Sulfinate-Salt-Mediated Radical Relay Cyclization of Cyclic Ethers with 2-Alkynylbenzonitriles toward 3-Alkylated 1-Indenones

Article abstract of DOI:10.1002/asia.201800211

A new sulfinate salt-mediated radical relay for the completion of C(sp³)?H bond indenylation of cyclic ethers with readily available 2-alkynylbenzonitriles by combining silver/tert-butyl peroxide (TBHP) was established, providing a wide range of 3-alkylated 1-indenones with generally good yields. Interestingly, the current reaction system can tolerate an S-centered radical and a C-centered radical in one pot, in which the S-centered radical promotes the formation of the C-centered radical to induce a radical cascade without disturbing the reaction process. A reaction mechanism is also proposed based on control experiments.

Full text of DOI:10.1002/asia.201800211

CHEMISTRY
AN ASIAN JOURNAL
www.chemasianj.org
Accepted Article
Title: Sulfinate Salt-Mediated Radical Relay Cyclization of Cyclic
Ethers with 2-Alkynylbenzonitriles toward 3-Alkylated 1-
Indenones
Authors: Bo Jiang, Xiao-Tong Zhu, Tian-Shu Zhang, Qi Zhao, Pei-Jun
Cai, Wen-Juan Hao, and Shu-Jiang Tu
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To be cited as: Chem. Asian J. 10.1002/asia.201800211
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10.1002/asia.201800211
Chemistry - An Asian Journal
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Sulfinate Salt-Mediated Radical Relay Cyclization of Cyclic Ethers
with 2-Alkynylbenzonitriles toward 3-Alkylated 1-Indenones
Xiao-Tong Zhu,[a],[b],[c] Tian-Shu Zhang,[a] Qi Zhao,[c] Pei-Jun Cai,*[a] Wen-Juan Hao,[c] Shu-Jiang Tu,*[c]
Bo Jiang*[c]
Dedication ((optional))
Abstract: A new sulfinate salt-mediated radical relay for the
completion of C(sp3)-H bond indenylation of cyclic ethers with readily
available 2-alkynylbenzonitriles by combining silver/ tert-butyl
peroxide (TBHP) was established, providing a wide range of 3-
alkylated 1-indenones with generally good yields. Interestingly, the
current reaction system can tolerate two different S-centered radical
and C-centered radical in a one pot, in which S-centered radical
promoted the formation C-centered radical to induce the radical
cascades without disturbing the reaction process. The reaction
mechanism was also proposed on the basis of control experiments.
still highly desirable.
PhO
O
O
O
N
N
H
N
N
O
O
N
2C Adrenegic Receptor antagonist Pfizer
Idazoxan
OMe
OH
OMe
OH
O
MeO
HO
O
O
O
(+)-Fragransin A2
(-)-Talaumidin
Figure 1. Cyclic Ether-Containing Natural Products and Drug Molecules
1-Indenones are prevalent in natural products and synthetically
Introduction
bioactive substances,[6] which show
a broad spectrum of
biological and pharmaceutical properties.[7] Consequently, a
large number of methods have been well established for the
synthesis of these compounds, including traditional
intramolecular Friedel–Crafts acylations,[8] Grignard reactions,[9]
Heck–Larock annulation[10] and related processes,[11] metal-
catalyzed C(sp2)–H activation of arenes,[12] and recent radical
addition-cyclization of ynones.[13] On the other hand, cyclic
ethers are ubiquitous structural motifs that widely appear in
natural products and active drug molecules (selected examples
are shown in Figure 1).[14] In view of the importance of 1-
indenones and cyclic esters and the continuation of our efforts
on the direct C(sp3)−H functionalization,[15] we became
interested in developing radical-triggered addition-cyclization of
2-alkynylbenzonitriles for the formation of cyclic ether-containing
1-indenones. Here, we describe a new and practical sulfinate
salt-mediated radical relay cyclization for achieving the C(sp3)-H
bond indenylation of cyclic ethers by employing silver/TBHP
system, offering a wide range of 3-alkylated 1-indenones with
generally good yields. This reaction pathway enables two C−C
Radical relay strategy is of current research interest and has
been recognized as a high-efficient synthetic method for the
synthesis of complex bioactive molecules due its excellent
functional group tolerance.[1] Specifically, the radical relay
cyclization provides a powerful synthetic alternative to rapidly
access densely functionalized cyclic molecular frameworks.[2]
Such transformation could avoid the time and cost consuming
prefunctionalizations, thereby featuring step and atom economy
with environmental sustainability.[3] Generally, the vast majority
of well-established radical relay cyclization involved the in situ
generation of the vinyl and aryl radicals to access complex
carbocycles via intramolecular 1,5-hydrogen abstraction and the
following cyclization.[4] Recently, there is increasing emphasis on
the radical-induced intermolecular hydrogen abstraction of
C(sp3)-H bonds adjacent to the oxygen of cyclic ethers to form
C-centered radical for radical relay cyclization, mainly depending
on the combination of metal catalysts, such as Cu, Fe, and Ni
salts, with peroxides.[5] Despite these limited significant
achievements, the development of new and facile radical
pathways for radical relay cyclization of cyclic ethers toward
synthesizing functionalized molecules under mild conditions is
and one C-O bond formation
via radical-induced
carbocyclization under the mild catalytic oxidative conditions. To
the best of our knowledges, there is no precedent report on the
construction of 3-alkylated 1-indenones through the radical
relay cyclization of 2-alkynylbenzonitriles with cyclic ethers.[16]
[a]
Dr X.-T. Zhu, Dr T.-S. Zhang, Prof. Dr P.-J. Cai
School of Chemical Engineering & Technology
China University of Mining and Technology, Xuzhou, 221116, P. R.
China
O
R1
O
H2O, TBHP, [Ag]
R2
R1
R2
+
E-mail: pjcai@cumt.edu.cn
sodium sulfinate
H
[b]
[c]
Dr X.-T. Zhu
Department of Chemistry,
N
3
O
2
1
Xuzhou Medical University, Xuzhou 221004, P. R. China
Q. Zhao, Dr W.-J. Hao, Prof. S.-J. Tu, Prof. Dr B. Jiang
School of Chemistry and Materials Science,
Jiangsu Normal University, Xuzhou, 221116, P. R. China
E-mail: jiangchem@jsnu.edu.cn; laotu@jsnu.edu.cn
TBHP
ArSO2
O
[Ag]
H2O
O
R1
1
R2
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
N
Scheme 1. C(sp3)-H Indenylation of Cyclic Ethers with 2-Alkynylbenzonitriles
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10.1002/asia.201800211
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Results and Discussion
results were given (entries 3-4). Next, we considered to employ
sulfinate salts as additives to promote the transformation due to
sulfinate salts were easily converted into sulfonyl radicals,[17]
which can abstract proton from 1,4-dioxane to generate its -
radicals. To our delight, the reaction in the presence of 2.0
equivalents of sodium methanesulfinate (CH3SO2Na) provided
the expected 1-indenone product 3a, albeit with a low 25% yield
(entry 5), indicating that sulfinate salts could serve as a radical
mediator to achieve the radical relay process. With these
preliminary results in hand, further optimization of the reaction
Our initial attempts focused on identifying the optimized
conditions for the reaction between 2-(phenylethynyl)benzonitrile
(1a) and 1,4-dioxane (2a) (Table 1). With CF3CO2Ag and tert-
butyl hydroperoxide (TBHP, 70% solution in water) as catalytic
oxidative system, the reaction was performed at 70 oC, but failed
to work (Table 1, entry 1). The similar inferior outcome was
observed when the reaction temperature was elevated to 120 oC
(entry 2). The use of bases, such as K2CO3 and Et3N, was
anticipated to improve this transformation, but very disappointed
Table 1. Optimization of the Reaction Conditions[a]
T (oC)
yield (%)[b]
entry
Ag salt (equiv)
Oxidant (equiv)
Additive (equiv)
NR[c]
NR
NR
NR
25
1
CF3CO2Ag (1.0)
CF3CO2Ag (1.0)
CF3CO2Ag (1.0)
CF3CO2Ag (1.0)
CF3CO2Ag (1.0)
CF3CO2Ag (1.0)
CF3CO2Ag (1.0)
CF3CO2Ag (1.0)
CF3CO2Ag (1.0)
-
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (4.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
DTBP (2.0)
TBPB (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
-
-
70
120
70
70
70
70
70
70
70
70
70
70
70
70
70
70
90
50
70
70
2
-
3
K2CO3 (2.0)
4
Et3N (2.0)
5
CH3SO2Na (2.0)
4-CH3C6H4SO2Na (2.0)
C6H5SO2Na (2.0)
4-ClC6H4SO2Na (2.0)
4-ClC6H4SO2Na (2.0)
4-ClC6H4SO2Na (2.0)
4-ClC6H4SO2Na (2.0)
4-ClC6H4SO2Na (2.0)
4-ClC6H4SO2Na (2.0)
4-ClC6H4SO2Na (2.0)
4-ClC6H4SO2Na (2.0)
4-ClC6H4SO2Na (2.0)
4-ClC6H4SO2Na (2.0)
4-ClC6H4SO2Na (2.0)
4-ClC6H4SO2Na (1.0)
4-ClC6H4SO2Na (2.0)
6
52
7
36
8
70
9
66
10
11
12
13
14
15
16
17
18
19
20
NR
32
CF3CO2Ag (0.3)
CF3CO2Ag (0.1)
AgNO3 (1.0)
trace
NR
trace
NR
NR
60
AgOTf (1.0)
CF3CO2Ag (1.0)
CF3CO2Ag (1.0)
CF3CO2Ag (1.0)
CF3CO2Ag (1.0)
CF3CO2Ag (1.0)
CF3CO2Ag (1.0)
43
58
NR
[a] Reaction conditions: 1a (0.2 mmol), 2a (2.0 mL), Ag salt (x equiv), oxidant (y equiv) additive (z equiv), and
H2O (0.6 equiv), 4.0 hours, air conditions. [b] Isolated yield based on 1a. [c] NR= No reaction.
