Nickel-Catalyzed Decarbonyloxidation of 3-Aryl Benzofuran-2(3H)-ones to 2-Hydroxybenzophenones

Article abstract of DOI:10.1021/acs.joc.0c00858

We have developed a protocol to facilitate the nickel-catalyzed decarbonyloxidation of 3-aryl benzofuran-2(3H)-ones to 2-hydroxybenzophenones under mild conditions, which is an efficient approach for the decarbonyloxidation of lactones in organic synthesis. A diverse range of substrates can undergo C(O)-O/C(O)-C bond cleavage to generate the target products in good yields. These 2-hydroxybenzophenones can be converted into a variety of compounds via reactions such as esterification, cyclization, and reduction.

Full text of DOI:10.1021/acs.joc.0c00858

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Article
Nickel-Catalyzed Decarbonyloxidation of 3-Aryl
Benzofuran-2(3H)-ones to 2-Hydroxybenzophenones
Zhou Tong, Zhi Tang, Chak-Tong Au, and Renhua Qiu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c00858 • Publication Date (Web): 02 Jun 2020
Downloaded from pubs.acs.org on June 2, 2020
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The Journal of Organic Chemistry
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Nickel-Catalyzed Decarbonyloxidation of 3-Aryl Benzofuran-2(3H)-
ones to 2-Hydroxybenzophenones
Zhou Tong,† Zhi Tang,† Chak-Tong Au, ‡ Renhua Qiu*,†
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†
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan
University, Changsha, 410082, P. R. China
‡
College of Chemistry and Chemical Engineering, Hunan Institute of Engineering, Xiangtan, 411100, P.R. China
Supporting Information Placeholder
NiCl2 (10mol%)
Nickel catalysis
OH O
Na2CO3 (2.0 eq)
TBHP (2.0 eq)
O
Mild temperature
Yield up to 99%
23 examples
O
R
Ar
R
Toluene, 80oC
Ar
ABSTRACT: We have developed a protocol to facilitate the nickel-catalyzed decarbonyloxidation of 3-aryl benzofuran-2(3H)-
ones to 2-hydroxybenzophenones under mild conditions, which is an efficient approach for the decarbonyloxidation of lactones in
organic synthesis. A diverse range of substrates can undergo C(O)−O/C(O)−C bond cleavage to generate the target products in
good yields. These 2-hydroxybenzophenones can be converted into a variety of compounds via reactions such as esterification,
cyclization, and reduction.
INTRODUCTION
Tsuji−Wilkinson reaction that first disclosed as a rhodium-mediated
reaction of aldehyde conversion to its parent alkane (Scheme 1a). 6 The
extension of this decarbonylation reaction to carboxyl and ketone substrates
has attracted much attention.7–11 The decarboxylation of aromatic acid under
harsh conditions (Scheme 1b) was developed by the Shepard,12 Nilsson,13
Cohen,14,15 Sheppard,16 and Schleyer17 groups. In 1982, Schleyer
successfully achieved decarboxylation with a nickel (180 °C) and palladium
(330 °C) catalyst under a H2 atmosphere.17 As for the decarbonylation of
ketones (Scheme 1c), Murakami et al. first reported such work in 1994 on
strained and unstrained cyclic aliphatic ketones using RhCl(PPh3)3 as
catalyst.18 Afterward, many decarboxylation coupling reactions were
reported.19 For example, Lundgren conducted decarboxylative carbonyl α-
arylation by coupling arylboron nucleophiles with malonic acid derivatives.
As for the catalytic decarbonylation of unstrained ketones, such as 1,2- and
1,3-diketones,20 alkynyl ketones21 and ketones bearing a directing group, it
was achieved with Rh catalysts. In 2017, Chatani et al. reported the first
nickel system capable of mediating the decarbonylation of simple diaryl
ketone.22
Owing to their high reactivity, 2-hydroxybenzophenones are important
building blocks in organic synthesis for medicinal chemicals.1 The
derivatives with 2-hydroxybenzophenone skeleton exhibit a variety of
biological activities. For example, 4-phenylchromenone is a building block
for calcium channel blockers (a),1c anti-influenza drug (b),1d anti-HAV drug
(c),1e and antispasmodic agents (d) (Figure 1).1f
O
O
(a)
(b)
(c)
(d)
O
O
S
S
O
O
HO
N
O
N
N
O
Anti-HAV Drug
O
O
HN
O
Calcium Channel Blockers
Anti-Influenza Drug
Antispasmodic Agents
Br
Figure 1. Bioactive 2-hydroxybenzophenone derivatives
To fulfill the increasing requirement of 2-hydroxybenzophenones in
organic synthesis and biological research, a number of valuable synthetic
routes were developed (Scheme S1). The classical, efficient and reliable
approach for the synthesis of 2-hydroxybenzophenones relies on the Fries
rearrangement of phenyl ester.2 Transition-metal-catalyzed synthesis of 2-
hydroxybenzophenones is also disclosed with a few examples. For instance,
the Pd-catalyzed ortho-C-H hydroxylation of benzophenones is an efficient
method.3 However, the yield was moderate and bromide substrates was not
compatible in this systems. Another route is the Rh-catalyzed oxidative
coupling of salicylaldehyde with arylboronic acid,4a,4b but a noble metal
catalyst was required. The third route is Rh–Cu catalyzed C ≡ C bond
cleavage reaction of alkynes with N-phenoxyacetamides,4c but only limited
examples are available for the synthesis of 2-hydroxybenzophenones with
electron-withdrawing groups. Therefore, developing a new protocol to
afford 2-hydroxybenzophenones is still valuable.
Scheme 1. Decarbonylation of carbonyl compounds
Previous work
a) Aldehyde (well developed)
c) Ketone (well developed)
[Rh or Ni]
O
O
Rh,Ru,Ir,Pd
RH
+
CO
RR'
+
CO
R
H
R
R'
d) Lactone (only two examples, with low yields)
b) Carboxylic acid (well developed)
R
hv
O
heat
+
CO2
RH
+
CO2
Ph
R
O
R
OH
O
Ph
This work
e) Decarbonyl oxidation of benzofuranone
OH
O
O
Ni cat.
O
R
Ar
TBHP
R
Ar
The cleavage of carbon–carbon (C-C) bond reaction is one of the most
important bond transformations in organic synthesis,5 especially the
decarbonylation, which has been recognized as a reliable synthetic method
to diversified organic products. The decarbonylation is known as the
Unlike the decarboxylation of aldehydes, carboxylic acids, and ketones,
there are only two examples till now for the decarboxylation of lactones
(Scheme 1d). In 1969, Richard reported the first decarboxylation reaction
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of α, γ-butyrolactone through photocatalysis.23 Unfortunately, the yield of
be noted that the effect of fluoride on the reaction is well tolerated, while in
the case of Pd-catalytic system, the yield was much lower.3
this method is very low (<11%). In 1971, Richard reported the
decarboxylation reaction of a different γ-butyrolactone, but the yield is still
not high (<51%).24 Therefore, despite the great progresses of extending the
decarbonylation reaction to carboxyl substrates, the decarbonylation of
lactones remains a big challenge.
1
2
3
Scheme 2. Investigation of benzo-ring scopea
NiCl2 (10 mol %)
O
4
5
6
7
8
9
OH
O
Na2CO3 (2.0 eq.)
O
R1
Recently, we developed an efficient method for the synthesis of 3-aryl
benzofuran-2(3H)-ones.25a Herein, we demonstrate the use of these
compounds as useful precursors for efficient synthesis of 2-
hydroxybenzophenones via nickel-catalyzed decarbonyloxidation of
lactones (Scheme 1e). The method uses cheap nickel as catalyst and the
reaction condition is mild. The protocol shows a broad substrate scope and
gram-scalable ability. It is noted that the target products can be converted
into a variety of compounds via esterification, cyclization, and reduction,
etc., which are bioactive skeletons. Finally, a possible mechanism is
proposed based on the control experiment.
TBHP (2.0 eq.)
R1
Toluene, 80 °C
1
2
OH
O
OH O
OH
O
OH
O
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2c
, 94%
O
2d
, 74%
O
2b
2e, 42%
, 99%
O
OH
OH
OH
O
OH
RESULTS AND DISCUSSION
Initially, we explored the nickel catalyzed reactions using 4-
methylbenzofuranone 1a as substrate under different reaction conditions
(Table 1). Four oxidants, AgBr, K2S2O8, PhI(OAc)2 and t-
butylhydroperoxide (TBHP, 70wt.% in H2O) were screened at the
conditions of 10 mol% of NiCl2, 2.0 eq. of base Na2CO3 in toluene solution
at 80 °C (entries 1−4). Among them, only TBHP gives the target product 2-
hydroxybenzophenone (2a) in over 99% yield (entry 4). The adoption of
other temperatures, solvents, bases and Ni catalysts would result in lower
yields (entries 5−14). It should be noted that the yield of 2a at 25 °C is 74%,
and the use of Ni(cod)2 instead can also give 2a in 91% yield. Also, it was
observed that the presence of NiCl2, base and TBHP is important in the
reaction system (entries 15−19).
