Synthesis of 3-aryl-1-indanones via CsF-promoted coupling of arylboronic acids with N-tosylhydrazones

Article abstract of DOI:10.3184/174751918X15161933697844

A series of 17 3-aryl-1-indanones, four of which are novel, were prepared in good yield via a CsF-promoted reductive cross-coupling of the monotosylhydrazone of a 1,3-indanedione with an arylboronic acid. The method demonstrates wide substrate scope and good functional group tolerance. Moreover, the 3-aryl-1-indanones could also be prepared on a multi-gram scale.

Full text of DOI:10.3184/174751918X15161933697844

40 RESEARCH PAPER
VOL. 42 JANUARY, 40–43
JOURNAL OF CHEMICAL RESEARCH 2018
Synthesis of 3-aryl-1-indanones via CsF-promoted coupling of arylboronic
acids with N-tosylhydrazones
Yueqiang Liu, Lingjuan Chen, Yan Liu*, Ping Liu and Bin Dai
School of Chemistry and Chemical Engineering, Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, Shihezi University,
Shihezi City 832004, P.R. China
A series of 17 3-aryl-1-indanones, four of which are novel, were prepared in good yield via a CsF-promoted reductive cross-coupling of the
monotosylhydrazone of a 1,3-indanedione with an arylboronic acid. The method demonstrates wide substrate scope and good functional
group tolerance. Moreover, the 3-aryl-1-indanones could also be prepared on a multi-gram scale.
Keywords: 3-aryl-1-indanone, 1,3-indanedione, tosylhydrazone, metal-free alkylation, cross-coupling reaction
3-Aryl-1-indanone is an important structural motif frequently
found in biologically active compounds, as illustrated by
the emboldened fragments in six drugs, A–F (Fig. 1).1,2
Thus, the synthesis of 3-aryl-1-indanone and its derivatives
by efficient methods has attracted considerable attention.3–5
The construction of the 3-aryl-1-indanone skeleton generally
uses one or other of the following methods: (a) tandem
Friedel–Crafts acylation and Nazarov cyclisation of arenes
with α,β-unsaturated acyl chlorides in the presence of AlCl3
(Scheme 1a);6–8 (b) rhodium-catalysed hydroacylation of
2-vinyl benzaldehyde systems (Scheme 1b);9,10 (c) zeolite-
catalysed cyclisation of arylvinylketones (Scheme 1c);11,12 (d)
superacid-catalysed reactions of arenes and cinnamic acid
(Scheme 1d);13–15 (e) gold-catalysed oxidative cyclisations of
cis-3-en-1-ynes to form cyclopentenone derivatives (Scheme
1e).16–18 Tosylhydrazones, which are diazo precursors, are
useful synthetic intermediates that have featured in several
recent reports.19–24 In 1994, Kabalka et al. first reported a
NHCH3
O
OH
O
HO
HN
N
N
F
N
OH
OH
Cl
OH
(+)-isopaucifloral F
Cl
A:
B:
C:
(+)-indatraline
HO
(+)-iranadalone
HO
OH
HO
OH
OH
HO
HO
HO
H
O
OH
OH
OH
OH
OH
F:
(+)-brazilin
OH
(+)-quadrangularin A
Fig. 1 Six drugs (A–F) featuring a 3-aryl-1-indanone motif.
OH
(+)-pallidol
D:
E:
O
R
+
R'
Cl
(a)
AlCl3
O
Ar
H
USY zeolite
(c)
[BINAPRh]
(b)
Ar
O
O
R
Ar
COOH
Arenes
Ar
IPrAuNTf2
H
CF3SO3
8-methylquinoline
(e)
(d)
Scheme 1 Synthetic strategies to 3-aryl-1-indanone.
* Correspondent. E-mail: liuyan1979810@aliyun.com

JOURNAL OF CHEMICAL RESEARCH 2018 41
facile metal-free alkylation of aryl aldehyde tosylhydrazones
with trialkylboranes.25,26 In 2009, Barluenga et al. developed a
metal-free coupling reaction between N-tosylhydrazones and
boronic acids.27 Subsequently, coupling reactions of various
sulfonylhydrazones with arylboronic acids were studied and
applied in organic synthesis. For example, (a) the parallel
synthesis of drug-like and drug fragment-like molecules by
Barluenga coupling;28 (b) stereoselective Csp3–Csp2 bond-
forming reactions by metal-free reductive coupling of cyclic
tosylhydrazones with boronic acids;29 (c) metal-free coupling of
saturated heterocyclic sulfonylhydrazones with boronic acids;30
(d) olefination of carbonyl compounds via reductive coupling
of alkenylboronic acids and tosylhydrazones.31 Here, based
on our previous work,32–38 we describe an efficient synthesis
of 3-arylindanones via a CsF-promoted coupling reaction of
1,3-indanedione monotosylhydrazones with arylboronic acids.
