Synthesis of dibenzopyranones and pyrazolobenzopyranones through copper(0)/Selectfluor system-catalyzed double C[sbnd]H activation/oxygen insertion of 2-arylbenzaldehydes and 5-arylpyrazole-4-carbaldehydes

Article abstract of DOI:10.1016/j.tet.2016.11.069

A mild and efficient protocol for the synthesis of dibenzopyranones and pyrazolobenzopyranones was developed involving a copper(0)/Selectfluor system-catalyzed double C[sbnd]H activation/oxygen insertion of 2-arylbenzaldehydes and 5-arylpyrazole-4-carbaldehydes. Preliminary mechanistic studies suggest that both water and dioxygen act as the oxygen source in the formation of pyranone scaffolds.

Full text of DOI:10.1016/j.tet.2016.11.069

Accepted Manuscript
Syntheis of dibenzopyranones and pyrazolobenzopyranones through copper(0)/
Selectfluor system-catalyzed double C-H activation/oxygen insertion of 2-
arylbenzaldehydes and 5-arylpyrazole-4-carbaldehydes
Jian Zhang, Dongdong Shi, Haifeng Zhang, Zheng Xu, Hanyang Bao, Hongwei Jin,
Yunkui Liu
PII:
S0040-4020(16)31249-2
10.1016/j.tet.2016.11.069
TET 28283
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 1 September 2016
Revised Date: 26 November 2016
Accepted Date: 28 November 2016
Please cite this article as: Zhang J, Shi D, Zhang H, Xu Z, Bao H, Jin H, Liu Y, Syntheis of
dibenzopyranones and pyrazolobenzopyranones through copper(0)/Selectfluor system-catalyzed
double C-H activation/oxygen insertion of 2-arylbenzaldehydes and 5-arylpyrazole-4-carbaldehydes,
Tetrahedron (2016), doi: 10.1016/j.tet.2016.11.069.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Synthesis of dibenzopyranones and
pyrazolobenzopyranones through
copper(0)/Selectfluor system-catalyzed
double C-H activation/oxygen insertion of 2-
arylbenzaldehydes and 5-arylpyrazole-4-
carbaldehydes
Leave this area blank for abstract info.
Jian Zhang, Dongdong Shi, Haifeng Zhang, Zheng Xu, Hanyang Bao, Hongwei Jin, Yunkui Liu
State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Zhejiang University of
Technology, Hangzhou 310014, China
O
Cu(0) (10 mol %)
Selectfluor (2.0 equiv)
K2CO3 (2.0 equiv)
O
H
O
R2 Ar2
R2 Ar2
CH3CN/H2O = 200:1 (V/V)
air, 25-50 °C, 24 h
R1
Ar1 R1
Ar1
H
Ar1 = aryl; Ar2 = aryl or pyrazolyl

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Syntheis of dibenzopyranones and pyrazolobenzopyranones through
copper(0)/Selectfluor system-catalyzed double C-H activation/oxygen insertion of 2-
arylbenzaldehydes and 5-arylpyrazole-4-carbaldehydes
Jian Zhang, Dongdong Shi, Haifeng Zhang, Zheng Xu, Hanyang Bao, Hongwei Jin and Yunkui Liu
State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Zhejiang University of Technology, Hangzhou 310014, China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A
mild and efficient protocol for the synthesis of dibenzopyranones and
pyrazolobenzopyranones was developed involving a copper(0)/Selectfluor system-catalyzed
double C-H activation/oxygen insertion of 2-arylbenzaldehydes and 5-arylpyrazole-4-
carbaldehydes. Preliminary mechanistic studies suggest that both water and dioxygen act as the
oxygen source in the formation of pyranone scaffolds.
Available online
2009 Elsevier Ltd. All rights reserved
.
Keywords:
Dibenzopyranones
Copper catalysis
Selectfluor
C-H activation
Annulation
1. Introduction
Despite much progress being made for the synthesis of
dibenzopyranones, most of the existing methods suffer from one
or more limitations including the use of prefunctionalized
precursors, expensive catalysts, multistep procedures, the
requirement of high or low temperature, and the employment of
toxic reagents. Therefore, it is highly desirable to develop novel
methods for the synthesis of dibenzopyranones from easily
available starting materials using inexpensive catalysts under
mild reaction conditions.
Dibenzopyranone scaffold is the key structure in a number of
natural products which display unique biological activities.1 For
example, Urolithin A (Figure 1-a) was known to effectively
inhibit cancer cell proliferation;1a Atenuisol (Figure 1-b) was
disclosed to show the high correlation with FabI-inhibition and
whole cell antibacterial activity;1b Sarolactone (Figure 1-c), a
compound isolated from Hypericum japonicum, was found to
exhibit antimicrobial properties.1c Besides, dibenzopyranones can
serve as useful intermediates for the synthesis of many
pharmaceutically interesting compounds2 as well as functional
molecules in materials science.3 Thus, the development of
efficient methods for the preparation of dibenzopyranones has
received increasingly attention in the past decades.4-10 Typically,
dibenzopyranones are synthesized through Baeyer-Villiger
oxidation of fluorenones (Scheme 1, path a)4 or by oxidation of
benzylic C-H bonds in 6H-benzo[c]chromenes (Scheme 1, path
b).5 Alternative methods include cross-coupling of aryl o-
benzoates (Scheme 1, path c),6 palladium-catalyzed C-H
activation/carbonylation of 2-arylphenols (Scheme 1, path d),7
intramolecular lactonization of 2-halobiarylcarboxylic acid
derivatives (Scheme 1, path e),8 tandem Suziki-Miyaura cross-
coupling/lactonization between 2-halobenzaldehydes and o-
OH
O
O
OH
O
HO
O
O
O
H3CO
OH
OH
HO
O
OH
(a) Urolithin A
(b) Altenuisol
(c) Sarolactone
Figure 1. Bioactive compounds containing dibenzopyranone scaffold
As part of our research interest in developing mild and
efficient catalyst systems for the construction of useful
molecules,11 we have recently disclosed that the combination of
copper powder and Selectfluor may generate an active XCuOH
species (X = F or BF4) which is easily able to undergo
oxycupration toward carbon-carbon multiple bonds and induce
hydroxyarylboronic acids (Scheme 1, path f),9 and others.10
———
Corresponding author. Tel.: fax: +86057188334137; e-mail addresses: ykuiliu@zjut.edu.cn (Y. Liu), jhwei828@zjut.edu.cn (H. Jin)

2
Tetrahedron
ACCEPTED MANUSCRIPT
successive tandem reactions.11a-c For example, in 2014, we
1). The catalytic activity of a series of copper and iron salts were
reported a Cu(0)/Selectfluor system-catalyzed concise synthesis
of 3-formyl-1-indenones from 1,5-enynes involving
cyclization/carbon-carbon bond cleavage sequence in which
double oxycuprations of 1,5-enynes were thought to be the key
steps.11b In 2015, we described a Cu(0)/Selectfluor system-
catalyzed facile synthesis of fluorinated fluorenones from 1,6-
studied for the reaction, and it was found that their catalytic
performances were inferior to that of Cu(0) powder (entries 6-13
vs 2, Table 1). Among several solvent systems investigated so far,
a combined solvent CH3CN/H2O = 200:1 (V/V) has proved to be
the most suitable medium for the reaction (entries 14-18 vs 2,
Table 1). Controlled experiments indicated that either the Cu(0)
powder or Selectfluor was indispensable for the reaction (entries
19, 20 vs 2, Table 1). Using 2.0 equivalents of Selectfluor is just
fine for the reaction while the excessive or deficient use of
Seletfluor would lead to a lower yield of 2a (entry 21 vs 2, Table
1). An attempt to use catalytic amounts of Selectfluor in the
presence of dioxygen gas (balloon, 1 atm) only gave a low yield
of 2a (25%, entry 22, Table 1). When Selectfluor was replaced
with NFSI (N-fluorobenzenesulfonimide), the reaction did not
take place and the starting material 1a was recovered (entry 23,
Table 1). Note that the use of 2 equivalents of K2CO3 is
necessary for the reaction otherwise a lower yield of 2a would be
obtained (entry 24 vs 2, Table 1). It was found that increasing the
reaction temperature gave a negative effect on the yield of 2a
(entry 25 vs 2, Table 1).
a
enynes
involving
an
oxycupration-triggered
annulation/fluorination sequence.11c Inspired by the finding that
the XCuOH species can easily undergo oxycupration toward
carbon-carbon multiple bonds, we envisioned that it may undergo
oxycupration toward C=O bonds as well. On the basis of this
assumption, it is reasonable to expect that dibenzopyranones
might be synthesized from 2-arylbenzaldehydes through an
oxycupration/C-H activation/oxidation sequence (Scheme 1, path
g). Herein we described our concept for the direct synthesis of
dibenzopyranones from 2-arylbenzaldehydes using the
Cu(0)/Selectfluor catalytic system as well as the related
mechanism studies. When our work approached completion, Ray
et al.12 reported
transformation of 2-arylbenzaldehydes to dibenzopyranones in
which 6 equivalents of TBHP act as the oxygen source for the
formation of pyranone scaffolds.
a
CuCl/TBHP system-catalyzed direct
With the optimized reaction conditions in hand, we then
investigated the substrate scope of the Cu(0)/Selectfluor system-
catalyzed double C-H activation/oxygen insertion of 2-
arylbenzaldehydes (Table 2). As shown in Table 2, a range of 2-
arylbenzaldehydes 1 with various substituents could be converted
to dibenzopyranones 2 in moderate to good yields (31-87%,
Table 2). Generally, both electron-donating and –withdrawing
substituents in the aryl ring of 1 were compatible with the
reaction conditions, among which include methyl, methoxy, tert-
butyl, halo (F, Cl, Br) and OCF3 groups. It was found that the
electronic nature of R1 has a significant effect on the reaction
outcome in terms of the yield. For instance, when R1 represents
electron-withdrawing group (e.g. F, Cl, Br, and OCF3), the
reaction proceeded more smoothly and gave higher yield of
product in comparison with those cases that R1 is electron-
donating group (2b-2e vs 2f; 2h-2k vs 2l, Table 2). In contrast, it
seemed that the electronic property of R2 has little effect on the
reaction outcome (2h, 2m, 2n, 2s, 2v except 2t, Table 2). When
1k was used, the reaction proceeded more smoothly by using
CuCl as the catalyst instead of the Cu(0) powder, and the desired
product 2k was obtained in 70% yield (1k, Table 2). For
substrate 1u, it is noteworthy that 50 ºC is a required temperature
for a better yield of 2u (50%, Table 2). Interestingly, when 2'-
chlorobiphenyl-2-carbaldehyde 1w was used, the reaction
underwent a competitive cross-dechlorinative C-O coupling
reaction to give a dibenzopyranone 2a in 67% yield while the
desired product 2w from the normal cross-dehydrogenative C-O
coupling reaction was not detected (1w, Table 2).
(a) previous synthetic strategies
O
OH
path d
path a
CO
R1
R2
R1
R2
O
O
O
R1
OH
X
path b
O
path e
R1
R1
R2
R2
R2
X = NO2, I, Br, Cl, H
O
X
R2
CHO
OH
O
path f
path c
R1
R1
R2
X
B(OH)2
X = Br, I
X = Br, I
(b) Our Concept
H O
2
Cu(0) + Selectfluor +
O
HO
O
O
CuX
H
X-Cu-OH
C-H activation
oxidation
O
R1
R1
R1
X = F or BF4
R2
R2
path g
R2
Scheme 1. Strategies for the synthesis of dibenzopyranones
2. Results and discussion
We commenced the study with 2-phenylbenzaldehyde 1a as
the model substrate, and the screening results are listed in Table 1.
When 1a was treated with Cu(0) powder (10 mol %), Selectfluor
(2.0 equiv), and NaHCO3 (2.0 equiv) in CH3CN/H2O (200/1, V/V)
at 25 ºC for 24 h, dibenzopyranone 2a was indeed obtained in
46% yield (entry 1, Table 1). Switching the base from NaHCO3
to K2CO3, the reaction proceeded more smoothly to give 2a in
92% yield (entry 2, Table 1). Several other bases (Na2CO3,
KHCO3, and Et3N) were investigated, and it was found that the
reaction failed to give the desired product 2a (entries 3-5, Table
Although there are a number of literatures on the synthesis of
dibenzopyranones,4-10,12 to the best of our knowledge, very few
have focused on the synthesis of heterocyclobenzopyranones.13
To broaden the synthetic application of the present method, we
next attempted to synthesize heterocyclobenzopyranones. We
commenced the study with substrates 3 containing pyrazole
moieties due to the potential utilities of pyrazole derivatives in
chemical, materials science and pharmaceutical fields.14 It was
found that the reaction generally required a higher temperature
Table 1. Optimization of reaction conditionsa
Entry
Catalyst
Oxidant
Base
Solvent
Yield %
46
1
2
3
4
Cu
Selectfluor
Selectfluor
Selectfluor
Selectfluor
NaHCO3
K2CO3
Na2CO3
KHCO3
CH3CN/H2O = 200:1
CH3CN/H2O = 200:1
CH3CN/H2O = 200:1
CH3CN/H2O = 200:1
Cu
92(86)c
Cu
n.r.
Cu
trace

