Organocatalytic Electrochemical C-H Lactonization of Aromatic Carboxylic Acids

Article abstract of DOI:10.1055/s-0036-1591558

An electrochemical strategy has been developed for radical arene carbon-oxygen bond formation. This reaction utilizes DDQ as a redox mediator, with inexpensive glassy carbon electrodes to facilitate an intramolecular lactonization of biphenyl-2-carboxylic

Full text of DOI:10.1055/s-0036-1591558

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–F
paper
A
en
L. Li et al.
Paper
Synthesis
Organocatalytic Electrochemical C–H Lactonization of Aromatic
Carboxylic Acids
Longji Lia§
Qi Yanga§
Zongbin Jiaa
R
GC
C
R
Sanzhong Luo*a,b
0
0
0
0
0-
0
0
1
8-
7
1
4
4-
0
4
7
R'
DDQ (10 mol%)
R'
O
O
COOH
2,6-lutidine (20 mol%), 5 mA/cm2
0.1 M nBu4NClO4/HFIP
undivided cell, rt
a Key Laboratory of Molecular Recognition and Function, Institute of
Chemistry, Chinese Academy of Sciences, Beijing, 100190, China;
Department of Chemistry, University of Chinese Academy of Sciences,
10049, Beijing, P. R. of China
25 examples
up to 94% yield
luosz@iccas.ac.cn
b Collaborative Innovation Center of Chemical Science and Engineering
(Tianjin), Tianjin, 300071, P. R. of China
§ These authors contributed equally.
Published as part of the Special Topic Modern Radical Methods and their
Strategic Applications in Synthesis
Received: 17.01.2018
Accepted after revision: 08.03.2018
Published online: 28.03.2018
metal catalyst is avoided, a stoichiometric amount of oxi-
dant is necessary. Visible-light photoredox catalyzed ver-
sions of the dehydrogenative lactonization of biphenyl-2-
carboxylic acid have also been reported (Scheme 1). A com-
bination of photocatalyst [Acr+-Mes] with (NH4)2S2O8 as the
terminal oxidant was used by Gonzalez-Gomez and co-
workers.9 In 2018, our group reported an oxidant-free
method by utilizing a photocatalyst/cobalt catalyst sys-
tem.10 Although much progress has been made in the pro-
cesses describe above, the need to use toxic and excess ex-
ternal co-oxidants or heavy metal catalysts does not meet
the guiding principles of green and sustainable chemistry.11
DOI: 10.1055/s-0036-1591558; Art ID: ss-2018-c0030-st
Abstract An electrochemical strategy has been developed for radical
arene carbon–oxygen bond formation. This reaction utilizes DDQ as a
redox mediator, with inexpensive glassy carbon electrodes to facilitate
an intramolecular lactonization of biphenyl-2-carboxylic acid deriva-
tives via aromatic carboxyl radical substitution to give 6H-ben-
zo[c]chromen-6-ones.
Key words electrochemical oxidation, aromatic radical substitution,
lactonization, 6H-benzo[c]chromen-6-one, redox mediator
Biaryl lactones and their derivatives are frequently
found in many natural products and pharmaceuticals and
widely used as intermediates in the total synthesis of axial-
ly chiral natural products.1 Developing efficient new meth-
ods for their preparation is a worthwhile endeavor. 6H-
Benzo[c]chromen-6-ones (benzocoumarins) are normally
prepared through the dehydrogenative lactonization of bi-
phenyl-2-carboxylic acids usually under ultraviolet irradia-
tion2 or using stoichiometric toxic reactants3 thus limiting
the actual applicability of these methodologies. In 2013,
Wang and co-workers4 reported the construction of biaryl
lactones using Pd(II)/Pd(IV)-catalyzed carbonyl-directed
C–H activation/C–O cyclization (Scheme 1). Also in 2013,
Martin and Gallardo-Donaire5 and Gevorgyan and co-work-
ers6 utilized the copper-catalyzed oxygenation reaction of
biphenyl-2-carboxylic acid, but this protocol is only effi-
cient for electron-neutral and electron-rich substrates. In
addition to palladium and copper, silver7 has also been
shown to catalyze C–H functionalization/C–O cyclization.