good yields of products 3g–i. Next, the coupling reactions of
meta-substituted and multi-substituted arylboronic acids were
investigated. The electronic properties of the substrates showed
no significant influence on the coupling reaction, affording
the coupled products 3k–m in 81–91% yields. To further
ascertain the applicable scope of the methodology, naphthalen-
Table 1 Optimisation of the reaction conditions (base, solvent) for the
reaction between 1,3-indanedione monotosylhydrazone (1a; R2 = H) and
phenylboronic acid (2a; R1 = Ph) in the presence of a base (Scheme 2)a
Entry
1
Base
Solvent
Additive
Yield (%)b
K2CO3
K2CO3
K2CO3
Cs2CO3
NaOH
Et3N
1,4-Dioxane
Toluene
–
88
2
–
73
3
THF
–
0
4
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
–
45
5
–
58
Results and discussion
6
–
0
Using a similar method to that described earlier by us,32 we
planned to investigate the base-catalysed reductive coupling
of monotosylhydrazones of 1,3-indanediones with arylboronic
acids (Scheme 2).
7
K3PO4
Na2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
Na2CO3
–
77
8
–
78c
50d
39e
93
9
–
Initially, in order to optimise the process, we investigated
the model reaction between the monotosylhydrazone of
1,3-indanedione (1a; R2 = H) and phenylboronic acid (2a;
R1 = Ph) in the presence of K2CO3 in 1,4-dioxane in argon at
110 °C. The results are presented in Table 1. Gratifyingly,
the desired product (3a) was isolated in 88% yield (entry
1). Encouraged by this initial result, a solvent screen was
performed using 1,4-dioxane, toluene and THF (entries 1–3).
1,4-Dioxane proved to be the optimal solvent (entry 1). The
base plays a crucial role in this type of reaction to promote
the formation of the diazomethane intermediate. Cs2CO3 and
NaOH gave lower yields (entries 4 and 5); Et3N was ineffective
(entry 6); K3PO4 and Na2CO3 afforded the desired product in
77 and 78% yields, respectively (entries 7 and 8). When the
amount of phenylboronic acid was reduced to 1.2 equiv. or the
reaction temperature was lowered to 80 °C, the yield of product
decreased significantly (entries 9, 10). We then attempted to
accelerate the coupling reaction using fluoride anion to facilitate
the cleavage of the C–B bond.39–41 It was gratifying that the
yield increased dramatically to 93% when 0.5 equiv. of CsF
was added in 1,4-dioxane in the presence of K2CO3 (entry 11).
Additionally, when Na2CO3 was used as base using the standard
reaction conditions, the yield increased to 97% (entry 12). It
was confirmed that under an air atmosphere a lower yield was
produced (entry 13). Finally, the optimised reaction conditions
were established as follows: tosylhydrazone (0.3 mmol),
arylboronic acid (0.45 mmol), Na2CO3 (0.45 mmol), CsF
(0.15 mmol), 1,4-dioxane (4 mL), 110 °C for 5 h under an argon
atmosphere.
10
11
12
13
–
CsF
CsF
CsF
97
81f
aReaction conditions: A mixture of 1,3-indanedione monotosylhydrazone (1a; R2 = H)
(0.3 mmol) and phenylboronic acid (2a; R1 = Ph) (0.45 mmol) in a solvent (4 mL) was
heated at 110 °C for 5 h under argon in the presence of a base (0.45 mmol), with or
without CsF (0.15 mmol).
bIsolated yields.
cReaction time 9 h.
d0.36 mmol 2a (R1 = Ph) was employed.
e80 °C.
fIn air.