3
5
Cu
Selectfluor
EtN3
CH3CN/H2O = 200:1
trace
20
ACCEPTED MANUSCRIPT
6
CuI
Selectfluor
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
CH3CN/H2O = 200:1
7
CuBr
CuCl
CuCl2
Cu(OAc)2
Cu(NO3)2
CuSO4
FeCl2
Cu
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
--
CH3CN/H2O = 200:1
CH3CN/H2O = 200:1
CH3CN/H2O = 200:1
CH3CN/H2O = 200:1
CH3CN/H2O = 200:1
CH3CN/H2O = 200:1
CH3CN/H2O = 200:1
DMSO/H2O = 200:1
dioxane/H2O = 200:1
DCE/H2O = 200:1d
CH3CN/H2O = 100:1
CH3CN/H2O = 500:1
CH3CN/H2O = 200:1
CH3CN/H2O = 200:1
CH3CN/H2O = 200:1
CH3CN/H2O = 200:1
CH3CN/H2O = 200:1
CH3CN/H2O = 200:1
CH3CN/H2O = 200:1
30
8
85
9
70
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
78
82
25
n.r.
n.r.
n.r.
n.r.
88
Cu
Cu
Cu
Cu
89
--
n.r.
n.r.
17e, 70f
25g
n.r.
72i, 75j
60k, 66l
Cu
Cu
Selectfluor
Selectfluor
NFSIh
Cu
Cu
Cu
Selectfluor
Selectfluor
Cu
aReaction condiitons: 1a (0.3 mmol), catalyst (10 mol %), oxidant (2.0 equiv), solvent (3 mL) at 25 ºC for 24 h unless otherwise noted.
bDetermined by GC using dodecane as an internal standard.
cIsolated yield.
dDCE: 1, 2-dichloroethane.
e,f1.0 and 3.0 equivalents of Selectfluor were used, respectively.
gUsing 0.3 equivalents of Selectfluor in the presence of O2 (balloon, 1 atm).
hNFSI: N-fluorobenzenesulfonimide.
i,jUsing 0.5 and 1.0 equivalents of K2CO3, respectively..
k,lThe reaction temperature is 50 and 80 oC, respectively.
(50 ºC) for the efficient formation of 4 in comparison with the
lactonization of 1 (Table 3 vs Table 2). Under the slightly
modified reaction conditions, a range of 3-methyl-1,5-diphenyl-
1H-pyrazole-4-carbaldehydes (3a-3e) could be intramolecularly
lactonized to pyrazolobenzopyranones 4 in moderate to good
yields catalyzed by the Cu(0)/Selectfluor system (55-72%, 4a-4e,
Table 3). For substrate 3 possessing two phenyl rings adjacent to
the formyl group, the cross-dehydrogenative C-O coupling
reaction predominantly took place in the phenyl ring substituted
with more strong electron-withdrawing groups (4g-4j, Table 3).
When 3f was used as the substrate, the reaction gave a
regioisomeric mixture of 4f and 4f' in a total yield of 62% with a
molar ratio of 1:0.41 determined by NMR analyses (3f, Table 3;
see in the Supporting Information). Similarly, the intramolecular
lactonization of 3k resulted in a regioisomeric mixture of 4k and
4k' in a total yield of 63% with a molar ratio of 1:0.94 (3k, Table
3; see in the Supporting Information).
application of 2a as a synthetic intermediate in the synthesis of
2'-hydroxybiphenyl-2-carboxylic acid 5, 6H-benzo[c]chromene 6,
and 6-phenyl-6H-benzo[c]chromen-6-ol 7. was carried out. Thus,
treatment of 2a with 5% (W/W) NaOH solution in acetonitrile
for 6 h afforded 5 in 98% yield (eq. 2, Scheme 2);15 the reduction
of 2a with NaBH4 in ethanol for 3 h gave 6 in 92% yield (eq. 3,
Scheme 2);16 the nucleophilic addition of PhMgBr to 2a in THF
delivered 7 in 94% yield (eq. 4, Scheme 2).17
To further demonstrate the synthetic potential of the present
method, the intramolecular lactonization of 1a at the gram-scale
was also carried out (eq. 1, Scheme 2). Thus, 1.8 g of 1a (10
mmol) could give 1.49 g of 2a in a yield of 76% under the
standard reaction conditions (eq. 1, Scheme 2). In addition, to
demonstrate the synthetic value of dibenzopyranones 2, the

