Iodine-Mediated Cyclization of ortho-Alkynylaryl Ketones for the Synthesis of Indenone Derivatives

Article abstract of DOI:10.1002/ejoc.201700968

A new method for the synthesis of indenone derivatives based on the I₂-promoted cyclization of ortho-alkynylaryl ketones has been developed. This method provides a metal-free and convenient route for the regioselective synthesis of indenones using ortho-alkynylaryl ketones with predefined substituents to give indenone products in moderate to good yields.

Full text of DOI:10.1002/ejoc.201700968

A Journal of
Accepted Article
Title: Iodine-mediated cyclization of ortho-alkynylarylketones for the
synthesis of indenone derivatives
Authors: Pennapa Chuangsoongnern, Chareef Surinrach, Jumreang
Tummatorn, Charnsak Thongsornkleeb, and Somsak
Ruchirawat
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201700968
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10.1002/ejoc.201700968
European Journal of Organic Chemistry
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Iodine-mediated cyclization of ortho‑alkynylarylketones for the
synthesis of indenone derivatives
Pennapa Chuangsoongnern,[b] Chareef Surinrach,[b] Jumreang Tummatorn,*[a][b]
Charnsak Thongsornkleeb,[a][b] and Somsak Ruchirawat[a][b]
Abstract: A new approach for the synthesis of indenone derivatives
using I2-promoted cyclization of ortho-alkynylarylketones has been
developed. This method provides a metal-free and convenient route
for regioselective synthesis of indenones employing ortho-
alkynylarylketones with predefined substituents to obtain indenone
products in moderate to good yields.
was first activated by I2 to generate carbocation intermediate
before further cyclization by the tethered alkyne resulting in the
formation of indenone product regioselectively (Scheme 1).4
Moreover, ortho‑alkynylarylketone substrates could also be
converted to indenone products employing a catalytic amount of
NaAuCl4.2H2O5 or a stoichiometric amount of Tf2NH.6 The
reaction mode of these two procedures is in reversal of the
previous method; alkyne moiety is initially promoted by such
reagents before the cyclization which was triggered by the
participation of ortho-keto moiety (Scheme 1).
Introduction
Indenone is an important core structure of several natural
products1 and synthetic bioactive compounds (Figure 1).2
Moreover, indenones are also used as a key intermediate in
many syntheses of more complex molecules. Therefore, the
development of synthetic strategy to construct indenones is still
an active area of research. Several reported methods employ
expensive transition metal catalysts to promote intermolecular
annulation between alkynes and coupling partners (Scheme 1).3
However, these methods suffer from the lack of regioselectivity
in the annulation process which make them not suitable for the
synthesis of unsymmetrical 2,3-disubstituted indenones. With
this restriction, the intramolecular cyclization of substrates with
predefined substituents is a more trusted strategy in controlling
the regioselectivity issue in the ring formation. Surprisingly, not
many methods are reported in the literature for this conversion.
2-(1-Alkynyl)benzylic alcohol is one of the substrates employed
to synthesize indenone using I2-mediated intramolecular
annulation. In this transformation, the benzylic hydroxyl group
Scheme 1. The synthesis of indenone derivatives
Figure 1. Indenone natural products.
[a]
[b]
Program on Chemical Biology, Chulabhorn Graduate Institute,
Center of Excellence on Environmental Health and Toxicology
(EHT), Ministry of Education, 54 Kamphaeng Phet 6, Laksi,
Bangkok 10210, Thailand
E-mail: jumreang@cri.or.th
Laboratory of Medicinal Chemistry, Chulabhorn Research Institute,
54 Kamphaeng Phet 6, Laksi, Bangkok 10210, Thailand
Scheme 2. The utilization of ortho‑alkynylarylketone substrates.
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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Since our research group has been interested in the utilization of
ortho‑alkynylarylketones to prepare polycyclic compounds,7
during our study we observed an unexpected result that
ortho‑alkynylarylketones could be activated by molecular iodine
to promote the cyclization to provide indedone products.
Surprisingly, the previously reported method demonstrated that
conversion of 1a to indenone 2a. Therefore, we speculated that
18O might be able to exchange with 16O of starting material
ketone 1a as well. From our study, we learn that H2O was
required in this transformation; therefore, the proposed
mechanism of this transformation was illustrated in Scheme 4.
Initially, the alkyne moiety was activated by molecular iodine to
form iodonium ion intermediate which underwent the cyclization
using the lone pair electron of ortho-carbonyl group to form a
five-membered oxocarbenium ion (A).8,11 Upon hydrolysis,
intermediate A was then converted to vinyl iodide (C) which
further reacted in the intramolecular nucleophilic addition of
ketone providing alcohol intermediate D. After proton transfer,
alpha-elimination of iodide proceeded and followed by the
elimination of water to obtain the final product.
the
same
substrates,
ortho‑alkynylarylketones
and
ortho‑alkynylarylaldehydes, could be oxidized by I2 to provide
1,4,5-tricarbonyl compounds when the reaction was carried out
in CH3CN/H2O at room temperature.8 These results implied that
I2 could play multiple important roles in the reaction of
ortho‑alkynylarylketones depending on the reaction conditions.
As molecular iodine is an environmentally friendly and
inexpensive reagent which has been established as a good
mediator and reagent in several organic reactions,9 therefore in
this work, we aim to develop a new methodology for the
synthesis of indenones using I2-mediated cyclization of
ortho‑alkynylarylketone substrates.
Table 1. Optimization condition.
Results and Discussion
Entry
Reagents
Time
(h)
O/N
Yield
(%)
3
In the optimization of conditions, we used (4-methoxyphenyl)(2-
(phenylethynyl)phenyl)methanone (1) as our screening substrate
(Table 1). Initially, compound 1 was treated with 0.5 eq of I2 in
DCM at 60°C for overnight. Unfortunately, the starting material
underwent the decomposition under these reaction conditions
providing the desired product in only 3% yields (entry 1). The
improvement of yield was achieved when 1.0 eq of I2 was
employed giving indenone 2 in 23% yield (entry 2). However, the
excess amount of I2 adversely affected the reaction in
decreasing the yield of the desired product (entry 3). Next, the
effect of solvents was investigated in entries 4-10. The reactions
were carried out in various AR grade solvents using 1.0 eq of I2
as a reagent. The results showed that the desired product was
obtained in most promising yields when the reactions were
carried out in CH3CN and MeOH. However, the reaction using
CH3CN gave a cleaner reaction product than MeOH. Therefore,
CH3CN was used as the solvent for further optimization. To
ensure that water was required for this conversion, the reactions
in entries 11 and 12 were then carried out. The results illustrated
that when the reaction was treated with 1.0 eq of I2 and H2O in
dry CH3CN at 60°C, the desired product was obtained in highest
yield (73%, entry 12). Therefore, the condition in entry 12 was
selected as the optimal conditions for this transformation. To
investigate the reaction mechanism of this transformation, the
reaction of compound 1a was performed using H2O-18O (97
atom %). The result from high-resolution mass-spectrometry
data showed that 18O could incorporate into the molecule of the
corresponding indenone product with the relative intensity of
18O/16O = 4:1 ratio. However, it is known that H218O is also able
to exchange with oxygen atom of ketone compounds.10
Therefore, we set up another experiment by treating indenone
2a (16O) with H218O under the same optimal conditions as shown
in Scheme 3. The result showed that 18O could exchange with
16O of ketone in indenone 2a providing the relative intensity of
18O/16O = 1:2.5 ratio which was lower than the ratio from the
1
2
I2 (0.5 eq), DCM, 60 °C
I2 (1.0 eq), DCM, 60 °C
I2 (3.0 eq), DCM, rt
O/N
2
23
9
3
4
I2 (1.0 eq), CH3CN, 60 °C
I2 (1.0 eq), Toluene, 60 °C
I2 (1.0 eq), CH3NO2, 60 °C
I2 (1.0 eq.), THF, 60 °C
I2 (1.0 eq), DMF, 60 °C
I2 (1.0 eq), MeOH, 60 °C
I2 (1.0 eq), DMSO, 60 °C
1
66
13
50
55
12
<68
27
5
3.5
1
6
7
1.5
O/N
1
8
9
10
1
11
12
I2 (1.0 eq), CH3CN (dry) , 60 °C
I2 (1.0 eq), H2O (1.0 eq), CH3CN (dry) , 60 °C
1.5
6
54
73
aIsolated Yields. bO/N = overnight
Scheme 3. 18O-labeling experiments
Scheme 4. Proposed reaction mechanism.
