Synthesis of 4-arylisocoumarins (=4-aryl-1H-2-benzopyran-1-ones) through acidic hydrolysis of (Z)-2-(1-aryl-2-methoxyethenyl)benzaldehydes, followed by oxidation

Article abstract of DOI:10.1002/hlca.201300239

4-Arylisocoumarins (=4-aryl-1H-2-benzopyran-1-ones) 6 were prepared from 2-(1-aryl-2-methoxyethenyl)-1-bromobenzenes 1. Successive treatment of these bromo styrenes with BuLi and 1-formylpiperidine gave a mixture of (E)- and (Z)-2-(1-aryl-2-methoxyethenyl)benzaldehydes 2. Hydrolysis of (Z)-isomers with conc. HBr, followed by pyridinium chlorochromate (PCC) oxidation of the resulting 1H-2-benzopyran-1-ol derivatives 4 (and 5), afforded the desired products. Copyright

Full text of DOI:10.1002/hlca.201300239

Helvetica Chimica Acta – Vol. 96 (2013)
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Synthesis of 4-Arylisocoumarins (¼4-Aryl-1H-2-benzopyran-1-ones) through
Acidic Hydrolysis of (Z)-2-(1-Aryl-2-methoxyethenyl)benzaldehydes,
Followed by Oxidation
by Kazuhiro Kobayashi*, Wataru Miyatani, and Minami Kuroda
Division of Applied Chemistry, Department of Chemistry and Biotechnology, Graduate School of
Engineering, Tottori University, 4 – 101 Koyama-minami, Tottori 680-8552, Japan
(phone/fax: þ 81(857)315263; e-mail: kkoba@chem.tottori-u.ac.jp)
4-Arylisocoumarins (¼4-aryl-1H-2-benzopyran-1-ones) 6 were prepared from 2-(1-aryl-2-methoxy-
ethenyl)-1-bromobenzenes 1. Successive treatment of these bromo styrenes with BuLi and 1-
formylpiperidine gave
a mixture of (E)- and (Z)-2-(1-aryl-2-methoxyethenyl)benzaldehydes 2.
Hydrolysis of (Z)-isomers with conc. HBr, followed by pyridinium chlorochromate (PCC) oxidation
of the resulting 1H-2-benzopyran-1-ol derivatives 4 (and 5), afforded the desired products.
Introduction. – Previously, we reported that 2-(1-aryl-2-methoxyethenyl)benzalde-
hydes 2, easily prepared from 2-(1-aryl-2-methoxyethenyl)-1-bromobenzenes 1
(Scheme 1), were converted into 3-aryl-2-methoxyinden-1-one phenylhydrazones on
treatment successively with PhNHNH2 and conc. HBr [1]. We were interested in
exploring the possibility of the transformation of these aldehydes into 4-arylisocou-
marins (¼4-aryl-1H-2-benzopyran-1-ones) 6 by acid hydrolysis, followed by oxidation
of the resulting 1H-2-benzopyran-1-ols 4. Herein, we report the results of our study,
which provide a new procedure for the synthesis of 4-arylisocoumarins 6. Isocoumarins
have attracted much attention from organic as well as medicinal chemists1), because
some of their derivatives have been shown to exhibit a variety of biological activities
[3], and a number of biologically active compounds with the isocoumarin skeleton have
been found in nature [4]. Therefore, several efficient methods for the preparation of
isocoumarins have been recently reported [5]. However, there have been few reports
on the synthesis of 4-substituted isocoumarins [6].
Scheme 1
Results and Discussion. – Our synthesis of 4-arylisocoumarins 6 from (Z)-2-(1-
aryl-2-methoxyethenyl)benzaldehydes 2, is outlined in Scheme 2. Successive treatment
1
)
For a recent excellent review, see [2].
