hao,*,a Guigen Li,b ShuꢀJiang Tu,*,a and Bo
Jiang*,a
aSchool of Chemistry and Chemical Engineering, Jiangsu Key Laboratory of Green Synthetic Chemistry
b
for Functional Materials, Jiangsu Normal University, Xuzhou 221116, P. R. China; Department of
Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409ꢀ1061, USA.
Eꢀmail wjhao@jsnu.edu.cn (WJH); laotu@jsnu.edu.cn(SJT); jiangchem@jsnu.edu.cn (BJ)
RECEIVED DATE
ABSTRACT. A new copperꢀcatalyzed sulfurꢀenabled dehydrobicyclization of 1,6ꢀenynes using
potassium sulfide as a sulfurating reagent has been established, providing a straightforward access
toward arylated indeno[1,2ꢀc]thiophenes with moderate to good yields. This sulfur incorporation
pathway involves Michael addition, 5ꢀexoꢀdig/5ꢀendoꢀtrig bicyclization and dehydrogenation sequence,
resulting in continuous multiple bondꢀforming events including C–S and C–C bonds to rapidly construct
functional organic molecules.
1
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 28
Introduction
1
2
3
4
5
6
7
8
9
Sulfurꢀcontaining compounds have extensively applied in pharmaceuticals, agrochemicals, and
functional materials, and served as synthetic intermediates.1 Organosulfur compounds are widespread in
natural products and synthetically bioactive molecules.2 Considerable efforts have been devoted to
powerful and reliable methods for the incorporation of sulfur into organic frameworks.3 Since Migita
and coꢀworkers reported Pdꢀcatalyzed coupling of thiols and aryl halides,4 a variety of transitionꢀmetal
species, such as Pd,5 Cu,6 Fe,7 and Rh8, have been utilized in C−S bond formation. However, in most
cases, the use of foulꢀsmelling and volatile sulfur sources such as thiols and disulfides is indispensable.
To address these issues, some alternative sulfur transfer reagents like thiourea,9 potassium ethyl
xanthogenate,10 thiocyanate,11 have been developed to construct C−S bond. Recently, metal sulfides as
promising sulfurating reagents were employed to synthesize Sꢀheterocycle through metalꢀcatalyzed
double C−S bonds formation.12 For example, Xi et al. developed Cuꢀcatalyzed double Sꢀalkenylation of
potassium sulfide with dienyl diiodides towards the formation of highly substituted thiophenes.12d
Afterward, Liang and coꢀworkers reported a copperꢀcatalyzed synthesis of benzothiazoles using
potassium sulfide as a sulfurating reagent.12e Li and coꢀworkers presented a copperꢀcatalyzed cascade
cyclization of 1,7ꢀenynes with potassium sulfide leading to 3,3aꢀdihydrothieno[3,4ꢀc]quinolinꢀ4(5H)ꢀ
ones.12f However, in sharp contrast, a practical metalꢀcatalyzed dehydrobicyclization of 1,6ꢀeyens with
potassium sulfide allowing direct formation of richly decorated indenoꢀfused thiophenes has met with
little success but represents a highly desirable methodology considering its bondꢀforming efficiency and
highly functional group tolerance.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The increasingly popular bicyclization strategy represents a uniquely powerful tool to access highly
functionalized polycyclic structures of chemical and biomedical importance.13 With both unsaturated
moieties, 1,6ꢀenynes are significant building blocks for metalꢀcatalyzed tandem additions and result in
functionalized cyclic structures via synergistic domino bicyclizations across C=C and C≡C bonds of
various substrates in an atomꢀ and stepꢀeconomical manner.14 In recent years, we have developed
2
ACS Paragon Plus Environment

Page 3 of 28
The Journal of Organic Chemistry
domino bicyclization reactions for polycyclic framework formations.15 As a continuation of our project
on these bicyclizations, we became interested in metalꢀcatalyzed cycloadditions between 1,6ꢀenynes and
nucleophiles. Considering the significant applications of Cuꢀcatalyzed C−S bond forming reactions,6 we
envisioned that in the presence of suitable copper catalyst, potassium sulfide could be engaged in
additional bondꢀforming events with C=C and C≡C bonds of 1,6ꢀenyne conjugate system12f, thereby
facilitating the construction of densely functionalized indeno[1,2ꢀc]thiophenes with concomitant
multiple CꢀS and C–C bond formation (Scheme 1). Herein, we would like to report the realization of
this concept via CuCl2ꢀcatalyzed cyclization cascades which enabled the oneꢀpot synthesis of important
indeno[1,2ꢀc]thiophenes. To the best of our knowledge, the present work represents the first example of
1,6ꢀenyneꢀdehydrobicyclization for forming important types of tricyclic products containing indene and
thiophene motifs using potassium sulfide as a sulfurating reagent through incorporation of a sulfur atom
into the desired structure system.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 1. Domino Synthesis of Indeno[1,2-c]thiophenes
Results and Discussion
Our initial investigations focused on the cascade cyclization of 1,6ꢀenynes 1a with K2S for reaction
condition optimization using different catalysts, bases and solvents (Table 1). Firstly, the reaction
between 1,6ꢀenynes 1a and K2S was conducted with 20 mol% CuCl2 and 3.0 equivalents of Cs2CO3 at
o
120 C under an argon atmosphere in N,Nꢀdimethylformamide (DMF) for 24 h. This set of conditions
gave the desired product 2a in a 35% yield, but with an intramolecular cycloaddition product 3a in a
50% yield16 (entry 1). To improve the yield of 2a, a series of different bases, including K2CO3, Et3N,
Bu3N, tꢀBuOLi, and diisopropylamine (DIPA), were then evaluated (entry 2ꢀ6), and the results showed
that DIPA was proven to be most effective for this transformation, affording a 67% chemical yield of 2a
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 28
(entry 6). Several other copper salts used in this reaction like CuCl, CuBr, CuI, Cu(OTf)2 and Cu(OAc)2,
all showed poor catalytic activities toward the formation of 2a (entries 7ꢀ11). Similarly, the inferior
outcomes were also observed when the reactions were carried out using FeCl3, PdCl2 and Pd(OAc)2 as
catalysts (entries 12ꢀ14). Afterwards, taking the combination of CuCl2 with DIPA, we varied other
parameters. The effect of the solvent was subsequently investigated. Unluckily, the use of other aprotic
solvents, such as 1,4ꢀdioxane, dimethyl sulphoxide (DMSO), acetonitrile (CH3CN), and toluene, failed
to improve the yield of 2a, but favorably gave access to product 3a (entries 15ꢀ18). It was also found
that the reaction temperatures affected the reaction efficiency. The relatively lower conversion into 2a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
o
was detected with reaction temperature being at either 110 C or 130 C (entries 19 and 20). An
increased or decreased loading of CuCl2 or DIPA did not significantly improve the yield (compare entry
6 vs entries 21–24). Adjusting the ratio of 1a with K2S to 1:4 decreased the yield of 2a (entry 25). The
identical reaction performed under air conditions dramatically lowered the yield to 27% (entry 26).
After careful optimizations, some water can promote this transformation, leading to the higher yield of
2a (75%) and suppressing the formation of 3a (entry 27). Without CuCl2 or DIPA, the reaction is
beneficial to form product 3a without observation of product 2a (entries 28ꢀ29).
Table 1. Optimization of Reaction Conditionsa
entry
cat. (mol %)
base
solvent
t / oC
yield (%)b
2a / 3a
35/50
1
2
3
4
5
CuCl2 (20)
CuCl2 (20)
CuCl2 (20)
CuCl2 (20)
CuCl2 (20)
Cs2CO3
K2CO3
Et3N
DMF
DMF
DMF
DMF
DMF
120
120
120
120
120
34/53
46/44
Bu3N
trace/80
44/41
tBuOLi
4
ACS Paragon Plus Environment

Page 5 of 28
The Journal of Organic Chemistry
6
CuCl2 (20)
CuCl (20)
CuBr (20)
CuI (20)
DIPA
DIPA
DIPA
DIPA
DIPA
DIPA
DIPA
DIPA
DIPA
DIPA
DIPA
DIPA
DIPA
DIPA
DIPA
DIPA
DIPA
DIPA
DIPA
DIPA
DIPA
DIPA
DIPA
ꢀ
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
120
120
120
120
120
120
120
120
120
67/16
32/56
32/50
33/51
40/43
23/37
15/47
34/61
37/50
15/57
10/62
24/47
trace/84
38/36
57/32
66/20
42/44
34/53c
54/32d
43/50e
27/56f
75/8g
1
2
3
4
5
6
7
8
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
Cu(OTf)2 (20)
Cu(OAc)2 (20)
FeCl3 (20)
PdCl2 (20)
Pd(OAc)2 (20)
CuCl2 (20)
CuCl2 (20)
CuCl2 (20)
CuCl2 (20)
CuCl2 (20)
CuCl2 (20)
CuCl2 (25)
CuCl2 (15)
CuCl2 (20)
CuCl2 (20)
CuCl2 (20)
CuCl2 (20)
CuCl2 (20)
ꢀ
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
1,4ꢀdioxane 120
DMSO
CH3CN
toluene
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
120
120
120
110
130
120
120
120
120
120
120
120
120
120
0/52g
CuCl2 (20)
trace/41g
aReaction conditions: 1a (0.5 mmol), K2S (3.0 mmol), catalyst (x mol %), base (3.0 equiv.) and solvent (4.0 mL) under argon
b
c
d
atmosphere for 24 h. Isolated yields based on 1a. Isolated yield using 4.0 equiv of DIPA. Isolated yield using 2.0 equiv of DIPA.
52
53
54
55
56
57
58
59
60
eIsolated yield in 1:4 ratio of 1a with K2S. fIsolated yield under air conditions. gIsolated yield using 6.0 equiv of H2O as additive.
After determining the optimal reaction conditions (Table 1, entry 27), we then set out to investigate the
scope of sulfurꢀenabled dehydrobicyclization toward the formation of indeno[1,2ꢀc]thiophenes 2 by
5
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 28
examining 1,6ꢀenyne component with potassium sulfide (Scheme 2). A wide range of 1,6ꢀenynes 1
smoothly reacted with potassium sulfide to deliver the corresponding densely functionalized indeno[1,2ꢀ
c]thiophenes 2aꢀ2y with yields ranging from 45%–79%. 1,6ꢀEnynes 1 possessing both arylvinyl and
arylalkynyl moieties attached by electronꢀdonating or electronꢀwithdrawing groups did not hamper the
reaction process. A large variety of diverse functional groups directly bounded phenyl ring, including
methyl, methoxy, ethyl, tꢀbutyl, fluoro, and chloro, can tolerate the catalytic conditions well. Electronic
properties of substituents on both arylvinyl and the arylalkynyl moieties imposed an obvious impact on
the reaction efficiency and the obtained yields. For instance, with the methyl group on the arylvinyl
moiety (Ar), upon treatment of substrates 1 with electronꢀdonating groups like methoxy (1c) and ethyl
(1d), and the desired products 2c and 2d were provided in 68% and 76% yields, respectively. In
contrast, the presence of a fluoro group of substrate 1g resulted in a 45% chemical yield. These
observations indicated that substrates 1 bearing electronꢀdonating groups showed the higher reactivity
than those with electronꢀwithdrawing counterparts. Alternatively, 1,6ꢀenynes 1h carrying a nꢀbutyl
group on the alkynyl moiety still showed high reactivity in current dehydrobicyclization, delivering the
corresponding product 2h in a 59% yield. Unluckily, 1,5ꢀenyne 4a was not an adaptable substrate for
this dehydrobicyclization reaction without observation of the expected product 5a, as the reaction did
not proceed at all under the standard conditions (Scheme 2, 5a). Highly substituted indeno[1,2ꢀ
c]thiophenes 2 were fully characterized by their NMR spectroscopy and HRMS. Furthermore, the
structure of product 2a was determined by single crystal Xꢀray diffraction (See Supporting Information).