4
Tetrahedron
ACCEPTED MANUSCRIPT
Table 2. Investigation of substrate scope in the
Cu(0)/Selecfluor system-catalyzed double C-H
O
activation/oxygen insertion of 2-arylbenzaldehydes 1a,b
CHO
Cu(0) (10 mol %)
Selectfluor (2.0 equiv)
K2CO3 (2.0 equiv)
Standard conditions
O
O
CHO
( 1 )
O
R2
R2
CH3CN/H2O = 200:1 (V/V)
25 oC, 24 h, air
R1
R1
1a
1
2
2a (1.49 g, 76%)
1.82 g (10 mmol)
O
O
O
O
O
O
O
O
O
O
COOH
5% NaOH
( 2 )
2a
HO
CH3CN, 6 h
OCF3
F
Cl
Br
2d
2b
(73%)
O
2a (86%)
(81%)
2c (80%)
2e
(82%)
O
O
O
O
5 (98%)
O
O
O
O
O
Cl
O
NaBH4 (2 equiv)
C2H5OH, r.t. 3 h
F
Cl
( 3 )
2a
2g
2h
(78%)
(76%)
O
2j
2f
(72%)
O
(53%)
O
2i (77%)
O
O
F
O
O
O
O
O
6 (92%)
F
Cl
OH
Br
2k (70%)c
O
(57%)
O
2l
2m (64%)
2n (76%)
2o (73%)
O
O
O
PhMgBr (1 equiv)
O
F
2a
( 4 )
Cl
Br
F
O
O
Cl
THF, 0 o
C
O
O
O
O
Cl
2p
2q (72%)
(62%)
2t (31%)
2r (81%)
2s (71%)
7 (94%)
O
O
F
O
O
CHO
O
O
O
O
O
Scheme 2. Gram-scale synthesis of 2a and its synthetic applications
+
Cl
OCF3
Cl
2w (0%)
d
2u
2a (67%)
(50%)
2v
1w
(87%)
To elucidate the mechanism of the double C-H
activation/oxygen insertion of 2-arylbenzaldehydes, some
mechanistic experiments were carried out (Scheme 3).
According to our initial assumption (path g, Scheme 1), we
believed that 2-arylbenzoic acid might be an intermediate for the
intramolecular lactonization of 1. When the preparative 2-
phenylbenzoic acid 88k was subjected to the standard reaction
conditions, 2a was indeed obtained in 95% yield (eq. 5, Scheme
3). When 1a reacted under the standard reaction conditions
except using a CH3CN/H2O18 = 200:1 (V/V) solvent system, the
O18-incorporated product 2a-O18 (m/z = 198) was detected (eq. 6,
Scheme 3; also see Figure S1, Supporting Information). On the
other hand, when 1a was subjected to the standard reaction
conditions except in the presence of an 18O2 atmosphere (balloon,
1 atm), the O18-incorporated product 2a-O18 (m/z = 198) was
also detected (eq. 7, Scheme 3; also see Figure S3, Supporting
Information). These results suggest that both water and dioxygen
acted as the oxygen source in the formation of pyranone
scaffolds. According to reported literatures,18 the 13C NMR
signals of the 18O-attached carbons generally shift to upfield
compared to the normal 16O-attached ones. Based on this rule, it
has been found that the incorporated 18O in 2a-O18 (both in eq. 6
and eq. 7) predominantly resides in the ester oxygen (δ aryl C-
O16: 151.39 ppm; δ aryl C-O18: 151.30 ppm) rather than the
carbonyl oxygen (see Figure S2 and S4, Supporting Information).
In addition, reaction of 1a in the presence of both H2O18 and 18O2
was also carried out, and the two 18O-incorporated product 2a-
(O18)2 (m/z = 200) was not detected, suggesting that the original
16O in the formyl group of 1a can not be substituted by 18O (eq. 8,
Scheme 3). Furthermore, an attempt to run the reaction of 1a
under an argon atmosphere was carried out, and the reaction
gave 2a in 36% yield (eq. 9, Scheme 3). In contrast, when 1a
was subjected to the standard reaction conditions except using a
dried solvent, the reaction could still give 2a in 69% yield (eq. 9,
Scheme 3). Note that the reaction could also proceed smoothly
and give 2a in 60% yield by using preparative HOCuF11a as a
catalyst (eq. 10, Scheme 3). Finally, the measurement of the
intermolecular KIE on the basis of the competitive C-O coupling
between 1a and 1a-d5 was carried out (eq. 11, Scheme 3). The
aAll reactions were carried out with 1 (0.3 mmol), Cu(0) (10 mol % based on
1), Selectfluor (2.0 equiv), and K2CO3 (2.0 equiv) in solvent (CH3CN/H2O =
200:1 (V/V), 3 mL) at 25 ºC for 24 h unless otherwise noted.
bIsolated yield.
cCu(0) powder was replaced with CuCl as the catalyst.
dThe reaction temperature is 50 ºC.
Table 3. Cu(0)/Selecfluor system-catalyzed double C-H
activation/oxygen insertion of 5-arylpyrazole-4-
carbaldehydes 3a,b
Cu(0) (10 mol %)
Selectfluor (2.0 equiv)
K2CO3 (2.0 equiv)
N
R2
R2
N
N
N
CH3CN/H2O = 200:1 (V/V)
50 oC, 24 h, air
R1
R1
O
CHO
O
3
4
Cl
N
N
N
N
N
N
N
N
N
N
Cl
F
O
O
O
O
O
O
O
O
O
O
4d (55%)
4e (60%)
4a (67%)
4c (72%)
4b (70%)
N
N
N
N
N
N
N
N
Br
Cl
O
O
O
O
O
O
O
O
4f
4f'
4h (63%)
4g (66%)
4f:4f'= 1:0.43 (62%)
Br
Cl
N
N
N
N
N
N
N
N
Br
Cl
Br
O
O
O
O
O
O
O
O
Cl
4k
4k'
4j (45%)
4k:4k'= 1: 0.94 (63%)
4i (50%)
aAll reactions were carried out with 1 (0.3 mmol), Cu(0) (10 mol % based on
1), Selectfluor (2.0 equiv), and K2CO3 (2.0 equiv) in solvent (CH3CN/H2O =
200:1 (V/V), 3 mL) at 50 ºC for 24 h unless otherwise noted.
bIsolated yields.

5
Cl
Cl
BF4
intermolecular kH/kD of 1a to 1a-d5 was determined to be 1.42
(Figure S3, see Supporting Information), suggesting that the
+
N
ACCEPTED MANUSCRIPT
N+
CH3CN
-
F-Cu-BF4
Cu(0)
N
-
N
2BF4
+
F
9
10
Selectfluor
B HX
cleavage of the C-H bond is the rate-determining step.
-
-Cu-X (X = F- or BF4
HO
11
)
H2
O
F-Cu-BF4
9
O
base
COOH
O
Standard conditions
O
OH
11
path A
( 5 )
H
O
β
-H elimination
fast
O
H
OCuX
11
8
1a
2a (95%)
8
11
12
H2
O
O
O
O
O
Cu (10 mol %)
Selectfluor (2.0 equiv)
path B
CHO
Selectfluor + base
O18
H2O
O
O
O
CuX
( 6 )
( 7 )
( 8 )
K2CO3 (2.0 equiv)
CH3CN:H2O18 = 200:1(V/V)
25 oC, 24 h
O
11
13
2a
CuX
2a-O18
(m/ z = 198)
1a
2a
(m/z = 196)
O
O
O
O-O
CuX
O
14
H+
O
O
Cu (10 mol %)
Selectfluor (2.0 equiv)
K2CO3 (2.0 equiv)
O-O
H
O
Cu(II)
Cu(I)
O
CHO
O18
+
Cu O-O
O2
16
X
O
CH3CN/H2O = 200:1 (V/V)
17
H
18
18O
2 (balloon, 1 atm)
Cu(I)
15
25 oC, 24 h
O
2a-O18
(m/ z = 198)
1a
2a
O
O
H2
(m/ z = 196)
O
O
H
O18
O18
O
O
O
Cu (10 mol %)
Selectfluor (2.0 equiv)
CHO
O18
2a
19
K2CO3 (2.0 equiv)
CH3CN:H2O18 = 200:1(V/V)
18O
2 (balloon, 1 atm)
2a-O18
2a-(O18
)
2
25 oC, 24 h
1a
2a
(m/z = 196)
Scheme 4. Proposed mechanism
(m/ z = 198)
(m/ z = 200)
(not detected)
Standard conditions
Standard conditions
1a
1a
2a
( 9 )
except under Ar atmosphere
yield = 36%
except using dried CH3CN
yield = 69%
HOCuF (10 mol %)
Selectfluor (2.0 equiv)
2a
( 10 )
1a
3. Conclusion
K2CO3 (2.0 equiv)
(yield = 60%)
CH3CN:H2O = 200:1(V/V)
25 oC, 24 h
In summary, we described an efficient method for the
synthesis of dibenzopyranones and pyrazolobenzopyranones
directly from 2-arylbenzaldehydes and 5-arylpyrazole-4-
carbaldehydes catalyzed by the Cu(0)/Selectfluor system.
Preliminary mechanistic studies disclosed that both water and
dioxygen acted as the oxygen source in the formation of
pyranone scaffolds. The present method for the construction of
dibenzopyranones has several advantages including mild
reaction conditions, the use of inexpensive copper catalyst, easy
availability of the starting materials, and capabilities for the
synthesis of heterocyclobenzopyranones.
O
O
O
Cu (10 mol %)
Selectfluor (2 equiv)
K2CO3 (2 equiv)
CHO
CHO
O
(11 )
CH3CN/H2O = 200:1 (V/V)
air, 25 °C, 3 h
D5
D4
1a (0.2 mmol)
2a
2a-d4
1a-d5 (0.2 mmol)
kH/kD = 1.42
Scheme 3. Preliminary mechanistic experiments
On the basis of the abovementioned mechanistic studies and
previous reports,11a-c,19
Cu(0)/Selectfluor
a
possible mechanism for the
system-catalyzed double C-H
activation/oxygen insertion of 2-phenylbenzaldehydes 1a was
proposed in Scheme 4. Firstly, the redox reaction between the
Cu(0) powder and Selectfluor may generate an intermediate F-
Cu-BF4 (9) and release a base 10.11a-c Then intermediate 9 may
be further converted into XCuOH (11, X = F or BF4) in the aid
of base 10 and/or K2CO3.11a-c Once the active XCuOH species
was generated, the reaction may proceed via two possible
pathways to form product 2a. One pathway (path A) might
involve an oxycupration of 11 toward the C=O bond in 1a
followed by a fast β-H elimination of the resulting intermediate
12 to give an intermediate 8. Intermediate 8 may be converted to
intermediate 13 in the presence of 11 (also see eq. 5, Scheme 3).
Intermediate 13 might undergo intramolecular cross-
dehydrogenative C-O coupling reaction8e,f,12 to afford
dibenzopyranone 2a and regenerate intermediate 11 in the
presence of Selecfluor and base (10 and/or K2CO3).11c On the
other hand, the direct proton abstraction from the formyl group
in 1a by 11 may form an intermediate 14 (path B). The oxidation
of 14 with dioxygen followed by a rearrangement of the resulting
intermediate 15 would deliver an intermediate 16,11a,19 which
may be further converted to an intermediate 17. In presence of
Cu(I) species, 17 might decompose to produce an intermediate
18 and hydroxy radical.12,20 Intermediate 18 may undergo
annulation to give an intermediate 19, which finally delivered the
product 2a after the abstraction of a proton by the hydroxy
radical.12
4. Experimental section
4.1 General methods
Unless otherwise stated, all reagents were purchased from
commercial suppliers and used without purifications. Melting
points are uncorrected. The 1H and 13C NMR spectra were
recorded on a Bruker AVANCE III 500 at 25 °C in CDCl3 at 500
MHz, 125 MHz, respectively, with TMS as internal standard.
Chemical shifts (δ) are expressed in ppm and coupling constants
J are given in Hz. The IR spectra were recorded on an FT-IR
spectrometer. GC-MS experiments were performed with an
Agilent 6890N GC system equipped with a 5973N mass-
selective detector with EI source; high resolution mass spectra
(HRMS) were obtained on a TOF MS instrument with EI source.
4.2 Typical experimental procedure for the synthesis of the
starting materials 2-arybenzaldehydes 1 (or 5-
arylpyrazole-4-carbaldehydes 3
)
These compounds were synthesized according to the literature
procedure.21 Typical procedure: 2-bromobenzaldehyde (0.92 g, 5
mmol), phenylboronic acid (0.67 g, 5.5 mmol), sodium
conbonate (0.53 g, 5 mmol), and Pd(OAc)2 (0.028 g, 0.125
mmol) were added to a flask (50 mL) equipped with a high-
vacuum PTFE valve-to-glass seal. The flask was opened to the
vacuum, pumped for 2-3 minutes and backfilled with an inert Ar
gas. The reaction mixture was stirred at room temperature

