A facile stereoselective synthesis of 2-perfluoroalkyl-3a,4,5,6-tetrahydroimidazo[1,5-b]isoxazoles

Article abstract of DOI:10.1016/j.jfluchem.2008.11.002

Methyl 2-perfluoroalkynoates 2 reacted readily with cyclic nitrones 1 via 1,3-dipolar cycloaddition at room temperature to give 2-perfluoroalkyl-3a,4,5,6-tetrahydroimidazo[1,5-b]isoxazoles 3 in good to excellent yields with high diastereoselectivity and r

Full text of DOI:10.1016/j.jfluchem.2008.11.002

Journal of Fluorine Chemistry 130 (2009) 295–300
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
A facile stereoselective synthesis of 2-perfluoroalkyl-3a,4,5,
6-tetrahydroimidazo[1,5-b]isoxazoles
a
a
a
Lei Lu a, Weiguo Cao a,b,c, , Jie Chen , Hui Zhang
, Jiaping Zhang , Huiyun Chen ,
*
a,**
Jiamei Wei a, Hongmei Deng d, Min Shao d
a Department of Chemistry, Shanghai University, Shanghai 200444, China
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, Shanghai 200032, China
c State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, Shanghai 200032, China
d Instrumental Analysis and Research Center, Shanghai University, Shanghai 200444, China
A R T I C L E I N F O
A B S T R A C T
Article history:
Methyl 2-perfluoroalkynoates 2 reacted readily with cyclic nitrones 1 via 1,3-dipolar cycloaddition at
room temperature to give 2-perfluoroalkyl-3a,4,5,6-tetrahydroimidazo[1,5-b]isoxazoles 3 in good to
excellent yields with high diastereoselectivity and regioselectivity.
Received 15 October 2008
Received in revised form 24 November 2008
Accepted 24 November 2008
Available online 30 November 2008
ß 2008 Elsevier B.V. All rights reserved.
Keywords:
Methyl 2-perfluoroalkynoates
Imidazoisoxazoles
1,3-Dipolar cycloaddition
Diastereoselectivity
Regioselectivity
1. Introduction
perfluoro-2-akynoates with cyclic nitrones, which provide a new
efficient and convenient tool in the good-yield synthesis of the
Fluorinated heterocycles represent an interesting class of
fluorinated compounds that have found their wide application
as agrochemicals, pharmaceuticals, and in the field of new material
science [1]. Consequently, much attention has been addressed to
develop new methodologies for the synthesis of these target
structures by synthetic chemists the world over [2]. The 1,3-
dipolar cycloaddition reactions of nitrones with a variety of
alkynes or olefins, within the building-block strategy, has received
particular attention for the synthesis of a variety of isoxazole
derivatives, which can be transformed into numerous attractive
building-block molecules for organic synthesis [3–5].
Though perfluoro-2-alkynoates exhibit high reactivity and
exclusive regioselectivity in most cases of the cycloadditions
[2c,6], there are merely scattered examples of 1,3-diploar cyc-
loaddition using them as dipolarphiles. Herein, we wish to report
the results of our studies on the 1,3-dipolar cycloaddition of
novel fluoroalkyl-tetrahydroimidazoisoxazole bicyclic system 3
with high regio- and stereo- selectivity.
2. Results and discussion
The D3-imidazoline 3-oxides 1, prepared according to the
reported procedure [7], undergo 1,3-cycloaddition with methyl 2-
perfluoroalkynoates 2 [8] to give 2-perfluoroalkyl-3a,4,5,6-tetra-
hydroimidazo[1,5-b]isoxazoles 3 at room temperature in good to
excellent yields, using CH2Cl2 as solvent (Scheme 1, Table 1).
All reactions went rapidly and completely within 4 h, though it
was found that cyclic nitrones 1 with an electron-donating group
on R2 reacted more readily with methyl 2-perfluoroalkynoates 2 to
give the product in higher yields than those with an electron-
withdrawing group on R2 (Table 1, 3d and 3g, 3h; 3m and 3n, 3p).
The high efficiency in the reaction between 1 and 2 may be
ascribed to strong electron-withdrawal of the RF group according
to the theory of frontier molecular orbitals (FMO theory) [6a,e].
Based on the theory, nitrone is a donor and alkyne is an acceptor of
electrons. Thus the strengthening of the acceptor properties
of substituents in alkyne explains why electron-withdrawing
group substituted-2-alkynoates such as perfluoro-2-alkynoates
* Corresponding author at: Department of Chemistry, Shanghai University, 99
Shang Da Rd., Shanghai 200444, China. Tel.: +86 21 66134856;
fax: +86 21 66134856.
** Corresponding author. Fax: +86 21 66134856.
E-mail addresses: wgcao@staff.shu.edu.cn (W. Cao), yehao7171@shu.edu.cn
(H. Zhang).
0022-1139/$ – see front matter ß 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2008.11.002

296
L. Lu et al. / Journal of Fluorine Chemistry 130 (2009) 295–300
Scheme 1. Synthesis of 3a,4,5,6-tetrahydroimidazo[1,5-b]isoxazoles 3.
Table 1
Synthesis of 3a,4,5,6-tetrahydroimidazo[1,5-b]isoxazoles 3.
Entry
N-oxide 1
R1
R2
RF
Product
Yielda (%)
Mp (8C)
1
2
1a
1b
1c
1d
1e
1f
p-MeOC6H4
p-MeOC6H4
p-MeC6H4
p-MeC6H4
p-MeOC6H4
p-MeOC6H4
p-MeC6H4
p-MeC6H4
p-MeOC6H4
p-MeC6H4
p-MeC6H4
p-MeOC6H4
p-MeC6H4
p-MeC6H4
p-MeOC6H4
p-MeC6H4
Ph
CF3
3a
3b
3c
3d
3e
3f
92
90
96
89
87
92
73
76
78
92
98
95
89
81
76
79
107.0–107.7
108.7–109.8
112.1–112.6
92.3–93.1
103.4–103.7
89.8–90.7
68.2–69.4
54.1–55.7
59.3–61.5
98.1–100.2
104.6–108.2
86.5–88.0
92.5–95.2
70.3–73.1
64.3–66.7
79.5–81.3
H
CF3
3
p-MeC6H4
p-MeOC6H4
p-MeC6H4
p-MeOC6H4
p-NO2C6H4
p-ClC6H4
p-ClC6H4
Ph
CF3
4
CF3
5
CF3
6
CF3
7
1g
1h
1i
CF3
3g
3h
3i
8
CF3
9
CF3
10
11
12
13
14
15
16
1j
n-C3F7
n-C3F7
n-C3F7
n-C3F7
n-C3F7
n-C3F7
n-C3F7
3j
1k
1b
1c
1h
1i
H
3k
3l
H
p-MeC6H4
p-ClC6H4
p-ClC6H4
p-NO2C6H4
3m
3n
3o
3p
1g
a
Isolated yields.
