Palladium-Catalyzed Cascade Cyclization/Alkynylation and Alkenylation of Alkynone O-Methyloximes with Terminal Alkynes

Article abstract of DOI:10.1002/adsc.201800444

A palladium-catalyzed cascade cyclization for the assembly of polyfunctionalized isoxazoles derivatives has been accomplished. This new protocol exhibits mild conditions, high efficiency, good functional group tolerance and broad substrate scope. Remarkably, the easy availability of starting materials along with the efficiency of the present strategy provides a new tool for the construction of structurally diverse isoxazole derivatives, becoming a promising application in synthetic and pharmaceutical chemistry. (Figure presented.).

Full text of DOI:10.1002/adsc.201800444

Title: Palladium-Catalyzed Cascade Cyclization/Alkynylation and
Alkenylation of Alkynone O-Methyloximes with Terminal Alkynes
Authors: Huanfeng Jiang, Jianxiao Li, Miao Hu, Chunsheng Li, Can Li,
Jiawei Li, and Wanqing Wu
This manuscript has been accepted after peer review and appears as an
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201800444
Link to VoR: http://dx.doi.org/10.1002/adsc.201800444

10.1002/adsc.201800444
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.200((will be filled in by the editorial sttaff))
Palladium-Catalyzed Cascade Cyclization/Alkynylation and
Alkenylation of Alkynone O-Methyloximes with Terminal
Alkynes
Jianxiao Li,+a Miao Hu,+a Chunsheng Li,a Can Li,a Jiawei Li,a Wanqing Wua and
Huanfeng Jianga,*
a
Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical
Engineering, South China University of Technology, Guangzhou 510640, P. R. China.
Fax: (+86) 20-87112906; E-mail: jianghf@scut.edu.cn
+ These authors contributed equally to this work.
Received: ((will be filled in by the editorial staff))
Abstract: A palladium-catalyzed cascade cyclization for the structurally diverse isoxazole derivatives, becoming a
assembly of polyfunctionalized isoxazoles derivatives has promising application in synthetic and pharmaceutical
been accomplished. This new protocol exhibits mild chemistry.
conditions, high efficiency, good functional group tolerance
and broad substrate scope. Remarkably, the easy availability Keywords:
Palladium-catalyzed;
alkynylation;
of starting materials along with the efficiency of the present alkenylation; alkynone O-methyloximes; terminal
strategy provides a new tool for the construction of
alkynes
electrophilic species. As
a
consequence, the
development of expeditious and practical synthetic
route for the straightforward preparing these
polyfunctionalized isoxazoles are still challenging.
Introduction
Heterocycles are ubiquitous building blocks in
numerous biologically active natural products,
functional materials molecules, agrochemicals, and
pharmaceuticals.[1] Isoxazoles represent a privileged
heteroaromatic motifs in pharmaceuticals and
bioactive natural products.[2] In particular, highly
substituted isoxazoles exhibit remarkable biological
and therapeutic activities, such as antinociceptive,
antimicrobial, antibiotic, anti-inflammatory, and
anticancer activities.[3] As depicted in Figure 1,
valdecoxib was established as a COX-2 inhibitor.[4]
Leflunomide was reported as a antirheumatic drug.[5]
Oxacillin was used as a β-lactam antibiotic.[6] In
addition, these structural skeleton represent
synthetically versatile intermediates for other
chemical transformations.[7] Considerable efforts
have been devoted to developing efficient synthetic
methodologies for the assembly of functionalized
isoxazole derivatives in the past few years.
Undoubtedly, [3 + 2] cycloaddition reactions of
alkynes with nitrile oxides represents the most
straightforward and efficient methods in the
construction of these important frameworks.[8]
However, most of these excellent strategies required
functionalized precursors, harsh conditions, and
provided poor chemo- and regioselectivities, reducing
their versatility and simplicity. Alternatively,
electrophilic cyclization of alkynone O-methyloximes
with a varieties of electrophilic agents have also been
investigated for constructing 4-haloisoxazoles and 4-
Figure 1. Selected examples of biologically active
isoxazoles
In addition, transition-metal-catalyzed cascade
approaches has been established as a powerful and
efficient synthetic methodologies for the construction
of complicated molecules with maximum atom and
step economy.[10] In this regard, great achievements
have been accomplished for the preparation of
diversely isoxazole derivatives via metal-catalyzed
cascade strategies of alkynyl oxime ethers (Scheme
1a). Using this strategy, Miyata and co-workers
discovered an elegant method for the synthesis of
trisubstituted isoxazoles through gold-catalyzed
cyclization/ Claisen-type rearrangement process.[11]
Subsequently, Ryu and co-workers developed an
unprecedented
cyclization/fluorination
gold-catalyzed
cascade
organoselenyl-isoxazoles.[9]
electrophilic reagents is limited to halogenated
However,
the
of 2-alkynone
O-
methyloximes for the synthesis of 4-fluoroisoxazole
derivatives in moderate to good yields under mild
1
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10.1002/adsc.201800444
Advanced Synthesis & Catalysis
reaction conditions.[12] Along these lines, Zeni and
co-workers disclosed a iron-promoted intramolecular
cyclization of alkynone O-methyloximes with
diorganyl diselenides for synthesis of 4-
organoselenylisoxazoles.[13] Especially, Chen and co-
workers demonstrated a nice protocol of palladium-
catalyzed cascade cyclization/alkenylation of
alkynone O-methyloximes with activated alkenes
(entries 7, 12-18), and we found that [C2O2mim]Cl
was the best solvent for this transformation.
Strikingly, when using 2 equiv [C2O2mim]Cl as the
additive and DMSO as the solvent, the corresponding
product 3a was detected in 78% GC yield (entry 20).
It is noted that, when the reaction was performed at
o
80 C, the desired product 3a was detected in 82%
GC yield (entry 21). Furthermore, when activated 4Å
(Scheme 1b).[14] Despite the undisputable significance, molecular sieves (MS) was added to the mixture, the
the direct and efficient synthetic methodologies to
construct 4-alkynylisoxazole derivatives with
excellent atom- and step-economy have not yet been
reported. Recently, we reported a straightforward
desired product 3a was detected in 88% yield by GC-
MS (entry 23). Finally, the efficiency of this reaction
was not changed when dry DMSO was used (entry
24).
NHC-palladium-catalyzed
cascade
annulation/alkynylation of 2-alkynylanilines with
terminal alkynes to afford 3-alkynylindoles in ionic
liquids.[15] Very recently, we have also successfully
developed a palladium-catalyzed regioselective three-
component cascade bisthiolation of terminal alkynes
using ionic liquids as the additive.[16] Inspired by the
aforementioned background and our long-standing
interest in Pd-catalyzed cross-coupling reactions in
ionic liquids,[17] herein we describe an efficient and
Table 1.Optimization of the reaction conditions [a]
Entry
1
Catalyst
PdCl2
Additive
-
Solvent
DMF
Yield/% [b]
N.D.
2
3
4
5
6
LiCl
LiBr
DMF
DMF
DMF
DMF
DMF
N.D.
N.D.
N.D.
6
PdCl2
PdCl2
practical
Pd-catalyzed
cascade
cyclization/
nBu4NCl
nBu4NI
nBu4NI
PdCl2
alkynylation and alkenylation of 2-alkynone O-
PdCl2
methyloximes with terminal alkynes (Scheme 1c).
Pd(OAc)2
15
7
Pd(TFA)2
Pd(PPh3)2Cl2
Pd(MeCN)2Cl2
Pd(PhCN)2Cl2
PdBr2
nBu4NI
nBu4NI
nBu4NI
nBu4NI
nBu4NI
nBu4NI
nBu4NI
nBu4NI
DMF
DMF
43
trace
9
8
9
DMF
10
11
12
13
14
DMF
12
DMF
18
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
DMSO
Toluene
DME
48
trace
trace
15
16
17
18
19
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
nBu4NI
nBu4NI
nBu4NI
NMP
[Bmim]Cl
[C2OHmim]Cl
[C2O2mim]Cl
[C2O2mim]Cl
DMSO
17
26
40
73
73
78
82
79
88 (80)
88
nBu4NI
-
20
[C2O2mim]Cl
[C2O2mim]Cl
[C2O2mim]Cl
[C2O2mim]Cl
[C2O2mim]Cl
21[c]
22[d]
23[e]
24[e], [f]
[a]
DMSO
DMSO
DMSO
DMSO
Scheme 1. Transition metal-catalyzed cascade cyclization
of alkynyl oxime ethers
Reactions were performed with 1a (0.10 mmol), 2a (0.12
Results and Discussion
mmol), catalyst (5 mol %), additive (2 equiv), solvent (1 mL)
under air at 60 C for 8 h. DME: 1,2-dimethoxyethane. NMP:
o
In our preliminary experiments, O-methyl oxime
(1a) and 1-ethynyl-4-methoxybenzene (2a) were
selected as the model system to screen the optimal
conditions, and the results are summarized in Table 1.
Initially, several additives were examined, and we
found that nBu4NI was the best additive for this
transformation (entries 1-5). Subsequently, different
palladium salts were examined (entries 5-11),
including Pd(OAc)2, Pd(TFA)2, Pd(PPh3)2Cl2,
Pd(MeCN)2Cl2, Pd(PhCN)2Cl2 and PdBr2, and readily
available Pd(TFA)2 exhibited efficient catalytic
activity (entry 7). Then, different solvents such as
DMSO, Toluene, DME, NMP, [Bmim]Cl,
[C2OHmim]Cl, [C2O2mim]Cl were also investigated
N-methyl-2-pyrrolidone.
methylimidazolium chloride. [C2OHmim]Cl: 1-hydroxyethyl-
3-methylimidazolium chloride. [C2O2mim]Cl: 1-
carboxymethyl-3-methylimidazolium chloride.
[b] Determined by GC using dodecane as the internal standard. N.
D. = not detected.
[c] At 80 oC.
[d] At 100 oC.
[e] 25 mg 4Å MS was used
[f] Dry DMSO was added
[Bmim]Cl:
1-butyl-3-
Having established the optimum reaction
conditions, we next investigated the substrate scopes
and limitations of the present protocol.
2
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10.1002/adsc.201800444
Advanced Synthesis & Catalysis
Representative results are summarized in Table 2.
Satisfactorily, both electron-donating and electron-
withdrawing substituents on the phenyl ring of
alkynes were well accommodated, generating the
desired products in moderate to good yields (3a-3i).
Gratifyingly, aryl alkynes with strong electron-
withdrawing groups, such as CF3 and CO2Me groups,
were amenable to this transformation, and furnished
the expected products 3g and 3h in 70% and 62%
yields, respectively. More importantly, N, N-dimethyl
substituted aryl alkyne was well tolerated, and
afforded the desired product 3i in 79% yield. As for
the synthetically attractive heteroaromatic alkyne,
such as 4-ethynylpyridine, could be successfully
converted into 3j in 83% yield. Prominently, various
structurally diverse aliphatic alkynes were compatible
with the current reaction conditions, furnishing the
corresponding products in satisfied yields (3k-3o).
were obtained in 79% and 75% yields, respectively.
Particularly, halo substituents, such as F, Cl, and Br,
were all nicely tolerated, thus providing the
possibility for further manipulation by transition
metal-catalyzed
coupling
reactions
(4f-4k).
Furthermore, aryl alkynes bearing strong electron-
withdrawing groups, such as trifluoromethyl, ester,
and aldehyde groups were also successfully
participated in the current cascade reaction, albeit
with somewhat reduced yields were observed (4l-4n).
2-Ethynylnaphthalene proved to be amenable
substrate under the reported conditions, and provided
the target product 4o in 61% yield. Particularly
noteworthy was the functional group tolerance of this
protocol, such as 2-ethynylpyridine was also perfectly
accommodated, furnishing the corresponding product
4p in 68% yield. However, when 3-ethynylthiophene
was used as the substrate under the standard
conditions, only a complex mixtures was obtained.
Unfortunately, aliphatic alkyne was not amenable to
this protocol and failed to convert to the desired
product 4r.
