Synthesis of 3-substituted isocoumarins via a cascade intramolecular Ullmann-type coupling-rearrangement process

Article abstract of DOI:10.1021/jo300916s

A simple and highly efficient strategy for the synthesis of 3-substituted isocoumarins through a copper(I)-catalyzed reaction of 1-(2-halophenyl)-1,3- diones has been developed. The procedure is based on a cascade copper-catalyzed intramolecular Ullmann-type C-arylation and rearrangement process. This methodology is tolerant of a wide range of substrates and applicable to library synthesis.

Full text of DOI:10.1021/jo300916s

Article
pubs.acs.org/joc
Synthesis of 3-Substituted Isocoumarins via a Cascade
Intramolecular Ullmann-Type Coupling−Rearrangement Process
Zhi-Yuan Ge,† Xiang-Dong Fei,† Ting Tang,† Yong-Ming Zhu,*,† and Jing-Kang Shen*,‡
†College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People’s Republic of China
‡Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People’s Republic of China
S
* Supporting Information
ABSTRACT: A simple and highly efficient strategy for the synthesis of 3-substituted isocoumarins through a copper(I)-
catalyzed reaction of 1-(2-halophenyl)-1,3-diones has been developed. The procedure is based on a cascade copper-catalyzed
intramolecular Ullmann-type C-arylation and rearrangement process. This methodology is tolerant of a wide range of substrates
and applicable to library synthesis.
involved multistep reaction sequences, harsh conditions, or
expensive catalysts. Recently, several copper-catalyzed inter-
molecular domino reactions from 2-halobenzoic acids or 2-
halobenzoic acid derivatives with 1,3-diketones have been
recognized as substantial methods for the synthesis of 3-
substituted isocoumarins (Scheme 2a).17 A similar method was
previously used in the synthesis of isoquinolinones.18 As part of
our continuing effort at the construction of heterocycles via
copper-catalyzed reactions,2,19 herein, we would like to report a
serendipitous finding, an atom-economical tandem process for
the construction of various 3-substituted isocoumarins by a
copper-catalyzed reaction of 1-(2-halophenyl)-3-phenylpro-
pane-1,3-diones (Scheme 2b).
INTRODUCTION
■
Recently, transition-metal-catalyzed coupling reactions, as a
powerful tool for the formation of C−C and C−X (X = N, O,
S) bonds, have gained much interest due to their high
regiospecificity and broad compatibility regarding functional
groups.1 In 2011, our group successfully synthesized isoflavones
from β-ketonaldehydes via CuI-catalyzed intramolecular
cyclization.2 We hypothesized that the same strategy might
be applicable to prepare flavones via the copper-catalyzed
tandem reaction of 1-(2-halophenyl)-3-phenylpropane-1,3-
dione. Simultaneously, a catalyst-free methodology for the
synthesis of flavones was reported (path a in Scheme 1).3
Unexpectedly, isocoumarin was obtained instead of flavone in
our ongoing experiments. Isocoumarins4 are an important class
of naturally occurring lactones that exhibit a broad range of
biological activities such as antimicrobial and antiallergic,5
antifungal,6 anticancer,7 and anti-HIV8 properties and are also
used as important intermediates for the synthesis of some
natural products.9 As a result, we transferred our research
objective to the synthesis of isocoumarin (path b in Scheme 1).
The wide range of biological activities has led to continued
interest in the synthesis of isocoumarin derivatives, especially
isocoumarins substituted in the 3-position. Various methods for
constructing these molecules have been reported,10 including
cyclization of 2-alkenyl or 2-allylbenzoic acid derivatives,11
condensation of benzoic acid derivatives with alkynes or
alkenes,12 palladium-catalyzed carbonylation of o-iodobenzyl
alkyl ketones or α-(o-haloaryl)-substituted ketones,13 micro-
wave-assisted reaction of homophthalic acid with acid chlorides
or esters,14 NHC-catalyzed oxidative cyclization of 2-alkynyl
benzaldehydes,15 and thermal cyclization reaction of δ-
ketoamides.16 These methods were presented as efficient
protocols for both carbon and heterocycle assembly. However,
the synthetic strategies for the construction of these molecules
RESULTS AND DISCUSSION
■
Using 1-(2-iodophenyl)-3-phenylpropane-1,3-dione 1a as the
model substrate, optimization of the reaction conditions was
investigated through systematic screening. As shown in Table 1,
several solvents were examined in the presence of CuI, 2-
picolinic acid, and K2CO3 (Table 1, entries 1−5), and the
expected product 2a was formed in 81% yield when toluene
was employed (Table 1, entry 5). To further improve the yield,
we surveyed a series of reaction conditions and found that 2-
picolinic acid, in comparison with other ligands or a ligand-free
condition, produced 2a in the best yield (Table 1, entries 6−8),
and only a small amount of 2a (less than a 5% yield) was
obtained in the absence of a catalyst and a ligand (Table 1,
entry 9). Our investigation of bases showed that K2CO3 was
optimal (Table 1, entries 5, 10, and 11). Then, the activity of
the catalyst was also investigated, and a comparison of catalysts
indicated that CuI was superior to the others (Table 1, entries
Received: May 6, 2012
Published: June 7, 2012
© 2012 American Chemical Society
5736
dx.doi.org/10.1021/jo300916s | J. Org. Chem. 2012, 77, 5736−5743

The Journal of Organic Chemistry
Article
Scheme 1. Cyclization of 1-(2-Halophenyl)-3-phenylpropane-1,3-diones
Scheme 2. Copper-Catalyzed Intermolecular and Intramolecular Reactions Leading to 3-Substituted Isocoumarins from 1,3-
Diketones
17 and 18), which were present in compound 1, were well
tolerated during the course of the reaction. R2 affected the
reaction significantly, with electron rich aromatics giving higher
yields than electron poor counterparts (Table 2, entries 2−11).
It is interesting that good yields were also obtained when R2
was a heteroaryl or aliphatic group (Table 2, entries 12−18).
Steric hindrance caused a considerable decrease in the yields
(Table 2, entries 8, 9, and 15). In addition, when the substrate
was changed from iodoarene to bromoarene, a slightly lower
yield was observed (Table 2, entry 19).
As illustrated in Table 3, this process was compatible with a
variety of electron-withdrawing and electron-donating groups
(Table 3, entries 1−4). It was noted that when R1 was an
electron-withdrawing group, higher yields were obtained (Table
3, entries 1, 3, and 4). Interestingly, the corresponding products
2a′ and 2b′ were produced in high yields when 1-(1-
bromonaphthalen-2-yl) was the substituent on substrates 1a′
and 1b′ (Table 3, entries 9 and 10) probably owing to the weak
aromaticity of the naphthalene ring. Besides, as an anticipated
4-substituted isocoumarin, the R3 substituent on 1 was also
tolerated, and the target product 4-methyl-3-phenyl-1H-
isochromen-1-one (2c′) was generated in moderate yield
(Table 3, entry 11).
