TBAI-catalyzed intramolecular annulation of chalcone oximes toward isoxazoles

Article abstract of DOI:10.1016/j.catcom.2017.11.008

A TBAI-catalyzed intramolecular annulation of chalcone oximes toward isoxazoles was developed, providing 3,5-diarylisoxazoles in good yields. Functional groups such as methoxy, ethyoxyl, chloro, bromo, fluoro and nitro were well tolerated in this reaction

Full text of DOI:10.1016/j.catcom.2017.11.008

CatalysisCommunications105(2018)43–47
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Catalysis Communications
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Short communication
TBAI-catalyzed intramolecular annulation of chalcone oximes toward
isoxazoles
⁎⁎
Ablimit Abdukadera,⁎, Yadong Sunb, Zengpeng Zhangb, Chenjiang Liua,b,
a
School of Chemistry and Chemical Engineering, Xinjiang University, Urumqi, 830046, PR China
b
Physics and Chemistry Detecting Center, Xinjiang University, Urumqi, 830046, PR China
A R T I C L E I N F O
A B S T R A C T
Keywords:
Annulation
Tetrabutylammonium iodide
Chalcone oxime
Isoxazoles
A TBAI-catalyzed intramolecular annulation of chalcone oximes toward isoxazoles was developed, providing
3,5-diarylisoxazoles in good yields. Functional groups such as methoxy, ethyoxyl, chloro, bromo, fluoro and
nitro were well tolerated in this reaction. Notably, the reaction ran under metal-free in water.
Metal-free
1. Introduction
catalyzed cascade reaction of 1,3-dicarbonyl compounds with benzy-
lamines through dual sp3 CeH bonds activation toward oxazoles [23].
Isoxazoles are important five-membered aromatic heterocycles that
presents in numerous pharmaceuticals and natural products [1–2].
Consequently, plenty of methods have been developed to construct this
motif [3]. Generally, isoxazoles could be formed via following ways: (1)
the [3 + 2] cycloaddition between nitrile oxides and alkynes [4–5]; (2)
cycloisomerization of alkynyl oxime ethers [6–8]; (3) condensation
reactions [9–11]; along with other strategies [12–14]. Although sig-
nificant achievements have been realized, new protocols for the
synthesis of diversified isoxazoles under environmentally friendly
conditions are still highly desired.
Recently, hypervalent iodine-promoted organic reactions which
have solved the problem of residual metal in transition-metal catalysis
have received considerable attentions [15–16]. Among them, the
combination of tetrabutylammonium iodide (TBAI) with of tert-butyl
hydroperoxide (TBHP) has been proved to be a powerful oxidation
system to construct CeC, CeN, CeO and CeS bonds [17–22]. This
system also performed high efficiency for the synthesis of heterocyclic
compounds such as isoquinoline-1,3(2H,4H)-diones, pyrazoles, imi-
dazo[1,5-c]quinazolines, azaspirocyclohexadienones and phenan-
thridines [23–29]. For example, in 2012, Zhu developed the TBAI-
To our knowledge, this catalytic combination has never been applied
in the isoxazoles synthesis. Herein, we wish to describe our work on
the TBAI-catalyzed intramolecular annulation of chalcone oximes to-
ward isoxazoles.
2. Results and discussion
Initially, the reaction of chalcone oxime (1a) catalyzed by TBAI and
TBHP was carried out. Delightedly, the product 2a was obtained in 58%
yield when toluene was used as the solvent (Table 1, entry 1). Subse-
quently, other solvents such as 1,4-dioxane, DMSO, DMF, EtOH, and
H2O were investigated (Table 1, entries 2–6). The results disclosed that
using H2O as clean and green solvent performed the best efficiency,
providing 2a in 90% yield (Table 1, entry 6). Other catalysts such as KI,
NaI and I2 were all inferior to TBAI (Table 1, entries 7–9). It should be
noted that the reaction did not occur when TBAI was replaced by TBACl
or TBABr, which disclosed that the iodide was necessary for the reac-
tion (Table 1, entries 10 and 11). The yield of 2a dropped obviously at a
lower temperature (60 °C), whereas no better result was obtained at
elevated temperature (80 °C) (Table 1, entry 6). The control experiment
⁎
Corresponding author.
⁎⁎
Correspondence to: Chenjiang Liu, School of Chemistry and Chemical Engineering, Xinjiang University, Urumqi, 830046, PR China.
E-mail addresses: ablimit1970@126.com, pxylcj@126.com (A. Abdukader).
https://doi.org/10.1016/j.catcom.2017.11.008
Received 11 September 2017; Received in revised form 22 October 2017; Accepted 14 November 2017
1566-7367/©2017ElsevierB.V.Allrightsreserved.

