Efficient synthesis of monosubstituted 3-alkynylfurans via Suzuki coupling

Article abstract of DOI:10.1055/s-2008-1072576

A convenient synthesis of monosubstituted 3-alkynyl-furans by Suzuki coupling reaction of 3-furanylboronic acid with substituted acetylene bromides is described. The internal alkyne products were attainable in 50-89% yields from substrates free of relatively acidic protons. Our protocol is expected to find applications in the synthesis of structurally related natural products.

Full text of DOI:10.1055/s-2008-1072576

PAPER
1729
Efficient Synthesis of Monosubstituted 3-Alkynylfurans via Suzuki Coupling
S
ynthesis of Mono
i
substitu
a
ted 3-Alky
o
nylfurans bao Yang,a,b Li Zhu,c,b Yuedong Zhou,d,b Zhong Li,*a Hongbin Zhai*b
a
School of Pharmacy, East China University of Science and Technology, Shanghai 200237, P. R. of China
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. of China
Fax +86(21)64166128; E-mail: zhaih@mail.sioc.ac.cn
Department of Chemistry, Shanghai University, Shanghai 200436, P. R. of China
Hefei National Laboratory for Physical Science at Microscale and Department of Chemistry,
University of Science and Technology of China, Hefei, Anhui 230026, P. R. of China
b
c
d
Received 29 December 2007; revised 18 February 2008
Ts
Abstract: A convenient synthesis of monosubstituted 3-alkynyl-
furans by Suzuki coupling reaction of 3-furanylboronic acid with
substituted acetylene bromides is described. The internal alkyne
products were attainable in 50–89% yields from substrates free of
relatively acidic protons. Our protocol is expected to find applica-
tions in the synthesis of structurally related natural products.
N
Boc
A
Figure 1 Protected propargylamine A
Key words: Suzuki coupling, monosubstituted 3-alkynylfurans, 3-
furanylboronic acid, bromoalkynes
contemporary organic chemists, although a few sporadic
synthetic approaches to them (e.g., from sodium tetra-
alkynylaluminates,8 or through Negishi9 or Stille10 cou-
pling) have been reported.
Conjugated alkynylfurans, especially 3-alkynylfurans, are
often present as part of the structure in several natural
products1 and designed bioactive agents,2 and also used as
intermediates in natural product synthesis.3
Recently we were interested in developing a convenient
and general method for the synthesis of monosubstituted
3-alkynylfurans. This paper discloses our investigations
centered at fast assembly of these internal alkynes by
Suzuki coupling reaction,11 a powerful transformation
that plays a more and more important role in modern or-
ganic synthesis.
Although polysubstituted 3-alkynylfurans could be easily
constructed via Sonogashira coupling of terminal alkynes
with the corresponding 3-halofurans,4,5 the reaction in-
volving simple 3-halofurans proves to be a dramatically
different case based both upon our own observations and
upon literature results. For example, no coupling product
could be isolated by the reaction of protected propargyl-
amine A (Figure 1) with 3-bromofuran in the presence of
Pd(PPh3)4/CuI, or Pd(PPh3)2Cl2/CuI (5–10 mol% of each
catalyst) in Et3N–DMF (1:1 to 2:1), or Et2NH alone at
55 °C to reflux temperatures for 8–20 hours. In addition,
only few papers6 describe the Sonogashira coupling reac-
tion of simple 3-halofurans. Among these, the Sonogash-
ira reaction of 3-bromofuran with propargyl alcohol6a and
methyl propargyl ether6b was reported to give the corre-
sponding coupling products in 7% and 25% yield, respec-
tively. In the synthesis of hispanolone, Wong6c–e
described three cases of Sonogashira coupling of parent 3-
bromofuran conducted in a large amount of Et2NH used as
both base and solvent, in which the alkyne substrate was