6
Tetrahedron
overnight. Upon completion, the reaction mixture was diluted
2H), 7.86–7.83 (m, 1H), 7.62–7.59 (m, 1H), 7.22–7.19 (m, 2H);
ACCEPTED MANUSCRIPT
with CH2Cl2 (3×20 mL) and the organic layer was dried over
Na2SO4, concentrated under the reduced pressure to give a dark
brown oil, which was further purified via column
chromatography on Silica gel (eluent: petroleum ether : EtOAc =
20:1) to give 2-phenylbenzaldehyde 1a (0.86 g, 95%).
13C NMR (125 MHz, CDCl3): δ 160.4, 151.8, 150.2, 135.1,
133.8, 130.7, 129.3, 124.2, 121.7, 120.9, 120.4 (d, J = 257.5 Hz),
116.9, 116.7, 110.1; HRMS (EI) for C14H7F3O3 [M+]: calcd.
280.0347, found 280.0353.
4.3.6 3-(tert-butyl)-6H-benzo[c]chromen-6-one (2f). Prepared
from 4'-tert-butylbiphenyl-2-carbaldehyde; isolated as white
4.3 Typical experimental procedure for the synthesis of 2 or
4
solid (40.1 mg, 53%), m.p. 154–156 C; IR (KBr, cm-1): ν =
o
1
1722, 1621; H NMR (500 MHz, CDCl3): δ 8.40 (dd, J1 = 8.0
1 (or 3, 0.3 mmol), Cu(0) powder (1.92 mg, 10 mol %),
Selectfluor (212.6 mg, 0.6 mmol), K2CO3 (82.8 mg, 0.6 mmol)
and CH3CN (3 mL) were added to a 10-mL flask. Then the
reaction mixture was stirred at 25 ºC (50 ºC for 3) for 24 h. Upon
completion, the resulting mixture was diluted with CH2Cl2 (10
mL) and filtered through Celite. After evaporation of the solvent
under vacuum, the residue was purified by column
chromatography on silica gel (100-200 mesh) using petroleum
ether-EtOAc (20/1, V/V) as eluent to give pure 2 (or 4).
Hz, J2 = 0.5 Hz, 1H), 8.10 (d, J = 8.5 Hz, 1H), 7.99 (dd, J1 = 6.0
Hz, J2 = 3.0 Hz, 1H), 7.84–7.80 (m, 1H), 7.56 (t, J = 8.0 Hz,
1H), 7.40–7.38 (m, 2H), 1.39 (s, 9H); 13C NMR (125 MHz,
CDCl3): δ 161.5, 154.8, 151.3, 135.0, 134.8, 130.6, 128.4, 122.4,
122.0, 121.5, 121.1, 115.4, 114.6, 35.1, 31.1; HRMS (EI) for
C17H16O2 [M+]: calcd. 252.1150, found 252.1146.
4.3.7 4-chloro-6H-benzo[c]chromen-6-one (2g). Prepared from
3'-chlorobiphenyl-2-carbaldehyde; isolated as white solid (52.6
mg, 76%), m.p. 184–186 oC; IR (KBr, cm-1): ν = 1741, 1605; 1H
NMR (500 MHz, CDCl3): δ 8.43 (dd, J1 = 8.0 Hz, J2 = 1.0Hz,
1H), 8.09 (d, J = 8.0 Hz, 1H), 8.04 (d, J = 2.5 Hz, 1H), 7.89–7.86
(m, 1H), 7.67–7.63 (m, 1H), 7.45 (dd, J1 = 8.5 Hz, J2 = 2.5 Hz,
1H), 7.33 (d, J = 9.0 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ
160.5, 149.8, 135.0, 133.6, 130.8, 130.3, 130.1, 129.6, 122.6,
121.8, 121.4, 119.4, 119.2; HRMS (EI) for C13H7ClO2 [M+]:
calcd. 230.0135, found 230.0138.
4.3.1 6H-benzo[c]chromen-6-one (2a).22 Prepared from
biphenyl-2-carbaldehyde; isolated as white solid (50.6 mg, 86%),
o
o
m.p. 85–86 C (lit.22 m.p. 88–89 C); IR (KBr, cm-1): ν = 1733,
1602; 1H NMR (500 MHz, CDCl3): δ 8.43 (dd, J1 = 7.5 Hz, J2 =
1.0Hz, 1H), 8.15 (d, J = 8.5 Hz, 1H), 8.09 (dd, J1 = 8.0 Hz, J2 =
1.5 Hz, 1H), 7.87–7.84 (m, 1H), 7.63–7.59 (m, 1H), 7.52–7.49
(m, 1H), 7.41–7.35 (m, 2H); 13C NMR (125 MHz, CDCl3): δ
161.2, 151.4, 134.8 (2C), 130.6, 130.5, 128.9, 124.6, 122.8,
121.7, 121.4, 118.1, 117.8; GC-MS (EI, 70 eV ): m/z (%) = 196
(100) [M+].
4.3.8 9-methyl-6H-benzo[c]chromen-6-one (2h).23 Prepared from
5-methylbiphenyl-2-carbaldehyde; isolated as white solid (49.2
mg, 78%), m.p. 94–95 oC (lit.23 m.p. 101–103 oC); IR (KBr, cm-
4.3.2 3-fluoro-6H-benzo[c]chromen-6-one (2b). Prepared from
4'-fluorobiphenyl-2-carbaldehyde; isolated as white solid (52.1
mg, 81%), m.p. 155–157 oC; IR (KBr, cm-1): ν = 1757, 1614; 1H
NMR (500 MHz, CDCl3): δ 8.38 (dd, J1 = 8.0 Hz, J2 = 1.0 Hz,
1H), 8.05–8.02 (m, 2H), 7.85–7.82 (m, 1H), 7.58 (t, J = 7.5 Hz,
1H), 7.11–7.07 (m, 2H); 13C NMR (125 MHz, CDCl3): δ 163.5
(d, J = 250.0 Hz), 160.7, 152.3 (d, J = 12.5 Hz), 135.0, 134.3,
130.7, 128.8, 124.4 (d, J = 10.0 Hz), 121.5, 120.6, 114.7 (d, J =
2.5 Hz), 112.4 (d, J = 22.5 Hz), 105.1 (d, J = 25.0 Hz); HRMS
(EI) for C13H7FO2 [M+]: calcd. 214.0430, found 214.0427.
1
1): ν = 1729, 1615; H NMR (500 MHz, CDCl3): δ 8.25 (d, J =
8.0 Hz, 1H), 8.02 (dd, J1 = 7.5 Hz, J2 = 1.5 Hz, 1H), 7.87 (s, 1H),
7.48–7.45 (m, 1H), 7.38–7.30 (m, 3H), 2.55 (s, 3H); 13C NMR
(125 MHz, CDCl3): δ 161.2, 151.4, 145.9, 134.7, 130.5, 130.2,
130.1, 124.4, 122.7, 121.8, 118.8, 118.1, 117.7, 22.2; GC-MS
(EI, 70 eV ): m/z (%) = 210 (46) [M+].
4.3.9
3-fluoro-9-methyl-6H-benzo[c]chromen-6-one
(2i).
Prepared
from 4'-fluoro-5-methylbiphenyl-2-carbaldehyde;
o
isolated as white solid (52.7 mg, 77%), m.p. 152–154 C; IR
(KBr, cm-1): ν = 1730, 1621; H NMR (500 MHz, CDCl3): δ
1
4.3.3 3-chloro-6H-benzo[c]chromen-6-one (2c). Prepared from
4'-chlorobiphenyl-2-carbaldehyde; isolated as white solid (55.3
mg, 80%), m.p. 132–133 oC; IR (KBr, cm-1): ν = 1757, 1606; 1H
NMR (500 MHz, CDCl3): δ 8.41 (dd, J1 = 8.0 Hz, J2 = 1.0Hz,
1H), 8.09 (d, J = 8.0 Hz, 1H), 8.01 (d, J = 8.5 Hz, 1H), 7.88–7.84
(m, 1H), 7.64–7.61 (m, 1H), 7.40 (d, J = 2.0 Hz, 1H), 7.34 (dd,
J1 = 8.5 Hz, J2 = 2.0Hz, 1H); 13C NMR (125 MHz, CDCl3): δ
160.6, 151.6, 136.0, 135.1, 134.1, 130.8, 129.2, 125.1, 123.8,
121.7, 121.0, 118.0, 116.8; HRMS (EI) for C13H7ClO2 [M+]:
calcd. 230.0135, found 230.0131.
8.24 (d, J = 8.5 Hz, 1H), 8.01(dd, J1 = 9.5 Hz, J2 = 4.5 Hz, 1H),
7.81 (s, 1H), 7.38 (d, J = 8.0 Hz, 1H), 7.08–7.04 (m, 2H), 2.56
(s, 3H); 13C NMR (125 MHz, CDCl3): δ 163.5 (d, J = 250.0 Hz),
160.8, 152.4 (d, J = 12.5 Hz), 146.2, 134.2, 130.7, 130.0, 124.3
(d, J = 10.0 Hz), 121.7, 118.1, 114.7 (d, J = 2.5 Hz), 112.2 (d, J
= 22.5 Hz), 105.1 (d, J = 25.0 Hz), 22.3; HRMS (EI) for
C14H9FO2 [M+]: calcd. 228.0587, found 228.0584.
4.3.10
3-chloro-9-methyl-6H-benzo[c]chromen-6-one
(2j).
Prepared from 4'-chloro-5-methylbiphenyl-2-carbaldehyde;
o
isolated as white solid (52.9 mg, 72%), m.p. 170–171 C; IR
4.3.4 3-bromo-6H-benzo[c]chromen-6-one (2d). Prepared from
4'-bromobiphenyl-2-carbaldehyde; isolated as white solid (60.3
mg, 73%), m.p. 140–141 oC; IR (KBr, cm-1): ν = 1752, 1612; 1H
NMR (500 MHz, CDCl3): δ 8.41 (d, J = 7.5 Hz, 1H), 8.10 (d, J =
8.0 Hz, 1H), 7.94 (d, J = 8.5 Hz, 1H), 7.86 (t, J = 8.0 Hz, 1H),
7.63 (t, J = 7.5 Hz, 1H), 7.56 (d, J = 1.5 Hz, 1H), 7.49(dd, J1 =
8.0 Hz, J2 = 1.5Hz, 1H); 13C NMR (125 MHz, CDCl3): δ 160.5,
151.6, 135.1, 134.1, 130.8, 129.3, 127.9, 124.0, 123.8, 121.7,
121.1, 121.0, 117.2; HRMS (EI) for C13H7BrO2 [M+]: calcd.
273.9629, found 273.9635.
1
(KBr, cm-1): ν = 1735, 1617; H NMR (500 MHz, CDCl3): δ
8.25 (d, J = 8.5 Hz, 1H), 7.95 (d, J = 8.5 Hz, 1H), 7.83 (s, 1H),
7.40 (d, J = 8.0 Hz, 1H), 7.34 (d, J = 1.0 Hz, 1H), 7.29 (dd, J1 =
8.5 Hz, J2 = 2.0 Hz, 1H), 2.56 (s, 3H); 13C NMR (125 MHz,
CDCl3): δ 160.6, 151.7, 146.2, 135.8, 134.0, 130.7, 130.5, 124.9,
123.7, 121.8, 118.5, 117.9, 116.8, 22.3; HRMS (EI) for
C14H9ClO2 [M+]: calcd. 244.0291, found 244.0295.
4.3.11 3-bromo-9-methyl-6H-benzo[c]chromen-6-one (2k).
Prepared from 4'-bromo-5-methylbiphenyl-2-carbaldehyde;
o
isolated as white solid (60.7 mg, 70%), m.p. 176–178 C; IR
4.3.5 3-(trifluoromethoxy)-6H-benzo[c]chromen-6-one (2e).
Prepared from 4'-(trifluoromethoxy)biphenyl-2-carbaldehyde;
isolated as white solid (68.9 mg, 82%), m.p. 86–87 oC; IR (KBr,
1
(KBr, cm-1): ν = 1741, 1614; H NMR (500 MHz, CDCl3): δ
8.28 (d, J = 8.0 Hz, 1H), 7.91 (d, J = 8.5 Hz, 1H), 7.87 (s, 1H),
7.53 (d, J = 2.0 Hz, 1H), 7.46 (dd, J1 = 8.5 Hz, J2 = 2.0 Hz, 1H),
7.42 (d, J = 8.5 Hz, 1H), 2.58 (s, 3H); 13C NMR (125 MHz,
CDCl3): δ 160.5, 151.8, 146.2, 134.1, 130.8, 130.6, 127.7, 123.9,
1
cm-1): ν = 1724, 1609; H NMR (500 MHz, CDCl3): δ 8.37 (dd,
J1 = 8.0 Hz, J2 = 1.0 Hz, 1H), 8.06 (dd, J1 = 8.5 Hz, J2 = 3.5 Hz,