2i
, 78%
O
2h
, 92%
O
2g
, 99%
O
2f
, 99%
O
OH
OH
OH
OH
O
Cl
2m,
83%
2l
2k,
, 73%
2j
82%
, 99%
F
a3-Aryl benzofuran-2(3H)-ones 1 (0.2 mmol), NiCl2 (10 mol%), Na2CO3
(2.0 eq.), TBHP (2.0 eq.), toluene (1.0 mL), under air condition, sealed tube,
isolated yield of 2.
The protocol also exhibits a high level of tolerance toward substrates
bearing para-position and ortho-position substituent on the 4-phenyl ring
(Scheme 3). First, the decarbonyloxidation was carried out using ortho-
chlrine (2n) and para-chlorine (2o) substrates, which resulted in
satisfactory yields. Then we used para-bromo substrate in the 4-phenyl ring
and the yield was up to 98%. We screened substrates with different groups
on the benzene ring as well as those with halogen-containing 4-benzene ring,
and found that the yields of the corresponding products (2q–2s) were 90–
99%. As for 2t with ortho-methyl group, the yield was low, possibly due to
steric effect. The substrates with electron-withdrawing groups (-CF3, -CN)
were also accommodated (2u–2v). The lower yield of cyano substrate can
be attributed to the effect of cyano group on nickel coordination. Overall,
the adaptability of the reaction system to functional groups is good, and
electron-withdrawing groups do not have significant inhibitory effect on the
reaction. It should be noted that 5,7-di-tert-butyl-3-(3,4-dimethylphenyl)-
benzofuran-2(3H)-one (1w, Antioxidant HP-136) with various groups on
the benzene ring successfully undergoes decarbonyloxidation, illustrating
that the method is suitable for multi-functionalized steric substrates. And 7-
Cyclohexyl-[1,3]dioxolo[4,5-f]benzofuran-6(7H)-one (1x) can get the
corresponding product (2x) in lower to 22% yield, due to the in-stable alkyl
intermediate.
Table 1. Survey on condition for 2a formationa
O
OH
O
O
Ni Cat. (10mol%)
Base, oxidant
solvent
temp., Time
2a
1a
temp
yieldb
(%)
base
(2.0 eq.)
oxidant
(2.0 eq.)
Ni
(mol%)
℃
)
solvent
(
Entry
1
2
3
NiCl2 (10)
NiCl2 (10)
NiCl2 (10)
Na2CO3
Na2CO3
Na2CO3
AgBr
toluene
toluene
toluene
80
80
80
0
0
0
K2S2O8
PhI(OAc)2
4
5
6
NiCl2 (10)
NiCl2 (10)
NiCl2 (10)
Na2CO3
Na2CO3
Na2CO3
TBHP
TBHP
TBHP
toluene
toluene
toluene
80
70
60
99%
＞
89%
86%
74%
46%
98%
99%
97%
88%
89%
91%
0
7
NiCl2 (10)
NiCl2 (10)
NiCl2 (10)
NiCl2 (10)
NiCl2 (10)
Na2CO3
Na2CO3
Na2CO3
K2CO3
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
-
toluene
DMF
25
80
80
80
80
80
80
80
80
80
8
9
THF
10
11
12
13
14
15
16
toluene
toluene
toluene
toluene
toluene
toluene
toluene
Cs2CO3
Scheme 3. Investigation of 4-Substituents scopea
Ni(OTf)2 (10) Na2CO3
Ni(acac)2 (10) Na2CO3
NiCl2 (10 mol %)
O
OH
O
Ni(cod)2(10)
NiCl2 (10)
NiCl2 (10)
Na2CO3
Na2CO3
-
Na2CO3 (2.0 eq.)
TBHP (2.0 eq.)
O
R2
R3
R3
R2
Toluene, 80 °C
TBHP
68%
1
2
17
18
19
-
-
-
Na2CO3
Na2CO3
Na2CO3
TBHP
TBHP
TBHP
toluene
toluene
toluene
80
120
140
10%
24%
30%
OH
O
OH O
OH
O
Cl
OH
O
Cl
aReaction conditions: Benzofuranone 1a (0.2 mmol), Ni source (mol% as
indicated), base (0.4 mmol), oxidant (0.4 mmol), and solvent (1.0 mL) were
stirred at a specified reaction temperature for 12 h under air. bIsolated yield.
Cl
Cl
2n, 99%
2o, 71%
2p, 80%
2q, 90%
OH
O
OH
O
OH
O
OH
O
Having optimized the reaction conditions, we proceeded to explore the
scope of this nickel-catalyzed decarbonyloxidation protocol using
benzofuranones with different functional groups in the phenyl ring. As
displayed in Scheme 2, a variety of benzofuranones were smoothly
transformed into the corresponding phenol products with moderate to
excellent yields. The results revealed that electron-donating substituents
such as 4-ethyl (2c), 2,4-dimethyl (2d), 3,5-dimethyl (2e), 4-isopropyl(2f),
4-tertbutyl (2g), 3-tertbutyl(2h), 2-tertbutyl(2i), 4-phenyl group (2j) and 4-
methoxy (2k) are well tolerated. The reason for the low yield of 2e (30%)
is that 1e produces a by-product 2e’ (35%, see SI) through the condensation
of benzofuranone with tert-butyl peroxide. Substrates with chlorine (2l,
73%) and fluorine (2m, 83%) at the para-position of phenyl ring were
explored and found to furnish the desired products in good yields. It should
Br
O
Br
Br
CF3
2s, 99%
2r, 98%
2u
, 82%
2t, 30%
OH
O
OH
O
OH
O
O
CN
2v, 50%
2w
2x
,22%
, 80%
a3-Aryl benzofuran-2(3H)-ones 1 (0.2 mmol), NiCl2 (10 mol%), Na2CO3
(2.0 eq.), TBHP (2.0 eq.), toluene (1.0 mL), under air condition, sealed tube,
isolated yield of 2.
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The Journal of Organic Chemistry
To demonstrate the synthetic utility of this decarbonyl oxidation reaction,
variety of biologically important oxygen-containing heterocyclic
2e’ cannot be converted to 2e in the presence of NiCl2 and/or TBHP, the
involvement of 2a’ as an intermediate can be discarded in the mechanism
(Scheme 6c). With a proper nickel catalyst, the yield of 2a could be up to
99%, indicating the importance of a nickel catalyst. To exclude the
possibility that CO2 might be generated from the base Na2CO3, we changed
the base to NaOAc and CO2 was still observed by GC analysis (Scheme 6d);
the phenomenon indicates the action of decarbonyloxidation in the reaction
mechanism. To clarify whether the reaction process is first hydrolyzed or
not, 1a was hydrolyzed with NaOH (Scheme 6e) to 1aa in 55% yield
(Scheme 6e),26e but 1aa cannot be converted to 2a in the absence of NiCl2
and TBHP. With NiCl2, 1aa is esterified to starting material 1a in 58% yield,
while with TBHP, the yield of 2a is only 21%. When adding NiCl2 and
TBHP together to 1aa, the yields of 1a and 2a are 30%, 32%, respectively.
It is significantly lower than that starting from 1a directly (Table 1, entry 4,
2a, >99%). These results indicate that 1aa maybe not a possible
intermediate in the possible mechanism.
a
1
2
3
4
5
6
7
8
compounds were prepared from 2-hydroxylated aryl ketone products. As
shown in Scheme 4, the ring-closing reaction can be carried out between 2-
hydroxybenzophenone and 2-bromo-acetophenone (3 in 99% yield,
Scheme 4a) or methyl bromoacetate (4 in 99% yield, Scheme 4b).26a Also
2a can be esterified with acetic anhydride (5 in 98% yield, Scheme 4c)26b or
trifluoroacetic anhydride (9 in 85% yield, Scheme 4g). The obtained 2-
benzoylphenyl 2,2,2-trifluoroacetate (9) can react with phenylboronic acid
to give coupling product (11 in 70% yield, Scheme 4h) or with the removal
26d
of trifluoroacetate to give benzophenone 10 (94% yield, Scheme 4i)
.
Also, 2a can be used for ring-closing reaction with acetic anhydride to
obtain 4-phenylchromenone compound (6 in 91% yield, Scheme 4d) 26b or
react with chlorosulfonyl isocyanate to obtain 4-phenylbenzo[e][1,2,3] -
oxathiazine 2,2-dioxide (7 in 76% yield) (Scheme 4e)26b. In the presence of
sodium hydroxide, 2o with chloride can be easily transformed to 9H-
xanthen-9-one 8 in 89% yield (Scheme 4f).26c
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
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50
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57
58
59
60
Scheme 6. Control experiments
Scheme 4. Divergent transformations of 2a.a
a) Radical Trapping Experiments
O
radical scavenge
(2 eq)
r
O
NiCl2 (10 mol%)
Na2CO3 (2.0 eq.)
TBHP (2.0 eq.)