present in the system at 5–6 mM concentration. Moreover,
coupling took place regioselectively at the C-2 position of
2,3-dibromofurans although 200 mol% of the terminal
alkynes were added.7
The search for Suzuki reaction parameters started with the
coupling of bromoalkyne 1a (Scheme 1) and 3-furanbo-
ronic acid (2) in the presence of Pd(OAc)2 and Na2CO3 in
boiling PrOH–H2O (5:1) for two hours. Unfortunately, no
desirable product could be obtained in this case. However,
when the reaction was run in the presence of Pd(PPh3)4
(10 mol%) and Ba(OH)2·8H2O in boiling DME–H2O (4:1)
for 30 minutes, 3-alkynylfuran 3a was formed in moder-
ate yield (50%). Furthermore, no substantial gain in the
product yield was observed by increasing the catalyst
loading from 10 to 20 mol%. Therefore, the catalyst usage
was fixed at 10 mol% for all subsequent experiments.11
Ts
O
B(OH)2
Ts
N
Boc
2
N
Boc
O
Br
"Pd", base
solvents, ∆
1a
3a
Scheme 1
In order to evaluate the scope of the current method, nine
additional 1-bromoalkynes 1b–j (Table 1) were examined
using the optimized reaction conditions. As a homologue
of 1a, the 1-bromoalkyne 1b (entry 2) coupled with 2 to
generate internal alkyne 3b in comparable yield (62%). It
is noteworthy that alkynes 1c and 1d (entries 3 and 4),
containing a secondary sulfonamide moiety, resulted in
It seems that highly efficient and practical assembly of
monosubstituted 3-alkynylfurans (i.e., no substitutions at
other positions of furan) remains a daunting challenge to
SYNTHESIS 2008, No. 11, pp 1729–1732
x
x.
x
x
.
2
0
0
8
Advanced online publication: 07.04.2008
DOI: 10.1055/s-2008-1072576; Art ID: F24407SS
© Georg Thieme Verlag Stuttgart · New York

1730
X. Yang et al.
PAPER
Bromoalkynes 1a–g;12 General Procedure
much lower yields of the coupling products due to re-
duced efficiency of the coupling reaction. These results, in
combination with those for 1a and 1b, suggest that the
amine nitrogen should be fully protected to ensure better
material conversion. For the alkyne components with an
ether functionality such as 1e and 1f (entries 5 and 6), the
reaction also went reasonably well and the coupling prod-
ucts were obtained in around 60% yields. Finally, the cou-
pling efficiency was greatly enhanced in the case of
arylacetylene bromides 1g–j (entries 7–10) where 3-(aryl-
alkynyl)furans 3g–j were formed in high yields (79–
89%).
In a round-bottomed flask, the respective terminal alkyne (3 mmol)
was dissolved in acetone (15 mL). After the addition of N-bromo-
succinimide (110 mol%) and AgNO3 (10 mol%), the mixture was
stirred for 1 h and diluted with Et2O (20 mL) and H2O (20 mL). The
two layers were separated and the aqueous layer was extracted with
Et2O (3 × 40 mL). The combined organic layers were washed with
brine (30 mL), dried (MgSO4), filtered, and concentrated. The resi-
due was purified by column chromatography or distillation to afford
the desired product.
1a
Purified by column chromatography (SiO2; EtOAc–PE, 1:10);
white solid (82%); mp 118–120 °C.
1H NMR (300 MHz, CDCl3) d = 1.36 (s, 9 H), 2.45 (s, 3 H), 4.64 (s,
2 H), 7.33 (d, J = 8.1 Hz, 2 H), 7.89 (d, J = 8.4 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 21.6, 27.8, 36.7, 44.0, 75.2, 85.0,
128.2, 129.2, 136.4, 144.5, 150.1.
Table 1 Pd(PPh3)4-Catalyzed Suzuki Coupling of Bromoalkynes
and 3-Furanboronic Acida
2, Pd(PPh3)4
Ba(OH)2⋅8H2O
O
R
Br
R
MS (ESI): m/z = 410 (M + Na).
DME–H2O
∆, 30 min
1
3
Anal. Calcd for C15H18BrNO4S: C, 46.40; H, 4.67; N, 3.61. Found:
C, 46.46; H, 4.69; N, 3.48.
Entry
R
Bromoalkyne Product
Yield (%)b
1b12
1
2
CH2N(Ts)Boc
(CH2)2N(Ts)Boc
CH2NHBs
CH2NHNs
CH2OBn
1a
1b
1c
1d
1e
1f
3a
3b
3c
3d
3e
3f
50
Purified by column chromatography (SiO2; EtOAc–PE, 1:10);
white solid (92%); mp 91–93 °C.