In general, the current protocol represents a new and practical pathway for directly constructing richly
decorated indeno[1,2ꢀc]thiophenes.17
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 2. Dehydrocyclization of 1,6-Enynes with K2Sa,b
6
ACS Paragon Plus Environment

Page 7 of 28
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
aReaction conditions: 1 (0.5 mmol), K2S (3 mmol), CuCl2 (20 mol %), DIPA (1.5 mmol), DMF (4 mL), and H2O (3.0 mmol) under
argon atmosphere and 120 oC for 24 h. bIsolated yields based on 1
To understand dehydrogenation process and the roles of water and base promoter, the reaction of 1,6ꢀ
enyne 1a was carried out in dry DMF solvent using dry DIPA as a base promoter, and a significantly
dropped yield (35%) of 2a was obtained (Scheme 3a), whereas using dry Et3N as a base promoter under
the same conditions, only trace amount of 2a was observed (Scheme 3b). These experimental outcomes
indicated that free proton from DIPA may be served a hydrogen acceptor to generate hydrogen gas
during dehydrogenation process. Compared with DIPA base, water is more suitable as a hydrogen
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 28
acceptor to facilitate dehydrogenation transformation under DIPAꢀmediated conditions. Upon
exchanging the carbonyl group for hydroxy functionality on the 1,6ꢀenyne unit, unactivated 1,6ꢀenyne 6
failed to give product 7 under the standard conditions (Scheme 3c), showing that the carbonyl group
located in the 1,6ꢀenyne unit plays a key role in the success of this reaction, which may activate alkenyl
and alkynyl groups of 1,6ꢀconjugated enynes 1.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 3. Control Experiments
Scheme 4. Proposed Mechanism
On the basis of literature reports12f,18 and from the observations of the experiment results, a possible
mechanism for the present dehydrobicyclization is proposed in Scheme 4. In the presence of Cu(II)
catalyst, Michael addition and subsequent 5ꢀexoꢀdig cyclization of 1,6ꢀenynes 1 and potassium sulfide
8
ACS Paragon Plus Environment

Page 9 of 28
The Journal of Organic Chemistry
occur to give indenone intermediate B, followed by Cu(II)ꢀcatalyzed intramolecular 5ꢀendoꢀtrig
cyclization to deliver intermediate C. Intermediate C undergoes an enolꢀketone tautomerization and
successive dehydrogenation18 mediated by DIPA to convert into the final indeno[1,2ꢀc]thiophenes 2.
Although a detailed mechanism for forming products 2 is not yet clear to us, it seems that free protons
from DIPA and water play an important role in the dehydrogenation process.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
In summary, we have developed an unprecedented cascade dehydrobicyclization reaction of 1,6ꢀenynes
using potassium sulfide as a sulfurating reagent, enabling a new Cu(II)ꢀcatalyzed protocol toward
arylated indeno[1,2ꢀc]thiophenes with substituted diversity in an atomꢀeconomic fashion. The reaction
pathway involves a twice Sꢀadditions and leads to the formation of two new ring and three new
chemical bonds. The annulation efficiency, high atomꢀeconomy, and flexible skeletal modification as
well as workable reaction conditions provide a facile and practical entry to potentially bioactive
indeno[1,2ꢀc]thiophenes in acceptable yields. A further investigation on evaluating biological activity of
these resultant compounds is currently underway.
Experimental Section
General procedure for the synthesis of Compounds 1
Example for the synthesis of 1a
Under argon conditions, 2ꢀiodophenylethanone (1.23 g, 5.0 mmol), ethynylbenzene (0.612 g. 6.0 mmol),
and Et3N (dry, 20 mL), Pd(PPh3)2Cl2 (0.1 mmol) and CuI (0.05 mmol) were successively introduced
o
into dry 100ꢀmL Shrek tube. Then the mixture was stirred at 50 C for 12 h. The reaction mixture was
diluted with EtOAc (60 mL) and washed with water (3 x 20 mL). The organic layer was dried over
Na2SO4, concentrated under the reduced pressure to give dark brown oil, which was further purified via
column chromatography on silica gel (petroleum ether and EtOAc) to give pure 1ꢀ(2ꢀ
(phenylethynyl)phenyl)ethanone in a 89% yield (0.979 g). Next, the resulting 1ꢀ(2ꢀ(phenylethynyl)
phenyl)ethanone (220 mg, 1.0 mmol) and 4ꢀmethylbenzaldehyde (144 mg, 1.2 mmol) were added into
o
4.0 mL of 95% EtOH at 0 C. Then, 10 % NaOH solution (1.0 mL) was slowly added into the reaction
9
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 28
o
system and stirred for 2.0 hours at 0 C. After the completion of reaction, 5% HCl solution was added
until the mixture was neutralized (pH = 7.0). The reaction mixture was extracted with diethyl ether (3 x
10 mL). The organic phase was separated and washed with saturated aqueous NH4Cl and dried over
Na2SO4. The solvent was evaporated and the crude material was purified by flash gel column
chromatography (petroleum ether and EtOAc) to afford pure 1,6ꢀenynes 1a in a 97% yield (322 mg).
1ꢀ(2ꢀ(Phenylethynyl)phenyl)ꢀ3ꢀ(pꢀtolyl)propꢀ2ꢀenꢀ1ꢀone (1a)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
Pale yellow solid, 277 mg, total 86%; mp 61ꢀ62 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.75ꢀ7.65 (m,
13
3H), 7.57ꢀ7.39 (m, 7H), 7.32ꢀ7.17 (m, 5H), 2.39 (s, 3H); C NMR (100 MHz, CDCl3; δ, ppm) 193.9,
144.7, 142.1, 141.1, 133.2, 132.3, 132.1, 130.7, 129.7, 128.6, 128.3, 124.9, 122.8, 121.5, 95.4, 88.0,
21.5; IR (KBr, v) 3045, 1654, 1598, 1583, 1509, 1490, 1437, 1326, 1249, 1200, 1019, 976, 813 cmꢀ1;
HRMS (APCIꢀTOF) m/z calcd for C24H19O, 323.1436 [M+H]+, found 323.1432.
3ꢀ(pꢀTolyl)ꢀ1ꢀ(2ꢀ(pꢀtolylethynyl)phenyl)propꢀ2ꢀenꢀ1ꢀone (1b)
Pale yellow solid, 297 mg, total 88%; mp 99ꢀ100 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.75ꢀ7.63 (m,
3H), 7.57ꢀ7.41 (m, 5H), 7.31ꢀ7.27 (m, 2H,), 7.19 (d, J = 8.0 Hz, 2H, Ar), 7.05 (d, J = 8.8 Hz, 2H), 2.40
13
(s, 3H), 2.34 (s, 3H); C NMR (100 MHz, CDCl3; δ, ppm) 194.0, 144.6, 142.0, 141.0, 138.8, 133.1,
132.2, 131.5, 130.7, 129.6, 129.0, 128.6, 128.2, 124.9, 121.8, 119.7, 95.7, 87.4, 21.5; IR (KBr, v) 3057,
3020, 1667, 1601, 1566, 1510, 1441, 1326, 1202, 1050, 1020, 976, 809 cmꢀ1; HRMS (APCIꢀTOF) m/z
calcd for C25H21O, 337.1592[M+H]+, found 337.1588.
1ꢀ(2ꢀ((4ꢀMethoxyphenyl)ethynyl)phenyl)ꢀ3ꢀ(pꢀtolyl)propꢀ2ꢀenꢀ1ꢀone (1c)
o
Pale yellow solid, 299 mg, total 85%; mp 82ꢀ83 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.73ꢀ7.63 (m,
3H), 7.57ꢀ7.48 (m, 4H), 7.45ꢀ7.41 (m, 1H), 7.34ꢀ7.30 (m, 2H), 7.19 (d, J = 8.0 Hz, 2H), 6.78ꢀ6.74 (m,
2H), 3.80 (s, 3H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3; δ, ppm) 194.0, 159.8, 144.4, 141.9, 141.0,
133.1, 132.9, 132.2, 130.7, 129.7, 128.6, 128.0, 125.0, 121.9, 114.9, 113.9, 95.6, 86.9, 55.3, 21.6; IR
(KBr, v) 3052, 3012, 1664, 1600, 1568, 1513, 1439, 1334, 1290, 1203, 1189, 1052, 1030, 978, 825 cmꢀ1;
HRMS (APCIꢀTOF) m/z calcd for C25H21O2, 353.1542[M+H]+, found 353.1510.
10
ACS Paragon Plus Environment

Page 11 of 28
The Journal of Organic Chemistry
1ꢀ(2ꢀ((4ꢀEthylphenyl)ethynyl)phenyl)ꢀ3ꢀ(pꢀtolyl)propꢀ2ꢀenꢀ1ꢀone (1d)
1
2
3
o
Pale yellow solid, 280 mg, total 80%; mp 50ꢀ51 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.72ꢀ7.64 (m,
4
5
6
3H), 7.57ꢀ7.42 (m, 5H), 7.31 (d, J = 8.0 Hz, 2H), 7.18 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 8.0 Hz, 2H),
7
8
13
2.67ꢀ2.60 (m, 2H), 2.40 (s, 3H), 1.26ꢀ1.19 (m, 3H); C NMR (100 MHz, CDCl3; δ, ppm) 194.0, 145.1,
9
144.6, 142.0, 141.0, 133.1, 132.2, 131.6, 130.7, 129.6, 128.7, 128.6, 128.2, 127.8, 124.9, 121.8, 119.9,
95.7, 87.4, 28.8, 21.6, 15.3; IR (KBr, v) 3050, 1698, 1597, 1558, 1507, 1456, 1385, 1327, 1180, 1021,
983, 872, 816 cmꢀ1; HRMS (APCIꢀTOF) m/z calcd for C26H23O, 351.1749[M+H]+, found 351.1753.
1ꢀ(2ꢀ((4ꢀ(tertꢀButyl)phenyl)ethynyl)phenyl)ꢀ3ꢀ(pꢀtolyl)propꢀ2ꢀenꢀ1ꢀone (1e)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
Pale yellow solid, 310 mg, total 82%; mp 75ꢀ76 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.73ꢀ7.64 (m,
3H), 7.57ꢀ7.42 (m, 5H), 7.34ꢀ7.28 (m, 3H), 7.24 (s, 1H), 7.18 (d, J = 7.6 Hz, 2H), 2.39 (s, 3H), 1.30 (s,
9H); 13C NMR (100 MHz, CDCl3; δ, ppm) 194.0, 151.9, 144.5, 142.0, 141.0, 132.2, 131.3, 130.7, 129.6,
128.7, 128.6, 128.4, 128.2, 125.2, 125.0, 121.8, 119.7, 95.7, 87.4, 34.8, 31.1, 21.5; IR (KBr, v) 3055,
1660, 1596, 1586, 1568, 1508, 1332, 1199, 1178,1091, 1053, 1023, 979, 836 cmꢀ1; HRMS (APCIꢀTOF)
m/z calcd forC28H27O, 379.2062 [M+H]+, found 379.2057.
