Combinatorial synthesis of isoxazole library and their liquid crystalline properties

Article abstract of DOI:10.1016/j.tet.2006.11.005

Six types of isoxazoles including 60 molecules were synthesized using combinatorial synthesis on solid support in a parallel fashion. Highly regioselective 1,3-dipolar cycloaddition of the nitrile oxides to the triple bond of the solid-attached ethynylben

Full text of DOI:10.1016/j.tet.2006.11.005

Tetrahedron 63 (2007) 652–665
Combinatorial synthesis of isoxazole library and
their liquid crystalline properties
b
b
Masahiro Tanaka,a Takeharu Haino,a, Keiko Ideta, Kanji Kubo,
*
Akira Morib and Yoshimasa Fukazawaa,
*
aDepartment of Chemistry, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima,
Hiroshima 739-8526, Japan
bInstitute for Materials Chemistry and Engineering, Kyushu University Kasuga, Fukuoka 816-8580, Japan
Received 21 April 2006; revised 31 October 2006; accepted 2 November 2006
Available online 17 November 2006
Abstract—Six types of isoxazoles including 60 molecules were synthesized using combinatorial synthesis on solid support in a parallel
fashion. Highly regioselective 1,3-dipolar cycloaddition of the nitrile oxides to the triple bond of the solid-attached ethynylbenzamides
gave isoxazoles on solid support in good yield. Thirty molecules of them exhibited mesomorphic properties. The combination of molecular
mechanics calculations and X-ray diffraction experiments of 2g and 3g revealed that the smectic phase of 2g had a bilayer structure, whereas
3g showed a monolayer liquid crystalline phase. These are supported in comparison with the single crystal structures of 2g and 3g.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
bearing an alkoxy chain at one end of the molecules and a
polar group at the other end were limited.6
Liquid crystals are partially ordered, anisotropic fluids, ther-
modynamically located between the solid state and the iso-
tropic liquid. Liquid crystalline phases represent intriguing
states of soft matter, combining order and mobility on a
molecular level.1 These unique phases create fascinating
systems, which respond to external (magnetic, electronic,
chemical, or mechanical) stimuli by finding a new configu-
ration.2 Thus, liquid crystalline materials have had great
impact on recent development of mobile information tech-
nologies with numerous applications in optoelectric devices.
Combinatorial chemistry is one of the most promising tools
for searching the desired functional compounds. Recently,
liquid crystalline libraries of troponoid7 and benzenoid am-
ides8 were prepared on solid support. In our previous report,
we have systematically investigated the substitution effect
on mesomorphic behaviors of anisometric 3,5-diphenyl
isoxazole-based compounds having a cyano group using
combinatorial chemistry.9 In this paper, we report the exten-
sive investigation of liquid crystalline properties for combi-
natorial library of 3,5-disubstituted isoxazoles.
Classical rod-like liquid crystalline molecules are composed
of anisometric units and flexible alkyl chains. Phenyl, biphe-
nyl, terphenyl, cyclohexyl, etc., are often incorporated as an
anisometric core. In recent years, many unique mesogens
have been reported. Troponoid, expanded poly aromatic,
metal-containing aromatic, fullerene-containing, self-
assembling, and hydrogen-bonded mesogens3 have been
developed with their unique functions. Among them,
bent-shaped (banana-shaped) liquid crystalline molecules
show unique chiral mesogenic phases.4 3,5-Disubstituted
isoxazole derivatives5 formally belong to the class of the
bent-shaped molecules; however, they exhibit classical
nematic and smectic mesophases. Structure–property rela-
tionships in isoxazole liquid crystals still remain fairly un-
charted. In particular, unsymmetrical diphenyl isoxazoles
1,3-Dipolar cycloaddition of nitrile oxide to triple bond is
one of the most potential synthetic ways for the construction
of an isoxazole core. In recent years, a number of solid-phase
synthesis of isoxazoles via 1,3-dipolar cycloaddition have
been reported.10 We applied this method to the combinato-
rial synthesis of the isoxazole library using polymer sup-
ported phenylacetylene. Our strategy for the synthesis of
the isoxazole liquid crystals on the solid support is outlined
in Figure 1.
Phenylacetylene unit is immobilized on a polymer support
by the amide linkage, which can be easily cleaved by acid
catalysis and simultaneously converted to cyano group.
The cycloaddition of nitrile oxides on solid support having
a variety of alkoxy substituents provides isoxazoles 1 and
2 after removal from the solid support. Isoxazoles 3–6 are
prepared by benzoylation of the resin-bound isoxazoles
having a hydroxyl group, followed by cleavage from solid
* Corresponding authors. Tel.: +81 824 24 7403; fax: +81 824 24 0724;
e-mail addresses: haino@sci.hiroshima-u.ac.jp; fukazawa@sci.hiroshima-u.
ac.jp
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.11.005

M. Tanaka et al. / Tetrahedron 63 (2007) 652–665
653
O
O
N
R1
R2
N
H
HOOC
R3
polymer support
R4
R1= O-n-CnH2n+1 or OH
R2, R3, R4= H or O-n-CnH2n+1 (n=1~10)
O
O
N
N
O
R2
NC
NC
R1
O
R3
R4
1: 3-cyano, R1= O-n-CnH2n+1
2: 4-cyano, R1= O-n-CnH2n+1
3: R2= R4= H, R3= O-n-CnH2n+1
4: R2= R3= O-n-CnH2n+1, R4= H
5: R2= R4= O-n-CnH2n+1, R3= H
6: R2= R3= R4= O-n-CnH2n+1
Figure 1. Synthetic strategy of isoxazole liquid crystal on solid support.
support. Isoxazole libraries 1–6 can allow us to carry out
the systematic evaluation of the substitution effect on meso-
morphism.
of the Fmoc group by treatment with piperidine in DMF,
the condensation reaction of ethynylbenzoic acid 8 or 9
with N,N0-diisopropylcarbodiimide (DIC) and 1-hydroxy-
benzotriazole (HOBt) gave the corresponding products 10
and 11. Resins 10 and 11 smoothly reacted with the nitrile
oxides, generated in situ upon treatment of hydroximinoyl
chlorides 12a–j11 and 13 with triethylamine, to provide the
resin-bound diphenyl isoxazole 14a–j, 15a–j, and 16
(Scheme 1). Completion of the cycloaddition reactions
was monitored by the disappearance of acetylene C–H
band that appeared around 3286 cmꢀ1 using FTIR spectro-
scopy. Trifluoromethanesulfonic anhydride worked nicely
2. Results and discussion
2.1. Library synthesis
Parallel synthesis of the isoxazole library on solid support
was carried out using parallel synthesizer MiniBlock. Rink
resin 7 was selected as a solid support. After the removal
Y1
O
Fmoc
1) 20%piperidine/DMF 1 hr.
O
O
Y2
2)
O
NH
NH
OMe
Y1 HOBt, DIC, DMF 24 hr.
HO
OMe
Y2
8: Y1 = H, Y2 = C CH
9: Y1 = C CH, Y2 = H
OMe
OMe
7
10: Y1 = H, Y2 = C CH
11: Y1 = C CH, Y2= H
Z1
O
O
HON
Cl
Z2
R1
NH
OMe
12a-j: R1 = O-n-CnH2n+1 (n = 1–10)
13: R1 = OTBS
Et3N, CH2Cl2 24 hr.
OMe
14a-j: Z1 = H, Z2
O
N
=
O-n-CnH2n+1
O
N
15a-j: Z1
=
Z2 = H
O-n-CnH2n+1
O
N
16: Z1 =
Z2 = H
OTBS
Scheme 1.

654
M. Tanaka et al. / Tetrahedron 63 (2007) 652–665
1
to cleave the linkage to liberate the desired isoxazoles 1a–j
or 2a–j into the solution (Scheme 2). After quick purification
of the crude products by column chromatography, the isox-
azoles were furnished in good yield (Table 1).
members 1a–6j were characterized by H and 13C NMR
spectroscopies, high-resolution mass spectrometry, and
elemental analysis.
2.2. Mesomorphic behavior
O
N
X2
X1
Tf2O, pyridine
CH2Cl2 3 hr.
14a-j, 15a-j
The phase transition temperatures and the thermal behavior
of compounds 1a–6j were investigated by polarized optical
microscopy and differential scanning calorimetric (DSC)
measurements. The results are summarized in Tables 1
and 2. Mesomorphic behaviors were found in compounds
2, whereas compounds 1 were not mesomorphic. This should
be due to the larger molecular dipole of compounds 2 pro-
duced by the presence of the cyano group at para-position.
The CN group of compounds 1 made molecular breadth
wider to decrease the thermal stability of mesomorphic
phases. Compounds 2 showed nematic (N) and smectic A
(SmA) phases; the N phase was characterized by the obser-
vation of schlieren textures, and the SmA phase was as-
signed by the observation of fan textures. Shorter chained
compounds 2a–f displayed an N phase, whereas a SmA
phase was observed in longer chained compounds 2i and
O-n-CnH2n+1
1a-j: X = H, X = CN
2a-j: X11 = CN, 2X2 = H
Scheme 2.
The tert-butyldimethylsilyl (TBS) group of 16 was removed
upon treatment with tetrabutylammonium fluoride. The con-
densation reaction of benzoic acid derivatives 17a–j, 18a–j,
19a–j, and 20a–j with N,N0-diisopropylcarbodiimide in the
presence of N,N-dimethylaminopyridine gave support-
bound isoxazoles 21a–j, 22a–j, 23a–j, and 24a–j. Liberation
of isoxazoles from the solid support upon treatment with
trifluoromethanesulfonic anhydride gave the desired isox-
azoles 3a–j, 4a–j, 5 a–j, and 6a–j (Scheme 3). All library
Table 1. Isolated yields and transition temperatures of isoxazoles 1 and 2a
R1
Yield (%)
Transition temp (ꢁC)
R1
Yield (%)
Transition temp (ꢁC)
1a
1b
1c
1d
1e
1f
1g
1h
1i
OCH3
72
85
49
64
77
61
88
62
71
65
Cr 159 Iso
Cr 157 Iso
Cr 138 Iso
Cr 131 Iso
Cr 116 Iso
Cr 112 Iso
Cr 109 Iso
Cr 110 Iso
Cr 114 Iso
Cr 112 Iso
2a
2b
2c
2d
2e
2f
OCH3
90
83
82
66
83
69
67
58
74
68
Cr 164 (12.1) N 223 (0.3) Iso
Cr 128 (26.8) N 199 (0.3) Iso
OC2H5
OC3H7
OC4H9
OC5H11
OC6H13
OC7H15
OC8H17
OC9H19
OC10H21
OC2H5
OC3H7
OC4H9
OC5H11
OC6H13
OC7H15
OC8H17
OC9H19
OC10H21
Cr 134 (26.4) [SmA 120b] N 178 (0.2) Iso
Cr 126 (27.8) N 185 (0.4) Iso
Cr 116 (29.2) N 180b Iso
Cr 112 (38.6) N 178 (0.6) Iso
Cr 113 (35.0) SmA 159 (0.1) N 178 (0.4) Iso
Cr 112 (31.4) SmA 168 (0.1) N 177 (0.1) Iso
Cr 92 (42.5) SmA 176 (2.5) Iso
Cr 93 (29.5) SmA 173 (3.4) Iso
2g
2h
2i
1j
2jc
a
Cr, crystals; N, a nematic phase; SmA, a smectic A phase; Iso, isotropic liquid. The transition temperatures and enthalpy changes (kJ/mol) shown in paren-
theses were obtained during the first heating process. [] means monotropic transition temperatures, which were obtained by cooling.
Data could not be determined from DSC.
b
c
A mixture of compound 2j and its regioisomer was reported.6
R2
O
N
O
R3
O
1) TBAF, THF 1 hr.
16
R4
O
R2
2)
O
NH
OMe
HOOC
R3
DIC, DMAP, DMF 24 hr.
R4
17a-j:R2= H, R3 = O-n-C H2n+1,R4 = H
,nR3 = O-n-CnH2n+1, R4 = H
21a-j: R2 = H, R3 = O-n-CnH2n+1, R4 = H
18a-j:R2 = O-n-CnH
19a-j: R2 = O-n-CnH2n+1 , R3 = H, R4 = O-n-CnH2n+1
OMe
22a-j: R2 = O-n-CnH
, R3 = O-n-CnH2n+1, R4 = H
23a-j: R2 = O-n-CnH2n+1, R3 = H, R4 = O-n-CnH2n+1
2n+1, R3 = O-n-CnH2n+1, R4 = O-n-CnH2n+1
24a-j: R2 = O-n-CnH2n+1
2n+1, R3 = O-n-CnH2n+1, R4 = O-n-CnH2n+1
20a-j: R2 = O-n-CnH2n+1
O N
O
R
2
Tf2O, pyridine
O
NC
CH2Cl2 3 hr.
R
3
R4
3a-j: R2 = H, R3 = O-n-CnH2n+1, R4 = H
4a-j: R2 = O-n-CnH
, R3 = O-n-CnH2n+1, R4 = H
5a-j: R2 = O-n-CnH2n+1, R3 = H, R4 = O-n-C H2n+1
6a-j: R2 = O-n-CnH2n+1
2n+1, R3 = O-n-CnH2n+1, nR4 = O-n-CnH2n+1
Scheme 3.