Table 1. Condition Optimizations for Isocoumarin
Synthesis
a
b
c
d
entry
catalyst
CuI
ligand
base
solvent
yield (%)
1
L1
L1
L1
L1
L1
L2
L3
−
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
K3PO4
K2CO3
K2CO3
K2CO3
K2CO3
1,4-dioxane
DMSO
DMF
50
8
2
CuI
3
CuI
<5
32
81
68
70
65
<5
44
38
58
65
<5
32
4
CuI
THF
5
CuI
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
6
CuI
7
CuI
8
CuI
9
−
CuI
−
10
11
12
13
14
15
L1
L1
−
CuI
Cu(OAc)2
Cu(OAc)2
Pd(OAc)2
Pd(OAc)2
L1
−
L4
To elucidate the reaction mechanism for the synthesis of the
3-substituted isocoumarin derivatives, the following three
control experiments were carried out (Scheme 3). Two
equivalents of the radical scavenger 2,2,6,6-tetramethylpiper-
idinyl-1-oxyl (TEMPO) did not have an observable effect on
the outcome of the reaction, suggesting that the reaction does
not proceed via a radical intermediate (Scheme 3a). The
product 2a was obtained in good yield when 1,3-diphenylpro-
pane-1,3-dione was added to the reaction system (Scheme 3b),
which implies the reaction is on an intramolecular mechanism
basis. Under the same reaction conditions, when N-benzoyl-2-
bromobenzamide was employed as starting material, 2-phenyl-
4H-3,1-benzoxazin-4-one was obtained in 42% yield (Scheme
3c), which supports the fact that the reaction mechanism may
involve an intramolecular Ullmann-type coupling process.
Based on the above experimental results, together with
related reports,17c,20 a plausible mechanism for the copper-
a
All reactions were run with 1a (0.5 mmol), catalyst (0.05 mmol),
ligand (0.1 mmol), base (1.0 mmol), and solvent (2 mL) under
nitrogen in a sealed tube for 6 h. L1, 2-picolinic acid; L2, ( )-trans-
1,2-diaminocyclohexane; L3, 1,10-phenanthroline; L4, triphenylphos-
phine (PPh3). The reaction temperature for 1,4-dioxane and toluene
b
c
was 110 °C; DMSO and DMF were at 120 °C, and THF was at 70 °C.
d
Isolated yield.
12−15). Therefore, the optimal reaction conditions were run in
the presence of CuI (10 mol %), 2-picolinic acid (20 mol %),
and K2CO3 (200 mol %) in anhydrous toluene (2 mL) within a
sealed tube under nitrogen at 110 °C.
With these results in hand, we sought to examine the scope
and generality of the method. As shown in Tables 2 and 3, the
catalyst system was tolerant of a wide range of substrates.
Various substituents, including aryl (Table 2, entries 1−11),
heteroaryl (Table 2, entries 12−16), and alkyl (Table 2, entries
5737
dx.doi.org/10.1021/jo300916s | J. Org. Chem. 2012, 77, 5736−5743

The Journal of Organic Chemistry
Article
a
Table 2. Synthesis of 3-Substituted Isocoumarins
a
The reactions were performed in a sealed tube with 1 (0.5 mmol), CuI (0.05 mmol), 2-picolinic acid (0.1 mmol), and K2CO3 (1.0 mmol) in
b
toluene (2 mL) at 110 °C under nitrogen. Isolated yield.
5738
dx.doi.org/10.1021/jo300916s | J. Org. Chem. 2012, 77, 5736−5743

The Journal of Organic Chemistry
Article
a
Table 3. Synthesis of Functionalized 3-Substituted Isocoumarins
a
The reactions were performed in a sealed tube with 1 (0.5 mmol), CuI (0.05 mmol), 2-picolinic acid (0.1 mmol), and K2CO3 (1.0 mmol) in
b
toluene (2 mL) at 110 °C under nitrogen. Isolated yield.
catalyzed tandem reaction of the 1,3-dione compound 1a is
proposed as shown in Scheme 4. Initially, copper iodide would
activate the 1,3-dione (1a) to generate a copper(I) complex, A,
which would then give rise to the four-membered ring
intermediate, B, via the intramolecular Ullmann-type coupling
process of the C−C bond. Then, release of ring strain from B
led rapidly to the ketene compound, C. Finally, ring closure
would lead to the desired six-membered annulation product, 2a.
5739
dx.doi.org/10.1021/jo300916s | J. Org. Chem. 2012, 77, 5736−5743

The Journal of Organic Chemistry
Article
Scheme 3. Investigation of the Reaction Mechanism for the Synthesis of the 3-Substituted Isocoumarin Derivatives
Scheme 4. A Plausible Reaction Mechanism
were carried out using time-of-flight mass spectrometry (TOF-MS) or
electrospray ionization (ESI) mass spectrometry.
During the conversion of 1a to 2a, the four-membered ring
transition state was produced, in which the copper(I) catalyst
would play a significant role.
General Procedure for the Synthesis of Compounds 2a−2c′.
A sealed tube was charged with a magnetic stir bar, 1,3-dione, 1 (0.5
mmol), CuI (0.05 mmol, 10 mg), 2-picolinic acid (0.1 mmol, 12 mg),
K2CO3 (1.0 mmol, 138 mg), and anhydrous toluene (2 mL). The tube
was purged with nitrogen gas, and its contents were stirred at 110 °C
for the indicated time. After reaction completion, the mixture was
filtered through a short plug of Celite and washed with EtOAc (3 mL,
two times). The combined filtrates were concentrated on a rotary
evaporator and purified on a silica gel column using petroleum ether/
EtOAc as the eluent to give the pure target product.
Characterization Data of the Isolated Compounds. 3-Phenyl-
1H-isochromen-1-one (2a). Eluent: petroleum ether/EtOAc (100:1).
Yield: for substrate 1a, 81% (90 mg); for substrate 1aa, 68% (76 mg).
White solid. Mp: 81−82 °C. 1H NMR (400 MHz, CDCl3): δ 8.30 (d, J
= 8.1 Hz, 1H), 7.87 (d, J = 7.8 Hz, 2H), 7.71 (t, J = 7.6 Hz, 1H),
7.53−7.39 (m, 5H), 6.94 (s, 1H). 13C NMR (101 MHz, CDCl3): δ
162.3, 153.5, 137.4, 134.8, 131.9, 129.9, 129.6, 128.8, 128.1, 125.9,
125.2, 120.5, 101.8. IR (KBr): ν = 3071, 1719, 1635, 1481, 1230, 1071,
1028, 1011, 765, 744, 684 cm−1. HRMS (EI): calcd for C15H10O2
[M]+, 222.0681; found, 222.0683.
