Studies on electrophilic cyclization of N-(buta-2,3-dienyl)amides with N-bromosuccinimide and its applications

Article abstract of DOI:10.1002/adsc.201300959

An efficient protocol for the synthesis of oxazoline and bisoxazoline derivatives via electrophilic cyclization of N-(buta-2,3-dienyl)amides with N-bromosuccinimide (NBS) at room temperature has been developed. Synthetic transformations of the obtained oxazolines have been successfully performed due to the presence of vinyl bromide units comprising an elimination reaction and a copper(I)- catalyzed C-N coupling reaction using diethylamine (Et₂NH) as the ligand.

Full text of DOI:10.1002/adsc.201300959

FULL PAPERS
DOI: 10.1002/adsc.201300959
Studies on Electrophilic Cyclization of N-(Buta-2,3-dienyl)amides
with N-Bromosuccinimide and its Applications
Nan Wang,a Bo Chen,b and Shengming Maa,b,*
a
Shanghai Key Laboratory of Green Chemistry and Chemical Process, Department of Chemistry, East China Normal
University, 3663 North Zhongshan Lu, Shanghai 200062, Peopleꢀs Republic of China
Fax : (+86)-21-6416-7510; e-mail: masm@sioc.ac.cn
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
b
Sciences, 345 Lingling Lu, Shanghai 200032, Peopleꢀs Republic of China
Received: October 28, 2013; Published online: February 6, 2014
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300959.
Abstract: An efficient protocol for the synthesis of comprising an elimination reaction and a copper(I)-
À
oxazoline and bisoxazoline derivatives via electro- catalyzed C N coupling reaction using diethylamine
philic cyclization of N-(buta-2,3-dienyl)amides with (Et2NH) as the ligand.
N-bromosuccinimide (NBS) at room temperature
has been developed. Synthetic transformations of the
obtained oxazolines have been successfully per- Keywords: N-(buta-2,3-dienyl)amides; electrophilic
formed due to the presence of vinyl bromide units cyclization; oxazolines
Introduction
oxazolines only in moderate yields and are not always
in harmony with highly functionalized substrates.
Oxazolines are frequently encountered motifs in natu- Moreover, the diversity of oxazolines is impeded by
ral products and biologically active compounds.[1] the limited commercial availability of b-amino alco-
They are also known as useful intermediates in organ- hols in the above two methods. Due to the impor-
ic synthesis and polymer chemistry;[2] furthermore, tance of the oxazoline nucleus, the development of
optically active oxazoline derivatives play an impor- facile, efficient and diverse synthetic methods is still
tant role in asymmetric synthesis, extensively serving highly desirable. Electrophilic cyclizations of function-
as auxiliaries and ligands.[3] Generally, there are two alized allenes have been established as an efficient
approaches to oxazolines: (i) the reaction of b-amino method for the synthesis of various heterocycles.[10]
alcohols with carboxylic acids and carboxylic acid de- This methodology profits from the presence of a resid-
rivatives;[4] (ii) the cyclodehydration reaction of b-hy- ual halogen atom which offers potential for the fur-
droxy amides promoted by Burgess reagent [methyl ther introduction of various functional groups. On the
N-(triethylammoniumsulfonyl)carbamate],[5] Vilsmei- basis of our continuing interest in this field,[11] we en-
er reagent (chloromethylene dimethyliminium chlo- visioned that the electrophilic cyclization of N-(buta-
ride),[6] DAST,[7] BF3·Et2O[8] and PPh3/DEAD[9] 2,3-dienyl)amides[12] may afford an novel approach to
(Scheme 1). Notably, many of these reagents furnish a-halovinyloxazolines.
Results and Discussion
The initial electrophilic cyclization experiment was
conducted by using N-(buta-2,3-dienyl)benzamide 1a
and 2.0 equiv. of I2 in CH3CN at room temperature.
The product of O-attack, 5-(1-bromovinyl)-2-phenyl-
4,5-dihydrooxazole 2a’, was detected in 46% yield as
1
determined by H NMR analysis of the crude product
(Table 1, entry 1). A series of solvents was examined
with no better results (Table 1, entries 2–7). Our pre-
Scheme 1. Known methods for the synthesis of oxazolines
and our approach.
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Nan Wang et al.
Table 1. Effect of solvent and various electrophilic reagents
on the cyclization of N-(buta-2,3-dienyl)amide 1a.[a]
Table 2. Effect of the loading of NBS on the cyclization of
N-(buta-2,3-dienyl)amide 1a.[a]
Entry
NBS [equiv.]
Time [min]
Yield of 2a [%][b]
Entry
Solvent
X+
Time
[min]
Yield of
1
2
3
4
5
6
1.0
1.2
2.0
3.0
4.0
5.0
27
10
15
10
21
21
70
81
62
70
65
56
G
2a/2a’ [%][b]
1
2
3
4
CH3CN
dioxane
THF
CH2Cl2
DMF
DMA
toluene
CH3CN/H2O (10:1)
CH3CN/H2O (4:1)
CH3CN
CH3CN
CH3CN
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
NIS
NBS
50
13
50
50
40
13
40
12
15
100
80
15
46 (2a’)
36 (2a’)
38 (2a’)
37 (2a’)
15 (2a’)
33 (2a’)
29 (2a’)
46 (2a’)
30 (2a’)
29 (2a’)
49 (2a’)
62 (2a)
5[c]
6[d]
7
[a]
The reaction was carried out with 1a (0.4 mmol), NBS
(x equiv.) in CH3CN (2 mL).
Determined by NMR spectroscopic analysis using 1,3,5-
trimethylbenzene as the internal standard.
[b]
8
9
10[e]
11
12
Table 3. Substrate scope for cyclization of N-(buta-2,3-dien-
AHCTUNGTRENNUNG
yl)amides 1 with NBS.[a]
[a]
The reaction was carried out with 1a (0.4 mmol), X+
(0.8 mmol) in 2 mL of the indicated solvent (dried as de-
scribed in the Supporting Information) under an argon
atmosphere.
Determined by NMR spectroscopic analysis using 1,3,5-
trimethylbenzene as the internal standard.
8% of starting material 1a remained.
[b]
[c]
[d]
[e]
Entry
R
Time [min]
Yield of 2 [%][b]
10% of starting material 1a remained.
Reaction temperature: 08C.
1
2
3
4
5
6
7
8
H (1a)
10
80
10
10
300
10
50
10
20
50
64 (2a)
60 (2b)
74 (2c)
81 (2d)
77 (2e)
80 (2f)
77 (2g)
78 (2h)
77 (2i)
76 (2j)
3-NO2 (1b)
4-CO2Me (1c)
4-CN (1d)
3,5-Cl2 (1e)
4-Cl (1f)
4-CF3 (1g)
4-F (1h)
vious work showed that H2O plays a role in electo-
philic cyclization.[13] However, a mixture of MeCN
and H2O did not improve the yield here (Table 1, en-
tries 8 and 9). The product was afforded in a relatively
poor yield at a lower temperature (08C) (Table 1,
entry 10). The yields were improved by employing N-
bromosuccinimide (NBS) instead of N-iodosuccin-
9
10
4-MeO (1i)
3-Me (1j)
[a]
The reaction was carried out with 1 (1.0 mmol) and NBS
(1.2 mmol) in CH3CN (4 mL).
