A simple and convenient synthesis of 2-(perfluoroalkyl)-4H-chromenes from salicyl N-tosylimines or salicylaldehydes and methyl 2-perfluoroalkynoates

Article abstract of DOI:10.1016/j.tet.2009.09.030

Et₃N-catalyzed reactions of salicyl N-tosylimines or salicylaldehydes with methyl 2-perfluoroalkynoates proceed smoothly at room temperature in dichloromethane (DCM) or dimethyl sulfoxide (DMSO) to give the corresponding fluorinated chromenes i

Full text of DOI:10.1016/j.tet.2009.09.030

Tetrahedron 65 (2009) 9152–9156
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A simple and convenient synthesis of 2-(perfluoroalkyl)-4H-chromenes from
salicyl N-tosylimines or salicylaldehydes and methyl 2-perfluoroalkynoates
,
,
Lei Lu a y, Jiamei Wei a y, Jie Chen a, Jiaping Zhang a, Hongmei Deng d, Min Shao d,
Hui Zhang a , Weiguo Cao
,
a,b,c,
*
*
a Department of Chemistry, Shanghai University, Shanghai 200444, PR China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, PR China
c Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, PR China
d Instrumental Analysis and Research Center, Shanghai University, Shanghai 200444, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 August 2009
Received in revised form 3 September 2009
Accepted 8 September 2009
Available online 11 September 2009
Et3N-catalyzed reactions of salicyl N-tosylimines or salicylaldehydes with methyl 2-perfluoroalkynoates
proceed smoothly at room temperature in dichloromethane (DCM) or dimethyl sulfoxide (DMSO) to give
the corresponding fluorinated chromenes in good to excellent yields with high regioselectivity.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
2-(Perfluoroalkyl)-4H-chromene
Salicyl N-tosylimine
Salicylaldehyde
Methyl 2-perfluoroalkynoate
Regioselectivity
1. Introduction
2-Perfluoroalkynoates have been widely used in synthesizing
fluorinated organic compounds especially as a modulator to enhance
4H-Chromenes are an important class of compounds being the
main components of many biologically active compounds, and are
widely employed as key intermediates in the synthesis of numerous
natural products and medicinal reagents.1 For example, substituted
4H-chromenes have displayed high antibacterial activity and
powerful anticancer properties by affecting tumor vasculature pro-
gression and inducing tumor necrosis in vivo.1e,i Thus, the develop-
ment of new efficient processes for their construction has been the
subject of increasing attention over the last couple of years.2
Although it is well known that the introduction of polyfluoroalkyl
groups into organic molecules can bring about some remarkable
changes in the properties of the derived fluorinated compounds, and
selective perfluoroalkylation has been recognized as an important
tool in developing new biologically important compounds,3 methods
for preparing polyfluoroalkyl-substituted 4H-chromenes remain
very limited.4
the yield and regioselectivity of Michael-type conjugate additions.5
As part of our ongoing efforts in developing synthetic approaches
for the synthesis of novel fluorinated heterocycles with potential
biological applications, we built upon the recent reports by Shi’s
group on the synthesis of the chromenes.2d,6 It was found that
although the amine-catalyzed reaction between ethyl 2-butynoate
and salicyl N-tosylimine did not give the substituted chromenes in
satisfactory yield under various reaction conditions, the reaction of
diethyl acetylenedicarboxylate with salicyl N-tosylimines or salicy-
laldehydes proceeded smoothly because of the substitution of the
methylgroupinethyl2-butynoatefortheelectron-withdrawingester
group.6c On considering the high electronegativity of polyfluoroalkyl
groups, we developed a new general and efficient methodology for
the preparation of perfluoroalkyl containing substituted 4H-chro-
menes from the Et3N-catalyzed reaction of salicyl N-tosylimines or
salicylaldehydes with methyl 2-perfluoroalkynoates. The structures
of these compounds were confirmed by IR, 1H NMR, 13C NMR, 19F
NMR, MS, and X-ray diffraction analysis as well.
2. Results and discussion
* Corresponding authors. Fax: þ86 21 6613 4856.
E-mail addresses: yehao7171@shu.edu.cn (H. Zhang), wgcao@staff.shu.edu.cn
(W. Cao).
Perfluoroalkyl containing substituted 4H-chromenes were
obtained from the Et3N-catalyzed reaction of salicyl N-tosylimines
y
With equal contribution to this work.
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.09.030

L. Lu et al. / Tetrahedron 65 (2009) 9152–9156
9153
or salicylaldehydes with methyl 2-perfluoroalkynoates (Scheme 1).
The structures of the producs were confirmed by IR, 1H NMR, 13
NMR, 19F NMR, and MS as well.
C
XH
CO2Me
R2
CO2Me
RF
R2
Et3N, r.t.
X
+
DCM or DMSO
O
OH
RF
R1
R1
1 or 4
2
3 or 5
1, 3 X=NTs, 4, 5 X=O; RF=CF3, C2F5, n-C3F7; R1=H, Me, OMe;R2=H, Cl, NO2
Scheme 1. Preparation of perfluoroalkyl containing 4H-chromenes.
Different solvents were first examined by using the reaction of
salicyl N-tosylimine 1a (1.0 equiv) with methyl 4,4,5,5,6,6,6-hep-
Figure 1. X-ray diffraction of 3b.
tafluorohex-2-ynoate 2a (1.2 equiv) as
a model. Using Et3N
(10 mol %) as catalyst and performing the reaction in different
solvents, the reaction could be completed in CH2Cl2 within 1 h at
room temperature giving the corresponding chromene 3a in 91%
yield (Table 1, entry 1). Both CHCl3 and DMSO proved to be good
(90% yield in CHCl3, 90% yield in DMSO, Table 1, entries 2 and 3),
while in THF, the yield was only 75% (Table 1, Entry 4). The reaction
yield remained unchanged when increased the amount of Et3N but
lower the yield while decreased the amount of Et3N. As a conse-
quence, we chose CH2Cl2 as the best solvent. We found optimal
reaction conditions were 1.0 equiv of 1, 1.2 equiv of 2, 10 mol % of
Et3N, and performing the reaction in CH2Cl2 at room temperature
(20 ꢀC) for 1 h.
