Copper(II)-catalyzed dehydrogenative cross-coupling between two azoles

Article abstract of DOI:10.1021/jo301128y

The copper(II)-catalyzed dehydrogenative coupling between two different azoles for the preparation of unsymmetrical biazoles has been developed. The current catalytic system can effectively control the chemoselectivity for heterocoupling over homocoupling.

Full text of DOI:10.1021/jo301128y

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Note
Copper(II)-Catalyzed Dehydrogenative Cross-Coupling between Two Azoles
Xurong Qin, Boya Feng, Jiaxing Dong, Xiaoyu Li, Ying Xue, Jingbo Lan, and Jingsong You
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo301128y • Publication Date (Web): 17 Aug 2012
Downloaded from http://pubs.acs.org on August 19, 2012
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Copper(II)-Catalyzed Dehydrogenative Cross-Coupling between
Two Azoles
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Xurong Qin, Boya Feng, Jiaxing Dong, Xiaoyu Li, Ying Xue, Jingbo Lan,* and
Jingsong You*
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Key Laboratory of Green Chemistry and Technology of Ministry of Education,
College of Chemistry, and State Key Laboratory of Biotherapy, West China Hospital,
West China Medical School, Sichuan University, 29 Wangjiang Road, Chengdu
610064 P. R. China
Eꢀmail: jsyou@scu.edu.cn; jingbolan@scu.edu.cn
R1
R2
X
N
N
X
20 mol% Cu(OAc)2
1.0 equiv pyridine
R1
R2
R3
R4
R1
R2
R4
R3
R2
R3
R1
R4
X
N
X
N
N
Y
Y
N
+
H
H
1.5 equiv Ag2CO3
xylene,140 °C, 24 h, O2
Y
N
N
Y
Selective formation
of unsymmetrical biazoles
Y = O, NR5
X = O, S
R3
R4
25 examples
52~78% yields
ABSTRACT: The copper(II)ꢀcatalyzed dehydrogenative coupling between two
different azoles for the preparation of unsymmetrical biazoles has been developed.
The current catalytic system can effectively control the chemoselectivity for
heteroꢀcoupling over homoꢀcoupling.
-----------------------------------------------------------------------------------------------------
Transition
metalꢀcatalyzed
crossꢀcoupling
reactions
of
nucleophiles
(organometallic reagents and hydrocarbons) with electrophiles (organohalides or
surrogates) are powerful synthetic tools to construct carbonꢀcarbon (C–C) bonds
and have made significant progress over the past decades.1,2 However, from the
viewpoint of synthetic simplicity and efficiency, atom economy and sustainable
chemistry, direct dehydrogenative coupling through the cleavage of two C–H
bonds would be one of the most ideal approaches for forming
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(hetero)aryl–(hetero)aryl bonds, which avoids prefunctionalization of both of
substrates prior to the coupling reaction.3 In recent years, a number of examples of
dehydrogenative crossꢀcoupling, including between arene and arene,4 between
heteroarene and arene,5 and between heteroarene and heteroarene,6 have been
reported. Nevertheless, some formidable challenges still remain to be overcome in
this area, including a competition between crossꢀcoupling and homoꢀcoupling. In
general, the three tactics may be used to achieve such a chemoselectivity: 1) the
use of two (hetero)arenes with distinctly different electronic characteristics; 2) the
chelationꢀdirected strategy; and 3) the utilization of an excessive amount of one of
the coupling components (up to 40–100 equivalents).
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Imidazoles, oxazoles and thiazoles are a class of privileged structural motifs in
bioactive natural products, pharmaceuticals, and organic functional materials, and
their functionalization has recently attracted extensive attention. Ofial and coꢀworkers
developed the palladium(II)ꢀcatalyzed dehydrogenative crossꢀcoupling of benzazoles
with azoles by using 1.5 equiv of one of coupling components.6d Recently, we
reported that the palladium(II)ꢀcatalytic system could give a high level of selectivity
of crossꢀcoupling between two structurally similar azoles even when the ratio of two
partners is 1: 1.6b While the copperꢀcatalytic systems effectively promote
homoꢀcoupling of azoles,7 however, the copperꢀcatalyzed crossꢀcoupling reactions
between two different azoles with high crossꢀcoupling selectivity have not been
reported yet. Herein, we describe for the first time a copperꢀcatalytic dehydrogenative
crossꢀcoupling between two azoles with high chemoselectivity.
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The dehydrogenative coupling reactions between two different azoles were
carried out at a ratio of 1: 1. The investigation started with the coupling of
benzothiazole and 5ꢀphenyloxazole in the presence of Cu(OAc)2 by using Ag2CO3
as the oxidant, and the crossꢀcoupling product 3a was obtained in 65% yield in
xylene for 24 h at 140 °C (Table 1, entry 1). The negative effect was observed
when an extra base such as Na2CO3 or tꢀBuOLi was employed (Table 1, entries
2ꢀ4). In controlled experiments, none or trace of crossꢀcoupling product was
observed in the absence of Cu(OAc)2 or Ag2CO3 (Table 1, entries 5, 6). Further
improvement of the reaction efficiency was achieved when pyridine (1.0 equiv)
was introduced as an additive, and 3a was obtained in 76% isolated yield (Table 1,
entry 7). When 40 mol% of pyridine was used, the yield of 3a decreased from 76%
to 70% (Table 1, entry 8). Subsequently, other copper salts (i.e., Cu(OTf)2, CuCl2,
and Cu(acac)2) were found to lead to lower catalytic efficiency (Table 1, entries
9ꢀ11). After screening a series of solvents, xylene turned out to be the best choice
(Table 1, entries 7, 12ꢀ15). In addtion, shortening reaction time, and decreasing
reaction temperature could significantly diminish yields (Table 1, entries 17ꢀ18).
Thus, the optimal reaction condition was obtained when 20 mol% of Cu(OAc)2
was employed in combination with Ag2CO3 (1.5 equiv), pyridine (1.0 equiv) in
xylene at 140 °C for 24 h under oxygen atmosphere.