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conditions was subsequently conducted. Gratifyingly, the
desired product 3a could be generated in 52% yield when
CH3SO2Na was replaced by sodium p-tolylsulfinate (4-
CH3C6H4SO2Na) (entry 6). Exchanging 4-CH3C6H4SO2Na for
sodium benzenesulfinate (C6H5SO2Na) delivered 36% yield of
3a (entry 7). In another case of sodium 4-chlorophenylsulfinate
(4-ClC6H4SO2Na), it showed the best performance to facilitate
the conversion of 1a into 3a, in which 70% yield was obtained
(entry 8). Increasing the amount of TBHP to 4.0 equivalents did
not improve the transformation (entry 9). Without CF3CO2Ag or
lowering its dosage, the unsatisfactory outcomes were observed
(entries 10-12). The use of other silver salts, such as silver
acetate (AgNO3) and silver trifluoromethanesulfonate (AgOTf)
completely suppressed the reaction process (entries 13-14). The
following screening of oxidants revealed that di-tert-butyl
peroxide (DTBP) and tert-butyl peroxybenzoate (TBPB) were
found to have a detrimental impact on the reaction yields
(entries 15-16). The reaction gave a relatively lower conversion
when the reaction temperature was adjusted to either 90 or 50
oC (entries 17-18). Moreover, lowering the dosage of 4-
ClC6H4SO2Na is not beneficial to the transformation (entry 19).
Without TBHP, the reaction did not work (entry 20).
functionalities were first investigated in combination with 1,4-
dioxane (2a) under the optimal conditions. Both electron-poor
and electron-rich groups at different positions of the arylalkynyl
moiety (R1) can all tolerate this radical relay system,
regioselectively providing the corresponding products 3b-3j in
67%-86% yields. Diverse substituents, such as fluoro (1b),
chloro (1c), bromo (1d), methyl (1e and 1f) ethyl(1g), t-butyl (1h)
and methoxy (PMP = p-methoxyphenyl, 1i and 1j), were suitable
for this transformation. Among them, substrates having electron-
donating groups exhibited better reactivity than those with
electron-withdrawing counterparts (3b-3d vs 3e and 3j-3i).
Interestingly, substrates bearing thienyl (1k) and cycloproyl (1l)
on the alkynyl moiety could be successfully converted into 1-
indanones 3k and 3l in 65% and 62% yields, respectively. The
electronic nature of substituents (R2) on the benzonitrile ring was
then evaluated. The reaction proceeded smoothly with various
functional groups, including methyl, fluoro and chloro, attached
by either C4 or C5 of the benzonitrile ring, delivering the
corresponding products 3m-3t in 68%-83% yields. Next, the
scope with respect to other cyclic ether components, such as
tetrahydrofuran (2b) and 1,3-dioxolane (2c), was evaluated. As
anticipated, both of these cyclic ethers were proven to be
suitable substrates, thus enabling the sulfinate-mediated radical
relay approach to afford the corresponding 1-indanones 3u-3y
with 62%-74% yields. The structure of 3c was confirmed by
single-crystal X-ray diffraction analysis (Figure 1).[18]
Figure 1. X-ray Structure of 3c
Scheme 2. Scope for the Reaction of 2-Alkynylbenzonitriles with Cyclic Ethers
Scheme 3. Control Experiments
With the optimized conditions, the scope of C(sp3)-H
functionalization was then investigated by examining various 2-
alkynylbenzonitriles and cyclic ethers, and the results are
illustrated in Scheme 2. 2-Alkynylbenzonitriles with diverse
To understand the mechanism of this reaction, several control
experiments were conducted. When 2,2,6,6-tetramethyl-1-
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piperidinyloxy (TEMPO)[19] as the radical scavenger was
subjected to the reaction system under the standard conditions,
the desired 1-indanone 3a was not generated (Scheme 3a), but
combining silver/TBHP, and a wide range of 3-alkylated 1-
indenones were synthesized with generally good yields. Notably,
cyclic ethers play dual roles as a C-centered radical precursor
as well as reaction media. Interestingly, the current
transformation can tolerate two different S-centered radical and
C-centered radical in the reaction system, in which S-centered
radical promoted the formation C-centered radical to induce the
radical cascades without disturbing the reaction process. This
chemistry is very rarely seen in organic community. Further
investigation and application of this attractive useful radical relay
strategy is underway in our laboratory.
both
TEMPO-1,4-dioxane
and
TEMPO-4-
chlorobenzenesulfonate adducts were detected by LCMS
analysis (See the Supporting Information). These results
showed that the transformation may include a radical process.
Next, 1,1-diphenylethylene, commonly used to capture the
sulfonyl radicals, was added into this reaction system (Scheme
3b), and the corresponding sulfonylation product 10 was
observed whether the desired product 3a was not detected,
suggesting that the in-situ-generated sulfonyl radical abstracts
the proton at -position of cyclic ether to give the corresponding
C-centered radical, thereby triggering addition-cyclization to the
final products via a radical relay process.
Experimental Section
General Information
All one-pot reactions were carried out in a 10-mL Schlenk tube and a 25-
mL Shrek tube equipped with a magnetic stir bar under air or argon
conditions. All melting points are uncorrected. The NMR spectra were
recorded in CDCl3 on a 400 MHz instrument with TMS as internal
standard. Chemical shifts (δ) were reported in ppm with respect to TMS.
Data are epresented as follows: chemical shift, multiplicity (s = singlet, d
= oublet, m = multiples), coupling constant (J, Hz) and ntegration. HRMS
analyses were carried out using a TOF-MS nstrument with an ESI source.
X-Ray crystallographic analysis was erformed with a SMART CCD and a
P4 diffractometer.
General Procedure for the Synthesis of Products 3.