M. Tanaka et al. / Tetrahedron 63 (2007) 652–665
Table 2. Isolated yields and transition temperatures of isoxazoles 3–6a
655
R2
R3
R4
Yield (%)
Transition temp (ꢁC)
3a
3b
3c
3d
3e
3f
3g
3h
3i
H
H
H
H
H
H
H
H
OCH3
OC2H5
OC3H7
OC4H9
OC5H11
OC6H13
OC7H15
OC8H17
OC9H19
OC10H21
OCH3
OC2H5
OC3H7
OC4H9
OC5H11
OC6H13
OC7H15
OC8H17
OC9H19
OC10H21
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
99
99
99
99
99
86
99
84
99
44
68
92
99
80
48
66
82
82
71
99
99
99
31
56
99
52
34
36
71
97
84
99
89
39
79
62
55
46
84
89
Cr 213 (36.3) N 352 Dec
Cr 187 (42.9) N 366 Dec
Cr 154 (28.1) SmA 221b N 355 Dec
Cr 159 (33.0) SmA 262b N 356 Dec
Cr 138 (25.8) SmA 278b N 340 Dec
Cr 130 (57.2) SmA 300b N 328 Dec
Cr 121 (27.4) SmA 291b N 304 Dec
Cr 116 (27.7) SmA 310b N 313 Dec
Cr 121 (49.2) SmA 318 Dec
Cr 118 (41.5) SmA 300 Dec
Cr 225 (45.6) N 284 (0.2) Iso
Cr 189 (43.5) SmA 193b N 250 (0.6) Iso
Cr 182 (35.6) SmA 222 (1.2) N 228 (0.4) Iso
Cr 172 (34.9) SmA 220 (4.0) Iso
Cr 159 (35.2) SmA 215 (4.9) Iso
Cr 156 (33.9) SmA 205 (2.2) Iso
Cr 152 (32.9) SmA 206 (2.3) Iso
Cr 151 (39.0) SmC 157b SmA 203 (4.0) Iso
Cr 147 (39.7) SmC 153b SmA 192 (3.6) Iso
Cr 145 (41.0) SmC 159b SmA 188 (3.7) Iso
Cr 223 Iso
Cr 194 Iso
Cr 175 Iso
Cr 152 Iso
Cr 144 Iso
Cr 137 Iso
Cr 135 Iso
Cr 141 Iso
Cr 128 Iso
Cr 133 Iso
Cr 214 Iso
Cr 192 Iso
Cr 188 Iso
Cr 139 Iso
Cr 117 Iso
Cr 102 Iso
Cr 102 Iso
H
H
3j
4a
4b
4c
4d
4e
4f
4g
4h
4i
OCH3
OC2H5
OC3H7
OC4H9
OC5H11
OC6H13
OC7H15
OC8H17
OC9H19
OC10H21
OCH3
OC2H5
OC3H7
OC4H9
OC5H11
OC6H13
OC7H15
OC8H17
OC9H19
OC10H21
OCH3
OC2H5
OC3H7
OC4H9
OC5H11
OC6H13
OC7H15
OC8H17
OC9H19
OC10H21
H
H
H
H
4j
5a
5b
5c
5d
5e
5f
5g
5h
5i
OCH3
OC2H5
OC3H7
OC4H9
OC5H11
OC6H13
OC7H15
OC8H17
OC9H19
OC10H21
OCH3
OC2H5
OC3H7
OC4H9
OC5H11
OC6H13
OC7H15
OC8H17
OC9H19
OC10H21
H
H
H
H
H
H
H
H
5j
H
6a
6b
6c
6d
6e
6f
6g
6h
6i
OCH3
OC2H5
OC3H7
OC4H9
OC5H11
OC6H13
OC7H15
OC8H17
OC9H19
OC10H21
Cr 109 Iso
Cr 112 Iso
Cr 107 Iso
6j
a
The transition temperatures and enthalpy changes (kJ/mol) shown in parentheses were obtained during the first heating process. The transition temperatures of
5 and 6 were determined by the microscopic observation SmC, a smectic C phase; Dec, decomposition.
Data could not be determined from DSC.
b
2j. Extension of the alkyl chain of 2 produced a SmA phase
2.3. X-ray diffraction study
in which the molecules are more ordered than in an N phase.
These trends suggest that the extension of the flexible alkyl
chains creates well ordered mesomorphic phases.
In order to obtain the structural information of molecular
array in the liquid crystalline phases, the X-ray diffraction
measurements (XRD) of 2g, 3d, 3g, 4g, and 4i were carried
out in the smectic phases. The smectic phase of 2g showed
the layer spacing d value (30.8 A) larger than the calculated
˚
molecular length of 2g (20 A), indicating that the molecules
should interdigitate and form a bilayer structure in the smec-
tic A phase. In contrast, the layer spacing d values of smectic
phases for 3d–4i are consistent with the calculated molecu-
lar lengths (Table 3). This suggested that these molecules
create simple monolayer structures in the smectic phases.
Compounds 3 and 4 exhibit smectic and nematic phases. The
additional benzene rings connected to the ester linkage in-
creased the thermal stability of the liquid crystalline phases
(2 vs 3), indicating that the segregation between the aromatic
units and the flexible chains is well established in the liquid
crystalline phases of 3. The mesophases of 4 are thermally
less stable than those of 3. The presence of the more alkyl
chains at meta-positions on the benzene ring increases the
volumes of the flexible chains due to their dynamic move-
ment; this should disrupt the order of the anisometric layers
to make it less stable. Smectic C (SmC) phases were
observed only in compounds 4h–j, determined from the
observation of broken-fan and schlieren textures. These
compounds have the two long alkyl chains at meta- and
para-position, bringing the slightly tilted arrays of the liquid
crystalline phases. Compounds 5 and 6 are not mesomor-
phic; their bulky chains should interrupt the segregation of
their anisometric units.
˚
2.4. Crystal structures
Crystal structures of 2g9 and 3g13 gave an insight into the
structures of the molecular arrays in the liquid crystalline
phases. In the X-ray crystallography of 2g, the rigid diphenyl
isoxazole cores nicely stack in the antiparallel orientation
due to the strong dipole–dipole interaction between the
cyano groups (Fig. 2). This antiparallel orientation

656
M. Tanaka et al. / Tetrahedron 63 (2007) 652–665
Table 3. Layer spacing d values and calculated molecular lengths of 2, 3,
and 4
solvent signal as internal standard. All NMR spectra were
recorded in CDCl3 unless otherwise indicated. Mass spectra
were recorded with a JEOL JMX-SX 102 mass spectrometer.
IR spectra were measured on a JASCO FT/IR-420S spec-
trometer. Elemental analyses were performed on a Perkin–
Elmer 2400CHN elemental analyzer. The mesomorphic
phase and the transition temperatures were observed by a
polarizing microscope Olympus (BHSP BH-2) equipped
with a hot stage (Linkam TH-600RMS). The enthalpy
changes were measured on a Shimadzu DSC-50 differential
scanning calorimeter. The X-ray diffraction measurements
were carried out with a Rigaku Rint 2100 system using
Ni-filtered Cu Ka radiation at various temperatures. The
measuring temperatures were controlled with a Linkam
HFS-91 hot stage. The X-ray diffraction analysis was
performed with Mac Science DIP2030 or Bruker SMART-
APEX at ambient temperature.
˚
d (A)
Compd
R1
Temp
(ꢁC)b
Molecular
˚
lengths (A)
c
2g
3d
3g
4g
4i
OC7H15
OC4H9
OC7H15
OC7H15
OC9H19
30.8 (SmA)a
23.1 (SmA)a
28.1 (SmA)a
30.9 (SmA)a
31.0 (SmC)a
32.1 (SmA)a
140
240
280
200
152
180
23.1
25.4
28.5
28.4
30.9
a
The mesogenic phases are indicated.
The XRD were measured at the temperatures.
The molecular lengths were calculated by MacroModel V. 6.5 using
b
c
amber* force field.12
All reactions were carried out under an argon atmosphere
unless otherwise noted. THF was freshly distilled from
Na–benzophenone. Dichloromethane (DCM) and dimethyl-
formamide (DMF) were freshly distilled from CaH2.
Column chromatography was performed using Merck silica
gel (70–230 mesh).
4.2. Preparations of benzohydroximoyl chloride 12a–j
4.2.1. 4-Methoxybenzohydroximoyl chloride 12a. See
Ref. 14.
4.2.2. 4-Ethoxybenzohydroximoyl chloride 12b. See
Ref. 15.
Figure 2. Packing of molecules (a) 2g and (b) 3g.
4.2.3. 4-Propoxybenzohydroximoyl chloride 12c. To a
solution of 4-propyloxybenzaldoxime16 (400 mg, 2.2 mmol)
in DMF (2 ml) at 0 ꢁC was added N-chlorosuccinimide
(300 mg, 2.25 mmol). After stirred at room temperature for
1 h, the reaction mixturewas poured into four volumes of wa-
ter and extracted with ether. The organic layer was washed
three times with water, dried over Na2SO4, and concentrated
under vacuum to give the product (430 mg, 91%). The
product prepared in this manner did not require further puri-
fication for conversionto the isoxazoles. 1H NMR (300 MHz,
CDCl3) d 7.77 (d, 2H, J¼9.0 Hz), 6.90 (d, 2H, J¼9.0 Hz),
3.95 (t, 2H, J¼6.6 Hz), 1.77–1.88 (m, 2H), 1.04 (t, 3H,
J¼7.5 Hz).
rationalizes that the bilayer structure of 2g forms in the SmA
phase.
In contrast, the crystal structure of 3g disclosed that the cyano
groups stay away from each other in the antiparallel orienta-
tion; the dipole–dipole interaction of the cyano groups is too
weak to provide the bilayer structure. As a result, the meso-
gens having 4-alkoxybenzene carbonyloxy groups form the
monolayer structures in their smectic phases.
3. Conclusion
We constructed 60 members of the isoxazole library using
combinatorial synthesis on solid support. The isoxazoles 2
and 3 with alkyl chains showed SmA and N phases while
the isoxazoles 4 with two alkyl chains presented SmC phases
in addition to SmA and N phases. Combinatorial synthesis of
liquid crystalline compounds has been shown to be potential
for the systematic investigation for their functions, resulting
from characteristics of their structures.
4.2.4. 4-Butoxybenzohydroximoyl chloride 12d. See
Ref. 17.
4.2.5. 4-Pentyloxybenzohydroximoyl chloride 12e. To
a
solution of 4-pentyloxybenzaldoxime16 (200 mg,
0.96 mmol) in DMF (2 ml) at 0 ꢁC was added N-chloro-
succinimide (133 mg, 1.0 mmol). After stirred at room tem-
perature for 1 h, the reaction mixture was poured into four
volumes of water and extracted with ether. The organic layer
was washed three times with water, dried over Na2SO4, and
concentrated under vacuum to give the product (209 mg,
96%). 1H NMR (300 MHz, CDCl3) d 7.77 (d, 2H, J¼
9.0 Hz), 6.90 (d, 2H, J¼9.0 Hz), 3.99 (t, 2H, J¼6.6 Hz),
1.75–1.85 (m, 2H), 1.35–1.49 (m, 4H), 0.93 (t, 3H, J¼
7.2 Hz).
4. Experimental
4.1. General
1H and 13C NMR spectra were measured with a Varian Mer-
cury 300 or JEOL-Lambda 500 spectrometer using a residual

M. Tanaka et al. / Tetrahedron 63 (2007) 652–665
657
4.2.6. 4-Hexyloxybenzohydroximoyl chloride 12f. To a
solution of 4-hexyloxybenzaldoxime16 (400 mg, 1.8 mmol)
in DMF (2 ml) at 0 ꢁC was added N-chlorosuccinimide
(240 mg, 1.8 mmol). After stirred at room temperature for
1 h, the reaction mixture was poured into four volumes of
water and extracted with ether. The organic layer was
washed three times with water, dried over Na2SO4, and con-
centrated under vacuum to give the product (439 mg, 90%).
1H NMR (300 MHz, CDCl3) d 7.76 (d, 2H, J¼8.7 Hz), 6.90
(d, 2H, J¼8.7 Hz), 3.99 (t, 2H, J¼6.6 Hz), 1.74–1.84 (m,
2H), 1.33–1.48 (m, 6H), 0.91 (t, 3H, J¼6.9 Hz).
(4 ml) at 0 ꢁC was added N-chlorosuccinimide (446 mg,
3.3 mmol). After stirred at room temperature for 1 h, the
reaction mixture was poured into four volumes of water
and extracted with ether. The organic layer was washed three
times with water, dried over Na2SO4, and concentrated
under vacuum to give the product (922 mg, 95%). 1H
NMR (300 MHz, CDCl3) d 7.72 (d, 2H, J¼9.0 Hz), 6.85
(d, 2H, J¼9.0 Hz), 0.98 (s, 9H), 0.22 (s, 6H).
4.3. Preparation of solid-attached phenylacetylene 10
Fmoc-NH-SAL resin (1 g, loading 0.61 mmol/g) was shaken
with 20% piperidine in DMF (10 ml) for 1 h. The resin was
washed with DMF, MeOH, and DCM (10 ml each). Bromo-
phenol blue test indicated the successful Fmoc-deprotection.
After drying in vacuo, the resin was divided into two equal
portions. Each resin portion was swollen in DMF (10 ml,
10 min), and after draining the solvent, m-ethynylbenzoic
acid (145 mg, 0.9 mmol), 1-hydroxybenzotriazole (140 mg,
0.9 mmol), N,N0-diisopropylcarbodiimide (0.2 ml, 1.2 mmol)
and DMF (15 ml) were added. After shaking for 24 h, the
resins were washed with DMF, MeOH, and DCM
(5ꢂ10 ml each).
4.2.7. 4-Heptyloxybenzohydroximoyl chloride 12g. To a
solution of 4-heptyloxybenzaldoxime16 (1 g, 5.17 mmol)
in DMF (5 ml) at 0 ꢁC was added N-chlorosuccinimide
(725 mg, 5.43 mmol). After stirred at room temperature
for 1 h, the reaction mixture was poured into four volumes
of water and extracted with ether. The organic layer was
washed three times with water, dried over Na2SO4, and con-
centrated under vacuum to give the product (1.28 g, 92%).
1H NMR (300 MHz, CDCl3) d 7.77 (d, 2H, J¼9.0 Hz),
6.90 (d, 2H, J¼9.0 Hz), 3.99 (t, 2H, J¼6.6 Hz), 1.75–1.84
(m, 2H), 1.31–1.45 (m, 8H), 0.89 (t, 3H, J¼6.9 Hz).
4.2.8. 4-Octyloxybenzohydroximoyl chloride 12h. To a
solution of 4-octyloxybenzaldoxime16 (450 mg, 1.8 mmol)
in DMF (2 ml) at 0 ꢁC was added N-chlorosuccinimide
(240 mg, 1.8 mmol). After stirred at room temperature for
1 h, the reaction mixture was poured into four volumes of
water and extracted with ether. The organic layer was
washed three times with water, dried over Na2SO4, and con-
centrated under vacuum to give the product (450 mg, 88%).
1H NMR (300 MHz, CDCl3) d 7.76 (d, 2H, J¼8.7 Hz), 6.90
(d, 2H, J¼8.7 Hz), 3.98 (t, 2H, J¼6.6 Hz), 1.74–1.84 (m,
2H), 1.29–1.47 (m, 10H), 0.88 (t, 3H, J¼6.6 Hz).
4.4. Preparation of solid-attached phenylacetylene 11
Fmoc-NH-SAL resin (1 g, loading 0.61 mmol/g) was shaken
with 20% piperidine in DMF (10 ml) for 1 h. The resin was
washed with DMF, MeOH, and DCM (10 ml each). Bromo-
phenol blue test indicated the successful Fmoc-deprotection.
After drying in vacuo, the resin was divided into two equal
portions. Each resin portion was swollen in DMF (10 ml,
10 min), and after draining the solvent, p-ethynylbenzoic
acid (145 mg, 0.9 mmol), 1-hydroxybenzotriazole (140 mg,
0.9 mmol), N,N0-diisopropylcarbodiimide (0.2 ml, 1.2 mmol),
and DMF (15 ml) were added. After shaking for 24 h, the
resins were washed with DMF, MeOH, and DCM
(5ꢂ10 ml each).
4.2.9. 4-Nonyloxybenzohydroximoyl chloride 12i. To a
solution of 4-pentyloxybenzaldoxime16 (200 mg, 0.76 mmol)
in DMF (2 ml) at 0 ꢁC was added N-chlorosuccinimide
(152 mg, 1.1 mmol). After stirred at room temperature for
1 h, the reaction mixture was poured into four volumes of
water and extracted with ether. The organic layer was
washed three times with water, dried over Na2SO4, and con-
centrated under vacuum to give the product (225 mg, 99%).
1H NMR (300 MHz, CDCl3) d 7.77 (d, 2H, J¼8.7 Hz),
6.90 (d, 2H, J¼8.7 Hz), 3.98 (t, 2H, J¼6.6 Hz), 1.77–1.81
(m, 2H), 1.28–1.46 (m, 12H), 0.88 (t, 3H, J¼6.9 Hz).
4.5. General procedure for the preparation of
3,5-diphenyl isoxazoles 1a–j and 2a–j
Twenty portions of the solid-attached phenylacetylenes 10
and 11 (50 mg, 0.03 mmol) were shaken with triethylamine
(0.04 ml) in DCM (1 ml) for 5 min. Solutions of benzo-
hydroximoyl chlorides 12a–j (0.24 mmol each) in DCM
(1 ml each) were added to the resin portions and the mixtures
were shaken for 24 h at room temperature. The resins were
washed with DMF, MeOH, and DCM (5ꢂ10 ml each).
The solid-attached isoxazoles with pyridine (14 ml,
0.18 mmol) and trifluoromethanesulfonic anhydride (10 ml,
0.06 mmol) in DCM (1.5 ml) were shaken for 3 h. After
filtering off the resins, the filtrates were concentrated, and
purified by column chromatography on SiO2 (100% DCM)
to give the isoxazoles 1a–j and 2a–j as white solid.
4.2.10. 4-Decyloxybenzohydroximoyl chloride 12j. To
a solution of 4-decyloxybenzaldoxime16 (550 mg, 2 mmol)
in DMF (2 ml) at 0 ꢁC was added N-chlorosuccinimide
(280 mg, 1.0 mmol). After stirred at room temperature for
1 h, the reaction mixture was poured into four volumes of
water and extracted with ether. The organic layer was
washed three times with water, dried over Na2SO4, and con-
centrated under vacuum to give the product (465 mg, 75%).
1H NMR (300 MHz, CDCl3) d 7.77 (d, 2H, J¼9.0 Hz), 6.90
(d, 2H, J¼9.0 Hz), 3.98 (t, 2H, J¼6.6 Hz), 1.74–1.84 (m,
2H), 1.27–1.51 (m, 14H), 0.88 (t, 3H, J¼6.6 Hz).
4.5.1. 3-(4-Methoxyphenyl)-5-(3-cyanophenyl)-isoxazole
1a. H NMR (300 MHz, CDCl3) d 8.11 (s, 1H), 8.07 (d,
1
1H, J¼7.8 Hz), 7.81 (d, 2H, J¼9.0 Hz), 7.73 (d, 1H, J¼
7.8 Hz), 7.63 (t, 1H, J¼7.8 Hz), 7.02 (d, 2H, J¼9.0 Hz),
6.88 (s, 1H), 3.88 (s, 3H); 13C NMR (75 MHz, CDCl3)
d 167.6, 162.8, 161.3, 133.2, 130.0, 129.7, 129.2, 128.7,
128.2, 121.0, 118.0, 114.4, 113.5, 98.7, 55.4; IR (KBr)
4.2.11. 4-[(tert-Butyldimethylsilyl)oxy]benzohydroxi-
moyl chloride 13. To a solution of 4-[(tert-butyldimethyl-
silyl)oxy]benzaldoxime18 (800 mg, 3.2 mmol) in DMF