Isolated yield.
ACHTUNGTRENNUNG
[b]
NBS revealed that an increase in the loading of NBS
was deleterious for the reaction (Table 2). The results
showed that 1.2 equiv. of NBS afforded the best ring were tolerated with only limited influence on the
result. Thus, we defined the reaction of N-(buta-2,3- yield.
dienyl) amides with 1.2 equiv. of NBS in CH3CN at
room temperature as the standard conditions verified with different types of substrates (Scheme 2):
(Table 2, entry 2). The heteroaromatic substituted oxazolines could be
The generality of this transformation was further
The scope of this transformation was investigated achieved in a preparatively useful yield under the
under the standard conditions. As shown in Table 3, standard conditions (2k and 2l). The presence of
the electrophilic cyclization may proceed smoothly naphthyl substituents did not alter the expected out-
for a wide range of substrates with full conversion come of the reaction (2m and 2o). However, when
within 10 min to 5 h. Different electron-withdrawing the substrate with an alkyl group was subjected to our
(NO2, COOMe, CN, Cl, CF3, F) (2b–2h; Table 3, en- standard conditions, the corresponding product (2o)
tries 2–8) and electron-donating groups (OMe, Me) was furnished in only 26% isolated yield accompanied
(2i and 2j; Table 3, entries 9 and 10) in the phenyl by an unidentified side product.
486
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Studies on Electrophilic Cyclization of N-(Buta-2,3-dienyl)amides
Scheme 2. Further substrate scope.
Scheme 3. Synthetic applications of 2-phenyl-5-(1-bromovin-
yl)-4,5-dihydrooxazoles 2.
In addition, the reaction may be easily conducted
with substrate 1m on a scale of 1 g affording 2m in
67% yield [Eq. (1)]. The reaction may also be extend-
ed to the synthesis of the bisoxazoline 2p in 56% Conclusions
yield via double bromocyclization of N1,N3-di(buta-
2,3-dienyl)isophthalamide 1p [Eq. (2)].
In conclusion, we have developed a facile and effi-
The obtained 2,5-substituted oxazolines could be cient protocol for the construction of oxazoline deriv-
conveniently converted into synthetically useful build- atives by electrophilic cyclization of N-(buta-2,3-dien-
À
ing blocks due to the presence of C=C Br subunits yl)amides with the low-cost and readily available re-
(Scheme 3). The elimination of HBr from 2 afforded agent NBS. The reaction enjoys features of mild reac-
the corresponding ethynyloxazolines 3a–3c by treat- tion conditions, short reaction time and high tolerance
ment with TBAF·3H2O.[14] The C N coupling of 2 toward functional groups. The bisoxazoline could also
À
with indole, another important heterocycle, was suc- been synthesized through this approach. In addition,
cessfully realized using 20 mol% of CuI as catalyst re- derivations of the obtained oxazoline derivatives to
sulting in the formation of 4a in 86% isolated yield. ethynyloxazolines and 1-(1H-indol-1-yl)vinyloxazo-
Interestingly, here the simplest diethylamine lines have been achieved. Further studies in this area
(40 mol%) was found to be the most suitable ligand are being conducted in our laboratory.
rather than 1,2-diamines which were commonly used
À
as ligands in copper-catalyzed C N cross-couplings of
vinyl halides and amines or azoles.[15] The presence of
CF3 and Cl at the phenyl ring was also tolerated (4b
Experimental Section
and 4c).
General Information
All reactions were carried out in oven-dried Schlenk tubes.
CH3CN, CH2Cl2, DMA and DMF were dried over calcium
hydride before distillation. 1,4-Dioxane, THF and toluene
Adv. Synth. Catal. 2014, 356, 485 – 492
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487

FULL PAPERS
Nan Wang et al.
were dried over Na wire before distillation. All the tempera-
tures are referred to the bath temperature. H NMR chemi-
1023 cmÀ1; MS (EI): m/z=299 (M+, 13.57), 117 (100); HR-
MS: m/z=298.9809, calcd. for C11H10INO [M+]: 298.9807.
5-(1-Bromovinyl)-2-(3-nitrophenyl)-4,5-dihydrooxazole
(2b): The reaction of 1b (218.0 mg, 1.0 mmol), NBS
(213.2 mg, 1.2 mmol), and CH3CN (4 mL) afforded 2b as
1
cal shifts were recorded in ppm in relative to TMS
(0.00 ppm). 13C NMR chemical shifts were recorded in ppm
in relative to CDCl3 (77.0 ppm). 19F NMR chemical shifts
were recorded in ppm relative to CFCl3 (0.00 ppm)
(F19CPD). IR spectra were recorded on the infrared spec-
trometer. Melting points were measured without correction.
Common reagents were purchased from commercial sources
and were used without further purification. Column chroma-
tography was performed using silica gel (300–400 mesh)
eluting with ethyl acetate and petroleum ether. TLC was
performed on glass-backed silica plates. All N-(buta-2,3-di-
enyl)amides 1 were prepared in accordance with the litera-
ture procedure.[12]
a
solid (petroleum ether/ethyl acetate=10:1); yield:
179.8 mg (60%); mp 65–65.38C (n-hexane/ethyl acetate);
1H NMR (300 MHz, CDCl3): d=8.80 (t, J=1.8 Hz, 1H,
ArH), 8.39–8.28 (m, 2H, ArH), 7.64 (t, J=8.1 Hz, 1H,
ArH), 6.04 (dd, J=2.2, 0.8 Hz, 1H, one proton in C=CH2),
5.68 (d, J=2.1 Hz, 1H, one proton in C=CH2), 5.26 (dd, J=
9.9, 7.2 Hz, 1H, OCH), 4.31 (dd, J=15.4, 10.4 Hz, 1H, one
proton in NCH2), 4.08 (dd, J=15.3, 7.2 Hz, 1H, one proton
in NCH2); 13C NMR (75 MHz, CDCl3): d=161.2, 148.0,
133.8, 130.9, 129.5, 128.8, 125.9, 123.1, 118.6, 81.9, 60.5; IR
(neat) 1652, 1625, 1524, 1445, 1345, 1299, 1251, 1171, 1107,
1074 cmÀ1
(81Br)+, 4.13], 296
; MS (EI): m/z=298 [MACHTUNTGNRUEGN
[M
AHCTUNGTRENNUNG
Synthesis of 5-(1-Bromovinyl)-2-phenyl-4,5-dihydro-
oxazole (2a); Typical Procedure I
44.47, H 3.05, N 9.43; found: C 44.56, H 3.15, N 9.07.