Notably, the first organocatalyzed procedure that enables
this transformation was developed by Martin and co-work-
ers;8 although the use of a toxic and expensive transition-
conditions
COOH
O
O
Chemical
Oxidant, cat. [Pd], [Cu], [Ag] or iodine compounds
Photochemical
UV or [Acr+-Mes], oxidant, blue LEDs
UV or [Acr+-Mes], Co(dmgH)2ClPy, blue LEDs
This work: indirect electrolysis, undivided cell,
constant current, DDQ (10 mol%), rt
Scheme 1 Catalytic intramolecular lactonization of biphenyl-2-carbox-
ylic acid
Electrochemistry provides an efficient method to
achieve the formation of a new chemical bond and the
transformation of a functional group.12 Kolbe electrolysis is
the oldest electroorganic reaction13 and is defined as the
electrochemical one-electron oxidation of carboxylate ions
that leads to radical homocoupling upon decarboxylation.
This method is very specific and versatile for the synthesis
of higher alkenes14 and 1,n-diesters.15 Due to the high
oxidation potential of the carboxylates,16 the Kolbe electrol-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F

B
L. Li et al.
Paper
Synthesis
ysis must proceed under high current density and electrode
potential with an expensive platinum plate electrode. In
2018, Zeng and co-workers reported the intramolecular
C–H/C–O oxidative coupling of aromatic carboxylic acids
using direct electrolysis.17 Indirect electrolysis using a re-
dox mediator catalyst is advantageous in its avoidance of
electrode passivation and kinetic inhibition, lowering elec-
trode potential, and allowing for better selectivity.18 We ex-
ploited this redox catalyst to mediate the electrochemical
oxidation for the generation of the aromatic carboxyl radi-
cals. DDQ can be regenerated from the anodic oxidation19 as
a redox catalyst, providing an alternative strategy for the
electrochemical transformations of organic compounds.20
Herein, we describe an electrochemical synthesis of biaryl
lactones via aromatic carboxyl radicals catalyzed by DDQ as
a redox mediator.
We commenced our studies using biphenyl-2-carboxyl-
ic acid (1a) as a model substrate with the system of DDQ as
the redox catalyst under controlled current electrolysis at 5
mA in an undivided cell using LiClO4/MeCN as the electro-
lyte solution with two graphite plates as anode and cathode
and this gave the desired 6H-benzo[c]chromen-6-one (2a)
in 16% yield after passing 4 F of charge (Table 1, entry 1); 1a
was completely consumed as indicated by TLC. According to
the reaction mechanism,21 deprotonation by a base to give
the carboxylate would render it more susceptible to oxida-
tion, hence we reasoned that the presence of a base would
be beneficial. To our delight, the addition of 1 equivalent of
2,6-lutidine gave an improved yield (58%) of 2a (entry 2).
The use of Na2CO3 or NaHCO3 led to comparable yields of 2a
(entries 3 and 4), but a dramatically lower yield of 2a was
obtained in the case of K2CO3 (entry 5). Encouraged by this
result, the search for the optimal quantity of 2,6-lutidine
was undertaken. Decreasing the amount of 2,6-lutidine had
no effect (entry 6). Notably, 2a was obtained in very low
yield in the absence of 2,6-lutidine, thereby demonstrating
the essential role of a base in the overall transformation.
We then turned our attention to solvent optimization.
Comparable yields of 2a were obtained when MeOH or TFE
(2,2,2-trifluoroethanol) were used as solvents (entries 7
and 8), while the yield increased to 80% when HFIP
(1,1,1,3,3,3-hexafluoropropan-2-ol) was employed (entry
9). Further screening of electrode materials demonstrated
that the glass carbon plate was preferable for the reaction
and 2a was obtained in 94% yield (entry 10); Pt as the anode
proved to be less active (entry 11).
Table 1 Reaction Optimizationa
DDQ (10 mol%)
solvent, additive
COOH
electrode, 5 mA/cm2
4 F, undivided cell, rt
O
O
1a
2a
Entry Solvent
Additive
Anode
Cathode Yieldb (%)
1
2
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeOH
TFE
–
C
C
C
C
C
C
C
C
C
C
C
C
16
58
50
53
27
53
57
64
80
94
83
2,6-lutidinec
C
c
3
Na2CO3
C
c
4
NaHCO3
C
c
5
K2CO3
C
6
2,6-lutidine
2,6-lutidine
2,6-lutidine
2,6-lutidine
2,6-lutidine
2,6-lutidine
C
7
C
8
C
9
HFIP
C
10
11
HFIP
GC
Pt
HFIP
a General conditions: 1a (0.10 mmol), DDQ (10 mol%), additive (20 mol%),
0.1 M supporting electrolyte solvent mixture (2.0 mL), r.t.
b Determined by 1H NMR analysis with an internal standard.
