NIS-mediated oxidative lactonization of 2-arylbenzoic acids for the synthesis of dibenzopyranones under metal-free conditions

Article abstract of DOI:10.1055/s-0033-1338568

A series of dibenzopyranones were synthesized from 2-arylbenzoic acids by a radical oxidative cyclization procedure mediated by N-iodosuccinimide (NIS). The methodology is distinguished by its practicality in terms of its wide substrate scope, good functi

Full text of DOI:10.1055/s-0033-1338568

PAPER
▌343
paper
NIS-Mediated Oxidative Lactonization of 2-Arylbenzoic Acids for the Synthesis
of Dibenzopyranones under Metal-Free Conditions
NIS-Mediated Oxidative C–H Lactonization of 2-Arylbenzoic Acids
Peng Gao, Yunyang Wei*
School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, P. R. of China
Fax +86(25)84317078; E-mail: ywei@mail.njust.edu.cn
Received: 10.10.2013; Accepted after revision: 11.11.2013
Table 1 Optimization of Reaction Conditionsa
Abstract: A series of dibenzopyranones were synthesized from 2-
O
arylbenzoic acids by a radical oxidative cyclization procedure me-
diated by N-iodosuccinimide (NIS). The methodology is distin-
guished by its practicality in terms of its wide substrate scope, good
functional group tolerance, and mild reaction conditions without the
use of transition metals.
O
OH
O
conditions
Key words: lactones, oxidation, carboxylic acids, cyclization, rad-
ical reaction
1a
2a
Entry Oxidant
(equiv)
Additive (equiv)
Solvent
Yieldb
(%)
Dibenzopyranones and their derivatives are an important
scaffold that can be found in many natural products and
pharmaceuticals because of their remarkable biological
and pharmacological activity.1a–d The dibenzopyranone
structural unit has also found application as an intermedi-
ate in the synthesis of useful axially chiral compounds.1e,f
As a consequence, extensive efforts have been made to
develop methods for the synthesis of these compounds,
including: cyclization of hydroxyl carboxylic acids;2
Baeyer–Villiger oxidation of fluorenones;3 transition-
metal-catalyzed C–O bond formation from 2′-halobiphe-
nyl-2-carboxylic acids;4 and C–H functionalization meth-
odologies, such as, palladium-catalyzed intramolecular
C–C bond formation of aryl 2-halobenzoates,5 Pd/Cu or
ruthenium-catalyzed C–H activation/carbonylation of
biphenyl-2-ol derivatives in the presence of carbon mon-
oxide,6 and palladium or copper-catalyzed C–H activa-
tion/C–O bond formation from 2-arylbenzoic acids.7
However, there are some problems associated with these
methodologies, such as the reliance on transition-metal
catalysts, the use of starting materials that are not readily
available, and the requirement for prefunctionalization.
To our knowledge, there are very few published methods
for the transformation of 2-arylbenzoic acids into diben-
zopyranones under metal-free conditions.8 As a continua-
tion of our efforts on the development of metal-free
oxidative reactions,9 we wished to develop simple meth-
ods for the preparation of dibenzopyranones; herein, we
report a new method for the synthesis of dibenzopyra-
nones from 2-arylbenzoic acids mediated by N-iodosuc-
cinimide.
1
NIS (1.5)
NIS (2.0)
NIS (2.5)
NBS (2.5)
NCS (2.5)
NIS (2.5)
NIS (2.5)
NIS (2.5)
NIS (2.5)
NIS (2.5)
NIS (2.5)
NIS (2.5)
NIS (2.5)
NIS (2.5)
NIS (2.5)
–
(CH2Cl)2
(CH2Cl)2
(CH2Cl)2
(CH2Cl)2
(CH2Cl)2
(CH2Cl)2
(CH2Cl)2
61
78
86
55
0
2
–
3
–
4
–
5
–
6
Na2CO3 (1.0)
NH4Cl (1.0)
77
34
76
53
68
0c
7
8
2-iodobenzoic acid (0.2) (CH2Cl)2
9
AIBN (0.2)
(CH2Cl)2
toluene
MeOH
10
11
12
13
14
15
–
–
–
–
–
–
DMSO
0c
CF3CH2OH 47
(CH2Cl)2
(CH2Cl)2
51d
38e
a Reaction conditions: 1a (0.5 mmol), oxidant, solvent (3 mL), visible
light, 75 °C, 4 h.
