Halocyclization of methyl 2-alkynylbenzoates to isocoumarins using cupric halides

Article abstract of DOI:10.1002/jccs.200800095

Treatment of methyl 2-alkynylbenzoates with two to three equivalents of CuX₂ (X = Cl or Br) in refluxing acetonitrile gave isocoumarins 2 in good to excellent chemical yields.

Full text of DOI:10.1002/jccs.200800095

Journal of the Chinese Chemical Society, 2008, 55, 643-648
643
Halocyclization of Methyl 2-Alkynylbenzoates to Isocoumarins Using
Cupric Halides
Ling-Yu Chin (
Yu-Hsiang Lo (
Faculty of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C.
), Chia-Ying Lee (
),
) and Ming-Jung Wu* (
)
Treatment of methyl 2-alkynylbenzoates with two to three equivalents of CuX2 (X = Cl or Br) in
refluxing acetonitrile gave isocoumarins 2 in good to excellent chemical yields.
Keywords: Halocyclization; Isocoumarins.
INTRODUCTION
Numerous natural products that contain isocoumarin
ditions gave compound 5 in 75% yield. Desilylation of 5
was carried out by treatment of 5 with potassium carbonate
in dry methanol to give 6 in 71% yield. Finally, compound
6 was coupled with aryl iodides 7a-b using Pd(PPh3)4 as
the catalyst to give the methyl 2-(arylethynyl)benzoates 1f
and 1g in 85% and 71% yields, respectively. Compound 10
was prepared starting from compound 8. (Eq. 2) Treatment
of compound 8 with Tf2O in the presence of Et3N in CH2Cl2
gave vinyl triflate 9. Vinyl triflate 9 was then converted to
compound 10 in the yield of 86% under Sonogashira reac-
tion conditions with 4b.
subunits exhibit a broad spectrum of biological activity, in-
cluding as potent irreversible inhibitors of blood coagula-
tion enzymes,1 inhibitors of human leukocyte elastase,2 as
antifungal,3 b-amyloid peptide production inhibitors4 and
as estrogen receptor beta selective ligands.5 Although many
synthetic methods to construct isocoumarins have been re-
ported,6 the electrophile induced cyclization of 2-alkynyl-
benzoates by Rossi7 and Larock8 proved to be a very effi-
cient method to these molecules. However, the chlorocy-
clization reaction of this type of reaction has not been re-
ported. We recently found that cupric halides, such as cu-
pric chloride and cupric bromide, are powerful halocy-
clization agents of 2-alkynylthioanisoles to benzothio-
phenes.9 We therefore anticipated that treatment of methyl
2-alkynylbenzoates under similar conditions would give
isocoumarins. During our investigation of this cyclization
reaction, a similar method for the synthesis of isocouma-
rins and a-Pyrone was reported.10 In this paper, we disclose
a general reaction of halocyclization of methyl 2-alkynyl-
benzoates using CuCl2 and CuBr2.
Scheme I
RESULTS AND DISCUSSION
The synthesis of methyl 2-alkynylbenzoates 1a-e is
outlined in Eq. 1. The palladium-catalyzed coupling reac-
tion of methyl 2-iodobenzoate (3) with alkynes 4a-e under
Sonogashira reaction conditions gave the compounds 1a-e
in 92-99% yields. On the other hand, compounds 1f-g were
synthesized as shown in Scheme I. Treatment of methyl
2-iodobenzoate (3) with trimethylsilylacetylene using
Pd(PPh3)4 as the catalyst under Sonogashira reaction con-
* Corresponding author. Tel: +886-7-3121101 ext 2220; Fax: +886-7-3125339; E-mail: mijuwu@kmu.edu.tw

644 J. Chin. Chem. Soc., Vol. 55, No. 3, 2008
Chin et al.
The first attempt for the halocyclization of methyl
2-(2-phenylethynyl)benzoate (1a) was carried out by the
treatment of 1a with two equivalents of CuCl2 in CH3CN at
room temperature. After stirring the reaction mixture for 24
h, the desired product 2a was obtained in the yield of 62%
and the starting material 1a was recovered in 11% yield.
We therefore increased the temperature by heating the reac-
tion mixture to reflux. Under this temperature, this reaction
went to completion after 2 h and the product 2a was ob-
tained in 98% yield. We also added 5 mol% of PdCl2 into
the reaction mixture of methyl 2-(2-phenylethynyl)benzo-
ate (1a) with two equivalents of CuCl2 in refluxing aceto-
nitrile. Surprisingly, the yield of the product 2a drops dra-
matically to 60%. It was also found that several uncharac-
terizable by-products were formed under these reaction
conditions.