c The amount of additive was 0.10 mmol (1 equiv).
ry 62–92% yields. In addition, the 3′-substituent has no ob-
vious influence on the reaction, and afforded the
corresponding products 2g,h in good yields. Meanwhile, re-
gardless of whether a methyl group was present in the 4-,
5-, or 6-positions, the corresponding products 2i–l were
obtained in moderate to good yields. When a phenyl group
was present in the 4- or 4′-positions, the desire products
2m,n were obtained in good yields. Notably, this transfor-
mation could also bear naphthalene well to give products
2o–r. The use of 3,3-diphenylacrylic acid and 2-(2,2-di-
phenylvinyl)benzoic acid was examined to explore the syn-
thetic potential of arene lactonization. 3,3-Diphenylacrylic
acid (1s) smoothly gave 4-phenyl-2H-chromen-2-one (2s)
in 91% yield and also, 2-(2,2-diphenylvinyl)benzoic acid
(1t) gave 3-(diphenylmethylene)isobenzofuran-1(3H)-one
(2t) in 63% yield; in these cases, tetrabutylammonium bro-
mide was found to perform better than DDQ as a redox me-
diator.
During the study using 2′-halobiphenyl-2-carboxylic ac-
ids 1u–w, the reaction gave only substitution product 2a
instead of C–H substitution product. Arene halides bearing
an ortho-halide substitute including chloride, bromide, and
fluoride, all underwent C-X radical substitution to give the
desired products in good yields (Scheme 3). This represents
a rare example of electrolysis-initiated aromatic radical
substitution.
With the optimized conditions in hand (Table 1, entry
10), we then explored the scope and generality of the reac-
tion. As shown in Scheme 2, a variety of biphenyl-2-carbox-
ylic acids 1 were cyclized to give the corresponding biaryl
lactones 2 in modest to excellent yields (up to 94%). It was
observed that both electron-withdrawing and electron-do-
nating groups were tolerated in the 4′-position and the de-
sired cyclization products 2b–f were obtained in satisfacto-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F

C
L. Li et al.
Paper
Synthesis
To gain additional insight into the reaction mechanism,
we performed a series of control experiments (Table 2).
First, we attempted to perform the reaction in the absence
of DDQ or 2,6-lutidine, but the yields dropped considerably
(entries 1 and 2). These experiments suggest that both DDQ
and 2,6-lutidine are essential for the high efficiency of reac-
tion. Also the reaction did not occur in the absence of an
electric current even in the presence of 1.5 equivalents of
DDQ. The electrolysis of 1a under the standard conditions
was performed in the presence of 2.0 equivalent of BHT
(3,5-di-tert-4-butyl-4-hydroxytoluene), a radical scavenger,
and this gave a trace amount of 2a (entry 5). While not yet
conclusive, these experiments imply that the reaction in-
volves a radical process. In addition, experiments focusing
on the kinetic isotopic effect (KIE) were also conducted to
gain additional insight into this reaction. The intra- and in-
termolecular KH/KD ratios were 1.19 and 1.20, respectively.
This result suggests that C–H bond cleavage was not in-
volved in the rate-determining step.
DDQ (10 mol%)
R
R
GC anode, graphite cathode
R'
2,6-lutidine (20 mol%), 5 mA/cm2
0.1 M nBu4NClO4/HFIP
undivided cell, rt
R'
COOH
O
O
1
2
O
O
O
O
O
O
O
O
CF3
Cl
F
2a, 94%
2b, 62%
2c, 80%
2d, 75%
O
O
O
O
O
O
O
F
O
Br
Cl
2e,92%
2f, 90%
2g, 80%
2h, 58%
O
O
O
O
O
O
O
O
Table 2 Mechanism Studies
2j, 82%
2k, 86%
2l, 79%
2i, 77%
a. Control experiments
O
O
O
O
O
O
O
DDQ (10 mol%)
Ph
Ph
O
GC anode, graphite cathode
2,6-lutidine (20 mol%), 5 mA/cm2
0.1 M nBu4NClO4/HFIP
4 F, undivided cell, rt
COOH
O
O
Cl
1a
2a
2m, 74%
2n, 80%
2o, 66%
2p, 76%
Entry
Variation from the standard conditions
Yield (%)
O
O
O
O
O
O
O
1
2
3
4
5
no DDQ
30
O
no 2,6-lutidine
50
Ph
no electric current
no electric current but 1.5 equiv DDQ
BHT
no reaction
no reaction
trace
Ph
2s, 91%a
2t, 63%a
2q, 80%
2r, 78%
Scheme 2 Substrate scope. a Bu4NBr was used instead of DDQ.