Toluene, 12 h, 80 o
O
OH
O
yield
99%
O
O
O
O
none
TEMPO
BHT
C
51%
28%
6, 91%
5, 98%
1a
2a
b) Catalyst Experiments
O
O
O
O
OH
O
O
O
O
O
Na2CO3 (2.0 eq.)
TBHP (2.0 eq.)
Toluene, 12 h, 80 o
O
O
d
c
+
O
O
C
O
O
N
Cl
e
Br
Br
1a
2a
11
99
2a'
88
C
S
OH
O
O
O
without NiCl2
with NiCl2
:
:
O
trace
b
N
S
O
c) By-product Experiments
X
4, 99%
O
O
R
O
O
NiCl2
a-e, g-i: R=H,X=H;
f: R=Me,X=Cl.
NR
NR
NR
O
7, 76%
OH
O
NaOH
TBHP
O
O
a
f
NiCl2
TBHP
F3C
O
O
O
S
S
2e'
2e
O
O
g
O
d) CO2 detection experiment
O
O
O
NiCl2 (10 mol%)
NaOAc (2.0 eq)
8, 89%
O
OH
O
O
F3C
O
3, 99%
CF3
TBHP (2.0 eq)
CO2
+
CF3
Toluene, 12 h, 80 o
C
GC analysis
1a
2a
O
O
F3C
e) Hydrolyzed experiment
S
O
B(OH)2
O
O
NR
HCOOH
O
O
OH
1) NaOH, 100 o
C
O
NiCl2
h
O
1a (58%)
2a (21%)
i
MeOH: H2O = 3:1
OH
TBHP
2) HCl
10, 94%
11, 70%
9, 85%
NiCl2
1a (30%) 2a (32%)
TBHP
aReaction conditions: (a) methyl bomoacetate, K2CO3, acetone, reflux, 2 h,
99%; (b) 2-bromoacetophenone, K2CO3, MeCN, 120 °C, 4 h, 99%; (c)
acetic anhydride, KOAc, MeCN, 150 °C, 4 h, 99%; (d) acetic anhydride,
DBU, MeCN, reflux, 8 h, 91%; (e) ClSO2NCO, toluene, reflux, 10 h, 76%;
(f) NaOH, H2O, 100 °C, 16 h, 89%; (g) trifluoromethanesulfonic anhydride,
Et3N, 80 °C, 12 h, 85 %; (h) Pd(PPh3)4, Na2CO3, toluene, H2O, 140 °C, 12
h, 70 %; (i) Pd(OAc)2, dppf, HCOOH, Et3N, DMSO, 25 °C, 12 h, 94%.
1a
1aa, 55%
Scheme 7. Plausible mechanism
O
O
O
O
O-
O
tBuO
tBuOOH
Na2CO3
2a'
1a
- tBuO
- OH-
It is known that systems containing peroxides are difficult to scale up,
because at elevated temperatures the reactions of peroxides could lead to
violent explosion. Furthermore, peroxides are highly active and the
production of by-products is common. Nonetheless, in this study, a gram
scale experiment was performed, and the yield is up to 77 % (Scheme 5).
Also, we observed the release of CO2 by GC analysis without any detection
of CO.
A
B
B'
[Ni]
tBuO
tBuO
fast
tBuOOH
slow
2 tBuOH
+ CO2
H2
O
OH
O
OOtBu
[Ni]
O
O
tBuOOH
-[Ni]
2a
OtBu
OtBu
Scheme 5. Gram-scale experiment
C
D
NiCl2 (10mol%, 65 mg)
Na2CO3 (2.0 eq., 1050 mg)
TBHP (2.0 eq., 975 uL)
O
OH
O
Although the exact mechanism is still unknown, based on the above
results and those reported in the literature,22,27 a possible pathway for the
decarbonyloxidation of 3-aryl benzofuran-2(3H)-ones is proposed (Scheme
O
+
CO2
7). At first, intermediate A is generated from benzofuranones (1a) in the
Toluene, 20 mL, N2, 36 h
GC
27a
presence of a base.
Then A reacts with TBHP to form B with the
2a, 0.82g, 77%
1a, 5 mmol, 1.12 g
generation of radical tBuO·, while B can isomerizes to carbon radical B’.
Then B or B’ can follow two pathways in the absence of a nickel catalyst.
The fast path is trapped by tBuO· to form byproduct 2a’; the other is a slow
one that B or B’ reacts with TBHP and tBuO· to form intermediate D. In
the presence of a nickel catalyst and with CO migration, radical B or B’
directly reacts with radical tBuO· to intermediate C.22a,22b Then with another
To gain insights into the reaction mechanism, several control
experiments were conducted. First, TEMPO and BHT affect the yield
significantly, indicating the involvement of free radicals (Scheme 6a). In
the case of catalyst absence, the product yield is extremely low (2a, 11%),
while the yield of by-product 2a’ is 88% (Scheme 6b). It was observed that
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equiv. of THBP, the reductive elimination of nickel leads to the formation
General Procedure for Synthesis of 1u and 1v. To a flask was added
3-(4-bromophenyl)-5-methylbenzofuran-2(3H)-one (120.0 mg, 0.4 mmol),
(4-cyanophenyl)boronic acid (119.0 mg, 0.8 mmol), Pd(PPh3)4 (46.0 mg,
0.04 mmol), K2CO3 (110.4 mg, 0.8 mmol), toluene (1.0 mL) and H2O (1.0
mL). Then put the flask in the reaction system at 140 C (oil bath) and
stirred for 12 h. The reaction mixture was dissolved in 2.0 mL ethyl acetate.
Dried by Rotary Evaporator, the residue was purified by column
chromatography (petroleum ether/ethyl acetate = 10/1) to obtain the
product.
5-Methyl-3-(4'-(Trifluoromethyl)-[1,1'-biphenyl]-4-yl)benzofuran-
2(3H)-one (1u). The representative general procedure mentioned above
was followed. Purification by PTLC on silica gel (petroleum ether/ethyl
acetate = 200/1) yielded the title compound 1u in 40% (58.8 mg) as a white
solid; 1H NMR (400 MHz, CDCl3) δ 7.72–7.65 (m, 4H), 7.60 (d, J = 8.1 Hz,
2H), 7.35 (d, J = 8.0 Hz, 2H), 7.19 (m, 1H), 7.10 (d, J = 8.2 Hz, 1H), 7.05
(s, 1H), 4.92 (s, 1H), 2.35 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 175.2,
151.9, 144.0, 139.7, 135.4, 134.4, 130.0, 129.6 (q, J = 32.3 Hz), 129.1,
129.0, 127.4, 126.7, 125.8 (q, J = 3.8 Hz), 125.7, 124.2 (q, J = 270.5 Hz),
110.6, 21.1. 19F NMR (376 MHz, CDCl3) δ -62.44. HRMS (EI) m/z: [M+]
calcd for C22H15F3O2 368.1024, Found 368.1018.
of intermediate D. Finally, D decomposes with the release of one CO2 and
two tBuOH molecules to give the target product 2a in the presence of
water.27b
1
2
3
4
5
6
7
8
CONCLUSIONS
In summary, we developed an efficient and convenient method for the
synthesis of 2-hydroxybenzophenone from benzofuranone using
inexpensive NiCl2 as catalyst, Na2CO3 as base, and TBHP as oxidant under
mild conditions. The reaction involves the decarbonyloxidation of lactone.
The catalytic system shows tolerance toward numerous substituted
benzofuranones, giving the corresponding products in good to excellent
yield. This protocol can be easily enlarged and applied.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
EXPERIMENTAL SECTION
General Information. All commercially available regents were used
without further purification. Nuclear magnetic resonance (NMR) spectra
was acquired at 298 K on a 400 MHz Bruker NMR spectrometer with the
sample dissolved in CDCl3. All values of chemical shift were reported in
parts per million (ppm) relative to the solvent signal with the coupling
constant (J) reported in hertz. All compounds were characterized by 1H
NMR, 13C NMR and EI (or HRMS (double focusing mass analyzer). For
substrates and products that contained F, selected ones were also
characterized by 19F NMR. Column chromatography was performed on
silica gel (300−400 mesh) using petroleum ether (PE)/ethyl acetate (EA) as
developing solvent.
4'-(5-Methyl-2-oxo-2,3-dihydrobenzofuran-3-yl)-[1,1'-biphenyl]-4-
carbonitrile (1v). The representative general procedure mentioned above
was followed. Purification by PTLC on silica gel (petroleum ether/ethyl
acetate = 200/1) yielded the title compound 1v in 57% (74.0 mg) as a white
solid; 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.4 Hz, 2H), 7.66 (d, J =
8.3 Hz, 2H), 7.59 (d, J = 8.3 Hz, 2H), 7.38–7.32 (m, 2H), 7.19 (m, 1H), 7.09
(d, J = 8.2 Hz, 1H), 7.04 (s, 1H), 4.92 (s, 1H), 2.35 (s, 3H). 13C{1H} NMR
(101 MHz, CDCl3) δ 175.1, 151.9, 144.8, 139.1, 135.8, 134.4, 132.7, 130.0,
129.1, 128.0, 127.7, 126.6, 125.7, 118.8, 111.2, 110.6, 49.6, 21.1. HRMS
(EI) m/z: [M+] calcd for C22H15NO2 325.1103, Found 325.1093.
