Oxidative rearrangement strategy for synthesis of 2,4,5-trisubstituted oxazoles utilizing hypervalent iodine reagent

Article abstract of DOI:10.1016/j.tet.2016.07.082

Hypervalent iodine (III)-intermediated direct oxidative rearrangement of 3-hydroxybut-2-enimidates affording oxazoles under mild conditions has been developed. This protocol provides a new methodology to the synthesis of compounds containing oxazole structure.

Full text of DOI:10.1016/j.tet.2016.07.082

Accepted Manuscript
Oxidative rearrangement strategy for synthesis of 2, 4, 5-trisubstituted oxazoles
utilizing hypervalent iodine reagent
Qing Liu, Xiaohui Zhang, Yang He, Muhammad Ijaz Hussain, Wen Hu, Yan Xiong,
Xiangming Zhu
PII:
S0040-4020(16)30753-0
10.1016/j.tet.2016.07.082
TET 27978
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 20 April 2016
Revised Date: 22 July 2016
Accepted Date: 30 July 2016
Please cite this article as: Liu Q, Zhang X, He Y, Hussain MI, Hu W, Xiong Y, Zhu X, Oxidative
rearrangement strategy for synthesis of 2, 4, 5-trisubstituted oxazoles utilizing hypervalent iodine
reagent, Tetrahedron (2016), doi: 10.1016/j.tet.2016.07.082.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Oxidative rearrangement strategy for
synthesis of 2, 4, 5-trisubstituted oxazoles
utilizing hypervalent iodine reagent
Leave this area blank for abstract info.
Qing Liua, Xiaohui Zhanga, , Yang Hea, Muhammad Ijaz Hussaina, Wen Hua , Yan Xionga,b,*, Xiangming Zhuc
aSchool of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400044, China
bState Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China
cSchool of Chemistry & Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland

ACCEPTED MANUSCRIPT
1
Tetrahedron
journal homepage: www.elsevier.com
Oxidative rearrangement strategy for synthesis of 2, 4, 5-trisubstituted oxazoles
utilizing hypervalent iodine reagent
Qing Liua, Xiaohui Zhanga, , Yang Hea, Muhammad Ijaz Hussaina, Wen Hua , Yan Xionga,b,*, Xiangming
Zhuc
aSchool of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400044, China
bState Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China
cSchool of Chemistry & Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Hypervalent iodine (III)-intermediated direct oxidative rearrangement of 3-hydroxybut-2-
enimidates affording oxazoles under mild conditions has been developed. This protocol provides
a new methodogy to the synthesis of compounds containing oxazole structure.
2009 Elsevier Ltd. All rights reserved.
Available online
Keywords:
3-hydroxybut-2-enimidate
Hypervalent iodine
Isoxazole
Oxazole
Rearrangement
Corresponding author. Tel.: +86 02365111748; fax: +86 02365111748; e-mail: xiong@cqu.edu.cn; xiaohuizhang@cqu.edu.cn.

ACCEPTED MANUSCRIPT
2
Tetrahedron
Introduction
trisubstituted oxazole from 3-hydroxybut-2-enimidate utilizing
hypervalent iodine reagent (Scheme 1c).
Oxazole fragments are the key building groups in the
synthesis of natural product related compunds and act as a
significant role with biological and/or pharmaceutical active
centers.1 Especially, 5-substituted oxazole-4-carboxylic acid
esters as one of the most valuable intermediate products are used
in the synthesis of a large number of biological active compounds
such as GW475151.2 Moreover, 2, 4, 5-trisubstituted oxazoles
also were found as an important class of heterocycle structure
products with biological activities such as thiopeptide3 and
siphonazole4. Therefore, tremendous strategies for the preparation
of oxazole motifs have been persued. The synthetic methods of 2,
4, 5-trisubstituted oxazole derivatives compose of metal catalyzed
intermolecular or intramolecular cross-coupling5-9 and metal-free
methods10. Metal-free methods have received considerable
attention in recent decades. Hanzawa et al. reported metal-free
annulation procedure for the formation of highly substituted
oxazole, which was achieved by the iodine (III)-mediated
synthesis of 2, 4, 5-trisubstituted oxazole derivatives (Scheme
1a).11 Using same hypervalent iodine as oxidant, Zhao et al.