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Table 2. Substrate Scope.
With the optimal conditions in hand, a wide variety of substrates
were synthesized and subjected to the optimal conditions.
Initially, the substituents R1 of the alkyne of ortho-acetylenyl
benzophenone derivatives 1 were varied as shown in Table 2.
With butyl and isopentyl as substituents, compounds 1a and 1b
were smoothly converted to the corresponding products 2a and
2b, respectively, in good yields. Exploring the influence of steric
hindrance of the substituent, compound 1c, containing t-butyl
group, was then examined under the optimal conditions. The
reaction provided compound 2c in only 17% yield as the minor
product together with compound 3c as the major product (68%).
This result implied that the ability of cyclization process was
diminished due to the steric blockade of t-butyl group present in
the molecule leading to the formation of 1,4-diketone 3c as the
major product. The proposed mechanism for the formation of
compound 3c was illustrated in Scheme 5.
Scheme 5. Proposed reaction mechanism for the formation of 3c.
Next, the substrate containing free hydroxyl group 1d was
subjected to the optimal conditions. The result revealed that
compound 1d could tolerate under the reaction conditions to
afford indenone 2d in 68% yield (entry 4). In other cases, the
substituents on the alkyne were varied using a variety of
substituted benzene (entries 5-8). With the electronically neutral
benzene as the substituent (1e), the reaction proceeded
smoothly and gave the corresponding product 2e in 65% yield.
Conversely, the reaction of substrate containing electron-rich
substituent 1f (para-methoxybenzene) gave indenone product 2f
in very low yield (9%) along with side product 4f in 65% yield.12
Scheme 6. Proposed mechanism for the formation of 1,5-diketone compound.
aIsolated Yields
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The presumable formation of compound 4f was that the electron
delocalization of para-methoxyphenyl could faciltate the ring
opening of iodonium ion to generate intermediate F. Then, the
lone pair electron of the ortho-carbonyl underwent the cyclization
onto iodo-allene to form oxonium ion which was then hydrolyzed
to obtain alpha-iodoketone H, followed by alpha-elimination of
iodide to form the final product (Scheme 6). Furthermore, other
substituents were investigated including para-chloro and para-
fluorobenzene. Both substrates could be converted to the
corresponding products in high yields. However, the substrate
containing the triisopropylsilyl group on the alkyne 1i was not
compatible with this protocol, proving compound 4i in 86% yield.
To further illustrate the ability of the current method, the
substituents on both sides of ketone (R1 and R2) were varied as
shown in Table 3. Initially, substrates with a variety of electron
densities on aryl ring (R1) were subjected to the reaction
conditions. The results showed that substrates with both
electron rich (1j) and electron deficient (1k and 1l) substituents
could be converted to the corresponding products in very good
yields (entries 1-3). In changing from R1 = aryl group to benzyl
group 1m, the reaction provided a complex mixture and only
compound 2m’ was isolable in 39% yield. The result in this case
suggested that the reaction possibly generated two enolate
intermediates resulting in the formation of side products. In this
case, the methylene proton of the benzyl group could compete
in the generation of the enolates which underwent the cyclization
to give the unexpected indenone product 2m’. Meanwhile, only
compound 2n was obtained in 23% when the substrate 1n
containing methyl group was subjected to these optimal
conditions. In the next investigation, the effect of the substituents
R2 was examined employing both electron-donating and
electron-withdrawing groups placed in different positions as
presented in entries 6-9. The reaction of compound 1o having a
methoxy group at the meta- position with respect to the alkyne
provided the desired product 2o in moderate yield (52%) while
compound 1p having a methoxy group at the para-position with
respect to the alkyne could provide the desired product in higher
yield (72%). These results implied that the efficiency of iodine-
activated alkyne might be reduced due to the influence of
inductive effect from the meta-methoxy group resulting in much
lower yield of the desired product 2o. Similar results were
obtained when substrates 1q and 1r bearing fluorine atom at the
meta-position with respect to the alkyne moiety were employed
providing the corresponding products in moderate yields.
Table 3. Substrate Scope.
To display the practicality of our method, gram-scale synthesis
was conducted as shown in Scheme 7. The reaction of
compound 1a was converted to the corresponding product 2a in
good yield (80%).
Scheme 7. Gram-scale syntheses of compound 2a
aIsolated Yields
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MHz, CDCl3)  197.5, 141.8, 137.4, 132.9, 132.2, 130.1, 129.9, 128.2,
128.1, 127.5, 122.3, 104.7, 77.3, 30.2, 27.7; HRMS (ESI-TOF) calcd for
C19H18NaO [M+Na]+ 285.1250, found 285.1243.
Conclusions
In conclusion, we have demonstrated the utility of
ortho‑alkynylarylketones in the synthesis of indenone derivatives
using molecular iodine-promoted cyclization. This method
provided a convenient and easy control of the regioselectivity in
the indenone products. In addition, this protocol could also be
applied to a broad range of substrates to give the corresponding
indenones in moderate to good yields.
(2-(10-Hydroxydec-1-ynyl)phenyl)(phenyl)methanone
(1d):
yield
313.9 mg (90%, colorless oil); IR (neat) max 3402, 2929, 2856, 1663,
1288, 928, 755, 703 cm-1; 1H NMR (300 MHz, CDCl3)  7.82-7.80 (m, 2H),
7.56 (tt, 1H, J = 7.5, 1.2 Hz), 7.49-7.33 (m, 6H), 3.63 (t, 2H, J = 6.6 Hz),
2.11-2.04 (m, 2H), 1.60-1.51 (m, 3H), 1.35-1.18 (m, 10H); 13C NMR (75
MHz, CDCl3)  197.4, 141.7, 137.3, 133.0, 132.5, 130.1, 130.0, 128.2,
128.1, 127.3, 122.5, 96.6, 78.6, 63.0, 32.7, 29.1, 29.0, 28.5, 28.1, 25.6,
19.2; HRMS (ESI-TOF) calcd for C23H26NaO2 [M+Na]+ 357.1825, found
357.1831.