1H NMR (300 MHz, CDCl3): d = 1.35 (s, 9 H), 2.45 (s, 3 H), 2.68
(t, J = 7.2 Hz, 2 H), 3.99 (t, J = 7.2 Hz, 2 H), 7.32 (d, J = 8.1 Hz, 2
H), 7.80 (d, J = 8.1 Hz, 2 H).
62
3
34
4
31c
66
1c
5
Purified by column chromatography (SiO2; PE–CH2Cl2, 1:3); white
solid (71%); mp 88–90 °C.
1H NMR (300 MHz, CDCl3): d = 3.89 (d, J = 6.3 Hz, 2 H), 4.95 (t,
J = 5.8 Hz, 1 H, NH), 7.51–7.64 (m, 3 H), 7.88–7.93 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 33.9, 45.0, 74.0, 127.3, 129.1,
133.0, 139.5.
6
(CH2)2OBn
Ph
57
7
1g
1h
1i
3g
3h
3i
79
8
4-O2NC6H4
4-MeOC6H4
4-MeC6H4
80c
85c
89c
9
MS (ESI): m/z = 328 (M + Na + MeOH), 296 (M + Na).
10
1j
3j
Anal. Calcd for C9H8BrNO2S: C, 39.43, H, 2.94; N, 5.11. Found: C,
39.45; H, 2.88; N, 5.07.
a Reaction conditions: 1 (120 mol%), 2 (100 mol%), Pd(PPh3)4 (10
mol%), Ba(OH)2·8H2O (500 mol%), DME–H2O (4:1). Bs = benzene-
sulfonyl, Ns = 4-nitrobenzenesulfonyl.
1d
b Isolated yields.
Purified by column chromatography (SiO2; PE–CH2Cl2, 1:3); white
c Amounts of bromoalkyne 1 and 2 used were 100 mol% and 120
mol%, respectively.
solid (82%); mp 152–153 °C.
1H NMR (300 MHz, acetone-d6): d = 2.92 (s, 1 H, NH), 4.01 (s, 2
H), 8.19 (d, J = 8.7 Hz, 2 H), 8.49 (d, J = 8.7 Hz, 2 H).
13C NMR (75 MHz, acetone-d6): d = 33.9, 45.3, 75.5, 124.8, 129.4,
In summary, we have accomplished a convenient synthe-
sis of monosubstituted 3-alkynylfurans 3 by Suzuki cou-
pling reaction of 3-furanboronic acid (2) with substituted
acetylene bromides 1. The internal alkynes were attain-
able as coupling products in 50–89% yields from most
substrates except those possessing relatively acidic pro-
tons. Our protocol is expected to find applications in the
synthesis of structurally related natural products.
147.4, 150.8.
MS (ESI): m/z = 317 (M+).
Anal. Calcd for C9H7BrN2O4S: C, 33.87; H, 2.21; N, 8.78. Found:
C, 33.98; H, 2.24; N, 8.63.
1e13
Purified by column chromatography (SiO2; EtOAc–PE, 1:15); light
yellow oil (96%).
1H NMR (300 MHz, CDCl3): d = 4.19 (s, 2 H), 4.59 (s, 2 H), 7.29–
All solvents and reagents were obtained from commercial sources
and used without further purification unless otherwise stated. NMR
spectra were recorded in CDCl3 or acetone-d6 (1H at 300 MHz and
13C at 75 MHz) on Bruker DPX-300 and Varian MERCURY 300
spectrometers, using TMS as the internal standard. Analytical sam-
ples were obtained by chromatography on silica gel (Shandong
Yantai Jiangyou Corp., China; 200–300 mesh).
7.36 (m, 5 H).
1f14
Purified by column chromatography (SiO2; EtOAc–PE, 1:15); col-
orless oil (53%).
1H NMR (300 MHz, CDCl3): d = 2.51 (t, J = 6.8 Hz, 2 H), 3.58 (t,
J = 6.9 Hz, 2 H), 4.54 (s, 2 H), 7.34–7.36 (m, 5 H).