3ꢀ(pꢀTolyl)ꢀ1ꢀ(2ꢀ(mꢀtolylethynyl)phenyl)propꢀ2ꢀenꢀ1ꢀone (1f)
o
Pale yellow solid, 286 mg, total 85%; mp 84ꢀ85 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.75ꢀ7.64 (m,
13
3H), 7.60ꢀ7.43 (m, 5H), 7.23ꢀ7.08 (m, 6H), 2.39 (s, 3H), 2.16 (s, 3H); C NMR (100 MHz, CDCl3; δ,
ppm) 193.9, 144.4, 141.1, 137.9, 133.1, 132.2, 132.1, 130.8, 128.7, 128.6, 128.3, 128.1, 124.9, 122.5,
121.6, 95.7, 87.7, 21.5, 20.9, 1.04; IR (KBr, v) 3055, 1683, 1596, 1509, 1488,1456, 1325, 1257,1199,
1177, 1052, 1020, 967, 813 cmꢀ1; HRMS (APCIꢀTOF) m/z calcd for C25H21O, 337.1592 [M+H]+, found
337.1598.
1ꢀ(2ꢀ((4ꢀFluorophenyl)ethynyl)phenyl)ꢀ3ꢀ(pꢀtolyl)propꢀ2ꢀenꢀ1ꢀone (1g)
o
Pale yellow solid, 286 mg, total 84%; mp 86ꢀ87 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.79ꢀ7.58 (m,
3H), 7.56ꢀ7.42 (m, 5H), 7.40ꢀ7.33 (m, 2H), 7.19 (d, J = 7.8 Hz, 2H), 6.98ꢀ6.85 (m, 2H), 2.40 (s, 3H);
13C NMR (100 MHz, CDCl3; δ, ppm) 193.8, 162.1 (JCF = 248.5 Hz), 143.4, 141.2, 133.5 (JCF = 8.4 Hz),
11
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 28
133.1, 132.1, 130.7, 129.7, 128.7, 128.5, 128.4, 124.9, 120.1, 118.8 (JCF = 3.4 Hz), 115.6 (JCF = 22.0
Hz), 94.2, 87.7, 21.6; IR (KBr, v) 3074, 3024, 1655, 1587, 1508, 1335,1227, 1181, 1157,1093, 1054,
1022, 982, 884 cmꢀ1; HRMS (APCIꢀTOF) m/z calcd for C24H18FO, 341.1342 [M+H]+, found 341.1340.
1ꢀ(2ꢀ(Hexꢀ1ꢀynꢀ1ꢀyl)phenyl)ꢀ3ꢀ(pꢀtolyl)propꢀ2ꢀenꢀ1ꢀone (1h)
1
2
3
4
5
6
7
8
9
1
Yellow oil, 272 mg, total 90%; H NMR (400 MHz, CDCl3; δ, ppm) 7.63ꢀ7.57 (m, 2H), 7.54ꢀ7.49 (m,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3H), 7.45ꢀ7.32 (m, 3H), 7.22 (d, J = 8.0 Hz, 2H), 2.39 (s, 3H), 2.38ꢀ2.33 (m, 2H), 1.49ꢀ1.41 (m, 2H),
1.40ꢀ1.28 (m, 2H), 0.84ꢀ0.77 (m, 3H); 13C NMR (100 MHz, CDCl3; δ, ppm) 194.6, 191.9, 144.3, 142.3,
141.0 ,133.2, 132.2, 130.4, 129.7, 128.5, 128.3, 127.6, 125.1, 122.3, 97.0, 30.6, 21.9, 21.5, 19.3, 13.5;
IR (KBr, v) 3058, 1655, 1600, 1559, 1485,1399, 1206, 1094, 974, 866 cmꢀ1; HRMS (APCIꢀTOF) m/z
calcd for C22H23O, 303.1743 [M+H]+, found 303.1718.
3ꢀPhenylꢀ1ꢀ(2ꢀ(phenylethynyl)phenyl)propꢀ2ꢀenꢀ1ꢀone (1i)
o
Pale yellow solid, 277 mg, total 90%; mp 77ꢀ78 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.78ꢀ7.71 (m,
2H), 7.68 (d, J = 7.6 Hz, 1H), 7.64ꢀ7.58 (m, 3H), 7.55ꢀ7.44 (m, 2H), 7.42ꢀ7.36 (m, 5H), 7.32ꢀ7.20 (m,
3H); 13C NMR (100 MHz, CDCl3; δ, ppm) 193.7, 144.4, 141.9, 134.9, 133.2, 131.6, 130.9, 130.6, 128.9,
129.8, 128.6, 128.4, 128.2, 125.8, 122.7, 121.6, 95.5, 88.0; IR (KBr, v) 3074, 3022, 1712, 1600, 1491,
1442, 1331, 1178, 1056, 956, 881 cmꢀ1; HRMS (APCIꢀTOF) m/z calcd for C23H17O, 309.1279 [M+H]+,
found 309.1280.
3ꢀPhenylꢀ1ꢀ(2ꢀ(pꢀtolylethynyl)phenyl)propꢀ2ꢀenꢀ1ꢀone (1j)
o
Pale yellow solid, 283 mg, total 88%; mp 78ꢀ79 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.81ꢀ7.69 (m,
13
2H), 7.69ꢀ7.58 (m, 4H), 7.58ꢀ7.31 (m, 6H), 7.28 (s, 1H), 7.04 (d, J = 8.0 Hz, 2H), 2.33 (s, 3H); C
NMR (100 MHz, CDCl3; δ, ppm) 193.8, 144.3, 141.8, 138.8, 134.9, 133.1, 131.5, 130.8, 130.5, 129.5,
129.0, 128.9, 128.8, 128.6, 128.2, 125.9, 121.8, 119.6, 95.8, 87.4, 21.5; IR (KBr, v) 3079, 3061, 3029,
1655, 1597, 1584, 1510, 1447, 1335, 1225, 1207, 1106, 1005, 1018, 978, 818 cmꢀ1; HRMS (APCIꢀTOF)
m/z calcd for C24H19O, 323.1486 [M+H]+, found 323.1438.
1ꢀ(2ꢀ((4ꢀMethoxyphenyl)ethynyl)phenyl)ꢀ3ꢀphenylpropꢀ2ꢀenꢀ1ꢀone (1k)
12
ACS Paragon Plus Environment

Page 13 of 28
The Journal of Organic Chemistry
Pale yellow solid, 304 mg, total 90%; mp 57ꢀ58 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.77ꢀ7.69 (m,
2H), 7.69ꢀ7.59 (m, 4H), 7.54ꢀ7.48 (m, 1H), 7.46ꢀ7.35 (m, 4H), 7.34ꢀ7.28 (m, 2H), 6.75 (d, J = 8.8 Hz,
2H), 3.79 (s, 3H); 13C NMR (100 MHz, CDCl3; δ, ppm) 193.8, 159.89 (s, 6H), 144.2, 141.7, 134.9,
133.1, 133.0, 130.9, 130.5, 128.9, 128.8, 128.5, 128.0, 125.9, 122.0, 114.8, 113.9, 95.8, 86.9, 55.3; IR
(KBr, v) 3056, 3024, 1665, 1606, 1574, 1512, 1494, 1447, 1332, 1289, 1251, 1205, 1174, 1051, 975,
827 cmꢀ1; HRMS (APCIꢀTOF) m/z calcd for C24H19O2, 339.1385 [M+H]+, found 339.1386.
1ꢀ(2ꢀ((4ꢀEthylphenyl)ethynyl)phenyl)ꢀ3ꢀphenylpropꢀ2ꢀenꢀ1ꢀone (1l)
o
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
Pale yellow solid, 289 mg, total 86%; mp 55ꢀ56 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.77ꢀ7.71 (m,
2H), 7.69ꢀ7.60 (m, 4H), 7.54ꢀ7.49 (m, 1H), 7.47ꢀ7.35 (m, 4H), 7.31 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 8.0
Hz, 2H), 2.63 (d, J = 7.6 Hz, 2H), 1.27ꢀ1.16 (m, 3H); 13C NMR (100 MHz, CDCl3; δ, ppm) 193.8, 145.1,
144.3, 141.9, 134.9, 133.2, 131.6, 130.9, 130.5, 128.9, 128.8), 128.6, 128.2, 127.9, 125.9, 121.9, 119.9,
95.9, 87.4, 28.8, 15.3; IR (KBr, v) 3062, 3027, 2342, 1662, 1607, 1509, 1448, 1330, 1205, 1157, 1092,
1054, 1018, 971, 832 cmꢀ1; HRMS (APCIꢀTOF) m/z calcd for C25H21O, 337.1592 [M+H]+, found
337.1591.
1ꢀ(2ꢀ((4ꢀ(tertꢀButyl)phenyl)ethynyl)phenyl)ꢀ3ꢀphenylpropꢀ2ꢀenꢀ1ꢀone (1m)
o
Pale yellow solid, 306 mg, total 84%; mp 85ꢀ86 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.77ꢀ7.70 (m,
2H), 7.68ꢀ7.59 (m, 4H), 7.54ꢀ7.35 (m, 5H), 7.32 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H), 1.30 (s,
9H); 13C NMR (100 MHz, CDCl3; δ, ppm) 193.8, 152.0, 144.3, 141.9, 134.9, 133.1, 131.3, 130.8, 130.4,
128.9, 128.8, 128.6, 128.2, 125.9, 125.3, 121.8, 119.6, 95.8, 87.4, 34.8, 31.1, 31.0; IR (KBr, v) 3084,
3053, 1662, 1599, 1505, 1447, 1334, 1203, 1115, 1053, 1021, 977, 832 cmꢀ1; HRMS (APCIꢀTOF) m/z
calcd for C27H25O, 365.1905 [M+H]+, found 365.1884.
3ꢀPhenylꢀ1ꢀ(2ꢀ(mꢀtolylethynyl)phenyl)propꢀ2ꢀenꢀ1ꢀone (1n)
o
Pale yellow solid, 283 mg, total 88%; mp 65ꢀ66 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.80ꢀ7.72 (m,
2H), 7.69ꢀ7.62 (m, 4H), 7.55ꢀ7.35 (m, 5H), 7.22 (d, J = 8.4 Hz, 1H), 7.18ꢀ7.07 (m, 3H), 2.16 (s, 3H);
13C NMR (100 MHz, CDCl3; δ, ppm) 193.7, 144.1, 142.0, 138.0, 134.9, 133.2, 132.2, 131.0, 130.5,
13
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 28
129.6, 128.9, 128.8, 128.6, 128.4, 128.2, 125.8, 122.4, 121.7, 95.9, 87.7, 21.0; IR (KBr, v) 3053, 1661,
1601, 1446, 1331, 1209, 1094, 1052, 1020, 974, 864 cmꢀ1; HRMS (APCIꢀTOF) m/z calcd for [M+H]+
C24H19O 323.1436, found 323.1438.