Experimental Section
Phenyl(2-(phenylethynyl)phenyl)methanone (1e):7 yield 541.0 mg
1
(97%, brown oil); IR (neat) max 1663, 1287, 928, 753, 701, 688 cm-1; H
General procedure for the synthesis of compound 1: (2-
iodophenyl)(4-methoxyphenyl)methanone (506.5 mg, 1.4979 mmol, 1.0
equiv) was dissolved in Et3N (3.5 mL/mmol) in a sealed tube. This
NMR (300 MHz, CDCl3)  7.90-7.86 (m, 2H), 7.63-7.40 (m, 7H), 7.26-
7.16 (m, 3H), 7.06-7.02 (m, 2H); 13C NMR (75 MHz, CDCl3)  197.0,
141.5, 137.3, 133.1, 132.5, 131.4, 130.3, 130.2, 128.7, 128.4, 128.1,
128.0, 122.6, 121.8, 95.1, 87.4; HRMS (ESI-TOF) calcd for C20H15O
[M+H]+ 283.1117, found 283.1122.
mixture was then added CuI (14.2 mg, 0.0749 mmol,
5 mol%),
PdCl2(PPh3)2 (21.0 mg, 0.0299 mmol, 2 mol%) and PPh3 (19.7 mg,
0.0749 mmol, 5 mol%) at room temperature and bubbled with argon for
30 min at room temperature before adding phenylacetylene (173 µL,
1.5728 mmol, 1.05 equiv). The reaction was stirred at 85 ºC for overnight
and quenched with sat. NH4Cl and extracted with EtOAc. The combined
organic layers were washed with brine, dried over Na2SO4, filtered and
concentrated under reduced pressure to provide the crude product which
was purified on silica gel (EtOAc/hexane: 1:9 to yield the corresponding
product 1 (463.5 mg, 99%). (Note: For the synthesis of compound 1k, 1l,
1m, 1o, and 1p the reactions employed 2-bromobenzophenone
derivatives as the starting material. In these cases, the reactions were
stirred at 85 ºC for 2 day).
(2-((4-Methoxyphenyl)ethynyl)phenyl)(phenyl)methanone (1f):14 yield
186.0 mg (56%, yellow solid); mp 90.8-93.6 °C; IR (neat) max 2215, 1664,
1
1511, 1288, 1249, 702 cm-1; H NMR (300 MHz, CDCl3  7.89-7.87 (m,
2H), 7.60-7.39 (m, 7H), 6.97 (d, 2H, J = 8.4 Hz), 6.72 (d, 2H, J = 8.7 Hz),
3.75 (s, 3H); 13C NMR (75 MHz, CDCl3)  197.1, 159.7, 141.2, 137.4,
133.0, 132.9, 132.3, 130.23, 130.17, 128.6, 128.3, 127.8, 122.2, 114.7,
113.7, 95.3, 86.3, 55.2 ; HRMS (ESI-TOF) calcd for C22H16NaO2 [M+Na]+
335.1043, found 335.1037.
(2-((4-Chlorophenyl)ethynyl)phenyl)(phenyl)methanone (1g): yield
(4-Methoxyphenyl)(2-(phenylethynyl)phenyl)methanone (1):13 yield
463.5 mg (99%, yellow oil); IR (neat) max 2940, 1651, 1580, 1412, 1330,
1122 cm-1; 1H NMR (300 MHz, CDCl3)  7.87 (dt, 2H, J = 9.0, 2.7 Hz),
7.62-7.59 (m, 1H), 7.51-7.40 (m, 3H), 7.27-7.17 (m, 3H), 7.12-7.08 (m,
2H), 6.94 (dt, 2H, J = 9.0, 2.7 Hz), 3.85 (s, 3H); 13C NMR (75 MHz,
CDCl3)  195.6, 163.7, 142.1, 132.6, 132.4, 131.4, 130.3, 129.9, 128.3,
128.2, 128.11, 128.06, 122.7, 121.6, 113.6, 94.7, 87.5, 55.5; HRMS (ESI-
TOF) calcd for C22H16NaO2 [M+Na]+ 335.1043, found 335.1048.
174.0 mg (56%, white solid); mp 98.5-99.4°C; IR (neat) max 1662, 1595,
1
1491, 1287, 1089, 927, 826, 753, 697 cm-1; H NMR (300 MHz, CDCl3

7.88-7.86 (m, 2H), 7.62-7.44 (m, 7H), 7.18 (d, 2H, J = 8.4 Hz), 6.97 (d,
2H, J = 8.4 Hz); 13C NMR (75 MHz, CDCl3)  196.8, 141.5, 137.3, 134.4,
133.1, 132.6, 132.5, 130.3, 130.2, 129.1, 128.7, 128.41,128.37, 121.5,
121.1, 93.9, 88.4; HRMS (ESI-TOF) calcd for C21H13ClNaO (Cl-35)
[M+Na]+ 339.0546, found 339.0542.
(2-((4-Fluorophenyl)ethynyl)phenyl)(phenyl)methanone (1h): yield
259.0 mg (89%, orange solid); mp 62.2-63.1 °C; IR (neat) max 1665,
1596, 1508, 1288, 1232, 1156, 928, 836, 702 cm-1; 1H NMR (300 MHz,
CDCl3)  7.89-7.86 (m, 2H), 7.62-7.45 (m, 7H), 7.05-7.00 (m, 2H), 6.93-
6.87 (m, 2H); 13C NMR (75 MHz, CDCl3)  196.7, 162.4 (d, JCF = 248 Hz),
141.3, 137.2, 133.2 (d, JCF = 8 Hz), 133.0, 132.3, 130.2, 130.0, 128.6,
128.3, 128.1, 121.5, 118.6 (d, J = 3 Hz), 115.2 (d, J = 0.3 Hz), 93.9, 87.1
(d, J = 1 Hz); HRMS (ESI-TOF) calcd for C21H13FNaO [M+Na]+ 323.0843,
found 323.0836.
(2-(Hex-1-ynyl)phenyl)(phenyl)methanone (1a):7 yield 250.1 mg (96%,
yellow oil); IR (neat) max 1667, 1597, 1285, 927, 755, 703 cm-1; 1H NMR
(300 MHz, CDCl3)  7.84-7.80 (m, 2H), 7.58-7.53 (m, 1H), 7.49-7.36 (m,
6H), 2.10 (t, 2H, J = 6.9 Hz), 1.21-1.14 (m, 4H), 0.78 (t, 3H, J = 7.2 Hz);
13C NMR (75 MHz, CDCl3)  197.4, 141.7, 137.3, 132.9, 132.5, 130.1,
129.9, 128.2, 128.0, 127.3, 122.5, 96.6, 78.6, 30.2, 21.7, 18.9, 13.5;
HRMS (ESI-TOF) calcd for C19H18NaO [M+Na]+ 285.1250, found
285.1255.