Synthesis of 7-Cyclohexyl-[1,3]dioxolo[4,5-f]benzofuran-6(7H)-one
(1x).25b A 10 mL oven-dried Schlenk tube equipped with a magnetic stirring
bar was added Pd(PPh3)4 (5 mol %, 57.8 mg), P(o-tolyl)3 (20 mol %, 60.8
mg) and sesamol (1.0 mmol, 138 mg) were transferred into an oven-dried
tube which was filled with nitrogen. Chlorobenzene (2.0 mL),
benzaldehyde (2 mmol, 224 uL), TFA (15 mol %, 11 uL) were added into
the reaction tube. Then a mixture of formic acid (3.0 mmol, 113.1 uL) and
acetic anhydride (3.0 mmol, 306.2 uL) which was stirred for 1.5 h at 30 °C,
added to the reaction tube. The mixture was stirred for 18h at 130 °C. After
the reaction was complete, the reaction mixture was filtered and
concentrated, column chromatography on silica gel (petroleum ether/ethyl
General Procedure for Synthesis of 1a-1t. The starting materials was
synthesized according to reported procedure.25a To a flask was added
Mandelic acid (3.04 g, 20 mmol), phenol (1.9 mL, 20 mmol) and Ni(OTf)2
(712 mg, 2 mmol). Then put the flask in the reaction system at 160 C (oil
bath) and stirred for 12 h. The reaction mixture was dissolved in 2.0 mL
ethyl acetate. Dried by Rotary Evaporator, the residue was purified by
column chromatography (petroleum ether/ethyl acetate = 20/1) to obtain the
product. 1a-1n, 1p, 1r, 1w have been reported in the published article of
this group.25
3-(2-Chlorophenyl)-7-methylbenzofuran-2(3H)-one
(1o).
The
1
acetate 50:1), yielded in 60% (156.8 mg) as a white solid; H NMR (400
representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 20/1)
yielded the title compound 1o in 68% (3.5 g) as a white solid; 1H NMR (400
MHz, CDCl3) δ 7.50 (d, J = 7.9 Hz, 1H), 7.37 – 7.26 (m, 2H), 7.18 (t, J =
13.9 Hz, 2H), 7.07 (t, J = 7.6 Hz, 1H), 7.00 (d, J = 7.6 Hz, 1H), 5.41 (s, 1H),
2.42 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 174.5, 152.3, 134.3, 133.8,
130.7, 130.2, 129.6, 127.4, 126.5, 124.3, 121.9, 121.1, 15.1. HRMS (EI)
m/z: [M+] calcd for C15H11ClO2 258.0448, Found 258.0438.
6-(Tert-butyl)-3-(4-chlorophenyl)benzofuran-2(3H)-one (1q). The
representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 20/1)
yielded the title compound 1q in 77% (4.6 g) as a white solid; 1H NMR (400
MHz, CDCl3) δ 7.41–7.38 (m, 2H), 7.28 (m, 2H), 7.24 (d, J = 1.6 Hz, 1H),
7.18 (m, 1H), 7.11 (t, J = 7.4 Hz, 1H), 4.90 (s, 1H), 1.41 (d, J = 1.3 Hz, 9H).
13C{1H} NMR (101 MHz, CDCl3) δ 175.5, 151.8, 147.8, 135.3, 129.1, 128.3,
128.1, 126.4, 126.2, 122.2, 110.1, 50.1, 34.7, 31.5. HRMS (EI) m/z: [M+]
calcd for C18H17ClO2 300.0917, Found 300.0916.
MHz, CDCl3) δ 6.74 (s, 1H), 6.64 (s, 1H), 5.96 (s, 2H), 3.53 (s, 1H), 2.04
(m, 1H), 1.70 (m, 4H), 1.56 (d, J = 10.9 Hz, 1H), 1.25 (m, 4H), 1.12 (m,
1H). 13C{1H} (101 MHz, CDCl3) δ 177.1, 148.2, 147.4, 144.0, 117.5, 104.8,
101.4, 94.2, 50.0, 41.3, 29.8, 28.7, 26.4, 26.1, 25.8. HRMS (EI) m/z: [M+]
calcd for C15H16O4 260.1049, Found 260.1044.
General Procedure for Synthesis of Products. A 10 mL oven-dried
Schlenk tube equipped with a magnetic stirring bar was added benzofuran-
2(3H)-ones 1 (0.24 mmol，1.0 equiv.), NiCl2 (0.02 mmol, 10 mol%, 2.6
mg), Na2CO3 (0.4 mmol, 2 equiv., 42.4 mg), TBHP (0.4 mmol, 2.0 equiv.,
39 μL), and toluene (1.0 mL) and was vigorously stirred at 80 C (oil bath)
for 12 h under air. Then the mixture was cooled to room temperature,
filtered and concentrated in vacuo. Further purification by flash column
chromatography on silica gel (eluting with petroleum ether/ethyl acetate)
provided the desired product.
(2-Hydroxy-5-methylphenyl)(phenyl)methanone
(2a)28.
The
representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 200/1)
yielded the title compound 2a in 99% (42.0 mg) as a yellow solid; mp: 70–
73 C; Reported mp: 81 C; Rf = 0.35 (petroleum ether/ethyl acetate =
200/1); 1H NMR (400 MHz, CDCl3) δ 11.85 (s, 1H), 7.67 (d, J = 7.6 Hz,
2H), 7.59 (t, J = 7.3 Hz, 1H), 7.51 (t, J = 7.4 Hz, 2H), 7.38 – 7.29 (m, 2H),
6.98 (d, J = 8.4 Hz, 1H), 2.25 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ
201.6, 161.1, 138.0, 137.4, 133.2, 131.8, 129.1, 128.3, 127.8, 118.8, 118.1,
20.4. GC-MS (EI) m/z: [M+] Calcd for C14H12O2 212, Found 212.
(2-Hydroxyphenyl)(phenyl)methanone (2b)29. The representative
general procedure mentioned above was followed. Purification by PTLC on
silica gel (petroleum ether/ethyl acetate = 200/1) yielded the title compound
2b in 99% (39.2 mg) as a yellow liquid; Rf = 0.36 (petroleum ether/ethyl
acetate = 200/1); 1H NMR (400 MHz, CDCl3) δ 12.03 (s, 1H), 7.68 (d, J =
7.6 Hz, 2H), 7.60 (m, 2H), 7.51 (t, J = 7.5 Hz, 3H), 7.08 (d, J = 8.4 Hz, 1H),
6.88 (t, J = 7.5 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3) δ 201.6, 163.2,
137.9, 136.3, 133.6, 131.9, 129.2, 128.3, 119.1, 118.6, 118.4. GC-MS (EI)
m/z: [M+] Calcd for C13H10O2 198, Found 198.
3-(4-Bromophenyl)-7-methylbenzofuran-2(3H)-one
(1s).
The
representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 200/1)
yielded the title compound 1s in 62% (3.7 g) as a white solid; 1H NMR (400
MHz, CDCl3) δ 7.47 (d, J = 7.8 Hz, 2H), 7.20 (d, J = 7.7 Hz, 1H), 7.13 (d,
J = 8.5 Hz, 2H), 7.08 (d, J = 7.7 Hz, 1H), 7.01 (d, J = 7.5 Hz, 1H), 4.86 (s,
1H), 2.38 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 174.4, 152.2, 134.1,
131.9, 130.8, 129.8, 125.7, 124.2, 122.3, 122.0, 121.0, 49.2, 14.9. HRMS
(EI) m/z: [M+] calcd for C15H11BrO2 301.9942, Found 301.9939.
3-(4-Bromophenyl)-4,6-dimethylbenzofuran-2(3H)-one (1t). The
representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 200/1)
yielded the title compound 1t in 60% (3.8 g) as a white solid; 1H NMR (400
MHz, CDCl3) δ 7.48 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 8.3 Hz, 2H), 7.00 (s,
1H), 6.81 (s, 1H), 4.81 (s, 1H), 2.32 (d, J = 13.7 Hz, 6H). 13C{1H} NMR
(101 MHz, CDCl3) δ 174.9, 150.3, 134.4, 134.0, 132.1, 131.4, 129.9, 125.8,
122.8, 122.1, 120.7, 49.6, 20.9, 15.0. HRMS (EI) m/z: [M+] calcd for
C16H13BrO2 316.0099, Found 316.0089.
ACS Paragon Plus Environment

Page 5 of 9
The Journal of Organic Chemistry
(5-Ethyl-2-hydroxyphenyl)(phenyl)methanone
(2c)30.