disclosed PhIO-mediated intermolecular oxidative coupling and
successive intramoleclar nucleophilic addition-elimination
towards synthesis of oxazoles (Scheme 1b).12
Results and discussion
We
firstly
chose
methyl
3-hydroxy-2-
(imino(phenoxy)methyl)but-2-enoate 2a as the model substrate to
examine the feasibility and reasonableness of this transformation.
This reaction was executed under 50 °C, subjecting 1.0 equiv of
iodobenzene diacetate 1a to 1.0 equiv of 2a in isopropanol (i-
PrOH) for 1 h and the desired product 3a was afforded in 20%
yield (Table 1, entry 1). The treatment of 2a with 1.2-1.8
equivalents of DIB yielded 12-35% of the product 3a, and 1.4
equivalents of DIB was found to be the best (Table 1, entries 2-5).
The different solvents such as ethanol, trifluoroethanol,
acetonitrile (CH3CN), toluene, dioxane and EGDME were
screened and lower yields were obtained (Table 1, entries 6-11).
Common alcohols with electron-donating group were more
favorable than that with electron-withdrawing group (Table 1,
entries 3 and 6 vs. entry 7). The chloroform promoted the
reaction to give the product 3a in 35% yield, which reaches the
same level of reactivity as in isopropanol (Table 1, entry 12).
Solvent screening studies revealed that DMF and DMSO are
detrimental to the reaction (Table 1, entries 13 and 14). Therefore,
we adopted chloroform with lower boiling point than isopropanol,
readily to move, as solvent for futher optimization of reaction
conditions. Fortunately, the structure of 3a was confirmed
oxazole through single-crystal X-ray diffraction analysis (Fig. 1).
Scheme 1. Synthesis of 2, 4, 5-trisubstituted oxazole
derivatives.
a) Hanzawa’s work
Table 1. Optimization of reaction conditions.a
b) Zhao’s work
Entry
1
DIB (x equiv)
Solvent
i-PrOH
Yieldb (%)
20
1.0
1.2
1.4
1.6
1.8
1.4
1.4
1.4
1.4
1.4
1.4
1.4
1.4
1.4
2
i-PrOH
33
3
i-PrOH
35
c) This work
4
i-PrOH
27
5
i-PrOH
12
6
CH3CH2OH
CF3CH2OH
CH3CN
Toluene
1,4-dioxane
EGDME
CHCl3
28
7
21
Different to above two pathways, we have reported
iodobenzene diacetate (DIB)-mediated oxidative Beckmann-type
rearrangement towards synthesis of benzoxazoles and
benzimidazoles and extended our method to preparation of
chlormidazol and clemizole.13 We have also developed oxidative
8
10
9
22
10
11
12
13
14
24
17
coupling reaction of anilines14 and oxidative cyanation15-17
,
35
covering hypervalent iodine-promoted cyanation of silyl enol
ethers via an umpolung strategy15 and tertiary or secondary
aimines via an oxidation/strecker reaction16,17. In our preliminary
work, the treatment of dicarbonyl compounds and
cyanatobenzene led to the formation of 3-hydroxybut-2-enimidate
directly18, which contains the substructures of enol and imine.
DMF
trace
N.R.c
DMSO
a Conditions: 2a (0.5 mmol) and DIB (specified) in solvent (1 mL) at 50 °C
for h. EGDME ethylene glycol dimethyl ether, DMF N,N-
1
=
=
dimethylformamide, DMSO = Dimethyl sulfoxide.