(2-(5-Methylhex-1-ynyl)phenyl)(phenyl)methanone (1b) : yield 215.6
mg (82%, yellow oil); IR (neat) max 2956, 1667, 1449, 1316, 1288, 927,
754, 703 cm-1; 1H NMR (300 MHz, CDCl3)  7.84-7.80 (m, 2H), 7.59-7.53
(m, 1H), 7.48-7.33 (m, 6H), 2.10 (t, 2H, J = 7.2 Hz), 1.47-1.33 (m, 1H),
1.13-1.05 (m, 2H), 0.75 (d, 6H, J = 6.6 Hz); 13C NMR (75 MHz, CDCl3) 
197.4, 141.8, 137.3, 133.0, 132.5, 130.1, 129.9, 128.2, 128.0, 127.3,
122.5, 96.7, 78.5, 37.0, 26.9, 22.0, 17.3; HRMS (ESI-TOF) calcd for
C20H20NaO [M+Na]+ 299.1406, found 299.1411.
Phenyl(2-((triisopropylsilyl)ethynyl)phenyl)methanone (1i): yield
310.7 mg (87%, white solid); mp 45.5-46.3 °C; IR (neat) max 2941, 2864,
2155, 1659, 1291, 773 cm-1; 1H NMR (300 MHz, CDCl3)  7.84-7.81 (m,
2H), 7.58-7.51 (m, 2H), 7.46-7.39 (m, 5H), 0.90 (d, 18H, J = 3.6 Hz),
0.94-0.85 (m, 3H); 13C NMR (75 MHz, CDCl3)  197.0, 142.4, 136.8,
133.2, 133.1, 130.3, 129.6, 128.33, 128.27, 127.6, 127.5, 104.0, 97.1,
18.4, 11.0; HRMS (ESI-TOF) calcd for C24H31OSi [M+H]+ 363.2139,
found 363.2138.
(2-(3,3-Dimethylbut-1-ynyl)phenyl)(phenyl)methanone (1c):7 yield
241.8 mg (97%, white solid); mp 59.2-60.0 °C; IR (neat) max 2969,
1664,1449, 1284, 753, 702 cm-1; 1H NMR (300 MHz, CDCl3)  7.85-7.82
(m, 2H), 7.59-7.54 (m, 1H), 7.48-7.36 (m, 6H), 0.94 (s, 9H); 13C NMR (75
(2-(Hex-1-ynyl)phenyl)(4-methoxyphenyl)methanone (1j):7 yield 216.4
mg (80%, yellow oil); IR (neat) max 2957, 2933, 1659, 1595, 1253, 1149,
929, 757 cm-1; 1H NMR (400 MHz, CDCl3)  7.80 (dt, 2H, J = 8.8, 2.0 Hz.),
7.46 (d, 1H, J = 7.2 Hz), 7.42-7.35 (m, 3H), 6.92 (dt, 2H, J = 8.8, 2.0 Hz),
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3.86 (s, 3H), 2.14 (t, 2H, J = 6.8 Hz), 1.23-1.11 (m, 4H), 0.78 (t, 3H, J =
7.2 Hz); 13C NMR (100 MHz, CDCl3)  196.0, 163.6, 142.2, 132.5, 132.4,
130.2, 129.5, 127.6, 127.3, 122.1, 113.4, 96.1, 78.5, 55.4, 30.3, 21.7,
19.0, 13.5 ; HRMS (ESI-TOF) calcd for C20H21O2 [M+H]+ 293.1536, found
293.1533.
(2-Fluoro-6-(hex-1-ynyl)phenyl)(phenyl)methanone (1q):7 Yield 242.9
mg (90%, yellow oil); IR (neat): υmax 2960, 2931, 2354, 1670, 1598, 1484,
1292, 704 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.86-7.83 (m, 2H), 7.59 ( tt,
1H, J = 7.5, 1.2 Hz), 7.48-7.43 (m, 2H), 7.39-7.32 (m, 1H), 7.27-7.25 (m,
1H), 7.08 (td, 1H, J = 9.0, 1.2 Hz), 2.14 (t, 2H, J = 6. Hz), 1.27-1.07 (m,
4H), 0.75 (t, 3H, J = 7.3 Hz); 13C NMR (75 MHz, CDCl3) δ 192.9, 159.0 (d,
JCF = 247 Hz), 136.8, 133.7, 130.5 (d, JCF = 9 Hz), 130.0 (d, JCF = 19 Hz),
(4-Chlorophenyl)(2-(hex-1-ynyl)phenyl)methanone (1k): yield 90.3 mg
(30%, colorless oil); IR (neat) max 2958, 2932, 2232, 1667, 1586, 1288,
1089, 927, 755 cm-1; 1H NMR (300 MHz, CDCl3)  7.76 (dt, 2H, J = 11.1,
2.4 Hz), 7.51-7.34 (m, 6H), 2.14-2.09 (m, 2H), 1.25-1.10 (m, 4H), 0.82-
0.78 (m, 3H); 13C NMR (75 MHz, CDCl3)  196.0, 141.1, 139.3, 135.6,
132.5, 131.4, 130.1, 128.4, 127.9, 127.4, 122.3, 96.9, 78.4, 30.1, 21.6,
18.9, 13.4; HRMS (ESI-TOF) calcd for C19H18ClO [M+H]+ 297.1041, found
297.1039.
129.7, 128.5, 128.0 (d, JCF = 3 Hz), 124.1 (d, JCF = 5 Hz), 115.2 (d, JCF
=
21.6 Hz), 96.9, 77.2 (d, JCF = 4 Hz), 30.1, 21.6, 18.9, 13.5; HRMS (ESI-
TOF) calcd for C19H17FNaO [M+Na]+ 303.1156 found 303.1165.
(4-Fluoro-2-(hex-1-ynyl)phenyl)(phenyl)methanone (1r):7 yield 274.2
mg (91%, yellow oil); IR (neat) max 2959, 2933, 1163, 1279, 748, 701
cm-1; 1H NMR (300 MHz, CDCl3)  7.80-7.77(m, 2H), 7.55 (t, 1H, J = 7.5
Hz), 7.45-7.40 (m, 3H), 7.15 (dd, 1H, J = 9.3, 2.4 Hz), 7.05 (td, 1H, J =
8.1, 2.7 Hz), 2.08 (t, 2H, J = 6.9 Hz), 1.20-1.14 (m, 4H), 0.80-0.75 (m,
3H); 13C NMR (75 MHz, CDCl3)  196.2, 163.2 (d, JCF = 249.3 Hz), 137.8
(d, JCF = 3 Hz), 137.3, 133.0, 130.5 (d, JCF = 9 Hz), 130.0, 128.2, 125.1
(d, JCF = 10 Hz), 119.3 (d, JCF = 23 Hz), 114.8 (d, JCF = 22 Hz), 98.0, 77.7
(d, JCF = 3 Hz), 30.0, 21.7, 18.9, 13.4; HRMS (ESI-TOF) calcd for
C19H18FO [M+H]+ 281.1336, found 281.1333.
(4-Fluorophenyl)(2-(hex-1-ynyl)phenyl)methanone (1l): yield 261.9 mg
(84%, brown oil); IR (neat) max 2957, 2933, 2871, 1668, 1597, 1287,
1
1234, 1148, 929, 849, 756 cm-1; H NMR (300 MHz, CDCl3)  7.85 -7.81
(m, 2H), 7.49-7.33 (m, 4H), 7.15-7.07 (m, 2H), 2.14-2.12 (m, 2H), 1.26-
1.10 (m, 4H), 0.80 (t, 3H, J = 6.9 Hz); 13C NMR (75 MHz, CDCl3)  195.9,
165.8 (d, JCF = 253.3 Hz), 141.4, 133.5 (d, JCF = 2.9 Hz), 132.8 (d, JCF
=
9.3 Hz), 132.6, 130.1, 127.9, 127.5, 122.4, 115.4 (d, JCF = 21.8 Hz), 96.8,
78.5, 30.2, 21.7, 18.9, 13.5; HRMS (ESI-TOF) calcd for C19H18FO [M+H]+
281.1336, found 281.1337.