Table 2. Chlorocyclization of methyl 2-alkynylbenzoates 1b-g
Cl
H
R
R
R
CH3CN
+
O
O
OCH3
reflux, 2 h
O
O
O
2
11
1
Entry
CuCl2 (eq)
R
Products, Yields (%)
1
2
3
4
5
6
7
2
2
2
2
2
2
3
(CH2)4CH3
2b, 85
CH2CH(CH3)2
C(CH3)3
2c, 97
2d, 97
(CH2)2OH
2e, 79
4-CF3C6H4
4-CH3OC6H4
4-CH3OC6H4
2f, 62
2g, 68 11g, 24
2g, 79
Table 3. Bromocyclization of methyl 2-alkynylbenzoates 1a-g
After finding the optimal reaction conditions for the
chlorocyclization of 1a, we then explored the generality of
the cyclization reactions of compounds 1b-g. The results
are summarized in Table 2. The reactions proceeded very
smoothly with different functional groups at the terminus
of alkynes. Even a bulky substituent, such as a tertiary
butyl group, (entry 3) gave the chlorocyclization product
2d in 97% yield. The free hydroxyl group has a little influ-
ence in this reaction. Under the standard reaction condi-
tions, cyclization of 1e gave 2e in 79% yield. The phenyl
group bearing an electron-withdrawing group, such as tri-
fluoromethyl, gave a little bit lower yield (entry 5). If only
R
Br
H
R
R
CH3CN
+
OCH3
O
O
reflux, 2 h
O
O
O
1
12
11
Entry CuBr2 (eq)
R
Products, Yields (%)
1
2
3
4
5
6
7
8
2
2
2
3
2
2
2
3
Ph
12a, 99
(CH2)4CH3
CH2CH(CH3)2
C(CH3)3
12b, 71
12c, 98
12d, 69
(CH2)2OH
12e, 81
4-CF3C6H4
4-CH3OC6H4
4-CH3OC6H4
12f, 97
12g, 70 11g, 23
12g, 89
Table 1. Cyclization of 1a with cupric chloride
Ph
Cl
Ph
two equivalents of CuCl2 were used for the cyclization of
1g, the chlorocyclization product 2g was obtained in 68%
yield along with 24% yield of 11g.11 However, the side-
product 11g can be eliminated by treatment of 1g with three
equivalents of CuCl2 (entry 7) and the desired product 2g
was obtained in 79% yield under these reaction conditions.
We have also found that treatment of CuBr2 with 1a-g
under the described reaction conditions gave the bromo-
cyclization adducts in good to excellent yields. The results
are summarized in Table 3. Treatment of 1g with two equiv-
CuCl2 (2 equiv.)
CH3CN
OCH3
O
O
O
1a
2a
Entry
Temp (°C)
Time (h)
Yields (%)
1
25
24
2
62(11)a
98
2
3b
reflux
reflux
2
60
a Recovered starting material.
b 5 mol % PdCl2 was added.

Synthesis of Isocoumarins
J. Chin. Chem. Soc., Vol. 55, No. 3, 2008 645
alents of CuBr2 gave the desired bromocyclization product
12g in 70% yield along with 11g in 23% yield. Again, this
side-product can be eliminated by using three equivalents
of CuBr2. A similar result was also observed for compound
1d. (entry 4) Thus, treatment of 1d with three equivalents
of CuBr2 gave 12d in 69% yield. These cyclization reac-
tions have also been extended to the cyclization of com-
pound 10. Thus, treatment of 10 with two equivalents of
CuCl2 under the described reaction conditions gave 2h in
98% yield. A similar result was obtained by the reaction of
compound 10 with CuBr2 (Eq. 3).
action of 1g as shown in Scheme II. The acids, HCl and
HBr, could be generated by the halogenation of 1g with
CuX2 on the anisole ring although we did not isolate any
halogenated side-products.
CONCLUSION
In summary, we have developed an efficient method
for the halocyclization reactions of methyl 2-alkynylben-
zoates to give the isocoumarin adducts. This methodology
should have its value for the application of the synthesis of
medicinally or materially important compounds.
EXPERIMENTAL
General procedure for cyclization compounds 2a-2h
To a stirred solution of 1a-1h (10 mmol) in CH3CN
(10 mL) was added CuCl2 (20 mmol). The resulting solu-
tion was heated to reflux and stirred at this temperature for
2 h. After cooling to room temperature, the reaction mix-
ture was quenched with saturated aqueous NH4Cl solution.