ꢀ 2013 Verlag Helvetica Chimica Acta AG, Zꢁrich

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of 1 with BuLi and 1-formylpiperidine under the conditions reported in [1] furnished 2
(Table). After chromatographic separation, compounds (Z)-2 were treated with equiv.
of conc. HBr at room temperature. The 1H-NMR spectra of the mixtures after aqueous
workup indicated that the products were mixtures of mainly cyclic hemiacetal
derivatives, 4-aryl-1H-2-benzopyran-1-ols 4, and cyclic methyl acetal derivatives, 4-
aryl-1-methoxy-1H-2-benzopyrans 5. The mixtures were subjected to the pyridinium
chlorochromate (PCC) oxidation without any purification to give the desired products
6 in moderate yields from (Z)-2 (cf. the Table). When the acid employed was conc. HI,
rather complicated mixtures of products were formed, and the yields of the desired
products after PCC oxidation considerably decreased (ca. 15%). The reactions using
conc. HCl were found to give even more disappointing results. As they gave
considerably complicated mixtures of products, we refrained from subjecting the
mixture to the next oxidation step. It should be noted that, surprisingly, the formation
of 6 from (E)-2 could not be achieved, because hydrolysis of (E)-2 gave results similar
to those of hydrolysis of (Z)-2 with conc. HCl.
Scheme 2
Table. Preparation of 4-Arylisocoumarins 6
Entry
1
2
Yielda)b) [%]
6
Yieldc) [%]
1
2
3
4
5
6
7
1a (R ¼ H, Ar¼ Ph)
2a [1]
2b
2c [1]
2d [1]
2e [1]
2f
79
62
76
79
67
79
77
6a
6b
6c
6d
6e
6f
6g
54
48
49
56
61
58
32
1b (R ¼ H, Ar¼ 3-MeꢀC6H4)
1c (R ¼ H, Ar¼ 4-MeꢀC6H4)
1d (R ¼ H, Ar¼ 4-ClꢀC6H4)
1e (R ¼ Cl, Ar¼ Ph)
1f (R ¼ Cl, Ar¼ 4-ClꢀC6H4)
1g (R ¼ MeO, Ar¼ Ph)
2g
a) Yields of isolated products. b) Each (E)/(Z) ratio is ca. 1 : 1. c) Yields of isolated products based on
(Z)-2.
The formation of hemiacetal derivatives 4 only from (Z)-2 may be rationalized by
cyclization of (Z)-2-(1-aryl-2-hydroxyethenyl)benzaldehydes 3, which were directly

Helvetica Chimica Acta – Vol. 96 (2013)
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and stereospecifically formed from (Z)-2. The initially formed hemiacetals 4 are
partially converted into methyl acetal derivatives 5. Both of 4 and 5 were oxidized with
PCC to lead to isocoumarins 6 as depicted in Scheme 2.
In conclusion, we have demonstrated that 4-arylisocoumarins 6 can be prepared by
a three-step sequence from 2-(1-aryl-2-methoxyethenyl)-1-bromobenzenes 1 via (Z)-2-
(1-aryl-2-methoxyethenyl)benzaldehydes 2. Although total yields of the desired
products are not so high due to the inadequacy of the corresponding (E)-isomers for
the present sequence, it may find some applications in organic synthesis because 4-
arylisocoumarins are rather difficult to prepare by previous methods.
Experimental Part
General. All org. solvents were dried over appropriate drying agents and distilled prior to use. TLC:
Merck silica gel 60 PF254. Column chromatography (CC): Wako Gel C-200E. M.p.: Laboratory Devices
MEL-TEMP II melting point apparatus; uncorrected. IR Spectra: PerkinꢀElmer Spectrum65 FTIR
spectrophotometer; ˜n in cmꢀ1. 1H- and 13C-NMR Spectra: in CDCl3 with TMS as an internal reference,
with JEOL ECP500 FT-NMR (1H and 13C) or JEOL LA400 FT-NMR (1H; spectrometer (at 500 or 400
(1H), and 125 MHz (13C)); d in ppm, J in Hz. EI-MS (70 eV): with JEOL JMS AX505 HA spectrometer;
m/z (rel. %).