b. Intramolecular and intermolecular KIE
D
vs
D5
COOH
KH/KD = 1.19
COOH
COOH
DDQ (10 mol%)
GC anode, graphite cathode
KH/KD = 1.20
HX
+
2,6-lutidine (20 mol%), 5 mA/cm2
0.1 M nBu4NClO4/HFIP
undivided cell, rt
R'
R'
COOH
O
O
X
Base on the mechanistic investigation above, we pro-
posed a plausible mechanism shown in Scheme 4. The se-
quence begins with DDQ engaged in a homogeneous elec-
tron transfer from biphenyl-2-carboxylic acid 1 to an O-
centered carboxylic radical I, DDQ was regenerate by the
anodic oxidation. That the transformation can be mediated
by DDQ is verified by the fact that that 2 is obtained in only
30% yield when 1 is electrolyzed in the absence of DDQ,
while the yield is 94%, in its presence (Table 2, entry 1 and
Table 1, entry 10). Carboxylic radical I undergoes addition
to the arene ring to form an aryl radical intermediate II. A
further anodic oxidation of aryl radical II then leads to 2.
O
O
O
O
O
O
2a
Cl
F
X = F (1u): 89% yield
X = Cl (1v): 84% yield
X = Br (1w): 77% yield
2d
2c
X = F (1y): 87% yield
X = Cl (1x): 66% yield
Scheme 3 C(sp2)–X bond cleavage
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F

D
L. Li et al.
Paper
Synthesis
The presence of 2,6-lutidine would facilitate the deprotona-
tion of both 1 and intermediate II, favoring the coupled
electron-transfer.
1H NMR (400 MHz, CDCl3): δ = 8.41 (dd, J = 8.0, 1.7 Hz, 1 H), 8.15 (t, J =
7.8 Hz, 2 H), 7.88 (td, J = 7.6, 1.5 Hz, 1 H), 7.75–7.63 (m, 1 H), 7.58 (dd,
J = 10.0, 2.2 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 160.4, 151.1, 135.3, 133.5, 132.5, 132.2,
131.0, 130.3, 124.5, 123.8, 122.3, 121.8, 121.3, 121.2, 121.1, 115.4,
115.3.
+
R
R'
R
3-Fluoro-6H-benzo[c]chromen-6-one (2c)10
O
OH
1
R'
A
N
O
D
E
White solid; yield: 17.0 mg (80%).
O
O
– e–
– H+
– e–
– H+
1H NMR (500 MHz, CDCl3): δ = 8.34 (dd, J = 7.9, 1.4 Hz, 1 H), 8.00 (dd,
J = 8.5, 6.0 Hz, 2 H), 7.81 (td, J = 7.7, 1.4 Hz, 1 H), 7.58 –7.50 (m, 1 H),
7.14–6.92 (m, 2 H).
2
DDQ
R
13C NMR (126 MHz, CDCl3): δ = 164.5, 162.5, 160.8, 152.2, 152.1,
135.2, 134.3, 130.7, 128.8, 124.5, 124.4, 121.6, 120.5, 114.7, 114.6,
112.6, 112.4, 105.2, 105.0.
R
R'
O
O
R'
H
O
O
I
II
3-Chloro-6H-benzo[c]chromen-6-one (2d)10
Scheme 4 Proposed mechanism
White solid; yield: 17.2 mg (75%).
1H NMR (500 MHz, CDCl3): δ = 8.39 (dd, J = 8.0, 1.3 Hz, 1 H), 8.06 (d, J =
8.0 Hz, 1 H), 7.98 (d, J = 8.5 Hz, 1 H), 7.84 (ddd, J = 8.3, 7.3, 1.4 Hz, 1 H),
7.66–7.55 (m, 1 H), 7.37 (d, J = 2.1 Hz, 1 H), 7.31 (dd, J = 8.5, 2.1 Hz, 1
H).
13C NMR (126 MHz, CDCl3): δ = 160.7, 151.6, 136.1, 135.2, 134.1,
130.9, 129.3, 125.2, 123.9, 121.8, 121.0, 118.1, 116.8.
