Fluorine-containing furan derivatives from the michael addition of ethyl 4,4,4-trifluoro-3-oxobutanoate with β-nitrostyrenes

Article abstract of DOI:10.1055/s-0029-1219199

Ethyl 4,4,4-trifluoro-3-oxobutanoate reacted with nitrostyrenes in the presence of Et₃N to afford ethyl 5-(hydroxyim-ino)-4-aryl-2- (trifluoromethyl)-2,5-dihydrofuran-3-carboxylates along with a small amount of ethyl 2-hydroxy-5-imino-4-aryl-2-(trifluoromethyl)-2,5-dihydrofuran-3- carboxylates. Treatment of ethyl 5-(hydroxyimino)-4-aryl-2-(trifluoromethyl)-2, 5-dihydro-furan-3-car-boxylates with 1.2 equivalents of TsOH in t-BuOH, afforded ethyl 2-hydroxy-5-imino-4-aryl-2-(trifluoromethyl)-2,5-dihydrofuran-3- carboxylates in good yields. However, ethyl 2-ethoxy or methoxy-5-oxo-4-aryl-2- (trifluoromethyl)-2,5-dihydrofuran-3-carboxylates were obtained as major products in EtOH or MeOH along with a small amount of ethyl 2-hydroxy-5-imino-4- aryl-2-(trifluoromethyl)-2,5-dihydrofuran-3-carboxylates.

Full text of DOI:10.1055/s-0029-1219199

830
LETTER
Fluorine-Containing Furan Derivatives from the Michael Addition of Ethyl
4,4,4-Trifluoro-3-oxobutanoate with b-Nitrostyrenes
S
ynthesis of Flu
i
orine-C
p
ontaining
F
i
n
D
n
s
g Song,*a,b Xianfu Li,a Chunhui Xing,b Dongmei Li,a Shizheng Zhu,*b Hongmei Deng,c Min Shaoc
a
b
c
Department of Chemistry, School of Science, Shanghai University, No. 99, Shangda Road, Shanghai 200444, P. R. of China
Fax +86(21)66132797; E-mail: lpsong@shu.edu.cn
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu,
Shanghai 200032, P. R. of China
Instrumental Analysis and Research Center, Shanghai University, Shanghai 200444, P. R. of China
Received 28 October 2009
O
R4
Abstract: Ethyl 4,4,4-trifluoro-3-oxobutanoate reacted with ni-
trostyrenes in the presence of Et3N to afford ethyl 5-(hydroxyim-
ino)-4-aryl-2-(trifluoromethyl)-2,5-dihydrofuran-3-carboxylates along
with a small amount of ethyl 2-hydroxy-5-imino-4-aryl-2-(trifluo-
romethyl)-2,5-dihydrofuran-3-carboxylates. Treatment of ethyl 5-
(hydroxyimino)-4-aryl-2-(trifluoromethyl)-2,5-dihydrofuran-3-car-
boxylates with 1.2 equivalents of TsOH in t-BuOH, afforded ethyl
2-hydroxy-5-imino-4-aryl-2-(trifluoromethyl)-2,5-dihydrofuran-3-
carboxylates in good yields. However, ethyl 2-ethoxy or methoxy-
5-oxo-4-aryl-2-(trifluoromethyl)-2,5-dihydrofuran-3-carboxylates
were obtained as major products in EtOH or MeOH along with a
small amount of ethyl 2-hydroxy-5-imino-4-aryl-2-(trifluorometh-
yl)-2,5-dihydrofuran-3-carboxylates.
O
N
R1
R1
O
OH
R5
NO2
R1
R1
R4
R5 = H
I
O
O
O
O
R4
R5
R2
R3
R2
R3
O
R5 = H or alkyl
II
Scheme 1 Preparation of furan derivatives from b-nitrostyrene and
1,3-diketone derivatives
Key words: Michael addition, cyclization, fluorine-containing
furans, 4,4,4-trifluoro-3-oxobutanone, b-nitro-stryene
In continuation of our study on enriching the synthetic
methods of fluorine-containing heterocycles, we investi-
gated the reactions of 1 with nitroalkenes. To a solution of
equimolar amounts of 1 and 2a (2.0 mmol) in DME (3.0
mL) was added a catalytic amount of Et3N (0.4 mmol).