Table 2. Substrate scope of O-methyl oxime 1 with
alkynes derivatives [a]
Table 3. Substrate scope of 1a with various aryl alkynes
derivatives [a]
[a] Reaction conditions: 1 (0.20 mmol), 2a (1.2 equiv), Pd(TFA)2
(5 mol %), 50 mg 4Å MS, [C2O2mim]Cl (2 equiv) and DMSO (2
mL) at 80 oC for 8 h. Yields referred to isolated yield.
[a] Reaction conditions: 1a (0.20 mmol), 2 (1.2 equiv), Pd(TFA)2
(5 mol %), [C2O2mim]Cl (2 equiv), HOAc (1.5 mL) and DMF
(0.5 mL) at 100 oC for 12 h. Yields referred to isolated yield.
Noteworthy,
4-vinyl
substituted
isoxazole
derivatives could be obtained in a similar reaction
conditions. We optimized the alkenylation of
alkynone O-methyloximes with terminal alkynes
reaction as follows: alkynone O-methyloximes 1
(0.20 mmol), terminal alkynes 2 (0.24 mmol),
Pd(TFA)2 (5 mol %), [C2O2mim]Cl (0.4 mmol),
With the positive results above, the scopes and
limitations of alkynone O-methyloxime derivatives
were further investigated. The results are summarized
in Table 4. Generally, aryl substituted (R3) alkynone
O-methyloximes with either an electron-donating or
electron-withdrawing group on the benzene ring were
well tolerated, delivering the desired products in
moderate to excellent yields (5a-5h). Additionally,
substrates containing three-, five- or six-membered-
ring-substituted aliphatic alkynes were good
candidates to deliver the corresponding products in
satisfactory yields (5i-5k). Similarly, linear chain
alkynes such as 1-pentyne, 1-hexyne, 3-methylbut-1-
o
HOAc (1.5 mL) and DMF (0.5 mL) at 100 C for 12
h.[18] As illustrated in Table 3, the position of the
substituents on the phenyl ring has a very limited
effect on the reaction efficiency (4a-4k). The E-
configuration of the product 4a was confirmed
unambiguously by an X-ray crystallographic
analysis.[19] Moreover, disubstituted substrates such
as 1-ethynyl-2,4-dimethylbenzene (1e) and 1,3-
dichloro-2-ethynylbenzene (1k) were also suitable
substrates, and the corresponding products 4e and 4k
yne,
but-3-yn-1-ylbenzene,
and
pent-4-yn-1-
ylbenzene were compatible with the optimized
3
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10.1002/adsc.201800444
Advanced Synthesis & Catalysis
conditions, furnishing the expected products in
moderate to good yields (5l-5o). Notably, the
heteroaromatic alkyne 2-ethynylthiophene could be
tolerated in this protocol, giving the expected product
5p in 73% yield. Gratifyingly, 2-ethynylnaphthalene
also proceeded smoothly to afford the corresponding
product 5q in satisfied yield. In addition, substituted
alkynone O-methyloxime derivatives bearing alkyl,
methoxyl, and halides groups survived the standard
conditions, producing the desired products in
synthetically useful yields (5r-5w). Satisfactorily,
several alkyl substituted O-methyloxime also proved
suitable for this transformation, giving the
corresponding products in moderate yields (5x-5z).
Examination of various R revealed that methyl is well
tolerated to afford the corresponding 3a in 88% yield.
For other substituents of alkynone oxime ethers with
low yields, the major byproduct was 3,5-
diphenylisoxazole (7), which was generated via the
direct protonolysis of C(sp2)-palladium species.
Scheme 3. Evaluating different substituents of alkynone
oximes
Table 4. Substrate scope of alkynone O-methyloximes 1
with 2j [a]
To demonstrate the efficiency and practicability of
this methodology, a gram-scale synthesis of 4a was
performed, as shown in Scheme 4. The reaction of
1.17 g of alkynone O-methyloxime 1a with
ethynylbenzene in the presence of 5 mol % Pd(TFA)2
catalyst provided 1.23g of the corresponding 4-vinyl
substituted isoxazole 4a in 76% yield.
Scheme 4. Scale-up synthesis of 4a
In addition, to gain some insight into the
mechanism of this cascade protocol, two control
experiments have been also conducted (Scheme 5).
When 3,5-diphenylisoxazole (8) was employed to
react with ethynylbenzene under the standard
conditions, unfortunately, no desired product 4a was
detected by GC-MS (eq 1). Similarly, when 4-chloro-
3,5-diphenylisoxazole (9) was subjected to the same
reaction conditions, no desired product was observed
as well (eq 2). All of these results described above
indicated that neither 8 nor 9 was a possible
intermediate in this current chemical transformation.
[a] Reaction conditions: 1 (0.20 mmol), 2j (1.2 equiv), Pd(TFA)2
(5 mol %), [C2O2mim]Cl (2 equiv), HOAc (1.5 mL) and DMF
(0.5 mL) at 100 oC for 12 h. Yields referred to isolated yield.
Satisfactorily, styryl substituted O-methyloxime
framework (1ba) was well tolerable under the
optimized conditions, furnishing functionalized
isoxazole 5ba in 58% yield (Scheme 2, eq 1). Double
alkyl substituted O-methyloxime, such as 1,3-
dicyclohexylprop-2-yn-1-one O-methyl oxime (1bb),
could also be applied for this reaction to give the
desired product 5bb in 64% yield (Scheme 2, eq 2).
Scheme 5. Control Experiments
Based on the above experiments, a plausible
reaction mechanism is proposed in Scheme 6. The
left pathway is initiated by trans-oxypalladation of
alkynone O-methyloximes (1), generating an
oxonium intermediate I.[12, 14] Subsequently, I could
Scheme 2. Palladium-catalyzed cascade cyclization/
alkenylation for the synthesis of 5ba and 5bb
14]
undergo the elimination of methyl chloride.[13,
Additionally, we turned our attention to the
influence of OR of alkynone oxime ethers for the
cascade cyclization/alkynylation (Scheme 3).
Simultaneously, in a weak acidity reaction medium,
the terminal alkynes coordinate with C(sp2)-
4
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10.1002/adsc.201800444
Advanced Synthesis & Catalysis
palladium species affords intermediate II.[20] Finally,
a reductive elimination gives the target products 3
and Pd(0). The oxidation of Pd(0) to Pd(II) by air
completes the catalytic cycle.[21] For the right
pathway, intermediate III may undergo alkynes
insertion to generate vinylpalladium intermediate
IV.[22] Then, protonolysis of vinylpalladium species
IV gives the desired products 4 and 5 in the presence
of an acid (HOAc) with regeneration of the
palladium(II) species to complete the catalytic cycle.
ISQ gas chromatograph-mass spectrometer at an ionization
voltage of 70 eV and equipped with a DB-WAX capillary
column (internal diameter: 0.25 mm, length: 30 m). The
data of HRMS was carried out on a high-resolution mass
spectrometer (LCMS-IT-TOF). IR spectra were recorded
in KBr disks with a Bruker TENSOR 27 spectrometer.
Melting points were determined with a Büchi Melting
Point B-545 instrument.
Typical procedure for the preparation of 4-
alkynylisoxazoles: A mixture of O-methyl oxime 1 (0.20
mmol), Pd(TFA)2 (5 mol %), [C2O2mim]Cl (2.0 equiv),
and DMSO (2 mL) was added to an Schlenk tube equipped
with a stir-bar. Then, terminal alkynes (0.24 mmol) were
quickly added to the tube under air atmosphere and stirred
at 80 oC for 8 h. After the reaction was finished, the
mixture was quenched by water and extracted with CH2Cl2
three times. The combined organic layers were dried over
anhydrous Na2SO4 and evaporated under vacuum. The
residue was purified by flash column chromatography on
silica gel (hexanes/ethyl acetate) to afford the desired
products 3.
[23]
Thus, all these observations indicated that the
acidity of the reaction medium plays an important
role for the reaction selectivity control for this type of
cascade cyclization.
4-((4-Methoxyphenyl)ethynyl)-3,5-diphenylisoxazole
(3a): Yield: 85% (59.7 mg) as a yellow solid; mp = 115.2 -
1
116.5 °C; H NMR (400 MHz, CDCl3) δ 8.27 (d, J = 7.6
Hz, 2H), 8.14 (dd, J = 6.8, 2.8 Hz, 2H), 7.59 - 7.42 (m, 8H),
6.90 (d, J = 8.8 Hz, 2H), 3.83 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 169.5, 162.5, 160.1, 132.9, 130.7, 130.2, 128.9,
128.7, 127.9, 127.5, 126.4, 114.9, 114.3, 97.7, 96.6, 78.4,
55.4 ppm; νmax(KBr)/cm-1 3058, 2927, 2217, 1605, 1505,
1247, 691; MS (EI) m/z 77, 105, 176, 220, 246, 309, 337,
351; HRMS-ESI (m/z): calcd for C24H17NNaO2, [M+Na]+:
374.1151, found 374.1155.
4-((3-Methoxyphenyl)ethynyl)-3,5-diphenylisoxazole
(3b): Yield: 81% (56.9 mg) as a yellow solid; mp = 77.5 -
1
Scheme 6. Proposed mechanism
78.7 °C; H NMR (400 MHz, CDCl3) δ 8.27 (dd, J = 8.0,
1.6 Hz, 2H), 8.14 (dd, J = 6.8, 3.2 Hz, 2H), 7.58 - 7.47 (m,
6H), 7.30 (t, J = 8.0 Hz, 1H), 7.13 (d, J = 7.6 Hz, 1H), 7.05
(d, J = 2.4 Hz, 1H), 6.94 (dd, J = 8.4, 2.4 Hz, 1H), 3.83 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 170.0, 162.6, 159.5,
130.8, 130.2, 129.7, 128.9, 128.7, 128.5, 127.9, 127.3,
126.5, 123.9, 123.7, 116.6, 115.1, 97.3, 96.4, 79.6, 55.4
ppm; νmax(KBr)/cm-1 3060, 2924, 2214, 1646, 1579, 1451,
686; MS (EI) m/z 77, 105, 176, 220, 246, 283, 351;
HRMS-ESI (m/z): calcd for C24H17NNaO2, [M+Na]+:
374.1151, found 374.1155.
Conclusion
In conclusion, we have successfully accomplished
an alternative and efficient approach for the synthesis
of 4-alkynylation and 4-alkenylation isoxazole
derivatives
via
palladium-catalyzed
cascade
cyclization of alkynone O-methyloximes with
terminal alkynes. The acidic ionic liquid
[C2O2mim]Cl as additive makes this transformation
green and high efficiency. Moreover, the present
methodology demonstrates excellent functional group
compatibility, excellent atom- and step-economy, and
mild reaction conditions. Notably, this synthetic
protocol provides a new tool for the construction of
4-((2-Methoxyphenyl)ethynyl)-3,5-diphenylisoxazole
(3c): Yield: 83% (58.3 mg) as a yellow solid; mp = 85.3 -
86.8 °C; 1H NMR (400 MHz, CDCl3) δ 8.40 (d, J = 7.2 Hz,
2H), 8.25 (dd, J = 6.8, 2.8 Hz, 2H), 7.58 - 7.48 (m, 6H),
7.45 (dd, J = 7.6, 1.2 Hz, 1H), 7.35 (dd, J = 11.6, 4.4 Hz,
1H), 6.95 (dd, J = 14.2, 7.6 Hz, 2H), 3.96 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 169.7, 162.3, 160.4, 132.8,
130.6, 130.2, 130.1, 128.8, 128.6, 128.6, 128.0, 127.4,
126.5, 120.6, 112.2, 110.7, 97.7, 93.6, 83.7, 55.8 ppm;
νmax(KBr)/cm-1 3059, 2923, 2210, 1646, 1584, 1452, 1249,
697; MS (EI) m/z 77. 105, 191, 219, 246, 322, 351;
HRMS-ESI (m/z): calcd for C24H17NNaO2, [M+Na]+:
374.1151, found 374.1148.
diversely isoxazole derivatives, becoming
promising application in synthetic
a
and
pharmaceutical chemistry.