Under air atmosphere, a mixture of 2-alkynyl benzonitriles (1, 1.0 equiv,
0.2 mmol), sodium 4-chlorobenzenesulfinate (2.0 equiv, 0.4 mmol),
(2,2,2-trifluoroacetyl)silver (1.0 equiv, 0.2 mmol ) and TBHP (70%
solution in water, 2.0 equiv, 0.4 mmol) in the mixed solvent of cyclic ether
(2, 2.0 mL) were added in a 10-mL reaction vial, which was sealed and
heated at 70 oC until TLC revealed that conversion of the starting
material 1 was completed. Then the reaction mixture was cooled to room
temperature, and dissolved in 20 mL ethyl acetate. The combined
organic layers were washed with water (2 x 10 mL). After that, the
organic phase was concentrated by vacuum distillation and was purified
by flash column chromatography (silica gel, mixtures of petroleum ether /
acetic ester, 16:1, v/v) to afford the desired products 3 as solid.
Scheme 4. Plausible mechanism
Based on the above results and literature survey,[5],[16]
a
plausible mechanism was presented in Scheme 4. The first step
is to generate the Ag(II) cation and the tert-butoxyl radical from
the oxidization of Ag(I) by the TBHP. The Ag(II) cation captures
a single electron from aryl sulfinate anion to produce sulfonyl
radical. Then, the proton at -position of 1,4-dioxane is
abstracted by sulfonyl radical to access C-centered radical A,
along with hydrosulfonyl product. The hydrosulfonyl product is
converted into the aryl sulfinate anion to complete the radical
relay cycle in the presence of tert-butoxyl anion or hydroxide
anion. The C-centered radical A triggers addition of substrate 1a
catalyzed by silver catalyst to give alkenyl radical intermediate B,
followed by 5-exo-dig cyclization and H-abstraction to afford
intermediate D, which is transformed into the target product 3a
via silver(I)-catalyzed hydrolysis in the presence of H2O.[20]
3-(1,4-dioxan-2-yl)-2-phenyl-1H-inden-1-one (3a)
Yellow solid, mp: 134-136 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.67 (d,
J = 7.2 Hz, 1H, Ar-H), 7.52 (d, J = 6.8 Hz, 1H, Ar-H), 7.48-7.37 (m, 4H,
Ar-H), 7.32-7.27 (m, 2H, Ar-H), 7.25-7.23 (m, 1H, Ar-H), 4.98 (dd, J1
=
3.2 Hz, J2 = 2.8 Hz, 1H, CH), 4.02-3.77 (m, 6H, 3CH2). 13C NMR (100
MHz, CDCl3; δ, ppm) 196.0, 151.5, 143.2, 135.2, 134.0, 130.4, 130.2,
129.5, 128.8, 128.5(2), 128.5(0), 123.5, 123.1, 73.7, 68.7, 66.5. IR (KBr,
ν, cm-1) 2977, 1719, 1655, 1578, 1459, 1222, 1122, 1091, 882. HR-MS
(ESI-TOF) m/z calcd for C19H16O3 [M+Na]+ 315.0997, found 315.0988.
3-(1,4-dioxan-2-yl)-2-(4-fluorophenyl)-1H-inden-1-one (3b)
Yellow solid, mp: 140-141 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.66 (d,
J = 7.6 Hz, 1H, Ar-H), 7.51 (d, J = 7.2 Hz, 1H, Ar-H), 7.44-7.40 (m, 1H,
Ar-H), 7.31-7.27 (m, 2H, Ar-H), 7.26-7.24 (m, 1H, Ar-H), 7.17-7.12 (m, 2H,
Ar-H), 4.94 (dd, J1 = 2.8 Hz, J2 = 3.2 Hz, 1H, CH), 4.01-3.80 (m, 6H,
3CH2). 13C NMR (100 MHz, CDCl3; δ, ppm) 196.0, 162.8 (J = 247.3 Hz),
151.5, 143.0, 134.1 (J = 11.2 Hz), 131.3 (J = 8.1 Hz), 130.2, 128.9, 126.2
(J = 3.4 Hz), 123.3 (J = 23.7 Hz), 115.6 (J = 21.5 Hz), 73.7, 68.6, 66.5(3),
66.5(0). IR (KBr, ν, cm-1) 3026, 1719, 1604, 1585, 1508, 1452, 1218,
1112, 1078, 882. HR-MS (ESI-TOF) m/z calcd for C19H15FO3 [M+Na]+
333.0903, found 333.0933.
Conclusions
In summary, starting from readily available 2-alkynylbenzonitriles
and simple cyclic ethers, we have designed and developed a
new sulfinate salt-mediated radical relay cyclization for the
realization of C(sp3)-H bond functionalization of cyclic ethers by
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2-(4-chlorophenyl)-3-(1,4-dioxan-2-yl)-1H-inden-1-one (3c)
Yellow solid, mp: 173-174 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.66 (d,
J = 7.6 Hz, 1H, Ar-H), 7.51 (d, J = 6.8 Hz, 1H, Ar-H), 7.44-7.40 (m, 3H,
3.77 (m, 6H, 3CH2), 3.85 (s, 3H, OCH3). 13C NMR (100 MHz, CDCl3; δ,
ppm) 196.5, 159.9, 150.2, 143.4, 134.8, 134.0, 130.8, 130.4, 128.6,
123.2, 123.1, 122.5, 114.1, 73.7, 68.6, 66.5(4), 66.5(0), 55.3. IR (KBr, ν,
cm-1) 2973, 1710, 1606, 1584, 1513, 1365, 1256, 1183, 1120, 1092,
1023, 918, 832. HR-MS (ESI-TOF) m/z calcd for C20H18O4 [M+Na]+
345.1103, found 345.1110.
3-(1,4-dioxan-2-yl)-2-(3-methoxyphenyl)-1H-inden-1-one (3j)
Yellow solid, mp: 156-157 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.67 (d,
J = 7.6 Hz, 1H, Ar-H), 7.51 (d, J = 7.2 Hz, 1H, Ar-H), 7.43-7.34 (m, 2H,
Ar-H), 7.27-7.23 (m, 1H, Ar-H), 6.96-6.93 (m, 1H, Ar-H), 6.88-6.85 (m, 2H,
Ar-H), 5.00 (dd, J1 = 3.2 Hz, J2 = 2.8 Hz, 1H, CH), 4.01-3.87 and 3.82-
3.77 (m, 6H, 3CH2), 3.84 (s, 3H, OCH3). 13C NMR (100 MHz, CDCl3; δ,
ppm) 195.9, 159.5, 151.7, 143.1, 135.1, 134.0, 131.5, 130.4, 129.5,
128.9, 123.5, 123.1, 121.7, 115.0, 114.3, 73.7, 68.6, 66.5, 55.3. IR (KBr,
ν, cm-1) 2974, 1710, 1602, 1576, 1455, 1356, 1289, 1167, 1111, 1098,
1044, 899. HR-MS (ESI-TOF) m/z calcd for C20H18O4 [M+Na]+ 345.1103,
found 345.1117.
Ar-H), 7.28-7.26 (m, 2H, Ar-H), 7.25-7.24 (m, 1H, Ar-H), 4.93 (dd, J1
=
3.2 Hz, J2 = 2.8 Hz, 1H, CH), 4.00-3.78 (m, 6H, 3CH2). 13C NMR (100
MHz, CDCl3; δ, ppm) 195.7, 151.9, 143.0, 134.7, 134.1, 134.0, 130.8,
130.2, 129.0, 128.8, 128.6, 123.5, 123.3, 73.7, 68.6, 66.5(3), 66.5(0). IR
(KBr, ν, cm-1) 2954, 1719, 1604, 1489, 1456, 1182, 1118, 1091, 1012,
909, 836. HR-MS (ESI-TOF) m/z calcd for C19H15ClO3 [M+Na]+ 349.0607,
found 349.0611.