2-(1-Aryl-2-methoxyethenyl)benzaldehydes 2a, 2c, 2d, and 2e were prepared from the correspond-
ing 2-(1-aryl-2-methoxyethenyl)-1-bromobenzenes 1 [7] as described in [1]. BuLi was supplied by Asia
Lithium Corporation. All other chemicals were commercially available.
2-[2-Methoxy-1-(3-methylphenyl)ethenyl]benzaldehyde (2b). The title compound was prepared
from 1-bromo-2-[2-methoxy-1-(3-methylphenyl)ethenyl]benzene (1b) [7] as described in [1].
Data of (E)-2b. Yellow oil. Rf (AcOEt/hexane 1:10) 0.41. IR (neat): 2841, 2744, 1694, 1632. 1H-NMR
(500 MHz): 2.29 (s, 3 H); 3.82 (s, 3 H); 6.17 (s, 1 H); 7.00 – 7.02 (m, 1 H); 7.18 – 7.19 (m, 3 H); 7.32 (ddd,
J ¼ 7.8, 7.5, 0.9, 1 H); 7.43 (td, J ¼ 7.5, 0.9, 1 H); 7.55 (td, J ¼ 7.5, 1.4, 1 H); 7.95 (dd, J ¼ 7.8, 1.4, 1 H); 10.09
(s, 1 H). Anal. calc. for C17H16O2 (252.31): C 80.93, H 6.39; found: C 81.01, H 6.42.
Data of (Z)-2b. Yellow oil. Rf (AcOEt/hexane 1:10) 0.35. IR (neat): 2839, 2747, 1694, 1634. 1H-NMR
(500 MHz): 2.78 (s, 3 H); .3.67 (s, 3 H); 6.75 (s, 1 H); 6.94 (d, J ¼ 7.4, 1 H); 6.97 (s, 1 H); 7.01 (d, J ¼ 7.4,
1 H); 7.15 (t, J ¼ 7.4, 1 H); 7.21 (d, J ¼ 7.5, 1 H); 7.40 (t, J ¼ 7.4, 1 H); 7.55 (ddd, J ¼ 8.0, 7.4, 1.1, 1 H); 7.99
(d, J ¼ 8.0, 1.1, 1 H); 10.07 (s, 1 H). Anal. calc. for C17H16O2 (252.31): C 80.93, H 6.39; found: C 80.82, H
6.49.
4-Chloro-2-[1-(4-chlorophenyl)-2-methoxyethenyl]benzaldehyde (2f). The title compound was
prepared from 1-bromo-4-chloro-2-[1-(4-chlorophenyl)-2-methoxyethenyl]benzene (1f) as described in
[1]. Compound 1f was prepared from 2-bromo-5-chlorobenzaldehyde according to the procedure for the
preparation of 1a [7] via (2-bromo-5-chlorophenyl)(4-chlorophenyl)methanol and (2-bromo-5-chloro-
phenyl)(4-chlorophenyl)methanone.
(2-Bromo-5-chlorophenyl)(4-chlorophenyl)methanol. Yield: 96%. Colorless oil. Rf (AcOEt/hexane
1
1:10) 0.34. IR (neat): 3310. H-NMR (500 MHz): 2.40 (d, J ¼ 3.4, 1 H); 6.10 (d, J ¼ 3.4, 1 H); 7.15 (dd,
J ¼ 8.6, 2.3, 1 H); 7.33 (s, 4 H); 7.46 (d, J ¼ 8.6, 1 H); 7.60 (d, J ¼ 2.3, 1 H). Anal. calc. for C13H9BrCl2O
(332.02): C 47.03, H 2.73; found: C 47.04, H 2.73.