General procedure for the synthesis of indenone derivatives;
Compound 1 (101.2 mg, 0.3240 mmol) was dissolved with dry CH3CN (6
mL/mmol) in sealed tube and then a mixture was added H2O (6 µL,
0.3240 mmol) and I2 (82.2 mg, 0.3240 mmol) at room temperature. The
reaction mixture was then heated to 65° C and stirred for 1 hr. The
reaction was quenched with sat. Na2S2O3 and extracted with EtOAc. The
combined organic layers were washed with brine, dried over Na2SO4,
filtered and concentrated under reduced pressure to provide the crude
product which was purified on silica gel (EtOAc/hexane: 1:9) to yield the
corresponding product 2 (73.8 mg, 73%).
1-(2-(Hex-1-ynyl)phenyl)-2-phenylethanone (1m): yield 41.4 mg (14%,
yellow oil); IR (neat) max 2960, 2869, 1723, 1601, 1453, 1276, 1261, 764,
750 cm-1; 1H NMR (300 MHz, CDCl3)  7.48 (t, 2H, J = 7.8 Hz), 7.38-
7.24 (m, 7H), 4.43(s, 2H), 2.45 (t, 2H, J = 6.6 Hz), 1.65-1.53 (m, 2H),
1.51-14.3 (m, 2H), 0.93 (t, 3H, J = 7.2 Hz); 13C NMR (75 MHz, CDCl3) 
201.5, 141.3, 134.5, 133.7, 130.6, 129.6, 128.4, 128.1, 127.5, 126.7,
121.9, 96.7, 79.3, 48.6, 30.5, 22.0, 19.3, 13.5; HRMS (ESI-TOF) calcd for
C20H20NaO [M+Na]+ 299.1406, found 299.1406.
3-(4-Methoxyphenyl)-2-phenyl-1H-inden-1-one (2):3h yield 73.8 mg
(73%, red solid); mp 119.5-120.0 °C; IR (neat) max 1704, 1605,1250,
1176, 1028, 753, 697 cm-1; 1H NMR (300 MHz, CDCl3)  7.47(d, 1H, J =
6.6 Hz), 7.27-7.23(m, 9H), 7.20-7.09(m, 1H), 6.82(d, 2H, J = 8.7 Hz),
3.74 (s, 3H) ); 13C NMR (75 MHz, CDCl3)  196.4, 160.4, 155.2, 145.1,
133.2, 131.6, 131.1, 131.0, 130.2, 130.0, 128.9, 128.0, 127.5, 124.8,
122.7, 121.2, 114.1, 55.2; HRMS (ESI-TOF) calcd for C22H17O [M+H]+
313.1223, found 313.1236.
1-(2-(Hex-1-ynyl)phenyl)ethanone (1n):15 yield 379.4 mg (88%, brown
oil); IR (neat) max 2958, 2932, 1682, 1356, 1279, 1274, 1257, 758 cm-1;
1H NMR (300 MHz, CDCl3)  7.65 (dd, 1H, J = 7.5, 0.9 Hz), 7.48 (dd, 1H,
J = 7.8, 0.9 Hz), 7.37 (td, 1H, J = 7.5, 1.5 Hz), 7.32 (td, 1H, J = 7.8, 1.5
Hz), 2.73 (s, 3H), 2.46 (t, 2H, J = 6.9 Hz),1.66-1.57 (m, 2H), 1.55-1.42 (m,
2H), 0.95 (t, 3H, J = 7.9 Hz); 13C NMR (75 MHz, CDCl3)  200.8, 140.7,
133.6, 130.7, 127.9, 127.2, 122.1, 96.5, 79.3, 30.2, 29.7, 21.7, 19.1,
13.2; HRMS (ESI-TOF) calcd for C14H16NaO [M+Na]+ 223.1093, found
223.1091.
2-Butyl-3-phenyl-1H-inden-1-one (2a):6 yield 83.7 mg (79%, yellow oil);
IR (neat) max 1703, 1608, 1456,934, 775, 720, 700 cm-1; 1H NMR (300
MHz, CDCl3)  7.53-7.42 (m, 6H), 7.31-7.26 (m, 1H), 7.21-7.16 (m, 1H),
6.99 (d, 1H, J = 6.9 Hz), 2.34 (t, 2H, J = 7.5 Hz), 1.52-1.42 (m, 2H), 1.35-
1.23 (m, 2H), 0.84 (t, 3H, J = 7.2 Hz); 13C NMR (75 MHz, CDCl3)  198.2,
154.9, 145.8, 135.5, 133.1, 132.8, 130.9, 129.0, 128.7, 128.1, 127.7,
122.3, 120.4, 31.3, 23.0, 22.7, 13.7; HRMS (ESI-TOF) calcd for
C19H18NaO [M+Na]+ 285.1250, found 285.1255.
(2-(Hex-1-ynyl)-4-methoxyphenyl)(phenyl)methanone (1o):7 yield
295.2 mg (89%, brown oil); IR (neat) max 2958, 2932, 2228, 1658, 1596,
1562, 1447, 1316, 1281, 1207, 1173, 1033, 923, 701 cm-1; 1H NMR (300
MHz, CDCl3)  7.80-7.77 (m, 2H), 7.56-7.51 (m, 1H), 7.45-7.40 (m, 3H),
6.98 (d, 1H, J = 2.7 Hz), 6.89 (dd, 1H, J = 8.7, 2.7 Hz), 3.85 (s, 3H), 2.12-
2.08 (m, 2H), 1.23-1.19 (m, 4H), 0.82-0.78 (m, 3H); 13C NMR (75 MHz,
CDCl3)  196.6, 161.0, 138.2, 133.9, 132.4, 130.9, 130.0, 128.0, 124.7,
117.4, 113.6, 96.7, 78.8, 55.4, 30.2, 21.8, 18.9, 13.5; HRMS (ESI-TOF)
calcd for C20H20NaO2 [M+Na]+ 315.1356, found 315.1348.
2-Isopentyl-3-phenyl-1H-inden-1-one (2b): yield 76.2 mg (78%, yellow
oil); IR (neat) max 2955, 1705, 1609, 1456, 1364, 775, 721, 701 cm-1; 1H
NMR (300 MHz, CDCl3)  7.53-7.41 (m, 6H), 7.29-7.24 (m, 1H), 7.19-
7.14 (m, 1H), 6.98 (d, 1H, J = 7.2 Hz.), 2.36-2.31 (m, 2H), 1.59-1.46 (m,
1H), 1.41-1.33 (m, 2H), 0.83 (d, 6H, J = 6.6 Hz); 13C NMR (75 MHz,
CDCl3)  198.2, 154.7, 145.8, 135.1, 133.1, 132.8, 131.0, 129.0, 128.7,
128.0, 127.7, 122.3, 120.4, 38.2, 28.1, 22.2, 21.2; HRMS (ESI-TOF)
calcd for C20H20NaO [M+Na]+ 299.1406, found 299.1415.