2 of the 4H-chromenes is formed, which could be explained by
our previous reported result.8
To test the generality of this methodology, we further subjected
the less reactive salicylaldehyde to the reaction. Performing the
reaction in CH2Cl2, the reaction of 2-hydroxybenzaldehyde 4a with
methyl 4,4,5,5,6,6,6-heptafluorohex-2-ynoate 2a became disor-
dered and 5a was isolated only in low yield (50%). However, when
the solvent was changed to DMSO, a high yield of 5a was observed
in 1 h. Under the revised optimal reaction conditions, several other
salicylaldehydes can also react with methyl 2-perfluoroalkyl pro-
piolates 2 to give the corresponding chromenes 5 as the sole
regioisomer in good to excellent yields (Table 2).
Table 1
Reaction of other salicyl N-tosylimines
fluoroalkynoates 2 (1.2 equiv) in the presence of 10 mol % of Et3N
1 (1.0 equiv) with methyl 2-per-
Table 2
Reactions of salicylaldehydes 4 (1.0 equiv) with methyl 2-perfluoroalkynoates 2
(1.2 equiv) in the presence of 10 mol % of Et3N
NHTs
CO2Me
R2
R2
CO2Me
NTs
+
OH
OH
Et3N, 1h
CH2Cl2, r.t.
CO2Me
R2
CHO
OH
R2
CO2Me
RF
Et3N, 1h
DMSO, r.t.
O
RF
+
RF
R1
R1
O
RF
R1
R1
1
2
3
4
2
5
Entry
1
R1
R2
2
RF
Product
Solvent
Yielda (%)
Entry
4
R1
H
OCH3
H
H
OCH3
H
R2
2
RF
Product
Yielda (%)
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1b
1c
1b
1c
1d
1b
1c
1d
H
H
H
H
OCH3
H
OCH3
H
CH3
OCH3
H
H
H
H
H
H
Cl
H
Cl
H
H
Cl
H
2c
2c
2c
2c
2c
2c
2a
2a
2c
2b
2b
2a
n-C3F7
n-C3F7
n-C3F7
n-C3F7
n-C3F7
n-C3F7
CF3
CF3
n-C3F7
C2F5
3a
3a
3a
3a
3b
3c
3d
3e
3f
CH2Cl2
CHCl3
DMSO
THF
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
91
90
90
75
92
86
90
79b
88
89
77
90
1
2
3
4
5
6
7
8
9
4a
4b
4c
4a
4b
4c
4d
4d
4e
H
H
Cl
H
H
Cl
H
H
2c
2c
2c
2a
2a
2a
2a
2c
2b
n-C3F7
n-C3F7
n-C3F7
CF3
CF3
CF3
CF3
n-C3F7
C2F5
5a
5b
5c
5d
5e
5f
5g
5h
5i
93
92
89
87
90
85
91
89
77
CH3
CH3
H
9
10
11
12
3g
3h
3i
NO2
C2F5
CF3
a
Isolated yield.
CH3
a
Isolated yield.
The reaction was carried out at 0 ꢀC.
b
On the basis of the previous reports,6,9,10 the proposed mecha-
nism is shown in Scheme 2. We consider the reaction of 1a with 2c
as an example. Et3N first abstracts a proton from imine 1a to gen-
erate the anion A and release Et3NHþ. Then, Michael addition oc-
curs between intermediate A and 2c to give intermediate B. Then,
intramolecular Mannich reaction occurs in intermediate B to afford
intermediate C and subsequent protonation gives product 3a and
regenerates Et3N. The reason why the reaction of the less reactive
salicylaldehyde with methyl 2-perfluoroalkynoates became com-
plicated in DCM is not known. One reasonable explanation is that
the proton transfer step for the conversion of intermediate C to 3a is
rate determining and the intramolecular Mannich reaction is a re-
versible one.8 Proton transfer in DMSO is much faster than in DCM,
which allows the Mannich reaction to be predominant.
Under these optimized reaction conditions, the reactions of
several other salicyl N-tosylimines 1 with methyl 2-perfluoro-
alkynoates 2 were also examined (Table 1, entries 5–12). The
corresponding fluorinated chromenes 3 were obtained in good to
excellent yields. The structure of final product was confirmed by
X-ray diffraction of 3b (Fig. 17). It is noteworthy that the yield of
3e was rather low under these reaction conditions because the
reaction system was complicated and made the isolation difficult.
But at 0 ꢀC, the reaction proceeded smoothly giving the sole
product 3e in the yield of 79%. Another distinguishing feature of
the reaction is its high regioselectivity: only one regioisomer
containing stronger electron-withdrawing substituent at position

9154
L. Lu et al. / Tetrahedron 65 (2009) 9152–9156
NHTs
4.2.1. Methyl 2-(heptafluoropropyl)-4-(tosylamino)-4H-chromene-3-
carboxylate 3a. A white solid: mp: 130.4–131.2 ꢀC; 1H NMR (CDCl3,
NTs
OH
CO2Me
500 MHz, ppm):
d 2.45 (3H, s, CH3), 3.46 (3H, s, OCH3), 5.10 (1H, d,
J¼9.0 Hz, CH), 5.65 (1H, d, J¼9.0 Hz, NH), 7.05–7.75 (8H, m, ArH). 19F
O
CF2CF2CF3
NMR (CDCl3, 470 MHz, ppm):
d
ꢁ80.75 (t, J¼9.4 Hz, 3F), ꢁ114.88 (m,
3a
1a
2F), ꢁ125.49 (m, 2F). 13C NMR (CDCl3, 125 MHz, ppm):
d 21.7, 48.5,
Et3N
1
2
52.8, 108.1 (CF2, tt, JF–C¼243.8 Hz, JF–C¼38.8 Hz), 110.3 (CF2, m),
1
2
113.1, 116.8, 117.6 (CF3, qt, JF–C¼275.0 Hz, JF–C¼31.0 Hz), 118.7,
126.2, 127.3, 129.6, 129.8, 130.2, 138.2, 140.1 (CCF2, t, 2JF–C¼27.0 Hz),
143.9 148.9, 164.8. MS (ESI) m/z: 550.0 (MþNa)þ. IR (KBr, cmꢁ1):
n
Et3NH
NTs
3302, 2953, 1739, 1693, 1459, 1339. Anal. Calcd for C21H16F7NO5S: C,
47.82; H, 3.06; N, 2.66. Found: C, 48.02; H, 3.31; N, 2.42.