Synthesis 2008, No. 11, 1729–1732 © Thieme Stuttgart · New York

PAPER
Synthesis of Monosubstituted 3-Alkynylfurans
1731
1g15
3b
Purified by vacuum distillation (60 °C/1 mmHg); light green oil
(56%).
Purified by column chromatography (SiO2; EtOAc–PE, 1:20);
white solid; mp 94–96 °C.
1H NMR (300 MHz, CDCl3): d = 7.30–7.34 (m, 3 H), 7.43–7.45 (m,
1H NMR (300 MHz, CDCl3): d = 1.34 (s, 9 H), 2.44 (s, 3 H), 2.84
(t, J = 7.5 Hz, 2 H), 4.05 (t, J = 7.5 Hz, 2 H), 6.38 (s, 1 H), 7.29 (d,
J = 8.1 Hz, 2 H), 7.34 (s, 1 H), 7.53 (s, 1 H), 7.83 (d, J = 7.8 Hz, 2
H).
2 H).
Bromalkynes 1h–j; General Procedure
A solution of CBr4 (200 mol%) in CH2Cl2 (10 mL) was added drop-
wise to a solution of PPh3 (400 mol%) in CH2Cl2 (5 mL) at 0 °C. Af-
ter stirring at 0 °C for 20 min, a solution of the corresponding aryl
aldehyde (3 mmol) was added dropwise to the mixture at 0 °C. The
resulting mixture was stirred at 0 °C for 1 h and filtered. The filtrate
was dried (Na2SO4) and concentrated. The residue was purified by
silica gel chromatography (CHCl3–PE, 1:5). A mixture of the ob-
tained dibromostyrene (2 mmol) and Bu4NBr (100 mol%) in THF–
H2O (4:3) and aq KOH (400 mol%) in a round-bottomed flask was
stirred at r.t. for 48 h. The resultant mixture was extracted with
EtOAc (3 × 40 mL). The combined organic layers were dried
(MgSO4), filtered, and concentrated. The residue was purified by
column chromatography.
13C NMR (75 MHz, CDCl3): d = 20.8, 21.5, 27.8, 45.2, 73.5, 84.4,
87.6, 107.5, 112.5, 127.8, 129.2, 137.1, 142.5, 144.2, 145.3, 150.7.
MS (ESI): m/z = 412 (M + Na), 290 (M – Boc).
HRMS (ESI): m/z calcd for C20H23NO5S + Na (M + Na): 412.1194;
found: 412.1189.
3c
Purified by column chromatography (SiO2; EtOAc–PE, 1:10); yel-
low solid; mp 88–90 °C.
1H NMR (300 MHz, CDCl3): d = 4.05 (d, J = 6.3 Hz, 2 H), 4.91 (t,
J = 5.7 Hz, 1 H, NH), 6.19 (d, J = 1.5 Hz, 1 H), 7.29 (s, 1 H), 7.36
(s, 1 H), 7.48–7.60 (m, 3 H), 7.92 (d, J = 7.2 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 33.7, 76.1, 84.9, 106.3, 112.2,
1h16
127.4, 129.0, 132.8, 139.7, 142.7, 145.8.
Purified by column chromatography (SiO2; CHCl3–PE, 1:5); white
solid (95%); mp 178–180 °C.
1H NMR (300 MHz, CDCl3): d = 7.60 (d, J = 8.7 Hz, 2 H), 8.19 (d,
J = 8.4 Hz, 2 H).
MS (ESI): m/z = 260 (M – H).
HRMS (ESI): m/z calcd for C13H11NO3S + Na (M + Na): 284.0365;
found: 284.0352.
1i17
3d
Purified by column chromatography (SiO2; CHCl3–PE, 1:5); light
yellow solid (93%); mp 39–40 °C.
Purified by column chromatography (SiO2; EtOAc–PE, 1:10);
white solid; mp 132–134 °C.
1H NMR (300 MHz, acetone-d6): d = 2.96 (s, 1 H, NH), 4.14 (s, 2
H), 6.23 (s, 1 H), 7.49 (s, 1 H), 7.58 (s, 1 H), 8.19 (d, J = 8.4 Hz, 2
H), 8.40 (d, J = 9.0 Hz, 2 H).