The aqueous layer was extracted with EtOAc (20 mL ´ 3).
The combined organic extracts were dried over anhydrous
MgSO4. After filtration and removal of solvent in vacuo,
the residue was purified by column chromatography on sil-
ica gel to yield the desired products.
A proposed mechanism for the formation of 2 and 12
is outlined in Scheme II. Cupric halide would first form a
complex with alkyne such as the intermediate 13. Intramo-
lecular cyclization would then take place to give the oxo-
nium ion 14. Nucleophilic substitution replacement of the
methyl group by the second equivalent of cupric halide
would lead to the desired products 2 and 12, respectively. It
was reported that heating the cupric bromide to the reflux-
ing acetonitrile temperature would generate bromine.12
Therefore, the formation of 12 could also be promoted di-
rectly by bromine as in the report by Gandour.13 The forma-
tion of 11g is proposed by the acid-catalyzed cyclization re-
4-Chloro-3-phenyl-1H-isochromen-1-one (2a)
The compound was purified by column chromatogra-
phy, eluting with hexane/EA (40:1) to give 98% of a white
solid, mp 142-143 °C. 1H NMR (CDCl3, 400 MHz) d 8.35
(dt, J = 8.0, 0.8 Hz, 1H), 7.95 (dt, J = 8.4, 0.8 Hz, 1H),
7.88-7.84 (m, 3H), 7.61 (td, J = 7.6, 0.8 Hz, 1H), 7.59-7.47
Scheme II A proposed mechanism of the formations of 2, 11 and 12

646 J. Chin. Chem. Soc., Vol. 55, No. 3, 2008
Chin et al.
(m, 3H); 13C NMR (CDCl3, 100 MHz) d 160.9, 150.4, 135.9,
135.3, 131.4, 130.2, 129.8, 129.3 (2C), 129.1, 128.2 (2C),
124.0, 120.5, 111.3; EA: calcd for C %: 70.19; H %: 3.53;
found C %: 70.17, H %: 3.52.
phy, eluting with hexane/EA (40:1) to give 62% of a white
solid, mp 141-142 °C. 1H NMR (CDCl3, 400 MHz) d 8.37
(dd, J = 8.0, 0.8 Hz, 1H), 8.01 (td, J = 8.0, 0.8 Hz, 3H), 7.91
(td, J = 7.2, 1.2 Hz, 1H), 7.75 (dd, J = 8.4, 0.4 Hz, 2H), 7.66
(td, J = 7.2, 1.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d
160.5, 148.8, 135.5, 134.8, 132.0, 131.7, 130.0, 129.8
(3C), 129.7, 125.3, 124.3 (2C), 120.7, 112.5; EA: calcd for
C %: 59.19; H %: 2.48; found C %: 59.23, H %: 2.50.
4-Chloro-3-(4-methoxyphenyl)-1H-isochromen-1-one
(2g)
4-Chloro-3-pentyl-1H-isochromen-1-one (2b)
The compound was purified by column chromatogra-
phy, eluting with hexane/EA(40:1) to give 85% of a yellow
liquid, 1H NMR (CDCl3, 400 MHz) d 8.25 (dt, J = 8.0, 0.8
Hz, 1H), 7.81-7.49 (m, 2H), 7.52 (td, J = 8.0, 2.0 Hz, 1H),
2.75 (t, J = 7.6 Hz, 2H), 1.73 (quin, J = 7.6 Hz, 2H), 1.38-
1.33 (m, 4H), 0.89 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3,
100 MHz) d 161.3, 154.6, 135.5, 135.2, 129.7, 128.3,
123.1, 120.1, 110.7, 31.1 (2C), 26.4, 22.3, 13.9; HRMS
(EI) calcd for C14H15ClO2 250.0761, found 250.0764.
4-Chloro-3-isobutyl-1H-isochromen-1-one (2c)
The compound was purified by column chromatogra-
phy, eluting with hexane/EA (40:1) to give 79% (three
equivalents of CuCl2 was used) of a yellow solid, mp
130-131 °C. 1H NMR (CDCl3, 400 MHz) d 8.33 (dd, J =
7.6, 0.4 Hz, 1H), 7.94 (dd, J = 7.6, 0.4 Hz, 1H), 7.86-7.83
(m, 3H), 7.58 (td, J = 8.0, 0.4 Hz, 1H), 7.01-6.97 (m, 2H),
3.88 (s, 3H); 13C NMR (CDCl3, 100 MHz) d 161.1, 160.8,
150.3, 136.2, 135.3, 130.9 (2C), 129.8, 128.7, 123.8,
123.7, 120.3, 113.6 (2C), 110.3, 55.4; EA: calcd for C %:
76.18; H %: 4.79; found C %: 75.89, H %: 4.79.