The mixture was then stirred at room temperature for 10
hours, however, no reaction occurred. Therefore, the reac-
tion temperature was raised to refluxing temperature, and
after stirring for five hours, TLC analysis showed that the
reaction had occurred. After evaporation of the solvent,
the residue was subjected to column chromatography on
silica gel using petroleum ether–ethyl acetate (5:1, v/v) as
the eluent. The product 3a was afforded in 83% yield as a
white solid (mp 129–130 °C). In addition, a more polar
compound 4a (white solid, mp 110–112 °C) was isolated
in about 5% yield (Equation 1).
Addition of nucleophiles to electron-deficient nitroal-
kenes was one of the important Michael addition reac-
tions.1 Because the versatile nitro functionality could be
easily transformed into an amine, nitrile oxide, ketone,
carboxylic acid, hydrogen, etc.,2 much attention had been
paid on this reaction, including the enantioselective pro-
cesses.3 In addition, 2-hydroxyimino-6,7-dihydro-4(5H)-
benzofuranone I or furan derivatives II could also be ob-
tained from the initial Michael addition reaction of b-
nitrostyrene with cyclohexane-1,3-diones or b-keto es-
ters, respectively (Scheme 1).4,5 Recently, 4-acetoxy-2-
amino-3-arylbenzofurans were synthesized from the 1-
aryl-2-nitroethylenes
and
cyclohexane-1,3-dinones
through a domino process.6 Among these studies, howev-
er, few attention was focused on the reaction of fluoro-
alkyl 1,3-diones or b-keto esters with the nitroalkenes,7
especially using the initial Michael addition followed by
intramolecular cyclization reaction to prepare fluorine-
containing heterocyclic compounds.
O
Ar
OH
EtO
O
O
N
O
F3C
Ar
OEt
F3C
Furthermore, it was well known that the selective incorpo-
ration of a fluorine atom or fluoroalkyl group into aromat-
ic or heterocyclic system frequently confer biological or
physical properties to such molecules.8 With this aim, we
reported the synthesis of a variety of trifluoromethyl-
containing heterocycles based on the fluorinated building-
block strategy.9
1
3
+
Et3N
+
DME, reflux
O
NO2
Ar
EtO
F3C
2
NH
O
OH
4
SYNLETT 2010, No. 5, pp 0830–0834
Advanced online publication: 14.01.2010
DOI: 10.1055/s-0029-1219199; Art ID: W17309ST
1
6.
3
.2
0
1
0
Equation 1 Et3N-catalyzed reaction of ethyl 4,4,4-trifluoro-3-oxo-
butanoate with b-nitrostyrenes
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Fluorine-Containing Furan Derivatives
831
To explore the scope and versatility of this method under
the same reaction conditions, a series of 1-aryl-2-nitro-
ethylenes was used as the starting materials to react with
1, and the results are summarized in Table 1.10 As shown
in entries 1–3 and 7–9, products 3a–c and 3g–i were ob-
tained in good to excellent yields along with a small
amount of 4a–c and 4g–i. Reaction of 1 with 1-furanyl-2-
nitroethylene 2f only gave 4f in an unsatisfactory yield
(27%, entry 6). When 1-(4-methoxyphenyl)-2-nitroethyl-
ene 2c was used as the starting material, 3c and 4c were
obtained in 74% and 10%, respectively. However, when
2e, which bears two methoxy substituents on the phenyl,
was used, 3e and 4e were isolated in 50% and 33% yields,
respectively. From entries 2–6, it could be deduced that
electron-donating groups on the aromatic ring of 2 facili-
tated the formation of 4. On the other hand, when 1-(4-
hydroxyphenyl)-2-nitroethylene 2d was used as the start-
ing material, the ratio of 3 to 4 was reversed (entry 4). For
example, it gave 4d as the major product in 52% and 3d
as a minor product in 37% yield.