4-((4-Ethoxyphenyl)ethynyl)-3,5-diphenylisoxazole (3d):
Yield: 86% (62.8 mg) as a yellow solid; mp = 107.4 -
1
108.8 °C; H NMR (400 MHz, CDCl3) δ 8.27 (d, J = 6.8
Hz, 2H), 8.14 (dd, J = 6.8, 3.0 Hz, 2H), 7.60 - 7.48 (m, 6H),
7.45 (d, J = 8.8 Hz, 2H), 6.89 (d, J = 8.8 Hz, 2H), 4.05 (q,
J = 7.2 Hz, 2H), 1.43 (t, J = 7.6 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 169.5, 162.5, 159.5, 132.9, 130.6, 130.2,
128.9, 128.7, 127.9, 127.5, 126.4, 114.8, 114.7, 97.7, 96.7,
78.3, 63.7, 14.7 ppm; νmax(KBr)/cm-1 3053, 2921, 2216,
1606, 1503, 1450, 1250, 689; MS (EI) m/z 77, 105, 206,
234, 281, 336, 368; HRMS-ESI (m/z): calcd for
C25H19NNaO2, [M+Na]+: 388.1308, found 388.1310.
Experimental Section
All reagents and catalysts were purchased as analytical
reagent grade and used without further purification. 1H and
13C NMR spectra were recorded using a Bruker DRX-400
spectrometer using CDCl3 or Acetone-d6 as solvent and
TMS as an internal standard. The chemical shifts are
referenced to signals at 7.26 and 77.0 ppm, respectively.
GC analyses were performed on
a
GC-7900
chromatograph with an FID and equipped with an AT.SE-
30 capillary column (internal diameter: 0.32 mm, length:
30 m). Mass spectra were recorded on a Thermo Scientific
4-((4-(Pentyloxy)phenyl)ethynyl)-3,5-diphenylisoxazole
(3e): Yield: 81% (65.9 mg) as a yellow solid; mp = 94.1 -
5
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10.1002/adsc.201800444
Advanced Synthesis & Catalysis
95.2 °C; 1H NMR (400 MHz, CDCl3) δ 8.27 (d, J = 6.8 Hz,
2H), 7.62 - 7.41 (m, 6H), 2.72 (t, J = 6.8 Hz, 2H), 2.48 (t, J
2H), 8.15 (dd, J = 6.4, 2.8 Hz, 2H), 7.51 (tt, J = 8.0, 4.2 Hz, = 7.2 Hz, 2H), 1.97 (p, J = 7.2 Hz, 2H); 13C NMR (100
6H), 7.45 (d, J = 8.8 Hz, 2H), 6.89 (d, J = 8.8 Hz, 2H),
MHz, CDCl3) δ 170.0, 162.9, 130.8, 130.3, 128.9, 128.7,
3.97 (t, J = 6.8 Hz, 2H), 1.90 - 1.72 (m, 2H), 1.51 - 1.34 (m, 128.5, 127.8, 127.3, 126.3, 118.8, 97.2, 94.5, 72.8, 24.3,
4H), 0.94 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
δ 169.5, 162.5, 159.7, 132.9, 130.6, 130.2, 128.9, 128.7,
127.9, 127.5, 126.4, 114.8, 114.6, 97.7, 96.7, 78.3, 68.2,
28.9, 28.2, 22.5, 14.0 ppm; νmax(KBr)/cm-1 3061, 2930,
2218, 1604, 1510, 1467, 1250, 690; MS (EI) m/z 115, 167,
210, 228, 300, 334, 407; HRMS-ESI (m/z): calcd for
C28H26NO2, [M+H]+: 408.1958, found 408.1957.
18.9, 16.2 ppm; νmax(KBr)/cm-1 3054, 2923, 2215, 1639,
1540, 1404, 1267, 686; MS (EI) m/z 77, 105, 152, 207,
258, 284, 312; HRMS-ESI (m/z): calcd for C21H16N2NaO,
[M+Na]+: 335.1155, found 335.1159.
5-(3,5-Diphenylisoxazol-4-yl)pent-4-yn-1-ol (3l): Yield:
73% (44.2 mg) as a yellow oil; 1H NMR (400 MHz,
CDCl3) δ 8.19 (d, J = 7.2 Hz, 2H), 8.05 (dd, J = 6.4, 2.8 Hz,
2H), 7.55 - 7.43 (m, 6H), 3.79 (t, J = 6.4 Hz, 2H), 2.64 (t, J
= 7.2 Hz, 2H), 1.90 (p, J = 6.8 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ 169.6, 162.8, 130.6, 130.1, 128.8, 128.6,
128.6, 127.8, 127.4, 126.2, 97.7, 97.1, 71.2, 61.5, 31.2,
16.4 ppm; νmax(KBr)/cm-1 3064, 2930, 2214, 1639, 1444,
1407, 1260, 688; MS (EI) m/z 77, 105, 219, 246, 274, 303;
HRMS-ESI (m/z): calcd for C20H17NNaO2, [M+Na]+:
326.1151, found 326.1155.
4-((4-Chlorophenyl)ethynyl)-3,5-diphenylisoxazole (3f):
Yield: 77% (54.7 mg) as a yellow solid; mp = 109.3 -
110.5 °C; 1H NMR (400 MHz, CDCl3) δ 8.24 (dd, J = 8.0,
1.6 Hz, 2H), 8.11 (dd, J = 6.8, 3.0 Hz, 2H), 7.58 - 7.49 (m,
6H), 7.44 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H); 13
C
NMR (100 MHz, CDCl3) δ 170.2, 162.6, 1345.0, 132.6,
130.9, 130.3, 129.0, 128.9, 128.7, 128.6, 127.9, 127.3,
126.5, 121.2, 97.1, 95.2, 80.8 ppm; νmax(KBr)/cm-1 3061,
2919, 2210, 1645, 1486, 1408, 687; MS (EI) m/z 77, 105,
189, 207, 281, 355; HRMS-ESI (m/z): calcd for
C23H14ClNNaO, [M+Na]+: 378.0656, found 378.0660.
4-(3-Methoxyprop-1-yn-1-yl)-3,5-diphenylisoxazole
(3m): Yield: 77% (44.5 mg) as a yellow solid; mp = 68.0 -
69.5 °C; 1H NMR (400 MHz, CDCl3) δ 8.24 - 8.15 (m, 2H),
8.05 (dd, J = 6.4, 2.8 Hz, 2H), 7.63 - 7.44 (m, 6H), 4.40 (s,
2H), 3.45 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.6,
162.8, 130.9, 130.2, 128.9, 128.7, 128.4, 127.8, 127.2,
126.4, 96.7, 92.7, 76.8, 60.6, 57.9 ppm; νmax(KBr)/cm-1
3066, 2923, 2214, 1562, 1445, 1090, 690; MS (EI) m/z 77,
105, 153, 184, 230, 258, 289; HRMS-ESI (m/z): calcd for
C19H15NNaO2, [M+Na]+: 312.0995, found 312.0996.
3,5-Diphenyl-4-((4-(trifluoromethyl)phenyl)ethynyl)-
isoxazole (3g): Yield: 70% (54.5 mg) as a yellow solid;
mp = 105.1 - 106.8 °C; 1H NMR (400 MHz, CDCl3) δ 8.24
(dd, J = 7.8, 2.0 Hz, 2H), 8.10 (dd, J = 6.8, 3.0 Hz, 2H),
7.63 (q, J = 8.8 Hz, 4H), 7.57 - 7.50 (m, 6H); 13C NMR
(100 MHz, CDCl3) δ 170.6, 162.7, 131.6, 131.1, 130.4,
129.0, 128.9, 128.8, 128.4 (q, J = 32.8 Hz), 128.3, 127.9,
127.1, 126.5, 125.5 (q, J = 3.8 Hz), 125.1 (q, J = 253.9 Hz),
96.8, 94.8, 82.3 ppm; νmax(KBr)/cm-1 3056, 2922, 2216,
1604, 1495, 1446, 1406, 691; MS (EI) m/z 77, 105, 189,
258, 284, 370, 389; HRMS-ESI (m/z): calcd for
C24H15F3NO, [M+H]+: 390.1100, found 390.1104.
4-(3,5-Diphenylisoxazol-4-yl)-2-methylbut-3-yn-2-ol
1
(3n): Yield: 75% (45.4 mg) as a yellow oil; H NMR (400
MHz, CDCl3) δ 8.18 (dd, J = 7.6, 2.0 Hz, 2H), 8.12 - 7.93
(m, 2H), 7.56 - 7.43 (m, 6H), 2.02 (s, 1H), 1.66 (s, 6H);
13C NMR (100 MHz, CDCl3) δ 170.1, 162.6, 130.8, 130.2,
128.8, 128.6, 128.4, 127.8, 127.2, 126.3, 101.1, 96.7, 72.9,
65.9, 31.1 ppm; νmax(KBr)/cm-1 3062, 2923, 2226, 1560,
1445, 1414, 1096, 696; MS (EI) m/z 77, 105, 166, 246,
288, 303; HRMS-ESI (m/z): calcd for C20H18NO2,
[M+H]+: 304.1332, found 304.1335.
Methyl 4-((3,5-diphenylisoxazol-4-yl)ethynyl)benzoate
(3h): Yield: 62% (47.0 mg) as a yellow solid; mp = 148.5 -
149.8 °C; 1H NMR (400 MHz, CDCl3) δ 8.26 (dd, J = 8.0,
1.6 Hz, 2H), 8.11 (dd, J = 6.8, 3.0 Hz, 2H), 8.06 (d, J = 8.4
Hz, 2H), 7.64 - 7.49 (m, 8H), 3.94 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 170.5, 166.4, 162.6, 131.2, 131.0, 130.4,
130.1, 129.7, 129.0, 128.7, 128.4, 127.9, 127.3, 127.2,
126.6, 96.9, 95.5, 82.8, 52.3 ppm; νmax(KBr)/cm-1 3052,
2922, 2217, 1640, 1407, 1275, 691; MS (EI) m/z 65, 91,
129, 188, 281, 341, 379; HRMS-ESI (m/z): calcd for
C25H17NNaO3, [M+Na]+: 402.1101, found 402.1109.
5-(3,5-Diphenylisoxazol-4-yl)-3-methylpent-1-en-4-yn-
1
3-ol (3o): Yield: 72% (45.3 mg) as a yellow oil; H NMR
(400 MHz, CDCl3) δ 8.18 (dd, J = 6.4, 3.0 Hz, 2H), 8.05
(dd, J = 6.8, 3.0 Hz, 2H), 7.60 - 7.36 (m, 6H), 6.07 (dd, J =
17.2, 10.4 Hz, 1H), 5.55 (d, J = 17.2 Hz, 1H), 5.19 (d, J =
10.4 Hz, 1H), 2.29 (s, 1H), 1.70 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 170.4, 162.6, 141.5, 130.9, 130.3, 128.9,
128.6, 128.3, 127.8, 127.1, 126.4, 114.2, 98.4, 96.6, 75.3,
69.0, 29.8 ppm; νmax(KBr)/cm-1 3064, 2926, 2220, 1562,
1446, 1406, 1098, 699; MS (EI) m/z 77, 105, 141, 165,
210, 272, 300, 315; HRMS-ESI (m/z): calcd for
C21H18NO2, [M+H]+: 316.1332, found 316.1337.
4-((3,5-Diphenylisoxazol-4-yl)ethynyl)-N, N-dimethyl-
aniline (3i): Yield: 79% (57.5 mg) as a yellow solid; mp =
142.7 - 144.2 °C; 1H NMR (400 MHz, CDCl3) δ 8.29 (d, J
= 7.2 Hz, 2H), 8.18 (d, J = 7.6 Hz, 2H), 7.60 - 7.44 (m,
6H), 7.40 (d, J = 8.8 Hz, 2H), 6.67 (d, J = 8.8 Hz, 21H),
2.98 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 168.9, 162.4,
150.5, 133.7, 132.6, 130.4, 130.1, 128.8, 128.6, 127.9,
127.6, 126.3, 111.9, 109.4, 98.2, 98.0, 77.6, 40.2 ppm;
νmax(KBr)/cm-1 3062, 2921, 2209, 1607, 1521, 1446, 1235,
694; MS (EI) m/z 77, 105, 231, 280, 364; HRMS-ESI
(m/z): calcd for C25H21N2O, [M+H]+: 365.1648, Found
365.1651.