The compound was purified by column chromatogra-
phy, eluting with hexane/EA (40:1) to give 97% of a brown
solid, mp 56-57 °C, 1H NMR (CDCl3, 400 MHz) d 8.26 (dt,
J = 8.4, 0.4 Hz, 1H), 7.82-7.77 (m, 2H), 7.53 (td, J = 8.0,
2.4 Hz, 1H), 2.64 (t, J = 7.2 Hz, 2H), 2.25-2.18 (m, 1H),
1.00 (d, J = 6.4 Hz, 6H); 13C NMR (CDCl3, 100 MHz) d
161.2, 153.9, 135.5, 135.2, 129.7, 128.4, 123.2, 120.1,
111.7, 39.8, 27.3, 22.2 (2C); EA: calcd for C %: 65.98; H
%: 5.50; found C %: 65.97, H %: 5.54.
3-(4-Methoxyphenyl)-1H-isochromen-1-one (11g)
When two equivalents of CuCl2 were used, 2g was
obtained in 68% yield along with 11g in 24% yield. The
compound was purified by column chromatography, eluting
with hexane/EA (40:1) to give a white solid, mp 142-143
°C. 1H NMR (CDCl3, 400 MHz) d 8.28 (d, J = 8.0 Hz, 1H),
7.82 (dd, J = 9.2, 2.0 Hz, 2H), 7.69 (td, J = 7.2, 1.2 Hz, 1H),
7.47-7.44 (m, 2H), 6.97 (dt, J = 9.2, 2.8 Hz, 2H), 6.83 (s,
1H), 3.86 (s, 3H); 13C NMR (CDCl3, 100 MHz) d 162.5,
161.1, 153.7, 137.9, 134.8, 129.6, 127.7, 126.8(2C), 125.7,
124.5, 120.1, 114.2 (2C), 100.2, 55.4; EA: calcd for C %:
76.18; H %: 4.79; found C %: 75.89, H %: 4.79.
4-Chloro-3-tert-butyl-1H-isochromen-1-one (2d)
The compound was purified by column chromatogra-
phy, eluting with hexane/EA (40:1) to give 97% of a white
solid, mp 129-130 °C, 1H NMR (CDCl3, 400 MHz) d 8.26
(ddd, J = 8.0, 1.2, 0.4 Hz, 1H), 7.89 (ddd, J = 8.0, 1.2, 0.4
Hz, 1H), 7.79 (td, J = 8.0, 1.6 Hz, 1H), 7.53 (td, J = 8.0, 1.2
Hz, 1H), 1.50 (s, 9H); 13C NMR (CDCl3, 100 MHz) d 161.0,
159.4, 136.7, 135.0, 129.4, 128.4, 123.2, 120.0, 110.8,
37.8, 28.3 (3C); EA: calcd for C %: 65.97; H %: 5.54;
found C %: 65.96, H %: 5.56.
4-Chloro-3-pentyl-6,7-dihydrocyclopenta[c]pyran-1-
(5H)-one (2h)
4-Chloro-3-(2-hydroxyethyl)-1H-isochromen-1-one (2e)
The compound was purified by column chromatogra-
phy, eluting with hexane/EA (1:1) to give 79% of a yellow
The compound was purified by column chromatogra-
phy, eluting with hexane/EA(40:1) to give 98% of a yellow
liquid, 1H NMR (CDCl3, 400 MHz) d 2.91-2.82 (m, 4H),
2.64 (t, J = 7.6 Hz, 2H), 2.10 (quin, J = 7.6 Hz, 2H), 1.67
(quin, J = 7.6 Hz, 2H), 1.36-1.30 (m, 4H), 0.89 (t, J = 7.2
Hz, 3H); 13C NMR (CDCl3, 100 MHz) d 160.7, 160.4,
158.7, 125.2, 111.5, 34.0, 31.1, 30.7, 30.6, 26.5, 22.3 (2C),
13.9; HRMS (EI) calcd for C13H17BrO2 240.0917, found
240.0917.