Table 1 Reaction of 1 with b-Nitrostyrenesa
Figure 1 The X-ray crystal structure of 4e
Entry Ar in 2
Products and yields (%)b
(Scheme 2). Furthermore, when compared with the non-
fluorinated substrates, most b-dicarbonyl compounds
studied resulted in the formation of either the normal
Michael adducts or the furan derivatives II. One excep-
tion was cyclohexane-1,3-diketones, which produced 2-
hydroxyimino-6,7-dihydro-4(5H)-benzofuranone I.4,5 To
the best of our knowledge, nonfluorinated analogues of 3
or 4 have not been reported.
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
Ph
3a
3b
3c
3d
83
79
74
37
50
4a
4b
4c
4d
4e
4f
5
4-MeC6H4
4-MeOC6H4
4-HOC6H4
8
10
52
33
27
5
3,4-(MeO)2C6H3 3e
d
furan-2-yl
4-BrC6H4
2-FC6H4
3f
3g
3h
3i
–
O
O
Ar
Ar
2g
2h
2i
72
94
70
4g
4h
4i
H
OH
OH
EtO
F3C
1,3-hydrogen migration EtO
F3C
tracec
3
N
N
O
O
4-O2NC6H4
3
a Reaction conditions: 1 (2.0 mmol), 2 (2.0 mmol), Et3N (0.4 mmol),
Scheme 2 1,3-Hydrogen migration to compound 3
DME (3.0 mL), reflux for 5 h.
b Isolated yields.
c Not isolated.
To verify the assumption that 3 could be converted to 4
under the acidic conditions, we further studied the trans-
formation of 3 in the presence of TsOH.13 Initially, 3a was
refluxed in EtOH with 0.2 equivalents of TsOH. After
stirring for one day, TLC showed that only a small amount
of 3a was converted. When the amount of TsOH was in-
creased to 1.2 equivalents (0.6 mmol, 103.0 mg), com-
plete conversion of 3a was observed within 4.5 hours.
After workup, a g-butyrolactone 5a was isolated in 83%
yield, which was also an important type of intermediate
and building block for fine chemicals and pharmaceuti-
cals,14 along with a small amount of 4a (12%, Equation 2).
Due to the participation of EtOH in the transformation
process, the expected product 4 was obtained in low yield.
Under the same conditions, hydrolysis of 3b,c,g–i pro-
ceeded similarly (Table 2). In addition, hydrolysis could
also be achieved in the presence of inorganic acids
(Table 2, entry 2).
d A complex mixture.
Spectral and microanalysis data supported the structure
assignment of 3 and 4.11 In the 1H NMR spectrum of 3a,
the chemical shift of 2-position of proton attached to the
furan moiety appeared as a quadruplet peak at d = 5.80
with a 3JH–F coupling constant of 5.1 Hz. Whereas in the
19F NMR spectrum, the chemical signal of CF3 was a dou-
blet peak at d = –76.52 with the same coupling constant.
In addition, the structure of 4e was further confirmed by
X-ray crystallographic analysis (Figure 1).12
In cases of such fluorinated substrates, analogous prod-
ucts I and II (Scheme 1) could not be formed due to the
presence of the strong electron-withdrawing CF3 group.
Hence, analogue I was readily isomerized to produce the
more stable compound 3 by 1,3-hydrogen migration
Synlett 2010, No. 5, 830–834 © Thieme Stuttgart · New York

832
L. Song et al.
LETTER
also explain why compound 4d was the major product in
O
Ar
our previous study (Table 1, entry 4).