658
M. Tanaka et al. / Tetrahedron 63 (2007) 652–665
3121, 2925, 2852, 2229, 1609, 1528, 1433, 1387, 1293,
1255, 1177 cmꢀ1; HRMS (EI+) calcd for C17H12N2O2:
276.0899, found: 276.0895. Anal. Calcd for C17H12N2O2:
C, 73.90; H, 4.38; N, 10.14. Found: C, 73.85; H, 4.70;
N, 9.83.
J¼7.8 Hz), 7.78 (d, 2H, J¼8.7 Hz), 7.73 (d, 1H, J¼7.8 Hz),
7.62 (t, 1H, J¼7.8 Hz), 6.99 (d, 2H, J¼8.7 Hz), 6.87 (s, 1H),
4.01 (t, 2H, J¼6.6 Hz), 1.77–1.84 (m, 2H), 1.32–1.50 (m,
6H), 0.91 (t, 3H, J¼7.5 Hz); 13C NMR (75 MHz, CDCl3)
d 167.5, 162.9, 160.9, 133.2, 130.0, 129.7, 129.2, 128.8,
128.2, 120.7, 118.0, 114.9, 113.5, 98.7, 68.2, 31.6, 29.1,
25.7, 22.6, 14.0; IR (KBr) 3126, 2952, 2924, 2855, 2230,
1611, 1529, 1438, 1389, 1293, 1254, 1178 cmꢀ1; HRMS
(EI+) calcd for C22H22N2O2: 346.1681, found: 346.1680.
Anal. Calcd for C22H22N2O2$0.2hexane: C, 76.62; H,
6.87; N, 7.70. Found: C, 76.43; H, 7.14; N, 7.75.
4.5.2. 3-(4-Ethoxyphenyl)-5-(3-cyanophenyl)-isoxazole
1b. H NMR (300 MHz, CDCl3) d 8.10 (s, 1H), 8.06 (d,
1
1H, J¼7.8 Hz), 7.78 (d, 2H, J¼9.0 Hz), 7.73 (d, 1H, J¼
7.8 Hz), 7.61 (t, 1H, J¼7.8 Hz), 6.99 (d, 2H, J¼9.0 Hz),
6.87 (s, 1H), 4.01 (q, 2H, J¼6.9 Hz), 1.45 (t, 3H, J¼
6.9 Hz); 13C NMR (75 MHz, CDCl3) d 167.5, 162.9,
160.7, 133.2, 130.0, 129.7, 129.2, 128.8, 128.2, 120.8,
118.0, 114.9, 113.5, 98.7, 63.6, 14.8; IR (KBr) 3123, 2981,
2925, 2226, 1613, 1529, 1440, 1387, 1293, 1252,
1177 cmꢀ1; HRMS (EI+) calcd for C18H14N2O2: 290.1055,
found: 290.1057. Anal. Calcd for C18H14N2O2$0.1hexane:
C, 74.68; H, 5.15; N, 9.42. Found: C, 74.40; H, 4.95; N, 9.03.
4.5.7. 3-(4-Heptyloxyphenyl)-5-(3-cyanophenyl)-isoxa-
zole 1g. H NMR (300 MHz, CDCl3) d 8.11 (s, 1H), 8.07
1
(d, 1H, J¼7.8 Hz), 7.79 (d, 2H, J¼8.7 Hz), 7.73 (d, 1H, J¼
7.8 Hz), 7.63 (t, 1H, J¼7.8 Hz), 7.00 (d, 2H, J¼8.7 Hz), 6.87
(s, 1H), 4.02 (t, 2H, J¼6.6 Hz), 1.77–1.86 (m, 2H), 1.29–
1.50 (m, 8H), 0.90 (t, 3H, J¼7.2 Hz); 13C NMR (75 MHz,
CDCl3) d 167.5, 162.9, 160.9, 133.2, 130.0, 129.7, 129.2,
128.8, 128.2, 120.7, 118.0, 115.0, 113.5, 98.7, 68.2, 31.9,
29.2, 29.0, 26.0, 22.6, 14.1; IR (KBr) 3124, 2961, 2912,
2854, 2234, 1612, 1530, 1436, 1392, 1301, 1264,
1177 cmꢀ1; HRMS (EI+) calcd for C23H24N2O2: 360.1838,
found: 360.1843. Anal. Calcd for C23H24N2O2$0.1hexane:
C, 76.70; H, 6.85; N, 7.68. Found: C, 76.54; H, 7.15; N, 7.46.
4.5.3. 3-(4-Propoxyphenyl)-5-(3-cyanophenyl)-isoxazole
1c. H NMR (300 MHz, CDCl3) d 8.10 (s, 1H), 8.07 (d,
1
1H, J¼7.8 Hz), 7.79 (d, 2H, J¼9.0 Hz), 7.73 (d, 1H, J¼
7.8 Hz), 7.63 (t, 1H, J¼7.8 Hz), 7.00 (d, 2H, J¼9.0 Hz),
6.87 (s, 1H), 3.99 (t, 2H, J¼6.6 Hz), 1.79–1.91 (m, 2H),
1.06 (t, 3H, J¼7.5 Hz); 13C NMR (75 MHz, CDCl3)
d 167.6, 162.9, 160.9, 133.2, 130.0, 129.7, 129.2, 128.8,
128.2, 120.8, 118.0, 115.0, 113.6, 98.7, 69.7, 22.5,
10.5; IR (KBr) 3101, 2964, 2876, 2233, 1612, 1529, 1439,
1387, 1293, 1252, 1180 cmꢀ1; HRMS (EI+) calcd for
C19H16N2O2: 304.1212, found: 304.1210. Anal. Calcd for
C19H16N2O2$0.4toluene$0.2H2O: C, 75.94; H, 5.73; N,
8.12. Found: C, 75.58; H, 5.55; N, 8.04.
4.5.8. 3-(4-Octyloxyphenyl)-5-(3-cyanophenyl)-isoxazole
1h. H NMR (300 MHz, CDCl3) d 8.10 (s, 1H), 8.06 (d,
1
1H, J¼7.8 Hz), 7.78 (d, 2H, J¼8.7 Hz), 7.73 (d, 1H, J¼
7.8 Hz), 7.63 (t, 1H, J¼7.8 Hz), 6.99 (d, 2H, J¼8.7 Hz),
6.87 (s, 1H), 4.01 (t, 2H, J¼6.6 Hz), 1.79–1.84 (m, 2H),
1.29–1.50 (m, 10H), 0.89 (t, 3H, J¼7.2 Hz); 13C NMR
(75 MHz, CDCl3) d 167.5, 162.9, 160.9, 133.2, 130.0,
129.7, 129.2, 128.8, 128.2, 120.7, 118.0, 115.0, 113.6,
98.7, 68.2, 31.8, 29.3, 29.2ꢂ2, 26.0, 22.7, 14.1; IR (KBr)
3123, 2960, 2921, 2854, 2236, 1616, 1533, 1437, 1390,
4.5.4. 3-(4-Butoxyphenyl)-5-(3-cyanophenyl)-isoxazole
1d. H NMR (300 MHz, CDCl3) d 8.10 (s, 1H), 8.07 (d,
1
1H, J¼7.8 Hz), 7.79 (d, 2H, J¼9.0 Hz), 7.73 (d, 1H, J¼
7.8 Hz), 7.63 (t, 1H, J¼7.8 Hz), 7.00 (d, 2H, J¼9.0 Hz),
6.87 (s, 1H), 4.02 (t, 2H, J¼6.6 Hz), 1.76–1.83 (m, 2H),
1.48–1.58 (m, 2H), 1.06 (t, 3H, J¼7.5 Hz); 13C NMR
(75 MHz, CDCl3) d 167.5, 162.9, 160.9, 133.2, 130.0,
129.7, 129.2, 128.8, 128.2, 120.7, 118.0, 114.9, 113.5,
98.7, 67.8, 31.2, 19.2, 13.8; IR (KBr) 3116, 2963, 2941,
2876, 2232, 1610, 1527, 1433, 1390, 1295, 1255,
1178 cmꢀ1; HRMS (EI+) calcd for C20H18N2O2: 318.1368,
found: 318.1371. Anal. Calcd for C20H18N2O2$0.05CH2Cl2:
C, 74.64; H, 5.65; N, 8.68. Found: C, 74.47; H, 5.31; N, 8.46.
1300, 1268, 1178 cmꢀ1
;
HRMS (EI+) calcd for
C24H26N2O2: 374.1994, found: 374.1998. Anal. Calcd for
C24H26N2O2: C, 76.98; H, 7.00; N, 7.48. Found: C, 76.75;
H, 7.27; N, 7.20.
4.5.9. 3-(4-Nonyloxyphenyl)-5-(3-cyanophenyl)-isoxazole
1i. 1H NMR (300 MHz, CDCl3) d 8.11 (s, 1H), 8.06 (d, 1H,
J¼7.8 Hz), 7.78 (d, 2H, J¼8.7 Hz), 7.73 (d, 1H, J¼7.8 Hz),
7.62 (t, 1H, J¼7.8 Hz), 6.99 (d, 2H, J¼8.7 Hz), 6.87 (s, 1H),
4.01 (t, 2H, J¼6.6 Hz), 1.78–1.83 (m, 2H), 1.28–1.50 (m,
12H), 0.90 (t, 3H, J¼7.2 Hz); 13C NMR (75 MHz, CDCl3)
d 167.5, 162.9, 160.9, 133.2, 130.0, 129.7, 129.2, 128.8,
128.2, 120.7, 118.0, 115.0, 113.5, 98.7, 68.2, 31.9, 29.5,
29.4, 29.2ꢂ2, 26.0, 22.7, 14.1; IR (KBr) 3121, 2958, 2922,
2850, 2235, 1613, 1532, 1436, 1390, 1296, 1263,
1176 cmꢀ1; HRMS (EI+) calcd for C25H28N2O2: 388.2151,
found: 388.2150. Anal. Calcd for C25H28N2O2$0.2hexane:
C, 77.56; H, 7.65; N, 6.90. Found: C, 77.38; H, 7.76; N, 6.62.
4.5.5. 3-(4-Pentyloxyphenyl)-5-(3-cyanophenyl)-isoxa-
zole 1e. H NMR (300 MHz, CDCl3) d 8.10 (s, 1H), 8.06
1
(d, 1H, J¼7.8 Hz), 7.78 (d, 2H, J¼8.4 Hz), 7.73 (d, 1H, J¼
7.8 Hz), 7.62 (t, 1H, J¼7.8 Hz), 7.00 (d, 2H, J¼8.4 Hz), 6.87
(s, 1H), 4.02 (t, 2H, J¼6.6 Hz), 1.77–1.87 (m, 2H), 1.37–
1.49 (m, 4H), 0.94 (t, 3H, J¼7.5 Hz); 13C NMR (75 MHz,
CDCl3) d 167.5, 162.9, 160.9, 133.2, 130.0, 129.7, 129.2,
128.8, 128.2, 120.7, 118.0, 114.9, 113.5, 98.7, 68.2, 28.9,
28.2, 22.4, 14.0; IR (KBr) 3103, 2972, 2936, 2869, 2232,
1609, 1530, 1431, 1390, 1296, 1261, 1178 cmꢀ1; HRMS
(EI+) calcd for C21H20N2O2: 332.1525, found: 332.1523.
Anal. Calcd for C21H20N2O2$0.05CH2Cl2: C, 75.10; H,
6.02; N, 8.32. Found: C, 75.45; H, 6.16; N, 7.93.
4.5.10. 3-(4-Decyloxyphenyl)-5-(3-cyanophenyl)-isoxa-
zole 1j. H NMR (300 MHz, CDCl3) d 8.11 (s, 1H), 8.06
1
(d, 1H, J¼7.8 Hz), 7.78 (d, 2H, J¼8.7 Hz), 7.73 (d, 1H, J¼
7.8 Hz), 7.62 (t, 1H, J¼7.8 Hz), 6.99 (d, 2H, J¼8.7 Hz), 6.87
(s, 1H), 4.01 (t, 2H, J¼6.6 Hz), 1.77–1.86 (m, 2H), 1.28–
1.54 (m, 14H), 0.88 (t, 3H, J¼6.9 Hz); 13C NMR
(75 MHz, CDCl3) d 167.5, 162.9, 160.9, 133.2, 130.0,
129.7, 129.2, 128.8, 128.2, 120.7, 118.0, 115.0, 113.5,
4.5.6. 3-(4-Hexyloxyphenyl)-5-(3-cyanophenyl)-isoxazole
1f. 1H NMR (300 MHz, CDCl3) d 8.10 (s, 1H), 8.06 (d, 1H,