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Table 1. Optimization of the Dehydrogenative Cross-Coupling of Benzothiazole with
5-Phenyloxazolea
N
N
N
N
Cu salt, additive
solvent
+
O
S
S
O
Ph
Ph
1a
2a
3a
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entry
Cu source
base
oxidant
additive
solvent
yield (%)b
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8
1
2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
ꢀ
ꢀ
Ag2CO3
ꢀ
ꢀ
xylene
xylene
xylene
xylene
xylene
xylene
xylene
xylene
xylene
xylene
xylene
toluene
dioxane
DCE
65
42
tꢀBuOLi
ꢀ
3
Na2CO3
ꢀ
ꢀ
trace
47
9
4
tꢀBuOLi
Ag2CO3
ꢀ
ꢀ
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5
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
trace
n.d
76
6
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
ꢀ
7
8c
Cu(OAc)2
Cu(OAc)2
Cu(OTf)2
CuCl2
pyridine
pyridine
pyridine
pyridine
pyridine
pyridine
pyridine
pyridine
pyridine
PivOH
pyridine
pyridine
pyridine
pyridine
pyridine
+ TEMPO
70
9
27
10
11
12
13
14
15
16
17d
18e
19f
20g
35
Cu(acac)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
46
70
46
56
DMF
65
xylene
xylene
xylene
xylene
xylene
trace
60
55
53
56
21h
Cu(OAc)2
ꢀ
Ag2CO3
xylene
76
a Reactions were carried out using Cu salt (20 mol%), base (1.5 equiv), oxidant (1.5 equiv)
additive (1.0 equiv), benzothiazole (0.25 mmol), 5ꢀphenyloxazole (0.25 mmol) and solvent
b
c
(1.0 mL) at 140 °C for 24 hours under oxygen atmosphere. Yield of isolated product.
pyridine (40 mol%). d for 12 hours. e at 120 °C. f under air atmosphere. g under N2 atmosphere. h
TEMPO (1.0 equiv). DMF = dimethyl formamide. DCE = 1,2ꢀdichloroethane. TEMPO =
2,2,6,6ꢀtetramethylꢀ1ꢀpiperidinyloxy.
Subsequently, the dehydrogenative crossꢀcouplings of benzothiazole 1a with
various oxazoles were conducted under the optimized conditions (Table 2; for
details, see Table S1). It was found that benzothiazole could react with a relatively
broad range of oxazoles to afford the crossꢀcoupling products with the
C2/C2'ꢀselectivity in satisfactory yields. The substituents on a benzene ring of
arylꢀsubstituted oxazoles 2 had a negligible effect on the crossꢀcoupling reactions
(Table 2, 3a-f). Chloro and bromo substituents on the aromatic ring were tolerant
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in this catalytic system, which could be subjected to further synthetic
transformations (Table 2, 3dꢀe). 5ꢀ(Pyridinꢀ2ꢀyl)ꢀoxazole could undergo the
coupling reaction to provide 3g in 70% yield. In addition, the catalytic system was
also suitable for other azoles (e.g., ethyl 4ꢀmethyloxazoleꢀ5ꢀcarboxylate,
2ꢀphenylꢀ1,3,4ꢀoxadiazole, and 1ꢀmethylꢀ1Hꢀbenzimidazole) (Table 2, 3h-j).
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Table 2. Selective Cross-Couplings of Benzothiazole with Azolesa,b,c
R1
R1
R2
R1
R2
R2
R1
S
N
S
N
S
N
N
S
N
N
X
20 mol% Cu(OAc)2
1.0 equiv pyridine
N
X
X
+
+
+
R2
X
1.5 equiv Ag2CO3
xylene,140 °C, 24 h, O2
N
X = O, NR3
3a - 3j
2aa - 2jj
2a - 2j
1aa
1a
N
S
N
O
N
S
N
O
N
S
N
OMe
O
3b 75%
(13%, 15%)
3c 75%
(10%, <5%)
3a 76%
(10%, 17%)
CN
N
S
N
N
S
N
N
S
N
O
O
O
3f 71%
(13%, <5%)
3e 69%
(13%, <5%)
Cl
3d 69%
(10%, 8%)
NO2
Br
N
N
N
S
N
O
N
S
N
N
S
O
O
CO2Et
N
3h 64%
(10%, <5%)
3i 78%
3g 70%
(12%, 18%)
(12%, <5%)
N
S
N
N
3j
67%
(13%, 18%)
a Reactions were carried out using Cu(OAc)2 (20 mol%), Ag2CO3 (1.5 equiv), pyridine (1.0 equiv),
benzothiazole (0.5 mmol), and azole 2 (0.5 mmol) at 140 oC for 24 h under oxygen atmosphere. b
Yields of isolated product. The yields in parentheses refer to the homocoupling products of
c
benzothiazole (1a) and azole 2, respectively. For the detailed structure information of compounds,
see Table S1.
The optimized conditions could be further extended to the reactions between
two nonꢀbenzofused azoles (Table 3; for details, see Table S2). A variety of
thiazole, oxazole, imidazole derivatives were coupled to each other in acceptable
yields. In comparison with the reactions between benzothiazole with azoles, the
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homoꢀcoupling tendency between two nonꢀbenzofused azoles was slightly
increased probably due to the least difference in πꢀelectronic characteristics. As
illustrated in Table 3, 4,5ꢀdimethylthiazole could be coupled efficiently at the
2ꢀposition with various oxazoles, affording the corresponding crossꢀcoupling
products in 62~73% yields (Table 3, 4aꢀe). Worthy of note was that some
troublesome functional groups such as halide, ester, aldehyde, vinyl, and nitro
could survive in the current catalytic system (Table 3, 4dꢀo). The C4 unsubstituted
thiazole was amenable to the dehydrogenative coupling at the C2 position in
synthetically useful yields (Table 3, 4k and 4l). Furthermore, the both C4 and C5
unsubstituted thiazole also selectively underwent the crossꢀcoupling at the C2
position (Table 3, 4m; for the copy of HHꢀCOSY spectrum of 4m, see SI).