7
123.6, 121.8, 121.0, 118.7, 117.3, 22.3; HRMS (EI) for
C14H9BrO2 [M+]: calcd. 287.9786, found 287.9790.
133.3, 130.9, 130.1, 124.8, 123.4, 122.8, 122.7, 117.9, 117.4;
ACCEPTED MANUSCRIPT
HRMS (EI) for C13H7ClO2 [M+]: calcd. 230.0135, found
230.0138.
4.3.12 3-(tert-butyl)-9-methyl-6H-benzo[c]chromen-6-one (2l).
Prepared from 4'-tert-butyl-5-methylbiphenyl-2-carbaldehyde;
4.3.18
Prepared
8-chloro-3-fluoro-6H-benzo[c]chromen-6-one
from 4-chloro-4'-fluorobiphenyl-2-carbaldehyde;
(2r).
o
isolated as white solid (45.5 mg, 57%), m.p. 124–126 C; IR
1
o
(KBr, cm-1): ν = 1740, 1611; H NMR (500 MHz, CDCl3): δ
isolated as white solid (60.4 mg, 81%), m.p. 208–210 C; IR
1
8.27 (d, J = 8.0 Hz, 1H), 7.97 (d, J = 8.5 Hz, 1H), 7.87 (s, 1H),
7.38–7.36 (m, 3H), 2.56 (s, 3H), 1.39 (s, 9H); 13C NMR (125
MHz, CDCl3): δ 161.5, 154.6, 151.5, 145.8, 134.9, 130.6, 129.7,
122.3, 121.8, 121.6, 118.7, 115.5, 114.6, 35.0, 31.1, 22.3; HRMS
(EI) for C18H18O2 [M+]: calcd. 266.1307, found 266.1301.
(KBr, cm-1): ν = 1746, 1608; H NMR (500 MHz, CDCl3): δ
8.37 (d, J = 2.0 Hz, 1H), 8.03–8.00 (m, 2H), 7.79 (dd, J1 = 8.5
Hz, J2 = 2.0 Hz, 1H), 7.14–7.10 (m, 2H); 13C NMR (125 MHz,
CDCl3): δ 163.7 (d, J = 250.0 Hz), 159.7, 152.1 (d, J = 12.5 Hz),
135.4, 135.0, 132.8, 130.2, 124.4 (d, J = 10.0 Hz), 123.3, 121.9,
114.0 (d, J = 3.8 Hz), 112.8 (d, J = 22.5 Hz), 105.4 (d, J = 25.0
Hz); HRMS (EI) for C13H6ClFO2 [M+]: calcd. 248.0040, found
248.0037.
4.3.13 9-fluoro-6H-benzo[c]chromen-6-one (2m).5c Prepared
from 5-fluorobiphenyl-2-carbaldehyde; isolated as white solid
o
o
(41.2 mg, 64%), m.p. 159–161 C (lit.5c m.p. 157–159 C); IR
(KBr, cm-1): ν = 1738, 1604; H NMR (500 MHz, CDCl3): δ
4.3.19 8-bromo -6H-benzo[c]chromen-6-one (2s). Prepared from
4-bromobiphenyl-2-carbaldehyde; isolated as white solid (58.6
mg, 71%), m.p. 162–164 oC; IR (KBr, cm-1): ν = 1735, 1598; 1H
NMR (500 MHz, CDCl3): δ 8.56 (d, J = 2.0 Hz, 1H), 8.05 (dd, J1
= 8.0 Hz, J2 = 1.5 Hz, 1H), 7.94 (dd, J1 = 8.5 Hz, J2 = 2.5 Hz,
1H), 7.82–7.78 (m, 1H), 7.55–7.52 (m, 1H), 7.41–7.36 (m, 2H);
13C NMR (125 MHz, CDCl3): δ 159.9, 151.2, 138.0, 133.7,
133.2, 130.9, 124.9, 123.5, 122.81, 122.78, 122.75, 118.0, 117.4;
HRMS (EI) for C13H7BrO2 [M+]: calcd. 273.9629, found
273.9626.
1
8.44 (dd, J1 = 9.0 Hz, J2 = 5.5 Hz, 1H), 7.97 (dd, J1 = 8.0 Hz, J2
= 1.5 Hz, 1H), 7.75 (dd, J1 = 9.5 Hz, J2 = 2.0 Hz, 1H), 7.56–7.52
(m, 1H), 7.40–7.35 (m, 2H),7.30–7.27 (m, 1H); 13C NMR (125
MHz, CDCl3): δ 167.0 (d, J = 255.0 Hz), 160.2, 151.7, 137.8 (d,
J = 10.0 Hz), 134.0 (d, J = 10.0 Hz), 131.3, 124.7, 123.0, 118.0,
117.9 (d, J = 1.3 Hz), 117.4 (d, J = 2.5 Hz), 117.0 (d, J = 22.5
Hz), 108.2 (d, J = 22.5 Hz); GC-MS (EI, 70 eV ): m/z (%) = 214
(100) [M+].
4.3.14 9-chloro-6H-benzo[c]chromen-6-one (2n).5c Prepared
from 5-chlorobiphenyl-2-carbaldehyde; isolated as white solid
4.3.20 8-methoxy -6H-benzo[c]chromen-6-one (2t).8f Prepared
o
o
(52.6 mg, 76%), m.p. 172–174 C (lit.5c m.p. 182–184 C); IR
from 4-methoxybiphenyl-2-carbaldehyde; isolated as white solid
(KBr, cm-1): ν = 1735, 1602; H NMR (500 MHz, CDCl3): δ
(21.0 mg, 31%), m.p. 153–155 C (lit.8f m.p. 149–151 C); IR
1
o
o
1
8.34 (d, J = 8.5 Hz, 1H), 8.08 (d, J = 2.0 Hz, 1H), 8.01 (dd, J1 =
8.0 Hz, J2 = 1.5 Hz, 1H), 7.55–7.51 (m, 2H), 7.39–7.35 (m, 2H);
13C NMR (125 MHz, CDCl3): δ 160.3, 151.7, 141.9, 136.4,
132.3, 131.2, 129.3, 124.8, 122.9, 121.8, 119.7, 118.0, 117.1;
GC-MS (EI, 70 eV ): m/z (%) = 230 (100) [M+].
(KBr, cm-1): ν = 1710, 1613; H NMR (500 MHz, CDCl3): δ
8.07 (d, J = 9.0 Hz, 1H), 8.01 (dd, J1 = 8.0 Hz, J2 = 1.0 Hz, 1H),
7.84 (d, J = 2.5 Hz, 1H), 7.47–7.41 (m, 2H), 7.38 (dd, J1 = 8.0
Hz, J2 = 1.0 Hz, 1H), 7.36–7.33 (m, 1H), 3.96 (s, 3H); 13C NMR
(125 MHz, CDCl3): δ 161.2, 160.2, 150.6, 129.4, 128.2, 124.6,
124.3, 123.5, 122.6, 122.2, 118.3, 117.7, 111.4, 55.8; GC-MS
(EI, 70 eV ): m/z (%) = 226 (38) [M+].
4.3.15 8-fluoro-6H-benzo[c]chromen-6-one (2o). Prepared from
4-fluorobiphenyl-2-carbaldehyde; isolated as white solid (46.9
mg, 73%), m.p. 139–141 oC; IR (KBr, cm-1): ν = 1717, 1608; 1H
NMR (500 MHz, CDCl3): δ 8.13 (dd, J1 = 9.0 Hz, J2 = 5.0 Hz,
1H), 8.05 (d, J = 3.0 Hz, 1H), 8.00 (dd, J1 = 7.5 Hz, J2 = 1.0 Hz,
1H),7.57–7.53 (m, 1H), 7.37 (d, J = 2.0 Hz, 1H), 7.33 (dd, J1 =
8.5 Hz, J2 = 2.0 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ 162.5
(d, J = 248.8 Hz), 160.1 (d, J = 2.5 Hz), 150.9, 131.3 (d, J = 2.5
Hz), 130.4, 124.8, 124.3 (d, J = 7.5 Hz), 123.2 (d, J = 8.8 Hz),
123.0 (d, J = 22.5 Hz), 122.6, 117.9, 117.4, 116.2 (d, J = 22.5
Hz); HRMS (EI) for C13H7FO2 [M+]: calcd. 214.0430, found
214.0428.
4.3.21 8-methoxy-3-(trifluoromethoxy)-6H-benzo[c]chromen-6-
one
(2u).
Prepared
from
4-methoxy-4'-
(trifluoromethoxy)biphenyl-2-carbaldehyde; isolated as white
solid (46.5 mg, 50%), m.p. 90–92 C; IR (KBr, cm-1): ν = 1733,
o
1615; 1H NMR (500 MHz, CDCl3): δ 7.94 (dd, J1 = 8.5 Hz, J2 =
5.0 Hz, 2H), 7.74 (d, J = 3.0 Hz, 1H), 7.38 (dd, J1 = 9.0 Hz, J2 =
3.0 Hz, 1H), 7.18–7.16 (m, 2H), 3.93 (s, 3H); 13C NMR (125
MHz, CDCl3): δ 160.5, 160.3, 150.7, 149.2, 127.0, 124.4,
123.42, 123.39, 122.0, 120.4(d, J = 256.3 Hz), 117.0, 116.9,
111.4, 110.0, 55.8; HRMS (EI) for C15H9F3O4 [M+]: calcd.
310.0453, found 310.0457.
4.3.16
3-chloro-8-fluoro-6H-benzo[c]chromen-6-one
(2p).
Prepared
from 4'-chloro-4-fluorobiphenyl-2-carbaldehyde;
4.3.22 7-fluoro -6H-benzo[c]chromen-6-one (2v). Prepared
o
isolated as white solid (46.2 mg, 62%), m.p. 192–193 C; IR
from 3-fluorobiphenyl-2-carbaldehyde; isolated as white solid
(KBr, cm-1): ν = 1733, 1607; H NMR (500 MHz, CDCl3): δ
(55.9 mg, 87%), m.p. 149–151 C; IR (KBr, cm-1): ν = 1729,
1
o
8.08 (dd, J1 = 8.5 Hz, J2 = 2.5 Hz, 1H), 8.03 (dd, J1 = 8.5 Hz, J2
= 2.5 Hz, 1H), 7.93 (d, J = 8.5 Hz, 1H), 7.59–7.55 (m, 1H), 7.37
(d, J = 2.0 Hz, 1H), 7.33 (dd, J1 = 8.5 Hz, J2 = 2.0 Hz, 1H); 13C
NMR (125 MHz, CDCl3): δ 162.7 (d, J = 250.0 Hz), 159.5 (d, J
= 3.8 Hz), 151.1, 136.0, 130.6 (d, J = 3.8 Hz), 125.3, 124.3 (d, J
= 7.5 Hz), 123.6, 123.3 (d, J = 23.8 Hz), 122.9 (d, J = 7.5 Hz),
118.1, 116.4 (d, J = 23.8 Hz), 116.1; HRMS (EI) for C13H6ClFO2
[M+]: calcd. 248.0040, found 248.0045.
1606; 1H NMR (500 MHz, CDCl3): δ 8.03 (dd, J1 = 8.0 Hz, J2 =
1.5 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.82–7.78 (m, 1H), 7.52–
7.49 (m, 1H), 7.36–7.33 (m, 2H), 7.28–7.25 (m, 1H); 13C NMR
(125 MHz, CDCl3): δ 163.6 (d, J = 266.3 Hz), 156.7 (d, J = 5.0
Hz), 151.6, 137.4, 136.2 (d, J = 11.3 Hz), 131.2, 124.7, 123.3,
117.7, 117.6 (d, J = 5.0 Hz), 117.1 (d, J = 2.5 Hz), 116.4 (d, J =
22.5 Hz), 110.2 (d, J = 6.3 Hz); HRMS (EI) for C13H7FO2 [M+]:
calcd. 214.0430, found 214.0435.
4.3.17 8-chloro-6H-benzo[c]chromen-6-one (2q). Prepared from
4-chlorobiphenyl-2-carbaldehyde; isolated as white solid (49.8
mg, 72%), m.p. 171–172 oC; IR (KBr, cm-1): ν = 1720, 1601; 1H
NMR (500 MHz, CDCl3): δ 8.38 (d, J = 2.0 Hz, 1H), 8.08 (d, J =
8.5 Hz, 1H), 8.03 (dd, J1 = 8.0 Hz, J2 = 1.5 Hz, 1H), 7.79 (dd, J1
= 8.5 Hz, J2 = 2.0 Hz, 1H), 7.54–7.50 (m, 1H), 7.40–7.36 (m,
1H); 13C NMR (125 MHz, CDCl3): δ 160.0, 151.2, 135.2, 135.1,
4.3.23
3-methyl-1-phenylchromeno[4,3-c]pyrazol-4(1H)-one
(4a).24 Prepared from 3-methyl-1,5-diphenyl-1H-pyrazole-4-
carbaldehyde; isolated as brown solid (55.5 mg, 67%), m.p. 222–
o
o
1
224 C (lit.24 226–227 C); IR (KBr, cm-1): ν = 1729, 1621; H
NMR (500 MHz, CDCl3): δ 7.64–7.60 (m, 3H), 7.58–7.54 (m,
2H), 7.46–7.39 (m, 2H), 7.11 (dd, J1 = 8.0 Hz, J2 = 1.5 Hz, 1H),
7.06–7.01 (m, 1H), 2.67 (s, 3H); 13C NMR (125 MHz, CDCl3): δ