(2-(Hex-1-ynyl)-5-methoxyphenyl)(phenyl)methanone
(1p):
yield
302.9 mg (98%, brown oil); IR (neat) max 2959, 1670, 1599, 1489, 1294,
1274, 1260, 750 cm-1; 1H NMR (300 MHz, CDCl3)  7.84-7.81 (m, 2H),
7.53 (tt, 1H, J = 7.2, 1.5 Hz), 7.45-7.36 (m, 3H), 6.96-6.93 (m, 2H), 3.80
(s, 3H), 2.08-2.03 (m, 2H), 1.17-1.11 (m, 4H), 0.78-0.75 (m, 3H); 13C
NMR (75 MHz, CDCl3)  197.0, 158.7, 143.0, 137.0, 133.7, 132.9, 130.0,
128.1, 116.1, 114.5, 112.9, 94.6, 78.1, 55.3, 30.2, 21.6, 18.8, 13.4;
HRMS (ESI-TOF) calcd for C20H21O2 [M+H]+ 293.1536, found 293.1537.
2-tert-Butyl-3-phenyl-1H-inden-1-one (2c):6 yield 11.9 mg (17%, yellow
solid); mp 108.4-109.2 °C; IR (neat) max 2955, 1701, 1607, 1595, 1482,
1
1456,1325, 770, 756, 733, 704 cm-1; H NMR (300 MHz, CDCl3)  7.47-
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700968
European Journal of Organic Chemistry
FULL PAPER
7.36 (m, 3H), 7.27-7.12 (m, 5H), 6.50-6.47 (m, 1H), 1.16 (s, 9H); 13C
NMR (75 MHz, CDCl3)  198.6, 154.1, 147.8, 141.6, 135.5, 133.4, 130.0,
128.2, 128.1,127.9, 121.8, 120.4, 33.7. 30.7, 29.7; HRMS (ESI-TOF)
calcd for C19H19O [M+H]+ 263.1430, found 263.1427.
1H, J = 6.9 Hz), 6.99-6.92 (m, 2H); 13C NMR (75 MHz, CDCl3)  196.4,
162.3 (d, JCF = 247 Hz), 155.3, 145.1, 133.5, 132.6, 131.7 (d, JCF = 8 Hz),
131.3, 130.6, 129.4, 129.0, 128.9, 128.4, 126.7 (d, JCF = 3.5 Hz), 123.0,
121.3, 115.2 (d, JCF = 21 Hz); HRMS (ESI-TOF) calcd for C21H14FO
[M+H]+ 301.1023, found 301.1026.
1-(2-Benzoylphenyl)-3,3-dimethylbutan-1-one (3c):16 yield 52.2 mg
(68%, yellow oil) ; IR (neat) max 2954, 1668, 1314, 1262, 930, 755, 714,
1-(2-Benzoylphenyl)ethanone (3i):19 yield 52.4 mg (86%, white solid);
mp 97.6-98.1 °C; IR (neat) max 1666, 1596, 1264, 929, 760, 707, 695
cm-1; 1H NMR (300 MHz, CDCl3)  7.91-7.88 (m, 1H), 7.76-7.73 (m, 2H),
7.64-7.51 (m, 3H), 7.44-7.39 (m, 3H), 2.52 (s, 3H); 13C NMR (75 MHz,
CDCl3)  198.3, 197.6, 140.7, 137.4, 137.1, 132.8, 132.1, 129.6, 129.2,
129.1, 128.3, 128.1, 27.3; HRMS (ESI-TOF) calcd for C15H13O2 [M+H]+
225.0910, found 225.0911.
1
699 cm-1; H NMR (300 MHz, CDCl3)  7.85-7.82 (m, 1H,), 7.74-7.73 (d,
2H, J = 7.2 Hz), 7.61-7.51 (m, 3H), 7.41 (t, 3H, J = 6.0 Hz), 2.75 (s, 2H),
0.95 (s, 9H); 13C NMR (75 MHz, CDCl3)  201.1, 197.8, 140.8, 139.8,
137.4, 132.8, 131.5, 129.6, 129.4, 128.8, 128.5, 128.3, 51.4, 31.5, 29.8;
HRMS (ESI-TOF) calcd for C19H21O2 [M+H]+ 281.1536, found 281.1532.
2-(6-Hydroxyhexyl)-3-phenyl-1H-inden-1-one (2d): yield 70.0 mg (68%,
yellow oil); IR (neat) max 3392, 2928, 1703, 1456, 701 cm-1; 1H NMR
(300 MHz, CDCl3)  7.54-7.42 (m, 6H), 7.28 (td, 1H, J = 7.8, 1.2 Hz),
7.18 (td, 1H, J = 7.4, 0.9 Hz), 6.99 (d, 1H, J = 7.2 Hz), 3.61 (t, 2H, J = 6.6
Hz), 2.33 (t, 2H, J = 7.5 Hz), 1.57-1.45 (m, 5H), 1.31-1.25 (m, 8H); 13C
NMR (75 MHz, CDCl3)  198.2, 155.0, 145.9, 135.5, 133.1, 132.9, 131.0,
129.0, 128.7, 128.1, 127.8, 122.4, 120.5, 63.0, 32.7, 29.5, 29.2, 29.12,
29.10, 25.6, 23.2; HRMS (ESI-TOF) calcd for C23H27O2 [M+H]+ 335.2006,
found 335.2011.
2-Butyl-3-(4-methoxyphenyl)-1H-inden-1-one (2j):4 yield 66.3 mg (78%,
yellow solid); mp 55.9-58.7 °C; IR (neat) max 2956, 2927, 1702, 1607,
1509, 1250, 1176, 1031 cm-1; 1H NMR (300 MHz, CDCl3  7.46-7.39 (m,
3H), 7.29 (t, 1H, J = 7.8 Hz), 7.19 (t, 1H, J = 6.9 Hz), 7.06-7.02 (m, 3H),
3.89 (s, 3H), 2.35 (t, 2H, J = 7.5 Hz), 1.59-1.43 (m, 2H), 1.37-1.25 (m,
2H), 0.86 (t, 3H, J = 7.2); 13C NMR (75 MHz, CDCl3)  198.4, 160.2,
154.8, 145.9, 134.8, 133.0, 131.3, 129.3, 128.0, 125.2, 122.2, 120.4,
114.2, 55.3, 31.4, 23.1, 22.8, 13.8; HRMS (ESI-TOF) calcd for C20H21O2
[M+H]+ 293.1536, found 293.1536.
2,3-Diphenyl-1H-inden-1-one (2e):3i yield 61.2 mg (65%, red solid); mp
149.8-150.3 °C ; IR (neat) max 1706, 1606, 1348, 752, 700 cm-1; 1H NMR
(300 MHz, CDCl3)  7.56 (d, 1H, J = 6.9 Hz), 7.40-7.31 (m, 6H), 7.28-
7.22 (m, 6H), 7.11 (d, 1H, J = 7.2 Hz); 13C NMR (75 MHz, CDCl3)  196.4,
155.3, 145.2, 133.4, 132.7, 132.3, 130.7, 129.9, 129.2, 128.9,128.7,
128.4, 128.0, 127.7, 122.9, 121.2; HRMS (ESI-TOF) calcd for C21H15O
[M+H]+ 282.3353, found 283.1116.