Table 3. Selective Cross-Couplings between Two Non-benzofused Azolesa,b,c
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R1
R2
R1
R2
R4
R3
R1
R2
R4
R3
R3
R4
R3
R1
X
N
X
N
Y
N
N
Y
X
N
N
Y
X
N
Y
N
20 mol% Cu(OAc)2
1.0 equiv pyridine
+
+
+
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R4
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xylene,140 °C, 24 h, O2
X = O, S
Y = O, NR5
1b - 1g, 2h
2a - 2k
1bb - 1gg, 2hh
2aa - 2kk
4a - 4o
N
S
N
O
N
S
N
O
N
S
N
OMe
O
4c 70%
(21%, trace)
4b 62%
(16%, 18%)
4a 65%
(13%, 19%)
N
N
S
N
O
N
S
N
O
N
S
N
O
EtO2C
OHC
CO2Et
4f 61%
(23%, 12%)
4e 73%
4d 73%
(23%, trace)
(18%, 8%)
Br
OHC
S
N
N
O
N
S
N
O
S
N
N
O
CO2Et
EtO2C
CO2Et
4g 63%
(21%, <5%)
4i 65%
(trace, 19%)
4h 70%
(trace, <5%)
EtO2C
EtO2C
MeO
S
N
N
O
S
N
O
N
S
N
N
CO2Et
O
4j 66%
(<5%, trace)
CO2Et
4l 65%
(13%, 11%)
4k 63%
(15%, 19%)
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EtO2C
NO2
EtO2C
O
N
N
S
N
N
O
O
N
N
N
N
CO2Et
4m 60%
(<5%, trace)
4o 52%d
(<5%, n.d)
4n 58%
(<5%, n.d)
a Reactions were carried out using Cu(OAc)2 (20 mol%), Ag2CO3 (1.5 equiv), pyridine (1.0 equiv),
azole 1 (0.5 mmol), and azole 2 (0.5 mmol) at 140 oC for 24 h under oxygen atmosphere. b Yields
of isolated product. The yields in parentheses refer to the homocoupling products of azole 1 and
azole 2, respectively. c For the detailed structure information of compounds, see Table S2. d Oxazole 1
(0.5 mmol), and imidazole 2 (0.75 mmol).
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Scheme 1. Kinetic Isotope Effect Study
S
N
N
O
S
N
N
standard conditions
+
eq. 1
eq. 2
H/D
KH/KD = 1.06
O
Ph
Ph
N
standard conditions
S
S
N
H/D
+
O
N
N
O
KH/KD = 1.04
Ph
Ph
Although the mechanism remains not completely clear at this stage, a plausible
catalytic cycles could involve 1) C–H cupration of one azole to generate the
organocopper species (Azole 1)–CuLn with a carbon–metal bond at the 2ꢀposition
of azole,7,8 2) subsequent formation of the critical mixed bisheteroaryl–Cu
intermediate (Azole 1)–Cu–(Azole 2), and 3) reductive elimination to afford the
unsymmetrical 2,2′ꢀbisazole. In order to gain mechanistic insights into the
reaction, two control experiments were investigated. First, TEMPO
(2,2,6,6ꢀtetramethylꢀ1ꢀpiperidinyloxy, 1.0 equiv) as a radical scavenger was
observed to display a neglectable effect on the reaction of 1a and 2a, ruling out a
radical pathway (Table 1, entry 21). Next, kinetic isotope effects (KIE) were
studied with regard to the CꢀH/D bonds for both coupling partners.9 The parallel
(independent) reactions were performed by the use of 2ꢀdeuterioꢀbenzothiazole
and 2ꢀdeuterioꢀ5ꢀphenyloxazole under the optimized condition (Scheme 1). The
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KIE values of 1.06 and 1.04 were observed for 2ꢀdeuterioꢀbenzothiazole and
2ꢀdeuterioꢀ5ꢀphenyloxazole, respectively (Scheme 1, eq. 1 and eq. 2; for details,
see SI). These results clearly indicated that the C2ꢀH bond breaking of azole was
not involved in the rateꢀdetermining step in the present reaction.
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In summary, the Cu(II)ꢀcatalyzed dehydrogenative couplings between two
different azoles have been developed. The current copperꢀcatalytic system is not
only suitable for a relatively wide range of azoles (e.g., thiazoles, oxazoles,
imidazoles, and oxadiazoles), but also compatible with the presence of functional
groups (e.g., halide, nitro, cyano, ester, aldehyde, and vinyl groups). We expect
that insights gained from our present study are helpful for the understanding of
transition metalꢀcatalyzed dehydrogenative crossꢀcouplings between two
hereoarenes.
EXPERIMENTAL SECTION
General Procedure for Dehydrogenative Cross-Couplings between Two Azoles. A
flameꢀdried Schlenk test tube with a magnetic stirring bar was charged with copper
species (20 mol%), Ag2CO3 (0.75 mmol), pyridine (0.5 mmol), azole 1 (0.5 mmol),
azole 2 (0.5 mmol), and xylene (1 mL) under 1 atm O2 atmosphere. The resulting
mixture was stirred for 10 min at room temperature, and then heated at 140 ºC for the
indicated time. The mixture was cooled to room temperature, diluted with CH2Cl2 (20
mL), filtered through a Celite pad, and washed with CH2Cl2 (10ꢀ20 mL). The organic
extracts were concentrated and the resulting residue was purified by column
chromatography on silica gel to provide the desired product and the homocoupling
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products .
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2ꢀ(5ꢀPhenyloxazolꢀ2ꢀyl)ꢀbenzothiazole (3a). The crude residue was purified by flash
column chromatography on silica gel to afford 3a as a white solid (106 mg, 76%), 1aa
(7 mg, 10%) and 2aa (12 mg, 17%) (petroleum/ethyl acetate = 15/1ꢀ8/1 v/v). 1H NMR
(400 MHz, CDCl3): δ = 7.38 (t, J = 7.2 Hz, 1H), 7.45ꢀ7.50 (m, 3H), 7.54ꢀ7.58 (m,
2H), 7.82 (d, J = 7.6 Hz, 2H), 7.95 (d, J = 8.0 Hz, 1H), 8.20 (d, J = 8.0 Hz, 1H) ppm.
13C NMR (100 MHz, CDCl3): δ = 121.9, 124.3, 124.4, 125.1, 126.7, 127.0, 127.1,
129.1, 129.5, 135.4, 153.6, 153.8, 154.5, 155.8 ppm. HRMS (ESI+): calcd for
C16H11N2OS [M+H]+ 279.0592, found 279.0594.
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2,2'ꢀBibenzothiazole (1aa, known compound). H NMR (400 MHz, CDCl3): δ =
7.39ꢀ7.71 (m, 4H), 7.92 (d, J = 7.6 Hz, 2H), 8.10ꢀ8.16 (m, 2H) ppm. 13C NMR (150
MHz, CDCl3): δ = 122.2, 124.2, 126.8, 127.0, 127.7, 129.2, 136.0 ppm. HRMS (ESI+):
calcd for C14H9N2S2 [M+H]+ 269.0207, found 269.0200.