8
Tetrahedron
ACCEPTED MANUSCRIPT
o
1
158.0, 153.3, 150.8, 141.7, 139.4, 131.1, 130.2, 129.9, 126.9,
66%), m.p. 195–197 C; IR (KBr, cm-1): ν = 1735, 1609; H
NMR (500 MHz, CDCl3): δ 8.19 (dd, J1 = 8.0 Hz, J2 = 1.5 Hz,
1H), 7.54–7.51 (m, 1H), 7.45–7.41 (m, 4H), 7.39–7.34 (m, 7H);
13C NMR (125 MHz, CDCl3): δ 157.8, 153.0, 149.4, 144.9,
138.9, 136.3, 131.9, 130.7, 129.4, 129.1, 128.8, 125.9, 125.4,
124.5, 122.9, 117.5, 114.7, 106.2; HRMS (EI) for C22H13ClN2O2
[M+]: calcd. 372.0666, found 372.0661.
123.9, 122.5, 118.1, 111.9, 106.4, 12.9; GC-MS (EI, 70 eV ): m/z
(%) = 276 (22) [M+].
4.3.24
7-fluoro-3-methyl-1-phenylchromeno[4,3-c]pyrazol-
4(1H)-one (4b). Prepared from 5-(4-fluorophenyl)-3-methyl-1-
phenyl-1H-pyrazole-4-carbaldehyde; isolated as brown solid
(61.8 mg, 70%), m.p. 224–226 C; IR (KBr, cm-1): ν = 1743,
o
1
1624; H NMR (500 MHz, CDCl3): δ 7.65–7.61 (m, 3H), 7.57–
4.3.30 7-bromo-1,3-diphenylchromeno[4,3-c]pyrazol-4(1H)-one
(4h). Prepared from 5-(4-bromophenyl)-1,3-diphenyl-1H-
pyrazole-4-carbaldehyde; isolated as brown solid (78.9 mg,
7.53 (m, 2H), 7.13 (dd, J1 = 9.0 Hz, J2 = 2.5 Hz, 1H), 7.09 (dd, J1
= 9.0 Hz, J2 = 5.5 Hz, 1H), 6.81–6.76 (m, 1H), 2.67 (s, 3H); 13C
NMR (125 MHz, CDCl3): δ 163.7(d, J = 251.3 Hz), 157.5, 154.6
(d, J = 12.5 Hz), 150.9, 141.2, 139.2, 130.3, 130.0, 126.9, 124.0
(d, J = 12.5 Hz), 111.8 (d, J = 22.5 Hz), 108.6 (d, J = 2.5 Hz),
105.5 (d, J = 21.3 Hz), 105.4; HRMS (EI) for C17H11FN2O2
[M+]: calcd. 294.0805, found 294.0808.
63%), m.p. 200–202 C; IR (KBr, cm-1): ν = 1739, 1590; H
NMR (500 MHz, CDCl3): δ 8.19 (dd, J1 = 7.5 Hz, J2 = 1.5 Hz,
1H), 7.55–7.51 (m, 3H), 7.45–7.41 (m, 4H), 7.38–7.31 (m, 5H);
13C NMR (125 MHz, CDCl3): δ 157.8, 153.0, 149.4, 144.9,
138.8, 132.0, 131.8, 130.7, 129.4, 129.1, 125.9, 125.9, 124.7,
124.5, 122.9, 117.5, 114.6, 106.2; HRMS (EI) for
C22H113BrN2O2 [M+]: calcd. 416.0160, found 416.0155.
o
1
4.3.25
7-chloro-3-methyl-1-phenylchromeno[4,3-c]pyrazol-
4(1H)-one (4c). Prepared from 5-(4-chlorophenyl)-3-methyl-1-
phenyl-1H-pyrazole-4-carbaldehyde; isolated as brown solid
4.3.31 9-chloro-1,3-diphenylchromeno[4,3-c]pyrazol-4(1H)-one
(4i). Prepared from 5-(2-chlorophenyl)-1,3-diphenyl-1H-
pyrazole-4-carbaldehyde; isolated as brown solid (55.9 mg,
(67.1 mg, 72%), m.p. 170–172 C; IR (KBr, cm-1): ν = 1745,
o
1
1621; H NMR (500 MHz, CDCl3): δ 7.64–7.61(m, 3H), 7.55–
o
1
7.53 (m, 2H), 7.38 (s, 1H), 7.01 (d, J = 2.0 Hz, 2H), 2.66 (s, 3H);
13C NMR (125 MHz, CDCl3): δ 157.2, 153.5, 150.9, 140.9,
139.1, 136.8, 130.3, 123.0, 126.8, 124.4, 123.2, 118.2, 110.4,
106.0, 12.8; HRMS (EI) for C17H11ClN2O2 [M+]: calcd.
310.0509, found 310.0505.
50%), m.p. 172–173 C; IR (KBr, cm-1): ν = 1746, 1610; H
NMR (500 MHz, CDCl3): δ 8.22 (dd, J1 = 7.5 Hz, J2 = 1.5Hz,
1H, ),7.53–7.50 (m, 1H), 7.48–7.44 (m, 1H),7.43–7.34 (m, 10H);
13C NMR (125 MHz, CDCl3): δ 157.2, 153.1, 149.1, 142.9,
138.9, 134.21, 132.1, 131.5, 130.6, 130.0, 129.1, 128.8, 127.2,
126.9, 124.8, 124.4, 122.8, 117.5, 114.7, 107.8; HRMS (EI) for
C22H13ClN2O2 [M+]: calcd. 372.0666, found 372.0669.
4.3.26 7-(tert-butyl)-3-methyl-1-phenylchromeno[4,3-c]pyrazol-
4(1H)-one (4d). Prepared from 5-(4-tert-butylphenyl)-3-methyl-
1-phenyl-1H-pyrazole-4-carbaldehyde; isolated as brown solid
4.3.32 9-bromo-1,3-diphenylchromeno[4,3-c]pyrazol-4(1H)-one
(4j). Prepared from 5-(2-bromophenyl)-1,3-diphenyl-1H-
pyrazole-4-carbaldehyde; isolated as brown solid (56.3 mg,
(54.8 mg, 55%), m.p. 210–212 C; IR (KBr, cm-1): ν = 1734,
o
1
1622; H NMR (500 MHz, CDCl3): δ 7.62–7.58 (m, 3H), 7.57–
o
1
7.53 (m, 2H), 7.44 (d, J = 2.0 Hz, 1H), 7.09 (dd, J1 =8.5 Hz, J2 =
1.5 Hz, 1H), 7.04 (d, J = 8.5 Hz, 1H), 2.67 (s, 3H), 1.30 (s, 9H);
13C NMR (125 MHz, CDCl3): δ 158.2, 155.4, 153.4, 150.7,
141.9, 139.4, 130.0, 129.8, 126.8, 122.0, 121.4, 114.7, 109.1,
106.0, 35.1, 30.9, 12.8; HRMS (EI) for C21H20N2O2 [M+]: calcd.
332.1525, found 332.1529.
45%), m.p. 198–199 C; IR (KBr, cm-1): ν = 1735, 1609; H
NMR (500 MHz, CDCl3): δ 8.22 (dd, J1 = 7.5 Hz, J2 = 1.5 Hz,
1H, ), 7.66 (d, J = 8.0 Hz,1H), 7.54–7.50 (m, 1H), 7.43–7.34 (m,
10H); 13C NMR (125 MHz, CDCl3): δ 157.2, 153.1, 149.0,
144.4, 138.9, 133.2, 132.1, 131.6, 130.6, 129.4, 129.1, 128.8,
127.5, 125.0, 124.5, 124.0, 122.9, 117.6, 114.8, 107.8; HRMS
(EI) for C22H13BrN2O2 [M+]: calcd. 416.0160, found 416.0167.
4.3.27
9-chloro-3-methyl-1-phenylchromeno[4,3-c]pyrazol-
4(1H)-one (4e). Prepared from 5-(2-chlorophenyl)-3-methyl-1-
phenyl-1H-pyrazole-4-carbaldehyde; isolated as brown solid
4.3.33
c]pyrazol-4(2H)-one (4k) and 7-bromo -3-(4’-chlorophenyl)-1-
phenylchromeno[4,3-c]pyrazol-4(1H)-one (4k') (4k:4k'
3-(4’-bromophenyl)-7-chloro-2-phenylchromeno[4,3-
o
(55.9 mg, 60%), m.p. 108–110 C; IR (KBr, cm-1): ν = 1795,
=
1676; 1H NMR (500 MHz, CDCl3): δ 7.44 (dd, J1 = 8.0 Hz, J2 =
0.5 Hz, 1H), 7.41–7.36 (m, 1H), 7.32–7.29 (m, 3H), 7.27–7.23
(m, 3H), 2.64 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 154.6,
153.6, 152.0, 145.7, 138.5, 134.2, 131.6, 131.3, 129.8, 129.0,
128.5, 128.3, 126.8, 124.7, 108.2, 107.7, 13.9; HRMS (EI) for
C17H11ClN2O2 [M+]: calcd. 310.0509, found 310.0512.
1:0.94). Prepared from 5-(4-bromophenyl)-1,3-diphenyl-1H-
pyrazole-4-carbaldehyde; isolated as Brown solid (85.4 mg,
1
63%); IR (KBr, cm-1): ν = 1743, 1612; H NMR (500 MHz,
CDCl3): δ 8.19 (d, J = 8.5 Hz, 2H, 4k), 8.11 (d, J = 8.5 Hz,
0.94H, 4k'), 7.69–7.60 (m, 6H, 4k), 7.53 (d, J = 8.5 Hz, 1.88H,
4k'), 7.48–7.42 (m, 5.82H, 3H for 4k, 2.82H for 4k'), 7.36–7.30
(m, 4.76H, 1H for 4k, 3.76H for 4k'), 7.19 (dd, J1 = 8.5 Hz, J2 =
2.0 Hz, 0.94H, 4k'), 6.92 (d, J = 8.5 Hz, 0.94H, 4k'); 13C NMR
(125 MHz, CDCl3): δ 157.1, 156.6, 153.3, 153.2, 151.6, 148.6,
145.1, 142.3, 139.2, 138.7, 136.2, 135.7, 132.0, 131.8, 130.8,
130.5, 130.2, 129.5, 129.2, 128.9, 128.6, 127.4, 127.0, 125.8,
125.6, 125.1, 125.0, 124.9, 123.8, 123.4, 121.1, 117.8, 113.3,
110.4, 105.8, 104.7; HRMS (EI) for C22H12BrClN2O2 [M+]:
calcd. 449.9771, found 449.9775.
4.3.28 1,3-diphenylchromeno[4,3-c]pyrazol-4(1H)-one (4f) and
2,3-diphenylchromeno[4,3-c] pyrazol -4(2H)-one (4f’) (4f:4f'=
1:0.41).
Prepared
from
1,3,5-triphenyl-1H-pyrazole-4-
carbaldehyde; isolated as brown solid (62.9 mg, 62%); IR (KBr,
cm-1): ν = 1736, 1609; 1H NMR (500 MHz, CDCl3): δ 8.23–8.20
(m, 2H, 4f), 7.69–7.63 (m, 3.64H, 2H for 4f; 1.64H for 4f'),
7.54–7.34 (m, 12.69H, 9H for 4f, 3.69H for 4f'), 7.11–7.04 (m,
1.41H, 1H for 4f, 0.41H for 4f'); 13C NMR (125 MHz, CDCl3): δ
157.8, 157.3, 153.2, 153.1, 152.6, 149.2, 146.2, 142.8, 139.6,
139.1, 131.2, 130.60, 130.57, 130.5, 130.4, 130.01, 129.95,
129.4, 129.24, 129.17, 128.9, 128.4, 128.3, 127.1, 127.0, 125.9,
124.4, 123.9, 122.8, 122.5, 117.9, 117.4, 114.8, 111.6, 106.1,
104.9; HRMS (EI) for C22H14N2O2 [M+]: calcd. 338.1055, found
338.1051.
4.4 Synthesis of 2'-hydroxy-(1,1'-biphenyl)-2-carboxylic acid
5
2a (58.8 mg, 0.3 mmol) and MeCN (3 mL) was added to a
flask (10 mL), then NaOH aqueous solution (5% (W/W), 2 mL)
was dropped. After stired for 3 h at room temperature, the
reaction mixture was wished with CH2Cl2 (3×5 mL ) and filtered
through Celite. After evaporation of the solvent under vacuum,
the residue was purified by column chromatography on silica gel
4.3.29 7-chloro-1,3-diphenylchromeno[4,3-c]pyrazol-4(1H)-one
(4g). Prepared from 5-(4-chlorophenyl)-1,3-diphenyl-1H-
pyrazole-4-carbaldehyde; isolated as brown solid (73.8 mg,