The
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 200/1)
yielded the title compound 2j in 99% (54.1 mg) as a yellow solid; mp:73–
76 C; Reported mp: 89–91 C; Rf = 0.43 (petroleum ether/ethyl acetate =
200/1); 1H NMR (400 MHz, CDCl3) δ 12.02 (s, 1H), 7.82 (s, 1H), 7.76 (t, J
= 9.1 Hz, 3H), 7.62 (t, J = 7.2 Hz, 1H), 7.53 (t, J = 7.4 Hz, 2H), 7.46 (d, J
= 7.4 Hz, 2H), 7.41 (t, J = 7.3 Hz, 2H), 7.32 (t, J = 7.1 Hz, 1H), 7.18 (d, J
= 8.6 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3) δ 201.6, 162.6, 139.8,
137.8, 135.1, 132.1, 132.0, 131.7, 129.2, 128.9, 128.4, 127.1, 126.6, 119.2,
118.9. GC-MS (EI) m/z: [M+] Calcd for C19H14O2 274, Found 274.
representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 200/1)
yielded the title compound 2c in 94% (42.5 mg) as a yellow solid; mp: 56–
59 C; Reported mp: 40–41 C; Reported melting point: 69–72 C; Rf =
0.35 (petroleum ether/ethyl acetate = 200/1); 1H NMR (400 MHz, CDCl3)
δ 11.86 (s, 1H), 7.68 (d, J = 7.4 Hz, 2H), 7.60 (t, J = 7.3 Hz, 1H), 7.52 (t, J
= 7.4 Hz, 2H), 7.37 (d, J = 10.3 Hz, 2H), 7.01 (d, J = 8.3 Hz, 1H), 2.55 (q,
J = 7.5 Hz, 2H), 1.17 (t, J = 7.5 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3)
δ 201.6, 161.3, 138.1, 136.3, 134.3, 132.1, 131.8, 129.1, 128.3, 118.8, 118.2,
27.9, 15.7. GC-MS (EI) m/z: [M+] Calcd for C15H14O2 226, Found 226.
1
2
3
4
5
6
7
8
(2-Hydroxy-5-methoxyphenyl)(phenyl)methanone
(2k)33.
The
representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 100/1)
yielded the title compound 2k in 82% (37.5 mg) as a yellow solid; mp: 68–
71 C; Reported mp: 82–84 C; Rf = 0.42 (petroleum ether/ethyl acetate =
(2-Hydroxy-4,6-dimethylphenyl)(phenyl)methanone (2d)31.
The
9
representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 200/1)
yielded the title compound 2d in 74% (33.4 mg) as a yellow liquid; Rf =
0.33 (petroleum ether/ethyl acetate = 200/1); 1H NMR (400 MHz, CDCl3)
δ 12.15 (s, 1H), 7.66 (d, J = 7.6 Hz, 2H), 7.58 (t, J = 7.3 Hz, 1H), 7.50 (t, J
= 7.3 Hz, 2H), 7.20 (d, J = 5.1 Hz, 2H), 2.29 (s, 3H), 2.22 (s, 3H). 13C{1H}
(100 MHz, CDCl3) δ 201.9, 159.6, 138.4, 138.4, 131.6, 130.8, 129.1, 128.2,
127.1, 126.9, 118.1, 20.4, 15.5. GC-MS (EI) m/z: [M+] Calcd for C15H14O2
226, Found 226.
(2-Hydroxy-4,6-dimethylphenyl)(phenyl)methanone (2e)32. The
representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 10/1)
yielded the title compound 2e in 42% (19.0 mg) as a yellow solid; mp: 100–
102 C; Reported mp: 143 C; Rf = 0.31 (petroleum ether/ethyl acetate =
10/1); 1H NMR (400 MHz, CDCl3) δ 9.38 (s, 1H), 7.66 (d, J = 7.7 Hz, 1H),
7.55 (t, J = 7.4 Hz, 1H), 7.44 (t, J = 7.4 Hz, 1H), 6.70 (s, 1H), 6.57 (s, 1H),
2.32 (s, 2H), 1.93 (s, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ 201.32,
159.3, 144.6, 140.4, 138.8, 132.6, 128.8, 128.6, 124.0, 120.3, 115.4, 22.5,
21.6. GC-MS (EI) m/z: [M+] Calcd for C15H14O2 226, Found 226.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
100/1); H NMR (400 MHz, CDCl3) δ 11.59 (s, 1H), 7.70 (d, J = 8.2 Hz,
2H), 7.60 (t, J = 6.9 Hz, 1H), 7.51 (t, J = 7.6 Hz, 2H), 7.15 (m, 1H), 7.04
(m, 2H), 3.70 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 201.2, 157.5,
151.4, 137.9, 132.0, 129.1, 128.4, 124.1, 119.2, 118.7, 116.4, 56.0. GC-MS
(EI) m/z: [M+] Calcd for C14H12O3 228, Found 228.
(5-Chloro-2-hydroxyphenyl)(phenyl)methanone
(2l)36.
The
representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 200/1)
yielded the title compound 2l in 73% (33.8 mg) as a yellow solid; mp:85–
89 C; Reported mp: 90–95 C; Rf = 0.39 (petroleum ether/ethyl acetate =
1
200/1); H NMR (400 MHz, CDCl3) δ 11.82 (s, 1H), 7.58 (d, J = 6.6 Hz,
2H), 7.52 (d, J = 6.9 Hz, 1H), 7.45 (m, 3H), 7.36 (d, J = 8.5 Hz, 1H), 6.94
(d, J = 8.6 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3) δ 200.5, 161.6, 137.2,
136.1, 132.4, 129.1, 128.5, 123.3, 120.0, 119.7. GC-MS (EI) m/z: [M+]
Calcd for C13H9ClO2 232, Found 232.
(5-Fluoro-2-hydroxyphenyl)(phenyl)methanone
(2m)37.
The
representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 200/1)
yielded the title compound 2m in 83% (35.8 mg) as a yellow solid; mp:73–
76 C; Reported mp: 77 C; Rf = 0.38 (petroleum ether/ethyl acetate =
(2-Hydroxy-5-isopropylphenyl)(phenyl)methanone
(2f)33.
The
representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 200/1)
yielded the title compound 2f in 99% (47.5 mg) as a yellow solid; mp: 76–
77 C; Reported mp: 70–73 C; Rf = 0.41 (petroleum ether/ethyl acetate =
200/1); 1H NMR (400 MHz, CDCl3) δ 11.87 (s, 1H), 7.69 (d, J = 7.2 Hz,
2H), 7.61 (t, J = 7.3 Hz, 1H), 7.52 (t, J = 7.5 Hz, 2H), 7.41 (d, J = 7.1 Hz,
2H), 7.02 (d, J = 9.2 Hz, 1H), 2.82 (m, 1H), 1.18 (d, J = 6.9 Hz, 6H) 13C{1H}
NMR (100 MHz, CDCl3) δ 201.5, 161.4, 139.0, 138.1, 134.8, 131.8, 130.8,
129.2, 128.3, 118.8, 118.2, 33.2, 24.0. GC-MS (EI) m/z: [M+] Calcd for
C16H16O2 240, Found 240.
1
200/1); H NMR (400 MHz, CDCl3) δ 11.76 (s, 1H), 7.71 (d, J = 7.5 Hz,
2H), 7.64 (t, J = 7.3 Hz, 1H), 7.55 (t, J = 7.4 Hz, 2H), 7.34 – 7.27 (m, 2H),
7.07 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3) δ 200.6 (d, J = 2 Hz), 159.4,
155.7, 153.3, 137.3, 132.3, 128.8 (d, J = 53.5 Hz), 123.9 (d, J = 23.5 Hz),
118.7 (d, J = 6.4 Hz) ,118.3 (d, J = 23.6 Hz). 19F NMR (376 MHz, CDCl3)
δ -124.0 (q, J = 8.2 Hz). GC-MS (EI) m/z: [M+] Calcd for C13H9FO2 216,
Found 216.
(2-Chlorophenyl)(2-hydroxy-5-methylphenyl)methanone (2n)38. The
representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 200/1)
yielded the title compound 2n in 99% (48.6 mg) as a yellow solid; mp:74–
78 C; Reported mp:76–77 C; Rf = 0.36 (petroleum ether/ethyl acetate =
(5-(Tert-butyl)-2-hydroxyphenyl)(phenyl)methanone (2g)34.
The
representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 200/1)
yielded the title compound 2g in 99% (50.2 mg) as a yellow solid; mp:57–
60 C; Reported mp: 67–68 C; Rf = 0.41 (petroleum ether/ethyl acetate =
200/1); 1H NMR (400 MHz, CDCl3) δ 11.86 (s, 1H), 7.70 (d, J = 7.9 Hz,
2H), 7.58 (t, J = 8.2 Hz, 3H), 7.52 (t, J = 7.6 Hz, 2H), 7.02 (d, J = 9.5 Hz,
1H), 1.25 (s, 9H). 13C{1H} NMR (101 MHz, CDCl3) δ 201.6, 161.0, 141.3,
138.1, 133.9, 131.9, 129.8, 129.2, 128.3, 118.4, 117.9, 34.1, 31.2. GC-MS
(EI) m/z: [M+] Calcd for C17H18O2 254, Found 254.