(2-Bromo-5-chlorophenyl)(4-chlorophenyl)methanone. Yield: 94%. White solid. M.p. 94 – 978
(hexane/CH2Cl2). IR (KBr): 1663. 1H-NMR (500 MHz): 7.32 (d, J ¼ 2.9, 1 H); 7.35 (dd, J ¼ 8.6, 2.9,
1 H); 7.46 (d, J ¼ 8.6, 2 H); 7.58 (d, J ¼ 8.6, 1 H); 7.74 (d, J ¼ 8.6, 2 H). Anal. calc. for C13H7BrCl2O
(330.00): C 47.31, H 2.14; found: C 47.08, H 2.27.
1-Bromo-4-chloro-2-[1-(4-chlorophenyl)-2-methoxyethenyl]benzene (1f). Yield: 89%. Ca. 1 :1
mixture of stereoisomers. Anal. samples of each isomer was obtained by CC (SiO2).
Data of (E)-1f. Colorless oil. Rf (THF/hexane 1:30) 0.47. IR (neat): 2837, 2747, 1690, 1629. 1H-NMR
(500 MHz): 3.83 (s, 3 H); 6.26 (s, 1 H); 7.17 (dd, J ¼ 8.6, 2.3, 1 H); 7.22 – 7.35 (m, 5 H); 7.51 (d, J ¼ 8.6,
1 H). Anal. calc. for C15H11BrCl2O (358.06): C 50.32, H 3.10; found: C 50.09, H 3.18.

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Data of (Z)-1f. Colorless oil. Rf (THF/hexane, 1:30) 0.37. IR (neat): 2843, 2746, 1697, 1636. 1H-NMR
(500 MHz): 3.77 (s, 3 H); 6.66 (s, 1 H); 7.02 (d, J ¼ 8.6, 2 H); 7.16 (dd, J ¼ 8.6, 2.3, 1 H); 7.21 – 7.24 (m,
3 H); 7.56 (d, J ¼ 8.6, 1 H). Anal. calc. for C15H11BrCl2O (358.06): C 50.32, H 3.10; found: C 50.23, H 3.26.
Data of (E)-2f. Yellow oil. Rf (AcOEt/hexane 1:15) 0.32. IR (neat): 2842, 2739, 1691, 1633. 1H-NMR
(500 MHz): 3.86 (s, 3 H); 6.25 (s, 1 H); 7.25 – 7.32 (m, 5 H); 7.42 (dt, J ¼ 8.6, 1.1, 1 H); 7.89 (d, J ¼ 8.6,
1 H); 9.97 (s, 1 H). Anal. calc. for C16H12Cl2O2 (307.17): C 62.56, H 3.94; found: C 62.53, H 4.11.
Data of (Z)-2f. Yellow oil. Rf (AcOEt/hexane 1:15) 0.25. IR (neat): 2840, 2742, 1691, 1629. 1H-NMR
(400 MHz): 3.76 (s, 3 H); 6.77 (s, 1 H); 7.06 (d, J ¼ 8.8, 2 H); 7.18 (d, J ¼ 2.0, 1 H); 7.26 (d, J ¼ 8.8, 2 H);
7.40 (dq, J ¼ 8.3, 1.0, 1 H); 7.93 (d, J ¼ 8.3, 1 H); 9.96 (s, 1 H). Anal. calc. for C16H12Cl2O2 (307.17): C
62.56, H 3.94; found: C 62.31, H 3.96.
4-Methoxy-2-(2-methoxy-1-phenylethenyl)benzaldehyde (2g). The title compound was prepared
from 1-bromo-4-methoxy-2-(2-methoxy-1-phenylethenyl)benzene (1g) [8] as described reported in [1].
Data of (E)-2g. Yellow oil. Rf (AcOEt/hexane 1:10) 0.28. IR (neat): 2839, 2756, 1684, 1634.
1H-NMR (500 MHz): 3.84 (s, 3 H); 3.86 (s, 3 H); 6.25 (s, 1 H); 6.80 (d, J ¼ 2.3, 1 H); 6.96 (dd, J ¼ 8.6, 2.3,
1 H); 7.19 (tt, J ¼ 7.4, 1.1, 1 H); 7.29 (dd, J ¼ 7.8, 7.4, 2 H); 7.41 (dd, J ¼ 7.8, 1.1, 2 H); 7.96 (d, J ¼ 8.6, 1 H);
9.96 (s, 1 H). Anal. calc. for C17H16O3 (268.31): C 76.10, H 6.01; found: C 76.04, H 6.23.