13C NMR (75 MHz, acetone-d6): d = 33.5, 76.0, 86.2, 107.1, 112.5,
124.7, 129.3, 144.0, 146.4, 147.4, 150.6.
1H NMR (300 MHz, CDCl3): d = 3.81 (s, 3 H), 6.83 (d, J = 8.7 Hz,
2 H), 7.38 (d, J = 8.7 Hz, 2 H).
1j17
Purified by column chromatography (SiO2; CHCl3–PE, 1:5); light
yellow oil (96%).
1H NMR (300 MHz, CDCl3): d = 2.35 (s, 3 H), 7.12 (d, J = 7.5 Hz,
2 H), 7.34 (d, J = 7.8 Hz, 2 H).
MS (ESI): m/z = 305 (M – H).
HRMS (ESI): m/z calcd for C13H10N2O5S + Na (M+ Na): 329.0211;
found: 329.0203.
Palladium-Catalyzed Suzuki Coupling Reaction of 3-Furanbo-
ronic Acid (2) with Various Terminal Bromoalkynes 1; General
Procedure
3e
Purified by column chromatography (SiO2; EtOAc–PE, 1:20); light
green oil.
Ba(OH)2·8H2O (500 mol%) was added to a well-stirred mixture
containing 3-furanboronic acid 2 (0.5 mmol), bromoalkyne 1 (120
mol%), and Pd(PPh3)4 (10 mol%) in DME (32 mL) and H2O (8 mL)
in a two-necked round-bottomed flask under N2 at r.t. The resultant
mixture was heated at reflux for 30 min, cooled to r.t., and poured
into cold H2O (40 mL). The mixture was extracted with Et2O (3 ×
40 mL). The combined organic extracts were dried (MgSO4), fil-
tered, and concentrated. The residue was purified by column chro-
matography to afford the desired product.
1H NMR (300 MHz, CDCl3): d = 4.36 (s, 2 H), 4.65 (s, 2 H), 6.46
(d, J = 1.5 Hz, 1 H), 7.33–7.38 (m, 6 H), 7.63 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 58.0, 71.7, 77.7, 87.0, 107.1, 112.6,
127.9, 128.1, 128.5, 137.5, 142.8, 146.0.
MS (ESI): m/z = 211 (3, M – H), 105 (83, M – BnO).
HRMS (EI): m/z calcd for C14H12O2: 212.0837; found: 212.0846.
3f
3a
Purified by column chromatography (SiO2; EtOAc–PE, 1:20); light
yellow oil.
1H NMR (300 MHz, CDCl3): d = 2.71 (t, J = 6.9 Hz, 2 H), 3.66 (t,
J = 6.9 Hz, 2 H), 4.59 (s, 2 H), 6.42 (d, J = 1.8 Hz, 1 H), 7.32–7.38
(m, 6 H), 7.57 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 20.8, 68.2, 72.4, 72.9, 88.4, 107.6,
112.6, 127.7, 128.4, 138.0, 142.5, 145.2 (with one low-field signal
absent).
Purified by column chromatography (SiO2; EtOAc–PE, 1:20);
white solid; mp 81–83 °C.
1H NMR (300 MHz, CDCl3): d = 1.35 (s, 9 H), 2.42 (s, 3 H), 4.80
(s, 2 H), 6.41 (s, 1 H), 7.27 (d, J = 7.8 Hz, 2 H), 7.37 (s, 1 H), 7.59
(s, 1 H), 7.93 (d, J = 8.1 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 21.6, 27.8, 36.6, 75.1, 84.8, 86.2,
106.8, 112.4, 128.2, 129.1, 136.6, 142.8, 144.3, 145.9, 150.2.
MS (ESI): m/z = 430 (M + Na + MeOH), 398 (M + Na.)
MS (ESI): m/z = 225 (4, M – 1), 105 (27, M – BnO).
HRMS (ESI): m/z calcd for C19H21NO5S + Na (M + Na): 398.1038;
found: 398.1033.
HRMS (EI): m/z calcd for C15H14O2: 226.0994; found: 226.0984.