1
200/1); H NMR (400 MHz, CDCl3) δ 11.84 (s, 1H), 7.58–7.48 (m, 2H),
7.44 (m, 1H), 7.41–7.35 (m, 2H), 7.03 (t, J = 5.8 Hz, 2H), 2.24 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3) δ 200.5, 161.2, 138.4, 137.5, 132.9, 131.1,
130.8, 130.1, 128.5, 128.3, 126.7, 119.0, 118.1, 20.4. GC-MS (EI) m/z: [M+]
Calcd for C14H11ClO2 246, Found 246.
(2-Chlorophenyl)(2-hydroxy-3-methylphenyl)methanone (2o). The
representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 200/1)
yielded the title compound 2o in 71% (35.0 mg) as a yellow solid; mp:86–
(4-(Tert-butyl)-2-hydroxyphenyl)(phenyl)methanone (2h).
The
representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 200/1)
yielded the title compound 2h in 92% (46.7 mg) as a yellow solid; mp: 68–
1
89 C; Rf = 0.38 (petroleum ether/ethyl acetate = 200/1); H NMR (400
1
69 C; Rf = 0.42 (petroleum ether/ethyl acetate = 200/1); H NMR (400
MHz, CDCl3) δ 11.82 (s, 1H), 7.48 (q, J = 8.0 Hz, 2H), 7.40 (t, J = 7.2 Hz,
1H), 7.36–7.31 (m, 2H), 7.02–6.95 (m, 2H), 2.20 (s, 3H). 13C{1H} NMR
(100 MHz, CDCl3) δ 200.8, 161.7, 137.9, 137.6, 131.1, 131.1, 130.8, 130.0,
128.5, 127.4, 126.6, 118.7, 118.4, 15.4. HRMS (ESI) m/z: [M+H] + calcd
for C14H12ClO2 247.0520, Found 247.0526.
MHz, CDCl3) δ 12.10 (s, 1H), 7.67 (d, J = 7.4 Hz, 2H), 7.58 (t, J = 7.3 Hz,
1H), 7.50 (m, 3H), 7.09 (s, 1H), 6.91 (d, J = 8.4 Hz, 1H), 1.33 (s, 9H).
13C{1H} NMR (100 MHz, CDCl3) δ 201.0, 163.3, 161.0, 138.1, 133.3, 131.7,
129.0, 128.3, 116.8, 116.4, 115.1, 35.4, 30.8. HRMS (ESI) m/z: [M+Na] +
calcd for C17H18O2Na+ 277.1199, Found 277.1203.
(4-Chlorophenyl)(2-hydroxy-5-methylphenyl)methanone (2p)39. The
representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 200/1)
yielded the title compound 2p in 80% (39.3 mg) as a yellow solid; mp:66–
69 C; Reported mp:85–87 C; Rf = 0.36 (petroleum ether/ethyl acetate =
(3-(Tert-butyl)-2-hydroxyphenyl)(phenyl)methanone (2i)35. The
representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 200/1)
yielded the title compound 2i in 78% (39.6 mg) as a yellow solid; mp: 65–
67 C; Reported mp: 53 C; Rf = 0.42 (petroleum ether/ethyl acetate =
1
200/1); H NMR (400 MHz, CDCl3) δ 11.74 (s, 1H), 7.67 (d, J = 8.3 Hz,
1
200/1); H NMR (400 MHz, CDCl3) δ 11.84 (s, 1H), 7.69 (d, J = 7.8 Hz,
2H), 7.54 (d, J = 8.3 Hz, 2H), 7.42–7.33 (m, 2H), 7.03 (d, J = 8.4 Hz, 1H),
2.30 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 200.2, 161.2, 138.3, 137.6,
136.4, 132.8, 130.6, 128.7, 128.0, 118.6, 118.3, 20.5. GC-MS (EI) m/z: [M+]
Calcd for C14H11ClO2 246, Found 246.
2H), 7.62 – 7.55 (m, 3H), 7.52 (t, J = 7.4 Hz, 2H), 7.02 (d, J = 8.3 Hz, 1H),
1.25 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ 201.6, 161.0, 141.3, 138.1,
133.9, 131.9, 129.8, 129.2, 128.3, 118.4, 117.9, 34.1, 31.2. GC-MS (EI) m/z:
[M+] Calcd for C17H18O2 254, Found 254.
(4-Hydroxy-[1,1'-biphenyl]-3-yl)(phenyl)methanone (2j)29. The
representative general procedure mentioned above was followed.
(4-(Tert-butyl)-2-hydroxyphenyl)(4-chlorophenyl)methanone (2q).
The representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 200/1)
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yielded the title compound 2q in 90% (51.8 mg) as a yellow liquid; Rf =
0.34 (petroleum ether/ethyl acetate = 200/1); 1H NMR (400 MHz, CDCl3)
δ 11.97 (s, 1H), 7.63 (d, J = 7.9 Hz, 2H), 7.48 (m, 3H), 7.09 (s, 1H), 6.92
(d, J = 8.5 Hz, 1H), 1.33 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ 199.5,
163.3, 161.3, 138.1, 136.4, 132.9, 130.5, 128.6, 116.5, 115.2, 35.4, 30.8.
122 C; Rf = 0.57 (petroleum ether/ethyl acetate = 50/1); H NMR (400
MHz, CDCl3) δ 13.39 (s, 1H), 7.11 (s, 1H), 6.46 (d, J = 1.1 Hz, 1H), 5.98
(d, J = 1.1 Hz, 2H), 3.15 – 3.00 (m, 1H), 1.89 – 1.83 (m, 4H), 1.52 (m, 2H),
1.41 – 1.32 (m, 2H), 1.29 – 1.20 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3)
δ 207.6, 162.8, 154.1, 140.4, 110.8, 106.4, 101.8, 99.0, 45.2, 29.6, 25.8,
25.8. HRMS (EI) m/z: [M+] calcd for C14H16O4 248.1049, Found 248.1044.
1
2
3
+
HRMS (ESI) m/z: [M+Na] calcd for C17H17ClO2Na+ 311.0809, Found
4
5
6
7
8
9
311.0814.
Synthesis of 3-(tert-butoxy)-4,6-dimethyl-3-phenylbenzofuran-
2(3H)-one (2e'). A 10 mL oven-dried Schlenk tube equipped with a
magnetic stirring bar was added 4,6-dimethyl-3-phenylbenzofuran-2(3H)-
one 1e (0.24 mmol，1.0 equiv.), NiCl2 (0.02 mmol, 10 mol%, 2.6 mg),
Na2CO3 (0.4 mmol, 2 equiv., 42.4 mg), TBHP (0.4 mmol, 2.0 equiv., 39
μL), and toluene (1.0 mL) and was vigorously stirred at 80 C (oil bath) for
12 h under air. Then the mixture was cooled to room temperature, filtered
and concentrated in vacuo. Further purification by flash column
chromatography on silica gel (eluting with petroleum ether/ethyl acetate)
(4-Bromophenyl)(2-hydroxy-5-methylphenyl)methanone (2r). The
representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 200/1)
yielded the title compound 2r in 98% (56.8 mg) as a yellow liquid; Rf =
0.37 (petroleum ether/ethyl acetate = 200/1); 1H NMR (400 MHz, CDCl3)
δ 11.69 (s, 1H), 7.66 (d, J = 7.1 Hz, 2H), 7.55 (d, J = 7.2 Hz, 2H), 7.36 –
7.29 (m, 2H), 6.98 (d, J = 8.4 Hz, 1H), 2.26 (s, 3H). 13C{1H} NMR (100
MHz, CDCl3) δ 200.3, 161.1, 137.7, 136.7, 132.8, 131.6, 130.6, 128.0,
126.7, 118.6, 118.30, 20.5. HRMS (ESI) m/z: [M+H]+ calcd for C14H12BrO2
291.0012, Found 291.0013.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
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provided the byproduct 2e'. H NMR (400 MHz, CDCl3) δ 7.35 (s, 5H),
6.82 (d, J = 11.1 Hz, 2H), 2.40 (s, 3H), 2.11 (s, 3H), 1.26 (s, 9H). 13C{1H}
NMR (101 MHz, CDCl3) δ 173.7, 154.3, 141.2, 137.8, 134.3, 129.3, 128.7,
127.0, 126.7, 121.1, 109.0, 81.4, 26.5, 21.9, 17.4, 1.0.
(4-Bromophenyl)(2-hydroxy-3-methylphenyl)methanone (2s). The
representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 200/1)
yielded the title compound 2s in 99% (57.4 mg) as a yellow liquid; Rf = 0.36
(petroleum ether/ethyl acetate = 200/1); 1H NMR (400 MHz, CDCl3) δ
12.19 (s, 1H), 7.72–7.59 (m, 2H), 7.55 (d, J = 7.1 Hz, 2H), 7.38 (t, J = 6.4
Hz, 2H), 6.78 (t, J = 7.7 Hz, 1H), 2.32 (s, 3H). 13C{1H} NMR (101 MHz,
CDCl3) δ 200.6, 161.6, 137.4, 136.9, 131.6, 130.8, 130.7, 127.6, 126.7,
Synthesis of 2-(2-hydroxy-5-methylphenyl)-2-phenylacetic acid
(1aa). To a flask was added 1a (1.12 g, 5 mmol), NaOH ( 0.39 g, 10 mmol)
and solvent (MeOH : H2O = 3 : 1) 40 mL. Then put the flask in the reaction
system at 80 C and stirred for 12 h. Acidified of cool reaction mixture.