1
2
3
4
5
6
7
8
1ꢀ(2ꢀ((4ꢀFluorophenyl)ethynyl)phenyl)ꢀ3ꢀphenylpropꢀ2ꢀenꢀ1ꢀone (1o)
9
o
Pale yellow solid, 290 mg, total 89%; mp 83ꢀ84 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.76ꢀ7.69 (m,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
2H), 7.67ꢀ7.43 (m, 6H), 7.43ꢀ7.31 (m, 5H), 6.96ꢀ6.88 (m, 2H); C NMR (100 MHz, CDCl3; δ, ppm)
193.6, 162.2 (JCF = 248.7 Hz), 144.4, 141.9, 134.8, 133.5 (JCF = 8.4 Hz), 133.1, 130.9, 130.6, 129.0,
128.8, 128.5, 128.4, 125.8, 121.4, 118.8 (JCF = 3.5 Hz), 115.6 (JCF = 22.0 Hz), 94.3, 87.7; IR (KBr, v)
3078, 3062, 3026, 1660, 1599, 1508, 1448, 1334, 1226, 1153, 1092, 1019, 981, 828 cmꢀ1 ; HRMS
(APCIꢀTOF) m/z calcd for C23H16FO, 327.1185 [M+H]+, found 327.1183.
1ꢀ(2ꢀ((4ꢀChlorophenyl)ethynyl)phenyl)ꢀ3ꢀphenylpropꢀ2ꢀenꢀ1ꢀone (1p)
Pale yellow solid, 296 mg, total 87%; mp 86ꢀ87 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.74ꢀ7.60 (m,
o
13
5H), 7.57ꢀ7.36 (m, 7H), 7.30 (s, 1H), 7.20 (d, J = 8.4 Hz, 2H); C NMR (100 MHz, CDCl3; δ, ppm)
193.7, 144.6, 142.0, 134.8, 132.7, 130.7, 128.8, 128.5, 125.8, 121.3, 121.2, 94.2, 88.9; IR (KBr, v) 3078,
3062, 1669, 1590, 1558, 1507, 1457, 1384, 1259, 1173, 1090, 975, 834 cmꢀ1; HRMS (APCIꢀTOF) m/z
calcd for C23H16ClO, 343.0890 [M+H]+, found 343.0872.
3ꢀ(4ꢀMethoxyphenyl)ꢀ1ꢀ(2ꢀ(phenylethynyl)phenyl)propꢀ2ꢀenꢀ1ꢀone (1q)
Pale yellow solid, 297 mg, total 88%; mp 70ꢀ71 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.71ꢀ7.65 (m,
o
3H), 7.58 (d, J = 8.8 Hz, 2H), 7.47ꢀ7.38 (m, 7H), 7.27ꢀ7.22 (m, 2H), 6.90 (d, J = 8.8 Hz, 2H), 3.86 (s,
3H); 13C NMR (100 MHz, CDCl3; δ, ppm) 193.7, 161.7, 144.4, 142.3, 133.2, 131.6, 130.7, 130.4, 130.0,
128.7, 128.6, 128.4, 128.3, 127.6, 123.6, 122.8, 121.5, 114.4, 95.3, 88.2, 55.4; IR (KBr, v) 3074, 1683,
1596, 1507, 1456,1255, 1172, 1105, 975, 868 cmꢀ1; HRMS (APCIꢀTOF) m/z calcd for C24H19O2,
339.1380 [M+H]+, found 339.1353.
3ꢀ(4ꢀMethoxyphenyl)ꢀ1ꢀ(2ꢀ(pꢀtolylethynyl)phenyl)propꢀ2ꢀenꢀ1ꢀone (1r)
Pale yellow solid, 296 mg, total 84%; mp 77ꢀ78 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.73ꢀ7.63 (m,
o
14
ACS Paragon Plus Environment

Page 15 of 28
The Journal of Organic Chemistry
3H), 7.58 (d, J = 8.4 Hz, 2H), 7.53ꢀ7.42 (m, 3H), 7.31ꢀ7.27 (m, 2H), 7.05 (d, J = 8.0 Hz, 2H), 6.90 (d, J
= 8.8 Hz, 2H), 3.86 (s, 3H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3; δ, ppm) 193.9, 161.7, 144.3,
142.2, 138.8, 133.0, 131.5, 130.6, 130.3, 129.0, 128.7, 128.2, 127.7, 123.7, 121.7, 119.7, 114.4, 95.6,
87.5, 55.4, 21.5; IR (KBr, v) 3057, 3009, 1655, 1596, 1512, 1441, 1306, 1293, 1180, 1024, 986, 816 cmꢀ
1; HRMS (APCIꢀTOF) m/z calcd for C25H21O2, 353.1542 [M+H]+, found 353.1546.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3ꢀ(4ꢀMethoxyphenyl)ꢀ1ꢀ(2ꢀ((4ꢀmethoxyphenyl)ethynyl)phenyl)propꢀ2ꢀenꢀ1ꢀone (1s)
o
Pale yellow solid, 313 mg, total 85%; mp 58ꢀ59 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.78ꢀ7.24 (m,
10H), 6.90 (d, J = 8.8 Hz, 2H), 6.76 (d, J = 8.8 Hz, 2H), 3.86 (s, 3H), 3.80 (s, 3H); 13C NMR (100 MHz,
CDCl3; δ, ppm) 193.9, 161.6, 159.8, 144.2, 142.0, 133.1, 133.0, 130.6, 130.3, 128.7, 128.0, 127.7, 123.8,
121.9, 114.9, 114.4, 114.1, 114.0, 95.5, 86.9, 55.3; IR (KBr, v) 3050, 3009, 1654, 1597, 1511, 1461,
1335, 1252, 1171, 1054, 1022, 985, 825 cmꢀ1; HRMS (APCIꢀTOF) m/z calcd for C25H21O3, 369.1491
[M+H]+, found 369.1494.
1ꢀ(2ꢀ((4ꢀ(tertꢀButyl)phenyl)ethynyl)phenyl)ꢀ3ꢀ(4ꢀmethoxyphenyl)propꢀ2ꢀenꢀ1ꢀone (1t)
o
Pale yellow solid, 315 mg, total 80%; mp 96ꢀ97 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.71ꢀ7.64 (m,
3H), 7.57 (d, J = 8.8 Hz, 2H), 7.52ꢀ7.42 (m, 3H), 7.33 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 8.4 Hz, 2H), 6.89
(d, J = 8.8 Hz, 2H), 3.86 (s, 3H), 1.30 (s, 9H); 13C NMR (100 MHz, CDCl3; δ, ppm) 193.9, 161.6, 151.9,
144.3, 142.2, 133.1, 131.3, 130.6, 130.3, 128.7, 128.2, 127.7, 125.2, 123.8, 121.7, 119.7, 114.3, 95.6,
87.5, 55.4, 34.8, 31.1; IR (KBr, v) 3061, 1654, 1596, 1570, 1508, 1422, 1305, 1252, 1176, 1026, 984,
824 cmꢀ1; HRMS (APCIꢀTOF) m/z calcd for C28H27O, 395.2011[M+H]+, found 395.2006.
3ꢀ(4ꢀMethoxyphenyl)ꢀ1ꢀ(2ꢀ(mꢀtolylethynyl)phenyl)propꢀ2ꢀenꢀ1ꢀone (1u)
o
Pale yellow solid, 285 mg, total 81%; mp 54ꢀ55 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.77ꢀ7.63 (m,
3H), 7.59 (d, J = 8.4 Hz, 2H), 7.54ꢀ7.42 (m, 3H), 7.28ꢀ7.04 (m, 4H), 6.90 (d, J = 8.8 Hz, 2H), 3.84 (s,
3H), 2.17 (s, 3H); 13C NMR (100 MHz, CDCl3; δ, ppm) 193.7, 161.7, 144.1, 142.3, 138.0, 133.1, 132.2,
130.7, 130.4, 129.5, 128.6, 128.3, 128.2, 127.6, 123.7, 122.5, 121.6, 114.4, 95.7, 87.8, 55.4, 21.0; IR
(KBr, v) 3058, 3034, 3005, 1655, 1596, 1572, 1513, 1424, 1306, 1293, 1255, 1182, 1024, 949, 824 cmꢀ1;
15
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 28
HRMS (APCIꢀTOF) m/z calcd for C25H21O2, 353.1542 [M+H]+, found 353.1540.
1
2
3
1ꢀ(2ꢀ((4ꢀFluorophenyl)ethynyl)phenyl)ꢀ3ꢀ(4ꢀmethoxyphenyl)propꢀ2ꢀenꢀ1ꢀone (1v)
4
5
6
7
8
9
Pale yellow solid, 296 mg, total 83%; mp 83ꢀ84 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.71ꢀ7.63 (m,
3H), 7.60ꢀ7.42 (m, 5H), 7.39ꢀ7.35 (m, 2H), 6.97ꢀ6.88 (m, 4H), 3.86 (s, 3H); 13C NMR (100 MHz,
CDCl3; δ, ppm) 193.8, 162.8 (JCF = 213.1 Hz), 143.4, 133.5 (JCF = 8.4 Hz), 131.8, 130.3, 128.5 (JCF =
3.5 Hz), 127.5, 123.7, 121.3, 118.9, 115.6 (JCF = 22.0 Hz), 114.4, 94.1, 87.8, 55.4; IR (KBr, v) 3098,
3060, 3043, 1663, 1589, 1513, 1462, 1439, 1421, 1337, 1303, 1258, 1221, 1173, 1094, 1054, 1024, 980,
836, cmꢀ1; HRMS (APCIꢀTOF) m/z calcd for C24H18FO2, 357.1291 [M+H]+, found 357.1284.
1ꢀ(2ꢀ((4ꢀChlorophenyl)ethynyl)phenyl)ꢀ3ꢀ(4ꢀmethoxyphenyl)propꢀ2ꢀenꢀ1ꢀone (1w)
o
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
Pale yellow solid, 316 mg, total 85%; mp 96ꢀ97 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.71ꢀ7.64 (m,
3H), 7.58ꢀ7.41 (m, 5H), 7.33ꢀ7.28 (m, 2H), 7.21 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 8.4 Hz, 2H), 3.86 (s,
3H); 13C NMR (100 MHz, CDCl3; δ, ppm) 193.7, 161.8, 144.6, 142.3, 134.6, 133.1, 132.7, 130.6, 130.3,
128.6, 128.5, 127.5, 123.6, 121.3, 121.1, 114.4, 93.9, 89.0, 55.4; IR (KBr, v) 3064, 1655, 1597, 1514,
1492, 1441, 1425, 1306, 1255, 1183, 1089, 1052, 1025, 986, 823 cmꢀ1; HRMS (APCIꢀTOF) m/z calcd
for C24H18ClO2, 373.0995 [M+H]+, found 373.0984.
3ꢀ(4ꢀChlorophenyl)ꢀ1ꢀ(2ꢀ(phenylethynyl)phenyl)propꢀ2ꢀenꢀ1ꢀone (1x)
o
Pale yellow solid, 304 mg, total 89%; mp 89ꢀ90 C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.75ꢀ7.65 (m,
3H), 7.61ꢀ7.44 (m, 5H), 7.39ꢀ7.23 (m, 7H); 2961, 2862, 6.76 (d, J = 8.8 Hz, 2H), 3.83 (d, J = 22.8 Hz,
6H); 13C NMR (100 MHz, CDCl3; δ, ppm) 193.4, 142.7, 141.7, 136.4, 133.4, 133.3, 131.5, 131.1, 129.7,
129.2, 128.9, 128.8, 128.5, 128.4, 128.3, 126.3, 122.6, 121.6, 95.7, 88.0; IR (KBr, v) 3061, 1659, 1601,
1561, 1489, 1440, 1403, 1328, 1205, 1091, 975, 821 cmꢀ1; HRMS (APCIꢀTOF) m/z calcd for C23H16ClO,
343.0890 [M+H]+, found 343.0881.