b Isolated yield.
c The reaction was carried out at reflux temperature.
d The reaction was carried out in darkness.
e The reaction was carried out at r.t.
phenylbenzoic acid (1a) with 1.5 equivalents of N-iodo-
succinimide as the oxidant in 1,2-dichloroethane at 75 °C
gave the 6H-benzo[c]chromen-6-one (2a) in 61% yield
(entry 1). Increasing the amount of N-iodosuccinimide in-
creased yield of the 2a and it was found 2.5 equivalents N-
iodosuccinimide was optimum for the transformation (en-
tries 2 and 3). Oxidants played a key role in the reaction;
N-bromosuccinimide showed low reactivity and gave 2a
in 55%, while N-chlorosuccinimide gave no product (en-
2-Phenylbenzoic acid (1a) was chosen as the model sub-
strate to examine the reaction of 2-arylbenzoic acids in the
presence of N-iodosuccinimide (Table 1). Reaction of 2-
SYNTHESIS 2014, 46, 0343–0347
Advanced online publication: 02.12.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1338568; Art ID: SS-2013-H0669-OP
© Georg Thieme Verlag Stuttgart · New York

344
P. Gao, Y. Wei
PAPER
tries 4 and 5). The influence of other additives on the re- With the optimized conditions in hand, the scope of this
action was then studied. It was found that when sodium N-iodosuccinimide-mediated oxidative lactonization was
carbonate added as a base, the yield of 2a decreased examined (Scheme 1). To our satisfaction, a variety of 2-
slightly (entry 6). To our surprise, the addition of ammo- arylbenzoic acids bearing electron-donating or electron-
nium chloride resulting in a dramatic decrease in the yield withdrawing groups in the aryl ring all reacted well and
of 2a to 34% (entry 7). The use of other additives, such as the corresponding products 2 were obtained in moderate
2-iodobenzoic acid and 2,2′-azobisisobutyronitrile, also to excellent yields. Compared to the substrates with elec-
did not improve the yield of 2a (entries 8 and 9). The use tron-withdrawing substituents, such as chloro and trifluo-
of various solvents was also examined, including 1,2-di- romethyl, substrates with electron-donating substituents
chloroethane, toluene, methanol, dimethyl sulfoxide, and such as methoxy, phenoxy, and methyl, gave higher yields
2,2,2-trifluoroethanol; 1,2-dichloroethane was the best of products. Interestingly, cyclization of meta-substituted
solvent for the reaction (entries 3 and 10–13). It should be (R2) 2-arylbenzoic acids gave two regioisomers with dif-
noted that when the reaction was carried out in darkness, ferent ratios. When methyl was in meta position of the
a lower yield of 2a was obtained and this observation sug- phenyl ring, the product ratio of para cyclization to ortho
gests that visible light may play a key role in this transfor- cyclization was 2g/2g′ 1.4:1. However, when methoxy
mation (entry 14). Decreasing the reaction temperature was in the meta position of the phenyl ring, the product ra-
from 75 °C to room temperature gave 2a in only 38% tio of para cyclization to ortho cyclization was 2j/2j′
yield (entry 15). Overall, the following optimized proce- 13:1. These results suggest that an electron-rich ring was
dure was chosen: N-iodosuccinimide (2.5 equiv) as oxi- more reactive in this reaction. It was also found cycliza-
dant in 1,2-dichloroethane at 75 °C (entry 3).