NTs
CO2Me
O
O
CF2CF2CF3
4.2.2. Methyl 2-(heptafluoropropyl)-8-methoxy-4-(tosylamino)-4H-
chromene-3-carboxylate 3b. A white solid: mp: 149.2–151.7 ꢀC; 1H
C
A
CO2Me
NMR (CDCl3, 500 MHz, ppm): d 2.44 (3H, s, CH3), 3.47 (3H, s, OCH3),
DCM or DMSO
O
3.85 (3H, s, CH3), 5.16 (1H, d, J¼8.8 Hz, CH), 5.62 (1H, d, J¼8.8 Hz,
NH), 6.84–7.74 (7H, m, ArH). 19F NMR (CDCl3, 470 MHz, ppm):
CF2CF2CF3
2c
d
ꢁ80.75 (t, J¼9.4 Hz, 3F), ꢁ114.70 (m, 2F), ꢁ125.51 (m, 2F). 13C NMR
NTs
OMe
1
(CDCl3, 125 MHz, ppm):
d
21.8, 48.7, 52.9, 56.6, 108.9 (CF2, tt, JF–
2
O
¼258.8 Hz, JF–C¼32.5 Hz), 110.3 (CF2, m), 112.3, 113.0, 117.7 (CF3,
C
1
2
CF2CF2CF3
qt, JF–C¼286.3 Hz, JF–C¼33.8 Hz), 119.7, 120.3, 125.9, 127.4, 129.9,
B
2
138.3, 139.3, 140.2 (t, CCF2, JF–C¼28.0 Hz), 143.9, 148.1, 164.9. MS
(EI) m/z (%): 557 (Mþ, 1), 402 (100), 387 (87), 370 (25), 210 (16), 155
Scheme 2. Mechanism for the formation of product 3a.
(10), 91 (60). IR (KBr, cmꢁ1):
n 3261, 2960, 1742, 1692, 1489, 1334.
3. Conclusions
Anal. Calcd for C22H18F7NO6S: C, 47.40; H, 3.25; N, 2.51. Found: C,
47.66; H, 3.51; N, 2.46.
In conclusion, we developed a new efficient process for the
synthesis of 4-functional 2-trifluoromethylated or perfluoroal-
kylated 4H-chromenes by reaction of methyl 2-perfluoroalkynoates
with salicyl N-tosylimines or salicylaldehydes. Compared to pre-
vious methods, this technique is simple, experimentally convenient
and proceeds smoothly under mild conditions in the presence of
Et3N. The corresponding fluorinated chromenes were obtained in
good to excellent yields with high regioselectivity. Efforts to
explore further applications of these products are currently in
progress in our laboratory.
4.2.3. Methyl 6-chloro-2-(heptafluoropropyl)-4-(tosylamino)-4H-chro-
mene-3-carboxylate 3c. A white solid: mp: 135.7–136.4 ꢀC; 1H NMR
(CDCl3, 500 MHz, ppm):
(1H, d, J¼9.0 Hz, CH), 5.54 (1H, d, J¼9.0 Hz, NH), 6.99–7.74 (7H, m,
ArH). 19F NMR (CDCl3, 470 MHz, ppm):
ꢁ80.73 (t, J¼9.4 Hz, 3F),
d 2.46 (3H, s, CH3), 3.55 (3H, s, OCH3), 5.22
d
114.96 (m, 2F), 125.49 (m, 2F). 13C NMR (CDCl3, 125 MHz, ppm):
d
21.8, 52.9, 56.6, 109.3 (CF2, tt, 1JF–C¼260.0 Hz, 2JF–C¼32.5 Hz), 110.9
(CF2, m), 112.3, 113.1, 118.3 (CF3, qt, 1JF–C¼285.0 Hz, JF–C¼33.8 Hz),
119.7, 120.3, 125.9, 127.4, 129.9, 138.3, 139.3, 140.2 (t, CCF2, 2JF–C¼28
.0 Hz), 143.9, 148.1, 164.9. MS (EI) m/z (%): 406 (100), 407 (16), 391
2
(70), 392 (10), 374 (35), 257 (16), 155 (12), 91 (36). IR (KBr, cmꢁ1):
n
4. Experimental
3259, 2973, 1733, 1673, 1458, 1362. Anal. Calcd for C21H15ClF7NO5S:
C, 44.89; H, 2.69; N, 2.49. Found: C, 44.71; H, 2.83; N, 2.35.
4.1. General information
4.2.4. Methyl 8-methoxy-2-(trifluoromethyl)-4-(tosylamino)-4H-chro-
All reagents and solvents were purchased from commercial
sources and used without further purification, except that salicyl N-
tosylimines 1 and methyl 2-perfluoroalkynoates 2 were prepared
according to reported literature.11,12 Melting points were un-
corrected. 1H, 19F, and 13C NMR spectra were recorded on 500 MHz
spectrometer. All chemical shifts are reported in parts per million
downfield (positive) of the standard: C6F6 for 19F, TMS for 1H and
13C NMR spectra. IR spectra were obtained on an FT-IR spectrom-
eter. Elemental analysis was performed on an elemental analysis
instrument. MS was run on a mass spectrometer. X-ray analysis was
performed on an X-ray spectrometer. Preparative TLC on silica gel
was performed by using self-coated GF254 plates, which were ac-
tivated immediately before use.
mene-3-carboxylate 3d. A white solid: mp: 191.4–193.2 ꢀC; 1H NMR
(CDCl3, 500 MHz, ppm):
d 2.44 (3H, s, CH3), 3.50 (3H, s, OCH3), 3.89
(3H, s, OCH3), 5.05 (1H, d, J¼9.0 Hz, CH), 5.66 (1H, d, J¼9.0 Hz, NH),
6.86–7.73 (7H, m, ArH). 19F NMR (CDCl3, 470 MHz, ppm):
d
ꢁ67.14
(s, 3F). 13C NMR (CDCl3, 125 MHz, ppm):
d 21.7, 48.2, 52.8, 56.5, 110
3
1
(d, CCF3, JF–C¼2.5 Hz), 112.1, 118.9 (CF3, q, JF–C¼273.0 Hz), 119.8,
120.5, 126.0, 126.6, 127.3, 129.7, 129.9, 138.3, 139.2, 142.5 (q, CCF3,
2JF–C¼37.0 Hz), 143.7, 147.9, 164.8. MS (EI) m/z (%): 457 (Mþ, 1), 302.1
(81), 287 (100), 270 (20), 243 .1 (10), 203 (11), 155 (9), 91 (29). IR
(KBr, cmꢁ1):
n 3313, 2959, 1737, 1697, 1487, 1340. Anal. Calcd for
C20H18F3NO6S: C, 52.51; H, 3.97; N, 3.06. Found: C, 52.39; H, 3.82; N,
3.22.