Data of (Z)-2g. Yellow oil. Rf (AcOEt/hexane 1:10) 0.20. IR (neat): 2839, 2757, 1682, 1641. 1H-NMR
(500 MHz): 3.72 (s, 3 H); 3.82 (s, 3 H); 6.69 (d, J ¼ 2.9, 1 H); 6.77 (s, 1 H); 6.95 (dd, J ¼ 9.2, 2.9, 1 H); 7.15
(dd, J ¼ 7.8, 1.1, 2 H); 7.20 (tt, J ¼ 7.4, 1.1, 1 H); 7.27 (dd, J ¼ 7.8, 7.4, 2 H); 7.99 (d, J ¼ 9.2, 1 H); 9.93 (s,
1 H). Anal. calc. for C17H16O3 (268.31): C 76.10, H 6.01; found: C 76.04, H 6.03.
4-Phenylisocoumarin (¼4-Phenyl-1H-2-benzopyran-1-one; 6a). Representative Procedure. To a
stirred soln. of 2-[(Z)-2-methoxy-1-phenylethenyl]benzaldehyde ((Z)-2a; 0.24 g, 1.0 mmol) in MeCN
(8 ml) at 08 was added conc. HBr (0.17 g, 1.0 mmol). After stirring at r.t. for 4 h, sat. aq. NaHCO3 (15 ml)
was added, and org. materials were extracted with AcOEt (3 ꢁ 10 ml). The combined extract was dried
(Na2SO4) and concentrated by evaporation. The residue was dissolved in CH2Cl2 (8 ml) and Celite
(0.80 g), and pyridinium chlorochromate (PCC; 1.0 g, 2.0 mmol) was added under stirring at r.t. After
stirring for 30 min at the same temp., the mixture was filtered by suction and the filtrate was concentrated
by evaporation. The residue was purified by prep. layer chromatography (PLC; SiO2; Rf (AcOEt/hexane
1:10) 0.30) to give 6a (0.12 g, 54%). White solid. M.p. 95 – 988 (hexane/CH2Cl2) ([6]: 94 – 958). IR (KBr):
1759, 1740, 1628, 1603. 1H-NMR (500 MHz): 7.39 – 7.41 (m, 3 H); 7.46 – 7.51 (m, 4 H); 7.56 (ddd, J ¼ 8.0,
7.4, 1.1, 1 H); 7.69 (ddd, J ¼ 8.0, 7.4, 1.1, 1 H); 8.40 (dd, J ¼ 8.0, 1.1, 1 H). MS: 222 (100, Mþ).
4-(3-Methylphenyl)isocoumarin (¼4-(3-Methylphenyl)-1H-2-benzopyran-1-one; 6b). Yellow vis-
cous oil. Rf (AcOEt/hexane 1:15) 0.37. IR (neat): 1732, 1630. 1H-NMR (400 MHz): 2.43 (s, 3 H); 7.19 –
7.38 (m, 4 H); 7.38 (t, J ¼ 7.8, 1 H); 7.42 (d, J ¼ 8.3, 1 H); 7.56 (ddd, J ¼ 8.3, 7.3, 1.5, 1 H); 7.69 (ddd, J ¼ 8.3,
7.3, 1.5, 1 H); 8.39 (dd, J ¼ 8.3, 1.4, 1 H). 13C-NMR: 21.4; 120.7; 121.3; 124.6; 126.8; 128.4; 128.7; 129.1;
129.9; 130.4; 132.9; 134.6; 136.8; 138.6; 142.1; 162.0. MS: 236 (100, Mþ). Anal. calc. for C16H12O2 (236.27):
C 81.34, H 5.12; found: C 81.20, H 5.36.