CONCLUSION
■
In summary, we have developed a new method for the synthesis
of 3-substituted isocoumarins. The protocol uses readily
available 1-(2-halophenyl)-1,3-diones (obtained from 2-haloar-
ylcarboxylic acid chloride with ketones)21 as starting materials
and CuI/2-picolinic acid as the catalyst system. The procedure
involves an intramolecular-sequential copper-catalyzed C−C
coupling reaction and a rearrangement process. Characterized
by mild reaction conditions, good to excellent yields, and a
wide functional-group tolerance, this protocol should be very
attractive in synthetic organic and medicinal chemistry.
EXPERIMENTAL SECTION
■
General Remarks. Chemicals and reagents were purchased from
commercial suppliers and used without special instructions. All
anhydrous solvents used in the reactions were dried and freshly
distilled. Thin-layer chromatography (TLC) was performed using
silica HSGF254 plates. Melting points were determined without
correction on a digital melting-point apparatus. 1H and 13C NMR
spectra were obtained from a solution in CDCl3 with tetramethylsilane
(TMS) as the internal standard using a 400:101 MHz (1H/13C) or
300:75 MHz (1H/13C) spectrometer, δ in parts per million, and J in
hertz. Infrared (IR) spectra were obtained using KBr tablets and
wavenumbers in cm−1. High-resolution mass spectra (HRMS) analyses
3-(4-Methoxyphenyl)-1H-isochromen-1-one (2b). Eluent: petro-
leum ether/EtOAc (50:1). Yield: 87% (110 mg). White solid. Mp:
1
115−116 °C. H NMR (400 MHz, CDCl3): δ 8.25 (d, J = 8.0 Hz,
1H), 7.78 (d, J = 8.7 Hz, 2H), 7.66 (t, J = 7.5 Hz, 1H), 7.50−7.36 (m,
2H), 6.93 (d, J = 8.7 Hz, 2H), 6.78 (s, 1H), 3.83 (s, 3H). 13C NMR
(101 MHz, CDCl3): δ 162.4, 161.0, 153.6, 137.8, 134.8, 129.5, 127.6,
126.7, 125.6, 124.4, 120.0, 114.1, 100.2, 55.3. IR (KBr): ν = 2999,
2845, 1739, 1633, 1603, 1512, 1262, 1065, 1023, 839, 817, 751, 685
5740
dx.doi.org/10.1021/jo300916s | J. Org. Chem. 2012, 77, 5736−5743

The Journal of Organic Chemistry
Article
cm−1. HRMS (EI): calcd for C16H12O3 [M]+, 252.0786; found,
252.0785.
7.45 (m, 4H), 7.06 (s, 1H). 13C NMR (75 MHz, CDCl3): δ 162.4,
153.4, 137.5, 134.9, 133.8, 133.1, 129.6, 128.8, 128.8, 128.6, 128.2,
127.6, 127.2, 126.8, 126.0, 125.2, 121.9, 120.5, 102.2. IR (KBr): ν =
3053, 1719, 1635, 1484, 1372, 1191, 1073, 852, 819, 748, 680 cm−1.
HRMS (EI): calcd for C19H12O2 [M]+, 272.0837; found, 272.0834.
3-(Benzo[d][1,3]dioxol-5-yl)-1H-isochromen-1-one (2k). Eluent:
petroleum ether/EtOAc (50:1). Yield: 81% (108 mg). White solid.
Mp: 160−162 °C. 1H NMR (400 MHz, CDCl3): δ 8.25 (d, J = 7.9 Hz,
1H), 7.68 (t, J = 7.5 Hz, 1H), 7.44 (t, J = 7.5 Hz, 2H), 7.40 (dd, J =
8.2, 1.7 Hz, 1H), 7.29 (d, J = 1.5 Hz, 1H), 6.85 (d, J = 8.2 Hz, 1H),
6.77 (s, 1H), 6.01 (s, 2H). 13C NMR (101 MHz, CDCl3): δ 162.6,
155.5, 137.4, 136.7, 134.8, 132.7, 131.0, 129.7, 129.5, 129.1, 128.2,
125.9, 125.8, 120.2, 105.9, 20.7. IR (KBr): ν = 3056, 1732, 1618, 1498,
1261, 1113, 1034, 927, 807, 759, 687 cm−1. HRMS (EI): calcd for
C16H10O4 [M]+, 266.0579; found, 266.0578.
3-(Pyridin-3-yl)-1H-isochromen-1-one (2l). Eluent: petroleum
ether/EtOAc (10:1). Yield: 69% (77 mg). Yellow solid. Mp: 162−
164 °C. 1H NMR (400 MHz, CDCl3): δ 9.12 (s, 1H), 8.67 (d, J = 3.2
Hz, 1H), 8.33 (d, J = 7.8 Hz, 1H), 8.20 (d, J = 7.7 Hz, 1H), 7.77 (t, J =
7.3 Hz, 1H), 7.56 (t, J = 7.2 Hz, 2H), 7.42 (dd, J = 7.2, 5.1 Hz, 1H),
7.04 (s, 1H). 13C NMR (101 MHz, CDCl3): δ 161.8, 151.0, 150.6,
146.5, 136.8, 135.1, 132.6, 129.8, 128.8, 128.1, 126.2, 123.6, 120.7,
103.0. IR (KBr): ν = 3038, 1730, 1641, 1486, 1244, 1069, 1022, 847,
803, 752 cm−1. HRMS (ESI): calcd for C14H10NO2 [M + H]+,
224.0706; found, 224.0711.
3-(Furan-2-yl)-1H-isochromen-1-one (2m). Eluent: petroleum
ether/EtOAc (150:1). Yield: 59% (63 mg). Red solid. Mp: 119−121
°C. 1H NMR (400 MHz, CDCl3): δ 8.26 (d, J = 8.0 Hz, 1H), 7.69 (t, J
= 7.5 Hz, 1H), 7.50 (s, 1H), 7.48−7.40 (m, 2H), 6.94 (d, J = 2.8 Hz,
1H), 6.85 (s, 1H), 6.53 (s, 1H). 13C NMR (101 MHz, CDCl3): δ
161.5, 146.8, 146.0, 144.0, 137.2, 134.9, 129.7, 127.9, 125.9, 120.4,
112.1, 110.1, 100.0. IR (KBr): ν = 3151, 1736, 1647, 1479, 1089, 1005,
886, 816, 749, 686 cm−1. HRMS (ESI): calcd for C13H9O3 [M + H]+,
213.0546; found, 213.0555.