tion of ortho-substituted (R1 or R2) substrates, 1b and 1f,
O
O
OH
O
R1
NIS (2.5 equiv)
R1
ClCH2CH2Cl, 75 °C
visible light
R2
R2
2
1
O
O
O
O
O
O
MeO
O
O
O
O
F
2a, 86%
2b, 62%
2c, 79%
2d, 86%
2e, 85%
O
O
O
O
O
O
O
O
O
O
OMe
2g, 73%, o/p =1.4:1
2h, 93%
2i, 89%
2f, 64%
O
O
O
O
O
O
O
O
O
O
OMe
F
Cl
OPh
OMe
O
2j, 76%, o/p =13:1
2k, 90%
2l, 89%
2m, 75%
O
O
O
O
O
O
F
O
CF3
O
Cl
2n, 67%
2o, trace
2p, 78%
2q, 74%
Scheme 1 Substrate scope
Synthesis 2014, 46, 343–347
© Georg Thieme Verlag Stuttgart · New York

PAPER
NIS-Mediated Oxidative C–H Lactonization of 2-Arylbenzoic Acids
345
gave relatively lower yields of the corresponding prod- Further work to understand the mechanism and extend the
ucts, 2b and 2f, presumably because steric hindrance by scope of the protocol is currently under investigation in
the ortho substituents makes the coplanar form of the two our laboratory.
benzene ring difficult to obtain. When 2-(furan-2-yl)ben-
zoic acid (1o), a heterocyclic substrate, was employed in
the reaction, the reaction was complex and only trace
amounts of the product 2o were detected.
All solvents and reagents were obtained from commercial sources
and used without further purification. NMR spectra were recorded
on a Bruker Avance 500 spectrometer. HRMS were recorded on a
Waters Micromass GCT Premier using ESI-TOF (EI-ToF). IR spec-
tra were recorded on a Nicolet-10 FTIR instrument. Melting points
were determined on Yamato melting point apparatus Model MP-21.
Silica gel (200–300 mesh) was used for column chromatographic
separations and purifications. Petroleum ether (PE) refers to the
fraction boiling in the 60–90 °C range.
For practical purposes, the synthesis of dibenzopyranone
2h from the corresponding 2-(4-methylphenyl)benzoic
acid (1h) was scaled up to a gram scale (Scheme 2). Since
the byproduct, pyrrolidine-2,5-dione, is soluble in water,
2h can be simply obtained by aqueous workup in 83%
yield with 96% purity.
Benzo[c]chromen-6-ones 2; General Procedure
To a solution of 2-arylbenzoic acid 1 (0.5 mmol) in ClCH2CH2Cl (3
mL) was added NIS (1.25 mmol) in one portion; the mixture was
heated to 75 °C for 4 h. After completion of the reaction, EtOAc (10
mL) was added and the mixture was washed with sat. Na2S2O3 (5
mL), then with H2O (2 × 5 mL). The organic layer was dried (anhyd
Na2SO4) and concentrated in vacuo. The crude products were puri-
fied by column chromatography (silica gel, PE–EtOAc, 50:1) to
provide the product 2. All the products were confirmed by 1H and
13C NMR spectra and new compounds were reconfirmed addition-
ally by HRMS.
O
O
OH
O
NIS (2.5 equiv)
ClCH2CH2Cl, 75 °C
visible light
1h, 5 mmol, 1.06 g
no column chromatography
2h, yield 83%, purity 96%
6H-Benzo[c]chromen-6-one (2a)7a
White solid; yield: 84.3 mg (86%); mp 91–92 °C.
Scheme 2 Gram-scale preparation of 2h
1H NMR (500 MHz, CDCl3): δ = 8.39 (dd, J1 = 1.2 Hz, J2 = 7.9 Hz,
1 H), 8.11 (d, J = 8.1 Hz, 1 H), 8.05 (dd, J1 = 1.3 Hz, J2 = 8.0 Hz, 1
H), 7.80–7.83 (m, 1 H), 7.55–7.59 (m, 1 H), 7.45–7.48 (m, 1 H),
7.31–7.36 (m, 2 H).