4-(4-Methylphenyl)isocoumarin (¼4-(4-Methylphenyl)-1H-2-benzopyran-1-one; 6c) [6a]. Pale-yel-
1
low solid. M.p. 988 (hexane/Et2O). IR (KBr): 1728, 1631. H-NMR (500 MHz): 2.44 (s, 3 H); 7.24 (s,
1 H); 7.29 (s, 4 H); 7.41 (d, J ¼ 8.0, 1 H); 7.55 (dd, J ¼ 8.0, 7.4, 1 H); 7.68 (ddd, J ¼ 8.0, 7.4, 1.1, 1 H); 8.39
(dd, J ¼ 8.0, 1.1, 1 H). 13C-NMR: 21.2; 120.5; 121.4; 124.7; 126.4; 128.4; 129.5; 129.7; 130.0; 134.6; 137.0;
138.3; 141.1; 162.1. MS: 236 (100, Mþ). Anal. calc. for C16H12O2 (236.27): C 81.34, H 5.12; found: C 81.11,
H 5.15.
4-(4-Chlorophenyl)isocoumarin (¼4-(4-Chlorophenyl)-1H-2-benzopyran-1-one; 6d) [6a]. White
solid. M.p. 164 – 1658 (hexane/CH2Cl2) ([6]: 165 – 1668). IR (KBr): 1745, 1628. 1H-NMR (500 MHz): 7.25
(d, J ¼ 8.0, 2 H); 7.33 – 7.35 (m, 2 H); 7.47 (d, J ¼ 8.0, 2 H); 7.57 (dd, J ¼ 8.0, 6.9, 1 H); 7.70 (ddd, J ¼ 8.0,
6.9, 1.7, 1 H); 8.40 (d, J ¼ 8.0, 1 H).
6-Chloro-4-phenylisocoumarin (¼6-Chloro-4-phenyl-1H-2-benzopyran-1-one; 6e). White solid.
M.p. 126 – 1288 (hexane/Et2O). IR (KBr): 1742, 1630. 1H-NMR (500 MHz): 7.30 (d, J ¼ 8.0, 1 H);
7.39 – 7.42 (m, 3 H); 7.50 – 7.56 (m, 4 H); 8.36 (d, J ¼ 8.0, 1 H). 13C-NMR (125 MHz): 119.6; 119.9; 124.4;
128.8; 129.1; 129.1; 129.8; 131.8; 132.3; 138.3; 141.7; 143.4; 161.2. MS: 256 (100, Mþ). Anal. calc. for
C15H9ClO2 (256.68): C 70.19, H 3.53; found: C 70.12, H 3.47.

Helvetica Chimica Acta – Vol. 96 (2013)
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6-Chloro-4-(4-chlorophenyl)isocoumarin (¼6-Chloro-4-(4-chlorophenyl)-1H-2-benzopyran-1-one;
1
6f). White solid. M.p. 200 – 2028 (hexane/Et2O). IR (KBr): 1745, 1630. H-NMR (500 MHz): 7.26 (s,
1 H); 7.30 (d, J ¼ 1.7, 1 H); 7.32 (d, J ¼ 8.6, 2 H); 7.49 (d, J ¼ 8.6, 2 H); 7.52 (dd, J ¼ 8.6, 1.7, 1 H); 8.32 (d,
J ¼ 8.6, 1 H). 13C-NMR: 118.9; 119.6; 124.1; 129.3; 129.4; 130.8; 131.0; 131.9; 135.0; 137.9; 141.9; 143.5;