Table 2 Yields of a series of 3-aryl-1-indanones (3; R1, R2 = various)
prepared from the reaction of the monotosylhydrazones of
1,3-indanedione (1; R2 = various) with an arylboronic acid (2; R1
various) in the presence of Na2CO3/CsF (Scheme 2)a
a
=
Entry
1
2
3
4
5
6
7
8
R1
R2
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Cl
Cl
H
Product
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3a
Yield (%)b
93
95
90
86
90
82
90
91
91
88
81
85
81
42
85
4-Me-C6H4
4-MeO-C6H4
4-Br-C6H4
4-F-C6H4
4-CF3-C6H4
4-CN-C6H4
4-COOEt-C6H4
4-Vinyl-C6H4
3-Cl-C6H4
3,4-Dichloro-C6H3
3,4,5-Trifluoro-C6H2
Naphthalen-2-yl
Thiophen-3-yl
n-Butyl
9
10
11
12
13
14
15
16
17c
After optimising the reaction conditions, we investigated the
substrate scope for this coupling reaction. As shown in Table 2,
the para-substituted arylboronic acid substrates bearing either
electron-withdrawing or electron-donating groups afforded the
desired products 3b–f in good to excellent yields. Substrates with
active groups such as -CN, -COOEt and -vinyl also produced
C6H5
4-Me-C6H4
C6H5
88
87
O
O
R2
R2
R2
R2
Base
aReaction conditions: A mixture of the monotosylhydrazone of a 1,3-indanedione (1; R2 =
various) (0.3 mmol) and an arylboronic acid (2; R1 = various) (0.45 mmol ) in 1,4-dioxane
(4 mL) was heated at 110 °C for 5 h under argon in the presence of Na2CO3 (0.45 mmol)
and CsF (0.15 mmol).
R1 B(OH)2
+
Solvent
T/o
t/h
C,
R1
NNHTs
1
3
2
bIsolated yields.
cN-tosylhydrazones 1a (4 mmol) and phenylboronic acids (6 mmol) were used.
Scheme 2

42 JOURNAL OF CHEMICAL RESEARCH 2018
(td, J = 7.5, 1.3 Hz, 1H), 7.43 (t, J = 7.5 Hz, 1H), 7.25 (dd, J = 7.8, 0.7
Hz, 1H), 7.15–7.03 (m, 2H), 7.05–6.93 (m, 2H), 4.57 (dd, J = 8.1, 3.9
Hz, 1H), 3.23 (dd, J = 19.2, 8.1 Hz, 1H), 2.63 (dd, J = 19.2, 3.9 Hz, 1H);
13C NMR (100 MHz, CDCl3): δ 205.7, 161.8 (d, J = 245.5 Hz), 157.7,
139.5 (d, J = 3.3 Hz), 136.8, 135.2, 129.2 (d, J = 8.1 Hz), 128.1, 126.8,
123.5, 115.8 (d, J = 21.3 Hz), 46.9 (d, J = 1.0 Hz), 43.8.
2-ylboronic acid and thiophen-3-ylboronic acid were employed as
coupling partners to obtain the desired products 3m and 3n in 85
and 81% yields, respectively. In addition, the coupling reaction
of butylboronic acid also provided coupling product 3o in 42%
yield. Furthermore, the cross-coupling reaction of 5,6-dichloro-
1H-indene-1,3(2H)-dione monotosylhydrazone also provided
the desired products 3p and 3q in good yields. Usefully, the
reductive cross-coupling of N-tosylhydrazones 1a (4 mmol) with
phenylboronic acids (6 mmol) could be scaled up to gram-scale,
affording the desired product 3a in 87% yield (entry 17).
3-(4-(Trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-one (3f):44
Light-yellow solid; m.p. 73.2–75.4 °C [lit.44 84–85 °C]; 1H NMR
(400 MHz, CDCl3): δ 7.84 (d, J = 7.7 Hz, 1H), 7.65–7.53 (m, 3H),
7.45 (t, J = 7.5 Hz, 1H), 7.25 (d, J = 7.7 Hz, 3H), 4.66 (dd, J = 8.2, 3.9
Hz, 1H), 3.26 (dd, J = 19.2, 8.1 Hz, 1H), 2.66 (dd, J = 19.2, 3.9 Hz,
1H); 13C NMR (100 MHz, CDCl3): δ 205.1, 156.8, 147.7 (q, J = 1.4
Hz), 136.8, 135.3, 129.4 (q, J = 32.5 Hz), 128.3, 128.0, 126.7, 125.9 (q,
J = 3.8 Hz), 124.0 (q, J = 271.0 Hz), 123.65, 46.5, 44.2.
Experimental
NMR spectra were obtained on a Bruker DPX-400 spectrometer
(1H NMR at 400 Hz, 13C NMR at 100 Hz) in CDCl3 using TMS as
internal reference. Chemical shifts (δ) are given in parts per million
(ppm) and coupling constants (J) are given in Hz. EI–mass spectra
were measured on an LC/Q–TOF MS (Micromass, England). All
products were isolated by short chromatography on a silica gel
(200–300 mesh) column using petroleum ether (60–90 °C). Unless
otherwise noted, 1,3-indanedione and its derivatives, arylboronic
acids, and bases and solvents of analytical grade quality were
purchased from Adamas-beta Pharmaceuticals, Inc.