3ꢀ(4ꢀChlorophenyl)ꢀ1ꢀ(2ꢀ((4ꢀmethoxyphenyl)ethynyl)phenyl)propꢀ2ꢀenꢀ1ꢀone (1y)
o
1
Pale yellow solid, 312 mg, 84%; mp 83ꢀ84 C; H NMR (400 MHz, CDCl3; δ, ppm) 7.88ꢀ7.15 (m,
13H), 6.83ꢀ6.69 (m, 2H), 3.79 (d, J = 18.8 Hz, 3H); 13C NMR (100 MHz, CDCl3; δ, ppm) 193.4, 160.0,
16
ACS Paragon Plus Environment

Page 17 of 28
The Journal of Organic Chemistry
142.3, 141.5, 136.3, 133.5, 133.0, 131.0, 129.6, 129.2, 128.8, 128.1, 126.3, 122.0, 114.7, 114.0, 96.0,
86.9, 55.3; IR (KBr, v) 3015, 1655, 1605, 1514, 1489, 1324, 1292, 1259, 1204,1139, 1092, 1053, 1021,
982, 822 cmꢀ1; HRMS (APCIꢀTOF) m/z calcd for C24H18ClO2 373.0995 [M+H]+, found 373.0984.
General procedure for the synthesis of products 2
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Example for the synthesis of 2a
A suspension of CuCl2 (0.10 mmol), diisopropanolamine (1.5 mmol, 3.0 equiv), K2S (3.0 mmol, 6.0
equiv), H2O (3.0 mmol, 6.0 equiv) in 3.0 mL of dimethylformamide (DMF) was stirred at room
temperature under an argon atmosphere for 30 min. 1,6ꢀEnyne 1a (1ꢀ(2ꢀ(Phenylethynyl)phenyl)ꢀ3ꢀ(pꢀ
tolyl)propꢀ2ꢀenꢀ1ꢀone, 0.5 mmol, 1.0 equiv) in 1.0 mL of DMF was added into the suspension. With
o
completion of the addition, the reaction system was stirred at 120 C for an additional 24 h. After
completion of the reaction (monitored by TLC), the reaction system was cooled to room temperature
and was diluted with cold water (30 mL), followed by neutralization with a suitable amount of 10% HCl.
Then, the crude solid was collected by Büchner filtration and purified by flash column chromatography
(silica gel, mixtures of petroleum ether/ethyl acetate) to afford the pure product 2a.
3ꢀPhenylꢀ1ꢀ(pꢀtolyl)ꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2a)
Yellow solid, 132 mg, 75% yield; mp 171ꢀ173 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 8.10 (d, J = 8.0
Hz, 2H), 7.74ꢀ7.69 (m, 3H), 7.55ꢀ7.46 (m, 4H), 7.37 (t, J = 7.6 Hz, 1H), 7.30ꢀ7.25 (m, 3H), 2.43 (s, 3H);
13C NMR (100 MHz, DMSOꢀd6; δ, ppm) 180.4, 143.9, 136.4, 136.1, 135.3, 135.2, 130.5, 128.7, 128.6,
127.3, 124.2, 123.7, 123.7, 123.4, 122.9, 122.6, 119.7, 115.7, 16.3; IR (KBr, v) 2915, 1697, 1604, 1532,
1489, 1312, 1263, 1186, 963, 770, 755, 728, 696 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for C24H17OS,
353.0995 [M+H]+, found 353.1019.
1,3ꢀDiꢀpꢀtolylꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2b)
Yellow solid, 130 mg, 71% yield; mp 186ꢀ188 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 8.10 (d, J = 8.0
Hz, 2H), 7.74 (d, J = 7.2 Hz, 1H), 7.59 (d, J = 8.0 Hz, 2H), 7.53 (d, J = 7.6 Hz, 1H), 7.40ꢀ7.30 (m, 5H),
7.27ꢀ7.26 (m, 1H), 2.47 (s, 3H), 2.43 (s, 3H); 13C NMR (100 MHz, CDCl3; δ, ppm) 185.7, 148.9, 141.6,
17
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 28
141.0, 140.7, 140.3, 139.0, 135.7, 134.1, 133.9, 129.7, 129.6, 129.4, 129.1, 128.5, 128.0, 127.83, 124.9,
121.0, 21.5, 21.4; IR (KBr, v) 2963, 1696, 1637, 1617, 1492, 1261, 1183, 1031, 962, 804, 762, 728 cmꢀ
1; HRMS (ESIꢀTOF) m/z calcd for C25H19OS, 367.1151 [M+H]+, found 367.1164.
1
2
3
4
5
6
7
8
3ꢀ(4ꢀMethoxyphenyl)ꢀ1ꢀ(pꢀtolyl)ꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2c)
9
Yellow solid; 130 mg, 68% yield; mp 225ꢀ227 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 8.10 (d, J = 8.4
Hz, 2H), 7.74 (d, J = 7.2 Hz, 1H), 7.62 (d, J = 8.8 Hz, 2H), 7.50 (d, J = 7.6 Hz, 1H), 9.39ꢀ7.35 (m, 1H),
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
7.30ꢀ7.25(m, 3H), 7.05 (d, J = 8.8 Hz, 2H), 3.92 (s, 3H), 2.43 (s, 3H); C NMR (100 MHz, CDCl3; δ,
ppm) 185.7, 160.1, 148.65, 141.6, 140.7, 140.3, 135.7, 133.9, 133.9, 130.0, 129.4, 129.1, 128.0, 127.8,
124.9, 124.8, 120.8, 114.4, 55.4, 21.5; IR (KBr, v) 2967, 1694, 1602, 1591, 1526, 1496, 1456, 1292,
1242, 1182, 1171, 1024, 960, 862, 819, 799, 766 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd forC25H19O2S,
383.1101 [M+H]+, found 383.1117.
3ꢀ(4ꢀEthylphenyl)ꢀ1ꢀ(pꢀtolyl)ꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2d)
Yellow solid; 144 mg, 76% yield; mp 170ꢀ171 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 8.10 (d, J = 8.0
Hz, 2H), 7.73 (d, J = 7.2 Hz, 1H), 7.61 (d, J = 8.0 Hz, 2H), 7.54 (d, J = 7.6 Hz, 1H), 7.39ꢀ7.35 (m, 3H),
7.30ꢀ7.25 (m, 3H), 2.77 (q, J = 7.6 Hz, 2H), 2.43 (s, 3H), 1.35 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3; δ, ppm) 185.7, 148.9, 145.3, 141.6, 141.0, 140.7, 140.3, 135.8, 134.2, 133.9, 129.8, 129.4,
129.1, 128.6, 128.5, 128.0, 127.8, 124.9, 121.0, 113.2, 28.8, 21.6, 15.5; IR (KBr, v) 3022, 2967, 1694,
1601, 1525, 1495 1311, 1006, 963, 818, 763, 726 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for C26H21OS,
381.1307 [M+H]+, found 381.1315.
3ꢀ(4ꢀ(tertꢀButyl)phenyl)ꢀ1ꢀ(pꢀtolyl)ꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2e)
Yellow solid, 120 mg, 59% yield; mp 208ꢀ210 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 8.10 (d, J = 8.0
Hz, 2H), 7.74 (d, J = 7.6 Hz, 1H), 7.64 (d, J = 8.4 Hz, 2H), 7.58ꢀ7.53(m, 3H), 7.41ꢀ7.37 (s, 1H), 7.30ꢀ
13
7.26 (m, 3H), 2.43 (s, 3H), 1.43 (s, 9H); C NMR (100 MHz, DMSOꢀd6; δ, ppm) 180.5, 146.9, 143.6,
136.3, 135.7, 135.5, 135.1, 130.5, 128.9, 128.7, 124.3, 124.2, 123.8, 123.0, 122.8, 122.6, 120.7, 119.6,
115.9, 29.6, 26.1, 16.3; IR (KBr, v) 2961, 1691, 1637, 1617, 1496, 1265, 1181, 1005, 963, 816, 794,
18
ACS Paragon Plus Environment

Page 19 of 28
The Journal of Organic Chemistry
761, 725 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for C28H25OS, 409.1621 [M+H]+, found 409.1599.
1
2
3
3ꢀ(mꢀTolyl)ꢀ1ꢀ(pꢀtolyl)ꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2f)
4
5
o
1
Yellow solid, 97 mg, 53% yield; mp 149ꢀ151 C; H NMR (400 MHz, CDCl3; δ, ppm) 8.10 (d, J = 8.0
Hz, 2H), 7.74 (d, J = 7.2 Hz, 1H), 7.53ꢀ7.51 (m, 3H), 7.43ꢀ7.36 (m, 2H), 7.30ꢀ7.26 (m, 4H), 2.48 (s,
3H), 2.44 (s, 3H); 13C NMR (100 MHz, CDCl3; δ, ppm) 185.7, 149.0, 141.6, 141.2, 140.7, 140.4,
138.79, 135.7, 134.1, 133.9, 132.4, 129.7, 129.4, 129.3, 129.0, 128.9, 128.1, 127.9, 125.7, 124.9, 121.0,
21.6, 21.5; IR (KBr, v) 3021, 2915, 1698, 1603, 1538, 1499, 1465, 1311, 1270, 1182, 1126, 1094, 814,
778, 759, 723 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for C25H19OS, 367.1151 [M+H]+, found 367.1168.
3ꢀ(4ꢀFluorophenyl)ꢀ1ꢀ(pꢀtolyl)ꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2g)
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
1
Yellow solid, 83 mg, 45% yield; mp 205ꢀ206 C; H NMR (400 MHz, CDCl3; δ, ppm) 8.09 (d, J = 8.0
Hz, 2H), 7.74 (d, J = 7.2 Hz, 1H), 7.67 (dd, J = 8.4 Hz, 5.2 Hz, 2H), 7.44ꢀ7.36 (m, 2H), 7.30ꢀ7.25 (m,
13
2H), 7.24ꢀ7.20 (m, 3H), 2.43 (s, 3H); C NMR (100 MHz, CDCl3; δ, ppm) 185.5, 163.0 (JCF = 247.9
Hz), 149.1, 141.6, 141.5, 140.5, 140.4, 135.7, 133.9, 132.4, 130.6 (JCF = 8.2 Hz), 129.5, 128.9, 128.5
(JCF = 3.4 Hz), 128.2, 127.8, 125.0, 120.7, 116.1 (JCF = 21.6 Hz), 21.5; IR (KBr, v) 2963, 1695,1603,
1528, 1497, 1261, 1157, 1095, 1030, 963, 807, 722 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for C24H16FOS,
371.0901 [M+H]+, found 371.0895
1,3ꢀDiphenylꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2h)
o
1
Yellow solid, 84 mg, 50% yield; mp 171ꢀ173 C; H NMR (400 MHz, CDCl3; δ, ppm) 8.20 (d, J = 7.2
13
Hz, 2H), 7.76ꢀ7.70 (m, 3H), 7.56ꢀ7.43 (m, 8H), 7.38 (t, J = 7.6 Hz, 1H);7.30ꢀ7.27 (m, 1H); C NMR
(100 MHz, CDCl3; δ, ppm) 185.6, 148.7, 141.5, 141.5, 140.6, 136.2, 134.3, 134.0, 132.4, 131.7, 121.0,
129.0, 128.8, 128.7, 128.2, 127.9, 125.0, 121.0; IR (KBr, v) 3050, 2963, 1696, 1599, 1528, 1485, 1442,
1309, 1261, 1192, 1072, 962, 801, 730 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for C23H15OS, 339.0838
[M+H]+, found 339.0847.