13C NMR (125 MHz, CDCl3): δ = 161.1, 151.3, 134.8, 134.7, 130.5,
130.4, 128.9, 124.5, 122.8, 121.7, 121.3, 118.0, 117.7.
To gain insights into the reaction pathway, 2,2,6,6-tetra-
methylpiperidine N-oxide (2.5 equiv), a radical-trapping
reagent, was added to the reaction system under the opti-
mized conditions and none of desired product 2a was
formed. According to the present results and unique prop-
erties of N-halo-substituted compounds,10 a radical cycli-
zation mechanism was proposed (Scheme 3). Reaction of
2-arylbenzoic acid 1 with N-iodosuccinimide formed 2-
arylbenzoic hypoiodous anhydride A. Homolytic cleav-
age of the O–I bond of A then occurred to provide oxygen-
centered radical B. Intramolecular attack of the oxygen-
centered radical on the phenyl ring led to the lactonization
to provide the final product 2.
10-Methyl-6H-benzo[c]chromen-6-one (2b)7a
White solid; yield: 65.1 mg (62%); mp 122–124 °C.
1H NMR (500 MHz, CDCl3): δ = 8.37 (d, J = 7.8 Hz, 1 H), 8.31 (d,
J = 8.2 Hz, 1 H), 7.65 (d, J = 7.4 Hz, 1 H), 7.46–7.49 (m, 2 H), 7.40
(dd, J1 = 1.3 Hz, J2 = 8.2 Hz, 1 H), 7.31–7.34 (m, 1 H), 2.90 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 161.7, 151.3, 139.0, 135.0, 133.6,
129.6, 129.2, 128.2, 127.2, 124.0, 122.9, 119.7, 118.0, 25.3.
8-Methyl-6H-benzo[c]chromen-6-one (2c)7a
White solid; yield: 83.0 mg (79%); mp 126–128 °C.
1H NMR (500 MHz, CDCl3): δ = 8.18 (s, 1 H), 7.98–8.02 (m, 2 H),
7.62 (dd, J1 = 1.4 Hz, J2 = 8.2 Hz, 1 H), 7.42–7.46 (m, 1 H), 7.29–
7.35 (m, 2 H), 2.49 (s, 3 H).
In summary, a simple and convenient N-iodosuccinimide-
mediated oxidative lactonization procedure was devel-
oped. Broad substrate scope, good functional group toler-
ance, and mild reaction conditions make the protocol a
potential approach for the synthesis of dibenzopyranones.
O
O
O
I
O
O
OH
light
R1
R1
R1
NIS
I
NHS
R2
R2
R2
1
A
B
O
O
O
NIS
R1
O
O
O
O
O
R1
N
H
N
I
NHS
R2
NIS
NHS
R2
C
2
Scheme 3 Proposed reaction mechanism
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 343–347

346
P. Gao, Y. Wei
PAPER
13C NMR (125 MHz, CDCl3): δ = 161.4, 151.0, 139.2, 136.0, 132.2,
130.4, 129.9, 124.5, 122.5, 121.7, 121.1, 118.2, 117.7, 21.3.
1.14 H), 7.44 (d, J = 2.9 Hz, 1 H), 7.21–7.27 (m, 1.11 H), 7.01 (dd,
J1 = 2.9 Hz, J2 = 9.0 Hz, 1.05 H), 3.96 (s, 0.22 H), 3.89 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 161.2, 160.5, 156.4, 145.6, 134.7,
134.6, 130.6, 128.9, 121.7, 121.4, 118.6, 118.5, 117.1, 114.1, 112.3,
106.4, 56.2, 55.9.
8-Methoxy-6H-benzo[c]chromen-6-one (2d)7b
White solid; yield: 97.2 mg (86%); mp 159–161 °C.