4-((3-Methoxyphenyl)ethynyl)-3-phenyl-5-(thiophen-2-
yl)isoxazole (3p): Yield: 75% (53.6 mg) as a yellow solid;
mp = 79.7 - 80.9 °C; 1H NMR (400 MHz, CDCl3) δ 8.28 (d,
J = 2.8 Hz, 1H), 8.14 (dd, J = 6.4, 3.0 Hz, 2H), 7.87 (d, J =
5.2 Hz, 1H), 7.56 - 7.49 (m, 3H), 7.47 (dd, J = 5.2, 3.0 Hz,
1H), 7.30 (t, J = 8.0 Hz, 1H), 7.14 (d, J = 7.6 Hz, 1H), 7.06
(s, 1H), 6.95 (dd, J = 8.4, 2.4 Hz, 1H), 3.84 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 167.1, 162.1, 159.5, 130.3,
129.7, 128.7, 128.5, 128.5, 127.8, 126.7, 126.1, 125.4,
124.0, 123.7, 116.6, 115.1, 96.5, 96.4, 79.4, 55.4 ppm;
3,5-Diphenyl-4-(pyridin-4-ylethynyl)isoxazole
(3j):
Yield: 83% (53.5 mg) as a yellow solid; mp = 146.5 -
1
147.9 °C; H NMR (400 MHz, CDCl3) δ 8.65 (d, J = 4.0
Hz, 2H), 8.23 (dd, J = 7.6, 2.4 Hz, 2H), 8.13 - 7.92 (m, 2H), νmax(KBr)/cm-1 3062, 2924, 2222, 1581, 1449, 1413, 1092,
7.56 (ddd, J = 9.2, 6.4, 4.0 Hz, 6H), 7.38 (d, J = 5.6 Hz,
2H); 13C NMR (100 MHz, CDCl3) δ 171.1, 162.7, 149.8,
131.3, 131.0, 130.5, 129.0, 128.8, 128.2, 127.9, 126.9,
126.6, 125.2, 96.4, 93.4, 84.8 ppm; νmax(KBr)/cm-1 3057,
2922, 2217, 1654, 1575, 1408, 696; MS (EI) m/z 77, 105,
135, 207, 281, 322; HRMS-ESI (m/z): calcd for
C22H15N2O, [M+H]+: 323.1179, found 323.1180.
687; MS (EI) m/z 73, 111, 186, 207, 281, 328, 357;
HRMS-ESI (m/z): calcd for C22H16NO2S, [M+H]+:
358.0896, found 358.0899.
5-(4-Ethylphenyl)-4-((3-methoxyphenyl)ethynyl)-3-
phenylisoxazole (3q): Yield: 84% (63.7 mg) as a yellow
oil; 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.0 Hz, 2H),
8.14 (dd, J = 6.8, 3.0 Hz, 2H), 7.60 - 7.46 (m, 3H), 7.36 (d,
J = 8.4 Hz, 2H), 7.29 (t, J = 8.0 Hz, 1H), 7.13 (d, J = 7.6
Hz, 1H), 7.04 (s, 1H), 6.93 (dd, J = 8.4, 2.4 Hz, 1H), 3.82
6-(3,5-Diphenylisoxazol-4-yl)hex-5-ynenitrile
(3k):
Yield: 65% (40.6 mg) as a yellow oil; 1H NMR (400 MHz,
CDCl3) δ 8.16 (d, J = 7.6 Hz, 2H), 8.01 (dd, J = 6.8, 2.4 Hz, (s, 3H), 2.72 (q, J = 7.6 Hz, 2H), 1.28 (t, J = 7.6 Hz, 3H);
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800444
Advanced Synthesis & Catalysis
13C NMR (100 MHz, CDCl3) δ 170.3, 162.5, 159.5, 147.5,
130.2, 129.7, 128.7, 128.6, 128.4, 127.9, 126.5, 124.9,
123.9, 123.8, 116.6, 115.0, 96.7, 96.2, 79.8, 55.4, 29.0,
15.3 ppm; νmax(KBr)/cm-1 3062, 2927, 2217, 1674, 1584,
1450, 1413, 1042, 690; MS (EI) m/z 77, 105, 133, 189,
207, 248, 307, 379; HRMS-ESI (m/z): calcd for
C26H22NO2, [M+H]+: 380.1645, found 380.1647.
(E)-4-(4-Methoxystyryl)-3,5-diphenylisoxazole
(4d):
Yield: 76% (53.6 mg) as a yellow solid; mp = 80.2 -
1
81.8 °C; H NMR (400 MHz, CDCl3) δ 7.84 (dd, J = 8.0,
1.6 Hz, 2H), 7.77 - 7.66 (m, 2H), 7.52 - 7.43 (m, 6H), 7.25
(d, J = 4.8 Hz, 2H), 6.84 (dd, J = 12.6, 10.2 Hz, 3H), 6.59
(d, J = 16.8 Hz, 1H), 3.80 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 165.6, 162.3, 159.7, 133.9, 129.9, 129.7, 129.6,
129.5, 128.9, 128.9, 128.7, 128.4, 127.6, 114.2, 113.6,
112.6, 55.4 ppm; νmax(KBr)/cm-1 3050, 2922, 1603, 1508,
1448, 1249, 696; MS (EI) m/z 77, 105, 145, 207, 276, 353;
HRMS-ESI (m/z): calcd for C24H19NNaO2, [M+Na]+:
376.1308, found 376.1300.
5-(4-(tert-Butyl)phenyl)-4-((3-methoxyphenyl)ethynyl)-
3-phenylisoxazole (3r): Yield: 83% (67.6 mg) as a yellow
oil; 1H NMR (400 MHz, CDCl3) δ 8.21 (d, J = 8.4 Hz, 2H),
8.14 (dd, J = 6.4, 3.0 Hz, 2H), 7.56 (d, J = 8.4 Hz, 2H),
7.51 (dd, J = 5.2, 1.8 Hz, 3H), 7.30 (t, J = 8.0 Hz, 1H),
7.14 (d, J = 7.6 Hz, 1H), 7.06 (s, 1H), 6.94 (dd, J = 8.4, 2.4
Hz, 1H), 3.83 (s, 3H), 1.37 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ 170.2, 162.5, 159.5, 154.4, 130.2, 129.7, 128.7,
128.6, 127.9, 126.3, 125.9, 124.6, 124.0, 123.9, 116.6,
115.0, 96.7, 96.2, 79.8, 55.4, 35.1, 31.2 ppm;
νmax(KBr)/cm-1 3063, 2928, 2211, 1583, 1461, 1411, 1040,
691; MS (EI) m/z 73, 135, 207, 282, 343, 372, 407;
HRMS-ESI (m/z): calcd for C28H25NNaO2, [M+Na]+:
430.1778, found 430.1773.
(E)-4-(2,4-Dimethylstyryl)-3,5-diphenylisoxazole (4e):
Yield: 79% (55.5 mg) as a yellow solid; mp = 134.2 -
135.4 °C; 1H NMR (400 MHz, CDCl3) δ 7.84 (dd, J = 8.0,
1.6 Hz, 2H), 7.69 (dd, J = 6.4, 3.0 Hz, 2H), 7.55 - 7.44 (m,
6H), 7.41 (d, J = 7.6 Hz, 1H), 6.99 (d, J = 8.0 Hz, 1H),
6.93 (s, 1H), 6.84 (s, 2H), 2.29 (s, 3H), 1.98 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 165.7, 162.4, 137.9, 135.8,
133.0, 131.9, 131.3, 130.0, 129.7, 129.5, 129.0, 128.9,
128.8, 128.4, 127.6, 127.0, 124.8, 115.7, 113.0, 21.1, 19.4
ppm; νmax(KBr)/cm-1 3053, 2922, 1605, 1499, 1448, 1252,
1029, 696; MS (EI) m/z 77, 105, 143, 231, 274, 322, 351;
HRMS-ESI (m/z): calcd for C25H21NNaO, [M+Na]+:
374.1515, found 374.1517.
Typical procedure for the preparation of 4-
alkenylisoxazoles: A mixture of O-methyl oxime 1
(0.20 mmol), Pd(TFA)2 (5 mol %), [C2O2mim]Cl (2.0
equiv), HOAc (1.5 mL), and DMSO (0.5 mL) was added
to an Schlenk tube equipped with a stir-bar. Then, terminal
alkynes (0.24 mmol) were quickly added to the tube under
(E)-4-(4-Fluorostyryl)-3,5-diphenylisoxazole (4f): Yield:
75% (51.2 mg) as a yellow solid; mp = 133.0 - 134.5 °C;
1H NMR (400 MHz, CDCl3) δ 7.82 (dd, J = 8.0, 1.6 Hz,
2H), 7.76 - 7.62 (m, 2H), 7.50 (ddd, J = 10.2, 5.2, 3.2 Hz,
6H), 7.28 (d, J = 2.8 Hz, 1H), 7.25 (d, J = 5.2 Hz, 1H),
7.06 - 6.96 (m, 2H), 6.88 (d, J = 16.8 Hz, 1H), 6.60 (d, J =
16.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 164.9 (d, J =
226.9 Hz), 162.3, 161.4, 133.1 (d, J = 3.3 Hz), 133.0,
130.1, 129.7, 129.5, 128.9, 128.9 (d, J = 23.0 Hz), 128.2,
127.9 (d, J = 8.0 Hz), 127.6, 115.8, 115.6 (d, J = 2.4 Hz),
115.6, 112.3 ppm; νmax(KBr)/cm-1 3055, 2923, 1600, 1504,
1448, 1228, 697; MS (EI) m/z 77, 105, 133, 207, 264, 312,
341; HRMS-ESI (m/z): calcd for C23H16FNNaO, [M+Na]+:
364.1108, found 364.1109.
o
air atmosphere and stirred at 100 C for 12 h. After the
reaction was finished, the mixture was quenched by water
and extracted with CH2Cl2 three times. The combined
organic layers were dried over anhydrous Na2SO4 and
evaporated under vacuum. The residue was purified by
flash column chromatography on silica gel (hexanes/ethyl
acetate) to afford the desired products 4 and 5.
(E)-3,5-Diphenyl-4-styrylisoxazole (4a): Yield: 81%
1
(52.3 mg) as a yellow solid; mp = 162.3 - 163.6 °C; H
NMR (400 MHz, CDCl3) δ 7.83 (dd, J = 7.6, 1.6 Hz, 2H),
7.70 (dd, J = 6.4, 2.4 Hz, 2H), 7.57 - 7.45 (m, 6H), 7.35 -
7.28 (m, 4H), 7.25 (dd, J = 10.8, 6.4 Hz, 1H), 6.97 (d, J =
16.8 Hz, 1H), 6.65 (d, J = 16.8 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 166.1, 162.3, 136.9, 134.4, 130.1, 129.6,
129.5, 129.0, 128.9, 128.8, 128.7, 128.3, 128.1, 127.7,
126.3, 115.9, 112.4 ppm; νmax(KBr)/cm-1 3058, 2923, 1579,
1450, 1408, 694; MS (EI) m/z 77, 105, 207, 246, 294, 306,
323; HRMS-ESI (m/z): calcd for C23H17NNaO, [M+Na]+:
346.1202, found 346.1197.
(E)-4-(3-Chlorostyryl)-3,5-diphenylisoxazole
(4g):
Yield: 78% (55.7 mg) as a yellow solid; mp = 118.6 -
1
119.8 °C; H NMR (400 MHz, CDCl3) δ 7.85 - 7.77 (m,
2H), 7.68 (dd, J = 6.4, 2.8 Hz, 2H), 7.56 - 7.45 (m, 6H),
7.27 (s, 1H), 7.24 - 7.19 (m, 2H), 7.16 - 7.11 (m, 1H), 6.97
(d, J = 16.8 Hz, 1H), 6.57 (d, J = 16.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 166.5, 162.3, 138.7, 134.7, 132.6,
130.2, 129.9, 129.7, 129.4, 129.1, 128.9, 128.8, 128.1,
127.9, 127.7, 126.2, 124.5, 117.4, 112.0 ppm;
νmax(KBr)/cm-1 3054, 2924, 1600, 1503, 1447, 1406, 695;
MS (EI) m/z 77, 105, 149, 217, 280, 328, 357; HRMS-ESI
(m/z): calcd for C23H16ClNNaO, [M+Na]+: 380.0813,
found 380.0820.