M. Tanaka et al. / Tetrahedron 63 (2007) 652–665
659
98.7, 68.2, 31.9, 29.5, 29.4, 29.3, 29.2, 26.0, 22.7, 14.1; IR
(KBr) 3131, 2953, 2916, 2850, 2232, 1611, 1531, 1436,
1390, 1299, 1262, 1177 cmꢀ1; HRMS (EI+) calcd for
C26H30N2O2: 402.2307, found: 402.2306. Anal. Calcd for
C26H30N2O2: C, 77.58; H, 7.51; N, 6.96. Found: C, 77.39;
H, 7.69; N, 6.83.
14.0; IR (KBr) 3139, 2962, 2926, 2858, 2224, 1607, 1531,
1499, 1434, 1290, 1252, 1181 cmꢀ1; HRMS (EI+) calcd
for C21H20N2O2: 332.1525, found: 332.1524. Anal. Calcd
for C21H20N2O2$0.2MeCN: C, 75.46; H, 6.10; N, 9.05.
Found: C, 75.32; H, 5.75; N, 9.17.
4.5.16. 3-(4-Hexyloxyphenyl)-5-(4-cyanophenyl)-isoxa-
1
4.5.11. 3-(4-Methoxyphenyl)-5-(4-cyanophenyl)-isoxa-
zole 2f. H NMR (300 MHz, CDCl3) d 7.93 (d, 2H, J¼
1
zole 2a. H NMR (300 MHz, CDCl3) d 7.94 (d, 2H, J¼
8.7 Hz), 7.77–7.80 (m, 4H), 6.99 (d, 2H, J¼8.7 Hz), 6.91
(s, 1H), 4.01 (t, 2H, J¼6.6 Hz), 1.76–1.86 (m, 2H), 1.32–
1.50 (m, 6H), 0.91 (t, 3H, J¼6.9 Hz); 13C NMR (75 MHz,
CDCl3) d 167.8, 162.9, 160.9, 132.8, 131.3, 128.2, 126.2,
120.7, 118.2, 115.0, 113.5, 99.4, 68.2, 31.6, 29.1, 25.7,
22.6, 14.0; IR (KBr) 3135, 2953, 2920, 2855, 2228, 1611,
1528, 1501, 1431, 1288, 1254, 1173 cmꢀ1; HRMS (EI+)
calcd for C22H22N2O2: 346.1681, found: 346.1681. Anal.
Calcd for C22H22N2O2: C, 76.28; H, 6.40; N, 8.09. Found:
C, 76.21; H, 6.72; N, 7.98.
8.7 Hz), 7.80 (d, 2H, J¼9.0 Hz), 7.79 (d, 2H, J¼8.7 Hz),
7.01 (d, 2H, J¼9.0 Hz), 6.91 (s, 1H), 3.88 (s, 3H); 13C
NMR (75 MHz, CDCl3) d 167.9, 162.9, 161.3, 132.8,
131.2, 128.2, 126.2, 121.0, 118.2, 114.4, 113.5, 99.4,
55.4; IR (KBr) 3109, 2963, 2840, 2230, 1611, 1530, 1500,
1431, 1297, 1254, 1178 cmꢀ1; HRMS (EI+) calcd for
C17H12N2O2: 276.0899, found: 276.0899. Anal. Calcd for
C17H12N2O2$0.25H2O: C, 72.72; H, 4.49; N, 9.98. Found:
C, 72.98; H, 4.42; N, 9.80.
4.5.12. 3-(4-Ethoxyphenyl)-5-(4-cyanophenyl)-isoxazole
2b. 1H NMR (300 MHz, CDCl3) d 7.93 (d, 2H, J¼8.7 Hz),
7.76–7.81 (m, 4H), 6.99 (d, 2H, J¼8.7 Hz), 6.90 (s, 1H),
4.10 (q, 2H, J¼6.9 Hz), 1.45 (t, 3H, J¼6.9 Hz); 13C NMR
(75 MHz, CDCl3) d 167.8, 162.9, 160.7, 132.8, 131.3,
128.2, 126.2, 120.8, 118.2, 114.9, 113.5, 99.4, 63.6, 14.7;
IR (KBr) 3107, 2997, 2938, 2886, 2231, 1611, 1529, 1499,
1437, 1296, 1254, 1179 cmꢀ1; HRMS (EI+) calcd for
C18H14N2O2: 290.1055, found: 290.1059. Anal. Calcd for
C18H14N2O2: C, 74.47; H, 4.86; N, 9.65. Found: C, 74.63;
H, 4.66; N, 9.62.
4.5.17. 3-(4-Heptyloxyphenyl)-5-(4-cyanophenyl)-isoxa-
1
zole 2g. H NMR (300 MHz, CDCl3) d 7.94 (d, 2H, J¼
8.7 Hz), 7.76–7.80 (m, 4H), 6.99 (d, 2H, J¼8.7 Hz), 6.91
(s, 1H), 4.01 (t, 2H, J¼6.6 Hz), 1.77–1.86 (m, 2H), 1.31–
1.57 (m, 8H), 0.90 (t, 3H, J¼6.9 Hz); 13C NMR (75 MHz,
CDCl3) d 167.8, 162.9, 160.9, 132.8, 131.3, 128.2, 126.2,
120.7, 118.2, 115.0, 113.5, 99.4, 68.2, 31.8, 29.2, 29.0,
26.0, 22.6, 14.1; IR (KBr) 3136, 2943, 2925, 2869, 2228,
1612, 1531, 1498, 1433, 1294, 1256, 1179 cmꢀ1; HRMS
(EI+) calcd for C23H24N2O2: 360.1838, found: 360.1835.
Anal. Calcd for C23H24N2O2$0.25hexane: C, 77.03; H,
7.26; N, 7.33. Found: C, 76.93; H, 7.13; N, 7.69.
4.5.13. 3-(4-Propoxyphenyl)-5-(4-cyanophenyl)-isoxa-
1
zole 2c. H NMR (300 MHz, CDCl3) d 7.94 (d, 2H, J¼
4.5.18. 3-(4-Octyloxyphenyl)-5-(4-cyanophenyl)-isoxa-
1
9.0 Hz), 7.77–7.81 (m, 4H), 7.00 (d, 2H, J¼9.0 Hz), 6.91
(s, 1H), 3.99 (t, 2H, J¼6.6 Hz), 1.79–1.91 (m, 2H), 1.06 (t,
3H, J¼7.5 Hz); 13C NMR (75 MHz, CDCl3) d 167.8,
162.9, 160.9, 132.8, 131.3, 128.2, 126.2, 120.7, 118.2,
115.0, 113.5, 99.4, 69.6, 22.5, 10.5; IR (KBr) 3109, 2973,
2933, 2876, 2229, 1611, 1530, 1498, 1432, 1298, 1261,
1176 cmꢀ1; HRMS (EI+) calcd for C19H16N2O2: 304.1212,
found: 304.1206. Anal. Calcd for C19H16N2O2: C, 74.98;
H, 5.30; N, 9.20. Found: C, 74.78; H, 4.92; N, 9.06.
zole 2h. H NMR (300 MHz, CDCl3) d 7.94 (d, 2H, J¼
8.7 Hz), 7.76–7.81 (m, 4H), 6.99 (d, 2H, J¼8.7 Hz), 6.91
(s, 1H), 4.01 (t, 2H, J¼6.6 Hz), 1.76–1.86 (m, 2H), 1.29–
1.47 (m, 10H), 0.89 (t, 3H, J¼6.9 Hz); 13C NMR
(75 MHz, CDCl3) d 167.8, 162.9, 160.9, 132.8, 131.3,
128.2, 126.2, 120.7, 118.2, 115.0, 113.5, 99.4, 68.2, 31.8,
29.3, 29.2ꢂ2, 26.0, 22.7, 14.1; IR (KBr) 3099, 2953, 2925,
2855, 2228, 1610, 1530, 1498, 1430, 1293, 1255,
1177 cmꢀ1; HRMS (EI+) calcd for C24H26N2O2: 374.1994,
found: 374.1989. Anal. Calcd for C24H26N2O2$
0.125CH2Cl2: C, 75.24; H, 6.87; N, 7.27. Found: C, 74.91;
H, 7.24; N, 6.96.
4.5.14. 3-(4-Butoxyphenyl)-5-(4-cyanophenyl)-isoxazole
2d. 1H NMR (300 MHz, CDCl3) d 7.93 (d, 2H, J¼8.7 Hz),
7.77–7.81 (m, 4H), 6.99 (d, 2H, J¼8.7 Hz), 6.91 (s, 1H),
4.02 (t, 2H, J¼6.6 Hz), 1.75–1.85 (m, 2H), 1.48–1.58 (m,
2H), 0.99 (t, 3H, J¼7.5 Hz); 13C NMR (75 MHz, CDCl3)
d 167.8, 162.9, 160.9, 132.8, 131.3, 128.2, 126.2, 120.7,
118.2, 115.0, 113.5, 99.4, 67.9, 31.2, 19.2, 13.8; IR (KBr)
3110, 2959, 2926, 2874, 2228, 1611, 1531, 1499, 1433,
4.5.19. 3-(4-Nonyloxyphenyl)-5-(4-cyanophenyl)-isoxa-
1
zole 2i. H NMR (300 MHz, CDCl3) d 7.93 (d, 2H, J¼
8.7 Hz), 7.76–7.81 (m, 4H), 6.99 (d, 2H, J¼8.7 Hz), 6.90
(s, 1H), 4.01 (t, 2H, J¼6.6 Hz), 1.76–1.86 (m, 2H), 1.28–
1.49 (m, 12H), 0.88 (t, 3H, J¼6.9 Hz); 13C NMR
(75 MHz, CDCl3) d 167.8, 162.9, 160.9, 132.8, 131.3,
128.2, 126.2, 120.7, 118.2, 115.0, 113.5, 99.4, 68.2, 31.9,
29.5, 29.4, 29.2ꢂ2, 26.0, 22.7, 14.1; IR (KBr) 3118, 2952,
2917, 2853, 2240, 1617, 1531, 1504, 1441, 1295, 1250,
1178 cmꢀ1; HRMS (EI+) calcd for C25H28N2O2: 388.2151,
found: 388.2151. Anal. Calcd for C25H28N2O2: C, 77.29;
H, 7.26; N, 7.21. Found: C, 77.26; H, 7.52; N, 7.06.
1297, 1260, 1177 cmꢀ1
C20H18N2O2: 318.1368, found: 318.1364. Anal. Calcd for
C20H18N2O2: C, 75.45; H, 5.70; N, 8.80. Found: C, 75.81;
H, 5.59; N, 8.75.
;
HRMS (EI+) calcd for
4.5.15. 3-(4-Pentyloxyphenyl)-5-(4-cyanophenyl)-isoxa-
1
zole 2e. H NMR (300 MHz, CDCl3) d 7.94 (d, 2H, J¼
8.7 Hz), 7.77–7.80 (m, 4H), 6.99 (d, 2H, J¼8.7 Hz), 6.91
(s, 1H), 4.02 (t, 2H, J¼6.6 Hz), 1.80–1.85 (m, 2H), 1.38–
1.48 (m, 4H), 0.94 (t, 3H, J¼7.2 Hz); 13C NMR (75 MHz,
CDCl3) d 167.8, 162.9, 160.9, 132.8, 131.3, 128.2, 126.2,
120.7, 118.2, 115.0, 113.5, 99.4, 68.2, 28.9, 28.2, 22.4,
4.5.20. 3-(4-Decyloxyphenyl)-5-(4-cyanophenyl)-isoxa-
zole 2j. H NMR (300 MHz, CDCl3) d 7.93 (d, 2H, J¼
1
8.7 Hz), 7.76–7.81 (m, 4H), 6.99 (d, 2H, J¼8.7 Hz), 6.91
(s, 1H), 4.01 (t, 2H, J¼6.6 Hz), 1.76–1.83 (m, 2H), 1.28–