5-(1-Bromovinyl)-2-(4-methoxycarbonylphenyl)-4,5-dihy-
drooxazole (2c): The reaction of 1c (231.4 mg, 1.0 mmol),
NBS (212.9 mg, 1.2 mmol), and CH3CN (4 mL) afforded 2c
as a solid (petroleum ether/ethyl acetate=30:1 to 10:1);
yield: 232.9 mg (74%); mp 109–1108C (n-hexane/ethyl ace-
tate); 1H NMR (300 MHz, CDCl3): d=8.13–8.00 (m, 4H,
ArH), 6.02 (dd, J=2.1, 0.6 Hz, 1H, one proton in C=CH2),
5.65 (d, J=2.1 Hz, 1H, one proton in C=CH2), 5.22 (dd, J=
9.9, 7.2 Hz, 1H, OCH), 4.28 (dd, J=15.3, 10.2 Hz, 1H, one
proton in NCH2), 4.06 (dd, J=15.3, 7.2 Hz, 1H, one proton
in NCH2), 3.95 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3):
d=166.3, 162.6, 132.6, 131.2, 131.1, 129.6, 128.1, 118.1, 81.5,
60.5, 52.3; IR (neat): n=1713, 1648, 1435, 1409, 1347, 1278,
1255, 1193, 1106, 1066, 1009 cmÀ1; MS (EI): m/z=311
To a dry Schlenk tube were added 1a (174.0 mg, 1.0 mmol),
NBS (213.8 mg, 1.2 mmol), and CH3CN (4 mL) under an
argon atmosphere. The mixture was stirred at room temper-
ature and monitored by TLC. After the reaction was com-
plete, the mixture was quenched with a saturated aqueous
solution of NaHCO3 (2 mL) and Na2S2O3 (2 mL). The re-
sulting mixture was extracted with ether (10 mLꢂ 3) and
dried over anhydrous MgSO4. After filtration and evapora-
tion, chromatography on silica gel (petroleum ether/ethyl
acetate=20:1 to 10:1) afforded 2a as a solid; yield: 162.9 mg
(64%); mp 55–568C (n-hexane/diethyl ether); 1H NMR
(300 MHz, CDCl3): d=8.01–7.94 (m, 2H, ArH), 7.54–7.39
(m, 3H, ArH), 6.00 (dd, J=2.1, 1.2 Hz, 1H, one proton in
C=CH2), 5.62 (d, J=2.4 Hz, 1H, one proton in C=CH2),
5.18 (dd, J=10.0, 7.0 Hz, 1H, OCH), 4.25 (dd, J=15.0,
9.9 Hz, 1H, one proton in NCH2), 4.03 (dd, J=15.0, 7.0 Hz,
1H, one proton in NCH2); 13C NMR (75 MHz, CDCl3): d=
163.4, 131.52, 131.50, 128.4, 128.1, 127.1, 117.7, 81.3, 60.5; IR
(neat): n=1652, 1448, 1344, 1300, 1275, 1252, 1059,
[MACHTNUTRGENNUG HCATUNGTRENNGUN
(81Br)+, 4.78], 309 [M(79Br)+, 5.27], 175 (100); anal. calcd.
for C13H12BrNO3: C 50.34, H 3.90, N 4.52; found: C 50.56,
H 3.92, N 4.86.
5-(1-Bromovinyl)-2-(4-cyanophenyl)-4,5-dihydrooxazole
(2d): The reaction of 1d (198.4 mg, 1.0 mmol), NBS
(212.9 mg, 1.2 mmol), and CH3CN (4 mL) afforded 2d as
a solid (petroleum ether/ethyl acetate=30:1 to 10:1); yield:
224.6 mg (81%); mp 109–1108C (n-hexane/ethyl acetate);
1H NMR (300 MHz, CDCl3): d=8.07 (d, J=8.4 Hz, 2H,
ArH), 7.73 (d, J=8.7 Hz, 2H, ArH), 6.02 (dd, J=2.4,
0.9 Hz, 1H, one proton in C=CH2), 5.66 (d, J=2.1 Hz, 1H,
one proton in C=CH2), 5.24 (dd, J=10.2, 7.2 Hz, 1H,
OCH), 4.29 (dd, J=15.5, 10.0 Hz, 1H, one proton in
NCH2), 4.07 (dd, J=15.6, 7.2 Hz, 1H, one proton in NCH2);
13C NMR (75 MHz, CDCl3): d=161.7, 132.1, 131.1, 131.0,
128.6, 118.5, 118.1, 114.8, 81.7, 60.5; IR (neat): n=2226,
1654, 1634, 1321, 1252, 1066 cmÀ1; MS (EI): m/z=278
1008 cmÀ1
(81Br)+, 5.45], 251
; MS (EI): m/z=253 [MACHTUNTGNRUEGN
[M
ACHTUNGTRENNUNG
52.41, H 4.00, N 5.56; found: C 52.42, H 3.98, N 5.33.
The following compounds were prepared according to
Typical Procedure I.
5-(1-Iodovinyl)-2-phenyl-4,5-dihydrooxazole (2a’): To
a dry Schlenk tube were added 1a (1.1125 g, 6.4 mmol), NIS
(1.6170 g, 7.2 mmol), and CH3CN (10 mL) under an argon
atmosphere. The mixture was stirred at room temperature
for 5 h as monitored by TLC, it was then quenched with a sa-
turated aqueous solution of NaHCO3 (5 mL) and Na2S2O3
(5 mL). The resulting mixture was extracted with ether
(50 mL) and dried over anhydrous MgSO4. After filtration
and evaporation, chromatography on silica gel (petroleum
ether/ethyl acetate=20:1) afforded 2a’ as an oil; yield:
[MACHTNUTRGENNUG HCATUNGTRENNGUN
(81Br)+, 4.72], 276 [M(79Br)+, 4.59], 142 (100); anal. calcd.
for C12H9BrN2O: C 52.01, H 3.27, N 10.11; found: C 51.99,
H 3.44, N 10.07.