1H NMR (500 MHz, CDCl3): δ = 8.01 (d, J = 8.8 Hz, 1 H), 7.95 (dd,
J1 = 1.1 Hz, J2 = 7.9 Hz, 1 H), 7.78 (d, J = 2.8 Hz, 1 H), 7.28–7.42
(m, 4 H), 3.92 (s, 3 H).
3-Phenoxy-6H-benzo[c]chromen-6-one (2k)
White solid; yield: 129.6 mg (90%); mp 148–150 °C.
13C NMR (125 MHz, CDCl3): δ = 161.2, 160.0, 150.5, 129.3, 128.1,
FT-IR: 1730, 1600, 1270, 1070, 813 cm–1.
124.6, 124.2, 123.4, 122.4, 122.1, 118.2, 117.6, 111.3, 55.8.
1H NMR (500 MHz, CDCl3): δ = 8.34 (dd, J1 = 0.8 Hz, J2 = 7.9 Hz,
1 H), 7.98 (q, J = 8.5 Hz, 1 H), 7.78 (m, 1 H), 7.52 (t, J = 7.9 Hz, 1
H), 7.39–7.43 (m, 2 H), 7.21 (t, J = 7.4 Hz, 1 H), 7.1 (d, J = 7.7 Hz,
1 H), 6.98 (dd, J1 = 2.5 Hz, J2 = 7.5 Hz, 1 H), 6.90 (d, J = 2.4 Hz, 1
H).
13C NMR (125 MHz, CDCl3): δ = 161.2, 159.8, 155.6, 152.4, 134.9,
134.8, 130.6, 130.1, 128.2, 124.6, 124.0, 121.3, 120.3, 120.0, 114.8,
113.0, 106.4.
9-Fluoro-6H-benzo[c]chromen-6-one (2e)
White solid; yield: 91.0 mg (85%); mp 171–172 °C.
FT-IR: 1730, 1610, 1280, 1200, 1100 cm–1.
1H NMR (500 MHz, CDCl3): δ = 8.42 (m, 1 H), 7.94 (d, J = 7.5 Hz,
1 H), 7.72 (dd, J1 = 2.3 Hz, J2 = 9.6 Hz, 1 H), 7.51 (m, 1 H), 7.35
(m, 2 H), 7.26 (td, J1 = 2.1 Hz, J2 = 8.6 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 167.0 (d, JC-F = 255.4 Hz), 160.2,
151.7, 137.7 (d, JC-F = 9.8 Hz), 134.0 (d, JC-F = 10.1 Hz), 131.3,
124.7, 123.0, 117.9, 117.8, 117.4, 117.0 (d, JC-F = 22.8 Hz), 108.1
(d, JC-F = 4.7 Hz).
HRMS (EI): m/z [M]+ calcd for C13H7FO2: 214.0430; found:
214.0428.
HRMS (EI): m/z [M]+ calcd for C19H12O3: 288.0785; found:
288.0784.
3-Fluoro-6H-benzo[c]chromen-6-one (2l)7a
White solid; yield: 95.2 mg (89%); mp 159–161 °C.
1H NMR (500 MHz, CDCl3): δ = 8.33 (d, J = 7.9 Hz, 1 H), 7.99 (t,
J = 7.2 Hz, 2 H), 7.80 (t, J = 7.7 Hz, 1 H), 7.54 (t, J = 7.6 Hz, 1 H),
7.02–7.07 (m, 2 H).
13C NMR (125 MHz, CDCl3): δ = 163.5 (d, JC-F = 248.3 Hz), 160.7,
152.1 (d, JC-F = 12.0 Hz), 135.1, 134.2, 130.6, 128.7, 124.3 (d,
JC-F = 9.7 Hz), 121.5, 120.4, 114.6, 112.4 (d, JC-F = 22.3 Hz), 105.0
(d, JC-F = 25.1 Hz).
1-Methyl-6H-benzo[c]chromen-6-one (2f)7a
White solid; yield: 67.2 mg (64%); mp 130–132 °C.