660
M. Tanaka et al. / Tetrahedron 63 (2007) 652–665
1.49 (m, 14H), 0.88 (t, 3H, J¼6.9 Hz); 13C NMR (75 MHz,
CDCl3) d 167.8, 162.9, 160.9, 132.8, 131.3, 128.2, 126.2,
120.7, 118.2, 115.0, 113.5, 99.4, 68.2, 31.9, 29.6, 29.5,
29.4, 29.3, 29.2, 26.0, 22.7, 14.1; IR (KBr) 3121, 2955,
2920, 2851, 2234, 1611, 1528, 1502, 1437, 1292, 1254,
1177 cmꢀ1; HRMS (EI+) calcd for C26H30N2O2: 402.2307,
found: 402.2305. Anal. Calcd for C26H30N2O2: C, 77.89;
H, 7.96; N, 6.61. Found: C, 77.95; H, 7.92; N, 6.88.
4.6.3. 3-[4-(4-Propoxybenzoyloxy)phenyl]-5-(4-cyano-
phenyl)-isoxazole 3c. H NMR (300 MHz, CDCl3) d 8.16
1
(d, 2H, J¼9.0 Hz), 7.91–7.98 (m, 4H), 7.80 (d, 2H, J¼
9.0 Hz), 7.36 (d, 2H, J¼9.0 Hz), 6.99 (d, 2H, J¼9.0 Hz),
6.97 (s, 1H), 4.02 (t, 2H, J¼6.6 Hz), 1.83–1.90 (m, 2H),
1.07 (t, 3H, J¼7.5 Hz); 13C NMR (125 MHz, CDCl3)
d 168.3, 164.6, 163.8, 162.6, 152.8, 132.9, 132.4, 131.1,
128.1, 126.3, 126.0, 122.6, 121.2, 118.1, 114.4, 113.7,
99.6, 69.8, 22.5, 10.4; IR (KBr) 3127, 2965, 2872, 2226,
1720, 1602, 1509, 1436, 1257, 1213, 1172 cmꢀ1; HRMS
(FAB+) calcd for C26H21N2O4 (M+H+): 425.1501, found:
425.1504. Anal. Calcd for C26H20N2O2$0.05CH2Cl2: C,
72.98; H, 4.73; N, 6.53. Found: C, 72.58; H, 4.78; N, 6.92.
4.6. General procedure for the preparation of
3,5-diphenyl isoxazoles 3a–j, 4a–j, 5a–j, and 6a–j
Forty portions of the solid-attached phenylacetylene 11
(50 mg, 0.03 mmol) were shaken with triethylamine
(0.04 ml) in DCM (1 ml) for 5 min. Solutions of 4-[(tert-
butyldimethylsilyl)oxy]benzohydroximoyl chloride 13
(0.24 mmol each) in DCM (1 ml each) were added to the
resin portions and the mixtures were shaken for 24 h at
room temperature. The resins were washed with DMF,
MeOH, and DCM (5ꢂ10 ml each). After drying in vacuo,
the resins were swollen in THF (1 ml, 30 min each). THF
solutions of TBAF (24 mg, 0.09 ml each) were added to the
resin portions, and the mixtures were stirred for 1 h. The
resins were washed with DMF, MeCN, and DCM (5ꢂ
10 ml each). Benzoic acids 17a–j,19 18a–j,20 19a–j,21 and
20a–j22 (0.24 mmol each), N,N0-diisopropylcarbodiimide
(0.05 ml, 0.3 mmol each), DMAP (11 mg, 0.09 mmol
each), and DMF (1.5 ml each) were added to the resin por-
tions. After shaking for 24 h at room temperature, the resins
were washed with DMF, MeCN, and DCM (5ꢂ10 ml each).
The polymer-attached isoxazoles with pyridine (14 ml,
0.18 mmol) and trifluoromethanesulfonic anhydride (10 ml,
0.06 mmol) in DCM (1.5 ml) were shaken for 4 h. After fil-
tering off the resins, the filtrates were concentrated, and pu-
rified by column chromatography on SiO2 (100% DCM) to
give the isoxazoles 3a–j, 4a–j, 5a–j, and 6a–j as white solid.
4.6.4. 3-[4-(4-butoxybenzoyloxy)phenyl]-5-(4-cyano-
phenyl)-isoxazole 3d. H NMR (300 MHz, CDCl3) d 8.16
1
(d, 2H, J¼9.3 Hz), 7.96 (d, 2H, J¼8.7 Hz), 7.93 (d, 2H, J¼
8.7 Hz), 7.80 (d, 2H, J¼9.0 Hz), 7.36 (d, 2H, J¼9.0 Hz),
6.99 (d, 2H, J¼9.3 Hz), 6.97 (s, 1H), 4.06 (t, 2H, J¼
6.6 Hz), 1.77–1.87 (m, 2H), 1.46–1.59 (m, 2H), 1.00 (t, 3H,
J¼7.2 Hz); 13C NMR (75 MHz, CDCl3) d 168.3, 164.7,
163.8, 162.6, 152.7, 132.9, 132.4, 131.1, 128.1, 126.3,
126.0, 122.6, 121.1, 118.2, 114.4, 113.7, 99.6, 68.0, 31.1,
19.2, 13.8; IR (KBr) 3126, 2944, 2875, 2226, 1721, 1602,
1509, 1435, 1257, 1213, 1173 cmꢀ1; HRMS (FAB+) calcd
for C27H23N2O4 (M+H+): 439.1658, found: 439.1662.
Anal. Calcd for C27H22N2O2: C, 73.96; H, 5.06; N, 6.39.
Found: C, 73.98; H, 5.16; N, 6.28.
4.6.5. 3-[4-(4-Pentyloxybenzoyloxy)phenyl]-5-(4-cyano-
phenyl)-isoxazole 3e. H NMR (300 MHz, CDCl3) d 8.16
1
(d, 2H, J¼9.0 Hz), 7.96 (d, 2H, J¼8.7 Hz), 7.92 (d, 2H, J¼
8.7 Hz), 7.80 (d, 2H, J¼8.7 Hz), 7.35 (d, 2H, J¼8.7 Hz),
6.99 (d, 2H, J¼9.0 Hz), 6.97 (s, 1H), 4.05 (t, 2H, J¼
6.6 Hz), 1.79–1.88 (m, 2H), 1.37–1.50 (m, 4H), 0.95 (t,
3H, J¼6.9 Hz); 13C NMR (75 MHz, CDCl3) d 168.2,
164.7, 163.7, 162.6, 152.7, 132.9, 132.4, 131.1, 128.0,
126.3, 126.0, 122.6, 121.1, 118.2, 114.4, 113.7, 99.6, 68.3,
28.8, 28.1, 22.4, 14.0; IR (KBr) 3128, 2947, 2872, 2228,
1720, 1603, 1511, 1435, 1260, 1216, 1174 cmꢀ1; HRMS
(FAB+) calcd for C28H25N2O4 (M+H+): 453.1814, found:
453.1815. Anal. Calcd for C28H24N2O2$0.1MeCN: C,
74.18; H, 5.36; N, 6.44. Found: C, 74.28; H, 4.98; N, 6.63.
4.6.1. 3-[4-(4-Methoxybenzoyloxy)phenyl]-5-(4-cyano-
phenyl)-isoxazole 3a. H NMR (300 MHz, CDCl3) d 8.18
1
(d, 2H, J¼9.0 Hz), 7.92–7.98 (m, 4H), 7.80 (d, 2H, J¼
8.7 Hz), 7.36 (d, 2H, J¼8.7 Hz), 7.01 (d, 2H, J¼9.0 Hz),
6.97 (s, 1H), 3.91 (s, 3H); 13C NMR (125 MHz, CDCl3)
d 168.3, 164.6, 164.1, 162.6, 152.8, 132.9, 132.4, 131.0,
128.1, 126.3, 126.1, 122.6, 121.5, 118.1, 114.0, 113.8,
99.6, 55.5; IR (KBr) 3127, 2975, 2924, 2847, 2229, 1731,
1604, 1510, 1433, 1258, 1213, 1163 cmꢀ1; HRMS (FAB+)
calcd for C24H17N2O4 (M+H+): 397.1188, found:
397.1187. Anal. Calcd for C24H16N2O2$0.2CH2Cl2$0.2H2O:
C, 70.85; H, 4.49; N, 6.51. Found: C, 71.09; H, 4.17; N, 6.28.
4.6.6. 3-[4-(4-Hexyloxybenzoyloxy)phenyl]-5-(4-cyano-
phenyl)-isoxazole 3f. H NMR (300 MHz, CDCl3) d 8.16
1
(d, 2H, J¼9.0 Hz), 7.96 (d, 2H, J¼8.7 Hz), 7.93 (d, 2H, J¼
8.7 Hz), 7.80 (d, 2H, J¼8.7 Hz), 7.36 (d, 2H, J¼8.7 Hz),
6.99 (d, 2H, J¼9.0 Hz), 6.97 (s, 1H), 4.06 (t, 2H, J¼
6.6 Hz), 1.78–1.88 (m, 2H), 1.33–1.51 (m, 6H), 0.92 (t,
3H, J¼6.9 Hz); 13C NMR (75 MHz, CDCl3) d 168.3,
164.7, 163.8, 162.6, 152.7, 132.9, 132.4, 131.1, 128.1,
126.3, 126.0, 122.6, 121.1, 118.1, 114.4, 113.7, 99.6, 68.4,
31.5, 29.0, 25.6, 22.6, 14.0; IR (KBr) 3127, 2920, 2874,
4.6.2. 3-[4-(4-Ethoxybenzoyloxy)phenyl]-5-(4-cyano-
phenyl)-isoxazole 3b. H NMR (300 MHz, CDCl3) d 8.16
1
(d, 2H, J¼9.0 Hz), 7.91–7.97 (m, 4H), 7.80 (d, 2H, J¼
9.0 Hz), 7.36 (d, 2H, J¼9.0 Hz), 6.99 (d, 2H, J¼9.0 Hz),
6.97 (s, 1H), 4.14 (q, 2H, J¼6.9 Hz), 1.47 (t, 3H, J¼
6.9 Hz); 13C NMR (75 MHz, CDCl3) d 168.3, 164.7,
163.5, 162.6, 152.7, 132.9, 132.4, 131.1, 128.1, 126.3,
126.0, 122.6, 121.2, 118.2, 114.4, 113.7, 99.6, 63.9, 14.7;
IR (KBr) 3124, 2983, 2936, 2224, 1734, 1606, 1509, 1432,
2227, 1721, 1604, 1510, 1435, 1257, 1214, 1173 cmꢀ1
;
HRMS (FAB+) calcd for C29H27N2O4 (M+H+): 467.1971,
found: 467.1973. Anal. Calcd for C29H26N2O2$0.25H2O:
C, 73.95; H, 5.65; N, 5.95. Found: C, 73.79; H, 5.85; N, 5.76.
1257, 1215, 1166 cmꢀ1
;
HRMS (FAB+) calcd for
4.6.7. 3-[4-(4-Heptyloxybenzoyloxy)phenyl]-5-(4-cyano-
phenyl)-isoxazole 3g. H NMR (300 MHz, CDCl3) d 8.15
C25H19N2O4 (M+H+): 411.1345, found: 411.1343. Anal.
Calcd for C25H18N2O2: C, 73.16; H, 4.42; N, 6.83. Found:
C, 72.82; H, 4.78; N, 7.09.
1
(d, 2H, J¼9.0 Hz), 7.95 (d, 2H, J¼8.7 Hz), 7.92 (d, 2H, J¼
8.7 Hz), 7.79 (d, 2H, J¼8.7 Hz), 7.35 (d, 2H, J¼8.7 Hz),

M. Tanaka et al. / Tetrahedron 63 (2007) 652–665
661
6.98 (d, 2H, J¼9.0 Hz), 6.96 (s, 1H), 4.05 (t, 2H, J¼6.6 Hz),
1.78–1.87 (m, 2H), 1.32–1.51 (m, 8H), 0.90 (t, 3H, J¼
6.9 Hz); 13C NMR (75 MHz, CDCl3) d 168.2, 164.6, 163.7,
162.6, 152.7, 132.9, 132.3, 131.1, 128.0, 126.3, 126.0,
122.6, 121.1, 118.1, 114.4, 113.7, 99.6, 68.4, 31.7, 29.1,
29.0, 25.9, 22.6, 14.1; IR (KBr) 3126, 2921, 2850, 2225,
1721, 1602, 1509, 1436, 1257, 1213, 1173 cmꢀ1; HRMS
(FAB+) calcd for C30H29N2O4 (M+H+): 481.2127, found:
481.2126. Anal. Calcd for C30H28N2O2: C, 74.98; H, 5.87;
N, 5.83. Found: C, 74.80; H, 5.99; N, 5.78.
(75 MHz, CDCl3) d 168.3, 164.7, 162.5, 153.8, 152.7,
148.9, 132.9, 131.1, 128.1, 126.3, 126.1, 124.6, 122.6,
121.5, 118.1, 113.7, 112.4, 110.4, 99.6, 56.1ꢂ2; IR (KBr)
3120, 2922, 2850, 2229, 1712, 1595, 1519, 1436, 1278,
1212, 1167, 1143 cmꢀ1
;
HRMS (FAB+) calcd for
C25H19N2O5 (M+H+): 427.1294, found: 427.1298. Anal.
Calcd for C25H18N2O2: C, 70.42; H, 4.25; N, 6.57. Found:
C, 70.21; H, 4.43; N, 6.49.
4.6.12. 3-[4-(3,4-Diethoxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 4b. H NMR (300 MHz, CDCl3)
1
4.6.8. 3-[4-(4-Octyloxybenzoyloxy)phenyl]-5-(4-cyano-
phenyl)-isoxazole 3h. H NMR (300 MHz, CDCl3) d 8.16
d 7.91–7.97 (m, 4H), 7.84 (dd, 1H, J¼8.4, 2.1 Hz), 7.80
(d, 2H, J¼8.7 Hz), 7.68 (d, 1H, J¼2.1 Hz), 7.35 (d, 2H, J¼
8.7 Hz), 6.94–6.97 (m, 2H), 4.15–4.24 (m, 4H), 1.48–1.54
(m, 6H); 13C NMR (75 MHz, CDCl3) d 168.3, 164.7,
162.6, 153.6, 152.7, 148.3, 132.9, 131.1, 128.1, 126.3,
126.1, 124.5, 122.6, 121.2, 118.1, 114.2, 113.7, 111.7,
99.6, 64.7, 64.6, 14.7, 14.6; IR (KBr) 3126, 2983, 2939,
2230, 1720, 1599, 1521, 1434, 1281, 1213, 1170,
1
(d, 2H, J¼9.0 Hz), 7.96 (d, 2H, J¼8.7 Hz), 7.93 (d, 2H, J¼
8.7 Hz), 7.80 (d, 2H, J¼8.7 Hz), 7.36 (d, 2H, J¼8.7 Hz),
6.97–7.00 (m, 3H), 4.05 (t, 2H, J¼6.6 Hz), 1.78–1.88 (m,
2H), 1.25–1.48 (m, 10H), 0.90 (t, 3H, J¼6.6 Hz); 13C
NMR (75 MHz, CDCl3) d 168.3, 164.7, 163.7, 162.6,
152.7, 132.9, 132.4, 131.1, 128.1, 126.3, 126.0, 122.6,
121.1, 118.2, 114.4, 113.7, 99.6, 68.4, 31.8, 29.3, 29.2,
29.1, 26.0, 22.6, 14.1; IR (KBr) 3127, 2919, 2851, 2227,
1721, 1604, 1509, 1436, 1257, 1213, 1173 cmꢀ1; HRMS
(FAB+) calcd for C31H31N2O4 (M+H+): 495.2284, found:
495.2283. Anal. Calcd for C31H30N2O2$0.5H2O: C, 73.94;
H, 6.20; N, 5.56. Found: C, 73.92; H, 6.03; N, 5.82.
1133 cmꢀ1
;
HRMS (FAB+) calcd for C27H23N2O5
(M+H+): 455.1607, found: 455.1606. Anal. Calcd for
C27H22N2O2$0.25H2O: C, 70.65; H, 4.94; N, 6.10. Found:
C, 70.60; H, 5.04; N, 6.10.
4.6.13. 3-[4-(3,4-Dipropoxybenzoyloxy)phenyl]-5-(4-cya-
nophenyl)-isoxazole 4c. 1H NMR (300 MHz, CDCl3)
d 7.91–7.97 (m, 4H), 7.83 (dd, 1H, J¼8.4, 2.1 Hz), 7.80
(d, 2H, J¼8.7 Hz), 7.68 (d, 1H, J¼2.1 Hz), 7.35 (d, 2H, J¼
8.7 Hz), 6.97 (s, 1H), 6.95 (d, 1H, J¼8.4 Hz), 4.03–4.09 (m,
4H), 1.83–1.97 (m, 4H), 1.05–1.11 (m, 6H); 13C NMR
(75 MHz, CDCl3) d 168.3, 164.8, 162.6, 154.0, 152.7,
148.7, 132.9, 131.1, 128.0, 126.3, 126.0, 124.5, 122.6,
121.1, 118.1, 114.7, 113.7, 112.0, 99.6, 70.8, 70.5, 22.5,
22.4, 10.5, 10.4; IR (KBr) 3128, 2967, 2878, 2225, 1726,
1596, 1519, 1432, 1279, 1199, 1170, 1142 cmꢀ1; HRMS
(FAB+) calcd for C29H27N2O5 (M+H+): 483.1920, found:
483.1915. Anal. Calcd for C29H26N2O2: C, 72.18; H, 5.43;
N, 5.81. Found: C, 72.23; H, 5.54; N, 5.77.
4.6.9. 3-[4-(4-Nonyloxybenzoyloxy)phenyl]-5-(4-cyano-
phenyl)-isoxazole 3i. H NMR (300 MHz, CDCl3) d 8.15
1
(d, 2H, J¼8.7 Hz), 7.96 (d, 2H, J¼8.7 Hz), 7.92 (d, 2H, J¼
8.7 Hz), 7.80 (d, 2H, J¼8.7 Hz), 7.35 (d, 2H, J¼8.7 Hz),
6.97–7.00 (m, 3H), 4.05 (t, 2H, J¼6.6 Hz), 1.78–1.85 (m,
2H), 1.28–1.48 (m, 12H), 0.89 (t, 3H, J¼6.6 Hz); 13C
NMR (75 MHz, CDCl3) d 168.2, 164.7, 163.7, 162.5,
152.7, 132.9, 132.3, 131.0, 128.0, 126.3, 126.0, 122.6,
121.0, 118.2, 114.3, 113.6, 99.6, 68.3, 31.9, 29.5, 29.3,
29.2, 29.1, 26.0, 22.7, 14.1; IR (KBr) 3127, 2918, 2848,
2233, 1729, 1607, 1510, 1434, 1260, 1209, 1173 cmꢀ1
;
HRMS (FAB+) calcd for C32H32N2O4 (M+H+): 509.2440,
found: 509.2442. Anal. Calcd for C32H31N2O2$0.2MeCN:
C, 75.30; H, 6.36; N, 5.96. Found: C, 75.41; H, 6.10; N, 5.97.
4.6.14. 3-[4-(3,4-Dibutoxybenzoyloxy)phenyl]-5-(4-cya-
nophenyl)-isoxazole 4d. 1H NMR (300 MHz, CDCl3)
d 7.92–7.98 (m, 4H), 7.83 (dd, 1H, J¼8.4, 1.8 Hz), 7.80
(d, 2H, J¼8.7 Hz), 7.67 (d, 1H, J¼1.8 Hz), 7.36 (d, 2H, J¼
8.7 Hz), 6.97 (s, 1H), 6.95 (d, 1H, J¼8.4 Hz), 4.07–4.13 (m,
4H), 1.80–1.91 (m, 4H), 1.47–1.59 (m, 4H), 0.97–1.03 (m,
6H); 13C NMR (75 MHz, CDCl3) d 168.3, 164.8, 162.6,
154.1, 152.7, 148.7, 132.9, 131.1, 128.1, 126.3, 126.0,
124.5, 122.6, 121.1, 118.1, 114.6, 113.7, 111.9, 99.6, 69.1,
68.8, 31.2, 31.1, 19.2, 19.1, 13.9, 13.8; IR (KBr) 3128,
2957, 2873, 2225, 1726, 1596, 1519, 1432, 1281, 1200,
1170, 1144 cmꢀ1; HRMS (FAB+) calcd for C31H31N2O5
(M+H+): 511.2233, found: 511.2233. Anal. Calcd for
C31H30N2O2: C, 72.92; H, 5.92; N, 5.49. Found: C, 73.07;
H, 5.98; N, 5.44.
4.6.10. 3-[4-(4-Decyloxybenzoyloxy)phenyl]-5-(4-cyano-
phenyl)-isoxazole 3j. H NMR (300 MHz, CDCl3) d 8.16
1
(d, 2H, J¼9.0 Hz), 7.96 (d, 2H, J¼8.7 Hz), 7.93 (d, 2H, J¼
8.7 Hz), 7.80 (d, 2H, J¼8.7 Hz), 7.36 (d, 2H, J¼8.7 Hz),
6.99 (d, 2H, J¼9.0 Hz), 6.97 (s, 1H), 4.05 (t, 2H, J¼
6.6 Hz), 1.78–1.85 (m, 2H), 1.29–1.49 (m, 14H), 0.89 (t,
3H, J¼6.9 Hz); 13C NMR (75 MHz, CDCl3) d 168.2,
164.6, 163.7, 162.6, 152.7, 132.9, 132.3, 131.1, 128.0,
126.3, 126.0, 122.6, 121.1, 118.1, 114.4, 113.7, 99.6, 68.4,
31.9, 29.5, 29.3ꢂ2, 29.1, 26.0, 22.7, 14.1; IR (KBr) 3127,
2918, 2850, 2227, 1721, 1603, 1509, 1436, 1258, 1213,
1173 cmꢀ1
;
HRMS (FAB+) calcd for C33H35N2O4
(M+H+): 523.2597, found: 523.2607. Anal. Calcd for
C32H31N2O2: C, 75.84; H, 6.56; N, 5.36. Found: C, 75.77;
H, 6.62; N, 5.24.
4.6.15. 3-[4-(3,4-Dipentyloxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 4e. H NMR (300 MHz, CDCl3)
1
4.6.11. 3-[4-(3,4-Dimethoxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 4a. H NMR (300 MHz, CDCl3)
d 7.96 (d, 2H, J¼8.7 Hz), 7.93 (d, 2H, J¼8.7 Hz), 7.88
(dd, 1H, J¼8.4, 2.1 Hz), 7.80 (d, 2H, J¼8.7 Hz), 7.68 (d,
1H, J¼2.1 Hz), 7.36 (d, 2H, J¼8.7 Hz), 6.97 (d, 1H, J¼
8.4 Hz), 6.97 (s, 1H), 3.99 (s, 3H), 3.98 (s, 3H); 13C NMR
d 7.92–7.98 (m, 4H), 7.83 (dd, 1H, J¼8.4, 2.1 Hz), 7.80
(d, 2H, J¼8.7 Hz), 7.67 (d, 1H, J¼2.1 Hz), 7.35 (d, 2H, J¼
8.7 Hz), 6.97 (s, 1H), 6.94 (d, 1H, J¼8.4 Hz), 4.06–4.12 (m,
4H), 1.84–1.91 (m, 4H), 1.37–1.52 (m, 8H), 0.92–0.97
(m, 6H); 13C NMR (75 MHz, CDCl3) d 168.3, 164.8,
162.6, 154.1, 152.8, 148.7, 132.9, 131.1, 128.1, 126.3,
1