Synthesis 2008, No. 11, 1729–1732 © Thieme Stuttgart · New York

1732
3g
X. Yang et al.
PAPER
References
Purified by column chromatography (SiO2; EtOAc–PE, 1:20); light
yellow oil.
1H NMR (300 MHz, CDCl3): d = 6.51 (d, J = 1.2 Hz, 1 H), 7.30–
7.33 (m, 3 H), 7.38 (d, J = 1.2 Hz, 1 H), 7.46–7.50 (m, 2 H), 7.67 (s,
1 H).
13C NMR (75 MHz, CDCl3): d = 80.4, 91.0, 107.6, 112.5, 123.1,
128.2, 128.3, 131.4, 142.8, 145.5.
(1) Massy-Westropp, R. A.; Reynolds, G. D.; Spotswood, T. M.
Tetrahedron Lett. 1966, 18, 1939.
(2) (a) Stewart, A. O.; Bhatia, P. A.; Martin, J. G.; Summers, J.
B.; Rodriques, K. E.; Martin, M. B.; Holms, J. H.; Moore, J.
L.; Craig, R. A.; Kolasa, T.; Ratajczyk, J. D.; Mazdiyasni,
H.; Kerdesky, F. A. J.; DeNinno, S. L.; Maki, R. G.; Bouska,
J. B.; Young, P. R.; Lanni, C.; Bell, R. L.; Carter, G. W.;
Brooks, C. D. W. J. Med. Chem. 1997, 40, 1955.
(b) Cocuzza, A. J.; Chidester, D. R.; Cordova, B. C.; Klabe,
R. M.; Jeffrey, S.; Diamond, S.; Weigelt, C. A.; Ko, S. S.;
Bacheler, L. T.; Erickson-Viitanen, S. K.; Rodgers, J. D.
Bioorg. Med. Chem. Lett. 2001, 11, 1389.
(3) (a) Crimmins, M. T.; Jung, D. K.; Gray, J. L. J. Am. Chem.
Soc. 1993, 115, 3146. (b) Zhan, Z. P.; Lang, K. Org. Biomol.
Chem. 2005, 3, 727.
(4) For the coupling reaction of polysubstituted 3-furanyl
bromides, see: (a) Eberbach, W.; Laber, N.; Bussenius, J.;
Fritz, H.; Rihs, G. Chem. Ber. 1993, 126, 975. (b) Zhang,
Y.; Herndon, J. W. J. Org. Chem. 2002, 67, 4177.
(c) Yasuhara, A.; Suzuki, N.; Sakamoto, T. Chem. Pharm.
Bull. 2002, 50, 143. (d) Sagar, P.; Fröhlich, R.; Würthwein,
E. U. Angew. Chem. Int. Ed. 2004, 43, 5694.
(5) For the coupling reaction of polysubstituted 3-furanyl
iodides, see: (a) Song, Z. Z.; Wong, H. N. C. Liebigs Ann.
Chem. 1994, 29. (b) Wong, M. K.; Leung, C. Y.; Wong, H.
N. C. Tetrahedron 1997, 53, 3497. (c) Bew, S. P.; Knight,
D. W. J. Chem. Soc., Chem. Commun. 1996, 1007. (d) Liu,
Y.; Zhou, S. Org. Lett. 2005, 7, 4609. (e) Tseng, J.-C.;
Chen, J.-H.; Luh, T.-Y. Synlett 2006, 1209.
(6) (a) Wender, P. A.; Paxton, T. J.; Williams, T. J. J. Am. Chem.
Soc. 2006, 128, 14814. (b) Rossi, R.; Carpita, A.; Lezzi, A.
Tetrahedron 1984, 40, 2773. (c) Cheung, W. S.; Wong, H.
N. C. Tetrahedron Lett. 1998, 39, 6521. (d) Cheung, W. S.;
Wong, H. N. C. Tetrahedron 1999, 55, 11001. (e)Wong,H.
N. C. Eur. J. Org. Chem. 1999, 1757.
MS (ESI): m/z = 168 (100, M+).
HRMS (EI): m/z calcd for C12H8O: 168.0575; found: 168.0579.
3h
Purified by column chromatography (SiO2; EtOAc–PE, 1:10); light
yellow solid; mp 148–150 °C.