4-(3-Oxo-2,3-dihydro-1H-inden-1-yl)benzonitrile (3g):46 Light-
1
yellow oil; H NMR (400 MHz, CDCl3): δ 7.84 (d, J = 7.7 Hz, 1H),
7.67–7.57 (m, 3H), 7.47 (t, J = 7.5 Hz, 1H), 7.34–7.17 (m, 3H), 4.65 (dd,
J = 8.2, 3.8 Hz, 1H), 3.27 (dd, J = 19.2, 8.2 Hz, 1H), 2.64 (dd, J = 19.2,
3.8 Hz, 1H);13C NMR (100 MHz, CDCl3): δ 204.7, 156.3, 149.2, 136.8,
135.4, 132.8, 128.5, 128.5, 126.7, 123.8, 111.1, 46.3, 44.4.
Ethyl
4-(3-oxo-2,3-dihydro-1H-inden-1-yl)benzoate
(3h):47
Light-yellow solid; m.p. 115.1–116.7 °C [lit.47 113–114 °C]; H NMR
(400 MHz, CDCl3): δ 7.99 (d, J = 8.4 Hz, 2H), 7.83 (d, J = 7.7 Hz,
1H), 7.58 (td, J = 7.5, 1.3 Hz, 1H), 7.44 (t, J = 7.5 Hz, 1H), 7.24 (dd,
J = 7.8, 0.9 Hz, 1H), 7.20 (d, J = 8.3 Hz, 2H), 4.64 (dd, J = 8.2, 3.9
Hz, 1H), 4.37 (q, J = 7.1 Hz, 2H), 3.26 (dd, J = 19.2, 8.1 Hz, 1H), 2.68
(dd, J = 19.2, 3.9 Hz, 1H), 1.38 (t, J = 7.1 Hz, 3H);13C NMR (100 MHz,
CDCl3): δ 205.3, 166.2, 157.1, 148.8, 136.8, 135.2, 130.2, 128.2, 127.6,
126.8, 123.6, 61.0, 46.5, 44.4, 14.3.
1
CsF-promoted coupling reaction of 1,3-indanedione monoto-
sylhydrazones and arylboronic acids; general procedure
A Schlenk tube (20 mL) was charged with a 1,3-indanedione
monotosylhydrazone (1) (0.5 mmol), an arylboronic acid (2)
(0.75 mmol), K2CO3 (0.75 mmol) and CsF (0.25 mmol). The tube
was degassed for 30 s and then filled with argon. This operation was
repeated three times. After 1,4-dioxane (5 mL) was added under an
argon atmosphere, the resulting reaction mixture was stirred at 110 °C
for 5 h. After the completion of the reaction, the reaction mixture
was allowed to cool to room temperature. Ethyl acetate (5 mL) and a
saturated solution of NaCl (5 mL) were added and the layers were
separated. The aqueous phase was extracted three times with ethyl
acetate (3 × 5 mL). The organic layer was then dried over anhydrous
MgSO4 and filtered and the solvent was removed under reduced
pressure. The crude mixture was purified by chromatography on silica
gel to yield the desired products.
3-(4-Vinylphenyl)-2,3-dihydro-1H-inden-1-one (3i): Light-yellow
1
oil; H NMR (400 MHz, CDCl3): δ 7.81 (d, J = 7.5 Hz, 1H), 7.57
(td, J = 7.5, 1.3 Hz, 1H), 7.42 (t, J = 7.4 Hz, 1H), 7.35 (d, J = 8.1 Hz,
2H), 7.26 (dd, J = 8.0, 1.2 Hz, 1H), 7.08 (d, J = 8.2 Hz, 2H), 6.69 (dd,
J = 17.6, 10.9 Hz, 1H), 5.72 (dd, J = 17.6, 0.9 Hz, 1H), 5.23 (dd, J = 10.9,
0.9 Hz, 1H), 4.57 (dd, J = 8.1, 3.9 Hz, 1H), 3.23 (dd, J = 19.2, 8.0 Hz,
1H), 2.68 (dd, J = 19.2, 3.9 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ
206.0, 157.9, 143.4, 136.9, 136.6, 136.4, 135.2, 128.0, 127.9, 127.0,
126.9, 123.6, 114.0, 46.9, 44.3; HRMS (ESI) m/z: Calcd for C17H15O+
(M+H)+: 235.11174; found: 235.11171.