EtO
O
Table 3 Reaction of 3a with 1.2 Equivalents of TsOH in Different
Solventsa
O
CF3
RO
O
O
Ar
OH
N
5
Entry
Solventb
EtOH
Products and yields (%)c
TsOH (1.2 equiv)
ROH, reflux
EtO
+
1
2
3
4
5
6
7
8
9
5a
5j
5k
–
83
74
46
–
4a
4a
4a
4a
4a
4a
4b
4h
4i
12
11
43
83
81
56
79
85
90
Ar
O
F3C
3
EtO
F3C
MeOH
i-PrOH
t-BuOH
DME
NH
O
OH
4
Equation 2 Transformation of 3 into 4 and 5 in the presence of 1.2
equiv of TsOH
–
–
benzene
t-BuOH
t-BuOH
t-BuOH
–
–
Table 2 Transformation of 3 into 4 and 5 with 1.2 Equivalents of
–
–
TsOH in EtOHa
–
–
Entry
Ar in 3
3a
Products and yields (%)b
–
–
1
2c
3
4
5
6
7
Ph
5a
5a
5b
5c
5g
5h
5i
83
48
76
80
79
82
78
4a
4a
4b
4c
4g
4h
4i
12
a Reaction conditions: 3 (0.5 mmol), TsOH (0.6 mmol), solvent (3.0
mL), reflux for 4 h.
3a
Ph
22
b Commercially available solvent, without further purification.
c Isolated yields.
3b
4-MeC6H4
4-MeOC6H4
4-BrC6H4
2-FC6H4
4-O2NC6H4
21
3c
traced
18
3g
It was interesting to note that 4 could be obtained directly
from reaction of 1 with 2 through one-pot tandem proce-
dure (Scheme 3). For example, after refluxing the reaction
mixture of 1 and 2c for four hours with a catalytic amount
of Et3N in t-BuOH, the starting materials were completely
transformed into 3c (monitored by TLC). After adding 1.2
equivalents of TsOH to the mixture, continually stirring
for four hours at refluxing temperature, and purifying by
column chromatography on silica gel, 4c was obtained in
68% yield. Compound 4g could also be directly synthe-
sized from 1 and 2g in 66% yield by the similar procedure.
3h
16
3i
traced
a Reaction conditions: 3 (0.5 mmol), TsOH (0.6 mmol, 103.0 mg),
EtOH (3.0 mL), reflux for 4 h.
b Isolated yields.
c 1.0 mL HCl (1.0 mol/L) was used instead of TsOH.
d Not isolated.
The structure identity of compound 5 was fully supported
by spectral and microanalysis data.15 According to the
structure of 5, it was clear that the solvent participated in
the hydrolysis of 3. In order to determine whether other al-
cohols, especially sterically hindered alcohols, such as i-
PrOH and t-BuOH could participate in the transformation
process of 3, thus, the acidic hydrolysis of 3a was carried
out in different alcohols (Table 3, entries 1–4). In EtOH
and MeOH, it could be transformed into 5a and 5j as ma-
jor products, along with a small amount of 4a (Table 3,
entries 1 and 2). While in i-PrOH, 4a and 5k were ob-
tained in approximate equal yields, however, in t-BuOH,
4a was the exclusive product (Table 3, entries 3 and 4). It
was clear that sterically hindered alcohols were less favor-
able to alkoxy participation. Hydrolyses of 3b, 3h, and 3i
were also carried out in t-BuOH and they also exclusively
gave 4b, 4h, and 4i, respectively (Table 3, entries 7–9).