5-(1-Bromovinyl)-2-(3,5-dichlorophenyl)-4,5-dihydrooxa-
zole (2e): The reaction of 1e (243.0 mg, 1.0 mmol), NBS
(215.5 mg, 1.2 mmol), and CH3CN (4 mL) afforded 2e as
a solid (petroleum ether/ethyl acetate=30:1 to 10:1); yield:
247.2 mg (77%); mp 68–698C (n-hexane/diethyl ether);
1H NMR (300 MHz, CDCl3): d=7.85 (d, J=2.1 Hz, 2H,
ArH), 7.48 (t, J=1.8 Hz, 1H, ArH), 6.00 (dd, J=2.3, 0.8 Hz,
1H, one proton in C=CH2), 5.65 (d, J=2.1 Hz, 1H, one
proton in C=CH2), 5.20 (dd, J=9.8, 7.4 Hz, 1H, OCH), 4.26
1
0.7358 g (38%); H NMR (300 MHz, CDCl3): d=8.00–7.93
(m, 2H, ArH), 7.52–7.37 (m, 3H, ArH), 6.45 (dd, J=1.8,
1.2 Hz, 1H, one proton in C=CH2), 5.89 (d, J=1.5 Hz, 1H,
one proton in C=CH2), 4.91 (dd, J=9.9, 7.2 Hz, 1H, OCH),
4.20 (dd, J=15.3, 9.9 Hz, 1H, one proton in NCH2), 3.88
(dd, J=15.3, 7.2 Hz, 1H, one proton in NCH2); 13C NMR
(75 MHz, CDCl3): d=163.2, 131.4, 128.3, 128.1, 127.1, 126.0,
110.5, 83.5, 61.4; IR (neat): n=1650, 1350, 1254, 1060,
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Studies on Electrophilic Cyclization of N-(Buta-2,3-dienyl)amides
(dd, J=15.3, 9.9 Hz, 1H, one proton in NCH2), 4.03 (dd, J=
15.5, 7.1 Hz, 1H, one proton in NCH2); 13C NMR (75 MHz,
CDCl3): d=161.2, 135.2, 131.4, 131.0, 129.9, 126.6, 118.5,
81.8, 60.5; IR (neat): n=3047, 1655, 1564, 1336, 1297, 1249,
1086 cmÀ1; MS (EI): m/z=325 [M(81Br, 37Cl, 37Cl)+, 0.85],
323 [M(81Br, 37Cl, 35Cl or 79Br, 37Cl, 37Cl)+, 4.72], 321
[M(81Br, 35Cl, 35Cl or 79Br,37Cl,35Cl)+, 10.09], 319
[M(79Br,35Cl,35Cl)+, 7.33], 185 (100); anal. calcd. for
C11H8BrCl2NO: C 41.16, H 2.51, N 4.36; found: C 41.11, H
2.47, N 4.15.
5-(1-Bromovinyl)-2-(4-chlorophenyl)-4,5-dihydrooxazole
(2f): The reaction of 1f (207.1 mg, 1.0 mmol), NBS
(213.9 mg, 1.2 mmol), and CH3CN (4 mL) afforded 2f as
a solid (petroleum ether/ethyl acetate=20:1 to 10:1); yield:
231.5 mg (80%); mp 62–638C (n-hexane/diethyl ether);
1H NMR (300 MHz, CDCl3): d=7.94–7.86 (m, 2H, ArH),
7.44–7.37 (m, 2H, ArH), 5.99 (dd, J=2.1, 0.9 Hz, 1H, one
proton in C=CH2), 5.63 (d, J=2.1 Hz, 1H, one proton in C=
CH2), 5.19 (dd, J=9.9, 7.2 Hz, 1H, OCH), 4.24 (dd, J=15.2,
10.1 Hz, 1H, one proton in NCH2), 4.02 (dd, J=15.5,
7.1 Hz, 1H, one proton in NCH2); 13C NMR (75 MHz,
CDCl3): d=162.2, 137.5, 131.2, 129.3, 128.5, 125.5, 117.8,
81.3, 60.3; IR (neat): n=1647, 1596, 1486, 1402, 1349, 1303,
1257, 1168, 1092, 1068, 1008 cmÀ1; MS (EI): m/z=289
[M(81Br,37Cl)+, 2.09], 287 [M(81Br,35Cl or 79Br,37Cl)+, 8.70],
285 [M(79Br,35Cl)+, 6.73], 151 (100); anal. calcd. for
C11H9BrClNO: C 46.11, H 3.17, N 4.89; found: C 46.25, H
3.24, N 4.78.
5-(1-Bromovinyl)-2-(4-methoxy-phenyl)-4,5-dihydrooxa-
zole (2i): The reaction of 1i (202.8 mg, 1.0 mmol), NBS
(213.8 mg, 1.2 mmol), and CH3CN (4 mL) afforded 2i as
a solid (petroleum ether/ethyl acetate=30:1 to 10:1); yield:
215.6 mg (77%); mp 83–848C (n-hexane/ethyl acetate);
1H NMR (300 MHz, CDCl3): d=7.95–7.88 (m, 2H, ArH),
6.97–6.90 (m, 2H, ArH), 5.99 (dd, J=2.1, 0.9 Hz, 1H, one
proton in C=CH2), 5.61 (d, J=2.1 Hz, 1H, one proton in C=
CH2), 5.16 (dd, J=9.9, 6.9 Hz, 1H, OCH), 4.23 (dd, J=14.8,
10.1 Hz, 1H, one proton in NCH2), 4.00 (dd, J=14.8,
6.8 Hz, 1H, one proton in NCH2), 3.85 (s, 3H, OCH3);
13C NMR (75 MHz, CDCl3): d=163.0, 162.1, 131.6, 129.8,
119.5, 117.4, 113.6, 81.0, 60.3, 55.2; IR (neat): n=1648, 1606,
1511, 1421, 1347, 1300, 1252, 1164, 1067, 1024 cmÀ1; MS
(EI): m/z=283 [MACTHNUTRGNENGU ACHTUGNTRENNUGN
(81Br)+, 13.92], 281 [M(79Br)+, 13.93], 147
(100); anal. calcd. for C12H12BrNO2: C 51.09, H 4.29, N 4.96;
found: C 50.96, H 4.49, N 4.88.