(E)-4-(4-Methylstyryl)-3,5-diphenylisoxazole
(4b):
Yield: 86% (57.9 mg) as a yellow solid; mp = 121.6 -
123.2 °C; 1H NMR (400 MHz, CDCl3) δ 7.83 (dd, J = 8.0,
1.6 Hz, 2H), 7.72 - 7.66 (m, 2H), 7.55 - 7.41 (m, 6H), 7.21
(d, J = 8.0 Hz, 2H), 7.12 (d, J = 8.0 Hz, 2H), 6.92 (d, J =
16.8 Hz, 1H), 6.62 (d, J = 16.8 Hz, 1H), 2.33 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 165.8, 162.3, 138.1, 134.3,
134.1, 130.0, 129.6, 129.4, 129.2, 128.9, 128.9, 128.7,
128.4, 127.6, 126.3, 114.9, 112.5, 21.2 ppm; νmax(KBr)/cm-
(E)-4-(4-Chlorostyryl)-3,5-diphenylisoxazole
(4h):
Yield: 79% (56.4 mg) as a yellow solid; mp = 124.2 -
125.8 °C; 1H NMR (400 MHz, CDCl3) δ 7.81 (dd, J = 7.6,
1.8 Hz, 2H), 7.68 (dd, J = 6.4, 3.0 Hz, 2H), 7.57 - 7.42 (m,
6H), 7.27 (d, J = 8.4 Hz, 2H), 7.21 (d, J = 8.8 Hz, 2H),
6.94 (d, J = 16.8 Hz, 1H), 6.58 (d, J = 16.8 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 166.3, 162.2, 135.3, 133.7,
132.8, 130.2, 129.7, 129.4, 129.0, 128.9, 128.8, 128.2,
127.7, 127.5, 116.5, 112.2 ppm; νmax(KBr)/cm-1 3055, 2923,
1597, 1492, 1448, 1402, 696; MS (EI) m/z 77, 105, 165,
217, 280, 328, 357; HRMS-ESI (m/z): calcd for
C23H17ClNO, [M+H]+: 358.0993, found 358.0995.
1
3052, 2922, 1577, 1493, 1448, 1268, 696; MS (EI) m/z
77, 105, 128, 217, 260, 308, 337; HRMS-ESI (m/z): calcd
for C24H19NNaO, [M+Na]+: 360.1359, found 360.1352.
(E)-4-(4-(tert-Butyl)styryl)-3,5-diphenylisoxazole (4c):
Yield: 83% (62.9 mg) as a yellow solid; mp = 119.3 -
120.7 °C; 1H NMR (400 MHz, CDCl3) δ 7.84 (dd, J = 8.0,
1.6 Hz, 2H), 7.71 (dd, J = 6.4, 3.0 Hz, 2H), 7.54 - 7.45 (m,
6H), 7.35 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H),
6.94 (d, J = 16.8 Hz, 1H), 6.64 (d, J = 16.8 Hz, 1H), 1.32
(s, 9H); 13C NMR (100 MHz, CDCl3) δ 165.8, 162.3, 151.4, (E)-4-(3-Bromostyryl)-3,5-diphenylisoxazole (4i): Yield:
134.2, 134.1, 129.9, 129.6, 129.5, 128.9, 128.8, 128.7,
128.3, 127.6, 126.1, 125.7, 115.1, 112.5, 34.7, 31.3 ppm;
νmax(KBr)/cm-1 3054, 2927, 1578, 1495, 1450, 1027, 696;
MS (EI) m/z 77, 105, 210, 271, 322, 379; HRMS-ESI
(m/z): calcd for C27H25NNaO, [M+Na]+: 402.1828, found
402.1822.
71% (56.9 mg) as a yellow solid; mp = 123.8 - 125.3 °C;
1H NMR (400 MHz, CDCl3) δ 7.80 (dd, J = 7.6, 1.8 Hz,
2H), 7.67 (dd, J = 6.8, 3.0 Hz, 2H), 7.50 (ddd, J = 10.2, 5.6,
3.2 Hz, 6H), 7.42 (s, 1H), 7.35 (dt, J = 7.2, 1.6 Hz, 1H),
7.22 - 7.11 (m, 2H), 6.95 (d, J = 16.8 Hz, 1H), 6.55 (d, J =
16.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 166.5, 162.3,
139.0, 132.5, 130.9, 130.3, 130.2, 129.8, 129.4, 129.1,
129.0, 128.9, 128.8, 128.1, 127.7, 124.9, 123.0, 117.4,
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800444
Advanced Synthesis & Catalysis
112.0 ppm; νmax(KBr)/cm-1 3056, 2922, 1597, 1496, 1408,
695; MS (EI) m/z 77, 105, 189, 217, 293, 372, 401;
HRMS-ESI (m/z): calcd for C23H17BrNO, [M+H]+:
402.0488, found 402.0484.
CDCl3) δ 166.1, 162.3, 134.3, 134.2, 133.6, 133.2, 130.1,
129.7, 129.0, 128.9, 128.8, 128.5, 128.3, 128.0, 127.8,
127.7, 126.7, 126.5, 126.2, 1240, 123.0, 116.2, 112.5 ppm;
νmax(KBr)/cm-1 3054, 2924, 1693, 1596, 1497, 1446, 1406,
697; MS (EI) m/z 77, 105, 165, 207, 281, 355, 373;
HRMS-ESI (m/z): calcd for C27H19NNaO, [M+Na]+:
396.1359, found 396.1363.
(E)-4-(4-Bromostyryl)-3,5-diphenylisoxazole (4j): Yield:
82% (65.7 mg) as a yellow solid; mp = 123.0 - 124.6 °C;
1H NMR (400 MHz, CDCl3) δ 7.80 (dd, J = 7.6, 1.6 Hz,
2H), 7.68 (dd, J = 6.8, 2.8 Hz, 2H), 7.58 - 7.46 (m, 6H),
7.42 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H), 6.95 (d,
J = 16.8 Hz, 1H), 6.56 (d, J = 16.8 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 166.3, 162.2, 135.8, 132.8, 131.8, 130.2,
129.7, 129.4, 129.0, 128.9, 128.8, 128.1, 127.8, 127.7,
121.9, 116.6, 112.1 ppm; νmax(KBr)/cm-1 3054, 2922, 1593,
1488, 1407, 696; MS (EI) m/z 77, 105, 193, 271, 321, 345,
401; HRMS-ESI (m/z): calcd for C23H17BrNO, [M+H]+:
402.0488, found 402.0485.
(E)-3,5-Diphenyl-4-(2-(pyridin-2-yl)vinyl)isoxazole (4p):
Yield: 68% (44.1 mg) as a yellow solid; mp = 135.0 -
1
136.7 °C; H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 4.0
Hz, 1H), 7.84 (dd, J = 7.6, 1.2 Hz, 2H), 7.76 - 7.68 (m, 2H),
7.63 (d, J = 16.0 Hz, 1H), 7.57 (dd, J = 7.6, 1.6 Hz, 1H),
7.54 - 7.45 (m, 6H), 7.12 (dd, J = 7.2, 5.0 Hz, 1H), 7.04 (d,
J = 8.0 Hz, 1H), 6.67 (d, J = 16.0 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 167.0, 162.4, 154.8, 149.7, 136.6, 132.6,
130.2, 129.7, 129.4, 129.1, 129.0, 128.8, 128.1, 127.9,
122.4, 120.2, 112.1 ppm; νmax(KBr)/cm-1 3055, 2924, 1692,
1644, 1577, 1411, 699; MS (EI) m/z 77, 105, 144, 193,
221, 295, 324; HRMS-ESI (m/z): calcd for C22H16N2NaO,
[M+Na]+: 347.1155, found 347.1157.
(E)-4-(2,6-Dichlorostyryl)-3,5-diphenylisoxazole (4k):
Yield: 75% (58.7 mg) as a yellow solid; mp = 115.3 -
116.6 °C; 1H NMR (400 MHz, CDCl3) δ 7.88 (dd, J = 8.0,
1.6 Hz, 2H), 7.80 - 7.71 (m, 2H), 7.50 (ddd, J = 11.6, 7.2,
2.4 Hz, 6H), 7.28 (d, J = 8.0 Hz, 2H), 7.11 - 7.00 (m, 2H),
6.67 (d, J = 16.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
166.8, 162.4, 134.4, 134.4, 130.2, 129.6, 129.3, 129.2,
128.9, 128.8, 128.6, 128.5, 128.0, 127.9, 127.9, 124.7,
112.0 ppm; νmax(KBr)/cm-1 3057, 2923, 1645, 1569, 1492,
1411, 698; MS (EI) m/z 77, 105, 148, 246, 293, 356, 391;
HRMS-ESI (m/z): calcd for C23H16Cl2NO, [M+H]+:
392.0603, found 392.0605.
(E)-4-(4-Chlorostyryl)-3-phenyl-5-(p-tolyl)isoxazole
(5a): Yield: 80% (59.4 mg) as a yellow solid; mp = 125.0 -
1
126.3 °C; H NMR (400 MHz, CDCl3) δ 7.73 - 7.63 (m,
4H), 7.50 - 7.44 (m, 3H), 7.30 (d, J = 8.0 Hz, 2H), 7.25 (d,
J = 6.4 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 6.92 (d, J = 16.8
Hz, 1H), 6.57 (d, J = 16.4 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 166.5, 162.2, 140.5, 135.4, 133.6, 132.4, 129.7,
129.7, 129.5, 128.9, 128.9, 128.8, 127.6, 127.5, 125.4,
116.7, 111.7, 21.6 ppm; νmax(KBr)/cm-1 3041, 2922, 1634,
1491, 1408, 1091, 697; MS (EI) m/z 91, 119, 149, 165,
280, 342, 371; HRMS-ESI (m/z): calcd for C24H18ClNNaO,
[M+Na]+: 394.0969, found 394.0975.
(E)-3,5-Diphenyl-4-(4-(trifluoromethyl)styryl)isoxazole
(4l): Yield: 70% (54.7 mg) as a yellow solid; mp = 132.8 -
134.6 °C; 1H NMR (400 MHz, CDCl3) δ 7.80 (dd, J = 7.6,
2.0 Hz, 2H), 7.68 (dd, J = 6.8, 3.0 Hz, 2H), 7.57 - 7.45 (m,
8H), 7.38 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 16.8 Hz, 1H),
6.65 (d, J = 16.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ
166.7, 162.3, 140.3, 132.4, 130.3, 129.8, 129.7 (q, J = 32.5
Hz), 129.3, 129.1, 128.9, 128.8, 128.0, 127.7, 126.4, 125.7
(q, J = 3.8 Hz), 124.1 (q, J = 271.9 Hz), 118.5, 112.0 ppm;
νmax(KBr)/cm-1 3058, 2924, 1608, 1494, 1409, 1323, 697;
MS (EI) m/z 77, 105, 183, 245, 345, 391; HRMS-ESI
(m/z): calcd for C24H17F3NO, [M+H]+: 392.1257, found
392.1261.
(E)-4-(4-Chlorostyryl)-5-(4-ethylphenyl)-3-phenyl-
1
isoxazole (5b): Yield: 81% (62.4 mg) as a yellow oil; H
NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.0 Hz, 2H), 7.70 -
7.63 (m, 2H), 7.48 (dd, J = 6.4, 3.6 Hz, 3H), 7.33 (d, J =
8.4 Hz, 2H), 7.26 (d, J = 8.6 Hz, 2H), 7.21 (d, J = 8.6 Hz,
2H), 6.94 (d, J = 16.8 Hz, 1H), 6.57 (d, J = 16.8 Hz, 1H),
2.72 (q, J = 7.6 Hz, 2H), 1.29 (t, J = 7.6 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 166.6, 162.2, 146.7, 135.4, 133.6,
132.4, 129.6, 129.5, 128.9, 128.9, 128.8, 128.5, 127.7,
127.5, 125.6, 116.7, 111.7, 28.9, 15.3 ppm; νmax(KBr)/cm-1
3044, 2926, 1609, 1490, 1446, 1408, 1092, 698; MS (EI)
m/z 73, 135, 207, 253, 283, 327, 385; HRMS-ESI (m/z):
calcd for C25H20ClNNaO, [M+Na]+: 408.1126, found
408.1123.