662
M. Tanaka et al. / Tetrahedron 63 (2007) 652–665
126.1, 124.5, 122.6, 121.1, 118.2, 114.6, 113.7, 111.9, 99.6,
69.4, 69.1, 28.8, 28.7, 28.2, 28.1, 22.4, 14.0; IR (KBr) 3128,
2955, 2858, 2227, 1720, 1595, 1522, 1430, 1284, 1207,
1171, 1146 cmꢀ1; HRMS (FAB+) calcd for C33H35N2O5
(M+H+): 539.2546, found: 539.2546. Anal. Calcd for
C33H34N2O2: C, 73.58; H, 6.36; N, 5.20. Found: C, 73.61;
H, 6.55; N, 5.09.
154.0, 152.7, 148.6, 132.9, 131.0, 128.0, 126.3, 126.0,
124.5, 122.6, 121.0, 118.2, 114.4, 113.6, 111.8, 99.6, 69.3,
69.0, 31.9, 29.6, 29.4, 29.3, 29.1, 29.0, 26.0, 25.9, 22.7,
14.1; IR (KBr) 3128, 2918, 2847, 2227, 1720, 1596, 1523,
1431, 1285, 1205, 1170, 1148 cmꢀ1; HRMS (FAB+) calcd
for C41H51N2O5 (M+H+): 651.3798, found: 651.3792.
Anal. Calcd for C41H50N2O2: C, 75.66; H, 7.74; N, 4.30.
Found: C, 75.70; H, 7.58; N, 4.20.
4.6.16. 3-[4-(3,4-Dihexyloxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 4f. H NMR (300 MHz, CDCl3)
1
4.6.20. 3-[4-(3,4-Didecyloxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 4j. H NMR (300 MHz, CDCl3)
1
d 7.91–7.98 (m, 4H), 7.83 (dd, 1H, J¼8.7, 2.1 Hz), 7.80
(d, 2H, J¼8.7 Hz), 7.67 (d, 1H, J¼2.1 Hz), 7.36 (d, 2H, J¼
8.7 Hz), 6.97 (s, 1H), 6.95 (d, 1H, J¼8.7 Hz), 4.06–4.12 (m,
4H), 1.81–1.92 (m, 4H), 1.34–1.53 (m, 12H), 0.89–0.94 (m,
6H); 13C NMR (75 MHz, CDCl3) d 168.3, 164.8, 162.6,
154.1, 152.8, 148.7, 132.9, 131.1, 128.1, 126.3, 126.0,
124.5, 122.6, 121.1, 118.1, 114.6, 113.7, 111.9, 99.6, 69.4,
69.1, 31.5, 29.1, 29.0, 25.7, 22.6, 14.0; IR (KBr) 3128,
2931, 2857, 2227, 1720, 1595, 1523, 1431, 1284, 1209,
1170, 1147 cmꢀ1; HRMS (FAB+) calcd for C35H39N2O5
(M+H+): 567.2859, found: 567.2856. Anal. Calcd for
C35H38N2O2$0.2MeCN: C, 73.96; H, 6.77; N, 5.36. Found:
C, 73.87; H, 6.68; N, 5.40.
d 7.91–7.97 (m, 4H), 7.83 (dd, 1H, J¼8.7, 2.1 Hz), 7.80
(d, 2H, J¼8.7 Hz), 7.67 (d, 1H, J¼2.1 Hz), 7.35 (d, 2H, J¼
8.7 Hz), 6.97 (s, 1H), 6.94 (d, 1H, J¼8.7 Hz), 4.05–4.12 (m,
4H), 1.81–1.90 (m, 4H), 1.28–1.49 (m, 24H), 0.85–0.91 (m,
6H); 13C NMR (75 MHz, CDCl3) d 168.3, 164.8, 162.6,
154.1, 152.8, 148.7, 132.9, 131.1, 128.1, 126.3, 126.1,
124.5, 122.6, 121.1, 118.1, 114.7, 113.7, 112.0, 99.6, 69.4,
69.1, 31.9, 29.6ꢂ2, 29.4ꢂ2, 29.3, 29.2, 29.0, 26.0ꢂ2,
22.7, 14.1; IR (KBr) 3128, 2918, 2848, 2227, 1721, 1595,
1523, 1431, 1285, 1208, 1170, 1148 cmꢀ1; HRMS (FAB+)
calcd for C43H55N2O5 (M+H+): 679.4111, found:
679.4128. Anal. Calcd for C43H54N2O2: C, 76.07; H, 8.02;
N, 4.13. Found: C, 76.29; H, 8.38; N, 4.36.
4.6.17. 3-[4-(3,4-Diheptyloxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 4g. H NMR (300 MHz, CDCl3)
1
4.6.21. 3-[4-(3,5-Dimethoxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 5a. H NMR (300 MHz, CDCl3)
1
d 7.91–7.98 (m, 4H), 7.83 (dd, 1H, J¼8.7, 2.1 Hz), 7.80
(d, 2H, J¼8.7 Hz), 7.67 (d, 1H, J¼2.1 Hz), 7.35 (d, 2H, J¼
8.7 Hz), 6.97 (s, 1H), 6.94 (d, 1H, J¼8.7 Hz), 4.05–4.12 (m,
4H), 1.81–1.92 (m, 4H), 1.25–1.54 (m, 16H), 0.87–0.92 (m,
6H); 13C NMR (75 MHz, CDCl3) d 168.3, 164.8, 162.6,
154.0, 152.7, 148.7, 132.9, 131.1, 128.1, 126.3, 126.0,
124.5, 122.6, 121.1, 118.1, 114.6, 113.7, 111.9, 99.6, 69.4,
69.1, 31.8, 29.2, 29.0, 26.0, 25.9, 22.6, 14.1; IR (KBr)
3128, 2931, 2855, 2227, 1720, 1595, 1523, 1431, 1284,
d 7.96 (d, 2H, J¼8.7 Hz), 7.94 (d, 2H, J¼8.7 Hz), 7.80 (d,
2H, J¼8.4 Hz), 7.35–7.38 (m, 4H), 6.97 (s, 1H), 6.74 (t,
1H, J¼2.1 Hz), 3.88 (s, 6H); 13C NMR (125 MHz, CDCl3)
d 168.3, 164.7, 162.5, 160.9, 152.6, 132.9, 131.1, 131.0,
128.1, 126.3ꢂ2, 122.5, 118.1, 113.7, 107.8, 106.6, 99.6,
55.7; IR (KBr) 3126, 2981, 2954, 2230, 1738, 1613, 1504,
1428, 1355, 1308, 1209, 1160 cmꢀ1; HRMS (FAB+) calcd
for C25H19N2O5 (M+H+): 427.1294, found: 427.1276.
Anal. Calcd for C25H18N2O2: C, 70.42; H, 4.25; N, 6.57.
Found: C, 70.63; H, 4.34; N, 6.44.
1207, 1170, 1147 cmꢀ1
;
HRMS (FAB+) calcd for
C37H43N2O5 (M+H+): 595.3172, found: 595.3193. Anal.
Calcd for C37H42N2O2: C, 74.72; H, 7.12; N, 4.71. Found:
C, 74.67; H, 7.13; N, 4.66.
4.6.22. 3-[4-(3,5-Diethoxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 5b. H NMR (300 MHz, CDCl3)
1
4.6.18. 3-[4-(3,4-Dioctyloxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 4h. H NMR (300 MHz, CDCl3)
d 7.92–7.97 (m, 4H), 7.80 (d, 2H, J¼8.7 Hz), 7.35 (d, 2H, J¼
8.7 Hz), 7.33 (d, 2H, J¼2.4 Hz), 6.97 (s, 1H), 6.73 (t, 1H, J¼
2.4 Hz), 4.09 (q, 4H, J¼6.9 Hz), 1.44 (t, 6H, J¼6.9 Hz);
13C NMR (75 MHz, CDCl3) d 168.3, 164.8, 162.5, 160.1,
152.5, 132.9, 131.1, 130.1, 128.1, 126.3, 126.2, 122.5,
118.1, 113.7, 108.3, 107.3, 99.6, 63.9, 14.7; IR (KBr)
3126, 2983, 2926, 2881, 2225, 1730, 1593, 1504, 1439,
1348, 1300, 1204, 1169 cmꢀ1; HRMS (FAB+) calcd for
C27H23N2O5 (M+H+): 455.1607, found: 455.1604. Anal.
Calcd for C27H22N2O2: C, 71.35; H, 4.88; N, 6.16. Found:
C, 71.56; H, 5.06; N, 6.11.
1
d 7.92–7.98 (m, 4H), 7.83 (dd, 1H, J¼8.7, 2.1 Hz), 7.80
(d, 2H, J¼8.7 Hz), 7.67 (d, 1H, J¼2.1 Hz), 7.35 (d, 2H, J¼
8.7 Hz), 6.97 (s, 1H), 6.95 (d, 1H, J¼8.7 Hz), 4.05–4.12 (m,
4H), 1.81–1.92 (m, 4H), 1.29–1.54 (m, 20H), 0.86–0.90 (m,
6H); 13C NMR (75 MHz, CDCl3) d 168.3, 164.8, 162.6,
154.0, 152.7, 148.7, 132.9, 131.1, 128.1, 126.3, 126.0,
124.5, 122.6, 121.1, 118.12, 114.6, 113.7, 111.9, 99.6,
69.4, 69.1, 31.8, 29.3, 29.2, 29.1, 29.0ꢂ3, 22.7, 14.1; IR
(KBr) 3128, 2919, 2847, 2226, 1720, 1595, 1523, 1431,
1284, 1206, 1170, 1148 cmꢀ1; HRMS (FAB+) calcd for
C39H47N2O5 (M+H+): 623.3485, found: 623.3481. Anal.
Calcd for C39H46N2O2: C, 75.21; H, 7.44; N, 4.50. Found:
C, 75.13; H, 7.38; N, 4.40.
4.6.23. 3-[4-(3,5-Dipropoxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 5c. H NMR (300 MHz, CDCl3)
1
d 7.92–7.98 (m, 4H), 7.81 (d, 2H, J¼8.7 Hz), 7.36 (d, 2H,
J¼8.7 Hz), 7.33 (d, 2H, J¼2.1 Hz), 6.97 (s, 1H), 6.74 (t,
1H, J¼2.1 Hz), 3.98 (t, 4H, J¼6.6 Hz), 1.78–1.90 (m, 4H),
1.06 (t, 6H, J¼7.2 Hz); 13C NMR (75 MHz, CDCl3)
d 168.3, 164.8, 162.6, 160.4, 152.6, 132.9, 131.1, 130.8,
128.1, 126.3ꢂ2, 122.5, 118.1, 113.8, 108.3, 107.4,
99.6, 70.0, 22.5, 10.5; IR (KBr) 3126, 2965, 2877, 2225,
4.6.19. 3-[4-(3,4-Dinonyloxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 4i. H NMR (300 MHz, CDCl3)
1
d 7.91–7.98 (m, 4H), 7.83 (dd, 1H, J¼8.7, 2.1 Hz), 7.80
(d, 2H, J¼8.7 Hz), 7.67 (d, 1H, J¼2.1 Hz), 7.35 (d, 2H, J¼
8.7 Hz), 6.98 (s, 1H), 6.94 (d, 1H, J¼8.7 Hz), 4.05–4.11 (m,
4H), 1.81–1.92 (m, 4H), 1.28–1.58 (m, 24H), 0.85–0.90 (m,
6H); 13C NMR (75 MHz, CDCl3) d 168.2, 164.8, 162.6,
1730, 1593, 1504, 1436, 1353, 1296, 1199, 1173 cmꢀ1
HRMS (FAB+) calcd for C29H27N2O5 (M+H+): 483.1920,
;