Similarly, transformation of 3a in DME or benzene as sol-
vent afforded the 4a in 81% and 56% yields, respectively
(Table 3, entries 5 and 6). Apparently, under acidic condi-
tions, the reaction predominantly afforded compound 4 as
the major product in aprotic solvents. These results could
R
O
O
O
F3C
OEt
TsOH
1
EtO
(1.2 equiv)
Et3N
NH
+
O
4 h
t-BuOH, reflux
4 h
F3C
NO2
OH
4c R = OMe, 68%
4g R = Br, 66%
R
2c,g
Scheme 3 One-pot, tandem reaction of 1 and 2 for the preparation
of 4
In summary, we have developed a new method to prepare
trifluoromethyl-substituted furan derivatives from ethyl
4,4,4-trifluoro-3-oxobutanoate and nitroalkenes through
initial Michael addition reaction followed by intramolec-
ular cyclization reaction. Reflux in t-BuOH, ethyl 5-(hy-
droxyimino)-4-aryl-2-(trifluoromethyl)-2,5-dihydrofuran-
3-carboxylates 3 could be exclusively transformed into
Synlett 2010, No. 5, 830–834 © Thieme Stuttgart · New York

LETTER
Synthesis of Fluorine-Containing Furan Derivatives
833
(9) (a) Li, X. F.; Song, L. P.; Xing, C. H.; Zhao, J. W.; Zhu, S.
Z. Tetrahedron 2006, 62, 2255. (b) Li, D. M.; Song, L. P.;
Li, X. F.; Xing, C. H.; Peng, W. M.; Zhu, S. Z. Eur. J. Org.
Chem. 2007, 3520. (c) Li, D. M.; Song, L. P.; Song, S. D.;
Zhu, S. Z. J. Fluorine Chem. 2007, 128, 952. (d) Song, S.
D.; Song, L. P.; Dai, B. F.; Yi, H.; Jin, G. F.; Zhu, S. Z.;
Shao, M. Tetrahedron 2008, 64, 5728. (e) Dai, B. F.; Song,
L. P.; Wang, P. Y.; Yi, H.; Cao, W. G.; Jin, G. F.; Zhu, S. Z.;
Shao, M. Synlett 2009, 1842.
(10) General Procedures for the Reaction of 1 with 2
To a 10 mL round-bottom flask containing ethyl 4,4,4-
trifluoro-3-oxobutanoate 1 (368.0 mg, 2.0 mmol)was added
DME (3.0 mL), 2a (298.0 mg, 2.0 mmol), and Et3N (0.4
mmol). The resulting mixture was stirred at refluxing
temperature. After stirring for 4.5 h, the TLC analysis
showed that the reaction was finished. The solvent was
evaporated, and the residue was purified by column
chromatography on a silica gel using PE–EtOAc (5:1, v/v) as
eluent to afford 3a (523.0 mg, 83%) along with a small
amount of 4a (31.0 mg, 5%).
ethyl 2-hydroxy-5-imino-4-aryl-2-(trifluoromethyl)-2,5-
dihydrofuran-3-carboxylates 4 in the presence of 1.2
equivalents of TsOH, while with less steric hindered alco-
hols, such as EtOH and MeOH, ethyl 2-alkoxy-5-oxo-4-
aryl-2-(trifluoromethyl)-2,5-dihydrofuran-3-carboxylates
5 was formed. In i-PrOH, 4 and 5 could be obtained in ap-
proximately equal amount. Furthermore, 4 could be di-
rectly synthesized by one-pot, tandem reaction of 1 with 2
in t-BuOH.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Acknowledgment
This work was supported by the National Natural Science Founda-
tion of China (NNSFC) (Nos.20672072, 20772080), Leading Aca-
demic Discipline Project of Shanghai Municipal Education
Commission (No. J50102), the Key Laboratory of Organofluorine
Chemistry, Shanghai Institute of Organic Chemistry, and the Inno-
vation Fund of Shanghai University.