(E)-Methyl
4-(2-(3,5-diphenylisoxazol-4-yl)vinyl)-
benzoate (4m): Yield: 63% (48.0 mg) as a yellow solid;
mp = 153.6 - 155.3 °C; 1H NMR (400 MHz, CDCl3) δ 7.97
(d, J = 8.4 Hz, 2H), 7.81 (dd, J = 7.6, 2.0 Hz, 2H), 7.69 (dd,
J = 6.8, 2.8 Hz, 2H), 7.59 - 7.39 (m, 6H), 7.34 (d, J = 8.4
Hz, 2H), 7.09 (d, J = 16.8 Hz, 1H), 6.66 (d, J = 16.8 Hz,
1H), 3.90 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 166.7,
166.7, 162.3, 141.2, 132.7, 130.3, 130.0, 129.8, 129.4,
129.3, 129.1, 128.9, 128.8, 128.0, 127.8, 126.1, 118.5,
112.1, 52.1 ppm; νmax(KBr)/cm-1 3056, 2926, 1604, 1495,
1413, 1276, 1116, 700; MS (EI) m/z 77, 105, 207, 262,
283, 322, 381; HRMS-ESI (m/z): calcd for C25H19NNaO3,
[M+Na]+: 404.1257, found 404.1262.
(E)-5-(4-(tert-Butyl)phenyl)-4-(4-chlorostyryl)-3-phenyl
-isoxazole (5c): Yield: 87% (71.8 mg) as a yellow solid;
mp = 134.8 - 136.3 °C; 1H NMR (400 MHz, CDCl3) δ 7.75
(d, J = 8.4 Hz, 2H), 7.68 (dd, J = 6.8, 3.0 Hz, 2H), 7.53 (d,
J = 8.4 Hz, 2H), 7.50 - 7.43 (m, 3H), 7.27 (d, J = 8.4 Hz,
2H), 7.22 (d, J = 8.8 Hz, 2H), 6.96 (d, J = 16.4 Hz, 1H),
6.58 (d, J = 16.4 Hz, 1H), 1.37 (s, 9H); 13C NMR (100
MHz, CDCl3) δ 166.5, 162.2, 153.6, 135.4, 133.6, 132.5,
129.6, 129.6, 128.9, 128.9, 128.7, 127.5, 127.4, 126.0,
125.3, 116.8, 111.7, 35.0, 31.2 ppm; νmax(KBr)/cm-1 3049,
2961, 1640, 1489, 1409, 1092, 698; MS (EI) m/z 77, 118,
161, 217, 280, 328, 398, 413; HRMS-ESI (m/z): calcd for
C27H25ClNO, [M+H]+: 414.1619, found 414.1622.
(E)-4-(2-(3,5-Diphenylisoxazol-4-yl)vinyl)benzaldehyde
(4n): Yield: 65% (45.6 mg) as a yellow solid; mp = 99.5 -
100.7 °C; 1H NMR (400 MHz, CDCl3) δ 9.97 (s, 1H), 7.81
(d, J = 8.0 Hz, 4H), 7.68 (dd, J = 6.8, 3.0 Hz, 2H), 7.53 (qd,
J = 5.5, 2.8 Hz, 6H), 7.42 (d, J = 8.0 Hz, 2H), 7.14 (d, J =
16.8 Hz, 1H), 6.68 (d, J = 16.8 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 191.4, 166.9, 162.2, 142.8, 135.6, 132.3,
130.4, 130.2, 129.8, 129.3, 129.1, 128.9, 128.9, 127.9,
(E)-4-(4-Chlorostyryl)-5-(4-pentylphenyl)-3-phenyl-
1
isoxazole (5d): Yield: 90% (76.9 mg) as a yellow oil; H
NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.0 Hz, 2H), 7.67
127.8, 126.7, 119.4, 112.0 ppm; νmax(KBr)/cm-1 3055, 2923, (dd, J = 6.8, 3.0 Hz, 2H), 7.48 (dd, J = 6.4, 3.6 Hz, 3H),
1693, 1596, 1494, 1405, 696; MS (EI) m/z 77, 105, 135,
207, 281, 322, 351; HRMS-ESI (m/z): calcd for
C24H17NNaO2, [M+Na]+: 374.1151, found 374.1157.
7.31 (d, J = 8.0 Hz, 2H), 7.26 (d, J = 8.8 Hz, 2H), 7.21 (d,
J = 8.8 Hz, 2H), 6.94 (d, J = 16.4 Hz, 1H), 6.57 (d, J =
16.8 Hz, 1H), 2.73 - 2.62 (m, 2H), 1.67 (dt, J = 14.8, 7.2
Hz, 2H), 1.45 - 1.29 (m, 4H), 0.91 (t, J = 6.8 Hz, 3H); 13
C
NMR (100 MHz, CDCl3) δ 166.6, 162.2, 145.5, 135.4,
133.6, 132.4, 129.6, 129.6, 129.1, 128.9, 128.8, 128.7,
127.6, 127.4, 125.5, 116.8, 111.7, 35.9, 31.5, 30.9, 22.6,
14.1 ppm; νmax(KBr)/cm-1 3040, 2929, 1606, 1490, 1450,
1092, 699; HRMS-ESI (m/z): calcd for C28H27ClNO,
[M+H]+: 428.1776, found 428.1775.
(E)-4-(2-(Naphthalen-2-yl)vinyl)-3,5-diphenylisoxazole
(4o): Yield: 61% (45.5 mg) as a yellow solid; mp = 145.2 -
147.0 °C; 1H NMR (400 MHz, CDCl3) δ 7.85 (dd, J = 8.0,
1.6 Hz, 2H), 7.82 - 7.72 (m, 5H), 7.63 - 7.54 (m, 2H), 7.53
- 7.46 (m, 6H), 7.45 - 7.39 (m, 2H), 7.08 (d, J = 16.8 Hz,
1H), 6.80 (d, J = 16.8 Hz, 1H); 13C NMR (100 MHz,
8
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10.1002/adsc.201800444
Advanced Synthesis & Catalysis
(E)-4-(4-Chlorostyryl)-5-(4-ethoxyphenyl)-3-phenyl-
isoxazole (5e): Yield: 82% (65.7 mg) as a yellow solid; mp
= 115.3 - 117.2 °C; 1H NMR (400 MHz, CDCl3) δ 7.77 (d,
J = 8.8 Hz, 2H), 7.71 (dd, J = 6.4, 2.8 Hz, 2H), 7.57 - 7.45
(m, 3H), 7.30 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H),
7.04 (d, J = 8.8 Hz, 2H), 6.95 (d, J = 16.4 Hz, 1H), 6.61 (d,
J = 16.8 Hz, 1H), 4.13 (q, J = 7.2 Hz, 2H), 1.49 (t, J = 7.2
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 166.4, 162.2,
160.5, 135.5, 133.6, 132.2, 129.6, 129.2, 128.9, 128.9,
128.7, 127.4, 120.5, 116.9, 114.9, 111.0, 63.7, 14.8 ppm;
νmax(KBr)/cm-1 3050, 2928, 1610, 1497, 1408, 1253, 1095,
699; MS (EI) m/z 73, 135, 207, 281, 372, 401; HRMS-ESI
(m/z): calcd for C25H20ClNNaO2, [M+Na]+: 424.1075,
found 424.1078.
111.4, 37.1, 31.9, 26.0 ppm; νmax(KBr)/cm-1 3052, 2955,
1645, 1489, 1447, 1413, 1090, 697; MS (EI) m/z 55, 69,
149, 217, 253, 280, 349; HRMS-ESI (m/z): calcd for
C22H21ClNO, [M+H]+: 350.1306, found 350.1310.
(E)-4-(4-Chlorostyryl)-5-cyclohexyl-3-phenylisoxazole
(5k): Yield: 76% (55.2 mg) as a yellow solid; mp = 93.2 -
1
94.8 °C; H NMR (400 MHz, CDCl3) δ 7.63 (dd, J = 5.6,
2.4 Hz, 2H), 7.52 - 7.42 (m, 3H), 7.37 - 7.27 (m, 4H), 6.76
(d, J = 16.8 Hz, 1H), 6.53 (d, J = 16.8 Hz, 1H), 3.13 - 2.93
(m, 1H), 1.94 (dd, J = 24.0, 12.4 Hz, 4H), 1.85 - 1.72 (m,
3H), 1.52 - 1.32 (m, 3H); 13C NMR (100 MHz, CDCl3) δ
173.8, 161.4, 135.6, 133.5, 130.7, 129.7, 129.6, 129.5,
128.9, 128.7, 127.4, 117.2, 110.7, 36.7, 30.9, 26.2, 25.7
ppm; νmax(KBr)/cm-1 3052, 2933, 1642, 1489, 1449, 1091,
696; MS (EI) m/z 77, 149, 217, 253, 280, 334, 363;
HRMS-ESI (m/z): calcd for C23H22ClNNaO, [M+Na]+:
386.1282, found 386.1288.
(E)-4-(4-Chlorostyryl)-5-(2-fluorophenyl)-3-phenyl-
1
isoxazole (5f): Yield: 73% (54.7 mg) as a yellow oil; H
NMR (400 MHz, CDCl3) δ 7.76 - 7.68 (m, 2H), 7.66 (dd, J
= 7.2, 1.6 Hz, 1H), 7.50 (dt, J = 5.6, 2.8 Hz, 4H), 7.31 (t, J
= 7.6 Hz, 1H), 7.23 (d, J = 8.4 Hz, 3H), 7.16 (d, J = 8.8 Hz,
2H), 6.83 (dd, J = 16.4, 1.2 Hz, 1H), 6.48 (d, J = 16.8 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 162.0, 161.9, 159.4 (d,
J = 253.6 Hz), 135.4, 133.6, 132.4 (d, J = 8.3 Hz), 131.8 (d,
J = 1.3 Hz), 130.9 (d, J = 2.3 Hz), 129.8, 129.2, 129.0,
128.9, 128.8, 127.5, 124.7 (d, J = 3.7 Hz), 116.7 (d, J =
21.3 Hz), 116.4, 116.3 (d, J = 3.6 Hz), 114.6 ppm;
νmax(KBr)/cm-1 3055, 2928, 1609, 1492, 1409, 700; MS
(EI) m/z 95, 149, 207, 300, 358, 375; HRMS-ESI (m/z):
calcd for C23H15ClFNNaO, [M+Na]+: 398.0718, found
398.0727.
(E)-5-Butyl-4-(4-chlorostyryl)-3-phenylisoxazole (5l):
Yield: 67% (45.2 mg) as a yellow oil; 1H NMR (400 MHz,
CDCl3) δ 7.74 - 7.60 (m, 2H), 7.58 - 7.45 (m, 3H), 7.38 -
7.29 (m, 4H), 6.79 (d, J = 16.4 Hz, 1H), 6.63 (d, J = 16.4
Hz, 1H), 2.95 (t, J = 7.6 Hz, 2H), 1.93 - 1.77 (m, 2H), 1.52
- 1.32 (m, 4H), 0.96 (t, J = 6.8 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 170.4, 161.5, 135.6, 133.5, 130.7, 129.6,
129.5, 128.9, 128.8, 128.7, 127.4, 117.2, 112.0, 31.5, 27.2,
26.5, 22.3, 13.9 ppm; νmax(KBr)/cm-1 3049, 2931, 1603,
1489, 1422, 1090, 695; MS (EI) m/z 77, 121, 149, 217,
253, 280, 351; HRMS-ESI (m/z): calcd for C22H22ClNNaO,
[M+Na]+: 374.1282, found 374.1286.