Inspired
by
oxidative
rearrangement
of
ortho-
b Isolated yields.
c N.R. = no reaction.
hydroxylbenzoimine, we envisioned that nucleophilic imine in 3-
hydroxybut-2-enimidates are capable of coordinating with
electron-deficient iodine of iodobenzene diacetate and
nucleophilic attack of enol to nitrogen would result in generation
of (iso)oxazole. As expected, we fortunately got the product
oxazoles from 3-hydroxybut-2-enimidates via an isoxazole
rearrangement. Herein, we would like to report synthesis of 2,4,5-

ACCEPTED MANUSCRIPT
3
none
none
none
none
none
none
7
1a
1a
1a
1b
1c
1d
rt
rt
rt
rt
rt
rt
1/2
1/3
1/6
1
40
2.7/1
1/1.7
1/10.2
8
54
9
61
d
10
11
12
N.R.
N.R.
10
-
d
1
-
d
1
-
TEMPO
(0.2)
13
14
15
1a
1a
1a
rt
rt
rt
1
1
1
17
66
75
1/0
1/0
1/0
BTA
Fig. 1. X-ray single crystal structure of 3a
(0.2)
BTA
The influences of different oxidants, temperatures, time and
additives on the reaction were examined with the results shown
(0.3)
a Conditions: 2a (0.5 mmol), oxidant (1, 1.4 eq.), CHCl3 (1 mL), temperature
o
in Table 2. Close to reaction at 50 C (Table 2, entry 1), the
(specified), time (specified). BTA
tetramethyl-1-piperidinyloxy.
b Isolated yield.
= benzotriazol, TEMPO = 2,2,6,6-
reaction could occur at ambient temperature as well and the
desired product 3a was obtained in 31% yield (Table 2, entry 2).
Temperature effect was significant to the reaction, and as a result,
lowering the temperature to -20 °C, the yield was improved to
67%, whereas isoxazole 4a became the major product (Table 2,
entry 3). Further lowering the temperature to -30 oC, the
reactivity dropped relatively (Table 2, entry 4). Oppositely, when
the temperature was elevated to 80°C, the yield decreased sharply,
and complex byproducts were observed (Table 2, entry 5). The
effects of the reaction time were then examined and as a result,
increasing reaction time to 2 h resulted in a slightly increase in
35% yield of 3a (Table 2, entry 6 vs. entry 2); Shortening the
reaction time to 0.5 h, 20 min and 10 min, the total yields were
obtained of isomers 3a and 4a in 40%, 54% and 61%,
respectively (Table 2, entries 7-9). With the reation time
prolonged, the content of 3a incresed significantly, and as a result,
only oxazole 3a was NMR-detected after 1 hour. With an attempt
to improve the yield of oxazole 3a, the different oxidants such as
ABX (1b), IBX (1c) and HTIB (1d) were examined, and all of
them were unsuccessful (Table 2, entries 10-12). To further
improve the reactivity, several additives such as TEMPO,
benzoylperoxide, AIBN, benzotriazol (BTA) were attempted
(Table 2, entries 13-15), and as a result benzotriazol was most
favorable to the reaction giving the oxazole 3a in yield of 75%
(for the detailed, see supporting information) (Table 2, entry 15).
Accordingly, the optimal conditions were identified 1.4
equivalents of DIB reacted with 3-hydroxybut-2-enimidate in
chloroform in the presence of 0.3 equivalent of BTA at room
temperature for an hour.
c The molar ratio of 3a and 4a determined by1H NMR spectroscopy.
d Not detected the ratio of two isomers.
With the optimized conditions in hand, the scope of 3-
hydroxybut-2-enimidate was investigated with the results shown
in Table 3. Various substituted substrates were studied including
methyl, ethyl, methoxy, ethoxy, fluoro, isopropyl and phenyl
groups. We probed the effect of substitution on the benzene ring
and the results showed that electron-withdrawing fluoro is more
benificial than electron-donating group to the reaction (Table 3,
entries 2-3). However, m-methoxy substituted benzene ring was
not compatible with this reaction under standard conditions.