3-(Thiophen-2-yl)-1H-isochromen-1-one (2n). Eluent: petroleum
ether/EtOAc (100:1). Yield: 85% (97 mg). Yellow solid. Mp: 109−
111 °C. 1H NMR (400 MHz, CDCl3): δ 8.29 (d, J = 7.9 Hz, 1H), 7.70
(t, J = 7.6 Hz, 1H), 7.61 (d, J = 3.7 Hz, 1H), 7.51−7.43 (m, 2H), 7.40
(d, J = 5.0 Hz, 1H), 7.12 (t, J = 4.3 Hz, 1H), 6.79 (s, 1H). 13C NMR
(75 MHz, CDCl3): δ 161.7, 149.4, 137.4, 135.6, 134.9, 129.8, 128.1,
127.9, 127.4, 126.1, 125.7, 120.3, 100.8. IR (KBr): ν = 3102, 1734,
1631, 1559, 1484, 1072, 1026, 840, 819, 755, 707 cm−1. HRMS (ESI):
calcd for C13H9O2S [M + H]+, 229.0318; found, 229.0330.
3-(1-Methyl-1H-indol-2-yl)-1H-isochromen-1-one (2o). Eluent:
petroleum ether/EtOAc (200:1). Yield: 53% (73 mg). Yellow solid.
Mp: 159−161 °C. 1H NMR (400 MHz, CDCl3): δ 8.35 (d, J = 7.9 Hz,
1H), 7.77 (t, J = 7.4 Hz, 1H), 7.67 (d, J = 7.9 Hz, 1H), 7.57 (t, J = 7.5
Hz, 2H), 7.45−7.32 (m, 3H), 7.22 (d, J = 6.7 Hz, 1H), 7.06 (s, 1H),
3.93 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 161.7, 145.0, 137.0,
136.9, 135.0, 129.8, 128.9, 127.3, 126.3, 125.3, 124.7, 120.9, 120.8,
119.2, 109.9, 109.6, 107.1, 32.3. IR (KBr): ν = 3062, 2942, 1732, 1637,
1347, 1215, 1058, 870, 841, 733, 683 cm−1. HRMS (ESI): calcd for
C18H14NO2 [M + H]+, 276.1019; found, 276.1024.
3-(1-Methyl-1H-indol-3-yl)-1H-isochromen-1-one (2p). Eluent:
petroleum ether/EtOAc (200:1). Yield: 93% (128 mg). Yellow solid.
Mp: 173−174 °C. 1H NMR (400 MHz, CDCl3): δ 8.30 (d, J = 7.8 Hz,
1H), 8.18 (d, J = 7.6 Hz, 1H), 7.68 (t, J = 7.4 Hz, 1H), 7.44 (t, J = 7.3
Hz, 2H), 7.34−7.18 (m, 4H), 6.97 (s, 1H), 3.78 (s, 3H). 13C NMR
(101 MHz, CDCl3): δ 162.5, 150.4, 138.2, 135.5, 134.6, 129.5, 127.3,
125.5, 125.4, 124.5, 123.0, 121.7, 120.9, 119.8, 109.3, 105.2, 102.8,
30.1. IR (KBr): ν = 3099, 2927, 1701, 1627, 1557, 1083, 832, 756, 746,
689 cm−1. HRMS (ESI): calcd for C18H14NO2 [M + H]+, 276.1019;
found, 276.1023.
3-p-Tolyl-1H-isochromen-1-one (2c). Eluent: petroleum ether/
EtOAc (200:1). Yield: 84% (99 mg). White solid. Mp: 113−115 °C.
1H NMR (400 MHz, CDCl3): δ 8.30 (d, J = 8.0 Hz, 1H), 7.78 (d, J =
8.2 Hz, 2H), 7.70 (t, J = 7.6 Hz, 1H), 7.53−7.40 (m, 2H), 7.27 (d, J =
5.7 Hz, 2H), 6.91 (s, 1H), 2.40 (s, 3H). 13C NMR (101 MHz,
CDCl3): δ 162.4, 153.8, 140.2, 137.6, 134.8, 129.5, 129.5, 129.1, 127.8,
125.8, 125.1, 120.3, 101.0, 21.3. IR (KBr): ν = 3068, 2919, 1737, 1626,
1509, 1482, 1237, 1070, 815, 751, 684 cm−1. HRMS (ESI): calcd for
C16H13O2 [M + H]+, 237.0910; found, 237.0910.
3-(4-Fluorophenyl)-1H-isochromen-1-one (2d). Eluent: petroleum
ether/EtOAc (200:1). Yield: 79% (95 mg). White solid. Mp: 132−133
1
°C. H NMR (400 MHz, CDCl3): δ 8.29 (d, J = 7.8 Hz, 1H), 7.92−
7.79 (m, 2H), 7.72 (t, J = 7.4 Hz, 1H), 7.49 (t, J = 7.3 Hz, 2H), 7.14 (t,
J = 8.2 Hz, 2H), 6.88 (s, 1H). 13C NMR (101 MHz, CDCl3): δ 164.9,
162.4, 162.1, 152.6, 137.3, 134.9, 129.6, 128.2, 127.2, 127.2, 125.9,
120.3, 116.0, 115.8, 101.5. IR (KBr): ν = 3098, 1722, 1641, 1599,
1508, 1234, 1069, 826, 745, 681 cm−1. HRMS (EI): calcd for
C15H9FO2 [M]+, 240.0587; found, 240.0587.
3-(4-Nitrophenyl)-1H-isochromen-1-one (2e). Eluent: petroleum
ether/EtOAc (20:1). Yield: 62% (83 mg). Yellow solid. Mp: 227−229
°C. 1H NMR (400 MHz, CDCl3): δ 8.32 (t, J = 8.7 Hz, 3H), 8.05 (d, J
= 8.8 Hz, 2H), 7.79 (t, J = 7.6 Hz, 1H), 7.59 (t, J = 8.7 Hz, 2H), 7.13
(s, 1H). 13C NMR (75 MHz, CDCl3): δ 161.4, 150.9, 148.2, 137.6,
136.4, 135.2, 129.8, 129.4, 126.6, 125.8, 124.1, 120.9, 104.8. IR (KBr):
ν = 3094, 1738, 1594, 1516, 1345, 1057, 860, 839, 762, 685 cm−1.
HRMS (EI): calcd for C15H9NO4 [M]+, 267.0532; found, 267.0534.
3-(4-(Benzyloxy)phenyl)-1H-isochromen-1-one (2f). Eluent: petro-
leum ether/EtOAc (50:1). Yield: 86% (141 mg). White solid. Mp:
1
135−137 °C. H NMR (400 MHz, CDCl3): δ 8.30 (d, J = 8.1 Hz,
1H), 7.84 (d, J = 8.9 Hz, 2H), 7.71 (t, J = 7.5 Hz, 1H), 7.52−7.32 (m,
7H), 7.06 (d, J = 8.8 Hz, 2H), 6.85 (s, 1H), 5.13 (s, 2H). 13C NMR
(75 MHz, CDCl3): δ 162.4, 160.2, 153.6, 137.8, 136.4, 134.8, 129.6,
128.6, 128.1, 127.7, 127.5, 126.8, 125.7, 124.7, 120.1, 115.05, 100.3,
70.0. IR (KBr): ν = 3067, 2934, 1736, 1675, 1601, 1510, 1257, 1072,
827, 785, 749, 669 cm−1. HRMS (EI): calcd for C22H16O3 [M]+,
328.1099; found, 328.1099.