(E)-5-(4-Chlorophenyl)-4-(4-chlorostyryl)-3-phenyl-
isoxazole (5g): Yield: 75% (58.7 mg) as a yellow solid;
mp = 148.0 - 149.7 °C; 1H NMR (400 MHz, CDCl3) δ 7.75
(d, J = 8.8 Hz, 2H), 7.67 (dd, J = 6.4, 3.0 Hz, 2H), 7.55 -
7.44 (m, 5H), 7.28 (d, J = 8.4 Hz, 2H), 7.22 (d, J = 8.8 Hz,
2H), 6.89 (d, J = 16.4 Hz, 1H), 6.59 (d, J = 16.8 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 165.0, 162.3, 136.3, 135.1,
133.9, 133.3, 129.8, 129.4, 129.2, 129.0, 128.9, 128.8,
128.7, 127.5, 126.6, 116.1, 112.5 ppm; νmax(KBr)/cm-1
3056, 2920, 1580, 1475, 1438, 1087, 737; MS (EI) m/z 77,
111, 139, 217, 280, 355, 391; HRMS-ESI (m/z): calcd for
C23H15Cl2NNaO, [M+Na]+: 414.0423, found 414.0426.
(E)-4-(4-Chlorostyryl)-5-isobutyl-3-phenylisoxazole
(5m): Yield: 72% (48.5 mg) as a yellow solid; mp = 95.5 -
1
97.3 °C; H NMR (400 MHz, CDCl3) δ 7.56 (dd, J = 6.8,
3.0 Hz, 2H), 7.46 - 7.32 (m, 3H), 7.27 - 7.16 (m, 4H), 6.66
(d, J = 16.4 Hz, 1H), 6.50 (d, J = 16.4 Hz, 1H), 2.71 (d, J =
7.2 Hz, 2H), 0.96 (s, 3H), 0.94 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 169.8, 161.4, 135.6, 133.5, 130.8, 129.6,
129.5, 128.9, 128.8, 128.7, 127.4, 117.2, 112.7, 35.3, 28.0,
22.6 ppm; νmax(KBr)/cm-1 3048, 2953, 1598, 1486, 1414,
1270, 1090, 698; MS (EI) m/z 57, 77, 114, 217, 280, 304,
337; HRMS-ESI (m/z): calcd for C21H20ClNNaO,
[M+Na]+: 360.1126, found 360.1130.
(E)-5-(4-Bromophenyl)-4-(4-chlorostyryl)-3-phenyl-
isoxazole (5h): Yield: 78% (67.8 mg) as a yellow solid;
mp = 126.2 - 127.8 °C; 1H NMR (400 MHz, CDCl3) δ 7.94
- 7.88 (m, 1H), 7.71 - 7.62 (m, 3H), 7.56 (d, J = 8.4 Hz,
1H), 7.48 (dd, J = 4.8, 1.4 Hz, 3H), 7.42 (d, J = 8.4 Hz,
1H), 7.29 (d, J = 8.5 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H),
6.93 - 6.81 (m, 1H), 6.62 (d, J = 16.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 163.4, 162.4, 134.9, 134.5, 134.0,
133.6, 131.1, 129.8, 129.3, 129.0, 128.9, 128.8, 127.9,
127.6, 126.5, 115.7, 113.2 ppm; νmax(KBr)/cm-1 3056, 2926,
1602, 1485, 1406, 697; MS (EI) m/z 91, 175, 202, 328,
370, 435; HRMS-ESI (m/z): calcd for C23H16BrClNO,
[M+H]+: 436.0098, found 436.0096.
(E)-4-(4-Chlorostyryl)-5-phenethyl-3-phenylisoxazole
1
(5n): Yield: 79% (60.8 mg) as a yellow oil; H NMR (400
MHz, CDCl3) δ 7.63 (dd, J = 6.4, 3.0 Hz, 2H), 7.51 - 7.40
(m, 3H), 7.33 - 7.24 (m, 4H), 7.19 (dd, J = 12.0, 5.6 Hz,
5H), 6.57 (d, J = 16.4 Hz, 1H), 6.30 (d, J = 16.4 Hz, 1H),
3.21 (dd, J = 11.4, 4.8 Hz, 2H), 3.12 (dd, J = 11.4, 4.8 Hz,
2H); 13C NMR (100 MHz, CDCl3) δ 168.8, 161.5, 140.2,
135.4, 133.6, 131.0, 129.7, 129.4, 128.9, 128.8, 128.7,
128.6, 128.5, 127.5, 126.6, 116.9, 112.9, 33.7, 28.7 ppm;
νmax(KBr)/cm-1 3042, 2941, 1599, 1487, 1415, 1089, 698;
MS (EI) m/z 77, 91, 149, 217, 280, 342, 385; HRMS-ESI
(m/z): calcd for C25H21ClNO, [M+H]+: 386.1306, found
386.1304.
(E)-4-(4-Chlorostyryl)-5-cyclopropyl-3-phenylisoxazole
1
(5i): Yield: 71% (49.4 mg) as a yellow oil; H NMR (400
(E)-4-(4-Chlorostyryl)-3-phenyl-5-(3-phenylpropyl)-
isoxazole (5o): Yield: 83% (66.2 mg) as a yellow oil; H
1
MHz, CDCl3) δ 7.66 - 7.59 (m, 2H), 7.55 - 7.44 (m, 3H),
7.36 - 7.26 (m, 4H), 6.82 (d, J = 16.4 Hz, 1H), 6.77 (d, J =
16.4 Hz, 1H), 2.25 - 2.13 (m, 1H), 1.33 - 1.22 (m, 2H),
1.20 - 1.09 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 170.2,
161.9, 135.7, 133.4, 130.7, 129.6, 129.4, 128.9, 128.8,
128.7, 127.4, 117.2, 112.3, 8.3, 8.2 ppm; νmax(KBr)/cm-1
3055, 2926, 1603, 1487, 1410, 1091, 698; MS (EI) m/z 59,
77, 103, 149, 253, 292, 321; HRMS-ESI (m/z): calcd for
C20H16ClNNaO, [M+Na]+: 344.0813, found 344.0814.
NMR (400 MHz, CDCl3) δ 7.64 (dd, J = 6.4, 2.8 Hz, 2H),
7.54 - 7.45 (m, 3H), 7.36 - 7.25 (m, 4H), 7.20 (dd, J = 12.4,
5.6 Hz, 5H), 6.68 (d, J = 16.4 Hz, 1H), 6.49 (d, J = 16.45
Hz, 1H), 2.93 (t, J = 7.6 Hz, 2H), 2.75 (t, J = 7.2 Hz, 2H),
2.17 (p, J = 7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ
169.9, 161.6, 141.1, 135.5, 133.5, 130.8, 129.7, 129.4,
128.9, 128.8, 128.7, 128.6, 128.5, 127.4, 126.2, 117.0,
112.2, 35.2, 28.8, 25.7 ppm; νmax(KBr)/cm-1 3035, 2932,
1600, 1489, 1415, 1264, 1091, 698; MS (EI) m/z 77, 91,
149, 207, 294, 355, 399; HRMS-ESI (m/z): calcd for
C26H23ClNO, [M+H]+: 400.1463, found 400.1460.
(E)-4-(4-Chlorostyryl)-5-cyclopentyl-3-phenylisoxazole
1
(5j): Yield: 75% (52.4 mg) as a yellow oil; H NMR (400
MHz, CDCl3) δ 7.70 - 7.58 (m, 2H), 7.55 - 7.40 (m, 3H),
7.32 - 7.26 (m, 4H), 6.77 (d, J = 16.4 Hz, 1H), 6.57 (d, J =
16.4 Hz, 1H), 3.50 - 3.32 (m, 1H), 2.15 - 2.04 (m, 2H),
1.97 (ddd, J = 20.4, 14.8, 7.6 Hz, 4H), 1.82 - 1.66 (m, 2H);
13C NMR (100 MHz, CDCl3) δ 173.2, 161.5, 135.6, 133.5,
130.9, 129.7, 129.6, 128.9, 128.8, 128.7, 127.4, 117.3,
(E)-4-(4-Chlorostyryl)-3-phenyl-5-(thiophen-2-yl)-
isoxazole (5p): Yield: 73% (53.1 mg) as a yellow solid;
mp = 111.3 - 112.9 °C; 1H NMR (400 MHz, CDCl3) δ 7.84
(dd, J = 2.8, 1.2 Hz, 1H), 7.68 (dd, J = 6.8, 3.0 Hz, 2H),
7.55 (dd, J = 5.2, 1.2 Hz, 1H), 7.46 (tt, J = 5.2, 3.2 Hz, 4H),
9
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800444
Advanced Synthesis & Catalysis
7.31 - 7.27 (m, 3H), 7.24 - 7.21 (m, 1H), 6.94 (d, J = 16.4
Hz, 1H), 6.64 (d, J = 16.8 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 162.6, 162.1, 135.2, 133.8, 133.1, 129.7, 129.3,
129.0, 128.9, 128.8, 128.7, 127.5, 126.9, 126.0, 125.7,
116.5, 111.7 ppm; νmax(KBr)/cm-1 3026, 2925, 1598, 1488,
1437, 696; MS (EI) m/z 83, 111, 149, 214, 267, 330, 363;
HRMS-ESI (m/z): calcd for C21H14ClNNaOS, [M+Na]+:
386.0377, found 386.0369.
(E)-4-(4-Chlorostyryl)-3-(3-methoxyphenyl)-5-phenyl-
1
isoxazole (5v): Yield: 76% (58.8 mg) as a yellow oil; H
NMR (400 MHz, CDCl3) δ 7.84 (d, J = 7.6 Hz, 2H), 7.58 -
7.50 (m, 3H), 7.42 (t, J = 8.0 Hz, 1H), 7.29 (dd, J = 12.4,
5.6 Hz, 6H), 7.15 - 7.03 (m, 1H), 6.98 (d, J = 16.4 Hz, 1H),
6.66 (d, J = 16.4 Hz, 1H), 3.85 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 166.3, 162.1, 159.8, 135.3, 133.7, 132.8,
130.6, 130.2, 129.9, 129.0, 128.9, 128.2, 127.7, 127.5,
121.3, 116.5, 115.9, 113.9, 112.2, 55.4 ppm; νmax(KBr)/cm-
1
3051, 2929, 1606, 1489, 1413, 1252, 694; MS (EI) m/z
(E)-4-(4-Chlorostyryl)-5-(naphthalen-2-yl)-3-phenyl-
isoxazole (5q): Yield: 66% (53.7 mg) as a yellow solid;
mp = 132.8 - 134.2 °C; 1H NMR (400 MHz, CDCl3) δ 8.30
(s, 1H), 7.98 - 7.82 (m, 4H), 7.76 - 7.66 (m, 2H), 7.61 -
7.44 (m, 5H), 7.26 (d, J = 8.4 Hz, 2H), 7.21 (d, J = 8.4 Hz,
2H), 7.00 (d, J = 16.8 Hz, 1H), 6.63 (d, J = 16.8 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 166.3, 162.4, 135.3, 133.8,
133.8, 133.1, 132.9, 129.7, 129.4, 128.9, 128.8, 128.7,
127.9, 127.8, 127.5, 127.5, 127.0, 125.5, 124.3, 116.6,
112.5 ppm; νmax(KBr)/cm-1 3054, 2924, 1595, 1489, 1408,
753; MS (EI) m/z 77, 105, 207, 310, 387, 407; HRMS-ESI
(m/z): calcd for C27H18ClNNaO, [M+Na]+: 430.0969,
found 430.0973.
77, 105, 149, 207, 283, 358, 387; HRMS-ESI (m/z): calcd
for C24H19ClNO2, [M+H]+: 388.1099, found 388.1098.
(E)-3-(3-Chlorophenyl)-4-(4-chlorostyryl)-5-phenyl-
1
isoxazole (5w): Yield: 70% (54.7 mg) as a yellow oil; H
NMR (400 MHz, CDCl3) δ 7.77 - 7.69 (m, 2H), 7.63 (s,
1H), 7.52 - 7.37 (m, 5H), 7.33 (d, J = 7.6 Hz, 1H), 7.20 (d,
J = 8.4 Hz, 2H), 7.15 (d, J = 8.8 Hz, 2H), 6.83 (d, J = 16.4
Hz, 1H), 6.50 (d, J = 16.8 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 166.6, 161.0, 135.1, 134.8, 133.9, 133.3, 131.2,
130.3, 130.0, 129.8, 129.1, 129.0, 128.9, 127.9, 127.6,
127.5, 127.0, 116.1, 112.0 ppm; νmax(KBr)/cm-1 3056, 2929,
1598, 1488, 1438, 694; MS (EI) m/z 77, 105, 149, 251,
328, 362, 391; HRMS-ESI (m/z): calcd for C23H16Cl2NO,
[M+H]+: 392.0603, found 392.0602.