Comparable to the methoxy on ester, ethyloxy group was found
more active to the transformation in 60% yield in the absence of
benzotriazol (Table 3, entry 4). Ethyloxy carbonyl and acetyl
groups at 2-C were beneficial to the reaction (Table 3, entries 5-
6). The effect of substitution R3 at α-position of hydroxyl groups
were also studied under the standard conditions and the results
revealed that ethyl and isopropyl substituted substrates give yield
in 54% and 60% in the absence of TBA, respectively (Table 3,
entries
7 and 8). In particular, 3-hydroxybut-2-enimidate
derivative with bulky phenyl groups also gave the desire product
3i in yield of 60% (Table 3, entry 9).
Table 3. Substrate Scope.a
Yieldb
Entry
1
R1
H
R2
R3
Table 2. Evaluation of oxidants, temperature and time on the
3
reaction.a
(%)
MeO
Me
75
3a
3b
3c
2
3
p-Et
p-F
MeO
MeO
Me
Me
41
64
Additive
s
(equiv)
Oxidant
Time
(h)
Yieldb
(%)
Ratio
(3a/4a)c
Entry
T (°C)
(1.4 equiv)
1
2
3
4
5
6
1a
1a
1a
1a
1a
1a
50
rt
1
1
1
1
1
2
none
none
35
1/0
1/0
1/8
31
none
none
none
none
-20
-30
80
rt
67
d
48
-
d
trace
35
-
1/0

ACCEPTED MANUSCRIPT
4
Tetrahedron
existed after 1 hour. (Fig. 2, V and VI). On the basis of these
results, we came to a conclusion that 3-hydroxybut-2-enimidates
was oxidized to form isoxazole firstly, and then isoxazole
decomposed completely to generate oxazole partially.
4
p-F
EtO
EtO
Me
Me
Me
Me
Et
60c
3d
5
6
7
H
70
3e
3f
H
68
H
MeO
54c
Fig. 2. Control experiments
Based on our experimental results, a plausible pathway was
proposed to explain the oxidative rearrangement process of 3-
hydroxybut-2-enimidate towards synthesis of oxazole as shown
in Fig. 3.13,19,20 The substrate would react with DIB to release an
acetic acid and produce intermediate A with the formation of
nitrogen-iodine bond. Followed by a nucleophilic attack of
hydroxyl, cyclization takes place and affords an isoxazole 4.
There have two possible pathways from isoxazole to oxazole: i)
with acetic acid generated continuously, isoxazole is protonated
to form intermediate B. Through a σ-bond shift, three-membered
ring intermediate C is formed, where a deprotonation gives rise
to the free structure D. ii) alternatively, under the conditions of
visible light shinning, the free radical intermediate E is generated
from homolytic cleavage of nitrogen-oxygen bond and π-bond
shift, which likewise reachs intermediate D. With the lone pair
electron attack of nitrogen, three-membered ring is broken and a
nitrile ylide F is formed. Followed by a nucleophilic attack of
enol anion to nitril ylide, the desired cyclic oxazole 3 is finally
assembled.
3g
8
9
H
H
MeO
Ph
i-Pr
60c
3h
3i
Ph
60
a Conditions: 2 (0.5 mmol), BTA (0.15 mmol) and DIB (0.7 mmol) in CHCl3
(1 mL) at room temperature for 1 h.
b Isolated yield.
c without BTA
To demonstrate the practicability of our method, a large-scale
experiment was conducted. Interestingly, methyl 5-methyl-2-
phenoxyoxazole-4-carboxylate 3a was obtained in yield of 68%
when treating 10 mmol of 3-hydroxybut-2-enimidate 2a under
standard conditions (Scheme 2).
COOR2
R3
H
COOR2
N
AcO
Ph
R3
CHCl3
rt
O
I
OAc
R1
R1
O
Scheme 2. Synthesis of oxazole 3a in a large-scale
.