1H NMR (300 MHz, CDCl3): d = 6.55 (s, 1 H), 7.45 (d, J = 1.8 Hz,
1 H), 7.62 (d, J = 7.5 Hz, 2 H), 7.76 (s, 1 H), 8.20 (d, J = 7.8 Hz, 2
H).
13C NMR (75 MHz, CDCl3): d = 86.1, 89.4, 106.9, 112.4, 123.7,
130.2, 132.0, 143.3, 146.5, 146.9.
MS (ESI): m/z = 213 (100, M+).
HRMS (EI): m/z calcd for C12H7NO3: 213.0426; found: 213.0422.
3i
Purified by column chromatography (SiO2; EtOAc–PE, 1:10); col-
orless oil.
1H NMR (300 MHz, CDCl3): d = 3.84 (s, 3 H), 6.53 (dd, J = 1.9, 0.7
Hz, 1 H), 6.88 (d, J = 8.4 Hz, 2 H), 7.41 (t, J = 2.1 Hz, 1 H), 7.45 (d,
J = 8.1 Hz, 2 H), 7.69 (dd, J = 1.4, 0.4 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 55.3, 79.0, 90.9, 107.8, 112.6,
114.0, 115.3, 132.9, 142.8, 145.3, 159.6.
MS (ESI): m/z = 198 (100, M+), 183 (51, M – Me).
HRMS (EI): m/z calcd for C13H10O2: 198.0681; found: 198.0685.
(7) (a) Bach, T.; Krüger, L. Synlett 1998, 1185. (b) Bach, T.;
Krüger, L. Eur. J. Org. Chem. 1999, 2045. (c) Bach, T.;
Krüger, L. Tetrahedron Lett. 1998, 39, 1729.
(8) Gelman, D.; Tsvelikhovsky, D.; Molander, G. A.; Blum, J.
J. Org. Chem. 2002, 67, 6287.
(9) (a) Liu, F.; Negishi, E.-i. J. Org. Chem. 1997, 62, 8591.
(b) Negishi, E.; Luo, F.-T.; Frisbee, R.; Matsushita, H.
Heterocycles 1982, 18, 117.
(10) Ng, S. C.; Novak, I.; Wang, L.; Huang, H. H.; Huang, W.
Tetrahedron 1997, 53, 13339.
3j
Purified by column chromatography (SiO2; EtOAc–PE, 1:10); light
yellow oil.
1H NMR (300 MHz, CDCl3): d = 2.35 (s, 3 H), 6.51 (d, J = 1.8 Hz,
1 H), 7.14 (d, J = 8.4 Hz, 2 H), 7.39 (s, 1 H), 7.40 (d, J = 8.1 Hz, 2
H), 7.67 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 21.5, 79.7, 91.1, 107.8, 112.6,
120.1, 129.1, 131.3, 138.4, 142.9, 145.4.
MS (ESI): m/z = 182 (100, M+).
(11) Chan, K. F.; Wong, H. N. C. Eur. J. Org. Chem. 2003, 82.
(12) Yoo, W. J.; Allen, A.; Villeneuve, K.; Tam, W. Org. Lett.
2005, 7, 5853.
HRMS (EI): m/z calcd for C13H10O: 182.0732; found: 182.0736.
(13) Kim, S.; Kim, S.; Lee, T.; Ko, H.; Kim, D. Org. Lett. 2004,
6, 3601.
Acknowledgment
(14) Boden, C. D. J.; Pattenden, G.; Ye, T. J. Chem. Soc., Perkin
Trans. 1 1996, 2417.
(15) Nie, X.; Wang, G. J. J. Org. Chem. 2006, 71, 4734.
(16) Huh, D. H.; Jeong, J. S.; Lee, H. B.; Ryu, H.; Kim, Y. G.
Tetrahedron 2002, 58, 9925.
The financial support was provided by grants from NSFC
(90713007; 20772141; 20625204; 20632030) and STCSM (‘Post-
Venus’ Program, 05QMH1416).
(17) Huh, D. H.; Ryu, H.; Kim, Y. G. Tetrahedron 2004, 60,
9857.
Synthesis 2008, No. 11, 1729–1732 © Thieme Stuttgart · New York