A. Abdukader et al.
CatalysisCommunications105(2018)43–47
Table 1
Optimization of reaction conditions.
Entry
Catalyst
Oxidant
Solvent
Yield (%)a
1
2
3
4
5
6
7
8
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
NaI
KI
I2
TBABr
TBACl
–
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
–
toluene
1,4-dioxane
DMF
DMSO
EtOH
H2O
H2O
H2O
H2O
H2O
58
48
55
80
75
90 (78)b(87)c
48
50
33
0
0
0
9
10
11
12
13
H2O
H2O
H2O
TBAI
11
a
Reaction conditions: 1a (0.5 mmol), catalyst (10 mol%), TBHP (70% in water, 2.0 equiv), solvent (2 mL), 70 °C, 12 h, air. Isolated yield.
60 °C.
80 °C.
b
c
demonstrated that the reaction could not occur without catalyst
(Table 1, entry 12) and only 11% yield of the product was obtained in
absence of TBHP (Table 1, entry 13).
studies, a plausible mechanism was proposed, as shown in Scheme 2.
The active iodide species Bu4NOI A, which is generated in situ from
the oxidation of Bu4NI by TBHP, reacts with chalcone oxime 1a to
give iodonium ion B [30–33]. The following intramolecular annu-
lation of B resulted in the intermediate C. Finally, intermediate C
underwent HI elimination [34–35], and then released the 3,5-di-
phenylisoxazole 2a.
In conclusion, we have developed a TBAI-catalyzed intramolecular
annulation of chalcone oximes toward isoxazoles under metal-free
conditions using H2O as the clean and green solvent. Functional
groups such as methoxy, ethyoxyl, chloro, bromo, fluoro and nitro
were well tolerated in this reaction, providing 3,5-diarylisoxazoles in
good yields.
With the optimized reaction conditions established, the scope of this
protocol was investigated as listed in Tables 2 and 3. A variety of
substituents on the chalcone oximes (R1) were explored firstly. As
shown in Table 2, either electron-donating groups such as methoxy,
ethyoxyl and methyl or electron-withdrawing groups such as chloro,
bromo and nitro on the aryl rings were well tolerated, affording the
corresponding 3,5-diarylisoxazole products in good yields (Table 2,
2a–2m). The reaction is insensitive to steric hindrance, for substrate
with ortho-substituent resulted in similar yield with the para-substituted
one (2b vs 2c; 2h vs 2i). High efficiency was performed for the reaction
of chalcone oxime with strong electron deficient nitro group (2g).
Notably, the tolerance of halide substituents such as Cl and Br, provides
possibilities for further functionalizations (Table 2, 2h–2k). 3-methyl-5-
phenylisoxazole 2n was also obtained in good yield when R1 was me-
thyl.
3. Experimental
Chemicals were either purchased or purified by standard techniques
without special instructions. 1H NMR and 13C NMR spectra were
measured on a 400 MHz spectrometer (1H 400 MHz, 13C 100 MHz),
using CDCl3 as the solvent with tetramethylsilane (TMS) as the internal
standard at room temperature. Chemical shifts (δ) are given in ppm
relative to TMS, the coupling constants J are given in Hz.
Next, various substituents on the chalcone oximes (R2) were
tested. Substrates with electron donating or withdrawing group all
reacted smoothly to generate the desired 3,5-diarylisoxazoles in
good yields. Notably, styryl analogue was also good reaction partner
leading to the corresponding 3-phenyl-5-styrylisoxazole in good
yield (Table 3, 3m).
Control experiments were carried out to gain mechanistic insight
into this reaction. The reaction could not be suppressed when radical
scavenger 2,2,6,6-tetramethylpiperidinooxy (TEMPO) or 2,6-di-tert-
butyl-4-methylphenol (BHT) was added (Scheme 1). These results
suggested that this transformation was not a radical process. Only 50%
yield of 2a were generated in the presence of KI (Table 1, entry 8).
However, if n-Bu4NCl was added, the yield was obviously improved to
80% (Scheme 1, Eq. (3)), suggesting that the combination of I− and
Bu4N+ was crucial for this transformation.
3.1. General procedure of TBAI-catalyzed intramolecular annulation of
chalcone oximes toward isoxazoles
To the mixture of 1a (0.5 mmol), n-Bu4NI (0.05 mmol, 19 mg),
TBHP (1.0 mmol, 70% in water) and 2 mL of H2O were successively
added into the tube. The reaction mixture was stirred at 70 °C under air
for 12 h. Then, the reaction mixture was cooled to room temperature
and quenched by the addition of a saturated solution of Na2S2O3
(5 mL). The mixture was extracted with ethyl acetate (3 × 10 mL) and
the combined organic phases were dried over anhydrous MgSO4. After
Based on the above experimental results and former relevant
44

A. Abdukader et al.
CatalysisCommunications105(2018)43–47
Table 2
Scope of substituents (R1) on the chalcone oximes.a
a
Reaction conditions: 1 (0.5 mmol), TBAI (10 mol%), TBHP (2.0 equiv), H2O (2 mL), 70 °C, 12 h, air. Isolated yield.
45

A. Abdukader et al.
CatalysisCommunications105(2018)43–47
Table 3
Scope of substituents (R2) on the chalcone oximes.a
a
Reaction conditions: 1 (0.5 mmol), TBAI (10 mol%), TBHP (2.0 equiv), H2O (2 mL), 70 °C, 12 h, air. Isolated yield.
Scheme 1. Mechanism studies.
46

A. Abdukader et al.
CatalysisCommunications105(2018)43–47
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