O
+
O
N
H
3
1a
2
- HOAc
R3
R3
H
O
COOR2
O
R1
O
COOR2
R1
O
N
N
I
F
Ph
OAc
A
In order to gain a better understanding of the mechanism,
several control experiments were performed with the results
shown in Fig. 2. The influence of reaction time on two isomers
3a and 4a was determined by the ratio of peak area and the
chemical shift value of methyl group in NMR spectra. The ratio
of 4a and 3a was 4.4:1 when the reaction proceeds for 5 minutes
(I, Fig. 2). The NMR sample stood for 15 days in dark and the
ratio of two structures remained the same basically (II, Fig. 2).
Under the same circumstances, this tube continue to stand under
visible light shinning for 54 days, and comparison of two methyl
peak area integrals found that the ratio of 4a and 3a decreased
significantly (III, Fig. 2). With the reaction time extended to 10
minutes, we discovered the yields increased and the ratio of 4a
and 3a was elevated to 10.2:1 (IV, Fig. 2). Continue to prolong
the reaction time to 20 and 30 minutes, respectively, the yield of
4a declined, the ratio of 3a rose gradually, and only oxazole 3a
- HOAc
- IPh
O
R3
O
N
O
hv
R1
N
N
COOR2
R3
R3
O
R1
COOR2
R1
O
D
O
COOR2
H
4
E
-H
H
O
R3
COOR2
H
O
O
N
R3
N
R1
O
COOR2
R1
B
C
Fig. 3. Proposed reaction mechanism.

ACCEPTED MANUSCRIPT
5
3H); 13C NMR (125 MHz, CDCl3): δ = 162.8, 158.1, 152.2,
151.2, 142.1, 129.3, 126.4, 119.4, 52.1, 28.4, 15.8, 12.0.
Conclusion
In conclusion, we have developed
a direct oxidative
4.2.4. Ethyl 2-(4-fluorophenoxy)-5-methyloxazole-4-carboxylate
(3c). Prepared from methyl-2-((4-fluorophenoxy)(imino)
methyl)3-hydroxybut-2-enoate; isolated as colorless solid (38
rearrangement strategy to synthesize 2, 4, 5-trisubstituted oxazole
by the use of hypervalent iodine reagent. A plausible mechanism
has been accordingly proposed to interpret the observed
reactivity.
1
mg, 30% yield). H NMR (500 MHz, CDCl3): δ = 7.34-7.31 (m,
2H), 7.10-7.07 (m, 2H), 3.86 (s, 3H), 2.59 (s, 3H); 13C NMR (125
MHz, CDCl3): δ = 162.6, 161.3, 159.4, 152.3, 149.0, 126.4, 121.2
(d, J = 8.8Hz), 116.6 (d, J = 23.8Hz), 52.1, 12.0.
Experimental section
4.1. General methods
4.2.5. Ethyl-2-(4-fluorophenoxy)-5-methyloxazole-4-carboxylate
(3d). Prepared from ethyl-2-((4-fluorophenoxy)(imino)methyl)-3-
hydroxybut-2-enoate; isolated as colorless solid (80 mg, 60%
yield). 1H NMR (500 MHz, CDCl3): δ = 7.34-7.32 (m, 2H), 7.10-
7.06 (m, 2H), 4.34 (q, J = 7.0 Hz, 2H), 2.58 (s, 3H), 1.36 (t, J = 7
Hz, 3H); 13C NMR (125 MHz, CDCl3): δ = 162.3, 161.3, 159.3,
152.1, 149.0, 126.8, 121.2 (d, J = 8.8 Hz), 116.6 (d, J = 23.8 Hz),
61.2, 14.5, 12.1.