2
like 4,4,4-trifluorobutynoates or acetylenedicarboxylates can
increase the rate of cycloaddition [3c,5,6,9].
LUMO of asymmetrically substituted alkyneð
’
21 and
4Þ. Interaction of the centers
is preferred. Maximum atomic
coefficients in the interacting molecular orbitals pertain to the
oxygen atom of the nitrone and to the carbon atom to ester group
’
2Þs and in
2
HOMO of the nitrone group ð
’ ’
23 and
2
Furthermore, the distinguishing feature of the studied reaction is
its high regioselectivity: only one regioisomer containing stronger
electron-withdrawing substituent at position 2 of the tetrahydroi-
midazo[1,5-b]isoxazol is formed (Scheme 1). Dipolar cycloaddition
of nitrones to electron-deficient alkynes is probably a type I
cycloaddition and is controlled by the interaction of HOMO of the
dipole and LUMO of the alkyne [4e,6b,c,9a]. Based on FMO theory,
high regioselectivity is the result of the significant difference of
coefficients squares of atomic wave functions at reaction centers in
with maximum values of ’
i
b
in alkyne. Regioisomer 3 is formed as a result of such overlapping,
that is observed in the experiment.
Since the assignment of configuration of 3 is difficult to be made
on the basis of 1H NMR spectroscopic data and NOESY experiments,
an X-ray diffraction analysis was used to elucidate the structures
of 3. A 3D perspective view of the crystal structure of 3a is shown in
Fig. 1 [10]. The adduct is proved unequivocally to be the cis-isomer
by X-ray differaction analysis, that is, the Ph ring and R2 were on
the same side of the bicyclic ring system [5b]. The fact that only one
signal observed in 19F NMR spectroscopy of 3a proves further
that the reactions of 1 with alkyne 2 are not only regiospecific
but also diastereospecific, affording only one diastereoisomer. Take
3a for an example, D3-imidazoline 3-oxide 1a possesses two
chiral centers, thus there exist four possible stereoisomers: A, B, C
and D (Fig. 2). In C and D, the N-anisyl group is in a cis relation-
ship with the phenyl group on C-3a. Accordingly, the steric
interactions between two vicinal aryl groups become so signi-
ficant that C and D are thermally too unstable to undergo the 1,3-
dipolar cycloaddition with alkynoates, which was proved by the
fact that no corresponding products were detected in the experi-
ment. For A and B, the fact that only one diastereoisomer was
obtained demonstrated that the reaction was a concerted pro-
cess guided with the Woodward–Hoffman rule. When the linear
molecule of 4,4,4-trifluorobutynoate approaches planar dipole N-
oxide 1a with the CF3 group being oriented towards the
oxygen atom of the N-oxide function, there are four different
routes, which are E, F, G and H, respectively. The alkynoate prefers
to approach the dipole from the less sterically hindered side of the
plane and thus afforded a pair of enantiomers (Scheme 2 and
Fig. 3).
Fig. 1. X-ray structure of 3a.

L. Lu et al. / Journal of Fluorine Chemistry 130 (2009) 295–300
297
Fig. 2. Four possible stereoisomers of 1.
Scheme 2. Formation of product 3.
4. Experimental
4.1. General
All reagents and solvents were purchased from commercial
sources and used without further purification. Melting points were
recorded on a WRS-1 instrument and uncorrected. IR spectra were
obtained on a Bruker Spectrometer. 1H, 19F and 13C NMR spectra
were recorded on a Bruker AVANCE-500 MHz instrument. All
chemical shifts are reported in parts per million downfield
(positive) of the standard: C6F6 for 19F, TMS for 1H and 13C NMR
spectra. Elemental analyses were performed on an Elementar Vario
EL-III instrument. MS spectra were run on an Agilent LC spectro-
meter. X-ray analysis was performed on a Bruker Smart Apex2 CCD
Spectrometer. Preparative TLC on silica gel was performed by
using self-coated GF254 plates, which were activated immediately
before use.
Fig. 3. Sterichindric approach diagram.
3. Conclusion
In summary, we developed a convenient method to synthesize
the regiospecific 2-perfluoroalkylsubstituted isoxazoles 3 with
high diasterselectivity, which were prepared readily from the 1,3-
dipolar cycloaddition reactions of cyclic nitrones 1 with methyl 2-
perfluoroalkynoates 2 in good to excellent yields. This work
4.2. General procedure for the preparation of compounds 1
At room temperature,
a-bromoacetophenone oxime
(2.5 mmol) was added to a solution of aromatic amine (5 mmol)
in ethanol and the mixture was stirred for 20 min followed by
adding aromatic aldehyde (5 mmol) or 35% water solution of
formaldehyde (5 mL) and then stirred for another 3 h at same
temperature. The formed precipitate was collected by filtration
and recrystallized from acetone to get 1a–e, 1j–k [7d] and 1f–i,
respectively.
provides
a simple procedure for the synthesis of fluorine-
containing bicyclic nitrogen heterocycles. Considering the con-
tributions of the method such as mild reaction conditions, easy
manipulation, simple work-up, etc., it should found applications in
organic synthesis.

298
L. Lu et al. / Journal of Fluorine Chemistry 130 (2009) 295–300
4.2.1. 1,2-Bis(4-methoxyphenyl)-4-phenyl-2,5-dihydro-1H-
imidazole 3-oxide (1f)
3JF = 2.5), 114.78, 116.98, 117.52 (q, 1JF = 254.0 Hz), 126.80, 127.74,
128.18, 128.50, 128.63, 128.71, 130.72, 140.13, 140.91, 149.96 (d,
2JF = 40.0 Hz), 153.65, 161.88. MS (ESI) m/z 497.2 (M + 1)+. IR (KBr)
3031, 2949, 2836, 1718, 1669, 1512, 1457, 1340 cmꢀ1. Anal. Cacld
for C27H23F3N2O4: C 65.32, H 4.67, N 5.64; Found: C 65.37, H 4.63, N
5.68.