In summary, we have developed an intramolecular lac-
tonization of biphenyl-2-carboxylic acids by electrochemi-
cal oxidation with DDQ as the redox catalyst. This method
provides a general and convenient access to 6H-ben-
zo[c]chromen-6-ones under mild, robust and environmen-
tally friendly conditions.
3-Bromo-6H-benzo[c]chromen-6-one (2e)10
White solid; yield: 25.2 mg (92%).
1H NMR (400 MHz, CDCl3): δ = 8.38 (dd, J = 8.0, 1.4 Hz, 1 H), 8.06 (d, J =
8.1 Hz, 1 H), 7.90 (d, J = 8.5 Hz, 1 H), 7.87–7.78 (m, 1 H), 7.67–7.56 (m,
1 H), 7.52 (d, J = 2.0 Hz, 1 H), 7.45 (dd, J = 8.5, 1.9 Hz, 1 H).
13C NMR (101 MHz, CDCl3): δ = 160.6, 151.7, 135.2, 134.2, 130.9,
129.4, 128.0, 124.1, 123.9, 121.8, 121.2, 121.1, 117.3.
Commercial reagents were used as received, unless otherwise indi-
cated. 1H, 13C NMR spectra were measured on a NMR instrument
(300, 400, or 500 MHz for 1H NMR, 75, 101, or 126 MHz for 13C NMR).
TMS served as the internal standard for 1H NMR, and CDCl3 served as
the internal standard for 13C NMR.
Lactones 2; General Procedure
3-Methyl-6H-benzo[c]chromen-6-one (2f)
To an oven-dried, undivided electrochemical cell equipped with a
magnetic stir bar, a Glass Carbon plate anode (10.0 mm × 20.0 mm),
and a graphite plate cathode (10.0 mm × 30.0 mm) were added redox
catalyst–DDQ (10 mol%), biphenyl-2-carboxylic acid 1 (0.10 mmol).
Then electrolyte solution (0.1 M nBu4NClO4 in HFIP, 2.0 mL), and 2,6-
lutidine (20 mol%) was added. The mixture was then stirred for 10
min. After that, the electrolysis was initiated at a control current of
5.0 mA. Each reaction was terminated upon full consumption of start-
ing material as determined by TLC analysis. The entire mixture was
then transferred to a chromatography column (silica gel, petroleum
ether/EtOAc 9:1–4:1) to afford the desired product.
White solid; yield: 19.0 mg (90%).
1H NMR (400 MHz, CDCl3): δ = 8.38 (d, J = 7.9 Hz, 1 H), 8.07 (d, J = 8.1
Hz, 1 H), 7.92 (d, J = 8.0 Hz, 1 H), 7.80 (td, J = 7.7, 7.0, 1.4 Hz, 1 H), 7.54
(t, J = 7.6 Hz, 1 H), 7.19–7.10 (m, 2 H), 2.45 (s, 3 H).
13C NMR 126 MHz, CDCl3): δ = 161.4, 151.3, 141.3, 135.0, 134.8, 130.5,
128.4, 125.7, 122.5, 121.5, 120.9, 117.9, 115.4, 21.5.
2-Fluoro-6H-benzo[c]chromen-6-one (2g)10
White solid; yield: 17.1 mg (80%).
1H NMR (500 MHz, CDCl3): δ = 8.40 (dd, J = 7.9, 1.3 Hz, 1 H), 8.02 (d, J =
7.8 Hz, 1 H), 7.85 (td, J = 7.7, 1.4 Hz, 1 H), 7.70 (dd, J = 9.1, 2.9 Hz, 1 H),
7.67–7.60 (m, 1 H), 7.34 (dd, J = 9.0, 4.7 Hz, 1 H), 7.19 (ddd, J = 9.0, 7.6,
2.9 Hz, 1 H).
6H-Benzo[c]chromen-6-one (2a)10
White solid; yield: 18.4 mg (94%).
1H NMR (500 MHz, CDCl3): δ = 8.37 (dd, J = 7.9, 1.4 Hz, 1 H), 8.08 (d, J =
8.0 Hz, 1 H), 8.02 (dd, J = 8.0, 1.5 Hz, 1 H), 7.80 (td, J = 7.8, 1.4 Hz, 1 H),
7.60–7.53 (m, 1 H), 7.46 (ddd, J = 8.5, 7.2, 1.6 Hz, 1 H), 7.38–7.28 (m, 2
H).