5,5'ꢀDiphenylꢀ2,2'ꢀbioxazole (2aa, known compound). 1H NMR (400 MHz, CDCl3): δ
= 7.38 (t, J = 7.2 Hz, 2H), 7.45 (t, J = 7.6 Hz, 4H), 7.57 (s, 2H), 7.79 (d, J = 7.6 Hz,
4H) ppm. 13C NMR (100 MHz, CDCl3): δ = 124.0, 125.0, 127.1, 129.2, 129.5, 153.2
ppm.
2ꢀ(5ꢀ(2ꢀMethoxyphenyl)oxazolꢀ2ꢀyl)benzothiazole (3b). The crude residue was
purified by flash column chromatography on silica gel to afford 3b as an offꢀwhite
solid (116 mg, 75%), 1aa (9 mg, 13%) and 2bb (13 mg, 15%) (petroleum/ethyl
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acetate = 8/1ꢀ5/1 v/v). H NMR (400 MHz, CDCl3): δ = 4.00 (s, 3H), 6.99 (d, J = 8.4
Hz, 1H), 7.07 (t, J = 7.6 Hz, 1H), 7.34 (t, J = 7.8 Hz, 1H), 7.45 (t, J = 7.4 Hz, 1H),
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7.53 (t, J = 7.6 Hz, 1H), 7.77 (s, 1H), 7.94 (d, J = 8.0 Hz, 1H), 8.05 (d, J = 7.6 Hz,
1H), 8.20 (d, J = 8.0 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 55.6, 111.0,
116.3, 121.0, 121.9, 124.3, 126.5, 126.9, 127.0, 128.4, 130.2, 135.4, 150.2, 153.9,
154.7, 156.3 ppm. HRMS (ESI+): calcd for C17H13N2O2S [M+H]+ 309.0698, found
309.0706.
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5,5'ꢀDi(2ꢀmethoxyphenyl)ꢀ2,2'ꢀbioxazole (2bb, known compound). M.p.: 233ꢀ235 °C.
1H NMR (400 MHz, CDCl3): δ = 4.00 (s, 6H), 6.99 (d, J = 8.4 Hz, 2H), 7.06 (t, J =
7.6 Hz, 2H ), 7.33 (t, J = 7.6 Hz, 2H), 7.76 (s, 2H), 8.00 (d, J = 7.6 Hz, 2H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 55.7, 111.0, 111.7, 116.5, 121.1, 122.4, 126.8, 130.1,
135.2, 156.2 ppm. HRMS (ESI+): calcd for C20H17N2O4 [M+H]+ 349.1188, found
349.1179.
2ꢀ(5ꢀ(4ꢀCyanophenyl)oxazolꢀ2ꢀyl)benzothiazole (3c). The crude residue was purified
by flash column chromatography on silica gel to afford 3c as an offꢀwhite solid (114
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mg, 75%) and 1aa (7 mg, 10%) (petroleum/ethyl acetate = 15/1ꢀ8/1 v/v). H NMR
(400 MHz, CDCl3): δ = 7.49 (t, J = 7.6 Hz, 1H), 7.57 (t, J = 8.0 Hz, 1H), 7.70 (s, 1H),
7.74 (d, J = 8.4 Hz, 2H), 7.91 (d, J = 8.4 Hz, 2H), 7.97 (d, J = 7.6 Hz, 1H), 8.21 (d, J
= 8.0 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 112.7, 118.4, 122.0, 124.6,
125.3, 126.8, 127.1, 127.3, 131.0, 133.0, 135.6, 151.5, 153.8, 153.8(4), 156.9 ppm.
HRMS (ESI+): calcd for C17H10N3OS [M+H]+ 304.0545, found 304.0530.
2ꢀ(5ꢀ(4ꢀChlorophenyl)oxazolꢀ2ꢀyl)benzothiazole (3d). The crude residue was purified
by flash column chromatography on silica gel to afford 3d as a white solid (108 mg,
69%), 1aa (7 mg, 10%) and 2dd (8 mg, 8%) (petroleum/ethyl acetate = 10/1ꢀ8/1 v/v).
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1H NMR (400 MHz, CDCl3): δ = 7.42 (d, J = 8.4 Hz, 2H), 7.47 (t, J = 7.6 Hz, 1H),
7.55ꢀ7.58 (m, 2H), 7.74 (d, J = 8.4 Hz, 2H), 7.95 (d, J = 8.0 Hz, 1H), 8.19 (d, J = 8.4
Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 122.0, 124.5, 124.6, 125.6, 126.3,
126.8, 127.1, 129.5, 135.4, 152.6, 153.8, 154.3, 156.0 ppm. HRMS (ESI+): calcd for
C16H10ClN2OS [M+H]+ 313.0202, found 313.0208.
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5,5'ꢀDi(4ꢀchlorophenyl)ꢀ2,2'ꢀbioxazole (2dd). M.p.: 233ꢀ235 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.44 (d, J = 8.4 Hz, 4H), 7.56 (s, 2H), 7.72 (d, J = 8.4 Hz, 4H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 124.4, 125.6, 126.2, 129.3, 129.6, 135.5 ppm. HRMS
(ESI+): calcd for C18H10Cl2N2NaO2 [M+Na]+ 379.0017, found 379.0047.
2ꢀ(5ꢀ(4ꢀBromophenyl)oxazolꢀ2ꢀyl)benzothiazole (3e, known compound). The crude
residue was purified by flash column chromatography on silica gel to afford 3e as a
white solid (123 mg, 69%), 1aa (9 mg, 13%) (petroleum/ethyl acetate = 10/1ꢀ8/1 v/v).
1H NMR (400 MHz, CDCl3): δ = 7.46 (t, J = 7.6 Hz, 1H), 7.53ꢀ7.57 (m, 3H), 7.59 (s,
1H), 7.66 (d, J = 8.4 Hz, 2H), 7.94 (d, J = 8.0 Hz, 1H), 8.18 (d, J = 8.0 Hz, 1H) ppm.
13C NMR (100 MHz, CDCl3): δ = 121.9, 123.6, 124.4, 124.6, 125.9, 126.4, 126.7,
127.0, 132.3, 135.4, 152.5, 153.7, 154.1, 155.9 ppm. HRMS (ESI+): calcd for
C16H10BrN2OS [M+H]+ 356.9697, found 356.9702.