2-(4-bromophenyl)-3-(1,4-dioxan-2-yl)-1H-inden-1-one (3d)
Yellow solid, mp: 188-189 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.67 (d,
J = 7.2 Hz, 1H, Ar-H), 7.59 (d, J = 8.4 Hz, 1H, Ar-H), 7.53-7.49 (m, 2H,
Ar-H), 7.44-7.40 (m, 2H, Ar-H), 7.32 (d, J = 8.4 Hz, 2H, Ar-H), 4.98 (dd,
J1 = 2.8 Hz, J2 = 3.2 Hz, 1H, CH), 4.02-3.79 (m, 6H, 3CH2). 13C NMR
(100 MHz, CDCl3; δ, ppm) 195.8, 151.9, 143.0, 134.4, 134.1, 133.1,
131.7, 131.6, 130.4, 130.0, 129.1, 123.6, 123.3, 73.7, 68.6, 66.5(3),
66.5(0). IR (KBr, ν, cm-1) 2961, 1719, 1604, 1585, 1484, 1451, 1180,
1116, 1088, 1010, 829. HR-MS (ESI-TOF) m/z calcd for C19H15BrO3
[M+Na]+ 393.0102, found 393.0084.
3-(1,4-dioxan-2-yl)-2-(thiophen-2-yl)-1H-inden-1-one (3k)
Orange solid, mp: 137-138 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.71
(d, J = 7.6 Hz, 1H, Ar-H), 7.51-7.48 (m, 2H, Ar-H), 7.40-7.36 (m, 1H, Ar-
H), 7.24-7.15 (m, 3H, Ar-H), 5.36 (dd, J1 = 3.2 Hz, J2 = 3.2 Hz, 1H, CH),
4.02-3.85 (m, 6H, 3CH2). 13C NMR (100 MHz, CDCl3; δ, ppm) 198.7,
143.6, 134.3, 128.9, 128.7, 127.9, 127.6, 123.8, 123.2, 74.3, 68.0, 66.7,
66.5. IR (KBr, ν, cm-1) 3073, 1720, 1619, 1586, 1483, 1461, 1113, 909.
HR-MS (ESI-TOF) m/z calcd for C17H14O3S [M+Na]+ 321.0561, found
321.0551.
3-(1,4-dioxan-2-yl)-2-(p-tolyl)-1H-inden-1-one (3e)
Yellow solid, mp: 148-149 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.66 (d,
J = 7.6 Hz, 1H, Ar-H), 7.51 (d, J = 6.8 Hz, 1H, Ar-H), 7.42-7.38 (m, 1H,
Ar-H), 7.27-7.26 (m, 1H, Ar-H), 7.25-7.20 (m, 4H, Ar-H), 4.99 (dd, J1
=
3.2 Hz, J2 = 3.2 Hz, 1H, CH), 4.03-3.79 (m, 6H, 3CH2), 2.40(s, 3H, CH3).
13C NMR (100 MHz, CDCl3; δ, ppm) 196.3, 150.9, 143.3, 138.6, 135.2,
134.0, 130.4, 129.3, 129.2, 128.7, 127.2, 123.4, 123.1, 73.7, 68.6,
66.5(1), 66.5(0). IR (KBr, ν, cm-1) 2979, 1717, 1601, 1453, 1327, 1180,
1113, 1090, 1032, 913, 881. HR-MS (ESI-TOF) m/z calcd for C20H18O3
[M+Na]+ 329.1154, found 329.1166.
2-cyclopropyl-3-(1,4-dioxan-2-yl)-1H-inden-1-one (3l)
Yellow solid, mp: 124-125 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.40-
7.38 (m, 1H, Ar-H), 7.31-7.27 (m, 2H, Ar-H), 7.12-7.08 (m, 1H, Ar-H),
4.98 (dd, J1 = 3.6 Hz, J2 = 3.6 Hz, 1H, CH), 4.00-3.77 (m, 6H, 3CH2),
1.74-1.67 (m, 1H, CH), 1.28-1.16 (m, 2H, CH2), 0.91-0.84 (m, 2H, CH2).
13C NMR (100 MHz, CDCl3; δ, ppm) 196.9, 150.6, 143.4, 135.8, 133.8,
130.5, 127.8, 122.3, 121.1, 73.9, 68.4, 66.8, 66.5, 8.1, 7.5, 7.4. IR (KBr, ν,
cm-1) 2965, 1706, 1603, 1453, 1279, 1177, 1114, 1065, 982, 906. HR-
3-(1,4-dioxan-2-yl)-2-(m-tolyl)-1H-inden-1-one (3f)
Yellow solid, mp: 145-146 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.66 (d,
J = 7.6 Hz, 1H, Ar-H), 7.51 (d, J = 7.2 Hz, 1H, Ar-H), 7.42-7.39 (m, 1H,
Ar-H), 7.35-7.32 (m, 1H, Ar-H), 7.25-7.20 (m, 2H, Ar-H), 7.12-7.07 (m, 2H,
Ar-H), 4.97 (dd, J1 = 2.8 Hz, J2 = 3.2 Hz, 1H, CH), 4.02-3.76 (m, 6H,
3CH2), 2.41(s, 3H, CH3). 13C NMR (100 MHz, CDCl3; δ, ppm) 196.1,
151.4, 143.2, 138.1, 135.4, 133.9, 130.4, 130.1, 129.4, 128.8, 128.4,
126.4, 123.4, 123.1, 73.7, 68.6, 66.5, 21.6. IR (KBr, ν, cm-1) 2974, 1718,
1599, 1460, 1365, 1284, 1173, 1115, 1097, 1034, 896. HR-MS (ESI-
TOF) m/z calcd for C20H18O3 [M+Na]+ 329.1154, found 329.1178.
3-(1,4-dioxan-2-yl)-2-(4-ethylphenyl)-1H-inden-1-one (3g)
MS (ESI-TOF) m/z calcd for
279.0991.
C
16H16O3 [M+Na]+ 279.0997, found
3-(1,4-dioxan-2-yl)-5-methyl-2-phenyl-1H-inden-1-one (3m)
Yellow solid, mp: 183-184 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.45-
7.37 (m, 5H, Ar-H), 7.30 (d, J = 6.8 Hz, 2H, Ar-H), 7.04 (d, J = 7.2 Hz, 1H,
Ar-H), 4.96 (dd, J1 = 2.8 Hz, J2 = 3.2 Hz, 1H, CH), 4.02-3.76 (m, 6H,
3CH2), 2.41 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3; δ, ppm) 195.7,
151.0, 145.0, 143.6, 135.7, 130.3, 129.5, 128.9, 128.4, 128.0, 124.6,
123.2, 73.8, 68.7, 66.5(5), 66.5(0), 22.3. IR (KBr, ν, cm-1) 2962, 1713,
1604, 1473, 1458, 1171, 1111, 1095, 1035, 913, 874. HR-MS (ESI-TOF)
m/z calcd for C20H18O3 [M+Na]+ 305.1178, found 305.1162.
Yellow solid, mp: 120-122 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.66 (d,
J = 7.2 Hz, 1H, Ar-H), 7.51 (d, J = 7.2 Hz, 1H, Ar-H), 7.42-7.38 (m, 1H,
Ar-H), 7.30-7.28 (m, 2H, Ar-H), 7.25-7.22 (m, 3H, Ar-H), 5.00 (dd, J1
=
3.2 Hz, J2 = 2.8 Hz, 1H, CH), 4.03-3.78 (m, 6H, 3CH2), 2.73-2.67(m, 2H,
CH2), 1.30-1.26(m, 3H, CH3). 13C NMR (100 MHz, CDCl3; δ, ppm) 196.3,
150.9, 144.8, 143.3, 135.2, 133.9, 130.4, 129.4, 128.7, 128.1, 127.4,
123.4, 123.1, 73.7, 68.6, 66.5, 28.7, 15.4. IR (KBr, ν, cm-1) 2966, 1705,
1606, 1586, 1454, 1181, 1111, 1076, 1033, 979, 879, 838. HR-MS (ESI-
TOF) m/z calcd for C21H20O3 [M+Na]+ 343.1310, found 343.1334.