161.0. MS: 290 (100, Mþ). Anal. calc. for C15H8Cl2O2 (291.13): C 61.88, H 2.77; found: C 61.83, H 2.71.
6-Methoxy-4-phenylisocoumarin (¼6-Methoxy-4-phenyl-1H-2-benzopyran-1-one; 6g). Pale-yellow
solid. M.p. 139 – 1418 (hexane/CH2Cl2). IR (KBr): 1724, 1636, 1605. 1H-NMR (500 MHz): 3.80 (s, 3 H);
6.78 (dd, J ¼ 2.5, 1 H); 7.08 (dd, J ¼ 8.8, 2.5, 1 H); 7.23 (s, 1 H); 7.39 – 7.41 (m, 2 H); 7.43 – 7.50 (m, 3 H);
8.32 (dd, J ¼ 8.8, 1 H). 13C-NMR: 55.6; 107.8; 114.5; 116.1; 120.5; 128.5; 128.9; 129.8; 132.4; 133.2; 139.1;
142.9; 161.8; 164.7. MS: 252 (100, Mþ). Anal. calc. for C16H12O3 (252.26): C 76.18, H 4.79; found: C 76.03,
H 4.92.
We are grateful to Mrs. Miyuki Tanmatsu of our university for recording mass spectra and
performing combustion analyses.
REFERENCES
[1] K. Kobayashi, W. Miyatani, N. Matsumoto, Helv. Chim. Acta 2013, 96, 239.
[2] S. Pal, V. Chatare, M. Pal, Curr. Org. Chem. 2011, 15, 782.
[3] A. Kurume, Y. Kamata, M. Yamashita, Q. Wang, H. Matsuda, M. Yoshikawa, I. Kawasaki, S. Ohta,
Chem. Pharm. Bull. 2008, 56, 1264; J. J. Heynekamp, L. A. Hunsaker, T. A. Vander Jagt, R. E.
Royer, L. M. Deck, D. L. Vander Jagt, Bioorg. Med. Chem. 2008, 16, 5285; S. L. Payne, S.
Rodoriguez-Aristegui, J. Bardos, C. Cano, R. T. Golding, I. R. Hardcastle, M. Peacock, N. Parveen,
R. J. Griffin, Bioorg. Med. Chem. Lett. 2010, 20, 3649; U. Haedke, M. Gçtz, P. Baer, S. H. L. Verhelst,
´
Bioorg. Med. Chem. 2012, 20, 633; M. Peuchmaur, M.-A. Lacour, J. Sevalle, V. Lisowski, Y. Touati-
Jallabe, F. Rodier, J. Martinez, F. Checler, J.-F. Hernandez, Bioorg. Med. Chem. 2013, 21, 1018.
[4] M. Rudyanto, K. Kobayashi, T. Honda, Heterocycles 2009, 79, 753; Z. Han, W. Mei, Y. Zhao, Y.
Deng, H. Dai, Chem. Nat. Compd. 2009, 45, 805; C. Kihampa, M. H. H. Nkunya, C. C. Joseph, S. M.
Magesa, A. Hassanali, M. Heydenreich, E. Kleinpeter, Phytochemistry 2009, 70, 1233; J.
Kornsakulkarn, C. Thongpanchang, S. Lapanun, K. Srichomthong, J. Nat. Prod. 2009, 72, 1341; J.
Arunpanichlert, V. Rukachaisirikul, Y. Sukpondma, S. Phongpaichit, S. Tewtrakul, N. Rungjindamai,
J. Sakayaroj, Chem. Pharm. Bull. 2010, 58, 1033; D. S. Zinad, K. A. Shaaban, M. A. Abdalla, T.
Islam, A. Schꢁffer, H. Laatsch, Nat. Prod. Commun. 2011, 6, 45; C. Boonlarppradab, C.
Suriyachadkun, S. Suphothina, P. Tobwor, J. Antibiot. 2011, 64, 267; M. Isaka, S. Palasarn, S.
Supothina, S. Komwijit, J. J. Lunagsa-ard, J. Nat. Prod. 2011, 74, 782; Y. Takenaka, N. Morimoto, N.
Hamada, T. Tanahashi, Phytochemistry 2011, 72, 1431; M.-J. Cheng, P.-H. Yang, M.-D. Wu, I.-S.