5-(1-Bromovinyl)-2-(m-tolyl)-4,5-dihydrooxazole (2j): The
reaction of 1j (186.6 mg, 1.0 mmol), NBS (214.0 mg,
1.2 mmol), and CH3CN (4 mL) afforded 2j as a solid (petro-
leum ether/ethyl acetate=10:1); yield: 202.2 mg (76%); mp
67–688C (n-hexane/diethyl ether); 1H NMR (300 MHz,
CDCl3): d=7.83–7.72 (m, 2H, ArH), 7.36–7.28 (m, 2H,
ArH), 6.01 (dd, J=2.1, 0.9 Hz, 1H, one proton in C=CH2),
5.62 (d, J=2.1 Hz, 1H, one proton in C=CH2), 5.18 (dd, J=
9.9, 6.9 Hz, 1H, OCH), 4.25 (dd, J=15.0, 10.2 Hz, 1H, one
proton in NCH2), 4.02 (dd, J=15.3, 6.9 Hz, 1H, one proton
in NCH2), 2.39 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3):
d=163.3, 137.9, 132.1, 131.4, 128.5, 128.1, 126.8, 125.1, 117.5,
81.0, 60.2, 21.0; IR (neat) n=1645, 1628, 1600, 1588, 1351,
1309, 1265, 1195, 1167, 1064, 1038 cmÀ1; MS (EI): m/z=267
5-(1-Bromovinyl)-2-[4-(trifluoromethyl)phenyl]-4,5-dihy-
drooxazole (2g): The reaction of 1g (241.5 mg, 1.0 mmol),
NBS (213.7 mg, 1.2 mmol), and CH3CN (4 mL) afforded 2g
as an oil (petroleum ether/ethyl acetate=10:1); yield:
241.9 mg (77%); 1H NMR (300 MHz, CDCl3): d=8.09 (d,
J=8.1 Hz, 2H, ArH), 7.69 (d, J=8.4 Hz, 2H, ArH), 6.01
(dd, J=2.1, 0.9 Hz, 1H, one proton in C=CH2), 5.65 (d, J=
2.1 Hz, 1H, one proton in C=CH2), 5.23 (dd, J=10.2,
6.9 Hz, 1H, OCH), 4.28 (dd, J=15.5, 10.1 Hz, 1H, one
proton in NCH2), 4.06 (dd, J=15.5, 7.1 Hz, 1H, one proton
in NCH2); 13C NMR (75 MHz, CDCl3): d=162.1, 133.0 (q,
J=32.4 Hz), 131.2, 130.5, 128.5, 125.3 (q, J=3.9 Hz), 123.6
(q, J=270.8 Hz), 118.1, 81.6, 60.5; 19F NMR (CDCl3,
282 MHz): d=À63.5; IR (neat): n=1655, 1620, 1412, 1320,
1257, 1166, 1121, 1108, 1701, 1015 cmÀ1; MS (EI): m/z=321
[MACHTNUTRGENNUG HCATUNGTRENNGUN
(81Br)+, 6.88], 265 [M(79Br)+, 7.06], 131 (100); anal. calcd.
for C12H12BrNO: C 54.16, H 4.54, N 5.26; found: C 54.23, H
4.62, N 5.08.
5-(1-Bromovinyl)-2-(furan-2-yl)-4,5-dihydrooxazole (2k):
The reaction of 1k (164.1 mg, 1.0 mmol), NBS (214.5 mg,
1.2 mmol), and CH3CN (4 mL) afforded 2k as an oil (petro-
leum ether/ethyl acetate=10:1 to 5:1); yield: 158.3 mg
1
(65%); H NMR (300 MHz, CDCl3): d=7.57 (d, J=1.2 Hz,
1H, furyl), 7.00 (d, J=3.6 Hz, 1H, furyl), 6.51 (dd, J=3.4,
1.6 Hz, 1H, furyl), 6.01 (dd, J=1.8, 0.9 Hz, 1H, one proton
in C=CH2), 5.64 (d, J=1.8 Hz, 1H, one proton in C=CH2),
5.17 (dd, J=10.0, 7.0 Hz, 1H, OCH), 4.25 (dd, J=15.2,
10.0 Hz, 1H, one proton in NCH2), 4.03 (dd, J=15.0,
6.9 Hz, 1H, one proton in NCH2); 13C NMR (75 MHz,
CDCl3): d=155.6, 145.4, 142.3, 130.8, 118.2, 114.6, 111.5,
81.4, 60.3; IR (neat): n=1672, 1480, 1402, 1341, 1167, 1092,
[MACHTUNGTRENNUNG ACHTUNGTRENNUGN
(81Br)+, 4.25], 319 [M(79Br)+, 4.41], 185 (100); HR-MS:
m/z=318.9818, calcd. for C12H979BrF3NO [M+]: 318.9820.
5-(1-Bromovinyl)-2-(4-fluorophenyl)-4,5-dihydrooxazole
(2h): The reaction of 1h (191.5 mg, 1.0 mmol), NBS
(213.7 mg, 1.2 mmol), and CH3CN (4 mL) afforded 2h as an
oil (petroleum ether/ethyl acetate=30:1 to 20:1); yield:
1007 cmÀ1
(81Br)+, 9.93], 241
; MS (EI): m/z=243 [MACHTUNTGNRUEGN
[MACTHNUTRGNEUNG
(79Br)+, 10.3], 107 (100); HR-MS: m/z=240.9742, calcd.
1
212.9 mg (78%); H NMR (300 MHz, CDCl3): d=8.01–7.95
for C9H879BrNO2 [M+]: 240.9738.
(m, 2H, ArH), 7.15–7.07 (m, 2H, ArH), 6.00 (dd, J=2.1,
1.2 Hz, 1H, one proton in C=CH2), 5.63 (d, J=2.1 Hz, 1H,
one proton in C=CH2), 5.19 (dd, J=10.1, 7.1 Hz, 1H,
OCH), 4.24 (dd, J=15.0, 9.9 Hz, 1H, one proton in NCH2),
4.02 (dd, J=15.0, 6.9 Hz, 1H, one proton in NCH2);
13C NMR (75 MHz, CDCl3): d=164.7 (d, J=250.6 Hz),
162.4, 131.4, 130.4 (d, J=8.8 Hz), 123.3 (d, J=3.0 Hz), 117.8,
115.5 (d, J=21.8 Hz), 81.4, 60.4; 19F NMR (CDCl3,
282 MHz): d=À108.2; IR (neat): n=1659, 1605, 1509, 1350,
5-(1-Bromovinyl)-2-(thien-2-yl)-4,5-dihydrooxazole (2l):
The reaction of 1l (179.0 mg, 1.0 mmol), NBS (214.7 mg,
1.2 mmol), and CH3CN (4 mL) afforded 2l as an oil (petro-
leum ether/ethyl acetate=10:1); yield: 176.1 mg (68%);
1H NMR (300 MHz, CDCl3): d=7.66–7.62 (m, 1H, thienyl),
7.50–7.46 (m, 1H, thienyl), 7.12–7.06 (m, 1H, thienyl), 6.01
(dd, J=2.1, 0.9 Hz, 1H, one proton in C=CH2), 5.63 (d, J=
1.8 Hz, 1H, one proton in C=CH2), 5.18 (dd, J=9.8, 7.0 Hz,
1H, OCH), 4.23 (dd, J=15.0, 9.9 Hz, 1H, one proton in
NCH2), 4.01 (dd, J=15.2, 6.8 Hz, 1H, one proton in NCH2);
13C NMR (75 MHz, CDCl3): d=159.0, 131.0, 130.4, 130.1,
129.5, 127.5, 117.9, 81.6, 60.3; IR (neat): n=1650, 1524,
ACTHNUTRGNEUNG
1206, 1159, 1071 cmÀ1; MS (EI): m/z=271 [M(81Br)+, 6.17],
269 [MACHTUNGTRENNUNG
(79Br)+, 6.52], 135 (100); HR-MS: m/z=268.9854,
calcd. for C11H979BrFNO [M+]: 268.9852.
Adv. Synth. Catal. 2014, 356, 485 – 492
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
489

FULL PAPERS
Nan Wang et al.