3-(3-Chlorophenyl)-2,3-dihydro-1H-inden-1-one (3j):1 Light-yellow
3-Phenyl-2,3-dihydro-1H-inden-1-one (3a):43 Light-yellow oil;
1H NMR (400 MHz, CDCl3): δ 7.81 (d, J = 7.6 Hz, 1H), 7.57 (td, J = 7.4,
1.3 Hz, 1H), 7.47–7.36 (m, 1H), 7.37–7.19 (m, 4H), 7.17–7.08 (m, 2H),
4.58 (dd, J = 8.0, 3.8 Hz, 1H), 3.23 (dd, J = 19.2, 8.1 Hz, 1H), 2.69 (dd,
J = 19.2, 3.9 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 205.9, 157.9,
143.6, 136.7, 135.0, 128.9, 127.8, 127.6, 126.9, 126.9, 123.4, 46.8, 44.4.
3-(p-Tolyl)-2,3-dihydro-1H-inden-1-one (3b):42 Light-yellow oil;
1H NMR (400 MHz, CDCl3): δ 7.80 (dt, J = 7.7, 1.0 Hz, 1H), 7.55 (td,
J = 7.5, 1.3 Hz, 1H), 7.40 (t, J = 7.2 Hz, 1H), 7.26 (dd, J = 7.5, 0.8 Hz,
1H), 7.12 (d, J = 7.7 Hz, 2H), 7.01 (d, J = 8.1 Hz, 2H), 4.54 (dd, J = 8.0,
3.9 Hz, 1H), 3.21 (dd, J = 19.2, 8.0 Hz, 1H), 2.67 (dd, J = 19.2, 3.9 Hz,
1H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 206.3, 158.3, 140.8,
136.8, 136.7, 135.2, 129.7, 127.9, 127.6, 126.9, 123.5, 47.0, 44.2, 21.1.
3-(4-Methoxyphenyl)-2,3-dihydro-1H-inden-1-one (3c):43 Light-
1
oil; H NMR (400 MHz, CDCl3): δ 7.82 (d, J = 7.7 Hz, 1H), 7.59 (td,
J = 7.5, 1.3 Hz, 1H), 7.44 (t, J = 7.5 Hz, 1H), 7.27 (d, J = 6.8 Hz, 1H),
7.24–7.20 (m, 1H), 7.11 (s, 1H), 7.00 (dt, J = 6.4, 2.3 Hz, 1H), 4.56 (dd,
J = 8.1, 3.9 Hz, 1H), 3.23 (dd, J = 19.2, 8.1 Hz, 1H), 2.65 (dd, J = 19.2,
3.9 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 205.4, 157.1, 145.8, 136.9,
135.4, 134.8, 130.3, 128.3, 127.9, 127.3, 126.9, 125.9, 123.7, 46.7, 44.2.
3-(3,4-Dichlorophenyl)-2,3-dihydro-1H-inden-1-one (3k):46 Light-
yellow oil; 1H NMR (400 MHz, CDCl3): δ 7.83 (d, J = 7.7 Hz, 1H), 7.61
(td, J = 7.5, 1.3 Hz, 1H), 7.46 (t, J = 7.5 Hz, 1H), 7.38 (d, J = 8.2 Hz,
1H), 7.27 (d, J = 8.3 Hz, 1H), 7.23 (d, J = 2.1 Hz, 1H), 6.95 (dd, J = 8.3,
2.2 Hz, 1H), 4.55 (dd, J = 8.1, 3.9 Hz, 1H), 3.24 (dd, J = 19.3, 8.1 Hz,
1H), 2.63 (dd, J = 19.2, 3.9 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ
205.0, 156.6, 144.1, 136.8, 135.5, 133.0, 131.2, 131.0, 129.8, 128.5,
127.1, 126.8, 123.8, 46.6, 43.7.
1
yellow oil; H NMR (400 MHz, CDCl3): δ 7.80 (d, J = 7.6 Hz, 1H),
3-(3,4,5-Trifluorophenyl)-2,3-dihydro-1H-inden-1-one (3l): Light-
yellow solid; m.p. 111.6–112.2 °C; 1H NMR (400 MHz, CDCl3): δ 7.83
(d, J = 7.7 Hz, 1H), 7.63 (td, J = 7.5, 1.3 Hz, 1H), 7.48 (t, J = 7.5 Hz, 1H),
7.28 (dd, J = 7.7, 0.9 Hz, 1H), 6.75 (dd, J = 8.4, 6.4 Hz, 2H), 4.54 (dd,
J = 8.2, 3.9 Hz, 1H), 3.23 (dd, J = 19.2, 8.2 Hz, 1H), 2.59 (dd, J = 19.1,
3.9 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 204.5, 156.0, 151.5 (ddd,
J = 251.0, 10.0, 4.1 Hz), 140.2 (td, J = 6.7, 4.6 Hz), 138.9 (dt, J = 250.0,
15.3 Hz), 136.9, 135.6, 128.7, 126.8, 123.9, 111.7 (dd, J = 15.6, 5.7 Hz),
46.5, 43.8; 19F NMR (376 MHz, CDCl3): δ −133.3, −162.3 (t, J = 20.6
Hz); HRMS (ESI) m/z: Calcd for C15H10F3O+ (M+H)+: 263.06783;
found: 263.06784.