13C NMR (126 MHz, CDCl3): δ = 160.9, 160.4, 158.4, 147.5, 147.4,
135.1, 134.0, 139.9, 130.8, 129.7, 122.0, 121.3, 119.4, 119.3, 119.3,
117.9, 117.7, 109.0, 108.8.
13C NMR (75 MHz, CDCl3): δ = 161.2, 151.3, 134.9, 134.8, 130.6, 130.5,
128.9, 124.6, 122.8, 121.7, 121.3, 118.1, 117.8.
2-Chloro-6H-benzo[c]chromen-6-one (2h)10
White solid; yield: 13.3 mg (58%).
1H NMR 500 MHz, CDCl3): δ = 8.40 (dd, J = 8.0, 1.4 Hz, 1H), 8.04 (d, J =
8.1 Hz, 1H), 7.99 (d, J = 2.4 Hz, 1H), 7.85 (td, J = 7.7, 1.4 Hz, 1H), 7.66 –
7.59 (m, 1H), 7.42 (dd, J = 8.7, 2.4 Hz, 1H), 7.30 (d, J = 8.8 Hz, 1H).
3-(Trifluoromethyl)-6H-benzo[c]chromen-6-one (2b)10
White solid; yield: 16.4 mg (62%).
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E
L. Li et al.
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Synthesis
13C NMR (75 MHz, CDCl3): δ = 160.7, 149.8, 135.2, 133.7, 130.9, 130.5,
130.2, 129.7, 122.7, 121.9, 121.4, 119.5, 119.3.
1H NMR (400 MHz, CDCl3): δ = 9.03 (s, 1 H), 8.54 (s, 1 H), 8.26–8.19
(m, 1 H), 8.03 (dd, J = 14.2, 8.2 Hz, 2 H), 7.69 (ddd, J = 8.3, 6.8, 1.3 Hz, 1
H), 7.60 (ddd, J = 8.1, 6.8, 1.2 Hz, 1 H), 7.48 (ddd, J = 8.4, 7.0, 1.5 Hz, 1
H), 7.39–7.26 (m, 2 H).
8-Methyl-6H-benzo[c]chromen-6-one (2i)10
13C NMR (126 MHz, CDCl3): δ = 161.1, 150.9, 136.3, 132.9, 132.5,
130.3, 129.7, 129.7, 129.6, 128.2, 127.3, 124.7, 123.0, 120.8, 119.3,
118.4, 118.0.
White solid; yield: 16.2 mg (77%).
1H NMR (400 MHz, CDCl3): δ = 8.20 (d, J = 1.9 Hz, 1 H), 8.01 (dd, J = 8.1,
6.5 Hz, 2 H), 7.66–7.59 (m, 1 H), 7.49–7.41 (m, 1 H), 7.37–7.28 (m, 2
H), 2.49 (s, 3 H).
13C NMR (126 MHz, CDCl3): δ = 161.5, 151.2, 139.4, 136.2, 132.4,
130.5, 130.0, 124.6, 122.7, 121.8, 121.3, 118.4, 117.8, 21.4.
3-Chloro-6H-naphtho[2,1-c]chromen-6-one (2p)10
White solid; yield: 21.3 mg (76%).
1H NMR (500 MHz, CDCl3): δ = 8.90 (s, 1 H), 8.39 (s, 1 H), 8.06 (d, J =
8.3 Hz, 1 H), 7.97 (t, J = 7.6 Hz, 2 H), 7.68 (d, J = 1.3 Hz, 1 H), 7.58 (d, J =
1.4 Hz, 1 H), 7.34–7.27 (m, 2 H).
13C NMR (126 MHz, CDCl3): δ = 161.0, 151.1, 136.3, 135.6, 133.2,
132.6, 130.0, 129.7, 128.9, 128.2, 127.6, 125.2, 124.0, 120.8, 118.8,
118.2, 117.1.
9-Methyl-6H-benzo[c]chromen-6-one (2j)10
White solid; yield: 17.2 mg (72%).
1H NMR (400 MHz, CDCl3): δ = 8.27 (d, J = 8.1 Hz, 1 H), 8.04 (dd, J = 8.0,
1.5 Hz, 1 H), 7.89 (s, 1 H), 7.46 (ddd, J = 8.6, 7.2, 1.5 Hz, 1 H), 7.41–7.28
(m, 3 H), 2.55 (s, 3 H).