1431, 1336, 1252, 1200, 1078, 1052, 1007 cmÀ1; MS (EI):
1.2 mmol), and CH3CN (4 mL) afforded 2o as an oil (petro-
leum ether/ethyl acetate=20:1 to 5:1); yield: 60.2 mg
(26%); and an unknown side product. H NMR (300 MHz,
m/z=259 [MACHTUNGTRENNUNG ACHTUGNTRENNUGN
(81Br)+, 11.66], 257 [M(79Br)+, 11.39], 123
(100); HR-MS: m/z=256.9511, calcd. for C9H879BrNOS
1
[M+]: 256.9510.
CDCl3): d=5.94–5.91 (m, 1H, one proton in C=CH2), 5.58
(d, J=1.8 Hz, 1H, one proton in C=CH2), 4.98 (dd, J=10.0,
7.0 Hz, 1H, OCH), 4.01 (dd, J=14.2, 10.0 Hz, 1H, one
proton in NCH2), 3.78 (dd, J=14.4, 6.9 Hz, 1H, one proton
in NCH2), 2.32 (t, J=7.8 Hz, 2H, CH2), 1.65 (quint, J=
7.6 Hz, 2H, CH2), 1.40 (sext, J=7.4 Hz, 2H, CH2), 0.93 (t,
J=7.4 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3): d=167.3,
131.8, 117.5, 80.8, 59.8, 27.8, 27.5, 22.2, 13.6; IR (neat): n=
3364, 3267, 3093, 2954, 2932, 2871, 1632, 1608, 1565, 1464,
1421, 1379, 1326, 1231, 1071 cmÀ1; MS (ESI): m/z=234
5-(1-Bromovinyl)-2-(naphth-1-yl)-4,5-dihydrooxazole
(2m): The reaction of 1m (224.0 mg, 1.0 mmol), NBS
(214.7 mg, 1.2 mmol), and CH3CN (4 mL) afforded 2m as
a
solid (petroleum ether/ethyl acetate=10:1); yield:
228.9 mg (76%); mp 74–758C (n-hexane/ethyl acetate);
1H NMR (300 MHz, CDCl3): d=9.18 (d, J=8.4 Hz, 1H,
ArH), 8.13 (d, J=7.2 Hz, 1H, ArH), 7.95 (d, J=8.1 Hz, 1H,
ArH), 7.86 (d, J=8.4 Hz, 1H, ArH), 7.64–7.45 (m, 3H,
ArH), 6.02 (s, 1H, one proton in C=CH2), 5.63 (d, J=
1.8 Hz, 1H, one proton in C=CH2), 5.18 (dd, J=9.8, 7.4 Hz,
1H, OCH), 4.40 (dd, J=15.2, 10.4 Hz, 1H, one proton in
NCH2), 4.19 (dd, J=14.8, 7.1 Hz, 1H, one proton in NCH2);
13C NMR (75 MHz, CDCl3): d=163.0, 133.6, 132.1, 131.8,
131.0, 129.0, 128.4, 127.4, 126.2, 126.1, 124.6, 123.7, 118.0,
80.2, 61.2; IR (neat): n=1643, 1587, 1509, 1325, 1269, 1188,
[MACHTNUTRGENNUG HCATUNGTRENNGUN
(81Br)+H+], 232 [M(79Br)+H+]; HR-MS: m/z=
231.0258, calcd. for C9H1479BrNO [M+]: 231.0259.
1,3-Bis[5-(1-bromovinyl)-4,5-dihydrooxazol-2-yl]benzene
(2p): The reaction of 1p (267.2 mg, 1.0 mmol), NBS
(428.6 mg, 2.4 mmol), and CH3CN (4 mL) afforded 2p as
a solid (petroleum ether/ethyl acetate=3:1 to 1.5:1); yield:
230.7 mg (56%); mp 129–1308C (n-hexane/ethyl acetate);
1H NMR (300 MHz, CDCl3): d=8.53 (dd, J=3.5, 1.7 Hz,
1H, ArH), 8.12 (ddd, J=7.7, 2.6, 1.8 Hz, 2H, ArH), 7.51 (t,
J=7.8 Hz, 1H, ArH), 6.02 (dd, J=2.1, 0.9 Hz, 2H, one
proton in C=CH2), 5.64 (d, J=2.4 Hz, 2H, one proton in C=
CH2), 5.21 (dd, J=9.9, 7.2 Hz, 2H, OCH), 4.27 (dd, J=15.3,
9.9 Hz, 2H, one proton in NCH2), 4.05 (dd, J=15.2, 7.0 Hz,
2H, one proton in NCH2); 13C NMR (75 MHz, CDCl3): d=
162.5, 131.2, 131.00, 130.97, 128.5, 127.8, 127.7, 127.4, 117.9,
81.4, 60.4; IR (neat): n=1653, 1358, 1337, 1280, 1231, 1207,
1160, 1061 cmÀ1; MS (EI): m/z=428 [M(81Br,81Br)+, 6.39],
426 [M(81Br,79Br)+, 12.52], 424 [M(79Br,79Br)+, 6.41], 290
(100); anal. calcd. for C16H14Br2N2O2: C 45.10, H 3.31, N
6.57; found: C 45.37, H 3.42, N 6.34.
1117, 1072 cmÀ1; MS (EI): m/z=303 [M
(81Br)+, 17.98], 301
ACHTUNGTRENNUNG
[M
ACHTUNGTRENNUNG
59.62, H 4.00, N 4.64; found: C 59.43, H 3.98, N 4.50.
Gram-Scale Synthesis of 2m
To a flame-dried Schlenk tube were added 1m (1.1186 g,
5.1 mmol), NBS (1.0688 g, 6.0 mmol), and CH3CN (10 mL).
After the reaction mixture had been stirred at room temper-
ature for 45 min as monitored by TLC, it was quenched with
a saturated aqueous solution of NaHCO3 (2 mL) and
Na2S2O3 (2 mL). The resulting mixture was extracted with
ether (30 mLꢂ3) and dried over anhydrous MgSO4. After
filtration and evaporation of the solvent, chromatography
on silica gel (petroleum ether/ethyl acetate=10:1) afforded
2m as a solid; yield: 0.9801 g (67%): 1H NMR (300 MHz,
CDCl3): d=9.18 (d, J=8.4 Hz, 1H, ArH), 8.13 (d, J=
7.5 Hz, 1H, ArH), 7.94 (d, J=8.4 Hz, 1H, ArH), 7.85 (d, J=
8.1 Hz, 1H, ArH), 7.64–7.44 (m, 3H, ArH), 6.00 (d, J=
0.9 Hz, 1H, one proton in C=CH2), 5.62 (d, J=1.8 Hz, 1H,
one proton in C=CH2), 5.16 (dd, J=9.9, 7.2 Hz, 1H, OCH),
4.38 (dd, J=15.3, 9.9 Hz, 1H, one proton in NCH2), 4.18
(dd, J=15.3, 6.9 Hz, 1H, one proton in NCH2).