3ꢀButylꢀ1ꢀ(pꢀtolyl)ꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2i)
o
1
Yellow solid, 100 mg, 59% yield; mp 125ꢀ126 C; H NMR (400 MHz, CDCl3; δ, ppm) 8.17ꢀ8.01 (m,
19
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 28
2H), 7.77ꢀ7.69 (m, 1H), 7.54ꢀ7.44 (m, 2H), 7.31ꢀ7.24 (m, 3H), 3.09ꢀ2.91 (m, 2H), 2.49 (s, 3H), 1.85ꢀ
1.72 (m, 2H), 1.60ꢀ1.49 (m, 2H), 1.12ꢀ0.95 (m, 3H); 13C NMR (100 MHz, CDCl3; δ, ppm) 185.7, 147.3,
141.7, 141.4, 141.1, 139.9, 135.9, 135.0, 133.9, 129.3, 127.6, 127.4, 124.9, 121.1, 33.0, 28.1, 22.4, 21.5,
13.9; IR (KBr, v) 3050, 3023, 2957, 1686, 1600, 1527, 1496, 1465, 1273, 1178, 1156, 998, 947, 813 cmꢀ
1; HRMS (ESIꢀTOF) m/z calcd for C22H21OS, 333.1308 [M+H]+, found 333.1309.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1ꢀPhenylꢀ3ꢀ(pꢀtolyl)ꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2j)
o
1
Yellow solid, 111 mg, 63% yield; mp 194ꢀ196 C; H NMR (400 MHz, CDCl3; δ, ppm) 8.21ꢀ8.19 (m,
2H), 7.74 (d, J = 7.2 Hz, 1H), 7.60 (d, J = 8.0 Hz, 2H), 7.54ꢀ7.44 (m, 4H), 7.40ꢀ7.33 (m, 3H), 7.30ꢀ7.26
(m, 1H), 2.48 (s, 3H); 13C NMR (100 MHz, CDCl3; δ, ppm) 185.7, 148.46, 141.5, 141.1, 140.7, 139.10,
136.17, 134.62, 133.99, 131.73, 129.90, 129.68, 129.46, 128.74, 128.5, 128.1, 127.9, 124.9, 121.0, 21.4;
IR (KBr, v) 2963, 1694, 1617, 1540, 1506, 1486, 1261, 1183, 1100,1040, 965, 802, 762, 726 cmꢀ1;
HRMS (ESIꢀTOF) m/z calcd for C24H17OS, 353.0994[M+H]+, found 353.1006.
3ꢀ(4ꢀMethoxyphenyl)ꢀ1ꢀphenylꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2k)
Yellow solid, 112 mg, 61% yield; mp 171ꢀ173 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) δ 8.20ꢀ8.18 (m,
2H), 7.74 (d, J = 7.6 Hz, 1H), 7.63 (d, J = 8.8 Hz, 2H), 7.51ꢀ7.42 (m, 4H),7.40ꢀ7.36 (m, 1H), 7.28ꢀ7.25
13
(m, 1H), 7.06 (d, J = 8.8 Hz, 2H), 3.92 (s, 3H); C NMR (100 MHz, CDCl3; δ, ppm) 185.7, 160.2,
148.2, 141.5, 140.8, 140.8, 136.1, 134.4, 134.0, 131.8, 130.0, 129.9, 128.7, 128.0, 127.9, 125.0, 124.6,
120.9, 114.4, 55.5; IR (KBr, v) 2955, 1699, 1605, 1522, 1506, 1478, 1296, 1253, 1173, 1106, 1029, 962,
832, 800, 762, 726 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for C24H17O2S, 369.0943 [M+H]+, found
369.0962.
3ꢀ(4ꢀEthylphenyl)ꢀ1ꢀphenylꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2l)
o
1
Yellow solid, 102 mg, 56% yield; mp 139ꢀ140 C; H NMR (400 MHz, CDCl3; δ, ppm) 8.21ꢀ8.18 (m,
2H), 7.74 (d, J = 7.2 Hz, 1H), 7.62 (d, J = 8.0 Hz, 2H), 7.54 (d, J = 7.6 Hz, 1H), 7.511ꢀ7.44 (m, 3H),
7.40ꢀ7.35 (m, 3H), 7.29ꢀ7.25 (m, 1H), 2.77 (q, J = 7.6 Hz, 2H), 1.35 (t, J = 7.6 Hz, 3H); 13C NMR (100
MHz, CDCl3; δ, ppm) 185.7, 148.4, 145.4, 141.5, 141.1, 140.7, 136.2, 134.7, 134.0, 131.7, 129.9, 129.7,
20
ACS Paragon Plus Environment

Page 21 of 28
The Journal of Organic Chemistry
128.7, 128.6, 128.5, 128.1, 127.9, 124.9, 121.0, 28.8, 15.4; IR (KBr, v) 2962, 1696, 1600, 1539, 1505,
1486, 1311, 1278, 1262, 1187, 1081 1041, 967, 857, 833, 779, 763, 724 cmꢀ1; HRMS (ESIꢀTOF) m/z
calcd for C25H19OS, 367.1151 [M+H]+, found 367.1159.
1
2
3
4
5
6
7
8
3ꢀ(4ꢀ(tertꢀButyl)phenyl)ꢀ1ꢀphenylꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2m)
9
o
1
Yellow solid, 122 mg, 62% yield; mp 161ꢀ162 C; H NMR (400 MHz, CDCl3; δ, ppm) 8.21ꢀ8.19 (m,
2H), 7.74 (d, J = 7.6 Hz, 1H), 7.64 (d, J = 8.4 Hz, 2H), 7.59ꢀ7.38 (m, 7H), 7.30ꢀ7.26 (m, 1H), 1.43 (s,
9H); 13C NMR (100 MHz, CDCl3; δ, ppm) 185.7, 152.3, 148.5, 141.5, 141.1, 140.8, 136.2, 134.7, 134.0,
131.4, 129.9, 129.5, 128.9, 128.3, 128.5, 128.3, 128.1, 127.9, 126.1, 125.9, 125.7, 124.9, 121.1, 34.9,
31.4, 31.3; IR (KBr, v) 2961, 1697, 1601, 1519, 1488, 1310, 1262, 1186, 1040, 963, 865, 795, 765 cmꢀ1;
HRMS (ESIꢀTOF) m/z calcd for C27H23OS, 395.1464 [M+H]+, found 395.1473.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1ꢀPhenylꢀ3ꢀ(mꢀtolyl)ꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2n)
o
1
Yellow solid, 104 mg, 59% yield; mp 123ꢀ125 C; H NMR (400 MHz, CDCl3; δ, ppm) 8.20 (m, 2H),
7.75 (d, J = 7.2 Hz, 1H), 7.54ꢀ7.37 (m, 8H), 7.31ꢀ7.26 (m, 2H), 2.48 (s, 3H); 13C NMR (100 MHz,
CDCl3; δ, ppm) 185.7, 148.6, 141.5, 141.3, 140.7, 138.8, 136.2, 134.6, 134.0, 132.3, 131.1, 129.9,
129.8, 129.3, 128.9, 128.8, 128.2, 127.9, 125.7, 125.0, 121.0, 21.5; IR (KBr, v) 3065, 2963, 1702, 1637,
1617, 1603, 1520, 1487, 1312, 1262, 1185, 1088, 1041, 971, 801, 778, 758 cmꢀ1; HRMS (ESIꢀTOF) m/z
calcd for C24H17OS, 353.0994 [M+H]+, found 353.1008.
3ꢀ(4ꢀFluorophenyl)ꢀ1ꢀphenylꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2o)
o
1
Yellow solid, 85 mg, 48% yield; mp 191ꢀ193 C; H NMR (400 MHz, CDCl3; δ, ppm) 8.19ꢀ8.17 (m,
2H), 7.74 (d, J = 7.2 Hz, 1H), 7.69ꢀ7.66 (m, 2H), 7.51ꢀ7.39 (m, 5H), 7.31ꢀ7.27 (m, 1H), 7.25ꢀ7.21 (s,
13
2H); C NMR (100 MHz, CDCl3; δ, ppm) 185.5, 163.1 (JCF = 248.1 Hz), 148.7, 141.7, 141.5, 140.4,
136.1, 134.1, 132.9, 131.6, 130.6 (JCF = 8.2 Hz), 130.1, 128.8, 128.5 (JCF = 3.4 Hz), 128.3, 127.9, 125.1,
120.8, 116.1 (JCF = 21.7 Hz); IR (KBr, v) 2963, 1696, 1600, 1522, 1502, 1488, 1261, 1221, 1187, 1158,
1097, 966, 835, 760 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for C23H14FOS, 357.0743 [M+H]+, found
357.0757.
21
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 28
3ꢀ(4ꢀChlorophenyl)ꢀ1ꢀphenylꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2p)
1
2
3
4
5
Yellow solid, 84 mg, 45% yield; mp 222ꢀ224 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 8.18 (dd, J = 8.0
Hz, 2.0 Hz, 2H), 7.75 (d, J = 7.2 Hz, 1H), 7.64 (d, J = 8.4 Hz, 2H), 7.52ꢀ7.38 (m, 7H), 7.31 (d, J = 7.6
6
7
13
Hz, 1H); C NMR (100 MHz, CDCl3; δ, ppm) 185.5, 148.9, 141.9, 141.5, 140.4, 136.2, 135.0, 134.1,
8
9
132.7, 131.5, 130.9, 130.1, 123.0, 129.3, 128.8, 128.4, 127.9, 125.1, 120.9; IR (KBr, v) 2963, 1697,
1602, 1520, 1488, 1397, 1261, 1091, 966, 862, 798, 760, 726 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for
C23H14ClOS, 373.0448 [M+H]+, found 373.0450.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1ꢀ(4ꢀMethoxyphenyl)ꢀ3ꢀphenylꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2q)
o
1
Yellow solid, 109 mg, 59% yield; mp 182ꢀ184 C; H NMR (400 MHz, CDCl3; δ, ppm) 8.21ꢀ8.19 (m,
2H), 7.75ꢀ7.69 (m, 3H), 7.55ꢀ7.48 (m, 4H), 7.38ꢀ7.36 (m, 1H), 7.30ꢀ7.26 (m, 1H), 7.01 (d, J = 8.8 Hz,
2H), 3.90 (s, 3H); 13C NMR (100 MHz, CDCl3; δ, ppm) 185.6, 161.1, 149.1, 141.7, 141.2, 140.5, 135.0,
133.8, 133.3, 132.6, 129.6, 129.0, 128.9, 128.7, 128.1, 124.9, 124.7, 121.0, 114.1, 55.4; IR (KBr, v)
2968, 1694, 1609, 1540, 1505, 1308, 1260, 1181, 1026, 967, 820, 798, 747 cmꢀ1; HRMS (ESIꢀTOF) m/z
calcd for C24H17O2S, 369.0943 [M+H]+, found 369.0949.