13C NMR (126 MHz, CDCl3): δ = 161.4, 151.6, 146.0, 134.9, 130.7,
130.4, 130.3, 124.5, 122.8, 122.0, 119.0, 118.3, 117.9, 22.4.
3-Methyl-6H-naphtho[2,1-c]chromen-6-one (2q)10
White solid; yield: 20.8 mg (80%).
10-Methyl-6H-benzo[c]chromen-6-one (2k)10
1H NMR (400 MHz, CDCl3): δ = 8.93 (s, 1 H), 8.40 (s, 1 H), 8.02 (d, J =
8.1 Hz, 1 H), 7.96 (dd, J = 14.9, 8.3 Hz, 2 H), 7.64 (ddd, J = 8.1, 6.7, 1.2
Hz, 1 H), 7.57–7.51 (m, 1 H), 7.14 (dd, J = 8.1, 1.6 Hz, 1 H), 7.11 (s, 1 H),
2.43 (s, 3 H).
13C NMR (126 MHz, CDCl3): δ = 161.8, 150.9, 141.0, 136.4, 132.9,
132.3, 130.0, 129.7, 129.6, 128.1, 127.0, 125.9, 122.8, 120.3, 119.2,
118.1, 115.8, 21.5.
White solid; yield: 18.0 mg (86%).
1H NMR (400 MHz, CDCl3): δ = 8.39 (dd, J = 7.9, 1.5 Hz, 1 H), 8.36–8.30
(m, 1 H), 7.66 (d, J = 7.5 Hz, 1 H), 7.49 (t, J = 7.7 Hz, 2 H), 7.42 (dd, J =
8.2, 1.6 Hz, 1 H), 7.38–7.30 (m, 1 H), 2.92 (s, 3 H).
13C NMR (126 MHz, CDCl3): δ = 161.8, 151.3, 139.2, 135.1, 133.6,
129.7, 129.3, 128.3, 127.3, 124.1, 122.9, 119.8, 118.0, 25.5.
3,9-Dimethyl-6H-benzo[c]chromen-6-one (2l)10
5H-Dibenzo[c,f]chromen-5-one (2r)10
White solid; yield: 17.7 mg (79%).
White solid; yield: 19.2 mg (78%).
1H NMR (400 MHz, CDCl3): δ = 8.25 (d, J = 8.1 Hz, 1 H), 7.90 (d, J = 8.0
Hz, 1 H), 7.84 (s, 1 H), 7.34 (dd, J = 8.1, 1.5 Hz, 1 H), 7.17–7.09 (m, 2 H),
2.54 (s, 3 H), 2.44 (s, 3 H).
1H NMR (400 MHz, CDCl3): δ = 8.50 (dd, J = 8.0, 1.5 Hz, 1 H), 8.39 (dd,
J = 7.9, 1.3 Hz, 1 H), 8.08 (d, J = 8.1 Hz, 1 H), 7.94 (d, J = 8.7 Hz, 1 H),
7.86–7.75 (m, 2 H), 7.67 (d, J = 8.7 Hz, 1 H), 7.52–7.59 (m, 3 H).
13C NMR (126 MHz, CDCl3): δ = 161.6, 151.6, 145.9, 141.2, 135.1,
130.7, 129.8, 125.7, 122.6, 121.7, 118.6, 118.0, 115.6, 22.4, 21.5.
13C NMR (126 MHz, CDCl3): δ = 161.2, 147.2, 135.4, 135.0, 134.3,
130.6, 128.6, 127.9, 127.7, 127.1, 124.5, 123.9, 122.3, 122.0, 121.2,
119.1, 113.0.
3-Phenyl-6H-benzo[c]chromen-6-one (2m)10
4-Phenyl-2H-chromen-2-one (2s)10
White solid; yield: 20.1 mg (74%).
1H NMR (400 MHz, CDCl3): δ = 8.40 (dd, J = 8.0, 1.4 Hz, 1 H), 8.10 (dd,
J = 14.3, 8.0 Hz, 2 H), 7.86–7.78 (m, 1 H), 7.65 (dd, J = 7.4, 1.7 Hz, 2 H),
7.60–7.55 (m, 3 H), 7.50 (t, J = 7.6 Hz, 2 H), 7.45–7.39 (m, 1 H).
13C NMR (126 MHz, CDCl3): δ = 161.3, 151.7, 143.5, 139.3, 135.0,
134.7, 130.7, 129.1, 128.9, 128.4, 127.1, 123.4, 123.3, 121.8, 121.2,
117.0, 115.9.