1
solid, mp 93-94 °C. H NMR (CDCl3, 400 MHz) d 8.25
(dd, J = 8.0, 0.8 Hz, 1H), 7.84-7.77 (m, 2H), 7.54 (td, J =
8.0, 2.0 Hz, 1H), 4.04 (t, J = 6.4 Hz, 2H), 3.07 (t, J = 6.4 Hz,
2H), 2.05 (bs, 1H); 13C NMR (CDCl3, 100 MHz) d 161.2,
151.4, 135.3, 135.2, 129.8, 128.8, 123.3, 120.2, 112.7,
59.5, 34.5; EA: calcd for C %: 58.81; H %: 4.04; found C
%: 58.56, H %: 4.02.
General procedure for cyclization compound 12a-12h
To a stirred solution of 1a-1h (10 mmol) in CH3CN
(10 mL) was added CuBr2 (20 mmol) and the resulting so-
lution was heated to reflux and stirred at this temperature
4-Chloro-3-(4-(trifluoromethyl)phenyl)-1H-isochromen-
1-one (2f)
The compound was purified by column chromatogra-

Synthesis of Isocoumarins
J. Chin. Chem. Soc., Vol. 55, No. 3, 2008 647
for 2 h. After cooling to room temperature, the reaction
mixture was quenched with a saturated aqueous solution of
NaCl. The aqueous layer was extracted with EtOAc (20 mL
´ 3). The combined organic extracts were dried over anhy-
drous MgSO4. After filtration and removal of solvent in
vacuo, the residue was purified by column chromatography
on silica gel to yield the desired products.
4-Bromo-3-(2-hydroxyethyl)-1H-isochromen-1-one
(12e)
The compound was purified by column chromatogra-
phy, eluting with hexane/EA (1:1) to give 81% of a brown
liquid, 1H NMR (CDCl3, 400 MHz) d 8.18 (dd, J = 7.2, 0.8
Hz, 1H), 7.77-7.75 (m, 2H), 7.50 (td, J = 8.4, 2.0 Hz, 1H),
4.02 (t, J = 6.4 Hz, 2H), 3.10 (t, J = 6.4 Hz, 2H), 2.02 (bs,
1H); 13C NMR (CDCl3, 100 MHz) d 161.4, 152.5, 135.4,
134.6, 129.6, 128.7, 125.8, 124.5, 120.2, 59.5, 36.7; HRMS
(EI) calcd for C14H15ClO2 267.9735, found 267.9733.
4-Bromo-3-(4-(trifluoromethyl)phenyl)-1H-isochromen-
1-one (12f)
4-Bromo-3-phenyl-1H-isochromen-1-one (12a)
The compound was purified by column chromatogra-
phy, eluting with hexane/EA (40:1) to give 99% of a white
solid, mp 126-127 °C. 1H NMR (CDCl3, 400 MHz) d 8.32
(dd, J = 7.6, 1.2 Hz, 1H), 7.94 (dt, J = 8.0, 0.4 Hz, 1H),
7.85-7.78 (m, 3H), 7.58 (td, J = 8.0, 1.2 Hz, 1H), 7.49-7.45
(m, 3H); 13C NMR (CDCl3, 100 MHz) d 161.0, 151.6,
136.5, 135.4, 132.6, 130.1, 129.7, 129.6 (2C), 129.1, 128.0
(2C), 126.6, 120.4, 101.4; EA: calcd for C %: 59.83; H %:
3.01; found C %: 59.87, H %: 3.02.
The compound was purified by column chromatogra-
phy, eluting with hexane/EA(40:1) to give 97% of a yellow
solid, mp 136-137 °C. 1H NMR (CDCl3, 400 MHz) d 8.37
(dd, J = 7.6, 0.8 Hz, 1H), 8.00 (td, J = 7.6, 0.8 Hz, 3H), 7.92
(td, J = 6.8, 1.2 Hz, 1H), 7.75 (dd, J = 8.4, 0.4 Hz, 2H), 7.65
(td, J = 7.6, 1.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d
160.9, 154.4, 135.9, 135.1, 131.3, 130.7, 130.4, 129.9
(3C), 127.1, 125.7, 125.4 (2C), 120.9, 102.6; EA: calcd for
C %: 52.06; H %: 2.18; found C %: 52.04, H %: 2.19.