1ꢀ(4ꢀMethoxyphenyl)ꢀ3ꢀ(pꢀtolyl)ꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2r)
Yellow solid, 136 mg, 71% yield; mp 189ꢀ191 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 8.19 (d, J = 8.8
Hz, 2H), 7.73 (d, J = 7.2 Hz, 1H), 7.58 (d, J = 8.0 Hz, 2H), 7.52 (d, J = 7.6 Hz, 1H), 7.38ꢀ7.24 (m, 4H),
6.99 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H), 2.47 (s, 3H); 13C NMR (100 MHz, DMSOꢀd6; δ, ppm) 180.4,
155.7, 143.6, 136.4, 135.6, 135.4, 133.7, 129.8, 128.6, 128.3, 124.4, 124.3, 123.3, 122.7, 119.6, 119.5,
115.7, 108.8, 50.2, 16.2; IR (KBr, v) 3026, 2971, 1690, 1603, 1537, 1501, 1301, 1283, 1221, 1158,
1114, 1025, 966, 833, 797, 760 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for C25H19O2S, 383.1101 [M+H]+,
found 383.1111.
1,3ꢀBis(4ꢀMethoxyphenyl)ꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2s)
o
1
Yellow solid, 157 mg, 79% yield; mp 196ꢀ197 C; H NMR (400 MHz, CDCl3; δ, ppm) 8.20ꢀ8.18 (m,
2H), 7.73 (d, J = 7.2 Hz, 1H), 7.62ꢀ7.60 (m, 2H), 7.49 (d, J = 7.6 Hz, 1H), 7.39ꢀ7.35 (m, 1H), 7.28ꢀ7.24
22
ACS Paragon Plus Environment

Page 23 of 28
The Journal of Organic Chemistry
13
(m, 1H), 7.04 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.8 Hz, 2H), 3.92 (s, 3H), 3.89 (s, 3H); C NMR (100
MHz, DMSOꢀd6; δ, ppm) 180.4, 155.7, 154.9, 143.4, 136.4, 135.4, 135.4, 129.7, 128.6, 128.1, 124.7,
124.3, 122.7, 119.6, 119.5, 119.5, 115.6, 109.1, 108.8, 50.2, 50.2; IR (KBr, v) 2926, 2835, 1690, 1609,
1507, 1497, 1304, 1258, 1179, 1041, 1024, 966, 835, 759 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for
C25H19O3S, 399.1049 [M+H]+, found 399.1059.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3ꢀ(4ꢀ(tertꢀButyl)phenyl)ꢀ1ꢀ(4ꢀmethoxyphenyl)ꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2t)
Yellow solid, 138 mg, 65% yield; mp 162ꢀ164 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 8.20 (d, J = 8.8
Hz, 2H), 7.74 (d, J = 7.2 Hz, 1H), 7.63 (d, J = 8.4 Hz, 2H), 7.57ꢀ7.53 (m, 3H), 7.39ꢀ7.37 (m, 1H), 9.29ꢀ
7.25 (m, 1H), 7.00 (d, J = 8.8 Hz, 2H), 3.90 (s, 3H), 1.42 (s, 9H); 13C NMR (100 MHz, CDCl3; δ, ppm)
185.7, 161.0, 152.1, 148.9, 141.7, 140.8, 140.6, 135.1, 133.8, 133.6, 129.6, 129.3, 128.3, 128.0, 125.9,
124.8, 124.7, 121.1, 114.0, 55.4, 34.9, 31.5, 31.3; IR (KBr, v) 2961, 1689, 1603, 1495, 1260, 1179,
1104, 1036, 964, 828, 797, 764 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for C28H25O2S, 425.1569 [M+H]+,
found 425.1556.
1ꢀ(4ꢀMethoxyphenyl)ꢀ3ꢀ(mꢀtolyl)ꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2u)
o
1
Yellow solid, 111 mg, 58% yield; mp 127ꢀ129 C; H NMR (400 MHz, CDCl3; δ, ppm) 8.22ꢀ8.18 (m,
2H), 7.74 (d, J = 7.2 Hz, 1H), 7.53ꢀ7.50 (m, 3H), 7.43ꢀ7.37 (m, 2H), 7.29ꢀ7.26 (m, 2H), 7.02ꢀ7.00 (m,
2H), 3.90 (s, 3H), 2.47 (s, 3H); 13C NMR (100 MHz, CDCl3; δ, ppm) 185.6, 161.0, 149.0, 141.7, 141.1,
140.6, 138.8, 135.0, 133.8, 1336, 132.4, 129.6, 129.6, 129.3, 128.8, 128.0, 125.7, 124.8, 124.7, 121.0,
114.0, 55.4, 21.5; IR (KBr, v) 2965, 1695, 1606, 1534,1505, 1307, 1260, 1180, 1029, 819, 757 cmꢀ1;
HRMS (ESIꢀTOF) m/z calcd for C25H19O2S, 383.1101 [M+H]+, found 383.1107.
3ꢀ(4ꢀFuorophenyl)ꢀ1ꢀ(4ꢀmethoxyphenyl)ꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2v)
o
1
Yellow solid, 95 mg, 49% yield; mp 208ꢀ210 C; H NMR (400 MHz, CDCl3; δ, ppm) 8.19 (d, J = 8.8
Hz, 2H), 7.75 (d, J = 7.2 Hz, 1H), 7.69ꢀ7.65 (m, 2H), 7.45ꢀ7.38 (m, 3H), 7.25ꢀ7.20 (m, 2H), 7.01 (d, J =
13
8.8 Hz, 2H), 3.90 (s, 3H); C NMR (100 MHz, CDCl3; δ, ppm) 185.5, 163.0 (JCF = 247.9 Hz), 161.1,
149.1, 141.7, 141.4, 140.3, 134.9, 133.9, 131.9, 130.6 (JCF = 8.1 Hz), 129.6, 128.6 (JCF = 3.4 Hz), 128.2,
23
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 28
125.0, 124.5, 120.7, 116.1 (JCF = 21.7 Hz), 114.1, 55.4; IR (KBr, v) 1695, 1607, 1500, 1308, 1259,
1226, 1181, 1026, 820, 730 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for C24H16FO2S, 387.0849 [M+H]+,
found 387.0859.
1
2
3
4
5
6
7
8
9
3ꢀ(4ꢀChlorophenyl)ꢀ1ꢀ(4ꢀmethoxyphenyl)ꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2w)
Yellow solid, 105 mg, 52% yield; mp 240ꢀ242 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 8.19 (d, J = 8.8
Hz, 2H), 7.75 (d, J = 7.2 Hz, 1H), 7.63 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H), 7.47 (d, J = 7.6 Hz,
1H), 7.39 (t, J = 7.2 Hz, 1H), 7.31 (d, J = 7.6 Hz, 1H), 7.01 (d, J = 8.8 Hz, 2H), 3.90 (s, 3H); 13C NMR
(100 MHz, CDCl3; δ, ppm) 185.5, 161.2, 149.3, 141.7, 141.7, 140.2, 135.0, 134.9, 133.9, 131.7, 131.1,
130.0, 130.0, 129.2, 128.3, 125.0, 124.5, 120.8, 114.1, 55.5; IR (KBr, v) 2924, 1713, 1642, 1490, 1247,
1004, 969, 830, 781, 765, 727 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for [M+H]+ C24H16ClO2S 403.0560,
found 403.0568.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1ꢀ(4ꢀChlorophenyl)ꢀ3ꢀphenylꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2x)
o
1
Yellow solid, 100 mg, 54% yield; mp 206ꢀ208 C; H NMR (400 MHz, CDCl3; δ, ppm) 8.17ꢀ8.15 (m,
2H), 7.74 (d, J = 7.2 Hz, 1H), 7.71ꢀ7.69 (m, 2H), 7.56ꢀ7.44 (m, 6H), 7.41ꢀ7.37 (m, 1H), 7.31ꢀ7.28 (m,
1H); 13C NMR (100 MHz, CDCl3; δ, ppm) 185.6, 147.1, 141.5, 141.4, 140.6, 136.5, 135.8, 134.5, 134.2,
132.2, 130.2, 129.2, 129.1, 129.0, 129.0, 128.7, 128.3, 125.1, 121.1; IR (KBr, v) 2963, 1697, 1602,
1536, 1484, 1263, 1185, 1095, 967, 855, 750 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for C23H14ClOS,
373.0448 [M+H]+, found 373.0442.
1ꢀ(4ꢀChlorophenyl)ꢀ3ꢀ(4ꢀmethoxyphenyl)ꢀ8Hꢀindeno[1,2ꢀc]thiophenꢀ8ꢀone (2y)
o
1
Yellow solid, 113 mg, 56% yield; mp 202ꢀ204 C; H NMR (400 MHz, CDCl3; δ, ppm) 8.20ꢀ8.14 (m,
2H), 7.75ꢀ7.72 (m, 1H), 7.62 (d, J = 8.4 Hz, 2H), 7.51ꢀ7.37 (m, 4H),7.31ꢀ7.16 (m, 1H) 7.07ꢀ6.99 (m,
2H), 3.92 (s, 3H); 13C NMR (100 MHz, CDCl3; δ, ppm) 185.7, 160.3, 146.6, 141.3, 140.9, 140.7, 135.7,
134.6, 134.1, 130.3, 13.0, 129.6, 129.2, 129.1, 128.9, 128.1, 125.0, 124.4, 120.9, 114.4, 114.1, 55.5; IR
(KBr, v) 2962, 1699, 1603, 1504, 1490, 1246, 1173, 1090, 1031, 963, 825, 728 cmꢀ1; HRMS (ESIꢀTOF)
m/z calcd for C24H16ClO2S, 403.0556 [M+H]+, found 403.0573.
24
ACS Paragon Plus Environment

Page 25 of 28
The Journal of Organic Chemistry
ASSOCIATED CONTENT
1
2
3
4
Supporting Information
5
6
7
8
13
1H and C NMR spectra for all pure products 1a-1y, 2aꢀ2y, and Xꢀray crystal data (CIF) for 2a. This
material is available free of charge via the Internet at http//pubs.acs.org.
Notes
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We are grateful for financial support from the NSFC (Nos. 21232004, 21332005, and 21472071), PAPD
of Jiangsu Higher Education Institutions, the Robert A. Welch Foundation (Dꢀ1361), the NIH
(R33DA031860), the Outstanding Youth Fund of JSNU (YQ2015003), NSF of Jiangsu Province
(BK20151163), NSF of JSNU (14XLR005), and NSF of Jiangsu Education Committee (15KJB150006).
REFERENCES
[1] (a) Metzner, P.; Thuillier A., Sulfur Reagents in Organic Synthesis; Katritzky, A. R.; MethꢀCohn, O.; W. Rees, C.
Eds.; Academic Press: London, 1994. (b) Bichler, P.; Love, J. In Topics of Organometallic Chemistry; Vigalok, A.
Ed.; Springer: Heidelberg, 2010; Vol. 31, p 39, (c) Ager, D. J. Chem. Soc. Rev. 1982, 11, 493. (d) McReynolds, M.
D.; Dougherty, J. M.; Hanson, P. R. Chem. Rev. 2004, 104, 2239. (e) Zyk, N. V.; Beloglazkina, E. K.; Belova, M.
A.; Dubinina, N. S. Russ. Chem. Rev. 2003, 72, 769. (f) Sizov, A. Y.; Kovregin, A. N.; Ermolov, A. F. Russ.
Chem. Rev. 2003, 72, 357.