Chen, M.-T. Hsich, Y.-L. Chen, G.-F. Yuan, Helv. Chim. Acta 2011, 94, 1638; M. Tsukada, M. Fukai,
K. Miki, T. Shiraishi, T. Suzuki, K. Nishio, T. Sugita, M. Ishino, K. Kinoshita, K. Takahashi, M. Shiro,
K. Koyama, J. Nat. Prod. 2011, 74, 1645; S.-X. Yang, J.-M. Gao, Q. Zhang, H. Laatsch, Bioorg. Med.
Chem. Lett. 2011, 21, 1887; Y. Takenaka, N. Hamada, T. Tanahashi, Heterocycles 2011, 83, 2157; V.
Rukachaisirikul, A. Rodoglin, Y. Sukpondma, S. Phongpaichit, J. Buatong, J. Sakayaroj, J. Nat. Prod.
2012, 75, 853; L.-Y. Ma, W.-Z. Liu, L. Shen, Y.-L. Huang, X.-G. Rong, Y.-Y. Xu, X.-D. Gao,
Tetrahedron 2012, 68, 2276; F. Yamasaki, S. Machida, A. Nakata, A. E. Nugroho, Y. Hirasawa, T.
Kaneda, O. Shirota, N. Hagane, T. Sugizaki, H. Morita, J. Nat. Med. 2013, 67, 212.
[5] X. Fan, Y. He, L. Cui, S. Guo, J. Wang, X. Zhang, Eur. J. Org. Chem. 2012, 673; T. Miura, K. Hiraga,
T. Toyoshima, M. Yamauchi, M. Murakami, Chem. Lett. 2012, 41, 798; L. Ackermann, J. Pospech, K.
Graczyk, K. Rauch, Org. Lett. 2012, 14, 930; Z. Li, J. Hong, L. Weng, X. Zhou, Tetrahedron 2012, 68,
1552; P. Zhao, D. Chen, G. Song, K. Han, X. Li, J. Org. Chem. 2012, 77, 1579; S. Cai, F. Wang, C. Xi,
Synthesis 2012, 44, 1892; R. K. Chinnagolla, M. Jerganmohan, Chem. Commun. 2012, 48, 2030; S.
Cai, F. Wang, C. Xi, J. Org. Chem. 2012, 77, 2331; P.-Y. Chen, K.-S. Huang, C.-C. Tsai, T.-P. Wang, E.-
C. Wang, Org. Lett. 2012, 14, 4930; V. Kavala, C.-C. Wang, D. K. Barange, C.-W. Kuo, P.-M. Lei, C.-F.
Yao, J. Org. Chem. 2012, 77, 5022; L. Liu, J. Hu, X.-C. Wang, M.-J. Zhong, X.-Y. Liu, S.-D. Yang, Y.-
M. Liang, Tetrahedron 2012, 68, 5391; X.-D. Fei, Z.-Y. Ge, T. Tang, Y.-M. Zhu, S.-J. Ji, J. Org. Chem.

2178
Helvetica Chimica Acta – Vol. 96 (2013)
2012, 77, 10321; M. Deponti, S. I. Kozhushkov, D. S. Yufit, L. Ackermann, Org. Biomol. Chem. 2013,
11, 142; X.-X. Guo, J. Org. Chem. 2013, 78, 1660; D. Nandi, D. Ghosh, S.-J. Chen, B.-C. Kuo, N. M.
Wang, H. M. Lee, J. Org. Chem. 2013, 78, 3445.
[6] K. Beautement, J. M. Clough, Tetrahedron Lett. 1984, 25, 3025; M. Lessi, T. Masini, L. Nucara, F.
Bellina, R. Rossi, Adv. Synth. Catal. 2011, 353, 501.
[7] K. Kobayashi, Y. Shirai, T. Nagaoka, H. Konishi, Synth. Commun. 2009, 39, 2866.
[8] K. Kobayashi, K. Hayashi, K. Miyamoto, O. Morikawa, H. Konishi, Synthesis 2006, 2934.
Received June 14, 2013