Synthesis of 5-Ethynyl-2-phenyl-4,5-dihydrooxazole
(3a); Typical Procedure II
To
a dry Schlenk tube were added sequentially 2a
(252.5 mg, 1.0 mmol), TBAF·3H2O (943.4 mg, 3.0 mmol),
and DMF (4 mL). The resulting solution was stirred at
1008C. When the reaction was complete as monitored by
TLC, the mixture was filtered through a short pad of silica
gel eluted with ether (50 mL). After evaporation, the resi-
due was purified by chromatography on silica gel (petrole-
um ether/ethyl acetate=20:1) to afford 3a as an oil; yield:
5-(1-Bromovinyl)-2-(naphth-2-yl)-4,5-dihydrooxazole (2n):
The reaction of 1n (223.9 mg, 1.0 mmol), NBS (214.3 mg,
1.2 mmol), and CH3CN (4 mL) afforded 2n as a solid (petro-
leum ether/ethyl acetate=10:1); yield: 233.2 mg (78%); mp
123–1248C (n-hexane/ethyl acetate); 1H NMR (300 MHz,
CDCl3): d=8.47 (s, 1H, ArH), 8.05 (dd, J=2.6, 1.7 Hz, 1H,
ArH), 7.95–7.82 (m, 3H, ArH), 7.60–7.48 (m, 2H, ArH),
6.05 (dd, J=1.8, 0.9 Hz, 1H, one proton in C=CH2), 5.65 (d,
J=2.4 Hz, 1H, one proton in C=CH2), 5.24 (dd, J=9.9,
6.9 Hz, 1H, OCH), 4.31 (dd, J=15.2, 10.1 Hz, 1H, one
proton in NCH2), 4.08 (dd, J=15.2, 7.1 Hz, 1H, one proton
in NCH2); 13C NMR (100 MHz, CDCl3): d=163.5, 134.7,
132.5, 131.5, 128.8, 128.7, 128.2, 127.7, 127.6, 126.5, 124.6,
124.3, 117.8, 81.3, 60.5; IR (neat): n=1644, 1588, 1510, 1326,
1
140.2 mg (82%); H NMR (300 MHz, CDCl3): d=7.98–7.93
(m, 2H, ArH), 7.52–7.37 (m, 3H, ArH), 5.24 (ddd, J=9.9,
7.8, 1.8 Hz, 1H, OCH), 4.32 (dd, J=14.4, 10.2 Hz, 1H, one
proton in NCH2), 4.11 (dd, J=14.6, 7.6 Hz, 1H, one proton
in NCH2), 2.64 (d, J=2.1 Hz, 1H, CꢀCH); 13C NMR
(75 MHz, CDCl3): d=163.1, 131.4, 128.2, 128.1, 126.9, 81.1,
75.3, 68.1, 61.9; IR (neat) n=1652, 1451, 1355, 1323, 1255,
1061, 1025 cmÀ1; MS (EI): m/z=171 (M+, 19.58), 117 (100);
HR-MS: m/z=171.0683, calcd. for C11H9NO [M+]: 171.0684.
Products 3b and 3c were prepared according to Typical
Procedure II.
1269, 1189, 1118, 1073 cmÀ1; MS (EI): m/z=303 [M
N
5-Ethynyl-2-(4-methoxycarbonylphenyl)-4,5-dihydrooxa-
zole (3b): The reaction of 2c (312.1 mg, 1.0 mmol),
TBAF·3H2O (945.3 mg, 3.0 mmol), and DMF (4 mL) afford-
ed 3b as a solid (petroleum ether/ethyl acetate=10:1 to
5:1); yield: 188.5 mg (82%); mp 112–1148C (n-hexane/ethyl
23.61], 301 [M
ACHTUNGTRENNUNG
C15H12BrNO: C 59.62, H 4.00, N 4.64; found: C 59.61, H
4.04, N 4.49.
5-(1-Bromovinyl)-2-butyl-4,5-dihydrooxazole (2o): The re-
action of 1o (152.9 mg, 1.0 mmol), NBS (213.6 mg,
1
acetate); H NMR (300 MHz, CDCl3): d=8.13–8.04 (m, 2H,
490
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ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2014, 356, 485 – 492

FULL PAPERS
Studies on Electrophilic Cyclization of N-(Buta-2,3-dienyl)amides
ArH), 8.04–7.98 (m, 2H, ArH), 5.28 (ddd, J=10.2, 7.8,
2.1 Hz, 1H, OCH), 4.35 (dd, J=14.8, 10.0 Hz, 1H, one
proton in NCH2), 4.12 (dd, J=15.2, 7.6 Hz, 1H, one proton
in NCH2), 3.92 (s, 3H, CH3), 2.72 (d, J=2.1 Hz, 1H, Cꢀ
CH); 13C NMR (75 MHz, CDCl3): d=166.1, 162.3, 132.4,
130.9, 129.3, 128.1, 80.9, 75.6, 68.4, 62.1, 52.1; IR (neat): n=
3247, 1707, 1651, 1286, 1116, 1065 cmÀ1; MS (EI): m/z=229
(M+, 13.83), 175 (100); anal. calcd. for C13H11NO3: C 68.11,
H 4.84, N 6.11; found: C 67.93, H 4.81, N 6.13.
J=8.1 Hz, 2H, ArH), 7.67 (d, J=8.7 Hz, 2H, ArH), 7.61 (d,
J=7.8 Hz, 1H, ArH), 7.47 (d, J=7.5 Hz, 1H, ArH), 7.22
(td, J=7.7, 1.4 Hz, 1H, ArH), 7.17–7.10 (m, 2H, ArH), 6.56
(d, J=2.7 Hz, 1H, ArH), 5.58 (s, 1H, one proton in C=
CH2), 5.50 (dd, J=10.1, 8.0 Hz, 1H, OCH), 5.44 (s, 1H, one
proton in C=CH2), 4.13 (dd, J=15.3, 10.2 Hz, 1H, one
proton in NCH2), 3.76 (dd, J=15.3, 7.8 Hz, 1H, one proton
in NCH2); 13C NMR (75 MHz, CDCl3): d=162.2, 142.4,
136.5, 133.1 (q, J=32.4 Hz), 130.5, 128.8, 128.5, 126.4, 125.4
(q, J=4.0 Hz), 123.7 (q, J=270.9 Hz), 122.6, 121.0, 120.5,
111.3, 110.6, 104.0, 79.5, 59.7; 19F NMR (CDCl3, 282 MHz):
d=À63.4; IR (neat): n=1658, 1455, 1320, 1162, 1132,
1074 cmÀ1; MS (EI): m/z=357 (M+ +1, 18.52), 356 (M+,
78.56), 167 (100); HR-MS: m/z=356.1131, calcd. for
C20H15F3N2O [M+]: 356.1136.