With HCl to pH = 2, and extracted with ethyl acetate (3x30 mL). The
organic layer was washed with brine, dried over anhydrous Na2SO4 and
evaporated under reduced pressure. 1H NMR (400 MHz, DMSO) δ 9.47 (s,
1H), 7.33 (d, J = 7.6 Hz, 1H), 7.29 (t, J = 6.5 Hz, 3H), 7.24 (t, J = 7.1 Hz,
1H), 6.87 (d, J = 8.1 Hz, 1H), 6.81 – 6.72 (m, 2H), 2.12 (s, 3H). 13C{1H}
NMR (101 MHz, DMSO) δ 174.2, 152.9, 139.4, 129.6, 129.3, 128.7, 128.6,
127.4, 127.1, 126.4, 115.3, 50.8, 20.8. HRMS (EI) m/z: [M+] calcd for
C15H14O3 242.0943, Found 242.0942.
+
118.1, 118.1, 15.6. HRMS (ESI) m/z: [M+H] calcd for C14H12BrO2
291.0011, Found 291.0012.
(4-Bromophenyl)(2-hydroxy-4,6-dimethylphenyl)methanone
(2t).
The representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 10/1)
yielded the title compound 2t in 30% (18.2 mg) as a yellow liquid; Rf = 0.39
(petroleum ether/ethyl acetate = 10/1); 1H NMR (400 MHz, CDCl3) δ 12.01
(s, 1H), 7.65 (d, J = 7.6 Hz, 2H), 7.54 (d, J = 7.5 Hz, 2H), 7.22 (s, 1H), 7.13
(s, 1H), 2.29 (s, 3H), 2.22 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 200.6,
159.6, 138.7, 137.1, 131.6, 130.6, 130.4, 127.3, 127.1, 126.5, 117.9, 20.5,
15.5. HRMS (ESI) m/z: [M+H] + calcd for C15H14BrO2 305.0169, Found
308.0170.
Synthesis of methyl 2-(3-phenylbenzofuran-2-yl)acetate (3).40 To a
flask was added 2b (100 mg, 0.5 mmol), 3a (57 μL, 0.6 mmol), K2CO3
(103.5 mg, 0.75 mmol) and toluene (10 mL). Then put the flask in the
reaction system at 80 C and reflux for 10 h.The reaction mixture was
dissolved in 2.0 mL ethyl acetate . Dried by Rotary Evaporator, the residue
was purified by column chromatography (petroleum ether/ethyl acetate =
5/1) to obtain the product 3 in 99 % (159.0 mg) as a colorless liquid. Rf =
(2-Hydroxy-5-methylphenyl)(4'-(trifluoromethyl)-[1,1'-biphenyl]-4-
yl)methanone (2u). The representative general procedure mentioned above
was followed. Purification by PTLC on silica gel (petroleum ether/ethyl
acetate = 50/1) yielded the title compound 2u in 82% (58.3 mg) as a yellow
solid; mp:171–172 C; Rf = 0.51 (petroleum ether/ethyl acetate = 50/1); 1H
NMR (400 MHz, CDCl3) δ 11.83 (s, 1H), 7.82–7.73 (m, 8H), 7.41 (s, 1H),
7.36 (d, J = 8.5 Hz, 1H), 7.01 (d, J = 8.5 Hz, 1H), 2.28 (s, 3H). 13C{1H}
NMR (101 MHz, CDCl3) δ 200.87, 161.2, 143.4, 143.1, 137.6, 137.5,
133.0,130.2 (d, J = 32.9 Hz) ,127.9, 127.6, 127.2, 125.9 (q, J = 3.7 Hz),
124.1 (q, J = 273.1 Hz), 118.8, 118.3, 20.5. 19F NMR (376 MHz, CDCl3) δ
-62.53. HRMS (ESI) m/z: [M+H] + calcd for C21H16F3O2 357.1070, Found
357.1080.
1
0.45 (petroleum ether/ethyl acetate =5/1); H NMR (400 MHz, CDCl3) δ
7.88–7.83 (m, 2H), 7.55 (t, J = 7.4 Hz, 1H), 7.43 (m, 4H), 7.11 (t, J = 7.5
Hz, 1H), 6.86 (d, J = 8.3 Hz, 1H), 4.56 (s, 2H), 3.69 (s, 3H). 13C{1H} NMR
(100 MHz, CDCl3) δ 196.1, 168.9, 155.6, 137.7, 133.0, 131.8, 123.0, 129.6,
128.2, 121.9, 112.7, 65.8, 52.2.
Synthesis of phenyl(3-phenylbenzofuran-2-yl)methanone (4).40 To a
flask was added 2b (100 mg, 0.5 mmol), 3b (110.0 μL, 0.6 mmol), K2CO3
(138 mg, 1.0 mmol) and acetonitrile (1.0 mL). Then put the flask in the
reaction system at 120 C and stirred for 4 h. The reaction mixture was
dissolved in 2 mL ethyl acetate. Dried by Rotary Evaporator, the residue
was purified by column chromatography (petroleum ether/ethyl acetate =
40/1) to obtain the product 4 in 99 % (151.5 mg) as a colorless liquid; Rf =
0.51 (petroleum ether/ethyl acetate = 40/1); 1H NMR (400 MHz, CDCl3) δ
7.89 (d, J = 7.3 Hz, 2H), 7.72 (d, J = 7.9 Hz, 1H), 7.66 (d, J = 8.4 Hz, 1H),
7.57–7.46 (m, 4H), 7.41–7.33 (m, 6H). 13C{1H} NMR (100 MHz, CDCl3)
δ 185.8, 154.6, 147.2, 137.3, 132.7, 131.0, 130.0, 129.9, 129.4, 128.4,
128.4, 128.3, 128.1, 124.0, 122.4, 112.4.
4'-(2-Hydroxy-5-methylbenzoyl)-[1,1'-biphenyl]-4-carbonitrile (2v).
The representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 20/1)
yielded the title compound 2v in 50% (31.6 mg) as a whitle solid; mp:183–
1
185 C; Rf = 0.67 (petroleum ether/ethyl acetate = 20/1); H NMR (400
MHz, CDCl3) δ 11.80 (s, 1H), 7.83–7.76 (m, 6H), 7.74 (d, J = 8.4 Hz, 2H),
7.42–7.32 (m, 2H), 7.00 (d, J = 8.4 Hz, 1H), 2.27 (s, 3H). 13C{1H} NMR
(100 MHz, CDCl3) δ 200.7, 161.2, 144.3, 142.4, 138.0, 137.6, 132.9, 132.8,
129.9, 127.9, 127.2, 118.7, 118.6, 118.3, 111.9, 20.5. HRMS (ESI) m/z:
[M+H] + calcd for C21H16NO2 314.1161, Found 314.1166.
Synthesis of 2-benzoylphenyl acetate (5).41 To a flask was added 2b
(40.0 mg, 0.2 mmol), 3c (110.0 μL, 0.6 mmol), NaOAc (54.4 mg, 0.4 mmol)
and acetonitrile (1.0 mL). Then put the flask in the reaction system at 150
C and stirred for 4 h.The reaction mixture was dissolved in 2.0 mL ethyl
acetate. Dried by Rotary Evaporator, the residue was purified by column
chromatography (petroleum ether/ethyl acetate = 10/1) to obtain the product
5 in 98 % (47.2 mg) as a colorless liquid. Rf = 0.42 (petroleum ether/ethyl
acetate =10/1); 1H NMR (400 MHz, CDCl3) δ 7.86–7.79 (m, 2H), 7.66–7.56
(m, 3H), 7.50 (t, J = 7.7 Hz, 2H), 7.41 – 7.35 (m, 1H), 7.24 (d, J = 8.1 Hz,
1H), 1.98 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 194.8, 169.1, 148.8,
137.1, 133.0, 132.3, 131.6, 130.5, 129.8, 128.4, 125.7, 123.2, 20.5.