4.2.5. Methyl 6-chloro-2-(trifluoromethyl)-4-(tosylamino)-4H-chro-
4.2. General procedure for preparation of compound 3
mene-3-carboxylate 3e. A white solid: mp: 155.4–156.8 ꢀC; 1H NMR
(CDCl3, 500 MHz, ppm): d 2.45 (3H, s, CH3), 3.58 (3H, s, OCH3), 5.29
To the solution of salicyl N-tosylimines (1.0 mmol) in CH2Cl2,
methyl 2-perfluoroalkynoates (1.2 mmol) and Et3N (10 mmol %)
were added and the mixture was stirred at room temperature for
1 h. After the completion of the reaction (monitored by TLC), the
products were purified by preparative TLC [eluent: petroleum ether
(60–90 ꢀC)/ethyl acetate] and recrystallized from dichloromethane
and petroleum ether (60–90 ꢀC) to give pure product 3.
(1H, d, J¼8.0 Hz, CH), 5.54 (1H, d, J¼8.0 Hz, NH), 7.04–7.68 (7H, m,
ArH). 19F NMR (CDCl3, 470 MHz, ppm):
(CDCl3, 125 MHz, ppm):
d
ꢁ67.46 (s, 3F). 13C NMR
3
d
21.7, 47.9, 53.0, 109.9 (d, CCF3, JF–
1
¼1.3 Hz), 118.4, 118.7 (CF3, q, JF–C¼275.0 Hz), 119.9, 127.2, 129.2,
C
2
129.9, 130.4, 131.1, 138.1, 142.5 (q, CCF3, JF–C¼37.0 Hz), 144.1, 147.7,
164.5. MS (EI) m/z (%): 461 (Mþ, 1), 306 (100), 307 (30), 291 (60),
292 (18), 274 (40). IR (KBr, cmꢁ1):
n 3285, 2924, 1728, 1682, 1483,

L. Lu et al. / Tetrahedron 65 (2009) 9152–9156
9155
1342. Anal. Calcd for C19H15F3NO5S: C, 49.41; H, 3.27; N, 3.03.
Found: C, 49.66; H, 3.18; N, 3.15.
4.3.1. Methyl 2-(heptafluoropropyl)-4-hydroxy-4H-chromene-3-car-
boxylate 5a. A white solid: mp: 109.0–109.6 ꢀC; 1H NMR (CDCl3,
500 MHz, ppm):
d
2.89 (1H, d, J¼7.3 Hz, OH), 3.87 (3H, s, OCH3),
4.2.6. Methyl 2-(heptafluoropropyl)-8-methyl-4-(tosylamino)-4H-
5.66 (1H, d, J¼7.3 Hz, CH), 7.13–7.54 (4H, m, ArH). 19F NMR (CDCl3,
chromene-3-carboxylate 3f. A white solid: mp: 154.1–155.6ꢀC; 1H
470 MHz, ppm):
d
ꢁ81.90 (t, J¼9.4 Hz, 3F), ꢁ115.36 (m, 2F), ꢁ126.39
NMR (CDCl3, 500 MHz, ppm):
d
2.26 (3H, s, CH3), 2.45 (3H, s, CH3),
(m, 2F). 13C NMR (CDCl3, 125 MHz, ppm):
d
53.1, 62.6, 109.0 (CF2, tt,
2
3.49 (3H, s, OCH3), 5.11 (1H, br s, CH), 5.63 (1H, br s, NH), 7.01–7.74
1JF–C¼270.0 Hz, JF–C¼32.5 Hz), 110.5 (CF2, m), 114.6, 116.8, 119.0
1
2
(7H, m, ArH). 19F NMR (CDCl3, 470 MHz, ppm):
d
ꢁ80.77
(CF3, qt, JF–C¼285.0 Hz, JF–C¼33.8 Hz), 120.5, 125.9, 129.4, 130.3,
2
(t, J¼9.4 Hz, 3F), ꢁ114.75 (m, 2F), ꢁ125.56 (m, 2F). 13C NMR (CDCl3,
141.1 (t, CCF2, JF–C¼29.0 Hz), 148.7, 166.1. MS (ESI) m/z: 397
1
125 MHz, ppm):
d
15.4, 21.7, 48.8, 52.8, 109.1 (CF2, tt, JF–
(MþNa)þ. IR (KBr, cmꢁ1):
n 3451, 2959, 1720, 1675, 1458, 1337. Anal.
¼260.0 Hz, 2JF–C¼32.5 Hz),110.9 (CF2, m),113.1,118.3,118.9 (CF3, qt,
Calcd for C14H9F7O4: C, 44.93; H, 2.42. Found: C, 45.18; H, 2.66.
C
2
1JF–C¼285.0 Hz, JF–C¼33.8 Hz), 125.6, 126.4, 126.9, 127.3, 129.8,
2
131.3, 138.3, 140.2 (t, CCF2, JF–C¼27 .5 Hz), 143.8, 147.5, 164.9. MS
4.3.2. Methyl 2-(heptafluoropropyl)-4-hydroxy-8-methoxy-4H-chro-
(EI) m/z (%): 510 (3), 386 (100), 371 (93), 354 (29). IR (KBr, cmꢁ1):
n
mene-3-carboxylate 5b. A white solid: mp: 113.9–114.5 ꢀC; 1H NMR
3305, 2957, 1722, 1688, 1474, 1335. Anal. Calcd for C22H18F7NO5S: C,
48.80; H, 3.35; N, 2.59. Found: C, 48.65; H, 3.43; N, 2.37.
(CDCl3, 500 MHz, ppm):
d
3.22 (1H, d, J¼3.5 Hz, OH), 3.85 (3H, s,
OCH3), 3.87 (3H, s, OCH3), 5.61 (1H, d, J¼3.5 Hz, CH), 6.89–7.18 (3H,
m, ArH). 19F NMR (CDCl3, 470 MHz, ppm):
d
ꢁ80.81 (t, J¼9.4 Hz, 3F),
4.2.7. Methyl 8-methoxy-2-(pentafluoroethyl)-4-(tosylamino)-4H-
ꢁ114.05 (m, 2F), ꢁ125.27 (m, 2F). 13C NMR (CDCl3, 125 MHz, ppm):
chromene-3-carboxylate 3g. A white solid: mp: 135.1–136.1 ꢀC; 1H
d
53.0, 56.5, 62.5, 108.9 (CF2, tt, 1JF–C¼270.0 Hz, 2JF–C¼32.5 Hz), 110.7
2
NMR (CDCl3, 500 MHz, ppm):
d
2.45 (3H, s, CH3), 3.48 (3H, s, OCH3),
(CF2, m), 112.3, 114.5, 117.8 (CF3, qt, 1JF–C¼272.0 Hz, JF–C¼38.0 Hz),
3.86 (3H, s, OCH3), 5.01 (1H, d, J¼8.5 Hz, CH), 5.64 (1H, d, J¼8.5 Hz,
120.2, 121.5, 125.6, 138.8, 140.9 (t, CCF2, 2JF–C¼29.0 Hz), 148.0, 166.2.