2ꢀ(5ꢀ(4ꢀNitrophenyl)oxazolꢀ2ꢀyl)benzothiazole (3f). The crude residue was purified by
flash column chromatography on silica gel to afford 3f as a yellow solid (115 mg,
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71%) and 1aa (9 mg, 13%) (petroleum/ethyl acetate = 3/1ꢀ2/1 v/v). H NMR (400
MHz, CDCl3): δ = 7.50 (t, J = 7.6 Hz, 1H), 7.57 (t, J = 7.6 Hz, 1H), 7.75 (s, 1H), 7.98
(d, J = 8.4 Hz, 3H), 8.22 (d, J = 8.0 Hz, 1H), 8.32 (d, J = 8.8 Hz, 2H) ppm. 13C NMR
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(100 MHz, CDCl3): δ = 122.0, 124.6, 124.7, 125.0, 125.5, 127.2, 127.3, 132.8, 135.6,
147.9, 151.2, 153.8, 157.2 ppm. HRMS (ESI+): calcd for C16H10N3O3S [M+H]+
324.0443, found 324.0423.
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2ꢀ(5ꢀ(Pyridinꢀ2ꢀyl)oxazolꢀ2ꢀyl)benzothiazole (3g). The crude residue was purified by
flash column chromatography on silica gel to afford 3g as a white solid (98 mg, 70%),
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1aa (8 mg, 12%) and 2gg (13 mg, 18%) (petroleum/ethyl acetate = 4/1ꢀ2/1 v/v). H
NMR (400 MHz, CDCl3): δ = 7.28ꢀ7.29 (m, 1H), 7.48 (t, J = 7.2 Hz, 1H), 7.55 (t, J =
7.6 Hz, 1H), 7.79 (t, J = 7.6 Hz, 1H), 7.94ꢀ7.98 (m, 3H), 8.20 (d, J = 8.0 Hz, 1H),
8.66 (s, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 120.2, 122.0, 123.8, 124.5, 126.9,
127.1, 127.6, 135.5, 137.1, 146.6, 150.2, 152.8, 153.8, 154.3, 156.4 ppm. HRMS
(ESI+): calcd for C15H10N3OS [M+H]+ 280.0545, found 280.0542.
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5,5'ꢀDi(pyridinꢀ2ꢀyl)ꢀ2,2'ꢀbioxazole (2gg, known compound). M.p.: 233ꢀ235 °C. H
NMR (400 MHz, CDCl3): δ = 7.29 (t, J = 6.0 Hz, 2H), 7.81 (t, J = 7.6 Hz, 2H), 7.89
(d, J = 8.0 Hz, 2H), 7.95 (s, 2H), 8.68 (s, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ =
120.0, 123.8, 127.4, 137.2, 146.6, 150.2, 150.9, 152.7 ppm. HRMS (ESI+): calcd for
C16H11N4O2 [M+H]+ 291.0882, found 291.0875.
Ethyl 2ꢀ(benzothiazolꢀ2ꢀyl)ꢀ4ꢀmethyloxazoleꢀ5ꢀcarboxylate (3h). The crude residue
was purified by flash column chromatography on silica gel to afford 3h as an
offꢀwhite solid (92 mg, 64%) and 1aa (7 mg, 10%) (petroleum/ethyl acetate =
15/1ꢀ8/1 v/v). 1H NMR (400 MHz, CDCl3): δ = 1.41 (t, J = 7.0 Hz, 3H), 2.60 (s, 3H),
4.41 (q, J = 7.0 Hz, 2H), 7.49 (t, J = 7.4 Hz, 1H), 7.55 (t, J = 7.4 Hz, 1H), 7.96 (d, J
= 7.6 Hz, 1H), 8.21 (d, J = 8.0 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 13.5,
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14.6, 61.6, 122.0, 125.0, 127.2, 127.3, 135.8, 139.0, 147.6, 153.3, 153.8, 156.2, 158.4
ppm. HRMS (ESI+): calcd for C14H13N2O3S [M+H]+ 289.0647, found 289.0650.
Diethyl 4,4'ꢀdimethylꢀ2,2'ꢀbioxazoleꢀ5,5'ꢀdicarboxylate (2hh, known compound).
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M.p.: 170ꢀ172 °C. H NMR (400 MHz, CDCl3): δ = 1.38 (t, J = 6.8 Hz, 6H), 2.56 (s,
6H), 4.38 (q, J = 6.8 Hz, 4H) ppm. 13C NMR (100 MHz, CDCl3): δ = 13.5, 14.4, 61.8,
139.3, 147.5, 150.1, 158.1 ppm. HRMS (ESI+): calcd for C14H16N2O6 [M+H]+
309.1087, found 309.1091.
2ꢀ(5ꢀPhenylꢀ1,3,4ꢀoxadiazolꢀ2ꢀyl)benzothiazole (3i, known compound). The crude
residue was purified by flash column chromatography on silica gel to afford 3i as an
offꢀwhite solid (109 mg, 78%) and 1aa (8 mg, 12%) (petroleum/ethyl acetate =
15/1ꢀ8/1 v/v). 1H NMR (400 MHz, CDCl3): δ = 7.54ꢀ7.58 (m, 5H), 7.99 (d, J = 7.6 Hz,
1H), 8.23 (d, J = 7.6 Hz, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 122.1, 123.1,
124.8, 127.4, 127.5, 127.7, 129.3, 132.6, 135.6, 150.9, 153.4, 160.3, 166.0 ppm.
HRMS (ESI+): calcd for C15H10N3OS [M+H]+ 280.0545, found 280.0549.
2ꢀ(Benzothiazolꢀ2ꢀyl)ꢀ1ꢀmethylꢀ1Hꢀbenzoimidazole (3j, known compound). The crude
residue was purified by flash column chromatography on silica gel to afford 3j as an
offꢀwhite solid (89 mg, 67%), 1aa (9 mg, 13%) and 2jj (12 mg, 18%)
(petroleum/ethyl acetate = 5/1ꢀ3/1 v/v). 1H NMR (400 MHz, CDCl3): δ = 4.42 (s, 3H),
7.33ꢀ7.41 (m, 2H), 7.44ꢀ7.48 (m, 2H), 7.51 (t, J = 7.6 Hz, 1H), 7.87 (d, J = 7.6 Hz,
1H), 7.97 (d, J = 8.0 Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 32.2, 110.2, 120.7, 121.9, 123.4, 124.0, 124.6, 126.3, 126.6, 135.5, 137.4,
142.9, 145.3, 154.2, 156.0 ppm. HRMS (ESI+): calcd for C15H12N3S [M+H]+
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1,1'ꢀDimethylꢀ2,2'ꢀbibenzoimidazole (2jj, known compound). M.p.: 170ꢀ172 °C. H
NMR (400 MHz, CDCl3): δ = 4.34 (s, 6H), 7.35ꢀ7.43 (m, 4H), 7.49 (d, J = 7.6 Hz,
2H), 7.88 (d, J = 7.6 Hz, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ = 32.6, 110.2,
120.5, 123.0, 124.1, 136.4, 142.7, 143.4 ppm. HRMS (ESI+): calcd for C16H15N4
[M+H]+ 263.1297, found 263.1287.