M. Tanaka et al. / Tetrahedron 63 (2007) 652–665
663
found: 483.1921. Anal. Calcd for C29H26N2O2: C, 72.18; H,
5.43; N, 5.81. Found: C, 72.22; H, 5.57; N, 5.83.
4.6.28. 3-[4-(3,5-Dioctyloxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 5h. H NMR (300 MHz, CDCl3)
1
d 7.92–7.98 (m, 4H), 7.81 (d, 2H, J¼8.7 Hz), 7.36 (d, 2H,
J¼8.7 Hz), 7.32 (d, 2H, J¼2.4 Hz), 6.97 (s, 1H), 6.73 (t,
1H, J¼2.4 Hz), 4.00 (t, 4H, J¼6.6 Hz), 1.76–1.83 (m, 4H),
1.25–1.47 (m, 20H), 0.89 (t, 6H, J¼6.6 Hz); 13C NMR
(125 MHz, CDCl3) d 168.4, 164.9, 162.4, 160.4, 152.7,
132.9, 131.1, 130.8, 128.1, 126.3ꢂ2, 122.5, 118.2, 113.8,
108.3, 107.5, 99.6, 68.5, 31.8, 29.3, 29.2ꢂ2, 26.0, 22.7,
14.1; IR (KBr) 3121, 2921, 2851, 2230, 1734, 1595, 1503,
1450, 1351, 1302, 1200, 1160 cmꢀ1; HRMS (FAB+) calcd
for C39H47N2O5 (M+H+): 623.3485, found: 623.3491.
Anal. Calcd for C39H46N2O2: C, 75.21; H, 7.44; N, 4.50.
Found: C, 75.11; H, 7.57; N, 4.50.
4.6.24. 3-[4-(3,5-Dibutoxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 5d. H NMR (300 MHz, CDCl3)
1
d 7.92–7.98 (m, 4H), 7.80 (d, 2H, J¼8.7 Hz), 7.36 (d, 2H,
J¼8.7 Hz), 7.33 (d, 2H, J¼2.4 Hz), 6.97 (s, 1H), 6.73 (t,
1H, J¼2.4 Hz), 4.02 (t, 4H, J¼6.6 Hz), 1.75–1.84 (m, 4H),
1.45–1.56 (m, 4H), 0.99 (t, 6H, J¼7.5 Hz); 13C NMR
(75 MHz, CDCl3) d 168.3, 164.8, 162.5, 160.4, 152.6,
132.9, 131.1, 130.8, 128.1, 126.3, 126.2, 122.5, 118.1,
113.7, 108.3, 107.3, 99.6, 68.1, 31.2, 19.2, 13.8; IR (KBr)
3129, 2957, 2872, 2224, 1733, 1592, 1500, 1438, 1350,
1301, 1209, 1171 cmꢀ1
;
HRMS (FAB+) calcd for
C31H31N2O5 (M+H+): 511.2233, found: 511.2231. Anal.
Calcd for C31H30N2O2: C, 72.92; H, 5.92; N, 5.49. Found:
C, 72.93; H, 6.02; N, 5.47.
4.6.29. 3-[4-(3,5-Dinonyloxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 5i. H NMR (300 MHz, CDCl3)
1
d 7.92–7.98 (m, 4H), 7.81 (d, 2H, J¼8.7 Hz), 7.36 (d, 2H,
J¼8.7 Hz), 7.32 (d, 2H, J¼2.4 Hz), 6.97 (s, 1H), 6.73 (t,
1H, J¼2.4 Hz), 4.01 (t, 4H, J¼6.6 Hz), 1.76–1.85 (m, 4H),
1.28–1.47 (m, 24H), 0.88 (t, 6H, J¼6.6 Hz); 13C NMR
(75 MHz, CDCl3) d 168.3, 164.8, 162.5, 160.4, 152.6,
132.9, 131.1, 130.8, 128.1, 126.3, 126.3, 122.5, 118.1,
113.7, 108.3, 107.3, 99.6, 68.5, 31.9, 29.5, 29.4, 29.2ꢂ2,
26.0, 22.7, 14.1; IR (KBr) 3124, 2922, 2852, 2230, 1734,
1595, 1505, 1450, 1350, 1302, 1200, 1160 cmꢀ1; HRMS
(FAB+) calcd for C41H51N2O5 (M+H+): 651.3798, found:
651.3795. Anal. Calcd for C41H50N2O2: C, 75.66; H, 7.74;
N, 4.30. Found: C, 75.55; H, 7.72; N, 4.30.
4.6.25. 3-[4-(3,5-dipentyloxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 5e. H NMR (300 MHz, CDCl3)
1
d 7.92–7.98 (m, 4H), 7.80 (d, 2H, J¼8.7 Hz), 7.35 (d, 2H, J¼
8.7 Hz), 7.32 (d, 2H, J¼2.4 Hz), 6.97 (s, 1H), 6.73 (t, 1H,
J¼2.4 Hz), 4.01 (t, 4H, J¼6.6 Hz), 1.76–1.86 (m, 4H),
1.36–1.49 (m, 8H), 0.94 (t, 6H, J¼6.6 Hz); 13C NMR
(75 MHz, CDCl3) d 168.3, 164.8, 162.5, 160.3, 152.5,
132.9, 131.0, 130.7, 128.1, 126.3, 126.2, 122.5, 118.1,
113.7, 108.2, 107.2, 99.6, 68.4, 28.8, 28.1, 22.4, 14.0; IR
(KBr) 3127, 2957, 2858, 2232, 1733, 1592, 1501, 1450,
1350, 1303, 1200, 1163 cmꢀ1; HRMS (FAB+) calcd for
C33H35N2O5 (M+H+): 539.2546, found: 539.2540. Anal.
Calcd for C33H34N2O2: C, 73.58; H, 6.36; N, 5.20. Found:
C, 73.61; H, 6.55; N, 5.09.
4.6.30. 3-[4-(3,5-Didecyloxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 5j. H NMR (300 MHz, CDCl3)
1
d 7.92–7.97 (m, 4H), 7.80 (d, 2H, J¼8.7 Hz), 7.35 (d, 2H,
J¼8.7 Hz), 7.32 (d, 2H, J¼2.4 Hz), 6.97 (s, 1H), 6.73 (t,
1H, J¼2.4 Hz), 4.01 (t, 4H, J¼6.6 Hz), 1.75–1.85 (m, 4H),
1.28–1.47 (m, 28H), 0.88 (t, 6H, J¼6.6 Hz); 13C NMR
(75 MHz, CDCl3) d 168.3, 164.8, 162.5, 160.3, 152.5,
132.9, 131.0, 130.7, 128.1, 126.3ꢂ2, 122.5, 118.2, 113.7,
108.2, 107.2, 99.6, 68.4, 31.9, 29.6, 29.5, 29.3ꢂ2, 29.1,
26.0, 22.7, 14.1; IR (KBr) 3123, 2921, 2851, 2229, 1733,
1594, 1503, 1450, 1350, 1302, 1201, 1159 cmꢀ1; HRMS
(FAB+) calcd for C43H55N2O5 (M+H+): 679.4111, found:
679.4116. Anal. Calcd for C43H54N2O2: C, 76.07; H, 8.02;
N, 4.13. Found: C, 75.82; H, 8.05; N, 4.39.
4.6.26. 3-[4-(3,5-Dihexyloxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 5f. H NMR (300 MHz, CDCl3)
1
d 7.92–7.98 (m, 4H), 7.81 (d, 2H, J¼8.7 Hz), 7.36 (d, 2H,
J¼8.7 Hz), 7.32 (d, 2H, J¼2.4 Hz), 6.97 (s, 1H), 6.73 (t,
1H, J¼2.4 Hz), 4.01 (t, 4H, J¼6.6 Hz), 1.76–1.85 (m, 4H),
1.32–1.50 (m, 12H), 0.91 (t, 6H, J¼6.9 Hz); 13C NMR
(125 MHz, CDCl3) d 168.4, 164.8, 162.6, 160.4, 152.6,
132.9, 131.1, 130.8, 128.1, 126.3ꢂ2, 122.5, 118.1, 113.8,
108.3, 107.3, 99.6, 68.5, 31.6, 29.1, 25.7, 22.6, 14.0; IR
(KBr) 3119, 2953, 2856, 2227, 1735, 1596, 1503, 1450,
1350, 1301, 1200, 1163 cmꢀ1; HRMS (FAB+) calcd for
C35H39N2O5 (M+H+): 567.2859, found: 567.2866. Anal.
Calcd for C35H38N2O2: C, 74.18; H, 6.76; N, 4.94. Found:
C, 74.19; H, 6.97; N, 4.94.
4.6.31. 3-[4-(3,4,5-Trimethoxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 6a. H NMR (300 MHz, CDCl3)
1
d 7.96 (d, 2H, J¼8.7 Hz), 7.95 (d, 2H, J¼8.7 Hz), 7.80 (d,
2H, J¼8.7 Hz), 7.47 (s, 2H), 7.36 (d, 2H, J¼8.7 Hz), 6.98
(s, 1H), 3.96 (s, 3H), 3.96 (s, 6H); 13C NMR (125 MHz,
CDCl3) d 168.4, 164.6, 162.5, 153.2, 152.6, 143.1, 132.9,
131.1, 128.1, 126.3, 126.1, 124.0, 122.6, 118.1, 113.8,
107.6, 99.6, 61.0, 56.4; IR (KBr) 3122, 2921, 2851, 2229,
1733, 1594, 1503, 1450, 1350, 1201, 1159 cmꢀ1; HRMS
(FAB+) calcd for C26H21N2O6 (M+H+): 457.1400, found:
457.1418. Anal. Calcd for C26H20N2O2: C, 68.42; H, 4.42;
N, 6.14. Found: C, 68.39; H, 4.50; N, 5.97.
4.6.27. 3-[4-(3,5-Diheptyloxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 5g. H NMR (300 MHz, CDCl3)
1
d 7.92–7.98 (m, 4H), 7.80 (d, 2H, J¼8.7 Hz), 7.36 (d,
2H, J¼8.7 Hz), 7.32 (d, 2H, J¼2.4 Hz), 6.97 (s, 1H), 6.73
(t, 1H, J¼2.4 Hz), 4.01 (t, 4H, J¼6.6 Hz), 1.76–1.85 (m,
4H), 1.32–1.47 (m, 16H), 0.90 (t, 6H, J¼6.6 Hz); 13C
NMR (75 MHz, CDCl3) d 168.3, 164.8, 162.5, 160.3,
152.6, 132.9, 131.1, 130.8, 128.1, 126.3, 126.3, 122.5,
118.2, 113.7, 108.2, 107.3, 99.6, 68.4, 31.8, 29.2, 29.0,
26.0, 22.6, 14.1; IR (KBr) 3120, 2923, 2854, 2227, 1735,
1596, 1503, 1450, 1351, 1301, 1200, 1172 cmꢀ1; HRMS
(FAB+) calcd for C37H43N2O5 (M+H+): 595.3172,
found: 595.3163. Anal. Calcd for C37H42N2O2$0.25MeCN:
C, 74.45; H, 7.12; N, 5.21. Found: C, 74.50; H, 7.34;
N, 5.22.
4.6.32. 3-[4-(3,4,5-Triethoxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 6b. H NMR (300 MHz, CDCl3)
1
d 7.92–7.98 (m, 4H), 7.81 (d, 2H, J¼8.7 Hz), 7.43 (s, 2H),
7.35 (d, 2H, J¼8.7 Hz), 6.97 (s, 1H), 4.12–4.22 (m, 6H),
1.47 (t, 6H, J¼7.2 Hz), 1.39 (t, 3H, J¼7.2 Hz); 13C NMR