NH), 6.85–7.75 (7H, m, ArH). 19F NMR (CDCl3, 470 MHz, ppm):
MS (ESI) m/z: 427 (MþNa)þ. IR (KBr, cmꢁ1):
n 3473, 2958, 1720,
d
ꢁ82.22 (s, 3F), 116.69 (m, 2F). 13C NMR (CDCl3, 125 MHz, ppm):
1675, 1488, 1336. Anal. Calcd for C15H11F7O5: C, 44.57; H, 2.74.
Found: C, 44.36; H, 2.70.
d
21.7, 48.5, 52.9, 56.5, 108.8 (CF2, qt, 1JF–C¼260.5 Hz, 2JF–C¼32.5 Hz),
1
2
112.3, 112.6, 117.5 (CF3, qt, JF–C¼280.0 Hz, JF–C¼33.8 Hz), 119.6,
120.3, 125.9, 127.3, 129.8, 138.2, 139.2, 140.5 (t, CCF2, 2JF–C¼28.0 Hz),
143.8, 148.0, 164.9. MS (EI) m/z (%): 476 (3), 388 (3), 352 (91), 337
4.3.3. Methyl 6-chloro-2-(heptafluoropropyl)-4-hydroxy-4H-chro-
mene-3-carboxylate 5c. A white solid: mp: 97.7–99.3 ꢀC; 1H NMR
(100), 320 (25), 293 (11). IR (KBr, cmꢁ1):
n
3310, 2957, 1737, 1685,
(CDCl3, 500 MHz, ppm):
d
3.18 (1H, d, J¼7.3 Hz, OH), 3.87 (3H, s,
1488, 1339. Anal. Calcd for C21H18F5NO6S: C, 49.71; H, 3.58; N, 2.76.
Found: C, 49.53; H, 3.39; N, 2.54.
OCH3), 5.61 (1H, d, J¼7.3 Hz, CH), 7.08–7.51 (3H, m, ArH). 19F NMR
(CDCl3, 470 MHz, ppm):
d
ꢁ80.77 (t, J¼9.4 Hz, 3F), ꢁ144.22 (m, 2F),
ꢁ125.27 (m, 2F). 13C NMR (CDCl3,125 MHz, ppm):
d 53.2, 62.2,108.9
1
2
4.2.8. Methyl 6-chloro-2-(pentafluoroethyl)-4-(tosylamino)-4H-chro-
(CF2, tt, JF–C¼270.0 Hz, JF–C¼32.5 Hz), 110.7 (CF2, m), 114.5, 117.8
1 2
mene-3-carboxylate 3h. A white solid: mp:143.5–145.3 ꢀC; 1H NMR
(CF3, qt, JF–C¼285.0 Hz, JF–C¼34.0 Hz), 118.3, 122.0, 129.1, 130.5,
2
(CDCl3, 500 MHz, ppm):
d
2.46 (3H, s, CH3), 3.56 (3H, s, OCH3), 5.21
131.0, 140.9 (t, CCF2, JF–C¼28.0 Hz), 147.1, 165.8. MS (ESI) m/z: 431
(1H, d, J¼9.0 Hz, CH), 5.54 (1H, d, J¼9.0 Hz, NH), 6.99–7.73 (7H, m,
(MþNa)þ. IR (KBr, cmꢁ1):
n 3334, 2925, 1731, 1692, 1482, 1335. Anal.
ArH). 19F NMR (CDCl3, 470 MHz, ppm):
d
ꢁ82.25 (s, 3F), ꢁ117.11 (m,
Calcd for C14H8ClF7O4: C, 41.15; H, 1.97. Found: C, 41.12; H, 1.92.
2F). 13C NMR (CDCl3,125 MHz, ppm):
d 21.7, 48.2, 53.1,108.8 (CF2, qt,
2
1JF–C¼260.5 Hz, JF–C¼32.5 Hz), 112.7, 117.1 (CF3, qt, 1JF–C¼280.0 Hz,
4.3.4. Methyl 4-hydroxy-2-(trifluoromethyl)-4H-chromene-3-carboxyl-
2JF–C¼33.8 Hz), 118.3, 119.9, 127.3, 129.1, 130.0, 130.4, 131.1, 137.9,
ate 5d. A white solid: mp: 86.6–88.1 ꢀC; 1H NMR (CDCl3, 500 MHz,
2
140.4 (t, CCF2, JF–C¼28.0 Hz), 144.3, 147.6, 164.5. MS (EI) m/z (%):
ppm):
d
3.17 (1H, d, J¼6.0 Hz, OH), 3.88 (3H, s, OCH3), 5.69 (1H, d,
480 (4), 358 (31), 356 (100), 341 (77), 324 (37). IR (KBr, cmꢁ1):
n
J¼6.0 Hz, CH), 7.16–7.50 (4H, m, ArH). 19F NMR (CDCl3, 470 MHz,
3321, 2962, 1731, 1688, 1482, 1340. Anal. Calcd for C20H15ClF5NO5S:
C, 46.93; H, 2.95; N, 2.74. Found: C, 46.88; H, 2.86; N, 2.61.
ppm):
d
ꢁ66.96 (s, 3F). 13C NMR (CDCl3,125 MHz, ppm):
d 53.0, 62.0,
3
1
111.3 (d, CCF3, JF–C¼1.2 Hz), 116.9, 119.1 (CF3, q, JF–C¼273.8 Hz),
120.5, 126.0, 129.6, 130.2, 143.5 (q, CCF3, 2JF–C¼37.9 Hz), 148.6, 166.0.
MS (EI) m/z (%): 304 (Mþ, 43), 287 (66), 271 (61), 245 (44), 203 (100).