3-(3-Chlorophenyl)-1H-isochromen-1-one (2g). Eluent: petroleum
ether/EtOAc (200:1). Yield: 80% (103 mg). White solid. Mp: 165−
167 °C. 1H NMR (400 MHz, CDCl3): δ 8.26 (d, J = 7.8 Hz, 1H), 7.81
(s, 1H), 7.70 (d, J = 6.1 Hz, 2H), 7.48 (t, J = 7.4 Hz, 2H), 7.35 (d, J =
4.0 Hz, 2H), 6.91 (s, 1H). 13C NMR (101 MHz, CDCl3): δ 161.8,
151.8, 136.9, 135.5, 134.9, 133.5, 130.0, 129.8, 129.6, 128.5, 126.1,
125.1, 123.1, 120.5, 102.6. IR (KBr): ν = 3109, 1726, 1634, 1604,
1486, 1235, 1064, 780, 750, 688 cm−1. HRMS (ESI): calcd for
C15H10ClO2 [M + H]+, 257.0364; found, 257.0362.
3-o-Tolyl-1H-isochromen-1-one (2h). Eluent: petroleum ether/
1
EtOAc (100:1). Yield: 74% (87 mg). White solid. Mp: 55−57 °C. H
NMR (400 MHz, CDCl3): δ 8.33 (d, J = 7.9 Hz, 1H), 7.73 (t, J = 7.6
Hz, 1H), 7.58−7.44 (m, 3H), 7.35 (t, J = 7.4 Hz, 1H), 7.28 (d, J = 7.6
Hz, 2H), 6.61 (s, 1H), 2.51 (s, 3H). 13C NMR (101 MHz, CDCl3): δ
162.6, 155.5, 137.4, 136.7, 134.8, 132.7, 131.0, 129.8, 129.5, 129.1,
128.2, 125.9, 125.8, 120.2, 105.9, 20.7. IR (KBr): ν = 3068, 2959,
1731, 1643, 1484, 1341, 1231, 1062, 844, 766, 688 cm−1. HRMS (EI):
calcd for C16H12O2 [M]+, 236.0837; found, 236.0838.
3-(2-Iodophenyl)-1H-isochromen-1-one (2i). Eluent: petroleum
ether/EtOAc (200:1). Yield: 61% (106 mg). White solid. Mp: 124−
126 °C. 1H NMR (400 MHz, CDCl3): δ 8.35 (d, J = 7.9 Hz, 1H), 7.97
(d, J = 7.9 Hz, 1H), 7.75 (t, J = 7.5 Hz, 1H), 7.62−7.47 (m, 3H), 7.43
(t, J = 7.5 Hz, 1H), 7.13 (t, J = 7.6 Hz, 1H), 6.73 (s, 1H). 13C NMR
(101 MHz, CDCl3): δ 162.2, 155.4, 140.2, 137.8, 136.8, 134.9, 131.0,
130.5, 129.7, 128.6, 128.2, 126.1, 120.6, 107.0, 96.4. IR (KBr): ν =
3071, 1717, 1653, 1482, 1338, 1299, 1070, 1010, 757, 743, 688 cm−1.
HRMS (ESI): calcd for C15H10IO2 [M + H]+, 348.9720; found,
348.9720.
3-(Naphthalen-2-yl)-1H-isochromen-1-one (2j). Eluent: petrole-
um ether/EtOAc (200:1). Yield: 81% (110 mg). White solid. Mp:
160−162 °C. 1H NMR (300 MHz, CDCl3): δ 8.44 (s, 1H), 8.32 (d, J
= 7.9 Hz, 1H), 7.97−7.79 (m, 4H), δ 7.72 (t, J = 7.6 Hz, 1H), 7.58−
3-tert-Butyl-1H-isochromen-1-one (2q). Eluent: petroleum ether/
1
EtOAc (100:1). Yield: 84% (85 mg). Colorless oil. H NMR (400
MHz, CDCl3): δ 8.25 (d, J = 7.9 Hz, 1H), 7.67 (t, J = 7.5 Hz, 1H),
7.45 (t, J = 7.6 Hz, 1H), 7.39 (d, J = 7.8 Hz, 1H), 6.31 (s, 1H), 1.33 (s,
9H). 13C NMR (101 MHz, CDCl3): δ 165.1, 163.0, 137.6, 134.6,
129.3, 127.5, 125.4, 120.0, 99.6, 35.6, 27.9. IR (KBr): ν = 2967, 2926,
1729, 1645, 1481, 1338, 1085, 1051, 1014, 952, 826, 767, 690 cm−1.
5741
dx.doi.org/10.1021/jo300916s | J. Org. Chem. 2012, 77, 5736−5743

The Journal of Organic Chemistry
Article
HRMS (ESI): calcd for C13H15O2 [M + H]+, 203.1067; found,
203.1061.
131.9, 129.7, 128.8, 125.0, 115.2, 107.5, 104.3, 102.2, 101.8. IR (KBr):
ν = 3105, 2926, 1704, 1598, 1484, 1262, 1053, 939, 877, 752, 680
cm−1. HRMS (ESI): calcd for C16H11O4 [M + H]+, 267.0652; found,
267.0658.
3-Cyclohexyl-1H-isochromen-1-one (2r). Eluent: petroleum ether/
1
EtOAc (200:1). Yield: 79% (90 mg). White solid. Mp: 91−92 °C. H
NMR (400 MHz, CDCl3): δ 8.24 (d, J = 7.8 Hz, 1H), 7.66 (t, J = 7.3
Hz, 1H), 7.43 (t, J = 7.4 Hz, 1H), 7.36 (d, J = 7.7 Hz, 1H), 6.23 (s,
1H), 2.44 (t, J = 11.1 Hz, 1H), 2.03 (d, J = 11.6 Hz, 2H), 1.85 (d, J =
11.9 Hz, 2H), 1.74 (d, J = 13.4 Hz, 1H), 1.54−1.17 (m, 5H). 13C
NMR (101 MHz, CDCl3): δ 163.1, 162.3, 137.7, 134.6, 129.4, 127.4,
125.2, 120.2, 100.8, 41.8, 30.5, 25.9, 25.8. IR (KBr): ν = 2927, 2851,
1722, 1649, 1482, 1160, 1061, 958, 897, 830, 760 cm−1. HRMS (ESI):
calcd for C15H17O2 [M + H]+, 229.1223; found, 229.1228.