White solid; mp: 165–167.6 8C; 1H NMR (500 MHz, CDCl3)
d
3.73 (3H, s, CH3O), 3.80 (3H, s, CH3O), 4.80 (1H, dd, J = 14.5, 2.8 Hz,
CH2), 5.14 (1H, dd, J = 14.5, 5.0 Hz, CH2), 6.09 (1H, m, CH), 6.57–
8.35 (13H, m, Ph). 13C NMR (125 MHz, CDCl3)
d 55.31, 55.47, 55.82,
73.45, 89.89, 113.83, 114.45, 115.19, 127.04, 127.41, 128.19,
128.85, 128.97, 129.51, 131.00, 138.76, 152.96. MS (ESI) m/z 397
(M + Na)+. IR (KBr) 3088, 3000, 2935, 2837, 1611, 1515 cmꢀ1. Anal.
Cacld for C23H22N2O3: C 73.78, H 5.92, N 7.48; Found: C 73.82, H
5.76, N 7.44.
4.3.2. Methyl cis-5-(4-methoxyphenyl)-3a-phenyl-2-
(trifluoromethyl)-3a,4,5,6-tetrahydroimidazo[1,5-b]isoxazole-3-
carboxylate (3b)
White solid; mp: 108.7–109.8 8C; 1H NMR (500 MHz, CDCl3)
d
3.43 (1H, d, J = 9.0 Hz, CH2), 3.69 (3H, s, CH3O), 3.78 (3H, s, CH3O),
4.13 (1H, d, J = 11.5 Hz, CH2), 4.67 (1H, d, J = 9.0 Hz, CH2), 5.03 (1H,
d, J = 11.5 Hz, CH2), 6.78–7.59 (9H, m, Ph). 19F NMR (470 MHz,
4.2.2. 2-(4-Nitrophenyl)-4-phenyl-1-p-tolyl-2,5-dihydro-1H-
imidazole 3-oxide (1g)
Yellow solid; mp: 174.5–175.6 8C; 1H NMR (500 MHz, CDCl3)
d
CDCl3)
d
ꢀ63.50 (s, CF3). 13C NMR (125 MHz, CDCl3)
d 52.14, 55.79,
2.25 (3H, s, CH3), 4.89 (1H, dd, J = 14.5, 2.0 Hz, CH2), 5.21 (1H, dd,
J = 14.5, 5.0, CH2), 6.27 (1H, m, CH), 6.47–8.33 (13H, m, Ph). 13C
57.99, 83.94, 110.82 (d, 3JF = 2.5), 114.98, 116.91, 117.65 (q,
1JF = 272.0 Hz), 127.26, 128.41, 128.52, 140.18, 140.60, 149.84 (d,
2JF = 39.5 Hz), 153.96, 161.69. MS (ESI) m/z 421.1 (M + 1)+. IR (KBr)
3060, 2957, 2829, 1710, 1668, 1515, 1443, 1347 cmꢀ1. Anal. Cacld
for C21H19F3N2O4: C 60.00, H 4.56, N 6.66; Found: C 60.02, H 4.59,
N 6.64.
NMR (125 MHz, CDCl3)
d 20.45, 53.27, 73.78, 88.65, 112.84,
124.10, 126.87, 127.32, 129.12, 129.01, 129.35, 130.36, 131.53,
131.76, 141.50, 142.79. MS (ESI) m/z 375.1 (M + 1)+. IR (KBr) 3067,
3030, 2861, 1617, 1522, 1447, 1349 cmꢀ1. Anal. Cacld for
C
22H19N3O3: C 70.76, H 5.13, N 11.25; Found: C 70.28, H 4.99,
N 11.03.
4.3.3. Methyl cis-3a-phenyl-5,6-di-p-tolyl-2-(trifluoromethyl)-
3a,4,5,6-tetrahydroimidazo[1,5-b]isoxazole-3-carboxylate (3c)
4.2.3. 2-(4-Chlorophenyl)-4-phenyl-1-p-tolyl-2,5-dihydro-1H-
imidazole 3-oxide (1h)
White solid; mp: 112.1–112.6 8C; 1H NMR (500 MHz, CDCl3)
d
2.23 (3H, s, CH3), 2.25 (3H, s, CH3), 3.70 (3H, s, CH3O), 4.12 (1H, d,
White solid; mp: 143.7–145 8C; 1H NMR (500 MHz, CDCl3)
d
J = 11.0 Hz, CH2), 4.77 (1H, d, J = 11.0 Hz, CH2), 5.98 (1H, s, CH),
2.41 (3H, s, CH3), 4.83 (1H, dd, J = 14.5, 3.0 Hz, CH2), 5.14 (1H, dd,
J = 14.5, 5.0 Hz, CH2), 6.14 (1H, m, CH), 6.48–8.33 (13H, m, Ph). 13
NMR (125 MHz, CDCl3) 20.44, 53.06, 89.13, 112.78, 127.06,
6.66–7.52 (13H, m, Ph). 19F NMR (470 MHz, CDCl3)
d
ꢀ63.74 (s,
C
CF3). 13C NMR (125 MHz, CDCl3)
d 20.48, 21.25, 52.24, 57.17, 81.86,
d
111.64 (d, 3JF = 2.5 Hz), 114.78, 117.68 (q, 1JF = 272.0 Hz), 126.86,
127.46, 128.13, 128.45, 128.58, 129.37, 129.90, 134.04, 138.38,
140.76, 148.81, 149.00 (d, 2JF = 39.5 Hz), 161.87. MS (ESI) m/z 495.1
(M + 1)+. IR (KBr) 3030, 2951, 2924, 1722, 1685, 1513, 1422,
1353 cmꢀ1. Anal. Cacld for C28H25F3N2O3: C 68.01, H 5.10, N 5.66;
Found: C 68.03, H 5.13, N 5.65.
126.14, 128.57, 128.90, 129.24, 129.54, 130.20, 131.22, 134.55,
134.68, 136.16, 141.77. MS (ESI) m/z 385.0 (M + Na)+. IR (KBr) 3093,
3029, 2860, 1618, 1519, 1447, 1352 cmꢀ1
C
.
Anal. Cacld for
22H19ClN2O: C 72.82, H 5.28, N 7.72; Found: C 72.83, H 5.17, N
7.71.