4.2.9. Methyl 8-methyl-2-(trifluoromethyl)-4-(tosylamino)-4H-chro-
mene-3-carboxylate 3i. a white solid: mp:148–149.5 ꢀC; 1H NMR
IR (KBr, cmꢁ1):
n 3383, 2951,1732,1677,1590,1490,1380. Anal. Calcd
(CDCl3, 500 MHz, ppm):
(3H, s, OCH3), 4.99 (1H, d, J¼8.5 Hz, CH), 5.65 (1H, d, J¼8.5 Hz, NH),
7.02–7.71 (7H, m, ArH). 19F NMR (CDCl3, 470 MHz, ppm):
ꢁ67.42
(s, 3F). 13C NMR (CDCl3, 125 MHz, ppm):
15.5, 21.7, 48.5, 52.8, 110.0
d
2.31 (3H, s, CH3), 2.44 (3H, s, CH3), 3.52
for C12H9F3O4: C, 52.56; H, 3.31. Found: C, 52.53; H, 3.26.
d
4.3.5. Methyl 4-hydroxy-8-methoxy-2-(trifluoromethyl)-4H-chro-
d
mene-3-carboxylate 5e. A white solid: mp: 118.1–118.8 ꢀC; 1H NMR
3
1
(d, CCF3, JF–C¼2.5 Hz), 116.8 (CF3, q, JF–C¼270.0 Hz), 118.5, 125.7,
126.5, 127.1, 127.3, 129.7, 131.3, 138.4, 142.7 (q, CCF3, 2JF–C¼37.0 Hz),
143.7, 147.6, 164.8. MS (EI) m/z (%): 441 (Mþ, 1), 410 (3), 372 (25),
(CDCl3, 500 MHz, ppm):
d
3.04 (1H, d, J¼5.8 Hz, OH), 3.89 (3H, s,
OCH3), 3.91 (3H, s, OCH3), 5.69 (1H, d, J¼5.8 Hz, CH), 6.92–7.21 (3H,
m, ArH). 19F NMR (CDCl3, 470 MHz, ppm):
(CDCl3, 125 MHz, ppm):
d
ꢁ66.58 (s, 3F). 13C NMR
286 (71), 271 (100), 254 (21). IR (KBr, cmꢁ1):
n
3302, 2927, 1737,
d
53.0, 56.5, 62.1, 111.2 (d, CCF3, JF–
3
1
1693, 1473, 1377. Anal. Calcd for C20H18F3NO5S: C, 54.42; H, 4.11; N,
3.17. Found: C, 54.26; H, 4.08; N, 3.23.
¼2.5 Hz), 112.2, 119.2 (CF3, q, JF–C¼273.8 Hz), 120.5, 121.5, 125.9,
C
2
138.7, 143.6 (q, CCF3, JF–C¼38.3 Hz), 148.0, 166.0. MS (EI) m/z (%):
274 (Mþ, 8), 273 (15), 257 (4), 241 (32), 215 (39), 173 (100). IR (KBr,
4.3. General procedure for preparation of compounds 5
cmꢁ1):
n 3411.15, 2963, 1722, 1682, 1486, 1373. Anal. Calcd for
C13H11F3O5: C, 51.32; H, 3.64. Found: C, 51.08; H, 3.57.
To the solution of salicyaldehyde (1.0 mmol) in DMSO (2 mL),
methyl 2-perfluoroalkynoates (1.2 mmol) and Et3N (10 mmol %)
were added and the mixture was stirred at room temperature for
1 h. After the completion of the reaction (monitored by TLC), the
products were purified by preparative TLC [eluent: petroleum ether
60–90 ꢀC/ethyl acetate] and recrystallized from dichloromethane
and petroleum ether (60–90 ꢀC) to give pure product 5.
4.3.6. Methyl 6-chloro-4-hydroxy-2-(trifluoromethyl)-4H-chromene-
3-carboxylate 5f. A white solid: mp: 124.7–126.4 ꢀC; 1H NMR
(CDCl3, 500 MHz, ppm):
d
3.22 (1H, d, J¼5.8 Hz, OH), 3.89 (3H, s,
OCH3), 5.66 (1H, d, J¼5.8 Hz, CH), 7.12–7.51 (3H, m, ArH). 19F NMR
(CDCl3, 470 MHz, ppm):
d
ꢁ66.87 (s, 3F). 13C NMR (CDCl3, 125 MHz,
ppm):
d
53.2, 61.8, 111.1 (d, CCF3, 3JF–C¼2.5 Hz), 118.4, 118.9 (CF3, q,

9156
L. Lu et al. / Tetrahedron 65 (2009) 9152–9156
2
1JF–C¼273.8 Hz), 121.9, 129.3, 130.5, 131.0 143.5 (q, CCF3, JF–
W. C. J. Nat. Prod. 2003, 66, 1531; (c) Yankep, E.; Njamen, D.; Fotsing, M. T.;
´ ˜
´
Fomum, Z. T.; Mbanya, J. C.; Giner, R. M.; Recio, M. C.; Manez, S.; Rıos, J. L. J. Nat.
Prod. 2003, 66, 1288; (d) Joulain, D.; Tabacchi, R. Phytochemistry 1994, 37, 1769;
(e) Kemnitzer, W.; Drewe, J.; Jiang, S.; Zhang, H.; Crogan-Grundy, C.; Labreque,
D.; Bubenick, M.; Attardo, G.; Denis, R.; Lamothe, S.; Gourdeau, H.; Tseng, B.;
Kasibhatla, S.; Cai, S. J. Med. Chem. 2008, 51, 417; (f) Doshi, J. M.; Tian, D.; Xing, C.
J. Med. Chem. 2006, 49, 7731; (g) Sciabola, S.; Carosati, E.; Cucurull-Sanchez, L.;
Baroni, M.; Mannhold, R. Bioorg. Med. Chem. 2007, 15, 6450; (h) Quaglia, W.;
Pigini, M.; Piergentili, A.; Giannella, M.; Marucci, G.; Poggesi, E.; Leonardi, A.;
Melchiorre, C. J. Med. Chem. 1999, 42, 2961; (i) Kemnitzer, W.; Drewe, J.; Jiang,
S.; Zhang, H.; Wang, Y.; Zhao, J.-H.; Jia, S.-J.; Herich, J.; Labreque, D.; Storer, R.;
Meerovitch, K.; Bouffard, D.; Rej, R.; Denis, R.; Blais, C.; Lamothe, S.; Attardo, G.;
Gourdeau, H.; Tseng, B.; Kasibhatla, S.; Cai, S. J. Med. Chem. 2004, 47, 6299.