1H NMR (500 MHz, CDCl3): δ = 8.37 (d, J = 7.9 Hz, 1 H), 8.31 (d,
J = 8.1 Hz, 1 H), 7.64 (d, J = 7.4 Hz, 1 H), 7.47 (m, 2 H), 7.40 (dd,
J1 = 1.3 Hz, J2 = 8.1 Hz, 1 H), 7.33 (m, 1 H), 2.90 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 161.2, 149.7, 135.2, 134.7, 131.8,
130.5, 128.7, 127.1, 124.0, 121.8, 121.1, 120.4, 117.8, 16.0.
3-Chloro-6H-benzo[c]chromen-6-one (2m)7a
White solid; yield: 86.3 mg (75%); mp 160–161 °C.
1H NMR (500 MHz, CDCl3): δ = 8.36 (d, J = 8.0 Hz, 1 H), 8.04 (d,
J = 8.1 Hz, 1 H), 7.95 (d, J = 8.5 Hz, 1 H), 7.81 (m, 1 H), 7.57 (t, J
= 7.6 Hz, 1 H), 7.35 (d, J = 1.8 Hz, 1 H), 7.29 (dd, J1 = 2.1 Hz, J2 =
8.5 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 160.5, 151.6, 136.0, 135.1, 134.0,
130.8, 129.2, 126.0, 123.8, 121.7, 121.0, 118.0, 116.7.
2-Methyl-6H-benzo[c]chromen-6-one (2g) and 4-Methyl-6H-
benzo[c]chromen-6-one (2g′)7b
White solid; yield: 76.7 mg (73%); mp 93–95 °C.
1H NMR (500 MHz, CDCl3): δ = 8.38 (m, 1.68 H), 8.08 (t, J = 7.3
Hz, 1.75 H), 7.87 (d, J = 7.9 Hz, 0.74 H), 7.77–7.81 (m, 2.67 H),
7.53–7.57 (m, 1.73 H), 7.31 (d, J = 7.3 Hz, 0.77 H), 7.17–7.26 (m,
2.86 H), 2.48 (s, 2.21 H), 2.44 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 161.3, 161.2, 149.7, 149.4, 135.1,
134.8, 134.7, 134.1, 131.8, 131.3, 130.6, 130.5, 128.7, 127.0, 124.0,
122.7, 121.6, 121.3, 121.1, 120.4, 117.7, 117.6, 117.5, 21.1, 16.0.
3-(Trifluoromethyl)-6H-benzo[c]chromen-6-one (2n)7a
White solid; yield: 88.5 mg (67%); mp 146–147 °C.
1H NMR (500 MHz, CDCl3): δ = 8.45 (dd, J1 = 0.94 Hz, J2 = 7.9 Hz,
1 H), 8.18 ((t, J = 9.1 Hz, 2 H), 7.88–7.91 (m, 1 H), 7.66–7.70 (m,
1 H), 7.63 (s, 1 H), 7.59 (d, J = 8.3 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 160.2, 151.0, 135.2, 133.4, 132.3
(d, JC-F = 33.0 Hz), 130.9, 130.1, 124.4, 123.6, 122.2, 121.7, 121.1,
115.3 (d, JC-F = 3.1 Hz).
3-Methyl-6H-benzo[c]chromen-6-one (2h)7a
White solid; yield: 97.7 mg (93%); mp 136–138 °C.
1H NMR (500 MHz, CDCl3): δ = 8.36 (d, J = 7.8 Hz, 1 H), 8.05 (d,
J = 8.1 Hz, 1 H), 7.90 (d, J = 8.1 Hz, 1 H), 7.77 (m, 1 H), 7.52 (t,
J = 7.7 Hz, 1 H), 7.13 (m, 2 H), 2.42 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 161.4, 151.4, 141.3, 136.0, 134.7,
130.6, 128.4, 126.7, 122.5, 121.4, 121.0, 117.9, 115.5, 21.4.
9-Fluoro-3-methyl-6H-benzo[c]chromen-6-one (2p)
White solid; yield: 88.9 mg (78%); mp 220–221 °C.