4.2.4. 2-(4-Chlorophenyl)-1-(4-methoxyphenyl)-4-phenyl-2,5-
dihydro-1H-imida zole 3-oxide (1i)
4.3.4. Methyl cis-6-(4-methoxyphenyl)-3a-phenyl-5-p-tolyl-2-
(trifluoromethyl)-3a,4,5,6-tetrahydroimidazo[1,5-b]isoxazole-3-
carboxylate (3d)
White solid; mp: 169.8–172.4 8C; 1H NMR (500 MHz, CDCl3)
d
3.73 (3H, s, CH3O), 4.80 (1H, dd, J = 14.5, 3.0 Hz, CH2), 5.14 (1H,
dd, J = 14.5, 5.5 Hz, CH2), 6.10 (1H, m, CH), 6.53–8.33 (13H, m,
White solid; mp: 92.3–93.1 8C; 1H NMR (500 MHz, CDCl3)
d
2.24 (3H, s, CH3), 3.71 (3H, s, CH3O), 3.72 (3H, s, CH3O), 4.13
Ph). 13C NMR (125 MHz, CDCl3)
d
53.42, 55.79, 89.42, 113.88,
(1H, d, J = 10.5 Hz, CH2), 4.74 (1H, d, J = 10.5 Hz, CH2), 5.95 (1H, s,
115.23, 127.04, 127.15, 128.90, 129.24, 129.62, 131.20, 134.61,
134.77, 136.19, 138.40, 153.18. MS (ESI) m/z 379.1 (M + 1)+. IR
(KBr) 3048, 3000, 2929, 2832, 1620, 1515, 1490, 1352 cmꢀ1. Anal.
Cacld for C22H19ClN2O2: C 69.75, H 5.05, N 7.39; Found: C 69.53,
H 5.24, N 7.43.
CH), 6.66–7.51 (13H, m, Ph). 19F NMR (470 MHz, CDCl3)
d
ꢀ63.77
(s, CF3). 13C NMR (125 MHz, CDCl3)
d 20.49, 52.26, 55.33,
57.33, 81.72, 87.59, 111.68 (d, 3JF = 2.5 Hz), 114.91, 117.67 (q,
1JF = 272.0 Hz), 126.85, 128.15, 128.45, 128.66, 128.84, 128.96,
129.90, 140.77, 143.78, 149.00 (d, 2JF = 39.5 Hz), 159.78,
161.87. MS (ESI) m/z 511.2 (M + 1)+. IR (KBr) 3060, 3034,
2997, 2894, 1723, 1687, 1512, 1442, 1353 cmꢀ1. Anal. Cacld for
4.3. General procedure for the preparation of compounds 3
C
28H25F3N2O4: C 65.88, H 4.94, N 5.49; Found: C 65.90, H 4.96, N
To the solution of imidazoline oxides (1.0 mmol) in CH2Cl2,
methyl 2-perfluoroalkynoates (1.1 mmol) was added and the
mixture was stirred at room temperature for 0.5–3 h. After the
completion of the reaction (monitored by TLC), the products were
purified by preparative TLC (elutent: petroleum ether 60–90 8C-
ethyl acetate) and recrystallized from dichloromethane and
petroleum ether (60–90 8C) to get pure product 3.
5.46.
4.3.5. Methyl cis-5-(4-methoxyphenyl)-3a-phenyl-6-p-tolyl-2-
(trifluoromethyl)-3a,4,5,6-tetrahydroimidazo[1,5-b]isoxazole-3-
carboxylate (3e)
White solid; mp: 103.4–103.7 8C; 1H NMR (500 MHz, CDCl3)
d
2.26 (3H, s, CH3), 3.71 (3H, s, CH3O), 3.72 (3H, s, CH3O), 4.15 (1H, d,
J = 11.0 Hz, CH2), 4.63 (1H, d, J = 11.0 Hz, CH2), 5.83 (1H, s, CH),
4.3.1. Methyl cis-5-(4-methoxyphenyl)-3a,6-diphenyl-2-
(trifluoromethyl)-3a,4,5,6-tetrahydroimidazo[1,5-b]isoxazole-3-
carboxylate (3a)
6.74–7.54 (13H, m, Ph). 19F NMR (470 MHz, CDCl3)
d
ꢀ63.74 (s,
CF3). 13C NMR (125 MHz, CDCl3)
d 21.16, 52.17, 55.62, 58.55, 81.27,
88.54, 111.53 (d, 3JF = 2.5 Hz), 114.65, 116.92, 117.58 (q,
1JF = 272.0 Hz), 126.69, 127.54, 128.39, 129.25, 138.38, 140.07,
140.96, 148.90 (d, 2JF = 39.5 Hz), 153.49, 161.81. MS (ESI) m/z 511.2
(M + 1)+. IR (KBr) 3060, 3033, 2997, 2894, 1722, 1687, 1512, 1442,
1352 cmꢀ1. Anal. Cacld for C28H25F3N2O4: C 65.88, H 4.94, N 5.49;
Found: C 65.94, H 4.86, N 5.52.
White solid; mp: 107.0–107.7 8C; 1H NMR (500 MHz, CDCl3)
d
3.72 (3H, s, CH3O), 3.73 (3H, s, CH3O), 4.15 (1H, d, J = 11.0 Hz, CH2),
4.65 (1H, d, J = 11.0 Hz, CH2), 5.88 (1H, s, CH), 6.73–7.54 (14H, m,
Ph). 19F NMR (470 MHz, CDCl3)
(125 MHz, CDCl3)
d
ꢀ63.74 (s, CF3). 13C NMR
d
52.30, 55.37, 58.68, 81.53, 88.73, 111.66 (d,

L. Lu et al. / Journal of Fluorine Chemistry 130 (2009) 295–300
299
4.3.6. Methyl cis-5,6-bis(4-methoxyphenyl)-3a-phenyl-2-
(trifluoromethyl)-3a,4,5,6-tetrahydroimidazo[1,5-b]isoxazole-3-
carboxylate (3f)
20.43, 52.26, 57.37, 82.32, 88.00, 108.54 (t–t, 1JF = 250.5 Hz,
2JF = 35.4 Hz), 114.49 (t–t, 1JF = 254.6 Hz, 2JF = 32.3 Hz), 114.91,
117.56 (q–t, 1JF = 275.8 Hz, 2JF = 30.8 Hz), 126.74, 127.56, 128.22,
128.49, 128.62, 128.71, 129.14, 129.64, 129,90, 137.04, 140.55,
143.82, 146.52 (d, 2JF = 29.4 Hz), 161.76. MS (ESI) m/z 603.2
White solid; mp: 89.8–90.7 8C; 1H NMR (500 MHz, CDCl3)
d 3.70
(9H, s, 3CH3O), 4.16 (1H, d, J = 11.0 Hz, CH2), 4.61 (1H, d, J = 11.0 Hz,
CH2), 5.80 (1H, s, CH), 6.74–7.55 (13H, m, Ph). 19F NMR (470 MHz,
(M + Na)+. IR (KBr) 3031, 2951, 1710, 1656, 1520, 1443, 1333 cmꢀ1
.