2-Butyl-3-(4-chlorophenyl)-1H-inden-1-one (2k):4 yield 38.8 mg (67%,
yellow oil); IR (neat) max 2957, 2929, 1705, 1606, 1490, 1457, 1091, 727
cm-1; 1H NMR (300 MHz, CDCl3) 7.51-7.45 (m, 3H), 7.40-7.37 (m, 2H),
7.32-7.17 (m, 2H), 6.94 (d, 1H, J = 7.2 Hz), 2.32 (t, 2H, J = 7.5 Hz), 1.48-
1.40 (m, 2H), 1.35-1.23 (m, 2H), 0.84 (t, 3H, J = 7.2); 13C NMR (75 MHz,
CDCl3)  197.9, 153.6, 145.5, 135.9, 135.0, 133.2, 131.3, 131.0, 129.2,
129.1, 128.3, 122.6, 120.2, 31.3, 23.0, 22.8, 13.7; HRMS (ESI-TOF)
calcd for C19H17NaO (Cl-35) [M+Na]+ 319.0860, found 319.0853.
2-(4-Methoxyphenyl)-3-phenyl-1H-inden-1-one (2f):3h yield 7.1 mg (9%,
red solid); mp 132.2-125.9 °C; IR (neat) max 2931, 1709, 1606, 1510,
1
1250, 1177 cm-1; H NMR (400 MHz, CDCl3)  7.56 (d, 1H, J = 6.8 Hz),
2-Butyl-3-(4-fluorophenyl)-1H-inden-1-one (2l): yield 72.2 mg (74%,
yellow oil); IR (neat) max 2957, 2926, 2860, 1705, 1601, 1508, 1456,
1225, 1157,853 cm-1; 1H NMR (300 MHz, CDCl3  7.37-7.30 (m, 3H),
7.19 (td, 1H, J = 7.8, 1.2 Hz), 7.15-7.07 (m, 3H), 6.86 (d, 1H, J = 7.2 Hz),
2.23 (t, 2H, J = 7.5 Hz), 1.42-1.32 (m, 2H), 1.26-1.13 (m, 2H), 0.75 (t, 3H,
J = 7.2);13C NMR (75 MHz, CDCl3)  198.0, 162.9 (d, JCF = 248 Hz),
7.41-7.37 (m, 4H), 7.35 (dd, 1H, J = 7.2, 0.8 Hz), 7.28-7.22 (m, 4H), 7.11
(d, 1H, J = 7.2 Hz), 6.80 (d, 2H, J = 9.2 Hz), 3.79 (s, 3H); 13C NMR (100
MHz, CDCl3)  197.0,159.2,153.8, 145.5, 133.4, 131.5, 133.0, 131.2,
130.7, 129.1, 128.8, 128.6, 128.5, 123.0, 122.9, 120.9, 113.6, 55.2;
HRMS (ESI-TOF) calcd for C22H16NaO2 [M+Na]+ 335.1040, found
335.1038.
153.9, 145.7, 135.6, 133.1, 130.8, 129.7 (d, JCF = 8 Hz), 128.7 (d, JCF
=
3.4 Hz), 128.2, 122.4, 120.2, 115.9 (d, JCF = 21 Hz), 31.3, 22.9, 22.7,
13.7; HRMS (ESI-TOF) calcd for C19H18FO [M+H]+281.1336, found
281.1334.
2-(2-Benzoylphenyl)-1-(4-methoxyphenyl)ethanone (4f):12 yield 56.4
mg (65%, yellow solid); mp 91.0-98.8 °C ; IR (neat) max 1658, 1598,
1260, 1168, 710, 698 cm-1; 1H NMR (300 MHz, CDCl3)  7.91 (d, 4H, J =
8.7 Hz), 7.59-7.25 (m, 7H), 6.86 (d, 2H, J = 8.7 Hz), 4.54 (s, 2H), 3.81(s,
3H); 13C NMR (75 MHz, CDCl3)  198.3, 195.6, 163.4, 138.4, 137.9,
134.9, 132.7, 131.9, 130.8, 130.5, 130.3, 130.0, 129.8, 128.2, 126.1,
113.6, 55.4, 42.6; HRMS (ESI-TOF) calcd for C22H19O3 [M+H]+ 331.1329,
found 331.1329.
3-Pentyl-2-phenyl-1H-inden-1-one (2m’): yield 32.3 mg (39%, orange
oil); IR (neat) max 2956, 2930, 2865, 1710, 1602, 1457, 756, 698 cm-1;
1H NMR (300 MHz, CDCl3  7.49 (d, 1H, J = 6.9 Hz), 7.45-7.31 (m, 6H),
7.27-7.22 (m, 1H), 7.17 (d, 1H, J = 7.2 Hz), 2.72-2.66 (m, 2H), 1.74-1.61
(m, 2H), 1.44-1.28 (m, 4H), 0.88 (t, 3H, J = 6.9 Hz); 13C NMR (75 MHz,
CDCl3)  196.7, 158.9, 145.2, 133.5, 133.31, 131.34, 130.8, 129.3, 128.7,
128.3, 127.7, 122.3, 119.9, 32.0, 27.8, 26.7, 22.3, 13.9; HRMS (ESI-
TOF) calcd for C20H20NaO [M+Na]+ 299.1406, found 299.1413.
2-(4-Chlorophenyl)-3-phenyl-1H-inden-1-one (2g):17 yield 50.6 mg
(70%, red solid); mp 145.6-146.5 °C; IR (neat) max 1709, 1607,
1
1487,1343, 1092, 775, 775, 728, 701 cm-1; H NMR (300 MHz, CDCl3) 
7.57-7.55 (m, 1H), 7.44-7.40 (m, 3H), 7.38-7.33 (m, 3H), 7.30-7.27 (m,
1H), 7.25-7.21 (m, 4H), 7.13 (d, 1H, J = 7.2 Hz); 13C NMR (75 MHz,
CDCl3)  196.1, 155.7, 145.0, 133.7, 133.5, 132.4, 131.2, 131.1, 130.6,
129.5, 129.2, 129.1, 128.9, 128.3, 123.0, 121.4; HRMS (ESI-TOF) calcd
for C21H14ClO (Cl-35) [M+H]+ 317.0728, found 317.0724.
2-Butyl-3-methyl-1H-inden-1-one (2n): yield 24.3 mg (23%, yellow oil);
IR (neat) max 2960, 2940, 2869, 2333, 1715, 1671, 1598, 1316, 1294,
1239, 747 cm-1; 1H NMR (300 MHz, CDCl3
 7.37-7.29 (m, 2H), 7.18-
7.13 (m, 1H), 7.00 (d, 1H, J = 7.2 Hz), 2.27 (t, 2H, J = 7.2 Hz), 2.11 (s,
3H), 1.49-1.25 (m, 4H), 0.93-0.89 (m, 3H); 13C NMR (75 MHz, CDCl3) 
198.2, 153.7, 135.2, 146.3, 133.2, 130.9, 128.0, 121.5, 118.5, 31.2, 22.6,
22.4, 13.9, 11.4; HRMS (ESI-TOF) calcd for C14H17O [M+H]+ 201.1274,
found 201.1270.