(11) Spectroscopic Data for Products 3 and 4
Compound 3a: colorless solid; mp 129–130 °C. 1H NMR
(300 MHz, CDCl3): d = 1.18 (t, J = 7.2 Hz, 3 H), 4.17 (qd,
J = 7.2 Hz, JAB = 10.8 Hz, 1 H), 4.25 (qd, J = 7.2 Hz,
JAB = 10.8 Hz, 1 H), 5.80 (q, 3JH–F = 5.1 Hz, 1 H), 7.13 (br, 1
H), 7.42–7.51 (m, 5 H). 13C NMR (75.5 MHz, CDCl3):
d = 13.6, 62.0, 82.4 (q, 2JC–F = 34.6 Hz), 121.9 (q, 1JC–F
=
References and Notes
282.0 Hz), 127.3, 128.1, 129.4, 130.3, 130.4, 143.4, 158.8,
160.7. 19F NMR (282 MHz, CDCl3): d = –76.52 (d, 3JH–
F = 5.1 Hz, 3 F). IR (KBr): 3412, 2986, 2917, 1720, 1662,
1497, 1252, 1151, 1003, 935, 692 cm–1. MS (70 eV, EI): m/
z (%) = 315 (100) [M+], 270 (38.8) [M – OEt]+, 246 (52.3)
(1) Perlmuter, P. In Conjugate Addition Reaction in Organic
Synthesis; Pergamon: Oxford, 1992.
(2) (a) The Nitro Group in Organic Synthesis; One, N., Ed.;
Wiley-VCH: New York, 2001. (b) Nef, J. U. Justus Liebigs
Ann. Chem. 1984, 280. (c) Ghosh, A. K.; Bilcer, G.; Schiltz,
G. Synthesis 2001, 2203. (d) Ballini, R.; Petrini, M.
Tetrahedron 2004, 60, 1017.
(3) (a) Wang, W.; Wang, J.; Li, H. Angew. Chem. Int. Ed. 2005,
44, 1369. (b) Mendler, B.; Kazmaier, U.; Huch, V.; Veith,
M. Org. Lett. 2005, 7, 2643. (c) Ji, J.; Barnes, D. M.; Zhang,
J.; King, S. A.; Wittenberger, S. J.; Morton, H. E. J. Am.
Chem. Soc. 1999, 121, 10215. (d) Barnes, D. M.; Ji, J.;
Fickes, M. G.; Fitzgerald, M. A.; King, S. A.; Morton, H. E.;
Plagge, F. A.; Preskill, M.; Wittenberger, S. J.; Zhang, J.
J. Am. Chem. Soc. 2002, 124, 13097. (e) Evans, D. A.;
Seidel, D. J. Am. Chem. Soc. 2005, 127, 9985.
(4) (a) Ansell, G. B.; Moore, D. W.; Nielsen, A. T. Chem.
Comm. 1970, 1602. (b) Ansell, G. B.; Moore, D. W.;
Nielsen, A. T. J. Chem. Soc. B 1971, 2376.
(5) (a) Boerg, F.; Schutze, G. R. Chem. Ber. 1957, 90, 1215.
(b) Yanami, T.; Ballatore, A.; Miyashita, M.; Kato, M.;
Yoshikoshi, A. J. Chem. Soc., Perkin Trans. 1 1978, 1144.
(6) Ishikawa, T.; Miyahara, T.; Asakura, M.; Higuchi, S. Org.
Lett. 2005, 7, 1211.
+
[M – CF3]+, 69 (7.5) [CF3 ]. Anal. Calcd for C14H12F3NO4:
C, 53.33; H, 3.81; N, 4.44. Found: C, 53.45; H, 3.85; N, 4.30.
Compound 4a: colorless solid; mp 110–112 °C. 1H NMR
(300 MHz, CDCl3): d = 1.21 (t, J = 7.2 Hz, 3 H), 4.30 (q,
J = 7.2 Hz, 2 H), 5.50 (s, 1 H), 6.84 (s, 1 H), 7.26–7.54 (m,
5 H). 19F NMR (282 MHz, CDCl3): d = –80.58 (s, 3 F). IR
(KBr): 3318, 2987, 1728, 1645, 1197, 1069, 733, 695 cm–1.