CDCl3)
d
ꢀ63.69 (s, CF3). 13C NMR (125 MHz, CDCl3)
d
52.25, 55.65,
Anal. Cacld for C29H23F7N2O3: C 60.00, H 3.99, N 4.83; Found: C
60.27, H 4.25, N 5.02.
58.84, 61.95, 81.17, 88.41, 111.66 (d, 3JF = 2.5 Hz), 113.97, 114.70,
117.24 (q, 1JF = 272.0 Hz), 126.75, 126.98, 128.13, 128.48, 128.90,
129.01, 130.44, 140.08, 141.08, 148.78 (d, 2JF = 39.0 Hz), 153.66,
161.85. MS (ESI) m/z 527.1 (M + 1)+. IR (KBr) 3001, 2954, 2837,
1716, 1675, 1512, 1441, 1346 cmꢀ1. Anal. Cacld for C28H25F3N2O5:
C 63.87, H 4.79, N 5.32; Found: C 63.71, H 4.86, N 5.61.
4.3.11. Methyl cis-2-(perfluoropropyl)-3a-phenyl-5-p-tolyl-3a,4,5,6-
tetrahydroimidazo[1,5-b]isoxazole-3-carboxylate (3k)
White solid; mp: 104.6–108.2 8C; 1H NMR (500 MHz, CDCl3)
d
2.27 (3H, s, CH3), 3.50 (1H, d, J = 10.0 Hz, CH2), 3.63 (3H, s, CH3O),
4.15 (1H, d, J = 11.5 Hz, CH2), 4.75 (1H, d, J = 10.0 Hz, CH2), 5.03 (1H,
4.3.7. Methyl cis-6-(4-nitrophenyl)-3a-phenyl-5-p-tolyl-2-
(trifluoromethyl)-3a,4,5,6-tetrahydroimidazo[1,5-b]isoxazole-3-
carboxylate (3g)
d, J = 11.5, CH2), 6.71–7.56 (9H, m, Ph). 19F NMR (470 MHz, CDCl3)
d
ꢀ80.52 (t, J = 9.4, CF3), ꢀ112.97 (m, CF2), ꢀ125.92 (m, CF2). 13C
NMR (125 MHz, CDCl3)
d 20.51, 52.13, 57.49, 76.12, 84.30, 108.39
Yellow solid; mp: 68.2–69.4 8C; 1H NMR (500 MHz, CDCl3)
d
(t–t, 1JF = 266.9 Hz, 2JF = 37.5 Hz), 110.38 (t–t, 1JF = 258.75 Hz,
2JF = 32.5 Hz), 114.17, 115.51, 117.70 (q–t, 1JF = 286.3 Hz,
2JF = 33.8 Hz), 127.12, 128.47, 128.61, 129.54, 130.05, 140.43,
143.85, 147.13 (t, 2JF = 28.8), 161.60. MS (ESI) m/z 505.1 (M + 1)+. IR
2.26 (3H, s, CH3), 3.72 (3H, s, CH3O), 4.10 (1H, d, J = 11.0 Hz, CH2),
4.82 (1H, d, J = 11.0 Hz, CH2), 6.10 (1H, s, CH), 6.66–8.10 (13H, m,
Ph). 19F NMR (470 MHz, CDCl3)
(125 MHz, CDCl3)
d
ꢀ63.71 (s, CF3). 13C NMR
d
20.50, 52.42, 61.30, 82.30, 87.13, 114.87,
(KBr) 3065, 3007, 2959, 2847, 1708, 1655, 1521, 1445, 1334 cmꢀ1
.
111.84 (d, 3JF = 2.5 Hz), 117.51 (q, 1JF = 273.0 Hz), 123.89, 126.74,
128.52, 128.58, 128.63, 128.75, 129.63, 129.98, 130.15, 139.24,
143.24, 144.38, 148.44 (d, 2JF = 39.0 Hz), 161.58. MS (ESI) m/z 548.0
(M + Na)+. IR (KBr) 3032, 2954, 2860, 1720, 1668, 1521, 1441,
1347 cmꢀ1. Anal. Cacld for C27H22F3N3O5: C 61.71, H 4.22, N 8.00;
Found: C 61.48, H 4.56, N 7.87.
Anal. Cacld for C23H19F7N2O3: C 54.77, H 3.80, N 5.55; Found: C
54.84, H 3.71, N 5.53.
4.3.12. Methyl cis-5-(4-methoxyphenyl)-2-(perfluoropropyl)-3a-
phenyl-3a,4,5,6-tetrahydroimidazo[1,5-b]isoxazole-3-carboxylate
(3l)
White solid; mp: 86.5–88.0 8C; 1H NMR (500 MHz, CDCl3)
d 3.45
4.3.8. Methyl cis-6-(4-chlorophenyl)-3a-phenyl-5-p-tolyl-2-
(trifluoromethyl)-3a,4,5,6-tetrahydroimidazo[1,5-b]isoxazole-3-
carboxylate (3h)
(1H, d, J = 10.0, CH2), 3.64 (3H, s, CH3O), 3.75 (3H, s, CH3O), 4.10
(1H, d, J = 11.0 Hz, CH2), 4.73 (1H, d, J = 10.0 Hz, CH2), 5.00 (1H, d,
J = 11.0 Hz, CH2), 6.77–7.55 (9H, m, Ph). 19F NMR (470 MHz, CDCl3)
White solid; mp: 54.1–55.7 8C; 1H NMR (500 MHz, CDCl3)
d
2.25
d
ꢀ80.53 (t, J = 9.4 Hz, CF3), ꢀ112.16 (m, CF2), ꢀ125.93 (m, CF2). 13
C
(3H, s, CH3), 3.71 (3H, s, CH3O), 4.09 (1H, d, J = 11.0 Hz, CH2), 4.77
(1H, d, J = 11.0 Hz, CH2), 5.98 (1H, s, CH), 6.65–7.50 (13H, m, Ph). 19
NMR (125 MHz, CDCl3)
d 52.12, 55.71, 58.09, 76.84, 84.39, 108.91
F
(t–t, 1JF = 258.8 Hz, 2JF = 32.5 Hz), 110.29 (t–t, 1JF = 258.8 Hz,
2JF = 32.5 Hz), 114.05, 114.96, 116.93, 117.69 (q–t, 1JF = 286.3 Hz,
2JF = 33.8 Hz), 127.12, 128.44, 128.59, 140.19, 140.51, 147.17 (t,
2JF = 28.75 Hz), 153.97, 161.60. MS (ESI) m/z 521.0 (M + 1)+. IR (KBr)
3065, 3003, 2955, 2838, 1734, 1672, 1516, 1475, 1353 cmꢀ1. Anal.