4-Bromo-3-(4-methoxyphenyl)-1H-isochromen-1-one
(12g)
4-Bromo-3-pentyl-1H-isochromen-1-one (12b)
The compound was purified by column chromatogra-
phy, eluting with hexane/EA(40:1) to give 71% of a yellow
liquid, 1H NMR (CDCl3, 400 MHz) d 8.26 (dd, J = 8.0, 1.2
Hz, 1H), 7.80-7.78 (m, 2H), 7.53 (td, J = 8.0, 2.0 Hz, 1H),
2.81 (t, J = 7.6 Hz, 2H), 1.75 (quin, J = 7.6 Hz, 2H), 1.41-
1.34 (m, 4H), 0.91 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3,
100 MHz) d 161.6, 155.8, 136.3, 135.3, 129.7, 128.4,
125.7, 120.2, 101.2, 33.4, 31.2, 26.6, 22.3, 13.9; HRMS
(EI) calcd for C14H15BrO2 294.0255, found 294.0255.
4-Bromo-3-isobutyl-1H-isochromen-1-one (12c)
The compound was purified by column chromatogra-
phy, eluting with hexane/EA(40:1) to give 98% of a yellow
liquid, 1H NMR (CDCl3, 400 MHz) d 8.25 (dt, J = 8.0, 0.8
Hz, 1H), 7.77 (td, J = 7.6, 0.8 Hz, 2H), 7.53-7.49 (m, 1H),
2.70 (d, J = 7.2 Hz, 2H), 2.26-2.19 (m, 1H), 1.00 (d, J = 6.8
Hz, 6H); 13C NMR (CDCl3, 100 MHz) d 161.4, 155.0,
136.2, 135.3, 129.6, 128.5, 125.8, 120.1, 102.0, 41.9, 27.4,
22.2 (2C); HRMS (EI) calcd for C13H13BrO2 280.0099,
found 280.0096.
The compound was purified by column chromatogra-
phy, eluting with hexane/EA(40:1) to give 89% of a yellow
solid, mp 150-151 °C. 1H NMR (CDCl3, 400 MHz) d 8.32
(dt, J = 8.0, 0.8 Hz, 1H), 7.95 (dd, J = 8.0, 0.8 Hz, 1H), 7.84
(td, J = 8.0, 0.8 Hz, 1H), 7.79-7.72 (m, 2H), 7.57 (td, J =
7.2, 0.8 Hz, 1H), 6.99 (dd, J = 7.2, 2.4 Hz, 2H), 3.87 (s,
3H); 13C NMR (CDCl3, 100 MHz) d 161.3, 160.8, 151.7,
136.8, 135.4, 131.3 (2C), 129.7, 128.8, 126.5, 124.9, 120.4,
113.4 (2C), 100.6, 55.4; EA: calcd for C %: 58.03; H %:
3.35; found C %: 57.96, H %: 3.37.
4-Bromo-3-pentyl-6,7-dihydrocyclopenta[c]pyran-1-
(5H)-one (12h)
The compound was purified by column chromatogra-
phy, eluting with hexane/EA(40:1) to give 98% of a yellow
liquid, 1H NMR (CDCl3, 400 MHz) d 2.86-2.71 (m, 4H),
2.58 (t, J = 7.6 Hz, 2H), 2.05 (quin, J = 8.0 Hz, 2H), 1.61
(quin, J = 7.2 Hz, 2H), 1.30-1.24 (m, 4H), 0.83 (t, J = 7.2
Hz, 3H); 13C NMR (CDCl3, 100 MHz) d 160.6, 160.2,
158.5, 125.0, 111.3, 33.9, 30.9, 30.6, 30.5, 26.3, 22.1 (2C),
13.7; HRMS (EI) calcd for C13H17BrO2 284.0412, found
284.0496.
4-Bromo-3-tert-butyl-1H-isochromen-1-one (12d)
The compound was purified by column chromatogra-
phy, eluting with hexane/EA (40:1) to give 69% of a white
solid, mp 123-124 °C, 1H NMR (CDCl3, 400 MHz) d 8.26
(ddd, J = 6.4, 1.2, 0.4 Hz, 1H), 7.96 (ddd, J = 7.2, 0.8, 0.4
Hz, 1H), 7.79 (td, J = 7.2, 1.6 Hz, 1H), 7.54 (td, J = 7.6, 1.2
Hz, 1H), 1.55 (s, 9H); 13C NMR (CDCl3, 100 MHz) d 161.2,
160.2, 137.5, 135.2, 129.3, 128.5, 125.9, 120.1, 100.5,
38.5, 28.5 (3C); EA: calcd for C %: 55.54; H %: 4.66;
found C %: 55.46, H %: 4.62.
Received November 30, 2007.

648 J. Chin. Chem. Soc., Vol. 55, No. 3, 2008
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