1H- and 13C-NMR spectra were recorded in CDCl3 solution on
500 MHz spectrometer at 20-25°C. 1H NMR spectra were
reported in parts per million using tetramethylsilane TMS (δ =
0.00 ppm) as an internal standard. The data of 1H NMR are
reported as follows: chemical shift, multiplicity (s = singlet, d =
doublet, t = triplet, q = quartet, quin = quintet, m = multiplet),
coupling constants (J, Hz), and integration. 13C NMR spectra
were reported in parts per million using solvent CDCl3 (δ = 77.2
ppm) as an internal standard. The data of 13C NMR are reported
as follows: chemical shift, multiplicity (s = singlet, d = doublet, t
= triplet, q = quartet, quin = quintet, m = multiplet), and coupling
constants (J, Hz). Reactions were monitored by TLC and column
chromatography was performed using silica gel. All the reagents
used were of analytical grade, purchased from commercial
suppliers and used without further purification unless otherwise
specified.
4.2.6. Ethyl-5-methyl-2-phenoxyoxazole-4-carboxylate (3e).
Prepared from ethyl-3-hydroxy-2-(imino(phenoxy)methyl)but-2-
1
enoate; isolated as liquid (47 mg, 38% yield). H NMR (500
MHz, CDCl3): δ = 7.41-7.38 (m, 2H), 7.34-7.32 (m, 2H), 7.25-
7.21 (m, 1H), 4.34 (q, J = 7.5 Hz, 2H), 2.58 (s, 3H); 1.36 (t, J =
7.5Hz, 3H); 13C NMR (125 MHz, CDCl3): δ = 162.3, 157.6,
153.3, 152.0, 130.4, 120.0, 127.1, 126.0, 119.4, 118.5, 61.1, 14.5,
12.1.
4.2.7 1-(5-methyl-2-phenoxyoxazol-4-yl)ethanone (3f). Prepared
from phenyl-2-acetyl-3-hydroxybut-2-enimidate; isolated as solid
(59 mg, 54% yield). 1H NMR (500 MHz, CDCl3): δ = 7.42 (t, J =
7.5 Hz, 2H), 7.37 (d, J = 7.5 Hz, 2H), 7.27-7.24 (m, 1H), 2.58 (s,
3H), 2.44 (s, 3H); 13C NMR (125 MHz, CDCl3): δ = 195.0,
156.8, 153.3, 150.1, 133.7, 130.0, 125.9, 119.3, 28.1, 12.2.
4.2. General procedure for synthesis of 3-hydroxybut-2-
enimidate (2a-i).18
Compound 2a-i were synthesized according to the reported
method: a mixture of ethyl acetoacetate (6 mmol), phenyl cyanate
(5 mmol) in diethyl ether (10 mL) at room temperature for 40
hours. After completion of the reaction monitored by TLC, the
volatile components were removed using a vacuum rotary
evaporator. Purification by column chromatography on silica gel
produced 3-hydroxybut-2-enimidates 2a-i.
4.2.8
Methyl-5-ethyl-2-phenoxyoxazole-4-carboxylate
(3g).
Prepared from methyl-3-hydroxy-2 (imino(phenoxy)methyl)pent-
1
2-enoate; isolated as liquid (67 mg, 54% yield). H NMR (500
MHz, CDCl3): δ = 7.42-7.38 (m, 2H), 7.35-7.33 (m, 2H), 7.25-
7.22 (m, 1H), 3.86 (s, 3H), 3.03 (q, J = 7.5 Hz, 2H), 1.29 (t, J =
7.5 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ = 162.7,157.8,
157.2, 153.3, 130.0, 126.0, 125.5, 119.5, 52.1, 19.6, 12.3.
4.3. General procedure for synthesis of oxazole derivatives
(3a-i).
Compound 3a-i was synthesized by adding DIB (0.7 mmol) to
3-hydroxybut-2-enimidate (2, 0.5 mmol) in 1 mL of CHCl3 at
room temperature for 1 hour. After completion of the reaction,
the reaction mixture was monitored by TLC, and the solvent was
removed using a vacuum rotary evaporator. Purification by
column chromatography on silica gel provided oxazoles 3.