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2ꢀ(4,5ꢀDimethylthiazolꢀ2ꢀyl)ꢀ5ꢀphenyloxazole (4a, known compound). The crude
residue was purified by flash column chromatography on silica gel to afford 4a as an
offꢀwhite solid (83 mg, 65%), 1bb (7 mg, 13%) and 2aa (14 mg, 19%)
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(petroleum/dichloromethane/ethyl acetate = 15/2/1ꢀ8/2/1 v/v). M.p.: 103ꢀ105 °C. H
NMR (400 MHz, CDCl3): δ = 2.45 (s, 6H), 7.34 (t, J = 7.2 Hz, 1H), 7.42ꢀ7.45 (m, 3H),
7.76 (d, J = 7.6 Hz, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ = 11.6, 14.9, 123.6,
124.7, 124.9, 127.3, 128.9, 130.0, 149.8, 150.7, 152.1, 155.9 ppm. HRMS (ESI+):
calcd for C14H13N2OS [M+H]+ 257.0749, found 257.0745.
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4,4',5,5'ꢀTetramethylꢀ2,2'ꢀbithiazole (1bb, known compound). H NMR (400 MHz,
CDCl3): δ = 2.35 (s, 6H), 2.37 (s, 6H) ppm. 13C NMR (100 MHz, CDCl3): δ = 11.7,
14.9, 128.3, 149.6, 157.2 ppm.
2ꢀ(4,5ꢀDimethylthiazolꢀ2ꢀyl)ꢀ5ꢀ(pyridinꢀ2ꢀyl)oxazole (4b, known compound). The
crude residue was purified by flash column chromatography on silica gel to afford 4b
as a yellow solid (80 mg, 62%), 1bb as a white solid (9 mg, 16%), and 2gg as a white
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solid (13 mg, 18%) (petroleum/ethyl acetate = 5/1ꢀ2/1 v/v). M.p.: 124ꢀ126 °C. H
NMR (400 MHz, CDCl3): δ = 2.44 (s, 6H), 7.22ꢀ7.25 (m, 1H), 7.74 (t, J = 7.6 Hz, 1H),
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7.82 (s, 1H), 7.85 (d, J = 8.0 Hz, 1H), 8.61ꢀ8.62 (m, 1H) ppm. C NMR (100 MHz,
CDCl3): δ = 10.6, 13.9, 118.7, 122.2, 126.0, 135.9, 143.6, 145.8, 148.6, 148.9, 150.0,
150.5, 155.6 ppm. HRMS (ESI+): calcd for C13H12N3OS [M+H]+ 258.0701, found
258.0696.
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2ꢀ(4,5ꢀDimethylthiazolꢀ2ꢀyl)ꢀ5ꢀ(2ꢀmethoxyphenyl)oxazole (4c, known compound).
The crude residue was purified by flash column chromatography on silica gel to
afford 4c as a pale yellow solid (100 mg, 70%), and 1bb as a white solid (12 mg, 21%)
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(petroleum/ethyl acetate = 10/1ꢀ5/1 v/v). M.p.: 164ꢀ165 °C. H NMR (400 MHz,
CDCl3): δ = 2.43 (s, 6H), 3.96 (s, 3H), 6.96 (d, J = 8.4 Hz, 1H), 7.02 (t, J = 7.6 Hz,
1H), 7.29 (t, J = 7.6 Hz, 1H), 7.65 (s, 1H), 7.96 (d, J = 7.6 Hz, 1H) ppm. 13C NMR
(150 MHz, CDCl3): δ = 11.6, 15.0, 55.6, 110.8, 116.6, 120.9, 126.6, 127.8, 129.6,
129.8, 148.8, 150.1, 150.7, 154.9, 156.0 ppm. HRMS (ESI+): calcd for C15H15N2O2S
[M+H]+ 287.0854, found 287.0851.
5ꢀ(4ꢀBromophenyl)ꢀ2ꢀ(4,5ꢀdimethylthiazolꢀ2ꢀyl)oxazole (4d, known compound). The
crude residue was purified by flash column chromatography on silica gel to afford 4d
as a yellow solid (122 mg, 73%), and 1bb as a white solid (13 mg, 23%)
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(petroleum/dichloromethane/ethyl acetate = 10/2/1ꢀ6/2/1 v/v). M.p.: 147ꢀ149 °C. H
NMR (400 MHz, CDCl3): δ = 2.44 (s, 6H), 7.44 (s, 1H), 7.54 (d, J = 8.0 Hz, 2H), 7.61
(d, J = 8.4 Hz, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ = 11.7, 15.0, 123.0, 124.2,
126.2, 126.3, 130.4, 132.2, 149.7, 150.9, 151.2, 156.2 ppm. HRMS (ESI+): calcd for
C14H12BrN2OS [M+H]+ 334.9854, found 334.9852.
Ethyl 2ꢀ(4,5ꢀdimethylthiazolꢀ2ꢀyl)ꢀ4ꢀmethyloxazoleꢀ5ꢀcarboxylate (4e, known
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compound). The crude residue was purified by flash column chromatography on silica
gel to afford 4e as a white solid (97 mg, 73%), 1bb as a white solid (10 mg, 18%) and
2hh as a white solid (6 mg, 8%) (petroleum/ethyl acetate = 10/1ꢀ5/1 v/v). M.p.:
95ꢀ97 °C. 1H NMR (400 MHz, CDCl3): δ = 1.37 (t, J = 7.2 Hz, 3H), 2.42 (s, 3H), 2.44
(s, 3H), 2.53 (s, 3H), 4.36 (q, J = 7.2 Hz, 2H) ppm. 13C NMR (150 MHz, CDCl3): δ =
11.8, 13.5, 14.4, 14.9, 61.4, 131.9, 137.8, 147.4, 148.4, 151.7, 156.5, 158.6 ppm.
HRMS (ESI+): calcd for C12H15N2O3S [M+H]+ 267.0803, found 267.0805.