Cacld for C23H19F7N2O4: C 53.08, H 4.03, N 5.73; Found: C 53.32, H
3.59, N 5.33.
NMR (470 MHz, CDCl3)
CDCl3)
d
ꢀ63.76 (s, CF3). 13C NMR (125 MHz,
d
21.45, 52.44, 57.37, 82.06, 88.05, 114.98, 111.84 (d,
3JF = 2.5 Hz), 117.88 (q, 1JF = 273.0 Hz), 127.05, 127.66, 128.33,
128.64, 128.78, 129.57, 130.09, 134.24, 138.58, 140.96, 144.01,
149.20 (d, 2JF = 39.0 Hz), 162.07. MS (ESI) m/z 515.1 (M + 1)+. IR
(KBr) 3032, 2953, 2921, 2854, 1717, 1668, 1516, 1440, 1346 cmꢀ1
.
Anal. Cacld for C27H22ClF3N2O3: C 62.98, H 4.31, N 5.44; Found: C
61.81, H 4.28, N 5.61.
4.3.13. Methyl cis-2-(perfluoropropyl)-3a-phenyl-5,6-di-p-tolyl-
3a,4,5,6-tetrahydroimidazo[1,5-b]isoxazole-3-carboxylate (3m)
4.3.9. Methyl cis-6-(4-chlorophenyl)-5-(4-methoxyphenyl)-3a-
phenyl-2-(trifluoromethyl)-3a,4,5,6-tetrahydroimidazo[1,5-
b]isoxazole-3-carboxylate (3i)
White solid; mp: 92.5–95.2 8C; 1H NMR (500 MHz, CDCl3)
d 2.21
(3H, s, CH3), 2.23 (3H, s, CH3), 3.65 (3H, s, CH3O), 4.17 (1H, d,
J = 11.0 Hz, CH2), 4.81 (1H, d, J = 11.0 Hz, CH2), 5.95 (1H, s, CH),
White solid; mp: 59.3–61.5 8C; 1H NMR (500 MHz, CDCl3)
d
3.71
6.68–7.71 (13H, m, Ph). 19F NMR (470 MHz, CDCl3)
d
ꢀ80.44 (t,
(3H, s, CH3O), 3.73 (3H, s, CH3O), 4.12 (1H, d, J = 10.5 Hz, CH2), 4.64
(1H, d, J = 10.5 Hz, CH2), 5.84 (1H, s, CH), 6.71–7.53 (13H, m, Ph).
J = 9.4, CF3), ꢀ112.11 (m, CF2), ꢀ125.63 (m, CF2). 13C NMR
(125 MHz, CDCl3)
d 20.44, 21.20, 52.25, 57.40, 82.17, 87.95,
19F NMR (470 MHz, CDCl3)
CDCl3)
d
ꢀ63.71 (s, CF3). 13C NMR (125 MHz,
108.59 (t–t, 1JF = 267.5 Hz, 2JF = 37.5 Hz), 110.39 (t–t,
1JF = 258.8 Hz, 2JF = 32.5 Hz), 114.86, 114.92, 117.68 (q–t,
1JF = 286.3 Hz, 2JF = 33.8 Hz), 126.74, 127.49, 128.18, 128.49,
128.64, 129.36, 129.87, 134.07, 138.39, 140.73, 143.87, 146.59
(t, 2JF = 28.8 Hz), 161.79. MS (ESI) m/z 595.1 (M + 1)+. IR (KBr) 3031,
2953, 2862, 1716, 1655, 1517, 1440, 1329 cmꢀ1. Anal. Cacld for
d
52.82, 56.27, 59.20, 81.91, 89.19, 112.18 (d, 3JF = 2.5 Hz),
115.30, 117.56, 118.22 (q, 1JF = 273.0 Hz), 127.34, 128.19, 128.68,
129.04, 129.89, 134.57, 139.03, 140.72, 141.60, 149.55 (d,
2JF = 39.0 Hz), 154.14, 162.45. MS (ESI) m/z 531.0 (M + 1)+. IR
(KBr) 3061, 3000, 2954, 2839, 1717, 1668, 1512, 1441, 1345 cmꢀ1
.
Anal. Cacld for C27H22ClF3N2O4: C 61.08, H 4.18, N 5.28; Found: C
61.10, H 4.28, N 5.57.
C30H25F7N2O3: C 60.61, H 4.24, N 4.71; Found: C 60.88, H 4.58, N
4.62.
4.3.10. Methyl cis-2-(perfluoropropyl)-3a,6-diphenyl-5-p-tolyl-
4.3.14. Methyl cis-6-(4-chlorophenyl)-2-(perfluoropropyl)-3a-
phenyl-5-p-tolyl-3a,4,5,6-tetrahydroimidazo[1,5-b]isoxazole-3-
carboxylate (3n)
3a,4,5,6-tetrahydroimidazo[1,5-b]isoxazole-3-carboxylate (3j)
White solid; mp: 98.1–100.2 8C; 1H NMR (500 MHz, CDCl3)
d
2.22 (3H, s, CH3), 3.64 (3H, s, CH3O), 4.17 (1H, d, J = 10.5 Hz, CH2),
4.83 (1H, d, J = 10.5 Hz, CH2), 5.99 (1H, s, CH), 6.68–7.50 (14H, m,
White solid; mp: 70.3–73.1 8C; 1H NMR (500 MHz, CDCl3)
d
2.22
(3H, s, CH3), 3.64 (3H, s, CH3O), 4.13 (1H, d, J = 11.0 Hz, CH2), 4.83
(1H, d, J = 11.0 Hz, CH2), 5.97 (1H, s, CH), 6.67–7.50 (13H, m, Ph). 19
NMR (470 MHz, CDCl3)
ꢀ80.45 (t, J = 9.4 Hz, CF3), ꢀ113.68 (m,
Ph). 19F NMR (470 MHz, CDCl3)
d
ꢀ80.44 (q, J = 9.4 Hz, CF3),
F
ꢀ112.49 (m, CF2), ꢀ125.65 (m, CF2). 13C NMR (125 MHz, CDCl3)
d
d

300
L. Lu et al. / Journal of Fluorine Chemistry 130 (2009) 295–300
CF2), ꢀ125.67 (m, CF2). 13C NMR (125 MHz, CDCl3)
d 20.39, 52.26,
(e) R. Filler, Y. Kobayashi, L.M. Yagupolskii, Organofluorine Compounds in Med-
icinal Chemistry and Biomedical Applications, Elsevier, Amsterdam, 1993.