4.2.9. Methyl-5-isopropyl-2-phenoxyoxazole-4-carboxylate (3h).
Prepared from methyl-3-hydroxy-2-(imino(phenoxy)methyl)-4-
1
methylpent-2-enoate; isolated as solid (78 mg, 60% yield). H
NMR (500 MHz, CDCl3): δ = 7.40 (t, J = 8.5 Hz, 2H), 7.35 (d, J
= 7.5 Hz, 2H), 7.24 (t, J = 7.0 Hz, 1H), 3.86 (s, 3H), 3.79-3.73 (m,
1H), 1.31 (d, J = 7.0 Hz, 6H); 13C NMR (125 MHz, CDCl3): δ =
162.7, 160.4, 157.7, 153.2, 130.0, 126.0, 124.4, 119.4, 52.1, 26.1,
20.8.
4.2.1. Methyl-5-methyl-3-phenoxyisoxazole-4-carboxylate (4a).
Prepared from methyl-3-hydroxy-2-(imino(phenoxy)methyl)but-
1
2-enoate; isolated as white solid. H NMR (500 MHz, CDCl3): δ
= 7.48-7.44 (m, 4H), 7.33 (t, J = 6.5 Hz, 1H), 3.82 (s, 3H), 2.43
(s, 3H); 13C NMR (125 MHz, CDCl3): δ = 199.8, 167.2, 156.8,
153.6, 130.4, 127.1, 118.5, 53.3, 51.4, 28.5.
4.2.10. (2-phenoxy-5-phenyloxazol-4-yl)(phenyl)methanone (3i).
Prepared
from
phenyl-2-benzoyl-3-hydroxy-3-
phenylacrylimidate; isolated as colorless solid (92 mg, 54%
yield). 1H NMR (500 MHz, CDCl3): δ = 8.09-8.07 (m, 2H), 7.94-
7.93 (m, 2H), 7.55-7.52 (m, 1H), 7.46-7.39 (m, 9H), 7.28-7.24
(m, 1H); 13C NMR (125 MHz, CDCl3): δ = 188.4, 157.4, 153.4,
150.7, 137.4, 133.2, 132.9, 130.5, 130.2, 130.0, 128.7, 128.3,
127.7, 127.1, 126.1, 119.3.
4.2.2. Methyl-5-methyl-2-phenoxyoxazole-4-carboxylate (3a).
Prepared from methyl-3-hydroxy-2-(imino(phenoxy)methyl)but-
2-enoate; isolated as colorless solid (36 mg, 31% yield). 1H NMR
(500MHz, CDCl3): δ =7.41-7.38 (m, 2H), 7.34-7.33 (m, 2H),
7.25-7.22 (m, 1H), 3.86 (s, 3H), 2.59 (s, 3H); 13C NMR (125
MHz, CDCl3): δ = 162.7, 157.7, 153.2, 152.2, 130.0, 126.5,
126.0, 119.5, 52.1, 12.0.
Acknowledgments
4.2.3. Methyl-2-(4-ethylphenoxy)-5-methyloxazole-4-carboxylate
(3b). Prepared from methyl-2-((4-ethylphenoxy)(imino)methyl)-
3-hydroxybut-2-enoate; isolated as colorless solid (47mg, 36%
yield). H NMR (500 MHz, CDCl3): δ = 7.24-7.19 (m, 4H), 3.85
(s, 3H), 2.64 (q, J = 8 Hz, 2H), 2.58 (s, 3H), 1.23 (t, J = 7.5 Hz,
We gratefully acknowledge funding from the National Natural
Science Foundation of china (No. 21372265), and the
Fundamental Research Funds for the Central Universities (No.
CDJZR14225502).
1

ACCEPTED MANUSCRIPT
6
Tetrahedron
Supplementary Material
Supplementary data (1H & 13C NMR spectra of the
compounds) associated with this article can be found in the
online version, at
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