MS (70 eV, EI): m/z (%) = 315 (3.6) [M+], 270 (4.3) [M –
OEt]+, 246 (34.4) [M – CF3]+, 200(100) [M – CF3 – EtOH]+,
+
69 (6.0) [CF3 ]. Anal. Calcd for C14H12F3NO4: C, 53.33; H,
3.81, N, 4.44. Found: C, 53.72; H, 3.95; N, 4.10.
(12) CCDC 292367 contains the supplementary crystallographic
data. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12, Union Road,
Cambridge CB2 1EZ, UK; fax: +44 (1223)336033.
(13) General Experimental Procedure for the
Transformation of 3 to 4 and 5
Reflux the solution of 3 (0.5 mmol), in ROH (3.0 mL) with
1.2 equiv (0.6 mmol, 103.0 mg) of TsOH for ca. 4 h, TLC
showed that 3 was completely transformed into 4 and 5 in
different ratios, which were correlated with the size of R in
the ROH. Compounds 4 and 5 were separated and purified
by column chromatography on a silica gel using PE–EtOAc
(10:1, v/v) as eluent.
(7) Bégué, J. P.; Bonnet-Delpon, D.; Dogbeavou, A. J. Fluorine
Chem. 1999, 54, 278.
(8) (a) Organofluorine Compounds. Chemistry and
Applications; Hiyama, T., Ed.; Springer: New York, 2000.
(b) Organofluorine Chemistry: Principles and Commercial
Applications; Banks, R. E.; Smart, B. E.; Tatlow, J. C., Eds.;
Plenum Press: New York, 1994. (c) Fluorine in Bioorganic
Chemistry; Welch, J. T.; Eshwarakrishman, S., Eds.; Wiley:
New York, 1991. (d) Fluorine-Containing Molecules.
Structure, Reactivity, Synthesis, and Applications; Liebman,
J. F.; Greenberg, A.; Dolbier, W. R. Jr., Eds.; VCH:
Weinheim, 1988.
(14) (a) Connolly, J. D.; Hill, R. A. Dictionary of Terpenoids,
Vol. 1; Chapman and Hall: London, 1991, 476–541.
(b) Koch, S. S. C.; Chamberlin, A. R. J. Org. Chem. 1993,
58, 2725; and references therein.
(15) Spectroscopic Data for Products 5
Compound 5a: colorless solid; mp 49–50 °C. 1H NMR (300
MHz, CDCl3): d = 1.26 (t, J = 7.2 Hz, 3 H), 1.34 (t, J = 7.2
Hz, 3 H), 3.74 (qd, J = 7.2 Hz, JAB = 8.4 Hz, 1 H), 3.83 (qd,
J = 7.2 Hz, JAB = 8.4 Hz, 1 H), 4.34 (q, J = 7.2 Hz, 2 H),
Synlett 2010, No. 5, 830–834 © Thieme Stuttgart · New York

834
L. Song et al.
LETTER
7.43–7.51 (m, 3 H), 7.62–7.65 (m, 2 H). 13C NMR (75.5
MHz, CDCl3): d = 13.6, 14.6, 61.3, 62.7, 102.6 (q,
1736, 1657, 1448, 1226, 1196 cm–1. MS (70 eV, EI): m/z (%)
= 344 (1.8) [M+], 299 (11.0) [M – OEt]+, 275 (27.9) [M –
2JC–F = 35.6 Hz), 120.5 (q, 1JC–F = 286.1 Hz), 126.8, 128.7,
129.0, 131.2, 137.9, 141.0, 161.4, 166.3. 19F NMR (282
MHz, CDCl3): d = –80.51 (s, 3 F). IR (KBr): 2988, 1797,
CF3]+, 201 (64.3) [M – OEt – Et – CF3]+, 69 (9.2) [CF3 ].
+
Anal. Calcd for C16H15F3O5: C, 55.81; H, 4.36. Found: C,
55.93; H, 4.41.
Synlett 2010, No. 5, 830–834 © Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.