7.56 (td, J = 7.6, 1.3 Hz, 1H), 7.40 (t, J = 7.5 Hz, 1H), 7.26 (dd, J = 7.7,
0.9 Hz, 1H), 7.04 (d, J = 8.7 Hz, 2H), 6.84 (d, J = 8.7 Hz, 2H), 4.53 (dd,
J = 8.0, 3.9 Hz, 1H), 3.79 (s, 3H), 3.21 (dd, J = 19.2, 8.0 Hz, 1H), 2.65 (dd,
J = 19.2, 3.9 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 206.3, 158.7, 158.4,
136.8, 135.9, 135.2, 128.7, 127.9, 126.9, 123.4, 114.4, 55.4, 47.1, 43.8.
3-(4-Bromophenyl)-2,3-dihydro-1H-inden-1-one (3d):42 Light-
1
yellow oil; H NMR (400 MHz, CDCl3): δ 7.81 (d, J = 7.7 Hz, 1H),
7.58 (td, J = 7.6, 1.2 Hz, 1H), 7.48–7.37 (m, 3H), 7.25 (dd, J = 7.7, 0.9
Hz, 1H), 7.00 (d, J = 8.4 Hz, 2H), 4.55 (dd, J = 8.1, 3.9 Hz, 1H), 3.23
(dd, J = 19.2, 8.1 Hz, 1H), 2.63 (dd, J = 19.2, 3.9 Hz, 1H); 13C NMR
(100 MHz, CDCl3): δ 205.5, 157.3, 142.9, 136.9, 132.1, 129.5, 128.2,
126.9, 121.0, 46.8, 44.0.
3-(Naphthalen-2-yl)-2,3-dihydro-1H-inden-1-one (3m):43 Light-
1
3-(4-Fluorophenyl)-2,3-dihydro-1H-inden-1-one (3e):43 Light-
yellow oil; 1H NMR (400 MHz, CDCl3): δ 7.81 (d, J = 7.7 Hz, 1H), 7.58
yellow oil; H NMR (400 MHz, CDCl3): δ 7.85 (d, J = 7.7 Hz, 1H),
7.85–7.74 (m, 3H), 7.66 (d, J = 1.7 Hz, 1H), 7.57 (td, J = 7.5, 1.3 Hz, 1H),

JOURNAL OF CHEMICAL RESEARCH 2018 43
3
4
5
K.P. Bogeso, J. Arnt, V. Boeck, A.V. Christensen, J. Hyttel and K.G. Jensen,
J. Med. Chem., 1988, 31, 2247.
X.H. Gu, H. Yu, A.E. Jacobson, R.B. Rothman, C.M. Dersch, C. George,
J.L. Flippen-Anderson and K.C. Rice, J. Med. Chem., 2000, 43, 4868.
B. Kim, S.-H. Kim, S.-J. Jeong, E.J. Sohn, J.H. Jung, M.H. Lee and S.-H.
Kim, J. Agric. Food. Chem., 2012, 60, 9882.
7.53–7.39 (m, 3H), 7.28 (dd, J = 7.7, 1.0 Hz, 1H), 7.14 (dd, J = 8.5, 1.8 Hz,
1H), 4.74 (dd, J = 8.1, 3.9 Hz, 1H), 3.30 (dd, J = 19.3, 8.1 Hz, 1H), 2.78 (dd,
J = 19.3, 3.9 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 206.1, 158.0, 141.0,
137.0, 135.3, 133.6, 132.6, 129.1, 128.1, 127.8, 127.7, 127.1, 126.6, 126.5,
126.0, 125.6, 123.6, 46.8, 44.7.
3-(Thiophen-3-yl)-2,3-dihydro-1H-inden-1-one (3n):43 Light-yellow oil;
1H NMR (400 MHz, CDCl3): δ 7.80 (d, J = 7.7 Hz, 1H), 7.59 (td, J = 7.5,
1.3 Hz, 1H), 7.42 (t, J = 7.4 Hz, 1H), 7.37 (dd, J = 7.7, 1.0 Hz, 1H), 7.29 (dd,
J = 5.0, 3.0 Hz, 1H), 7.04 (ddd, J = 3.0, 1.3, 0.6 Hz, 1H), 6.82 (dd, J = 5.0,
1.3 Hz, 1H), 4.72 (dd, J = 8.1, 3.8 Hz, 1H), 3.20 (dd, J = 19.1, 8.0 Hz, 1H),
2.69 (dd, J = 19.1, 3.9 Hz, 1H);13C NMR (100 MHz, CDCl3): δ 205.7, 157.4,
144.0, 136.6, 135.1, 128.1, 126.9, 126.8, 126.7, 123.6, 121.2, 46.1, 39.7.