9
(100-200 mesh) using petroleum ether-EtOAc (10/1, V/V) as
eluent to give pure 5.
was purified by column chromatography (hexane/EtOAc =
ACCEPTED MANUSCRIPT
95:5 (V/V) to provide the corresponding methyl esters as pale
yellow oils.
4.4.1
2'-hydroxy-(1,1'-biphenyl)-2-carboxylic
acid
(5).25
A NaOH aqueous solution (7 mL, 1 M) was added to a
stirring mixture of the desired ester (1.8 mmol) in MeOH (7 mL)
under Ar atmosphere. The reaction mixture was heated to 50 ºC
for 12 h. Upon completion, the reaction mixture was
concentrated under reduced pressure. The residue was quenched
with 6 M HCl until pH < 3 and was extracted with EtOAc (3×10
mL). The combined layers were washed with brine (1×5 mL),
dried over anhydrous MgSO4, filtered and concentrated under
reduced pressure to afford the desired pure biaryl 2-carboxylic
acids 8
Prepared from 6H-benzo[c]chromen-6-one; isolated as white
solid (63.0 mg, 98%), m.p. 90–91 oC (lit.25 93 oC); 1H NMR (500
MHz, CDCl3): δ 8.41 (d, J = 7.5 Hz, 1H), 8.13 (d, J = 8.0 Hz,
1H), 8.07 (d, J = 8.0 Hz, 1H), 7.84 (t, J = 7.5 Hz, 1H), 7.60 (t, J
= 7.0 Hz, 1H), 7.49 (t, J = 8.0 Hz, 1H), 7.39–7.34 (m, 2H); 13C
NMR (125 MHz, CDCl3): δ 161.2, 151.3, 134.82, 134.77, 130.6,
130.4, 128.9, 124.5, 122.8, 121.7, 121.3, 118.1, 117.8.
4.5 Synthesis of 6H-benzo[c]chromen 6
2a (58.8 mg, 0.3 mmol), NaBH4 (17.1 mg, 0.45 mmol) and
EtOH (3 mL) was added to a flask (10 mL) and stired for 6 h at
room temperature. The reaction mixture was wished with CH2Cl2
(3×5 mL ) and filtered through Celite. After evaporation of the
solvent under vacuum, the residue was purified by column
chromatography on silica gel (100-200 mesh) using petroleum
ether-EtOAc (10/1, V/V) as eluent to give pure 6.
4.7.1.1 (1,1'-biphenyl)-2-carboxylic acid (8). Prepared from
methyl biphenyl-2-carboxylate6; isolated as Pink solid; 1H NMR
(500 MHz, CDCl3): δ 11.39 (s, 1H), 7.97 (d, J = 7.5 Hz, 1H),
7.61–7.57 (m, 2H), 7.36–7.36 (m, 7H); 13C NMR (125 MHz,
CDCl3): δ 173.4, 143.4, 141.0, 132.1, 131.2, 130.7, 129.3, 128.5,
128.1, 127.4, 127.2.
4.7.2
Subjection of 8 to the standard reaction conditions
4.5.1 6H-benzo[c]chromen (6). Prepared from 6H-
benzo[c]chromen-6-one; isolated as white solid (50.3 mg, 92%),
8 (0.3 mmol), Cu(0) powder (1.92 mg, 10 mol %), Selectfluor
(212.6 mg, 0.6 mmol), K2CO3 (82.8 mg, 0.6 mmol) and CH3CN
(3 mL) were added to a 10-mL flask. Then the reaction mixture
was stirred at 25 ºC for 24 h. Upon completion, the resulting
mixture was diluted with CH2Cl2 (10 mL) and filtered through
Celite. After evaporation of the solvent under vacuum, the
residue was purified by column chromatography on silica gel
(100-200 mesh) using petroleum ether-EtOAc (20/1, V/V) as
eluent to give pure 2a (55.9 mg, 95%).
o
1
m.p. 130–132 C; H NMR (500 MHz, CDCl3): δ 7.52–7.50 (m,
1H), 7.42–7.40 (m, 2H), 7.29–7.26 (m, 2H), 7.12 (dd, J1 = 7.5
Hz, J2 = 1.5 Hz, 1H), 7.02–6.99 (m, 1H), 6.95 (d, J = 8.5 Hz,
1H), 4.48–4.42 (m, 2H); 13C NMR (125 MHz, CDCl3): δ 152.9,
138.9, 136.5, 130.9, 130.8, 129.4, 129.3, 128.6, 128.5, 127.8,
120.8, 116.4, 63.7.
4.6 Synthesis of 6-phenyl-6H-benzo[c]chromen-6-ol 7
Under an atmosphere of Ar gas, 2a (58.8 mg, 0.3 mmol) and
THF (3 mL) was added to a flask (10 mL), then PhMgBr (0.4
mL) was dropped. After stired for 3 h at room temperature, the
reaction mixture was quenched with saturated ammonium
chloride solution and diluted with CH2Cl2 (3×5 mL) and filtered
through Celite. After evaporation of the solvent under vacuum,
the residue was purified by column chromatography on silica gel
(100-200 mesh) using petroleum ether-EtOAc (6/1, V/V) as
eluent to give pure 7.
4.7.3
Reaction of 1a in CH3CN-H2O18 (200:1, V/V)
1a (0.3 mmol), Cu(0) powder (1.92 mg, 10 mol %),
Selectfluor (212.6 mg, 0.6 mmol), K2CO3 (82.8 mg, 0.6 mmol)
and CH3CN:H2O18 = 200:1 (V/V, 3 mL) were added to a 10-mL
flask. Then the reaction mixture was stirred at 25 ºC for 24 h.
Upon completion, the resulting mixture was sampled for GC-MS
analysis (see Figure S1).
4.7.4
Reaction of 1a under the standard reaction
4.6.1 6-phenyl-6H-benzo[c]chromen-6-ol (7). Prepared from 6H-
benzo[c]chromen-6-one; isolated as white solid (77.4 mg, 94%),
conditions except in the presence of 18O2 atmosphere
o
1
m.p. 81–83 C; H NMR (500 MHz, CDCl3): δ 8.01–7.98 (m,
2H), 7.63 (s, 1H), 7.55–7.52 (m, 2H), 7.48–7.44 (m, 1H), 7.42–
7.37 (m, 3H), 7.32–7.27 (m, 2H), 7.12–7.09 (m, 1H), 7.04 (dd, J1
= 8.0 Hz, J2 = 1.0 Hz, 1H), 6.92 (dd, J1 = 8.0 Hz, J2 = 1.0 Hz,
1H); 13C NMR (125 MHz, CDCl3): δ 151.3, 143.0, 135.4, 129.4,
128.7, 128.5, 128.1, 127.7, 127.5, 126.8, 126.3, 123.1, 123.0,
121.7, 121.1, 117.8, 99.2.
1a (0.3 mmol), Cu(0) powder (1.92 mg, 10 mol %),
Selectfluor (212.6 mg, 0.6 mmol), K2CO3 (82.8 mg, 0.6 mmol)
and CH3CN:H2O = 200:1 (V/V, 3 mL) were added to a 10-mL
flask. The flask was opened to the vacuum, pumped for 2-3
minutes and backfilled with 18O2 gas using a balloon. Then the
reaction mixture was stirred at 25 ºC for 24 h. Upon completion,
the resulting mixture was sampled for GC-MS analysis (see
Figure S2).
4.7 Mechanistic Studies
4.7.5
Reaction of 1a under the standard reaction
conditions except in the presence of 18O2 atmosphere
and H2O18
4.7.1
Preparation of (1,1'-biphenyl)-2-carboxylic acid 8
8
was synthesized according to reported literature.8k
Procedure: To a solution of phenylboronic acid (2.1 mmol) in
dry THF (4.5 mL) was added a prepared suspension of
PdCl2(PPh3)2 in dry THF (0.5 mL, 0.1 M). The suspension was
stirred and a Na2CO3 aqueous solution (5 mL, 0.8 M) was added.
The reaction mixture was stirred under Ar atmosphere for 2 min.
at room temperature. Finally, methyl 2-iodobenzoate (294 ꢀL, 2
mmol) was added and the reaction mixture was heated at 80 ºC
for 12 h under Ar atmosphere. The resultant mixture was
extracted with EtOAc (3×10 mL). The combined layers were
washed with brine (1×5 mL), dried over anhydrous MgSO4,
filtered and concentrated under reduced pressure. The residue
1a (0.3 mmol), Cu(0) powder (1.92 mg, 10 mol %),
Selectfluor (212.6 mg, 0.6 mmol), K2CO3 (82.8 mg, 0.6 mmol)
and CH3CN:H2O18 = 200:1 (V/V, 3 mL) were added to a 10-mL
flask. The flask was opened to the vacuum, pumped for 2-3
minutes and backfilled with 18O2 gas using a balloon. Then the
reaction mixture was stirred at 25 ºC for 24 h. Upon completion,
the resulting mixture was sampled for GC-MS analysis. It has
been found that the two 18O-incorporated product 2a-(O18)2 (m/z
= 200) was not detected.