2. For recent examples on the synthesis of 4H-chromenes, see: (a) Elinson, M. N.;
Dorofeev, A. S.; Miloserdov, F. M.; Ilovaisky, A. I.; Feducovich, S. K.; Belyakov, P.
A.; Nikishin, G. I. Adv. Synth. Catal. 2008, 350, 591; (b) Nishikata, T.; Yamamoto,
Y.; Miyaura, N. Adv. Synth. Catal. 2007, 349, 1759; (c) Aristegui, S. R.; El-Murr, M.
D.; Golding, B. T.; Griffin, R. J.; Hardcastle, I. R. Org. Lett. 2006, 8, 5927; (d) Shi,
Y.; Shi, M. Chem.dEur. J. 2006, 12, 3374; (e) Ye, L.; Sun, X.; Zhu, C.; Tang, Y. Org.
Lett. 2006, 8, 3853; (f) van Otterlo, W. A. L.; Ngidi, E. L.; Kuzvidza, S.; Morgans,
G. L.; Moleele, S. S.; de Koning, C. B. Tetrahedron 2005, 61, 9996; (g) Kidwai, M.;
Saxena, S.; Khan, M. K. R.; Thukral, S. S. Bioorg. Med. Chem. Lett. 2005, 15, 4295;
(h) Yavari, I.; Djahaniani, H.; Nasiri, F. Synthesis 2004, 679.
¼38.3 Hz), 147.1, 165.8. MS (EI) m/z (%): 308 (Mþ, 38), 307 (44), 291
C
(73), 275 (90), 249 (97), 207 (100). IR (KBr, cmꢁ1):
n 3505, 2955,
1721, 1678,1483, 1372. Anal. Calcd for C12H8ClF3O4: C, 46.70; H, 2.61.
Found: C, 46.58; H, 2.64.
4.3.7. Methyl 4-hydroxy-8-methyl-2-(trifluoromethyl)-4H-chromene-
3-carboxylate 5g. A white solid: mp: 88–89.7 ꢀC; 1H NMR (CDCl3,
500 MHz, ppm):
d
2.35 (3H, CH3), 3.01 (1H, d, J¼6.0 Hz, OH), 3.89
(3H, s, OCH3), 5.70 (1H, d, J¼6.0 Hz, CH), 7.15–7.35 (3H, m, ArH). 19
F
NMR (CDCl3, 470 MHz, ppm):
d
ꢁ66.88 (s, 3F). 13C NMR (CDCl3,
125 MHz, ppm):
d
15.6, 52.9, 62.4, 111.1 (d, CCF3, 3JF–C¼2.5 Hz), 119.2
1
(CF3, q, JF–C¼273.8 Hz), 120.2, 125.5, 126.5, 127.1, 131.4, 143.9 (q,
CCF3, 2JF–C¼38.3 Hz), 147.1, 166.1. MS (EI) m/z (%): 288 (Mþ, 20), 287
(25), 271 (48), 255 (44), 229 (48), 187 (100). IR (KBr, cmꢁ1):
n 3367,
2953, 1731, 1672, 1470, 1377. Anal. Calcd for C13H11F3O4: C, 54.17; H,
3.85. Found: C, 54.01; H, 4.01.
3. (a) Welch, J. T. Tetrahedron 1987, 43, 3123; (b) Organofluorine Chemistry: Prin-
ciples and Commercial Applications; Banks, R. E., Smart, B. E., Tatlow, J. C., Eds.;
Plenum: New York, NY, 1994; (c) Bergstrom, D. E.; Swartling, D. J. Fluorine
Substituted Analogues of Nucleic Acid Components. In Fluorine-Containing
Molecules, Structure, Reactivity, Synthesis and Applications; Liebman, J. F.,
Greenberg, A., Dolbier, W. R., Jr., Eds.; VCH: New York, NY, 1988; pp 259–308;
(d) Chambers, R. D. Fluorine in Organic Chemistry; CRC: Boca Raton, FL, 2004; (e)
Organic Chemistry in Medicinal Chemistry and Biomedical Applications; Filler, R.,
Ed.; Elsevier: Amsterdam, The Netherlands, 1993; (f) Uneyama, K. Organo-
fluorine Chemistry; Blackwell: Malden, MA, 2006.
4. (a) Sosnovskikh, V. Y.; Usachev, B. I.; Sevenard, D. V.; Roeschenthaler, G. J. Org.
Chem. 2003, 68, 7747; (b) El Kharrat, S.; Laurent, P.; Blancou, H. J. Org. Chem.
2006, 71, 8637; (c) El Kharrat, S.; El Kharrat, R.; Laurent, P.; Blancou, H. Synthesis
2007, 3542; (d) Sosnovskikh, V. Y.; Moshkin, V. S.; Irgashev, R. A. Tetrahedron
Lett. 2006, 47, 8543; (e) Sosnovskikh, V. Y.; Moshkin, V. S.; Kodess, M. I. Tetra-
hedron 2008, 64, 7877; (f) Medebielle, M.; Keirouz, R.; Okada, E.; Shibata, D.;
Dolbier, W. R., Jr. Tetrahedron Lett. 2008, 49, 589.
4.3.8. Methyl 4-hydroxy-8-methyl-2-(heptafluoropropyl)-4H-chro-
mene-3-carboxylate 5h. A white solid: mp: 92–92.8 ꢀC; 1H NMR
(CDCl3, 500 MHz, ppm):
d
2.30 (3H, CH3), 3.05 (1H, d, J¼6.0 Hz, OH),
3.86 (3H, s, OCH3), 5.63 (1H, d, J¼6.0 Hz, CH), 7.13–7.33 (3H, m,
ArH). 19F NMR (CDCl3, 470 MHz, ppm):
d
ꢁ80.80 (t, J¼9.4 Hz, 3F),
ꢁ144.07 (m, 2F), ꢁ125.26 (m, 2F). 13C NMR (CDCl3, 125 MHz, ppm):
d
15.4, 52.9, 62.8, 108.7 (CF2, tt, 1JF–C¼270.0 Hz, 2JF–C¼32.5 Hz), 111.4
(CF2, m), 114.4, 118.9 (CF3, qt, 1JF–C¼285.0 Hz, 2JF–C¼34.0 Hz), 120.2,
125.4, 126.4, 126.8, 131.4, 141.1 (t, CCF2, 2JF–C¼28 .0 Hz), 147.1, 166.2.