(E)-4-(4-Chlorostyryl)-5-phenyl-3-(o-tolyl)isoxazole (5r):
Yield: 77% (57.1 mg) as a yellow oil; 1H NMR (400 MHz,
CDCl3) δ 7.85 - 7.78 (m, 2H), 7.61 - 7.49 (m, 3H), 7.40 (d,
J = 7.2 Hz, 2H), 7.33 (d, J = 7.2 Hz, 2H), 7.21 (d, J = 8.4
Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 16.4 Hz,
1H), 6.26 (d, J = 16.4 Hz, 1H), 2.28 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 166.0, 162.2, 137.3, 135.5, 133.5,
130.5, 130.4, 130.2, 130.0, 129.8, 129.3, 129.1, 128.8,
128.1, 127.8, 127.4, 126.1, 116.5, 112.9, 19.8 ppm;
νmax(KBr)/cm-1 3055, 2926, 1590, 1488, 1410, 1090, 696;
MS (EI) m/z 65, 105, 194, 266, 354, 371; HRMS-ESI
(m/z): calcd for C24H18ClNNaO, [M+Na]+: 394.0969,
found 394.0973.
(E)-4-(4-Chlorostyryl)-5-phenyl-3-propylisoxazole (5x):
Yield: 76% (49.1 mg) as a yellow oil; 1H NMR (400 MHz,
CDCl3) δ 7.75 - 7.64 (m,2H), 7.57 - 7.46 (m, 3H), 7.44 -
7.28 (m, 4H), 6.80 (d, J = 16.4 Hz, 1H), 6.64 (d, J = 16.4
Hz, 1H), 2.95 (t, J = 7.2 Hz, 2H), 1.98 - 1.82 (m, 2H), 1.10
(t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 170.2,
161.5, 135.6, 133.5, 130.8, 129.6, 129.5, 128.9, 128.8,
128.7, 127.4, 117.2, 112.1, 28.4, 21.0, 14.0 ppm;
νmax(KBr)/cm-1 3044, 2957, 1638, 1482, 1089, 773, 698;
MS (EI) m/z 77, 114, 149, 217, 253, 280, 323; HRMS-ESI
(m/z): calcd for C20H19ClNO, [M+H]+: 324.1150, found
324.1152.
(E)-4-(4-Chlorostyryl)-5-phenyl-3-(p-tolyl)isoxazole (5s):
Yield: 82% (60.8 mg) as a yellow solid; mp = 137.5 -
138.7 °C; 1H NMR (400 MHz, CDCl3) δ 7.80 (dd, J = 7.6,
1.6 Hz, 2H), 7.57 (d, J = 8.0 Hz, 2H), 7.53 - 7.44 (m, 3H),
7.34 - 7.24 (m, 3H), 7.22 (d, J = 8.8 Hz, 3H), 6.93 (d, J =
16.4 Hz, 1H), 6.61 (d, J = 16.4 Hz, 1H), 2.42 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 166.2, 162.2, 139.7, 135.4,
133.7, 132.7, 130.1, 129.5, 129.0, 128.9, 128.8, 128.2,
127.7, 127.5, 126.4, 116.7, 112.1, 21.5 ppm; νmax(KBr)/cm-
(E)-4-(4-Chlorostyryl)-3-cyclopentyl-5-phenylisoxazole
1
(5y): Yield: 70% (48.9 mg) as a yellow oil; H NMR (400
MHz, CDCl3) δ 7.79 - 7.66 (m, 2H), 7.54 - 7.42 (m, 3H),
7.34 (q, J = 8.8 Hz, 4H), 6.91 (d, J = 16.4 Hz, 1H), 6.83 (d,
J = 16.4 Hz, 1H), 3.32 (p, J = 7.6 Hz, 1H), 2.12 (td, J =
11.8, 6.8 Hz, 2H), 1.99 (td, J = 14.4, 7.2 Hz, 2H), 1.93 -
1.81 (m, 2H), 1.78 - 1.66 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 166.2, 165.8, 135.6, 133.6, 131.4, 129.9, 129.0,
128.9, 128.4, 127.6, 127.5, 117.6, 112.3, 37.0, 31.6, 25.6
ppm; νmax(KBr)/cm-1 3044, 2942, 1642, 1574, 1484, 1238,
1086, 763, 692; MS (EI) m/z 77, 105, 191, 253, 280, 308,
349; HRMS-ESI (m/z): calcd for C22H21ClNO, [M+H]+:
350.1306, found 350.1309.
1
3052, 2927, 1592, 1489, 1412, 1090, 696; MS (EI) m/z
77, 105, 149, 194, 294, 342, 371; HRMS-ESI (m/z): calcd
for C24H18ClNNaO, [M+Na]+: 394.0969, found 394.0975.
(E)-4-(4-Chlorostyryl)-3-(4-ethylphenyl)-5-phenyl-
1
isoxazole (5t): Yield: 82% (63.1 mg) as a yellow oil; H
NMR (400 MHz, CDCl3) δ 7.85 - 7.76 (m, 2H), 7.60 (d, J
= 8.0 Hz, 2H), 7.55 - 7.44 (m, 3H), 7.29 (dd, J = 14.8, 8.2
Hz, 4H), 7.22 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 16.4 Hz,
1H), 6.62 (d, J = 16.4 Hz, 1H), 2.72 (q, J = 7.6 Hz, 2H),
1.29 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
166.1, 162.2, 146.0, 135.4, 133.7, 132.7, 130.1, 129.0,
128.9, 128.8, 128.3, 128.3, 127.7, 127.5, 126.6, 116.7,
112.1, 28.8, 15.4 ppm; νmax(KBr)/cm-1 3053, 2934, 1605,
1487, 1416, 1270, 1089, 698; MS (EI) m/z 77, 105, 149,
208, 280, 321, 385; HRMS-ESI (m/z): calcd for
C25H20ClNNaO, [M+Na]+: 408.1126, found 408.1124.
(E)-3-(tert-Butyl)-4-(4-chlorostyryl)-5-phenylisoxazole
1
(5z): Yield: 79% (53.4 mg) as a yellow oil; H NMR (400
MHz, CDCl3) δ 7.61 (dd, J = 6.4, 2.8 Hz, 2H), 7.46 - 7.36
(m, 3H), 7.26 (d, J = 8.4 Hz, 2H), 7.19 (d, J = 8.4 Hz, 2H),
6.95 (d, J = 16.4 Hz, 1H), 6.28 (d, J = 16.4 Hz, 1H), 1.48
(s, 9H); 13C NMR (100 MHz, CDCl3) δ 175.9, 162.1, 135.4,
133.5, 133.1, 129.9, 129.4, 128.9, 128.8, 128.6, 127.4,
117.3, 110.6, 34.4, 29.2 ppm; νmax(KBr)/cm-1 3053, 2964,
1643, 1479, 1282, 1086, 764, 694; MS (EI) m/z 77, 114,
149, 245, 280, 322, 337; HRMS-ESI (m/z): calcd for
C21H21ClNO, [M+H]+: 338.1306, found 338.1309.
(E)-4-(4-Chlorostyryl)-3-(4-methoxyphenyl)-5-phenyl-
1
isoxazole (5u): Yield: 73% (56.5 mg) as a yellow oil; H
4-((E)-4-Chlorostyryl)-5-phenyl-3-((E)-styryl)isoxazole
NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.0 Hz, 2H), 7.62
(d, J = 8.4 Hz, 2H), 7.55 - 7.39 (m, 3H), 7.24 (t, J = 8.2 Hz, - 114.6 °C; H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 7.6
(5ba): Yield: 58% (44.5 mg) as a yellow solid; mp = 113.2
1
4H), 7.00 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 16.4 Hz, 1H),
6.63 (d, J = 16.4 Hz, 1H), 3.86 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 166.1, 161.9, 160.8, 135.4, 133.7, 132.7,
130.2, 130.1, 129.0, 128.9, 128.3, 127.6, 127.5, 121.6,
116.8, 114.3, 112.1, 55.4 ppm; νmax(KBr)/cm-1 3051, 2934,
1607, 1487, 1429, 1251, 1091, 696; MS (EI) m/z 77, 105,
207, 281, 327, 387; HRMS-ESI (m/z): calcd for
C24H19ClNO2, [M+H]+: 388.1099, found 388.1103.
Hz, 2H), 7.52 (dt, J = 12.8, 10.6 Hz, 6H), 7.43 - 7.32 (m,
7H), 7.03 (d, J = 11.2 Hz, 1H), 6.99 (d, J = 11.6 Hz, 1H),
6.87 (d, J = 16.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
-1
166.1, 159.5, 136.1, 135.4, 133.9, 133.1, 133.0, 130.1,
3057, 2931, 1591, 1486, 1445, 1408, 694129.1, 129.0,
128.9, 128.8, 128.0, 127.6, 127.5, 127.2, 117.1, 114.5,
112.5 ppm; νmax(KBr)/cm; MS (EI) m/z 77, 105, 149, 292,
354, 383; HRMS-ESI (m/z): calcd for C25H18ClNNaO,
[M+Na]+: 406.0969, found 406.0972.
10
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800444
Advanced Synthesis & Catalysis
(E)-4-(4-Chlorostyryl)-3,5-dicyclohexylisoxazole (5bb):
Yield: 64% (47.3 mg) as a yellow oil; 1H NMR (400 MHz,
CDCl3) δ 7.38 (d, J = 7.6 Hz, 2H), 7.32 (d, J = 8.2 Hz, 2H),
6.75 (d, J = 16.4 Hz, 1H), 6.62 (d, J = 16.4 Hz, 1H), 2.92 (t,
J = 10.6 Hz, 1H), 2.78 (t, J = 10.4 Hz, 1H), 2.03 (d, J =
12.4 Hz, 2H), 1.93 – 1.81 (m, 6H), 1.70 (dd, J = 24.8, 11.2
Hz, 4H), 1.64 - 1.53 (m, 1H), 1.49 - 1.15 (m, 6H); 13C
NMR (100 MHz, CDCl3) δ 173.0, 165.8, 135.9, 133.3,
129.3, 128.9, 127.4, 117.5, 110.1, 36.5, 36.2, 31.4, 30.9,
26.4, 26.2, 26.1, 25.7 ppm; νmax(KBr)/cm-1 3052, 2928,
1594, 1443, 1093; MS (EI) m/z 83, 125, 149, 204, 244,
286, 301, 369; HRMS-ESI (m/z): calcd for calcd for
C23H29ClNO, [M+H]+: 370.1932, found 370.1937.
[7] a) P. G. Baraldi, A. Barco, S. Benetti, G. P. Pollini, D.
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Supporting Information
Copies of the 1H NMR and 13C NMR spectra for all
compounds are available in the supporting Information.
Acknowledgements
This work was supported by the financial support from the
National Key Research China and Development Program of
China (2016YFA0602900), the National Natural Science
Foundation of China (21502055, 21490572 and 21420102003),
and the Fundamental Research Funds for the Central Universities
(2015ZM150 and 2015ZY001).
[10] For selected reviews, a) R. Jana, T. P. Pathak, M. S.
Sigman, Chem. Rev. 2011, 111, 1417-1492; b) Y. Xia,
Y. Zhang, J. Wang, ACS Catal. 2013, 3, 2586-2598; c)
A. V. Gulevich, A. S. Dudnik, N. Chernyak, V.
Gevorgyan, Chem. Rev. 2013, 113, 3084-3213; d) X.-F.
Wu, H. Neumann, M. Beller, Chem. Rev. 2013, 113, 1-
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Int. Ed. 2014, 53, 4038-4040; f) X.-H. Yang, R.-J. Song,
Y.-X. Xie, J.-H. Li, ChemCatChem 2016, 8, 2429-2445.
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11
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Advanced Synthesis & Catalysis
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FULL PAPER
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13
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