White solid; yield: 20.2 mg (91%).
1H NMR (500 MHz, CDCl3): δ = 7.59–7.51 (m, 4 H), 7.50 (dd, J = 8.1, 1.6
Hz, 1 H), 7.46 (ddd, J = 6.2, 4.2, 2.7 Hz, 2 H), 7.42 (dd, J = 8.3, 1.2 Hz, 1
H), 7.26–7.21 (m, 1 H), 6.39 (s, 1 H).
13C NMR (126 MHz, CDCl3): δ = 160.9, 155.8, 154.3, 135.4, 132.1,
129.8, 129.0, 128.6, 127.2, 124.3, 119.2, 117.5, 115.4.
8-Phenyl-6H-benzo[c]chromen-6-one (2n)10
3-(Diphenylmethylene)isobenzofuran-1(3H)-one (2t)10
White solid; yield: 21.8 mg (80%).
White solid; yield: 18.3 mg (63%).
1H NMR (400 MHz, CDCl3): δ = 8.65 (d, J = 2.0 Hz, 1 H), 8.20 (d, J = 8.3
Hz, 1 H), 8.08 (td, J = 8.2, 1.7 Hz, 2 H), 7.71 (dd, J = 7.6, 1.7 Hz, 2 H),
7.52–7.34 (m, 6 H).
1H NMR (500 MHz, CDCl3): δ = 7.90 (d, J = 7.6 Hz, 1 H), 7.60–7.54 (m, 2
H), 7.52 (dd, J = 4.8, 1.9 Hz, 3 H), 7.44–7.28 (m, 7 H), 6.30 (d, J = 8.0 Hz,
1 H).
13C NMR (126 MHz, CDCl3): δ = 161.3, 151.2, 141.7, 138.9, 133.5,
133.4, 130.4, 129.2, 128.5, 128.4, 127.1, 124.7, 122.8, 122.4, 122.6,
118.0, 117.8.
13C NMR (126 MHz, CDCl3): δ = 167.3, 142.6, 139.7, 137.7, 137.5,
132.0, 130.7, 130.6, 129.5, 129.5, 128.9, 128.3, 128.3, 125.4, 125.0,
125.0, 123.7.
6H-Naphtho[2,1-c]chromen-6-one (2o)10
White solid; yield: 16.2 mg (66%).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F

F
L. Li et al.
Paper
Synthesis
Funding Information
(7) Dai, J.-J.; Xu, W.-T.; Wu, Y.-D.; Zhang, W.-M.; Gong, Y.; He, X.-P.;
Zhang, X.-Q.; Xu, H.-J. J. Org. Chem. 2015, 80, 911.
(8) Wang, X.; Gallardo-Donaire, J.; Martin, R. Angew. Chem. Int. Ed.
2014, 53, 11084.
(9) Ramirez, N. P.; Bosque, I.; Gonzalez-Gomez, J. C. Org. Lett. 2015,
17, 4550.
We thank the Natural Science Foundation of China (21390400,
21502198 and 21521002) for financial support. S.L. is supported by
the National Program of Top-notch Young Professionals and Chinese
Academy of Sciences (QYZDJ-SSW-SLH023).
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(10) Yang, Q.; Jia, Z.-B.; Li, L.-J.; Zhang, L.; Luo, S.-Z. Org. Chem. Front.
2018, 5, 237.
(11) Matlack, A. S. Introduction to Green Chemistry; Marcel Dekker:
New York, 2001.
(12) For reviews, see: (a) Yoshida, J. L.; Karaoka, K.; Horcajada, R.;
Nagaki, A. Chem. Rev. 2008, 108, 2265. (b) Ogibin, Y. N.; Elison,
M. N.; Nikishin, G. I. Russ. Chem. Rev. 2009, 78, 89. (c) Yan, M.;
Kawamata, Y.; Baran, P. S. Chem. Rev. 2017, 117, 13230.
(13) Kolbe, H. Justus Liebigs Ann. Chem. 1849, 69, 257.
(14) Rabjohn, N.; Flasch, G. W. J. Org. Chem. 1981, 46, 4082.
(15) (a) Linstead, R. P.; Lunt, J. C.; Weedon, B. C. L. J. Chem. Soc. 1950,
3333. (b) Seko, M.; Yomiyama, A.; Isoya, T. Hydrocarbon Process.
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1591558.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F