MS (EI) m/z (%): 388 (Mþ, 17), 371 (46), 357 (22), 355 (41), 329 (59),
187 (100). IR (KBr, cmꢁ1):
n 3473, 2961, 1722, 1674, 1472, 1363. Anal.
Calcd for C15H11F7O4: C, 46.41; H, 2.86. Found: C, 46.40; H, 2.88.
5. (a) Froissard, J.; Greiner, J.; Pastor, R.; Cambon, A. J. Fluorine Chem. 1981, 17, 249;
(b) Froissard, J.; Greiner, J.; Pastor, R.; Cambon, A. J. Fluorine Chem. 1984, 26, 47;
(c) Ding, W.; Zhang, P.; Cao, W. Tetrahedron Lett. 1987, 28, 81; (d) Ding, W.; Pu, J.;
Zhang, C.; Cao, W. J. Chem. Soc., Perkin Trans. 1 1991, 1369; (e) Ding, W.; Cao, W.;
Xu, Z.; Yao, Y.; Shi, Z.; Han, Z. J. Chem. Soc., Perkin Trans. 1 1993, 855; (f) Cao, W.;
Ding, W.; Yi, T.; Zhu, Z. J. Fluorine Chem. 1997, 81, 153; (g) Cao, W.; Ding, W.;
Ding, W.; Huang, H. J. Fluorine Chem. 1997, 83, 21; (h) Cao, W.; Ding, W.; Huang,
T.; Huang, H.; Wei, C. J. Fluorine Chem. 1998, 91, 99; (i) Cao, W.; Ding, W.; Liu, R.;
Huang, T.; Cao, J. J. Fluorine Chem. 1999, 95, 135; (j) Ding, W.; Cao, W.; Xu, Z.; Shi,
Z.; Yao, Y. Chin. J. Chem. 1993, 11, 81; (k) Cao, W.; Shi, Z.; Fan, C.; Ding, W. J.
Fluorine Chem. 2002, 116, 117.
4.3.9. Methyl 4-hydroxy-6-nitro-2-(pentafluoroethyl)-4H-chromene-
3-carboxylate 5i. A white solid: mp: 105.7–106.7 ꢀC; 1H NMR
(CDCl3, 500 MHz, ppm): d 3.47 (1H, br s, OH), 3.91 (3H, s, OCH3), 5.75
(1H, br s, CH), 7.29–8.49 (3H, m, ArH). 19F NMR (CDCl3, 470 MHz,
ppm):
ppm):
d
ꢁ82.05 (s, 3F), ꢁ116.48 (m, 2F). 13C NMR (CDCl3, 125 MHz,
1
2
d
53.5, 61.7, 109.0 (CF2, qt, JF–C¼270.0 Hz, JF–C¼32.5 Hz),
1 2
114.8, 118.0, 118.2 (CF3, qt, JF–C¼285.0 Hz, JF–C¼34.0 Hz), 121.6,
2
125.6, 125.9, 140.8 (t, CCF2, JF–C¼28 .0 Hz), 145.1, 152.4, 165.3. MS
(EI) m/z (%): 369 (Mþ, 8), 368 (23), 352 (24), 338 (23), 317 (32), 310
6. (a) Shi, Y.; Shi, M. Org. Lett. 2005, 7, 3057; (b) Zhao, G.; Shi, Y.; Shi, M. Org. Lett.
2005, 7, 4527; (c) Guo, Y.; Shi, Y.; Lia, H.; Shi, M. Tetrahedron 2006, 62, 5875.
7. CCDC-683461 (3b) contains all crystallographic details of this publication and is
available free of charge at www.ccdc.cam.ac.uk/consts/retrieving.html or can be
ordered from the following address: Cambridge Crystallographic Data Centre,
12 Union Road, GB-Cambridge CB21EZ; fax: þ44 1223 336 033; or deposit@
(100). IR (KBr, cmꢁ1):
n 3492, 2964, 1721, 1684, 1483, 1350. Anal.
Calcd for C13H8F5O6: C, 42.29; H, 2.18; N, 3.79. Found: C, 42.43; H,
2.25; N, 3.63.
ccdc.cam.ac.uk. Unit cell parameters: a: 9.5269 Å; b: 11.2132 Å; c: 12.9275 Å; a:
72.580;
b: 76.271; g: 67.682; space group: P-1.
Acknowledgements
8. Qian, J.; Cao, W.; Zhang, H.; Chen, J.; Zhu, S. J. Fluorine Chem. 2007, 128, 207.
9. (a) Murray, W. V.; Francois, D.; Maden, A.; Turchi, I. J. Org. Chem. 2007, 72, 3097;
(b) Cao, W.; Ding, W.; Wang, L.; Song, L.; Zhang, Q. J. Fluorine Chem. 2001, 109,
201.
10. (a) Price, K. E.; Broadwater, S. J.; Jung, H. M.; McQuade, D. T. Org. Lett. 2005, 7,
147; (b) Price, K. E.; Broadwater, S. J.; Walker, B. J.; McQuade, D. T. J. Org. Chem.
2005, 70, 3980; (c) Raheem, I. T.; Jacobsen, E. N. Adv. Synth. Catal. 2005, 347,
1701; (d) Buskens, P.; Klankermayer, J.; Leitner, W. J. Am. Chem. Soc. 2005, 127,
16762; (e) Aggarwal, V. K.; Fulford, S. Y.; Lloyd-Jones, G. C. Angew. Chem., Int. Ed.
2005, 44, 1706.
The authors are grateful to the National Natural Science Foun-
dation of China (Grant No. 20872088) and Leading Academic Dis-
cipline Projects of Shanghai Municipal Education Commission
(Grant Nos. 08ZZ44 and J50102) for their financial support.
References and notes
11. Jin, T.; Feng, G.; Yang, M.; Li, T.; Jin, T.; Feng, G.; Yang, M.; Li, T. Synth. Commun.
2004, 34, 1277.
1. (a) Ito, C.; Itoigawa, M.; Kanematsu, T.; Ruangrungsi, N.; Mukainaka, T.; Tokuda,
H.; Nishino, H.; Furukawa, H. Phytochemistry 2003, 64, 1265; (b) Rukachaisir-
ikul, V.; Kamkaew, M.; Sukavisit, D.; Phongpaichit, S.; Sawangchote, P.; Taylor,
´
12. (a) Hamper, B. C. Org. Synth. 1992, 70, 246; (b) Jeannin, O.; Fourmigue, M.
Chem.dEur. J. 2006, 12, 2994.