2-(4-Fluorophenyl)-3-phenyl-1H-inden-1-one (2h):18 yield 68.5 mg
(71%, orange solid); mp 115.8-116.5 °C; IR (neat) max 1705, 1604, 1592,
1508, 1492,1343, 1225, 1159, 853, 7742 cm-1; 1H NMR (300 MHz, CDCl3
 7.58 (d, 1H, J = 6.6 Hz), 7.44-7.35 (m, 6H), 7.31-7.21 (m, 3H), 7.13 (d,
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10.1002/ejoc.201700968
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2-Butyl-6-methoxy-3-phenyl-1H-inden-1-one (2o): yield 51.4 mg (49%,
yellow oil); IR (neat) max 2956, 2932, 2859, 1702, 1478, 1430, 1279,
1221, 1024; cm-1; 1H NMR (300 MHz, CDCl3)  7.52 (m, 5H), 7.08 (d, 1H,
J = 2.4 Hz), 6.88 (d, 1H, J = 7.8 Hz), 6.71 (dd, 1H, J = 8.1, 2.4 Hz), 3.81
(s, 3H), 2.30 (t, 2H, J = 7.5 Hz), 1.51-1.41 (m, 2H), 1.35-1.22 (m, 2H),
0.84 (t, 3H, J = 7.2 Hz); 13C NMR (75 MHz, CDCl3)  198.0, 160.4, 155.9,
137.6, 134.3, 133.1, 129.0, 128.7, 127.7, 121.2, 115.7, 110.4, 55.7, 31.4,
23.0, 22.7, 13.7; HRMS (ESI-TOF) calcd for C20H21O2 [M+H]+ 293.1536,
found 293.1529.
J = 7.2 Hz); 13C NMR (75 MHz, CDCl3)  198.2, 154.9, 145.8, 135.5,
133.1, 132.8, 130.9, 129.0, 128.7, 128.1, 127.7, 122.3, 120.4, 31.3, 23.0,
22.7, 13.7; HRMS (ESI-TOF) calcd for C19H19O [M+H]+ (O-18) 265.1473,
found 26.1471.
Acknowledgements
This research work was supported in part by grants from
Chulabhorn Research Institute, Mahidol University, the Center of
Excellence on Environmental Health and Toxicology, Science &
2-Butyl-5-methoxy-3-phenyl-1H-inden-1-one (2p): yield 69.4 mg (72%,
orange solid); mp 56.6-61.4 °C; IR (neat) max 2957, 2861, 1700, 1594,
1473, 1366, 1219, 1099, 701 cm-1; 1H NMR (300 MHz, CDCl3)  7.52-
7.40 (m, 6H), 6.58-6.55 (m, 2H), 3.79 (s, 3H), 2.33 (t, 2H, J =7.8 Hz),
1.52-1.41 (m, 2H), 1.34-1.22 (m, 2H, J = 7.2 Hz), 0.83 (t, 3H, J = 7.5 Hz);
13C NMR (75 MHz, CDCl3)  196.8, 164.2, 152.7, 148.6, 137.2, 132.8,
128.8, 128.7, 127.8, 124.2, 123.7, 109.8, 109.3, 55.6, 31.3, 22.7, 23.1,
13.7; HRMS (ESI-TOF) calcd for C20H20NaO2 [M+Na]+ 315.1356, found
315.1354.
Technology
Postgraduate
Education
and
Research
Development Office (PERDO), Ministry of Education, and
Thailand Research Fund (RSA6080085).
Keywords: indenone • iodine • ortho-alkynylarylketones •
cyclization• metal-free
2-Butyl-4-fluoro-3-phenyl-1H-inden-1-one (2q): yield 56.8 mg (56%,
yellow oil) ); IR (neat) max 2957, 2927, 2858, 1709, 1607, 1469, 1238,
1008, 759, 699 cm-1; 1H NMR (300 MHz, CDCl3)  7.49-7.41 (m, 5H),
7.32-7.26 (m, 1H), 7.22-7.15 (m, 1H), 7.03-6.96 (m,1H), 2.27 (t, 2H, J =
7.8 Hz), 1.49-1.39 (m, 2H), 1.33-1.21 (m, 2H), 0.82 (t, 3H, J = 7.2 Hz);
13C NMR (75 MHz, CDCl3)  196.8 (d, JCF = 2 Hz) 155.5 (d, JCF = 254
Hz), 153.8 (d, JCF = 3 Hz), 136.7 (d, JCF = 3 Hz), 133.7 (d, JCF = 3 Hz),
133.6, 130.5 (d, JCF = 7 Hz), 128.9, 128.3, 128.1, 127.6 (d, JCF = 2 Hz),
123.0 (d, JCF = 23 Hz), 118.5 (d, JCF = 3 Hz), 31.3, 22.8 , 22.7, 13.7;
HRMS (ESI-TOF) calcd for C19H18FO [M+H]+ 281.1336, found 281.1340.
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2-Butyl-6-fluoro-3-phenyl-1H-inden-1-one one (2r): yield 64.1mg (56%,
orange oil); IR (neat) max 2930, 1708, 1473, 109, 699 cm-1; 1H NMR (300
MHz, CDCl3)  7.54-7.41 (m, 5H), 7.18-7.16 (m, 1H), 6.94-6.91 (m, 2H),
2.35-2.29 (t, 2H, J = 7.5 Hz), 1.51 (m, 2H), 1.35-1.23 (m, 2H), 0.86-0.81
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=
248 Hz), 155.1 (d, JCF = 2 Hz), 141.2 (d, JCF = 4 Hz), 135.7 (d, JCF = 5
Hz), 133.3 (d, JCF = 7 Hz), 132.6, 129.3, 128.8, 127.6, 121.4 (d, JCF = 8
Hz), 118.1 (d, JCF = 23 Hz), 111.1 (d, JCF = 25 Hz), 31.3, 23.1, 22.7, 13.7;
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Labeling experiment with H218O for the synthesis of compound 2a-
18O: Compound 2a (83.0 mg, 0.3163 mmol) was dissolved with dry
CH3CN (6 mL/mmol) in sealed tube and then a mixture was added H218O
(6 µL, 0. 0.3163 mmol) and I2 (80.3 mg, 0.3163 mmol) at room
temperature. The reaction mixture was then heated to 65° C and stirred
for 1 hr. The reaction was quenched with sat. Na2S2O3 and extracted with
EtOAc. The combined organic layers were washed with brine, dried over
Na2SO4, filtered and concentrated under reduced pressure to provide the
crude product. This crude product submitted for HRMS measurement.
Ratio of Compound 2a:2a-18O: = 1:2.5.
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Entry for the Table of Contents (Please choose one layout)
Layout 2:
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The utility of ortho‑alkynylarylketones in the synthesis of indenone derivatives using
molecular iodine-promoted cyclization has been demonstrated. This strategy
provided a convenient and easy control of the regioselectivity to obtain indenone
products with a broad range of substituents in moderate to good yields.
Iodine-promoted cyclization
Pennapa Chuangsoongnern, Chareef
Surinrach, Jumreang Tummatorn,*
Charnsak Thongsornkleeb and Somsak
Ruchirawat
Page No. – Page No.
Iodine-mediated cyclization of ortho-
alkynylarylketones for the synthesis
of indenone derivatives
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