2-(4-(tert-butyl)phenyl)-3-(1,4-dioxan-2-yl)-1H-inden-1-one (3h)
Yellow solid, mp: 157-158 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.67 (d,
J = 7.2 Hz, 1H, Ar-H), 7.51 (d, J = 6.8 Hz, 1H, Ar-H), 7.49-7.46 (m, 2H,
Ar-H), 7.42-7.38 (m, 1H, Ar-H), 7.27-7.24 (m, 3H, Ar-H), 5.02 (dd, J1 = 3.2
Hz, J2 = 2.8 Hz, 1H, CH), 4.04-3.81 (m, 6H, 3CH2), 1.36 (s, 9H, C4H9).
13C NMR (100 MHz, CDCl3; δ, ppm) 196.3, 151.6, 151.0, 143.3, 135.1,
133.9, 130.5, 129.1, 128.7, 127.2, 125.5, 123.4, 123.1, 73.7, 68.7,
66.5(1), 66.5(0), 34.7, 31.3. IR (KBr, ν, cm-1) 2961, 1710, 1604, 1587,
1454, 1396, 1364, 1182, 1113, 1099, 1035, 914, 881. HR-MS (ESI-TOF)
m/z calcd for C23H24O3 [M+Na]+ 371.1623, found 371.1627.
3-(1,4-dioxan-2-yl)-2-(4-methoxyphenyl)-5-methyl-1H-inden-1-one
(3n)
Orange solid, mp: 154-155 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.42
(s, 1H, Ar-H), 7.39 (d, J = 7.2 Hz, 1H, Ar-H), 7.28-7.27 (m, 1H, Ar-H),
7.26-7.24 (m, 1H, Ar-H), 7.02-6.96 (m, 3H, Ar-H), 4.97 (dd, J1 = 3.2 Hz,
J2 = 2.8 Hz, 1H, CH), 4.03-3.88 and 3.83-3.77 (m, 6H, 3CH2), 3.85 (s, 3H,
OCH3), 2.40 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3; δ, ppm) 196.1,
159.8, 149.7, 144.9, 143.8, 135.3, 130.8, 128.6, 128.0, 124.3, 123.1,
122.7, 114.0, 73.8, 68.7, 66.6, 66.5, 55.3, 22.3. IR (KBr, ν, cm-1) 2963,
1718, 1603, 1508, 1460, 1251, 1174, 1112, 1092, 1030, 910, 827. HR-
MS (ESI-TOF) m/z calcd for C21H20O4 [M+Na]+ 359.1259, found
359.1271.
6-chloro-3-(1,4-dioxan-2-yl)-2-phenyl-1H-inden-1-one (3o)
Yellow solid, mp: 164-165 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.61 (d,
J = 7.6 Hz, 1H, Ar-H), 7.48-7.36 (m, 5H, Ar-H), 7.31-7.28 (m, 2H, Ar-H),
3-(1,4-dioxan-2-yl)-2-(4-methoxyphenyl)-1H-inden-1-one (3i)
4.98 (dd, J1 = 4.0 Hz, J2 = 4.0 Hz, 1H, CH), 3.96-3.78 (m, 6H, 3CH2). 13
C
Red solid, mp: 143-144 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.64 (d, J
= 7.2 Hz, 1H, Ar-H), 7.50 (d, J = 6.8 Hz, 1H, Ar-H), 7.41-7.37 (m, 1H, Ar-
H), 7.29-7.27 (m, 1H, Ar-H), 7.26-7.21 (m, 2H, Ar-H), 7.00-6.97 (m, 2H,
Ar-H), 4.96 (dd, J1 = 2.8 Hz, J2 = 3.2 Hz, 1H, CH), 4.03-3.90 and 3.84-
NMR (100 MHz, CDCl3; δ, ppm) 194.7, 151.4, 141.2, 135.3, 134.9, 133.1,
132.0, 129.8, 129.4, 128.7, 128.6, 124.5, 123.7, 73.6, 68.5, 66.5. IR (KBr,
ν, cm-1) 2963, 1716, 1600, 1493, 1462, 1183, 1108, 1037, 979, 910. HR-
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10.1002/asia.201800211
Chemistry - An Asian Journal
FULL PAPER
MS (ESI-TOF) m/z calcd for C19H15ClO3 [M+Na]+ 349.0607, found
349.0596.
6-chloro-3-(1,4-dioxan-2-yl)-2-(4-methoxyphenyl)-1H-inden-1-one
(3p)
Red solid, mp: 171-172 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.58 (d, J
= 8.0 Hz, 1H, Ar-H), 7.45 (s, 1H, Ar-H), 7.36-7.34 (m, 1H, Ar-H), 7.27-
122.9, 122.5, 75.5, 69.0, 31.6, 26.5. IR (KBr, ν, cm-1) 2977, 1711, 1619,
1583, 1493, 1452, 1181, 1100, 1057. HR-MS (ESI-TOF) m/z calcd for
C19H16O2 [M+Na]+ 299.1048, found 299.1041.
2-(4-methoxyphenyl)-3-(tetrahydrofuran-2-yl)-1H-inden-1-one (3v)
Yellow solid, mp: 145-146 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.51 (d,
J = 7.2 Hz, 1H, Ar-H), 7.38-7.33 (m, 2H, Ar-H), 7.28-7.27 (m, 1H, Ar-H),
7.25-7.20 (m, 2H, Ar-H), 6.98-6.94 (m, 2H, Ar-H), 5.03 (dd, J1 = 6.8 Hz,
J2 = 6.8 Hz, 1H, CH), 4.19-4.13 (m, 1H, CH), 3.92-3.86 (m, 1H, CH), 3.84
(s, 3H, OCH3), 2.30-2.09 (m, 4H, 2CH2). 13C NMR (100 MHz, CDCl3; δ,
ppm) 196.8, 159.6, 154.9, 143.2, 134.1, 133.7, 130.9(0), 130.8(8), 128.3,
123.0, 122.8, 122.3, 113.8, 75.6, 69.0, 55.3, 31.5, 26.6. IR (KBr, ν, cm-1)
2979, 1707, 1606, 1511, 1467, 1344, 1251, 1177, 1056, 1032, 878. HR-
7.23 (m, 2H, Ar-H), 7.00-6.96 (m, 2H, Ar-H), 4.98 (dd, J1 = 4.0 Hz, J2
=
4.0 Hz, 1H, CH), 3.96-3.88 and 3.83-3.78 (m, 6H, 3CH2), 3.85 (s, 3H,
OCH3). 13C NMR (100 MHz, CDCl3; δ, ppm) 195.1, 160.0, 150.1, 141.5,
134.9, 134.6, 133.1, 132.0, 130.7, 124.2, 123.6, 122.0, 114.1, 73.7, 68.5,
66.5(0), 66.4(7), 55.4. IR (KBr, ν, cm-1) 2974, 1708, 1604, 1510, 1463,
1384, 1253, 1174, 1113, 1099, 1034, 919, 834. HR-MS (ESI-TOF) m/z
calcd for C20H17ClO4 [M+H]+ 379.0713, found 379.0725.
MS (ESI-TOF) m/z calcd for
329.1155.