7-Fluoro-3-phenyl-1H-isochromen-1-one (2s). Eluent: petroleum
ether/EtOAc (200:1). Yield: 89% (107 mg). White solid. Mp: 154−
156 °C. 1H NMR (400 MHz, CDCl3): δ 7.95 (d, J = 8.2 Hz, 1H), 7.86
(d, J = 6.3 Hz, 2H), 7.55−7.39 (m, 5H), 6.94 (s, 1H). 13C NMR (75
MHz, CDCl3): δ 163.4, 161.4, 160.1, 153.1, 134.0, 131.6, 130.0, 128.8,
128.2, 128.1, 125.1, 123.5, 123.2, 122.1, 122.0, 115.3, 115.0, 101.0. IR
(KBr): ν = 3086, 1714, 1618, 1501, 1334, 1256, 1067, 864, 816, 758,
679 cm−1. HRMS (ESI): calcd for C15H10FO2 [M + H]+, 241.0659;
found, 241.0659.
5-Methyl-3-phenyl-1H-isochromen-1-one (2z). Eluent: petroleum
ether/EtOAc (500:1). Yield: 72% (85 mg). White solid. Mp: 100−102
°C. 1H NMR (400 MHz, CDCl3): δ 8.14 (d, J = 7.9 Hz, 1H), 7.87 (d,
J = 7.1 Hz, 2H), 7.52 (d, J = 7.3 Hz, 1H), 7.48−7.38 (m, 3H), 7.35 (t,
J = 7.6 Hz, 1H), 7.02 (s, 1H), 2.53 (s, 3H). 13C NMR (101 MHz,
CDCl3): δ 162.6, 153.0, 136.1, 135.7, 133.5, 132.1, 129.8, 128.7, 127.6,
127.4, 125.2, 120.5, 98.5, 18.8. IR (KBr): ν = 3039, 2963, 1719, 1632,
1381, 1231, 1077, 1032, 948, 759, 702, 685 cm−1. HRMS (ESI): calcd
for C16H13O2 [M + H]+, 237.0910; found, 237.0917.
2-Phenyl-4H-benzo[f ]isochromen-4-one (2a′). Eluent: petroleum
ether/EtOAc (100:1). Yield: 98% (133 mg). Yellow solid. Mp: 186−
189 °C. 1H NMR (400 MHz, CDCl3): δ 8.35 (d, J = 6.7 Hz, 1H), 8.18
(d, J = 8.5 Hz, 1H), 7.95 (d, J = 6.8 Hz, 2H), 7.87 (d, J = 6.4 Hz, 1H),
7.80 (d, J = 8.5 Hz, 1H), 7.66 (d, J = 2.4 Hz, 2H), 7.61 (s, 1H), 7.53−
7.41 (m, 3H). 13C NMR (75 MHz, CDCl3): δ 162.5, 154.8, 136.6,
135.9, 132.0, 130.2, 129.3, 128.8, 128.3, 127.7, 127.23, 125.4, 124.1,
123.9, 117.4, 97.4. IR (KBr): ν = 3052, 1716, 1631, 1564, 1345, 1098,
1062, 855, 827, 757, 688 cm−1. HRMS (ESI): calcd for C19H13O2 [M
+ H]+, 273.0910; found, 273.0929.
6,7-Dimethoxy-3-phenyl-1H-isochromen-1-one (2t). Eluent: pe-
troleum ether/EtOAc (10:1). Yield: 76% (107 mg). Yellow solid. Mp:
1
2-tert-Butyl-4H-benzo[f ]isochromen-4-one (2b′). Eluent: petro-
169−171 °C. H NMR (400 MHz, CDCl3): δ 7.83 (d, J = 5.9 Hz,
leum ether/EtOAc (30:1). Yield: 91% (115 mg). White solid. Mp:
2H), 7.64 (s, 1H), 7.42 (d, J = 8.1 Hz, 3H), 6.86 (d, J = 4.1 Hz, 2H),
4.00 (s, 3H), 3.98 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 162.2,
155.1, 152.6, 149.7, 133.1, 132.0, 129.6, 128.7, 124.9, 113.6, 109.4,
106.4, 101.5, 56.2. IR (KBr): ν = 3071, 3007, 2941, 1712, 1610, 1514,
1387, 1238, 1060, 891, 835, 781, 703 cm−1. HRMS (ESI): calcd for
C17H15O4 [M + H]+, 283.0965; found, 283.0965.
1
127−129 °C. H NMR (400 MHz, CDCl3): δ 8.32 (d, J = 7.7 Hz,
1H), 8.18 (d, J = 8.6 Hz, 1H), 7.89 (d, J = 7.4 Hz, 1H), 7.80 (d, J = 8.6
Hz, 1H), 7.73−7.61 (m, 2H), 7.07 (s, 1H), 1.42 (s, 9H). 13C NMR
(101 MHz, CDCl3): δ 166.7, 163.2, 136.8, 136.0, 129.1, 128.9, 127.8,
127.8, 127.0, 124.1, 124.0, 117.0, 95.2, 36.1, 28.1. IR (KBr): ν = 2965,
1870, 1715, 1638, 1565, 1331, 1091, 1048, 870, 818, 751 cm−1. HRMS
(ESI): calcd for C17H17O2 [M + H]+, 253.1223; found, 253.1226.
4-Methyl-3-phenyl-1H-isochromen-1-one (2c′). Eluent: petroleum
ether/EtOAc (200:1). Yield: 78% (92 mg). White solid. Mp: 68−70
7-Chloro-3-phenyl-1H-isochromen-1-one (2u). Eluent: petroleum
ether/EtOAc (150:1). Yield: 96% (123 mg). White solid. Mp: 182−
183 °C. 1H NMR (400 MHz, CDCl3): δ 8.28 (s, 1H), 7.87 (d, J = 6.6
Hz, 2H), 7.67 (d, J = 8.3 Hz, 1H), 7.53−7.35 (m, 4H), 6.94 (s, 1H).
13C NMR (75 MHz, CDCl3): δ 161.1, 153.8, 135.8, 135.2, 133.7,
131.4, 130.2, 129.0, 128.8, 127.4, 125.2, 121.5, 100.9. IR (KBr): ν =
3104, 1718, 1637, 1474, 1324, 1226, 1075, 868, 764, 687 cm−1. HRMS
(ESI): calcd for C15H10ClO2 [M + H]+, 257.0364; found, 257.0364.
6-Chloro-3-phenyl-1H-isochromen-1-one (2v). Eluent: petroleum
ether/EtOAc (100:1). Yield: 93% (119 mg). White solid. Mp: 220−
221 °C. 1H NMR (400 MHz, CDCl3): δ 8.24 (d, J = 8.3 Hz, 1H), 7.87
(d, J = 5.8 Hz, 2H), 7.54−7.38 (m, 5H), 6.88 (s, 1H). 13C NMR (101
MHz, CDCl3): δ 161.5, 154.9, 141.5, 138.9, 131.5, 131.3, 130.4, 128.9,
128.5, 125.4, 118.7, 100.7. IR (KBr): ν = 3108, 1713, 1640, 1447,
1326, 1242, 1063, 893, 769, 756, 681 cm−1. HRMS (ESI): calcd for
C15H10ClO2 [M + H]+, 257.0364; found, 257.0364.