6
7
8
9
B.W. Rockett and C.R. Hauser, J. Org. Chem., 1964, 29, 1394.
I. Smonou and M. Orfanopoulos, Synth. Commun., 1990, 20, 1387.
W. Yin, Y. Ma, J. Xu and Y. Zhao, J. Org. Chem., 2006, 71, 4312.
K. Kundu, J.V. McCullagh and A.T. Morehead Jr, J. Am. Chem. Soc., 2005,
127, 16042.
10 Y. Oonishi, J. Ogura and Y. Sato, Tetrahedron Lett., 2007, 48, 7505.
11 D.B. Bruce, A.J.S. Sorrie and R.H. Thomson, J. Chem. Soc., 1953, 2403.
12 A. Sani Souna Sido, S. Chassaing, M. Kumarraja, P. Pale and J. Sommer,
Tetrahedron Lett., 2007, 48, 5911.
1
3-Butyl-2,3-dihydro-1H-inden-1-one (3o):45 Light-yellow oil; H NMR
13 D. Kuck, E. Neumann and A. Schuster, Chem. Ber., 1994, 127, 151.
14 R. Rendy, Y. Zhang, A. McElrea, A. Gomez and D.A. Klumpp, J. Org.
Chem., 2004, 69, 2340.
15 A.G. Posternak, R.Y. Garlyauskayte and L.M. Yagupolskii, J. Fluorine
Chem., 2010, 131, 274.
(400 MHz, CDCl3): δ 7.73 (d, J = 7.7 Hz, 1H), 7.60 (td, J = 7.5, 1.2 Hz, 1H),
7.51 (dd, J = 7.7, 0.9 Hz, 1H), 7.37 (t, J = 7.4 Hz, 1H), 3.46–3.26 (m, 1H),
2.85 (dd, J = 19.0, 7.5 Hz, 1H), 2.36 (dd, J = 19.1, 3.3 Hz, 1H), 2.02–1.86
(m, 1H), 1.61–1.27 (m, 7H), 0.99–0.87 (m, 2H); 13C NMR (100 MHz,
CDCl3): δ 206.7, 159.2, 136.9, 134.7, 127.6, 125.7, 123.6, 43.3, 38.4, 36.0,
29.9, 22.9, 14.1.
16 D. Vasu, H.-H. Hung, S. Bhunia, S.A. Gawade, A. Das and R.-S. Liu,
Angew. Chem. Int. Ed., 2011, 50, 6911.
17 S. Bhunia, S. Ghorpade, D.B. Huple and R.-S. Liu, Angew. Chem. Int. Ed.,
2012, 51, 2939.
18 Y. Wang and L. Zhang, Synthesis, 2015, 47, 289.
5,6-Dichloro-3-phenyl-2,3-dihydro-1H-inden-1-one
(3p):
Light-
yellow oil; 1H NMR (400 MHz, CDCl3): δ 7.87 (s, 1H), 7.39–7.26 (m, 4H),
7.14–7.08 (m, 2H), 4.53 (dd, J = 8.2, 3.9 Hz, 1H), 3.26 (dd, J = 19.4, 8.1
Hz, 1H), 2.73 (dd, J = 19.4, 4.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ
203.4, 156.8, 142.5, 139.8, 136.4, 133.3, 129.3, 129.0, 127.7, 127.6, 125.1,
47.1, 44.1; HRMS (ESI) m/z: Calcd for C15H11Cl2O+ (M+H)+: 277.01815;
found: 277.01705.
19 J. Wang, H. Li and Y. Zhang, Synthesis, 2013, 45, 3090.
20 S.T. Muller and T. Wirth, ChemSusChem, 2015, 8, 245.
21 J. Barluenga and C. Valdés, Angew. Chem. Int. Ed., 2011, 50, 7486.
22 K. Xu, C. Shen and S. Shan, Chin. J. Org. Chem., 2015, 35, 294.
23 Z. Liu, Y. Zhang and J. Wang, Chin. J. Org. Chem., 2013, 33, 687.
24 Q. Xiao, Y. Zhang and J. Wang, Acc. Chem. Res., 2013, 46, 236.
25 G.W. Kabalka, J.T. Maddox, E. Bogas and S.W. Kelley, J. Org. Chem., 1997,
62, 3688.