C
20H18O3 [M+Na]+ 329.1154, found
3-(1,4-dioxan-2-yl)-5-fluoro-2-phenyl-1H-inden-1-one (3q)
Yellow solid, mp: 162-163 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.52-
7.49 (m, 1H, Ar-H), 7.48-7.44 (m, 2H, Ar-H), 7.43-7.39 (m, 2H, Ar-H),
7.31-7.29 (m, 2H, Ar-H), 6.93-6.88 (m, 1H, Ar-H), 4.97 (dd, J1 = 4.0 Hz,
J2 = 4.0 Hz, 1H, CH), 3.96-3.76 (m, 6H, 3CH2). 13C NMR (100 MHz,
CDCl3; δ, ppm) 194.2, 166.6 (J = 252.4 Hz), 149.5 (J = 2.3 Hz), 146.3 (J
= 10.0 Hz), 136.4, 129.8, 129.4, 128.8, 128.6, 126.2 (J = 3.1 Hz), 124.9
(J = 10.0 Hz), 114.4 (J = 23.0 Hz), 112.5 (J = 26.0 Hz), 73.6, 68.6,
66.4(9), 66.4(7). IR (KBr, ν, cm-1) 2970, 1719, 1599, 1468, 1450, 1189,
1112, 1091, 1031, 910. HR-MS (ESI-TOF) m/z calcd for C19H15FO3
[M+Na]+ 333.0903, found 333.0930.
5-methyl-2-phenyl-3-(tetrahydrofuran-2-yl)-1H-inden-1-one (3w)
Yellow solid, mp: 166-167 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.44-
7.40 (m, 3H, Ar-H), 7.37-7.33 (m, 1H, Ar-H), 7.31-7.28 (m, 2H, Ar-H),
7.16 (s, 1H, Ar-H), 7.04 (d, J = 7.6 Hz, 1H, Ar-H), 5.01 (dd, J1 = 7.2 Hz, J2
= 6.4 Hz, 1H, CH), 4.19-4.14 (m, 1H, CH), 3.91-3.86 (m, 1H, CH), 2.38 (s,
3H, CH3), 2.30-2.08 (m, 4H, 2CH2). 13C NMR (100 MHz, CDCl3; δ, ppm)
196.1, 155.5, 144.5, 143.4, 134.9, 130.8, 129.6, 128.6, 128.5, 128.2,
128.1, 123.7, 122.9, 75.6, 69.0, 31.6, 26.5, 22.3. IR (KBr, ν, cm-1) 2981,
1710, 1605, 1492, 1356, 1107, 1053. HR-MS (ESI-TOF) m/z calcd for
C20H18O2 [M+Na]+ 313.1204, found 313.1202.
3-(1,4-dioxan-2-yl)-5-fluoro-2-(4-methoxyphenyl)-1H-inden-1-one (3r)
Yellow solid, mp: 173-174 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.50-
7.46 (m, 1H, Ar-H), 7.39-7.36 (m, 1H, Ar-H), 7.28-7.27 (m, 1H, Ar-H),
7.25 (s, 1H, Ar-H), 7.00-6.97 (m, 2H, Ar-H), 6.89-6.84 (m, 1H, Ar-H), 4.98
(dd, J1 = 4.0 Hz, J2 = 4.4 Hz, 1H, CH), 3.97-3.88 and 3.84-3.76 (m, 6H,
3CH2), 3.85 (s, 3H, OCH3). 13C NMR (100 MHz, CDCl3; δ, ppm) 194.6,
166.6 (J = 252.2 Hz), 160.1, 148.1 (J = 2.4 Hz), 146.6 (J = 10.0 Hz),
136.0, 130.8, 126.2 (J = 3.0 Hz), 124.7 (J = 10.0 Hz), 122.1, 114.1 (J =
22.9 Hz), 114.1(4), 112.2 (J = 26.0 Hz), 73.6, 68.5, 66.5(3), 66.5(0). IR
(KBr, ν, cm-1) 2976, 1719, 1611, 1590, 1467, 1365, 1254, 1187, 1119,
1097, 1020, 908, 833. HR-MS (ESI-TOF) m/z calcd for C20H17FO4
[M+Na]+ 363.1009, found 363.1035.
3-(1,3-dioxolan-2-yl)-2-(4-methoxyphenyl)-1H-inden-1-one (3x)
Yellow solid, mp: 148-159 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.52 (d,
J = 7.2 Hz, 1H, Ar-H), 7.44-7.40 (m, 2H, Ar-H), 7.37-7.35 (m, 2H, Ar-H),
7.25-7.20 (m, 1H, Ar-H), 6.99-6.95 (m, 2H, Ar-H), 5.85 (s, 1H, CH), 4.27-
4.25 (m, 2H, CH2), 4.10-4.06 (m, 2H, CH2), 3.65 (s, 3H, OCH3). 13C NMR
(100 MHz, CDCl3; δ, ppm) 196.7, 160.1, 147.6, 143.0, 137.5, 134.0,
131.2, 130.3, 128.4, 123.2, 122.6, 122.0, 113.9, 99.8, 65.6, 55.3. IR (KBr,
ν, cm-1) 2967, 1712, 1604, 1493, 1453, 1345, 1255, 1178, 1118, 1087,
1034, 960. HR-MS (ESI-TOF) m/z calcd for C19H16O4 [M+Na]+ 331.0946,
found 331.0943.
3-(1,3-dioxolan-2-yl)-5-methyl-2-phenyl-1H-inden-1-one (3y)
o
1
Orange solid, mp: 148-159 C; H NMR (400 MHz, CDCl3; δ, ppm) 7.46-
7.42 (m, 5H, Ar-H), 7.41-7.37 (m, 1H, Ar-H), 7.19 (s, 1H, Ar-H), 7.04 (d, J
= 7.2 Hz, 1H, Ar-H), 5.82 (s, 1H, CH), 4.29-4.26 (m, 2H, CH2), 4.09-4.05
(m, 2H, CH2), 2.38 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3; δ, ppm)
195.9, 148.5, 144.9, 143.1, 138.4, 129.8(0), 129.7(7), 128.7, 128.6, 128.3,
127.9, 124.0, 123.4, 99.6, 65.6, 22.3. IR (KBr, ν, cm-1) 2977, 1716, 1600,
1459, 1355, 12560, 1179, 1112, 1079, 1038, 988, 833. HR-MS (ESI-
TOF) m/z calcd for C19H16O3 [M+Na]+ 315.0997, found 315.0980.
3-(1,4-dioxan-2-yl)-6-fluoro-2-phenyl-1H-inden-1-one (3s)
o
1
Orange solid, mp: 206-207 C; H NMR (400 MHz, CDCl3; δ, ppm) 7.66-
7.63 (m, 1H, Ar-H), 7.48-7.38 (m, 3H, Ar-H), 7.30-7.27 (m, 2H, Ar-H),
7.24-7.21 (m, 1H, Ar-H), 7.09-7.04 (m, 1H, Ar-H), 4.97 (dd, J1 = 3.6 Hz,
J2 = 3.6 Hz, 1H, CH), 3.97-3.76 (m, 6H, 3CH2). 13C NMR (100 MHz,
CDCl3; δ, ppm) 194.5, 163.4 (J = 249.5 Hz), 151.7 (J = 2.2 Hz), 138.6 (J
= 3.5 Hz), 135.4 (J = 4.9 Hz), 132.8 (J = 7.0 Hz), 129.9, 129.3, 128.6 (J =
8.0 Hz), 124.7 (J = 7.5 Hz), 119.2 (J = 22.4 Hz), 111.7 (J = 24.5 Hz), 73.6,
68.5, 66.5. IR (KBr, ν, cm-1) 2978, 1715, 1477, 1269, 1198, 1112, 1085,
984, 878. HR-MS (ESI-TOF) m/z calcd for C19H15FO3 [M+Na]+ 333.0903,
found 333.0930.
Acknowledgements
3-(1,4-dioxan-2-yl)-6-fluoro-2-(4-methoxyphenyl)-1H-inden-1-one (3t)
o
1
We are grateful for financial support from the NSFC (21472071),
PAPD of Jiangsu Higher Education Institutions, the Outstanding
Youth Fund of JSNU (YQ2015003), NSF of Jiangsu Province
(BK20151163).