1
°C. H NMR (400 MHz, CDCl3): δ 8.26 (dd, J = 8.0, 1.2 Hz, 1H),
7.68−7.61 (m, 3H), 7.55−7.49 (m, 3H), 7.45 (d, J = 8.4 Hz, 1H), 7.39
(t, J = 7.5 Hz, 1H), 2.17 (s, 3H). 13C NMR (101 MHz, CDCl3): δ
178.8, 160.9, 156.0, 133.4, 133.3, 130.1, 128.9, 128.4, 125.8, 124.6,
122.4, 117.8, 117.5, 11.7. IR (KBr): ν = 3052, 2929, 1636, 1615, 1574,
1470, 1396, 1368, 1138, 1015, 755, 701cm−1. HRMS (ESI): calcd for
C16H13O2 [M + H]+, 237.0910; found, 237.0915.
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Copies of H and 13C NMR spectra. This material is available
6-Fluoro-3-phenyl-1H-isochromen-1-one (2w). Eluent: petroleum
free of charge via the Internet at http://pubs.acs.org.
ether/EtOAc (500:1). Yield: 64% (77 mg). White solid. Mp: 169−170
1
°C. H NMR (400 MHz, CDCl3): δ 8.37−8.25 (m, 1H), 7.87 (d, J =
AUTHOR INFORMATION
■
5.8 Hz, 2H), 7.46 (d, J = 5.7 Hz, 2H), 7.17 (dd, J = 17.9, 8.8 Hz, 3H),
6.90 (s, 1H). 13C NMR (75 MHz, CDCl3): δ 168.4, 165.0, 161.3,
154.8, 140.2, 140.1, 133.0, 132.9, 131.5, 130.3, 128.8, 127.5, 127.4,
125.4, 116.9, 116.6, 116.2, 115.9, 111.6, 111.3, 101.2, 100.9. IR (KBr):
ν = 3106, 1716, 1622, 1347, 1258, 1068, 885, 827, 757, 679 cm−1.
HRMS (ESI): calcd for C15H10FO2 [M + H]+, 241.0659; found,
241.0661.
Corresponding Author
*E-mail: zhuyongming@suda.edu.cn, jkshen@mail.shcnc.ac.cn.
Notes
The authors declare no competing financial interest.
7-Methoxy-3-phenyl-1H-isochromen-1-one (2x). Eluent: petrole-
um ether/EtOAc (30:1). Yield: 47% (59 mg). White solid. Mp: 165−
167 °C. 1H NMR (400 MHz, CDCl3): δ 7.83 (d, J = 7.2 Hz, 2H), 7.71
(d, J = 2.6 Hz, 1H), 7.47−7.34 (m, 4H), 7.28 (dd, J = 8.6, 2.7 Hz, 1H),
6.88 (s, 1H), 3.89 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 162.3,
159.7, 151.8, 132.2, 131.2, 129.5, 128.8, 127.5, 125.0, 124.6, 121.8,
110.2, 101.5, 55.7. IR (KBr): ν = 3099, 2925, 1713, 1634, 1499, 1356,
1263, 1073, 1027, 859, 779, 759 cm−1. HRMS (ESI): calcd for
C16H13O3 [M + H]+, 253.0859; found, 253.0864.
7-Phenyl-5H-[1,3]dioxolo[4,5-g]isochromen-5-one (2y). Eluent:
petroleum ether/EtOAc (10:1). Yield: 62% (83 mg). Yellow solid.
Mp: 189−191 °C. 1H NMR (400 MHz, CDCl3): δ 7.85 (d, J = 6.5 Hz,
2H), 7.64 (s, 1H), 7.44 (d, J = 7.7 Hz, 3H), 6.85 (s, 2H), 6.11 (s, 2H).
13C NMR (75 MHz, CDCl3): δ 161.9, 153.7, 152.7, 148.3, 135.1,
ACKNOWLEDGMENTS
■
We gratefully acknowledge the financial support by PAPD (A
Project Funded by the Priority Academic Program Develop-
ment of Jiangsu Higher Education Institutions) and NSFC
(National Natural Science Foundation of China, 81172954).
REFERENCES
■
(1) (a) Gerbino, D. C.; Mandolesi, S. D.; Schmalz, H.-G.; Podesta,
́
J.
C. Eur. J. Org. Chem. 2009, 3964−3972. (b) Buden
́
, M. E.; Vaillard, V.
A.; Martin, S. E.; Rossi, R. A. J. Org. Chem. 2009, 74, 4490−4498.
(2) Li, Q.-L.; Zhu, Y.-M. Helv. Chim. Acta 2011, 94, 1304−1309.
(3) Zhao, J.; Zhao, Y.; Fu, H. Angew. Chem. 2011, 123, 3853−3857.
5742
dx.doi.org/10.1021/jo300916s | J. Org. Chem. 2012, 77, 5736−5743

The Journal of Organic Chemistry
Article
(4) (a) Mali, R. S.; Babu, K. N. J. Org. Chem. 1998, 63, 2488−2492.
(b) Hauser, F. M.; Baghdanov, V. M. J. Org. Chem. 1988, 53, 4676−
4681. (c) Barry, R. D. Chem. Rev. 1964, 64, 229−260.
C.-J. J. Org. Chem. 2012, 77, 2331−2336. (c) Kavala, V.; Wang, C.-C.;
Barange, D. K.; Kuo, C.-W.; Lu, P.-M.; Yao, C.-F. J. Org. Chem. 2012,
77, 5022−5029.
(18) Wang, F.; Liu, H.; Fu, H.; Jiang, Y.; Zhao, Y. Org. Lett. 2009, 11,
2469−2472.
(5) Yoshikawa, M.; Harada, E.; Naitoh, Y.; Inoue, K.; Matsuda, H.;
Shimoda, H.; Yamahara, J.; Murakami, N. Chem. Pharm. Bull. 1994, 42,
2225−2230.
(19) (a) Liu, Q.-L.; Wen, D.-D.; Hang, C.-C.; Li, Q.-L.; Zhu, Y.-M.
Helv. Chim. Acta 2010, 93, 1350−1354. (b) Liu, R.; Zhu, Y.-M.; Qin,
L.-N.; Ji, S.-J. Synth. Commun. 2008, 38, 249−254. (c) Liu, R.; Zhu, Y.-
M.; Qin, L.-N.; Ji, S.-J.; Katayama, H. Heterocycles 2007, 71, 1755−
1763. (d) Zhu, Y.-M.; Qin, L.-N.; Liu, R.; Ji, S.-J.; Katayama, H.
Tetrahedron Lett. 2007, 48, 6262−6266.
(6) (a) Nozawa, K.; Yamada, M.; Tsuda, Y.; Kawai, K.; Nakajima, S.
Chem. Pharm. Bull. 1981, 29, 2689−2691. (b) Meepagala, K. M.;
Sturtz, G.; Wedge, D. E. J. Agric. Food Chem. 2002, 50, 6989−6992.