5-Ethynyl-2-[4-(trifluoromethyl)phenyl]-4,5-dihydrooxa-
zole (3c): The reaction of 2g (321.5 mg, 1.0 mmol),
TBAF·3H2O (949.5 mg, 3.0 mmol), and DMF (4 mL) afford-
ed 3c (petroleum ether/ethyl acetate=10:1); yield: 139.4 mg
1
(58%); H NMR (300 MHz, CDCl3): d=8.06 (d, J=8.1 Hz,
2H, ArH), 7.67 (d, J=7.8 Hz, 2H, ArH), 5.29 (ddd, J=10.2,
7.8, 2.1 Hz, 1H, OCH), 4.36 (dd, J=14.8, 10.0 Hz, 1H, one
proton in NCH2), 4.14 (dd, J=14.7, 7.8 Hz, 1H, one proton
in NCH2), 2.68 (d, J=2.4 Hz, 1H, CꢀCH); 13C NMR
(75 MHz, CDCl3): d=162.1, 133.1 (q, J=32.5 Hz), 130.4,
128.6, 125.3 (q, J=3.8 Hz), 123.7 (q, J=270.8 Hz), 80.9, 75.7,
68.6, 62.2; 19F NMR (CDCl3, 282 MHz): d=À63.5; IR
(neat): n=1656, 1414, 1320, 1168, 1128, 1074, 1019 cmÀ1; MS
(EI): m/z=239 (M+, 10.29), 185 (100); HR-MS: m/z=
239.0561, calcd. for C12H8F3NO [M+]: 239.0558.
2-(3,5-Dichlorophenyl)-5-[1-(1H-indol-1-yl)vinyl]-4,5-di-
hydrooxazole (4c): The reaction of CuI (38.6 mg, 0.2 mmol),
K3PO4 (423.1 mg, 2.0 mmol), 2e (321.8 mg, 1.0 mmol), indole
(233.1 mg, 2.0 mmol), diethylamine (31.0 mg, 0.4 mmol), and
1,4-dioxane (1 mL) afforded 4c as an oil (petroleum ether/
ethyl acetate=20:1 to 10:1 for the first round, petroleum
ether/ethyl acetate=20:1 to 10:1 for the second round);
1
yield: 281.2 mg (78%); H NMR (300 MHz, CDCl3): d=7.85
(d, J=1.8 Hz, 2H, ArH), 7.61 (d, J=7.8 Hz, 1H, ArH),
7.48–7.43 (m, 2H, ArH), 7.26–7.10 (m, 3H, ArH), 6.57 (dd,
J=3.3, 0.6 Hz, 1H, ArH), 5.58 (s, 1H, one proton in C=
CH2), 5.50 (dd, J=10.2, 7.5 Hz, 1H, and OCH), 5.46 (s, 1H,
one proton in C=CH2) 4.12 (dd, J=15.3, 10.2 Hz, 1H, one
proton in NCH2), 3.72 (dd, J=15.4, 7.6 Hz, 1H, one proton
in NCH2); 13C NMR (75 MHz, CDCl3): d=161.2, 142.2,
136.5, 135.2, 131.4, 130.0, 128.7, 126.5, 126.4, 122.6, 121.0,
120.5, 111.4, 110.5, 104.0, 79.7, 59.6; IR (neat): n=1653,
1563, 1456, 1313, 1256, 1214, 1088 cmÀ1; MS (EI): m/z=360
[M(37Cl,37Cl)+, 4.66], 358 [M(37Cl,35Cl)+, 26.41], 356
[M(35Cl,35Cl)+, 39.91], 167 (100); HR-MS: m/z=356.0484,
calcd. for C19H1435,35Cl2N2O [M+]: 356.0483.
Synthesis of 5-[1-(1H-indol-1-yl)vinyl]-2-phenyl-4,5-
dihydrooxazole (4a); Typical Procedure III
CuI (38.5 mg, 0.2 mmol) and K3PO4 (423.7 mg, 2.0 mmol)
were added to a screw-capped reaction tube with a Teflon-
lined septum. The tube was evacuated and backfilled with
argon three times. Then 2a (252.2 mg, 1.0 mmol), indole
(235.9 mg, 2.0 mmol), diethylamine (27.4 mg, 0.4 mmol), and
1,4-dioxane (1 mL) were added under an argon atmosphere.
The reaction tube was sealed and the mixture was stirred at
1308C for 48 h. When the reaction was completed, the mix-
ture was filtered through a short pad of silica gel eluted with
ethyl acetate (50 mL). After evaporation, the residue was
purified by chromatography on silica gel (petroleum ether/
ethyl acetate=20:1 to 10:1 to 5:1) to afford 4a as an oil;
yield: 249.5 mg (86%); 1H NMR (300 MHz, CDCl3): d=
8.03–7.97 (m, 2H, ArH), 7.62 (d, J=7.8 Hz, 1H, ArH),
7.54–7.40 (m, 4H, ArH), 7.26–7.10 (m, 3H, ArH), 6.57 (d,
J=3.0 Hz, 1H, ArH), 5.61 (s, 1H, one proton in C=CH2),
5.51 (dd, J=9.9, 7.8 Hz, 1H, OCH), 5.49 (s, 1H, one proton
in C=CH2), 4.14 (dd, J=14.8, 10.0 Hz, 1H, one proton in
NCH2), 3.75 (dd, J=15.0, 7.5 Hz, 1H, one proton in NCH2);
13C NMR (75 MHz, CDCl3): d=163.4, 142.7, 136.5, 131.6,
Acknowledgements
Financial support from the National Natural Science Founda-
tion of China (21232006) and the National Basic Research
Program of China (2011CB808700) is greatly appreciated.
We thank Mr. Shangze Wu in this group for reproducing the
results of the preparation of 2f, 2o, 3b.
128.8, 128.4, 128.2, 127.2, 126.5, 122.5, 121.0, 120.4, 110.8, References
110.6, 103.8, 79.1, 59.7; IR (neat): n=1651, 1456, 1320, 1214,
1060, 1026 cmÀ1; MS (EI): m/z=289 (M+ +1, 20.66), 288
(M+, 100); HR-MS: m/z= 288.1260, calcd. for C19H16N2O
[M+]: 288.1263.
Products 4b and 4c were prepared according to Typical
Procedure III.
5-[1-(1H-Indol-1-yl)vinyl]-2-[4-(trifluoromethyl)phenyl]-
4,5-dihydrooxazole (4b): The reaction of CuI (38.5 mg,
0.2 mmol), K3PO4 (423.1 mg, 2.0 mmol), 2g (321.2 mg,
1.0 mmol), indole (234.3 mg, 2.0 mmol), diethylamine
(28.9 mg, 0.4 mmol), and 1,4-dioxane (1 mL) afforded 4b as
an oil (petroleum ether/ethyl acetate=10:1 to 5:1); yield:
233.2 mg (65%); 1H NMR (300 MHz, CDCl3): d=8.07 (d,
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