Ethyl 4ꢀmethylꢀ2ꢀ(5ꢀphenyloxazolꢀ2ꢀyl)thiazoleꢀ5ꢀcarboxylate (4f). The crude residue
was purified by flash column chromatography on silica gel to afford 4f as a white
solid (96 mg, 61%), 1cc (20 mg, 23%) and 2aa (9 mg, 12%) (petroleum/ethyl acetate
= 15/1ꢀ8/1 v/v). mp: 123ꢀ125 °C. 1H NMR (400 MHz, CDCl3): δ = 1.36 (t, J = 8.0 Hz,
3H), 2.84 (s, 3H), 4.35 (q, J = 7.2 Hz, 2H), 7.37 (t, J = 7.0 Hz, 1H), 7.43 (t, J = 7.4
Hz, 2H), 7.52 (s, 1H), 7.77 (d, J = 7.6 Hz, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 14.4, 17.6, 61.8, 124.3, 125.0, 127.0, 129.2, 129.6, 130.2, 153.4, 155.2, 155.7, 161.6,
161.9 ppm. HRMS (ESI+): calcd for C16H15N2O3S [M+H]+ 315.0803, found
315.0806.
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Diethyl 4,4'ꢀdimethylꢀ2,2'ꢀbithiazoleꢀ5,5'ꢀdicarboxylate (1cc, known compound). M.p.:
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184ꢀ186 °C. H NMR (400 MHz, CDCl3): δ = 1.36 (t, J = 7.2 Hz, 6H), 2.77 (s, 6H),
4.33 (q, J = 7.2 Hz, 4H) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.4, 17.6, 61.7,
124.7, 161.4, 162.0 ppm. HRMS (ESI+): calcd for C14H17N2O4S2 [M+H]+ 341.0630,
found 341.0624.
Ethyl 2ꢀ(5ꢀ(ethoxycarbonyl)ꢀ4ꢀmethylthiazolꢀ2ꢀyl)ꢀ4ꢀmethyloxazoleꢀ5ꢀcarboxylate (4g,
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known compound). The crude residue was purified by flash column chromatography
on silica gel to afford 4g as a white solid (102 mg, 63%), and 1cc as a pale yellow
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solid (18 mg, 21%) (petroleum/ethyl acetate = 10/1ꢀ7/1 v/v). M.p.: 122ꢀ124 °C. H
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NMR (400 MHz, CDCl3): δ = 1.34ꢀ1.40 (m, 6H), 2.53 (s, 3H), 2.79 (s, 3H), 4.32ꢀ4.42
(m, 4H) ppm. 13C NMR (100 MHz, CDCl3): δ = 13.4, 14.3, 14.4, 17.5, 61.6, 61.9,
125.5, 138.6, 147.5, 154.3, 155.5, 158.2, 161.5, 161.8 ppm. HRMS (ESI+): calcd for
C14H17N2O5S [M+H]+ 325.0858, found 325.0851.
Ethyl 2ꢀ(5ꢀformylꢀ4ꢀmethylthiazolꢀ2ꢀyl)ꢀ4ꢀmethyloxazoleꢀ5ꢀcarboxylate (4h, known
compound). The crude residue was purified by flash column chromatography on silica
gel to afford 4h as an offꢀwhite solid (98 mg, 70%) (petroleum/ethyl acetate =
15/1ꢀ8/1 v/v). M.p.: 123ꢀ125 °C. 1H NMR (400 MHz, CDCl3): δ = 1.40 (t, J = 7.2 Hz,
3H), 2.57 (s, 3H), 2.85 (s, 3H), 4.40 (q, J = 7.2 Hz, 2H), 10.16 (s, 1H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 13.5, 14.4, 16.5, 61.8, 135.4, 139.1, 147.8, 155.3, 157.8,
158.2, 162.7, 182.2 ppm. HRMS (ESI+): calcd for C12H13N2O4S [M+H]+ 281.0596,
found 281.0599.
4ꢀMethylꢀ2ꢀ(5ꢀphenyloxazolꢀ2ꢀyl)thiazoleꢀ5ꢀcarbaldehyde (4i, known compound).
The crude residue was purified by flash column chromatography on silica gel to
afford 4i as a yellow solid (88 mg, 65%), and 2aa as a white solid (14 mg, 19%)
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(petroleum/ethyl acetate = 10/1ꢀ5/1 v/v). M.p.: 152ꢀ154 °C. H NMR (400 MHz,
CDCl3): δ = 2.85 (s, 3H), 7.39 (t, J = 7.2 Hz, 1H), 7.45 (t, J = 7.2 Hz, 2H), 7.57 (s,
1H), 7.78 (d, J = 7.2 Hz, 2H), 10.15 (s, 1H) ppm. 13C NMR (150 MHz, CDCl3): δ =
16.5, 124.8, 125.1, 126.8, 129.2, 129.8, 134.3, 153.9, 155.0, 159.0, 162.6, 182.3 ppm.
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HRMS (ESI+): calcd for C14H11N2O2S [M+H]+ 271.0541, found 271.0544.
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Ethyl 2ꢀ(5ꢀ(2ꢀmethoxyethyl)ꢀ4ꢀmethylthiazolꢀ2ꢀyl)ꢀ4ꢀmethyloxazoleꢀ5ꢀcarboxylate (4j,
known compound). The crude residue was purified by flash column chromatography
on silica gel to afford 4j as an offꢀwhite solid (102 mg, 66%) (petroleum/ethyl acetate
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= 7/1ꢀ4/1 v/v). M.p.: 64ꢀ66 °C. H NMR (400 MHz, CDCl3): δ = 1.37 (t, J = 7.2 Hz,
3H), 2.45 (s, 3H), 2.53 (s, 3H), 3.03 (t, J = 6.2 Hz, 2H), 3.36 (s, 3H), 3.57 (t, J = 6.0
13
Hz, 2H), 4.36 (q, J = 7.2 Hz, 2H) ppm. C NMR (150 MHz, CDCl3): δ = 13.5, 14.4,
15.3, 27.5, 58.9, 61.3, 71.9, 134.0, 137.8, 147.4, 149.7, 151.7, 156.6, 158.6 ppm.
HRMS (ESI+): calcd for C14H19N2O4S [M+H]+ 311.1066, found 311.1065.