[2] (a) R.E. Banks, B.E. Smart, J.C. Tatlow, Organofluorine Chemistry, Principles and
Commercial Applications, Plenum Press, New York, 1994;
(b) G.G. Furin, in: O.A. Attanasi, D. Spinelli (Eds.), Targets in Heterocyclic Systems,
vol. 2, Societa Chimica Italiana, Roma, 1998, pp. 355–441;
(c) S. Zhu, Y. Wang, W. Peng, L. Song, G. Jin, Curr. Org. Chem. 6 (2002) 1057–1096;
(d) Y.V. Burgart, V.I. Saloutin, O. Chupakhin, Heterocycles 69 (2006) 593–620;
(e) K. Burger, L. Hennig, J. Spengler, F. Albericio, Heterocycles 69 (2006) 569–592;
(f) A. Pace, I. Pibiri, S. Buscemi, N. Vivona, L. Malpezzi, J. Org. Chem. 69 (2004)
4108–4115;
57.35, 82.40, 87.49, 108.08 (t–t, 1JF = 243.8 Hz, 2JF = 38.8 Hz),
110.33 (t–t, 1JF = 258.8 Hz, 2JF = 32.5 Hz), 114.97, 117.71 (q–t,
1JF = 270.0 Hz, 2JF = 32.5 Hz), 126.68, 128.34, 128.57, 128.83,
128.98, 129.11, 129.71, 129.97, 134.50, 135.63, 140.34, 143.64,
146.32 (t, 2JF = 29.38 Hz), 161.64. MS (ESI) m/z 615.0 (M + 1)+. IR
(KBr) 3062, 3032, 2953, 2858, 1716, 1657, 1517, 1441, 1330 cmꢀ1
Anal. Cacld for C29H22ClF7N2O3: C 56.64, H 3.61, N 4.56; Found: C
56.87, H 3.85, N 4.21.
.
(g) V. Petrov, W. Marshall, J. Fluorine Chem. 128 (2007) 729–735;
(h) K.A. Khistiaey, M.S. Novikov, A.F. Khlebnikov, J. Magull, Tetrahedron Lett. 49
(2008) 1237–1240;
4.3.15. Methyl cis-6-(4-chlorophenyl)-5-(4-methoxyphenyl)-2-
(perfluoropropyl)-3a-phenyl-3a,4,5,6-tetrahydroimidazo[1,5-
b]isoxazole-3-carboxylate (3o)
(i) G.G. Furin, Chem. Heterocycl. Compd. 42 (2006) 285–319.
[3] (a) K.V. Gothelf, K.A. Jorgensen, Chem. Commun. 16 (2000) 1449–1458;
(b) R.F. Jones, J.N. Martin, Chemistry of Heterocyclic Compounds, vol. 59, John
Wiley & Sons Ltd., 2002, pp. 1–81;
White solid; mp: 64.3–66.7 8C; 1H NMR (500 MHz, CDCl3)
d 3.65
(c) K. Rueck-Braun, T.E. Freysoldt, F. Wierschem, Chem. Soc. Rev. 34 (2005) 507–
516;
(d) P.C.R. Pedro Merino, Chimie 8 (2005) 775–788;
(3H, s, CH3O), 3.68 (3H, s, CH3O), 4.16 (1H, d, J = 11.5 Hz, CH2), 4.70
(1H, d, J = 11.5 Hz, CH2), 5.82 (1H, s, CH), 6.71–7.52 (13H. m, Ph).
19F NMR (470 MHz, CDCl3)
d
ꢀ80.44 (t, J = 9.4 Hz, CF3), ꢀ112.14 (m,
(e) H. Pellissier, Tetrahedron 63 (2007) 3235–3285;
(f) V. Nair, T.D. Suja, Tetrahedron 63 (2007) 12247–12275;
(g) J. Revuelta, S. Cicchi, A. Goti, A. Brandi, Synthesis (2007) 485–504.
[4] (a) V. Ja¨ger, P.A. Colinas, in: A. Padwa, W.H. Pearson (Eds.), Synthetic Applications
of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Pro-
ducts, Wiley, New Jersey, 2003, p. 416;
CF2), ꢀ125.68 (m, CF2). 13C NMR (125 MHz, CDCl3)
d 52.26, 55.55,
58.88, 81.94, 88.34, 108.06 (t–t, 1JF = 243.8 Hz, 2JF = 38.8 Hz),
110.33 (t–t, 1JF = 258.8 Hz, 2JF = 32.5 Hz), 117.43, 117.50 (q–t,
1JF = 292.5 Hz, 2JF = 31.9 Hz), 126.59, 127.12, 128.31, 128.60,
128.79, 129.16, 130.76, 134.56, 135.61, 139.85, 140.68, 146.32
(t, 2JF = 30.0 Hz), 154.02, 161.64. MS (ESI) m/z 631.0 (M + 1)+. IR
(b) M. Frederickson, Tetrahedron 53 (1997) 403–425;
(c) U. Chiacchio, A. Rescifina, G. Romeo, in: O.A. Attanasi, D. Spinelli (Eds.),
Targets in Heterocyclic Systems, vol. 1, Italian Society of Chemistry, Rome, 1997,
p. 225;
(d) K.B.G. Torssell, Nitrile Oxides Nitrones and Nitronates in Organic Synthesis,
VCH, Weinheim, 1988;
(e) A. Padwa, W.H. Pearson (Eds.), The Chemistry of Heterocyclic Compounds, Vol.
59, Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry, Wiley, New
York, 2002.