Orange solid, mp: 200-201 C; H NMR (400 MHz, CDCl3; δ, ppm) 7.62-
7.59 (m, 1H, Ar-H), 7.26-7.19 (m, 4H, Ar-H), 7.07-6.96 (m, 3H, Ar-H),
4.97 (dd, J1 = 3.6 Hz, J2 = 3.6 Hz, 1H, CH), 3.98-3.88 and 3.84-3.76 (m,
6H, 3CH2), 3.85 (s, 3H, OCH3). 13C NMR (100 MHz, CDCl3; δ, ppm)
194.9, 163.3 (J = 249.1 Hz), 159.9, 150.4 (J = 2.2 Hz), 138.8 (J = 3.5 Hz),
135.0 (J = 4.8 Hz), 132.8 (J = 7.0 Hz), 130.7, 124.4 (J = 7.4 Hz), 122.2,
119.1 (J =22.4 Hz), 114.1, 111.6 (J = 24.5 Hz), 73.7, 68.5, 66.5(0),
66.4(8). IR (KBr, ν, cm-1) 2972, 1713, 1609, 1511, 1475, 1371, 1251,
1180, 1114, 1099, 920, 836. HR-MS (ESI-TOF) m/z calcd for C20H17FO4
[M+Na]+ 363.1009, found 363.0999.
Keywords: Radical Relay • C(sp3)-H Bond Functionalization •
Carbocyclization • 1-Indenones • Cyclic Ethers
[1]
a) J. Xuan, A. Studer, Chem. Soc. Rev. 2017, 46, 4329-4346; b) W.
Zhang, F. Wang, S. D. McCann, D. Wang, P. Chen, S. Stahl, G. Liu,
Science 2016, 353, 1014-1018; c) X.-D. An, Y.-Y. Jiao, H. Zhang, Y.
Gao, S. Yu, Org. Lett. 2018, 20, 401-404; d) S. Feng, T. Li, C. Du, P.
Chen, D. Song, J. Li, X. Xie, X. She, Chem. Commun. 2017, 53, 4585-
4588; e) L. Wang, W. Sha, Q. Dai, X. Feng, W. Wu, H. Peng, B. Chen,
J. Cheng, Org. Lett. 2014, 16, 2088-2091.
2-phenyl-3-(tetrahydrofuran-2-yl)-1H-inden-1-one (3u)
Yellow solid, mp: 156-157 oC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.53 (d,
J = 7.2 Hz, 1H, Ar-H), 7.44-7.41 (m, 2H, Ar-H), 7.38-7.33 (m, 3H, Ar-H),
7.32-7.28 (m, 2H, Ar-H), 7.25-7.22 (m, 1H, Ar-H), 5.03 (dd, J1 = 7.2 Hz,
J2 = 6.8 Hz, 1H, CH), 4.19-4.13 (m, 1H, CH), 3.92-3.86 (m, 1H, CH),
2.31-2.10 (m, 4H, 2CH2). 13C NMR (100 MHz, CDCl3; δ, ppm) 196.4,
156.1, 143.0, 134.4, 133.7, 130.9, 130.7, 129.6, 128.6, 128.2, 128.1,
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[2]
a) E. A. Wappes, S. C. Fosu, T. C. Chopko, and D. A. Nagib, Angew.
Chem. Int. Ed. 2016, 55, 9974-9978; b) E. A. Wappes, K. M. Nakafuku,
D. A. Nagib, J. Am. Chem. Soc. 2017, 139, 10204-10207; c) H. Zhu, J.
G. Wickenden, N. E. Campbell, J. C. T. Leung, K. M. Johnson, G. M.
Sammis, Org. Lett. 2009, 11, 2019-2022; d) A.-F. Wang, W.-J. Hao, Y.-
L. Zhu, G. Li, P. Zhou, S.-J. Tu, B. Jiang, ACS Omega 2018, 3, 1482-
1491; e) Z.-Z. Chen, S. Liu, G. Xu, S. Wu, J.-N. Miao, B. Jiang, W.-J.
Hao, S.-L. Wang, S.-J. Tu, G. Li, Chem. Sci. 2015, 6, 6654-6658; g) H.
Zhu, J. C. T. Leung, G. M. Sammis, J. Org. Chem. 2015, 80, 965-979.
For selected examples, see: (a) Z.-J. Shen, Y.-N. Wu, C.-L. He, L. He,
W.-J. Hao, A.-F. Wang, S.-J. Tu, B. Jiang, Chem. Commun. 2018, 54,
445-448; b) J. Li, W.-W. Zhang, X.-J. Wei, F. Liu, W.-J. Hao, S.-L.
Wang, G. Li, S.-J. Tu, B. Jiang, J. Org. Chem. 2017, 82, 6621-6628; c)
Y.-L. Zhu, B. Jiang, W.-J. Hao, A.-F. Wang, J.-K. Qiu, P. Wei, D. Wang,
G. Li, S.-J. Tu, Chem. Commun. 2016, 52, 1907-1910; d) A.-F. Wang,
Y.-L. Zhu, S.-L. Wang, W.-J. Hao, G. Li, S.-J. Tu, B. Jiang, J. Org.
Chem. 2016, 81, 1099-1105; e) W. Hao, X. Wu, J. Z. Sun, J. C. Siu, S.
N. MacMillan, S. Lin, J. Am. Chem. Soc. 2017, 139, 12141-12144; f) Y.-
Q. Wang, Y.-T. He, L.-L. Zhang, X.-X. Wu, X.-Y. Liu, Y.-M. Liang, Org.
Lett. 2015, 17, 4280-4283.
Cacchi, J. Org. Chem. 1993, 58, 4579-4583; c) R. C. Larock, Q. Tian, A.
A. Pletnev, J. Am. Chem. Soc. 1999, 121, 3238-3239.
[11] a) J. Zhang, D. Wu, X. Chen, Y. Liu, Z. Xu, J. Org. Chem. 2014, 79,
4799-4808; b) S. Chen, J. Yu, Y. Jiang, F. Chen, J. Cheng, Org. Lett.
2013, 15, 4754-4757; c) M. E. Domaradzki, Y. Long, Z. She, X. Liu, G.
Zhang, Y. Chen, J. Org. Chem. 2015, 80, 11360-11368; d) Y. Harada, J.
Nakanishi, H. Fujihara, M. Tobisu, Y. Fukumoto, N. Chatani, J. Am.
Chem. Soc. 2007, 129, 5766-5771; e) S. V. Gagnier, R. C. Larock, J.
Am. Chem. Soc. 2003, 125, 4804-4807; f) P. Zhao, F. Wang, K. Han, X.
Li, Org. Lett. 2012, 14, 5506-5509; g) B. Suchand, G. Satyanarayana, J.
Org. Chem. 2017, 82, 372-381.
[3]
[12] a) Y. Kuninobu, T. Matsuki, K. Takai, Org. Lett. 2010, 12, 2948-2950; b)
B.-J. Li, H.-Y. Wang, Q.-L. Zhu, Z.-J. Shi, Angew. Chem., Int. Ed. 2012,
51, 3948-3952; c) S. Chen, J. T. Yu, Y. Jiang, F. Chen, J. Cheng, Org.
Lett. 2013, 15, 4754-4757; d) Z. Qi, M. Wang, X. Li, Org. Lett. 2013, 15,
5440-5443; e) X. Yan, S. Zou, P. Zhao, C. Xi, Chem. Commun. 2014,
50, 2775-2777; f) P. Zhao, Y. Liu, C. Xi, Org. Lett. 2015, 17, 4388-4391.
[13] a) X. Q. Pan, J. P. Zou, G. L. Zhang, W. Zhang, Chem. Commun. 2010,
46, 1721-1723; b) J. Zhou, G. L. Zhang, J. P. Zou, W. Zhang, Eur. J.
Org. Chem. 2011, 2011, 3412-3429; c) C. Pan, B. Huang, W. Hu, X.
Feng, J. T. Yu, J. Org. Chem. 2016, 81, 2087-2093; d) X. S. Zhang, J.
Y. Jiao, X. H. Zhang, B. L. Hu, X. G. Zhang, J. Org. Chem. 2016, 81,
5710-5716.