26 G.W. Kabalka, J.T. Maddox and E. Bogas, J. Org. Chem., 1994, 59, 5530.
27 J. Barluenga, M. Tomas-Gamasa, F. Aznar and C. Valdes, Nat. Chem.,
2009, 1, 494.
28 S. Nakagawa, K.A. Bainbridge, K. Butcher, D. Ellis, W. Klute and T.
Ryckmans, ChemMedChem, 2012, 7, 233.
5,6-Dichloro-3-(p-tolyl)-2,3-dihydro-1H-inden-1-one (3q): Light-
yellow oil; 1H NMR (400 MHz, CDCl3): δ 7.86 (s, 1H), 7.36 (d, J = 0.7 Hz,
1H), 7.14 (d, J = 8.0 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 4.49 (dd, J = 8.0, 4.0
Hz, 1H), 3.24 (dd, J = 19.4, 8.0 Hz, 1H), 2.71 (dd, J = 19.4, 4.0 Hz, 1H),
2.34 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 203.6, 157.0, 139.8, 139.5,
137.3, 136.3, 133.2, 130.0, 129.0, 127.5, 125.0, 47.2, 43.7, 21.2; HRMS
(ESI) m/z: Calcd for C16H13Cl2O+ (M+H)+: 291.03380; found: 291.03424.
29 M. Plaza, M.C. Perez-Aguilar and C. Valdes, Chemistry, 2016, 22, 6253.
30 D.M. Allwood, D.C. Blakemore, A.D. Brown and S.V. Ley, J. Org. Chem.,
2014, 79, 328.
Acknowledgements
We gratefully acknowledge financial support of this work by the
National Natural Science Foundation of China (No. 21563025), the
Program for Changjiang Scholars and Innovative Research Team
in University (No. IRT_15R46) and the Yangtze River Scholar
Research Project of Shihezi University (No. CJXZ201601).
31 M.C. Perez-Aguilar and C. Valdes, Angew. Chem. Int. Ed., 2012, 51, 5953.
32 X. Shen, N. Gu, P. Liu, X. Ma, J. Xie, Y. Liu, L. He and B. Dai, RSC Adv.,
2015, 5, 63726.
33 X. Shen, N. Gu, P. Liu, X. Ma, J. Xie, Y. Liu and B. Dai. Chin. J. Chem.,
2016, 34, 1033.
34 X. Shen, P. Liu, Y. Liu, Y. Liu and B. Dai, Tetrahedron, 2017, 73, 785.
35 X. Shen, P. Liu, Y. Liu and B. Dai, Tetrahedron, 2017, 73, 6558.
36 Y. Liu, P. Liu, Y. Liu, and Y. Wei, Chin. J. Chem., 2017, 35, 1141.
37 Y. Liu, P. Liu, Y. Liu and Y. Wei, Lett. Org. Chem., 2017, 14, 557.
38 Y. Liu, P. Liu, Y. Liu, Y. Wei and B. Dai, Lett. Org. Chem., 2017, 14, 748.
39 M. Plaza, M.C. Perez-Aguilar and C. Valdes, Chemistry, 2016, 22, 6253.
40 S. Nave, R.P. Sonawane, T.G. Elford and V.K. Aggarwal, J. Am. Chem.
Soc., 2010, 132, 17096.
41 J. Lozada, Z. Liu and D.M. Perrin, J. Org. Chem., 2014, 79, 5365.
42 J. González, J. Santamaría and A. Ballesteros, Angew. Chem. Int. Ed.,
2015, 54, 13678.
43 G. Yue, K. Lei, H. Hirao and J. Zhou, Angew. Chem. Int. Ed., 2015, 54,
6531.
44 P.K. Tiwari and I.S. Aidhen, Eur. J. Org. Chem., 2016, 2016, 2637.
45 E.J. Rastelli, N.T. Truong and D.M. Coltart, Org. Lett., 2016, 18, 5588.
46 J. Cossy and D. Belotti, Synlett, 2003, 10, 1515.
Electronic Supplementary Information
The ESI is available through: http://ingentaconnect.com/
content/stl/jcr/2018/00000042/00000001/art00010
Received 4 December 2017; accepted 2 January 2018
Paper 1705135
https://doi.org/10.3184/174751918X15161933697844
Published online: 31 January 2018
References
1
K.P. Bogeso, A.V. Christensen, J. Hyttel and T. Liljefors, J. Med. Chem., 1985,
28, 1817.
2
B.H. Lee, Y.L. Choi, S. Shin and J.-N. Heo, J. Org. Chem., 2011, 76, 6611.
47 A. Püschl and H.C. Rudbeck, Synthesis, 2005, 2, 291.