Synthesis of 4-phenyl-2H-chromen-2-one (6).41 To a flask was added
2b (100 mg, 0.5 mmol), 3d (153 μL, 1.5 mmol), DBU (228 μL, 1.5 mmol)
and acetonitrile (1.0 mL). Then put the flask in the reaction system at 80 C
and reflux for 8 h. The reaction mixture was dissolved in 2.0 mL ethyl
acetate . Dried by Rotary Evaporator, the residue was purified by column
chromatography (petroleum ether/ethyl acetate = 10/1) to obtain the product
6 in 91 % (101.2 mg) as a white solid. Rf = 0.42 (petroleum ether/ethyl
acetate =10/1); 1H NMR (400 MHz, CDCl3) δ 7.50–7.41 (m, 5H), 7.37 (m,
2H), 7.29 (d, J = 8.3 Hz, 1H), 7.18–7.13 (m, 1H), 6.27 (s, 1H). 13C{1H}
(3,5-Di-tert-butyl-2-hydroxyphenyl)(3,4-dimethylphenyl)-
methanone (2w). The representative general procedure mentioned above
was followed. Purification by PTLC on silica gel (petroleum ether/ethyl
acetate = 200/1) yielded the title compound 2x in 80% (54.0 mg) as a yellow
solid; mp:161–163 C; Rf = 0.35 (petroleum ether/ethyl acetate = 200/1);
1H NMR (400 MHz, CDCl3) δ 12.71 (s, 1H), 7.57 (s, 1H), 7.49 (s, 2H), 7.42
(d, J = 7.7 Hz, 1H), 7.24 (d, J = 7.1 Hz, 1H), 2.34 (d, J = 8.6 Hz, 6H), 1.47
(s, 9H), 1.25 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ 202.3, 160.4,
141.1, 139.5, 137.7, 136.6, 136.2, 130.8, 130.7, 129.2, 128.0, 127.2, 118.4,
+
35.2, 34.2, 31.3, 29.4, 19.9, 19.7. HRMS (ESI) m/z: [M+H] calcd for
C23H31O2 339.2319, Found 339.2316.
Cyclohexyl(6-hydroxybenzo[d][1,3]dioxol-5-yl)methanone (2x). The
representative general procedure mentioned above was followed.
Purification by PTLC on silica gel (petroleum ether/ethyl acetate = 50/1)
yielded the title compound 2x in 22% (10.8 mg) as a white solid; mp:120–
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The Journal of Organic Chemistry
NMR (100 MHz, CDCl3) δ 160.6, 155.6, 154.1, 135.1, 131.9, 129.7, 128.9,
128.4, 127.0, 124.2, 118.9, 117.2, 115.1.
AUTHOR INFORMATION
1
2
3
4
5
6
7
8
Synthesis of 4-phenylbenzo[e][1,2,3]oxathiazine 2,2-dioxide (7).41 To
a flask was added 2b (100 mg, 0.5 mmol), 3e (44 μL, 0.5 mmol), and toluene
10 mL. Then put the flask in the reaction system at 80 C and reflux for 10
h. The reaction mixture was dissolved in 2.0 mL ethyl acetate. Dried by
Rotary Evaporator, the residue was purified by column chromatography
(petroleum ether/ethyl acetate = 5/1) to obtain the product 7 in 76 % (99.2
mg) as a colorless liquid. Rf = 0.52 (petroleum ether/ethyl acetate = 10/1);
1H NMR (400 MHz, CDCl3) δ 7.79–7.72 (m, 3H), 7.69–7.62 (m, 2H), 7.55
(t, J = 7.7 Hz, 2H), 7.38 (t, J = 8.3 Hz, 2H). 13C{1H} NMR (100 MHz,
CDCl3) δ 176.5, 154.5, 137.1, 133.6, 133.3, 131.9, 130.6, 128.9, 125.9,
119.4, 116.5.
Corresponding Author
*E-mail: renhuaqiu1@hnu.edu.cn (R.Q.).
Author Contributions
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
The authors thank the Natural Science Foundation of China
(21676076, 21878081, 21971060), Hu-Xiang High Talent
(2018RS3042) and Recruitment Program for Foreign Experts of
China (WQ20164300353) for financial support. R. Qiu thanks Prof.
Nobuaki Kambe (Osaka University) and Prof. Shuang-Feng Yin
(Hunan University) for helpful discussion. Prof. Chak-Tong Au
thanks the HNU for an adjunct professorship.
9
Synthesis of 2-methyl-9H-xanthen-9-one (8).42 To a flask was added
2p (49.2 mg, 0.2 mmol), NaOH (8.0 mg, 0.4 mmol), and H2O 1.0 mL. Then
put the flask in the reaction system at 100 C and reflux for 16 h. The
reaction mixture was dissolved in 2.0 mL ethyl acetate. Dried by Rotary
Evaporator, the residue was purified by column chromatography (petroleum
ether/ethyl acetate = 20/1) to obtain the product 8 in 89 % (37.2 mg) as a
colorless liquid. Rf = 0.68 (petroleum ether/ethyl acetate = 20/1); 1H NMR
(400 MHz, CDCl3) δ 8.32 (d, J = 8.0 Hz, 1H), 8.09 (s, 1H), 7.69 (t, J = 7.8
Hz, 1H), 7.47 (m, 2H), 7.35 (t, J = 8.6 Hz, 2H), 2.44 (s, 3H). 13C{1H} NMR
(100 MHz, CDCl3) δ 177.2, 156.1, 154.3, 1356.0, 134.6, 133.6, 126.6,
125.9, 123.6, 121.7, 121.4, 117.9, 117.7, 20.8.
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the product 9 in 85 % (1.25 mg) as a colorless liquid. Rf = 0.36 (petroleum
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1
ether/ethyl acetate =20/1); H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.0
Hz, 2H), 7.60 (m, 3H), 7.46 (m, 3H), 7.41 (d, J = 8.3 Hz, 1H). 13C{1H}
NMR (100 MHz, CDCl3) δ 192.7, 146.8, 136.5, 133.8, 132.8, 132.4, 131.3,
130.1, 128.6, 128.1, 122.4, 118.5 (q, J = 318.6 Hz). 19F NMR (376 MHz,
CDCl3) δ -73.6.
Synthesis of benzophenone (10).44To a flask was added 9 (58.8 mg, 0.2
mmol), Pd(OAc)2 (2.2 mg, 0.01 mmol), DPPF (5.5 mg, 0.01 mmol),
HCOOH (15 μL, 0.4 mmol), Et3N (56 μL, 0.4 mmol), and DMSO (1.0 mL).
Then put the flask in the reaction system at 25 C and stirred for 12 h. The
reaction mixture was dissolved in 2.0 mL ethyl acetate. Dried by Rotary
Evaporator, the residue was purified by column chromatography (petroleum
ether/ethyl acetate = 20/1) to obtain the product 10 in 94 % (34.6 mg) as a
white solid. Rf = 0.52 (petroleum ether/ethyl acetate =20/1); 1H NMR (400
MHz, CDCl3) δ 7.81 (d, J = 7.8 Hz, 4H), 7.59 (t, J = 7.4 Hz, 2H), 7.48 (t, J
= 7.6 Hz, 4H). 13C{1H} NMR (100 MHz, CDCl3) δ 196.7, 137.6, 132.4,
130.0, 128.2.
Synthesis
of
phenyl(4'-(trifluoromethyl)-[1,1'-biphenyl]-2-
yl)methanone (11).45 To a flask was added 9 (58.8 mg, 0.2 mmol), 4-
trifluoromethylphenylboronic acid (76 mg, 0.4mmol), Pd(PPh3)4 (23.0 mg,
0.02 mmol), Na2CO3 ( 42.4 mg, 0.4 mmol), toluene (1.0 mL) and H2O (1.0
mL). Then put the flask in the reaction system at 140 C and stirred for 12
h. The reaction mixture was dissolved in 2.0 mL ethyl acetate . Dried by
Rotary Evaporator, the residue was purified by column chromatography
(petroleum ether/ethyl acetate = 20/1) to obtain the product 11in 70 % (45.4
1
mg) as a white solid. Rf = 0.52 (petroleum ether/ethyl acetate =20/1); H
NMR (400 MHz, CDCl3) δ 7.68 (d, J = 7.7 Hz, 2H), 7.61 (t, J = 7.3 Hz,
1H), 7.57 – 7.43 (m, 6H), 7.38 (d, J = 8.1 Hz, 2H), 7.32 (t, J = 7.7 Hz, 2H).
13C{1H} (100 MHz, CDCl3) δ 198.1, 143.9, 139.9, 139.0, 137.3, 133.2,
130.6, 130.2, 129.9, 129.4 (q, J = 32.3 Hz), 129.3, 129.0, 128.3, 127.7,
125.2 (q, J = 3.8 Hz), 124.1 (q, J = 270.3 Hz). 19F NMR (376 MHz, CDCl3)
δ -62.6.
Procedure for gram scale experiment. To a flask was added 1a (1.12
g, 5 mmol), NiCl2 (65 mg, 0.5 mmol), Na2CO3 (4.24 g, 10 mmol), TBHP
(975 μL, 5 mmol) and toluene (1.0 mL). Then put the flask in the reaction
system at 80 C and stirred for 36 h. The reaction mixture was dissolved in
2.0 mL ethyl acetate. Dried by Rotary Evaporator, the residue was purified
by column chromatography (petroleum ether/ethyl acetate = 100/1) to
obtain the product.
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ASSOCIATED CONTENT
Supporting Information
Detailed experimental procedures, characterization data, spectra
copies of the 1H, 19F, 13C NMR.
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