[4]
For selected examples, see: a) B. Jiang, J. Li, Y.-Y. Pan, W.-J. Hao, G.
Li, S.-J. Tu, Chin. J. Chem. 2017, 35, 323-334; b) J. Li, W.-J. Hao, P.
Zhou, Y.-L. Zhu, S.-L. Wang, S.-J. Tu, B. Jiang, RSC Adv. 2017, 7,
9693-9703; (c) J.-K. Qiu, B. Jiang, Y.-L. Zhu, W.-J. Hao, D.-C. Wang, J.
Sun, P. Wei, S.-J. Tu, G. Li, J. Am. Chem. Soc. 2015, 137, 8928-8931;
(d) M. Hu, J.-H. Fan, Y. Liu, X.-H. Ouyang, R.-J. Song, J.-H. Li, Angew.
Chem., Int. Ed., 2015, 54, 9577-9580; (e) Y. Li, G.-H. Pan, M. Hu, B.
Liu, R.-J. Song, J.-H. Li, Chem. Sci. 2016, 7, 7050-7054; (f) Y. Li, B. Liu,
R.-J. Song, Q.-A. Wang, J.-H. Li, Adv. Synth. Catal. 2016, 358, 1219-
1228.
[14] a) S. D. Roughley, A. M. Jordan, J. Med. Chem. 2011, 54, 3451-3479;
b) C. E. Rye, D. Barker, Synlett. 2009, 20, 3315-3319; c) S. M. Miles, S.
P. Marsden, R. J. Leatherbarrow, W. J. Coates, J. Org. Chem. 2004, 69,
6874-6882; d) V. Mammoli, A. Bonifazi, F. Del Bello, E. Diamanti, M.
Giannella, A. L. Hudson, L. Mattioli, M. Perfumi, A. Piergentili, W.
Quaglia, F. Titomanlio, M. Pigini, Bioorg. Med. Chem. 2012, 20, 2259-
2265.
[5]
For selected examples, see: a) W.-J. Fu, M. Zhu, G.-L Zou, C. Xu, Z.-Q.
Wang, B.-M. Ji, J. Org. Chem. 2015, 80, 4766-4770; b) W.-T. Wei, R.-J.
Song, X.-H. Ouyang, Y. Li, H.-B. Li, J.-H. Li, Org. Chem. Front. 2014, 1,
484-489; c) W.-T. Wei, M.-B. Zhou, J.-H. Fan, W. Liu, R.-J. Song, Y. Liu,
M. Hu, P. Xie, J.-H. Li, Angew. Chem., Int. Ed. 2013, 52, 3638-3641; (d)
S.-L. Zhou, L.-N. Guo, S. Wang, X.-H. Duan, Chem. Commun. 2014, 50,
3589-3591; e) S. Feng, X. Xie, W. Zhang, L. Liu, Z. Zhong, D. Xu, X.
She, Org. Lett. 2016, 18, 3846-3849; f) Y. Xu, Y. Chen, W. Li, Q. Xie, L.
Shao, J. Org. Chem. 2016, 81, 8426-8435.
[15] a) N.-N. Wang, W.-J. Hao, T.-S. Zhang, G. Li, Y.-N. Wu, S.-J. Tu, B.
Jiang, Chem. Commun. 2016, 52, 5144-5147; b) T.-S. Zhang, W.-J.
Hao, N.-N. Wang, G. Li, D.-F. Jiang, S.-J. Tu, B. Jiang, Org. Lett. 2016,
18, 3078-3081; c) J. Sun, J.-K. Qiu, Y.-N. Wu, W.-J. Hao, C. Guo, G. Li,
S.-J. Tu, B. Jiang, Org. Lett. 2017, 19, 754-757.
[16] X.-T. Zhu, Q. Zhao, F. Liu, A.-F. Wang, P.-J. Cai, W.-J. Hao, S.-J. Tu, B.
Jiang, Chem. Commun. 2017, 53, 6828-6831.
[17] a) F. Xiao, H. Chen, H. Xie, S. Chen, L. Yang, G.-J. Deng, Org. Lett.
2014, 16, 50-53; b) R. S. Rohokale, S. D. Tambe, U. A. Kshirsagar, Org.
Biomol. Chem. 2018, 16, 536-540; c) T. C. Johnson, B. L. Elbert, A. J.
M. Farley, T. W. Gorman, C. Genicot, B. Lallemand, P. Pasau, J. Flasz,
J. L. Castro, M. MacCoss, D. J. Dixon, R. S. Paton, C. J. Schofield, M.
D. Smith, M. C. Willis, Chem. Sci. 2018, 9, 629-633; d) A. K. Singh, R.
Chawla, L. D. S. Yadav, Tetrahedron Lett. 2014, 55, 2845-2848.
[18] CCDC 1822243 (3c) contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre.
[6]
[7]
a) L. M. X. Lopes, M. Yoshida, O. R. Gottlieb, Phytochemicals 1984, 23,
2021-2024; b) D. C. Harrowven, N. A. Newman, C. A. Knight,
Tetrahedron Lett. 1998, 39, 6757-6760.
a) G. M. Anstead, S. R. Wilson, J. A. Katzenellenbogen, J. Med. Chem.
1989, 32, 2163-2171; b) R. E. McDevitt, M. S. Malamas, E. S. Manas,
R. J. Unwalla, Z. B. Xu, C. P. Miller, H. A. Harris, Bioorg. Med. Chem.
Lett. 2005, 15, 3137-3142; c) C. H. Park, X. Siomboing, S. Yous, B.
Gressier, M. Luyckx, P. Chavatte, Eur. J. Med. Chem. 2002, 37, 461-
468.
[19] a) J.-K. Qiu, W.-J. Hao, D.-C. Wang, P. Wei, J. Sun, B. Jiang, S.-J. Tu,
Chem. Commun. 2014, 50, 14782-14785; b) F.-L. Yang, S.-K. Tian,
Angew. Chem. Int. Ed. 2013, 52, 4929-4932; c) Z. Yang, W.-J. Hao, S.-
L. Wang, J.-P. Zhang, B. Jiang, G. Li, S.-J. Tu, J. Org. Chem. 2015, 80,
9224-9230; d) Y.-L. Zhu, D.-C. Wang, B. Jiang, W.-J. Hao, P. Wei, A.-F.
Wang, J.-K. Qiu, S.-J. Tu, Org. Chem. Front. 2016, 3, 385-393.
[20] a) B. Liu, C.-Y. Wang, M. Hu, R.-J. Song, F. Chen, J.-H. Li, Chem.
Commun. 2017, 53, 1265-1268; b) Y.-M. Li, S.-S. Wang, F. Yu, Y. Shen,
K.-J. Chang, Org. Biomol. Chem. 2015, 13, 5376-5380.
[8]
[9]
a) C. F. Koelsch, J. Am. Chem. Soc. 1932, 54, 2487-2493; b) R. L.
Frank, H. Eklund, J. W. Richter, C. R. Vanneman, A. N. Wennerberg, J.
Am. Chem. Soc. 1944, 66, 1-4; c) M. B. Floyd, G. R. Allen, J. Org.
Chem. 1970, 35, 2647-2653.
a) E. D. Bergmann, J. Org. Chem. 1956, 21, 461-464; b) C. Manning, M.
R. McClory, J. J. McCullough, J. Org. Chem. 1981, 46, 919-930; c) G.
M. Anstead, J. L. Ensign, C. S. Petersonand, J. A. Katzenellenbogen, J.
Org. Chem, 1989, 54, 1485-1491.
[10] a) W. Tao, L. J. Silverberg, A. L. Rheingold, R. F. Heck,
Organometallics 1989, 8, 2550-2559; b) R. C. Larock, M. J. Doty, S.
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Xiao-Tong Zhu, Tian-Shu Zhang, Qi
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Sulfinate Salt-Mediated Radical Relay
Cyclization of Cyclic Ethers with 2-
Alkynylbenzonitriles toward 3-
Alkylated 1-Indenones
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