10
Tetrahedron
ACCEPTED MANUSCRIPT
4.7.6
Reaction of 1a under the standard reaction
conditions except under an argon atmosphere
Supplementary Material
Supplementary data (charts for mechanistic studies as well as
copies of 1H & 13C NMR spectra of the compounds) associated
with this article can be found in the online version, at http://.
1a (0.3 mmol), Cu(0) powder (1.92 mg, 10 mol %),
Selectfluor (212.6 mg, 0.6 mmol), K2CO3 (82.8 mg, 0.6 mmol)
and CH3CN:H2O = 200:1 (V/V, 3 mL) were added to a 10-mL
flask equipped with a high-vacuum PTFE valve-to-glass seal.
Then the resultant mixture in the sealed tube was frozen by
immersion of the flask in liquid N2. When solvent was
completely frozen, the flask was opened to the vacuum (high
vacuum) and pumped for 2-3 minutes, with the flask still
immersed in liquid N2. The flask was then closed and warmed
until solvent completely melted. This process was repeated three
times and after the last cycle the flask was backfilled with an
inert Ar gas. Then the reaction mixture was stirred at 25 ºC for
24 h. Upon completion, the resulting mixture was diluted with
CH2Cl2 (10 mL) and filtered through Celite. After evaporation of
the solvent under vacuum, the residue was purified by column
chromatography on silica gel (100-200 mesh) using petroleum
ether-EtOAc (20/1, V/V) as eluent to give pure 2a (21.2 mg,
36%).
References and notes
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4.7.7
Reaction of 1a under the standard reaction
conditions except using dried CH3CN
The procedure is similar to the one described in 4.3 except
using a dried CH3CN. The reaction gave pure 2a in 69% yield
(40.6 mg).
4.7.8
Reaction of 1a under the standard reaction
conditions except using HOCuF as a catalyst
1a (0.3 mmol), HOCuF (10 mol %, prepared according to our
previous work11a), Selectfluor (212.6 mg, 0.6 mmol), K2CO3
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1
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We are grateful to the Natural Science Foundation of China
(No. 21172197 and 21372201) and Zhejiang Province (Grant No.
Y407168), the Foundation of Education of Zhejiang Province
(Grant No. Z200803599) and the Opening Foundation of
Zhejiang Provincial Top Key Discipline for financial support.

11
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