(c) Engelmeier, D.; Hadacek, F.; Hofer, O.; Lutz-Kutschera, G.; Nagl,
M.; Wurz, G.; Greger, H. J. Nat. Prod. 2004, 67, 19−25.
(7) (a) Kawano, T.; Agata, N.; Kharbanda, S.; Avigan, D.; Kufe, D.
Cancer Chemother. Pharmacol. 2007, 59, 329−335. (b) Riveiro, M. E.;
Moglioni, A.; Vazquez, R.; Gomez, N.; Facorro, G.; Piehl, L.; De Celis,
E. R.; Shayo, C.; Davio, C. Bioorg. Med. Chem. 2008, 16, 2665−2675.
(8) (a) Shikishima, Y.; Takaishi, Y.; Honda, G.; Ito, M.; Takeda, Y.;
Kodzhimatov, O. K.; Ashurmetov, O.; Lee, K. H. Chem. Pharm. Bull.
2001, 49, 877−880. (b) Goldman, M. E.; Salituro, G. S.; Bowen, J. A.;
Williamson, J. M.; Zink, L.; Schleif, W. A.; Emini, E. A. Mol. Pharmacol.
1990, 38, 20−25.
(20) (a) Michalak, J.; Gębicki, J.; Bally, T. J. Chem. Soc., Perkin Trans.
2 1993, 7, 1321−1325. (b) Lear, Y.; Durst, T. Can. J. Chem. 1997, 75,
817−824.
(21) Heller, S. T.; Natarajan, S. R. Org. Lett. 2006, 8, 2675−1678.
(9) (a) Barber, J.; Carter, R. H.; Garson, R. J.; Staunton, J. J. Chem.
Soc., Perkin Trans. 1 1981, 2577−2583. (b) Beugelmans, R.; Ginsburg,
H.; Bois-Choussy, M. J. Chem. Soc., Perkin Trans. 1 1982, 1149−1152.
(c) Lewis, C. N.; Staunton, J.; Sunter, D. C. J. Chem. Soc., Perkin Trans.
1 1988, 747−754. (d) Minami, T.; Nishimoto, A.; Nakamura, Y.;
Hanaoka, H. Chem. Pharm. Bull. 1994, 42, 1700−1702. (e) Nomoto,
S.; Mori, K. Liebigs Ann. 1997, 721−723.
(10) (a) Pal, S.; Chatare, V.; Pal, M. Curr. Org. Chem. 2011, 15, 782−
800. (b) Napolitano, E. Org. Prep. Proced. Int. 1997, 29, 631−664.
(11) (a) Korte, D. E.; Hegedus, L. S.; Wirth, R. K. J. Org. Chem. 1977,
42, 1329. (b) Sakamoto, T.; An-Naka, M.; Kondo, Y.; Yamanaka, H.
Chem. Pharm. Bull. 1986, 34, 2754−2759. (c) Sashida, H.; Kawamukai,
A. Synthesis 1999, 7, 1145−1148. (d) Bellina, F.; Ciucci, D.;
Vergamini, P.; Rossi, R. Tetrahedron 2000, 56, 2533−2545. (e) Biagetti,
M.; Bellina, F.; Carpita, A.; Stabile, P.; Rossi, R. Tetrahedron 2002, 58,
5023−5038. (f) Yao, T.; Larock, R. C. J. Org. Chem. 2003, 68, 5936−
5942. (g) Rossi, R.; Carpita, A.; Bellina, F.; Stabile, P.; Mannina, L.
Tetrahedron 2003, 59, 2067−2081. (h) Uchiyama, M.; Ozawa, H.;
Takuma, K.; Matsumoto, Y.; Yonehara, M.; Hiroya, K.; Sakamoto, T.
Org. Lett. 2006, 8, 5517−5520. (i) Hellal, M.; Bourguignon, J.-J.; Bihel,
F. J.-J. Tetrahedron Lett. 2008, 49, 62−65. (j) Shahzad, S. A.; Venin, C.;
Wirth, T. Eur. J. Org. Chem. 2010, 18, 3465−3472.
(12) (a) Batu, G.; Stevenson, R. J. Org. Chem. 1980, 45, 1532−1534.
(b) Larock, R. C.; Varaprath, S.; Lau, H. H.; Fellows, C. A. J. Am.
Chem. Soc. 1984, 106, 5274−5284. (c) Liao, H.-Y.; Cheng, C.-H. J.
Org. Chem. 1995, 60, 3711−3716. (d) Subramanian, V.; Batchu, V. R.;
Barange, D.; Pal, M. J. Org. Chem. 2005, 70, 4778−4783. (e) Cherry,
K.; Parrain, J.; Thibonnet, P. J.; Duchene, A.; Abarbri, M. J. Org. Chem.
2005, 70, 6669−6675. (f) Ueura, K.; Satoh, T.; Miura, M. J. Org.
Chem. 2007, 72, 5362−5367. (g) Wang, L. L.; Zhang, X. J.; Jiang, Y.
W.; Ma, D. W. Sci. China, Ser. B: Chem. 2009, 52, 1616−1621.
(h) Wetzel, I.; Bracher, F.; Krauss, J. Z. Naturforsch. 2009, 64b, 313−
318.
́
(13) (a) Negishi, E.; Coperet, C.; Sugiham, T.; Shimoyama, I.;
Zhang, Y.; Wu, G.-Z.; Tour, J. M. Tetrahedron 1994, 50, 425−436.
(b) Andrew, C. T.; Mark, R. F.; Michael, C. W. Chem. Commun. 2009,
6744−6746.
(14) (a) Khan, K. M.; Ahmed, S.; Khan, Z. A.; Rani, M.; Perveen, S.;
Shahnaz, C.; Choudhary, M. I.; Atta-ur-Rahman. Lett. Org. Chem.
2005, 2, 532−534. (b) Tajudeen, S. S.; Khan, F. N. Synth. Commun.
2007, 37, 3649−3656. (c) Khan, K. M.; Ahmed, S.; Khan, Z. A.; Rani,
M.; Perveen, S.; Voelter, W. Nat. Prod. Res. 2008, 22, 1120−1127.
(15) Park, J. H.; Bhilare, S. V.; Youn, S. W. Org. Lett. 2011, 13, 2228−
2231.
(16) Kurume, A.; Kamata, Y.; Yamashita, M.; Wang, Q.; Matsuda, H.;
Yoshikawa, M.; Kawasaki, I.; Ohta, S. Chem. Pharm. Bull. 2008, 56,
1264−1269.
(17) (a) Fan, X.-S.; He, Y.; Cui, L.-Y.; Guo, S.-H.; Wang, J.-J.; Zhang,
X.-Y. Eur. J. Org. Chem. 2012, 4, 673−677. (b) Cai, S.-J.; Wang, F.; Xi,
5743
dx.doi.org/10.1021/jo300916s | J. Org. Chem. 2012, 77, 5736−5743