FT-IR: 3090, 1730, 1610, 1300, 1190, 856 cm–1.
3-Methoxy-6H-benzo[c]chromen-6-one (2i)7a
White solid; yield: 100.6 mg (89%); mp 141–143 °C.
1H NMR (500 MHz, CDCl3): δ = 8.38 (d, J = 8.0 Hz, 1 H), 8.02 (d,
J = 8.1 Hz, 1 H), 7.96 (d, J = 8.8 Hz, 1 H), 7.80 (t, J = 7.7 Hz, 1 H),
7.52 (t, J = 7.6 Hz, 1 H), 6.93 (dd, J1 = 2.4 Hz, J2 = 8.8 Hz, 1 H),
6.88–6.90 (m, 1 H), 3.90 (s, 3 H).
1H NMR (500 MHz, CDCl3): δ = 8.40 (m, 1 H), 7.81 (d, J = 7.9 Hz,
1 H), 7.68 (dd, J1 = 2.4 Hz, J2 = 9.7 Hz, 1 H), 7.22 (td, J1 = 2.3 Hz,
J2 = 8.5 Hz, 1 H), 7.15–7.17 (m, 2 H), 2.46 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 167.0 (d, JC-F = 254.9 Hz), 160.5,
151.7, 142.3, 138.0 (d, JC-F = 9.7 Hz), 133.9 (d, JC-F = 10.1 Hz),
125.8, 122.7, 118.0, 117.4, 116.5 (d, JC-F = 22.9 Hz), 114.8, 107.8
(d, JC-F = 23.4 Hz), 21.5.
13C NMR (125 MHz, CDCl3): δ = 161.6, 161.4, 152.7, 135.2, 134.8,
130.6, 127.7, 123.8, 121.1, 120.1, 112.5, 112.2, 101.7, 55.7.
HRMS (EI): m/z [M]+ calcd for C14H9FO2: 228.0587; found:
2-Methyl-6H-benzo[c]chromen-6-one (2j) and 4-Methyl-6H-
benzo[c]chromen-6-one (2j′)7b
228.0592.
White solid; yield: 85.9 mg (76%); mp 156–158 °C.
3-Chloro-8-methyl-6H-benzo[c]chromen-6-one (2q)
White solid; yield: 90.3 mg (74%); mp 176–178 °C.
FT-IR: 3080, 2920, 1730, 1620, 1300, 1100, 859 cm–1.
1H NMR (500 MHz, CDCl3): δ = 8.37 (dd, J1 = 0.9 Hz, J2 = 7.9 Hz,
1 H), 8.00–8.06 (m, 1.07 H), 7.77–7.81 (m, 1.06 H), 7.54–7.59 (m,
Synthesis 2014, 46, 343–347
© Georg Thieme Verlag Stuttgart · New York

PAPER
NIS-Mediated Oxidative C–H Lactonization of 2-Arylbenzoic Acids
347
1H NMR (500 MHz, CDCl3): δ = 8.12 (s, 1 H), 7.89 (m, 2 H), 7.60
(dd, J1 = 1.2 Hz, J2 = 8.1 Hz, 1 H), 7.24–7.30 (m, 2 H), 2.47 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 160.7, 151.2, 139.6, 136.2, 135.3,
131.4, 130.5, 124.9, 123.5, 121.6, 120.7, 117.8, 115.8, 21.3.
HRMS (EI): m/z [M]+ calcd for C14H9ClO2: 244.0289; found:
Trauner, D. Org. Lett. 2011, 13, 1386. (c) Carlson, E. J.;
Riel, A. M. S.; Dahl, B. J. Tetrahedron Lett. 2012, 53, 6245.
(3) (a) Renz, M.; Meunier, B. Eur. J. Org. Chem. 1999, 737.
(b) Mehta, G.; Pandey, P. N. Synthesis 1975, 404.
(4) (a) Thasana, N.; Worayuthakarn, R.; Kradanrat, P.; Hohn,
E.; Young, L.; Ruchirawat, S. J. Org. Chem. 2007, 72, 9379.