[2] (a) Cody, G. D.; Boctor, N. Z.; Filley, T. R.; Hazen, R. M.; Scott, J. H.; Sharma, A.; Yoder, Jr. H. S. Science 2000,
289, 1337. (b) Wattenberg, L. W.; Sparnins, V. L.; Barany, G. Can. Res. 1989, 49, 2689. (c) Jacob, C. Nat. Prod.
Rep. 2006, 23, 851. (d) Tang, Y.ꢀQ.; Sattler, I.; Thiericke, R.; Grabley, S. Eur. J. Org. Chem. 2001, 261.
[3] For selected review; see: (a) Kondo, T.; Mitsudo, T.ꢀa. Chem. Rev. 2000, 100, 3205. (b) Beletskaya, I. P.;
Ananikov, V. P. Chem. Rev. 2011, 111, 1596. (c) Liu, H.; Jiang, X. Chem.ꢀAsian J. 2013, 8, 2546. (d) Shen, C.;
Zhang, P.; Sun, Q.; Bai, S.; Hor, T. S. A.; Liu, X. Chem. Soc. Rev. 2015, 44, 291.
25
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 28
[4] (a) Migita, T.; Shimizu, T.; Asami, Y.; Shiobara, J.; Kato, Y.; Kosugi, M. Bull. Chem. Soc. Jpn., 1980, 53, 1385.
(b) Kosugi, M.; Shimizu, T.; Migita, T. Chem. Lett. 1978, 13.
1
2
3
4
5
6
7
8
[5] (a) Mann, G.; Baranano, D.; Hartwig, J. F.; Rheingold, A. L.; Guzei, I. A. J. Am. Chem. Soc. 1998, 120, 9205. (b)
Murata, M.; Buchwald, S. L. Tetrahedron 2004, 60, 7397. (c) Itoh, T.; Mase, T. Org. Lett. 2004, 6, 4587. (d)
FernandezꢀRodroeguez, M. A.; Shen, Q.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 2180. (e) Itoh, T.; Mase, T.
Org. Lett., 2007, 9, 3687. (f) Lee, J. Y.; Lee, P. H. J. Org. Chem. 2008, 73, 7413. (g) Dahl, T.; Tornoe, C. W.;
BangꢀAndersen, B.; Nielsen, P.; Jorgensen, M. Angew. Chem., Int. Ed. 2008, 47, 1726. (h) Eichman, C. C.;
Stambuli, J. P. J. Org. Chem. 2009, 74, 4005.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
[6] (a) Bates, C. G.; Gujadhur, R. K.; Venkataraman, D. Org. Lett. 2002, 4, 2803. (b) Jammi, S.; Sakthivel, S.; Rout,
L.; Mukherjee, T.; Mandal, S.; Mitra, R.; Saha, P.; Punniyamurthy, T. J. Org. Chem. 2009, 74, 1971. (c) Larsson,
P.ꢀF.; Correa, A.; Carril, M.; Norrby, P.ꢀO.; Bolm, C. Angew. Chem., Int. Ed. 2009, 48, 5691. (d) Xu, H.ꢀJ.; Zhao,
Y.ꢀQ.; Feng, T.; Feng, Y.ꢀS. J. Org. Chem. 2012, 77, 2878. (e) Kumar, S.; Engman, L. J. Org. Chem. 2006, 71,
5400. (f) Taniguchi, N. J. Org. Chem. 2007, 72, 1241. (g) Zhang, S.; Qian, P.; Zhang, M.; Hu, M.; Cheng, J. J.
Org. Chem. 2010, 75, 6732. (h) Hao, W.; Zeng, J.; Cai, M. Chem. Commun. 2014, 50, 11686.
[7] (a) Correa, A.; Carril, M.; Bolm, C. Angew. Chem., Int. Ed. 2008, 47, 2880. (b) Wu, J.ꢀR.; Lin, C.ꢀH.; Lee, C.ꢀF.
Chem. Commun. 2009, 4450. (c) Lin, Y.ꢀY.; Wang, Y.ꢀJ.; Lin, C.ꢀH.; Cheng, J.ꢀH.; Lee, C.ꢀF. J. Org. Chem. 2012,
77, 6100. (d) Wang, H.; Wang, L.; Shang, J.; Li, X.; Wang, H.; Gui, J.; Lei, A. Chem. Commun. 2012, 48, 76.
[8] (a) Arisawa, M.; Ichikawa, T.; Yamaguchi, M. Org. Lett. 2012, 14, 5318. (b) Arisawa, M.; Suzuki, T.; Ishikawa,
T.; Yamaguchi, M. J. Am. Chem. Soc. 2008, 130, 12214. (c) Ajiki, K.; Hirano, M.; Tanaka, K. Org. Lett. 2005, 7,
4193.
[9] (a) Firouzabadi, H.; Iranpoor, N.; Gholinejad, M. Adv. Synth. Catal. 2010, 352, 119. (b) Kuhn, M.; Falk, F. C.;
Paradies, J. Org. Lett. 2011, 13, 4100.
[10](a) Prasad, D. J. C.; Sekar, G. Org. Lett. 2011, 13, 1008. (b) Ke, F.; Qu, Y.; Jiang, Z.; Li, Z.; Wu, D.; Zhou, X.
Org. Lett. 2011, 13, 454.
[11]Li, Y.; Nie, C.; Wang, H.; Li, X.; Verpoort, F.; Duan, C. Eur. J. Org. Chem. 2011, 7331.
[12]Metal sulfides as sulfurating reagents; Na2S, sees: (a) Shvartsberg, M. S.; Ivanchikova, I. D. ARKIVOC 2003, 87.
26
ACS Paragon Plus Environment

Page 27 of 28
The Journal of Organic Chemistry
(b) Ma, D.; Xie, S.; Xue, P.; Zhang, X.; Dong, J.; Jiang, Y. Angew. Chem., Int. Ed. 2009, 48, 4222. (c) Li, C.ꢀL.;
Zhang, X.ꢀG.; Tang, R.ꢀY.; Zhong, P.; Li, J.ꢀH. J. Org. Chem. 2010, 75, 7037. K2S, see: (d) You, W.; Yan, X.;
Liao, Q.; Xi, C. Org. Lett. 2010, 12, 3930. (e) Zhang, X.; Zeng, W.; Yang, Y.; Huang, H.; Liang, Y. Org. Lett.
2014, 16, 876. (f) Liu, Y.; Zhang, J.ꢀL.; Song, R.ꢀJ.; Li, J.ꢀH. Org. Lett. 2014, 16, 5838. KSCN, sees: (g) Ke, F.;
Qu, Y.; Jiang, Z.; Li, Z.; Wu, D.; Zhou, X. Org. Lett. 2011, 13, 454. Na2S2O3, sees: (h) Qiao, Z.; Liu, H.; Xiao, X.;
Fu, Y.; Wei, J.; Li, Y.; Jiang, X. Org. Lett. 2013, 15, 2594. (i) Qiao, Z.; Wei, J.; Jiang, X. Org. Lett. 2014, 16,
1212.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
[13](a) Negishi, E. Acc. Chem. Res. 1987, 20, 65. (b) Li, Y.; Xu, X.; Shi, H.; Pan, L.; Liu, Q. J. Org. Chem. 2014, 79,
5929. (c) Li, L.; Zhao, Y.ꢀL.; Wang, H.; Li, Y.ꢀJ.; Xu, X.; Liu, Q. Chem. Commun. 2014, 50, 6458. (d) Pi, R.;
Zhou, M.ꢀB.; Yang, Y.; Gao, C.; Song, R.ꢀJ.; Li, J.ꢀH.; Chem. Commun. 2015, 51, 13550. (e) Tang, H.ꢀT.; Xiong,
K.; Li, R.ꢀH.; Ding, Z.ꢀC.; Zhan, Z.ꢀP. Org. Lett. 2015, 17, 326. (f) Zhu, C.; Ma, S. Angew. Chem. Int. Ed. 2014,
53, 13532. (g) Ye, J.; Ma, S. Angew. Chem., Int. Ed. 2013, 52, 10809.
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
[14](a) Zhuo, L.ꢀG.; Zhang, J.ꢀJ.; Yu, Z.ꢀX. J. Org. Chem. 2012, 77, 8527. (b) Li, B.ꢀS.; Yang, B.ꢀM.; Wang, S.ꢀH.;
Zhang, Y.ꢀQ.; Cao, X.ꢀP.; Tu, Y.ꢀQ. Chem. Sci. 2012, 3, 1975. (c) Ishida, M.; Tanaka, K. Org. Lett. 2013, 15,
2120. (d) Lee, Y. T.; Kang, Y. K.; Chung, Y. K. J. Org. Chem. 2009, 74, 7922. (e) Brissy, D.; Skander, M.;
Jullien, H.; Retailleau, P.; Marinetti, A. Org. Lett. 2009, 11, 2137. (f) Lu, L.; Liu, X.ꢀY.; Shu, X.ꢀZ.; Ji, K.; Yang,
K.ꢀG.; Liang, Y.ꢀM. J. Org. Chem. 2009, 74, 474, and references cited therein'.
[15](a) Qiu, J.ꢀK.; Jiang, B.; Zhu, Y.ꢀL.; Hao, W.ꢀJ.; Wang, D.ꢀC.; Sun, J.; Wei, P.; Tu, S.ꢀJ.; Li, G. J. Am. Chem. Soc.
2015, 137, 8928. (b) Chen, Z.ꢀZ.; Liu, S.; Hao, W.ꢀJ.; Xu, G.; Wu, S.; Miao, J.ꢀN.; Jiang, B.; Wang, S.ꢀL.; Tu, S.ꢀ
J.; Li, G. Chem. Sci. 2015, 6, 6654. (c) Zhou, P.; Hao, W.ꢀJ.; Zhang, J.ꢀP.; Jiang, B.; Li G.; Tu, S.ꢀJ. Chem.
Commun. 2015, 51, 13012. (d) Gao, Q.; Zhou, P.; Liu, F.; Hao, W.ꢀJ.; Yao, C.; Jiang, B.; Tu, S.ꢀJ. Chem.
Commun. 2015, 51, 9519. (e) Tu, X.ꢀJ.; Hao, W.ꢀJ.; Ye, Q.; Wang, S.ꢀL.; Jiang, B.; Li, G.; Tu, S.ꢀJ. J. Org. Chem.
2014, 79, 11110.
[16]The synthesis of benzo[b]fluorenones see: (a) Zhao, Q.; Hu, Q.; Wen, L.; Wu, M.; Hua Y. Adv. Synth. Catal. 2012,
354, 2113. (b) Hao, W.ꢀJ.; Zhou, P.; Yang, Z.; Jiang, B.; Zhang, J.ꢀP.; Tu, S.ꢀJ. Tetrahedron 2016, 72, 2206.
[17](a) MacDowell, D. W. H.; Jeffries, A. T. J. Org. Chem. 1971, 36, 1053. (b) MacDowell, D. W. H.; Jeffries, A. T.
J. Org. Chem. 1970, 35, 871. (c) Le Bihan, Jean Y.; Dabard, R., C. R. l'Academie. Sci., Ser. III, 1972, 274, 726. (d)
27
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 28
Harrison, P. A.; Russell, R. A.; Warrener, R. N.; PaddonꢀRow, M. N. Tetrahedron Lett. 1977, 3291.
1
2
3
4
[18]Wu, J.; Talwar, D.; Johnston, S.; Yan, M.; Xiao, J. Angew. Chem. Int. Ed. 2013, 52, 6983.
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
28
ACS Paragon Plus Environment