664
M. Tanaka et al. / Tetrahedron 63 (2007) 652–665
(75 MHz, CDCl3) d 168.3, 164.7, 162.5, 143.0, 152.8, 152.6,
132.9, 131.1, 128.1, 126.3, 126.2, 123.6, 122.6, 118.1, 113.7,
108.7, 99.6, 69.1, 64.9, 15.6, 14.8; IR (KBr) 3109, 2980,
2929, 2229, 1735, 1593, 1500, 1435, 1340, 1194,
(M+H+): 667.3747, found: 667.3740. Anal. Calcd for
C41H50N2O2: C, 73.85; H, 7.56; N, 4.20. Found: C, 73.89;
H, 7.73; N, 4.14.
1133 cmꢀ1
;
HRMS (FAB+) calcd for C29H27N2O6
4.6.37. 3-[4-(3,4,5-Triheptyloxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 6g. H NMR (300 MHz, CDCl3)
(M+H+): 499.1869, found: 499.1864. Anal. Calcd for
C29H26N2O2: C, 69.87; H, 5.26; N, 5.62. Found: C, 69.72;
H, 5.34; N, 5.56.
1
d 7.92–7.97 (m, 4H), 7.80 (d, 2H, J¼8.7 Hz), 7.42 (s, 2H),
7.34 (d, 2H, J¼8.7 Hz), 6.97 (s, 1H), 4.03–4.09 (m, 6H),
1.73–1.89 (m, 6H), 1.26–1.54 (m, 24H), 0.87–0.91 (m,
9H); 13C NMR (75 MHz, CDCl3) d 168.3, 164.8, 162.5,
153.0, 152.7, 143.2, 132.9, 131.0, 128.1, 126.3, 126.2,
123.5, 122.6, 118.1, 113.7, 108.6, 99.6, 73.6, 69.3, 31.9,
31.8, 30.3, 29.3, 29.2, 29.0, 26.0ꢂ2, 22.6ꢂ2, 14.1ꢂ2; IR
(KBr) 3128, 2923, 2853, 2233, 1733, 1587, 1502, 1432,
4.6.33. 3-[4-(3,4,5-Tripropoxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 6c. H NMR (300 MHz, CDCl3)
1
d 7.92–7.98 (m, 4H), 7.80 (d, 2H, J¼8.7 Hz), 7.43 (s, 2H),
7.35 (d, 2H, J¼8.7 Hz), 6.97 (s, 1H), 4.01–4.08 (m, 6H),
1.74–1.93 (m, 6H), 1.04–1.10 (m, 9H); 13C NMR
(75 MHz, CDCl3) d 168.3, 164.8, 162.5, 153.0, 152.6,
143.2, 132.9, 131.1, 128.1, 126.3, 126.2, 123.5, 122.6,
118.1, 113.7, 108.7, 99.6, 75.2, 70.8, 23.5, 22.6, 10.6,
10.5; IR (KBr) 3125, 2965, 2876, 2231, 1732, 1590, 1502,
1433, 1336, 1196, 1122 cmꢀ1; HRMS (FAB+) calcd for
C32H33N2O6 (M+H+): 541.2339, found: 541.2339. Anal.
Calcd for C32H32N2O2: C, 71.09; H, 5.97; N, 5.18. Found:
C, 71.09; H, 6.08; N, 5.14.
1338, 1192, 1119 cmꢀ1
;
HRMS (FAB+) calcd for
C44H57N2O6 (M+H+): 709.4217, found: 709.4216. Anal.
Calcd for C44H56N2O2: C, 74.55; H, 7.96; N, 3.95. Found:
C, 74.61; H, 8.17; N, 4.12.
4.6.38. 3-[4-(3,4,5-Trioctyloxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 6h. H NMR (300 MHz, CDCl3)
1
d 7.92–7.98 (m, 4H), 7.81 (d, 2H, J¼8.7 Hz), 7.42 (s, 2H),
7.35 (d, 2H, J¼8.7 Hz), 6.97 (s, 1H), 4.03–4.09 (m, 6H),
1.73–1.89 (m, 6H), 1.25–1.57 (m, 30H), 0.86–0.90 (m,
9H); 13C NMR (75 MHz, CDCl3) d 168.3, 164.8, 162.6,
153.0, 152.7, 143.2, 132.9, 131.0, 128.1, 126.3, 126.2,
123.5, 122.6, 118.6, 113.7, 108.6, 99.6, 73.6, 69.3, 31.9,
31.8, 30.3, 29.5, 29.3ꢂ2, 26.1, 22.7ꢂ2, 14.1; IR (KBr)
3137, 2954, 2854, 2227, 1732, 1588, 1500, 1431, 1339,
1202, 1119 cmꢀ1; HRMS (FAB+) calcd for C47H63N2O6
(M+H+): 751.4686, found: 751.4686. Anal. Calcd for
C47H62N2O2$0.5MeCN$0.5EtOAc: C, 73.63; H, 8.34; N,
4.29. Found: C, 74.68; H, 8.55; N, 4.14.
4.6.34. 3-[4-(3,4,5-Tributoxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 6d. H NMR (300 MHz, CDCl3)
1
d 7.92–7.98 (m, 4H), 7.81 (d, 2H, J¼8.7 Hz), 7.42 (s, 2H),
7.35 (d, 2H, J¼8.7 Hz), 6.97 (s, 1H), 4.05–4.10 (m, 6H),
1.71–1.88 (m, 6H), 1.47–1.59 (m, 6H), 0.88–1.02 (m, 9H);
13C NMR (75 MHz, CDCl3) d 168.3, 164.8, 162.6, 153.0,
152.7, 143.2, 132.9, 131.1, 128.1, 126.3, 126.2, 123.5,
122.6, 118.1, 113.7, 108.6, 99.6, 73.2, 69.0, 32.3, 31.3,
19.3, 19.1, 13.9, 13.8; IR (KBr) 3129, 2931, 2871, 2231,
1731, 1592, 1504, 1432, 1337, 1195, 1128 cmꢀ1; HRMS
(FAB+) calcd for C35H39N2O6 (M+H+): 583.2808, found:
583.2811. Anal. Calcd for C35H38N2O2: C, 72.14; H, 6.57;
N, 4.81. Found: C, 72.35; H, 6.61; N, 4.81.
4.6.39. 3-[4-(3,4,5-Trinonyloxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 6i. H NMR (300 MHz, CDCl3)
1
d 7.96 (d, 2H, J¼8.4 Hz), 7.93 (d, 2H, J¼8.4 Hz), 7.80 (d,
2H, J¼8.7 Hz), 7.42 (s, 2H), 7.34 (d, 2H, J¼8.7 Hz), 6.98
(s, 1H), 4.03–4.09 (m, 6H), 1.72–1.88 (m, 6H), 1.28–1.49
(m, 36H), 0.85–0.90 (m, 9H); 13C NMR (75 MHz, CDCl3)
d 168.3, 164.8, 162.5, 153.0, 152.6, 143.1, 132.9, 131.0,
128.1, 126.3, 126.1, 123.4, 122.6, 118.2, 113.7, 108.5,
99.6, 73.6, 69.2, 31.9ꢂ2, 30.3, 29.7, 29.6, 29.4, 29.3, 26.1,
26.0, 22.7ꢂ2, 14.1; IR (KBr) 3136, 2925, 2854, 2226,
1732, 1588, 1500, 1432, 1339, 1202, 1119 cmꢀ1; HRMS
(FAB+) calcd for C50H69N2O6 (M+H+): 793.5156, found:
793.5160. Anal. Calcd for C47H62N2O2$0.5MeCN: C,
75.29; H, 8.61; N, 4.30. Found: C, 75.14; H, 8.81; N, 4.40.
4.6.35. 3-[4-(3,4,5-Tripentyloxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 6e. H NMR (300 MHz, CDCl3)
1
d 7.92–7.98 (m, 4H), 7.80 (d, 2H, J¼8.7 Hz), 7.42 (s, 2H),
7.35 (d, 2H, J¼8.7 Hz), 6.98 (s, 1H), 4.03–4.10 (m, 6H),
1.73–1.89 (m, 6H), 1.37–1.51 (m, 12H), 0.91–0.96 (m,
9H); 13C NMR (75 MHz, CDCl3) d 168.3, 164.8, 162.5,
153.0, 152.6, 143.2, 132.9, 131.0, 128.1, 126.3, 126.2,
123.5, 122.6, 118.1, 113.7, 108.6, 99.6, 73.6, 69.2, 30.0,
28.9, 28.2, 28.1, 22.5, 22.4, 14.1, 14.0; IR (KBr) 3131,
2936, 2871, 2237, 1733, 1588, 1500, 1432, 1341, 1200,
1116 cmꢀ1
;
HRMS (FAB+) calcd for C38H45N2O6
(M+H+): 625.3278, found: 625.3276. Anal. Calcd for
C38H44N2O2: C, 73.05; H, 7.10; N, 4.48. Found: C, 73.02;
H, 7.25; N, 4.33.
4.6.40. 3-[4-(3,4,5-Tridecyloxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 6j. H NMR (300 MHz, CDCl3)
1
d 7.96 (d, 2H, J¼8.4 Hz), 7.94 (d, 2H, J¼8.4 Hz), 7.81 (d,
2H, J¼8.7 Hz), 7.42 (s, 2H), 7.35 (d, 2H, J¼8.7 Hz), 6.98
(s, 1H), 4.03–4.09 (m, 6H), 1.72–1.88 (m, 6H), 1.27–1.49
(m, 42H), 0.85–0.90 (m, 9H); 13C NMR (75 MHz, CDCl3)
d 168.3, 164.8, 162.5, 153.0, 152.6, 143.2, 132.9, 131.0,
128.1, 126.3, 126.2, 123.4, 122.6, 118.1, 113.7, 108.5,
99.6, 73.6, 69.3, 31.9ꢂ2, 30.3, 29.7ꢂ2, 29.6ꢂ2, 29.4,
29.3ꢂ2, 26.1, 26.0, 22.7, 14.1; IR (KBr) 3130, 2920, 2851,
4.6.36. 3-[4-(3,4,5-Trihexyloxybenzoyloxy)phenyl]-5-(4-
cyanophenyl)-isoxazole 6f. H NMR (300 MHz, CDCl3)
1
d 7.92–7.98 (m, 4H), 7.81 (d, 2H, J¼8.7 Hz), 7.42 (s, 2H),
7.35 (d, 2H, J¼8.7 Hz), 6.97 (s, 1H), 4.04–4.09 (m, 6H),
1.72–1.89 (m, 6H), 1.25–1.54 (m, 18H), 0.89–0.93 (m,
9H); 13C NMR (75 MHz, CDCl3) d 168.3, 164.8, 162.6,
153.0, 152.7, 143.2, 132.9, 131.1, 128.1, 126.3, 126.2,
123.5, 122.6, 118.1, 113.7, 108.6, 99.6, 73.6, 69.3, 31.7,
31.5, 30.3, 29.2, 25.7ꢂ2, 22.7, 22.6, 14.1, 14.0; IR (KBr)
3140, 2931, 2859, 2229, 1736, 1588, 1503, 1432, 1337,
1191, 1117 cmꢀ1; HRMS (FAB+) calcd for C41H51N2O6
2234, 1736, 1588, 1502, 1433, 1338, 1191, 1120 cmꢀ1
;
HRMS (FAB+) calcd for C53H75N2O6 (M+H+): 835.5625,
found: 835.5632. Anal. Calcd for C47H62N2O2: C, 76.22;
H, 8.93; N, 3.35. Found: C, 76.55; H, 8.88; N, 3.62.

M. Tanaka et al. / Tetrahedron 63 (2007) 652–665
665
11. Liu, K. C.; Shelton, B. R.; Howe, R. K. J. Org. Chem. 1980, 45,
3916–3918.
References and notes
12. Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.;
Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still,
W. C. J. Comput. Chem. 1990, 11, 440–467.
1. Demus, D.; Goodby, J.; Gray, G. W.; Spiess, H.-W.; Vill, V.
Handbook of Liquid Crystals; VCH: Weinheim, 1998.
€
2. Lagerwall, S.; Dahlgren, A.; Jagemalm, P.; Rudquist, P.;
D’have, K.; Pauwels, H.; Dabrowski, R.; Drzewinski, W. Adv.
13. Crystallographic data for 3g: C30H28N2O4, FW¼480.55,
ꢀ
˚
˚
˚
monoclinic space group P21, a¼8.222(6) A, b¼5.964(5) A,
Funct. Mater. 2001, 11, 87–94; Kirsch, P.; Bremer, M.
Angew. Chem., Int. Ed. 2000, 39, 4216–4235.
3. Hudson, S. A.; Maitlis, P. M. Chem. Rev. 1993, 93, 861–885;
Bruce, D. W. Acc. Chem. Res. 2000, 33, 831–840;
Tschierske, C. J. Mater. Chem. 1998, 8, 1485–1508.
4. Pelzl, G.; Diele, S.; Weissflog, W. Adv. Mater. 2001, 11, 87–94;
Watanabe, J.; Niori, T.; Choi, S. W.; Takanishi, Y.; Takezoe, H.
Jpn. J. Appl. Phys. 1998, 37, L401–L403.
3
ꢁ
˚
c¼50.82(4) A, b¼93.001(14) , V¼2489(3) A , T¼293(2) K,
and Z¼4; of 6781 total unique reflections, 3930 were consid-
ered observed at the level of jFoj > 2:0sjFoj. The structure
was solved by the direct method (Sir 97). Full-matrix least
squares refinements converged to a conventional R factor of
0.093, wR¼0.27, GOF¼0.99. Supplementary crystallographic
data have been deposited at the Cambridge Crystallographic
Data Centre, UK as supplementary publication number
CCDC no. 604935.
5. Brown, D. H.; Styring, P. Liq. Cryst. 2003, 30, 23–30; Gallardo,
H.; Zucco, C.; Da Silva, L. Mol. Cryst. Liq. Cryst. 2002, 373,
181–190; Bartulin, J.; Martinez, R.; Gallardo, H.; Muller, J.;
Taylor, T. R. Mol. Cryst. Liq. Cryst. 1993, 225, 175–182;
Bartulin, J.; Martinez, R.; M€uller, H. J.; Fan, Z. X.; Haase,
W. Mol. Cryst. Liq. Cryst. 1992, 220, 67–75; Barbera, J.;
Cativiela, C.; Serrano, J. L.; Zurbano, M. M. Liq. Cryst.
1992, 11, 887–897; Seguel, C. G.; Borchers, B.; Haase, W.;
Aguilera, C. Liq. Cryst. 1992, 11, 899–903; Iglesias, R.;
Serrano, J. L.; Sierra, T. Liq. Cryst. 1997, 22, 37–46.
6. Barbera, J.; Gimenez, R.; Serrano, J. L.; Alcala, R.;
Villacampa, B.; Villalba, J.; Ledoux, I.; Zyss, J. Liq. Cryst.
1997, 22, 265–273.
7. Hashimoto, M.; Mori, A.; Inoue, H.; Nagamiya, H.; Doi, T.;
Takahashi, T. Tetrahedron Lett. 2003, 44, 1251–1254.
8. Mori, A.; Akahoshi, I.; Hashimoto, M.; Doi, T.; Takahashi, T.
Tetrahedron Lett. 2004, 45, 813–815; Hioki, H.; Fukutaka,
M.; Takahashi, H.; Kodama, M.; Kubo, K.; Ideta, K.; Mori,
A. Tetrahedron Lett. 2004, 45, 7591–7594; Hioki, H.;
Fukutaka, M.; Takahashi, H.; Kubo, M.; Matsushita, K.;
Kodama, M.; Kubo, K.; Ideta, K.; Mori, A. Tetrahedron
2005, 61, 10643–10651.
14. Katritzky, A. R.; Button, M. A. C.; Denisenko, S. N.
J. Heterocycl. Chem. 2000, 37, 1505–1510.
15. Wang, H. J.; Ling, W.; Lu, L. J. Fluorine Chem. 2001, 111,
241–246.
16. Weissflog, W.; Schubert, H. J. Prakt. Chem. 1976, 318,
785–794.
17. Peake, C. J.; Strickland, J. H. Synth. Commun. 1986, 16,
763–765.
18. Miller, C. P.; Kaufman, D. H. Synlett 2000, 1169–1171.
19. Malthete, J.; Canceill, J.; Gabard, J.; Jacques, J. Tetrahedron
1981, 37, 2815–2821; Nakai, H.; Konno, M.; Kosuge, S.;
Sakuyama, S.; Toda, M.; Arai, Y.; Obata, T.; Katsube, N.;
Miyamoto, T.; Okegawa, T.; Kawasaki, A. J. Med. Chem.
1988, 31, 84–91.
20. Borisch, K.; Diele, S.; Goring, P.; Kresse, H.; Tschierske, C.
J. Mater. Chem. 1998, 8, 529–543.
21. Pickaert, G.; Ziessel, R. Synthesis 2004, 16, 2716–2726;
Soerme, P.; Arnoux, P.; Kahl-Knutsson, B.; Leffler, H.; Rini,
J. M.; Nilsson, U. J. J. Am. Chem. Soc. 2005, 127, 1737–
1743; Mertesdorf, C.; Ringsdorf, H. Liq. Cryst. 1989, 5,
1757–1772.
22. Ungar, G.; Abramic, D.; Percec, V.; Heck, J. A. Liq. Cryst.
1996, 21, 73–86; Terazzi, E.; Torelli, S.; Bernardinelli, G.;
Rivera, J.-P.; Benech, J.-M.; Bourgogne, C.; Donnio, B.;
Guillon, D.; Imbert, D.; Buenzli, J.-C. G.; Pinto, A.;
Jeannerat, D.; Piguet, C. J. Am. Chem. Soc. 2005, 127,
888–903.
9. Haino, T.; Tanaka, M.; Ideta, K.; Kubo, K.; Mori, A.;
Fukazawa, Y. Tetrahedron Lett. 2004, 45, 2277–2279.
10. Fuchi, N.; Doi, T.; Takahashi, T. Chem. Lett. 2005, 34, 438–
439; Fuchi, N.; Doi, T.; Cao, B.; Kahn, M.; Takahashi, T.
Synlett 2002, 285–289; Bose, D. S.; Jayalakshmi, B.
Synthesis 1999, 64–65; Kantorowski, E. J.; Kurth, M. J. Mol.
Divers. 1997, 2, 207–216.