(b) Ceylan, S.; Klande, T.; Vogt, C.; Friese, C.; Kirschning,
A. Synlett 2010, 2009.
244.0290.
(5) (a) Harayama, T.; Yasuda, H. Heterocycles 1997, 46, 61.
(6) (a) Inamoto, K.; Kadokawa, J.; Kondo, Y. Org. Lett. 2013,
15, 3962. (b) Luo, S.; Luo, F.-X.; Zhang, X.-S.; Shi, Z.-J.
Angew. Chem. Int. Ed. 2013, 52, 10598.
Acknowledgment
We are grateful to Nanjing University of Science and Technology
for financial support.
(7) (a) Li, Y.; Ding, Y.-J.; Wang, J.-Y.; Su, Y.-M.; Wang, X.-S.
Org. Lett. 2013, 15, 2574. (b) Donaire, J. G.; Martin, R.
J. Am. Chem. Soc. 2013, 135, 9350.
(8) (a) Togo, H.; Muraki, T.; Yokoyama, M. Tetrahedron Lett.
1995, 36, 7089. (b) Togo, H.; Muraki, T.; Hoshina, Y.;
Yamaguchi, K. J. Chem. Soc., Perkin Trans. 1 1997, 787.
(c) Muraki, T.; Togo, H.; Yokoyama, M. J. Chem. Soc.,
Perkin Trans. 1 1999, 1713. (d) Furuyama, S.; Togo, H.
Synlett 2010, 2325.
(9) (a) Gao, P.; Liu, J.-J.; Wei, Y.-Y. Org. Lett. 2013, 15, 2872.
(b) Gao, P.; Wei, Y.-Y. Heterocycl. Commun. 2013, 19, 113.
(c) Gao, P.; Wei, Y.-Y. J. Chem. Res. 2013, 506. (d) Zhu, C.-
J.; Wei, Y.-Y. ChemSusChem 2011, 4, 1082. (e) Liu, H.-X.;
Wei, Y.-Y. Tetrahedron Lett. 2013, 54, 7089.
(10) (a) Beebe, T. R.; Howard, F. M. J. Am. Chem. Soc. 1969, 91,
3379. (b) McDonald, C.; Holcomb, H.; Kennedy, K.;
Kirkpatrick, E.; Leathers, T.; Vanemon, P. J. Org. Chem.
1989, 54, 1213. (c) Kolvari, E.; Choghamarani, A. G.;
Salehi, P.; Shirini, F.; Zolfigol, M. A. J. Iran. Chem. Soc.
2007, 4, 126.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
n
nfomartit
References
(1) (a) Bringmann, G.; Menche, D. Acc. Chem. Res. 2001, 34,
615. (b) Hertweck, C.; Luzhetskyy, A.; Rebets, Y.;
Bechthold, A. Nat. Prod. Rep. 2007, 24, 162. (c) Bringmann,
G.; Gulder, T.; Gulder, T. A. M.; Breuning, M. Chem. Rev.
2011, 111, 563. (d) Zhang, Y.-J.; Abe, T.; Tanaka, T.; Yang,
C.-R.; Kouno, I. J. Nat. Prod. 2001, 64, 1527. (e) Pfundstein,
B.; El Desouky, S. K.; Hull, W. E.; Haubner, R.; Erben, G.;
Owen, R. W. Phytochemistry 2010, 71, 1132. (f) Shepherd,
M. D.; Kharel, M. K.; Zhu, L. L.; van Lanen, S. G.; Rohr, J.
Org. Biomol. Chem. 2010, 8, 3851.
(2) (a) Kemperman, G. J.; Horst, B. T.; de Goor, D. V.; Roeters,
T.; Bergwerff, J.; der Eem, R. V.; Basten, J. Eur. J. Org.
Chem. 2006, 3169. (b) Hager, A.; Mazunin, D.; Mayer, P.;
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 343–347