(KBr) 3061, 3000, 2954, 2837, 1716, 1658, 1512, 1441, 1330 cmꢀ1
.
Anal. Cacld for C29H22ClF7N2O4: C 55.21, H 3.51, N 4.44; Found: C
55.59, H 3.77, N 4.26.
4.3.16. Methyl cis-6-(4-nitrophenyl)-2-(perfluoropropyl)-3a-phenyl-
5-p-tolyl-3a,4,5,6-tetrahydroimidazo[1,5-b]isoxazole-3-carboxylate
(3p)
[5] (a) N. Coskun, B. Yilmaz, Syn. Commun. 34 (2004) 1617–1623;
(b) N. Coskun, F. Tirli Tat, O. Ozel Guven, Tetrahedron 57 (2001) 3413–3417;
(c) M. Nishiuchi, H. Sato, N. Umemoto, S. Murakami, Chem. Lett. 37 (2008) 146–
147;
Yellow solid; mp: 79.5–81.3 8C; 1H NMR (500 MHz, CDCl3)
d
(d) M. Lager, P. Dietrich, D. Weinrich, K. Rueck-Braun, Heterocycles 74 (2007)
743–761;
(e) E. Coutouli-Argyropoulou, C. Xatzis, N.G. Argyropoulos, Nucleos. Nucleot.
Nucl. Acids 27 (2008) 84–100;
(f) F. Machetti, L. Cecchi, E. Trogu, F. De Sarlo, Eur. J. Org. Chem. 26 (2007) 4352–
4359;
2.24 (3H, s, CH3), 3.68 (3H, s, CH3O), 4.14 (1H, d, J = 11.5 Hz, CH2),
4.86 (1H, d, J = 11.5 Hz, CH2), 6.08 (1H, s, CH), 6.68–8.07 (13H, m,
Ph). 19F NMR (470 MHz, CDCl3)
d
ꢀ80.47 (t, J = 10.0 Hz, CF3),
ꢀ114.29 (m, CF2), ꢀ125.77 (m, CF2). 13C NMR (125 MHz, CDCl3)
d
20.43, 52.40, 57.38, 83.65, 87.26, 108.23 (t–t, 1JF = 258.5 Hz,
2JF = 35.5 Hz), 110.26 (t–t, 1JF = 258.8 Hz, 2JF = 32.5 Hz), 114.98,
117.60 (q–t, 1JF = 285.0 Hz, 2JF = 31.3 Hz), 123.82, 126.63, 126.99,
128.54, 128.59, 128.66, 129.65, 130.12, 139.87, 143.31, 144.38,
146.15 (t, 2JF = 30.0 Hz), 148.12, 161.48. MS (ESI) m/z 626.0
(M + 1)+. IR (KBr) 3035, 2960, 2854, 1734, 1660, 1523, 1442,
1349 cmꢀ1. Anal. Cacld for C29H22F7N3O5: C 55.69, H 3.55, N 6.72;
Found: C 55.49, H 3.50, N 6.47.
(g) C. Pillard, V. Desvergnes, S. Py, Tetrahedron Lett. 48 (2007) 6209–6213.
[6] For some examples, see:
(a) K. Funabiki, T. Ishihar, H. Yamanak, J. Fluorine Chem. 71 (1995) 5–7;
(b) W.V. Murray, D. Francois, A. Maden, I. Turchi, J. Org. Chem. 72 (2007) 3097–
3099;
(c) S.A. Popov, N.V. Chukanov, G.V. Romanenko, T.V. Rybalova, Y.V. Gatilov, V.A.
Reznikov, J. Heterocycl. Chem. 43 (2006) 277–291;
(d) Y. Shen, J. Zheng, Y. Huang, Synthesis (1985) 970–971;
(e) J.P. Be´gue´, D. Bonnet-Delpon, T. Lequeux, Tetrahedron Lett. 34 (1993) 3279–
3282;
ˇ
´ ˇ
(f) S. Man, M. Necas, J.-P. Bouillon, H. Baillia, D. Harakat, M. Potacek, Tetrahedron
61 (2005) 2387–2393;
(g) S.J. Coats, J.S. Link, D. Gauthier, D.J. Hlasta, Org. Lett. 7 (2005) 1469–1472;
(h) P. He, S. Zhu, Mini-Rev. Org. Chem. 1 (2004) 417–435.
[7] (a) N.A. LeBel, J.J. Whang, J. Am. Chem. Soc. 81 (1959) 6334–6335;
(b) N. Coskun, D. Su˝ mengen, Syn. Commun. 23 (1993) 1699–1706;
(c) N. Coskun, O. Asutay, Chim. Acta Turc 25 (1997) 69–72;
(d) N. Coskun, O. Asutay, Chim. Acta Turc 27 (1999) 17–23.
[8] (a) B.C. Hamper, Org. Synth. 70 (1992) 246–255;
Acknowledgements
The authors are grateful to the National Natural Science
Foundation of China (20872088), Leading Academic Discipline
Project of Shanghai Municipal Education Commission and the
Foundation of Education Commission of Shanghai Municipality
(Nos. 08ZZ44 and J50102) for their financial support.
´
(b) O. Jeannin, M. Fourmigue, Chem. Eur. J. 12 (2006) 2994–3005.
[9] (a) K.V. Gothelf, K.A. Jørgensen, Chem. Rev. 98 (1998) 863–909;
(b) Y. Tomioka, C. Nagahiro, Y. Nomura, H. Maruoka, J. Heterocycl. Chem. 40
(2003) 121–127;
References
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[1] (a) K. Burger, U. Wucherpfenning, E. Brunner, Adv. Heterocycl. Chem. 60 (1994)
1–64;
[10] CCDC-651153 (3a) 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: +44 1223 336 033 or deposit@ccdc.cam.
ac.uk.;
(b) R. Filler, in: R.E. Banks (Ed.), Organofluorine Chemicals and Their Industrial
Applications, Ellis Horwood, Chichester, 1979;
(c) R. Filler, Y. Kobayashi, Biomedical Aspects of Fluorine Chemistry, Kodansha &
Elsevier Biomedical, Tokyo, 1982;
˚
˚
˚
Unit cell parameters (3a): a: 10.8599 A; b: 10.9551 A; c: 11.3368 A; alpha:
(d) J.T. Welch, Tetrahedron 43 (1987) 3123–3197;
90.300; beta: 110.034; gamma: 106.2780; space group: P-1.