Ethyl 2ꢀ(5ꢀ(ethoxycarbonyl)thiazolꢀ2ꢀyl)ꢀ4ꢀmethyloxazoleꢀ5ꢀcarboxylate (4k, known
compound). The crude residue was purified by flash column chromatography on silica
gel to afford 4k as a white solid (98 mg, 63%), 1ff as a pale yellow solid (12 mg,
15%), and 2hh as a white solid (15 mg, 19%) (petroleum/ethyl acetate = 10/1ꢀ7/1 v/v).
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M.p.: 116ꢀ118 °C. H NMR (400 MHz, CDCl3): δ = 1.39ꢀ1.42 (m, 6H), 2.57 (s, 3H),
4.38ꢀ4.44 (m, 4H), 8.52 (s, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 13.4, 14.3,
14.4, 61.6, 62.3, 132.8, 138.8, 147.5, 149.7, 155.3, 157.6, 158.2, 160.6 ppm. HRMS
(ESI+): calcd for C13H15N2O5S [M+H]+ 311.0702, found 311.0703.
Diethyl 2,2'ꢀbithiazoleꢀ5,5'ꢀdicarboxylate (1ff, known compound). M.p.: 183ꢀ185 °C.
1H NMR (400 MHz, CDCl3): δ = 1.39 (t, J = 7.2 Hz, 6H), 4.38 (q, J = 7.2 Hz, 4H),
8.45 (s, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.4, 62.2, 132.2, 149.4, 161.0
165.1 ppm. HRMS (ESI+): calcd for C12H13N2O4S2 [M+H]+ 313.0317, found
313.0317.
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Ethyl 2ꢀ(5ꢀphenyloxazolꢀ2ꢀyl)thiazoleꢀ5ꢀcarboxylate (4l, known compound). The
crude residue was purified by flash column chromatography on silica gel to afford 4l
as a yellow solid (97 mg, 65%), 1ff as a pale yellow solid (10 mg, 13%) and 2aa as a
white solid (8 mg, 11%) (petroleum/ethyl acetate = 10/1ꢀ7/1 v/v). M.p.: 104ꢀ107 °C.
1H NMR (400 MHz, CDCl3): δ = 1.39 (t, J = 7.2 Hz, 3H), 4.39 (q, J = 7.2 Hz, 2H),
7.37 (t, J = 7.2 Hz, 1H), 7.44 (t, J = 7.2 Hz, 2H), 7.53 (s, 1H), 7.77 (d, J = 7.6 Hz, 2H),
8.51 (s, 1H) ppm. 13C NMR (150 MHz, CDCl3): δ = 14.4, 62.2, 124.4, 125.0, 126.9,
129.2, 129.6, 131.5, 149.5, 153.5, 155.1, 158.9, 161.0 ppm. HRMS (ESI+): calcd for
C15H12N2O3S [M+H]+ 301.0647, found 301.0652.
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Ethyl 4ꢀmethylꢀ2ꢀ(thiazolꢀ2ꢀyl)oxazoleꢀ5ꢀcarboxylate (4m, known compound). The
crude residue was purified by flash column chromatography on silica gel to afford 4m
as a pale yellow solid (71 mg, 60%) (petroleum/ethyl acetate = 10/1ꢀ5/1 v/v). M.p.:
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106ꢀ108 °C. H NMR (400 MHz, CDCl3): δ = 1.39 (t, J = 7.2 Hz, 3H), 2.56 (s, 3H),
4.38 (q, J = 7.2 Hz, 2H), 7.57 (d, J = 2.4 Hz, 1H), 8.03 (d, J = 2.0 Hz, 1H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 13.4, 14.4, 61.5, 123.0, 138.3, 145.3, 147.4, 153.8,
156.2, 158.5 ppm. HRMS (ESI+): calcd for C10H11N2O3S [M+H]+ 239.0490, found
239.0495.
Ethyl 4ꢀmethylꢀ2ꢀ(1ꢀvinylꢀ1Hꢀimidazolꢀ2ꢀyl)oxazoleꢀ5ꢀcarboxylate (4n, known
compound). The crude residue was purified by flash column chromatography on silica
gel to afford 4n as a white solid (72 mg, 58%) (petroleum/ethyl acetate = 4/1ꢀ2/1 v/v).
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M.p.: 151ꢀ153 °C. H NMR (400 MHz, CDCl3): δ = 1.36 (t, J = 7.2 Hz, 3H), 2.54 (s,
3H), 4.36 (q, J = 7.2 Hz, 2H), 5.07 (d, J = 8.8 Hz, 1H), 5.36 (d, J = 15.6 Hz, 1H), 7.26
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(s, 1H), 7.45 (s, 1H), 8.14 (dd, J = 15.6 Hz, J = 8.8 Hz, 1H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 13.4, 14.4, 61.3, 104.1, 118.8, 130.5, 131.4, 134.2, 137.3, 146.7, 153.4,
158.6 ppm. HRMS (ESI+): calcd for C12H14N3O3 [M+H]+ 248.1035, found 248.1034.
Ethyl 4ꢀmethylꢀ2ꢀ(1ꢀmethylꢀ4ꢀnitroꢀ1Hꢀimidazolꢀ2ꢀyl)oxazoleꢀ5ꢀcarboxylate (4o,
known compound). The crude residue was purified by flash column chromatography
on silica gel to afford 4o as a white solid (73 mg, 52%) (petroleum/ethyl acetate =
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2/1ꢀ1/1 v/v). M.p.: 155ꢀ157 °C. H NMR (400 MHz, CDCl3): δ = 1.36 (t, J = 7.2 Hz,
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3H), 2.53 (s, 3H), 4.22 (s, 3H), 4.35 (q, J = 7.2 Hz, 2H), 7.92 (s, 1H) ppm. C NMR
(100 MHz, CDCl3): δ = 13.4, 14.4, 37.2, 61.6, 124.0, 133.8, 138.2, 146.7, 151.9,
158.3 ppm. HRMS (ESI+): calcd for C11H13N4O5 [M+H]+ 281.0886, found 281.0890.
ACKNOWLEDGEMENT
This work was supported by grants from the National NSF of China (Nos 21172155,
20972102, 21025205, 21021001 and J1103315/J0104) and the National Basic
Research Program of China (973 Program, 2011CB8086600). We thank the Centre of
Testing & Analysis, Sichuan University for NMR measurements.
Supporting Information. Data and copies of NMR for compounds, and detailed
heteroꢀcouplings and homoꢀcouplings. This material is available free of charge via the
Internet at http://pubs.acs.org.
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