Metal-free dual sp3 C-H functionalization: I2- promoted domino oxidative cyclization to construct 2,5-disubstituted oxazoles

Article abstract of DOI:10.1016/j.tet.2012.10.072

An I₂-promoted sp³ C-H functionalization has been developed for the synthesis of 2,5-disubstituted oxazoles from easily available methyl ketones and benzylamines without any metal and peroxide catalyst. This domino oxidative cyclization process involves the cleavage of C-H bond and the formation of C-N, C-O bonds.

Full text of DOI:10.1016/j.tet.2012.10.072

Tetrahedron 69 (2013) 22e28
Contents lists available at SciVerse ScienceDirect
Tetrahedron
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Metal-free dual sp3 CeH functionalization: I2-promoted domino
oxidative cyclization to construct 2,5-disubstituted oxazoles
*
Qing-He Gao, Zhuan Fei, Yan-Ping Zhu, Mi Lian, Feng-Cheng Jia, Mei-Cai Liu, Neng-Fang She ,
*
An-Xin Wu
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China
a r t i c l e i n f o
a b s t r a c t
An I2-promoted sp3 CeH functionalization has been developed for the synthesis of 2,5-disubstituted
oxazoles from easily available methyl ketones and benzylamines without any metal and peroxide
catalyst. This domino oxidative cyclization process involves the cleavage of CeH bond and the formation
of CeN, CeO bonds.
Article history:
Received 13 September 2012
Received in revised form 16 October 2012
Accepted 26 October 2012
Available online 2 November 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
I2-promoted
sp3 CeH functionalization
Domino oxidative cyclization
Oxazoles
1. Introduction
typically classified into cyclization of acyclic precursors,8 oxidation
of oxazolines,9 and the coupling of the prefunctionalized oxazoles
The direct CeH bond functionalization, especially sp3 CeH bond
functionalization for the construction of carbonecarbon and car-
boneheteroatom bonds has become an important synthetic strat-
egy.1 CeH functionalization generally makes use of the metal
catalyzed activation and subsequent functionalization of sp2 and
sp3 CeH bonds, which directly install important functional groups
to enhance the structural complexity of easily-prepared sub-
strates.2 In recent years, many excellent results of CeH bond
functionalization have been achieved based on the metal-mediated
approaches.3 On the other hand, organic reactions carried out un-
der metal-free conditions also received much attention and great
progress has been achieved in this area.4 Nevertheless, only a few
metal-free systems, such as TBHP, quaternary ammonium iodide/
TBHP, PhI(OAc)2, I2/PhI(OAc)2, I2/TBHP, and I2, focused on CeH
functionalization.5 In this paper, an I2-promoted sp3 CeH func-
tionalization for accessing 2,5-disubstituted oxazoles is described.
Oxazole is an important five-membered heterocycle found in
many natural products, drugs, and biologically active compounds.6
In particular, 2,5-disubstituted oxazoles have been evaluated to
show activity against diabetes, Gram-positive and Gram-negative
bacterial infections, breast cancer, and pancreatic cancer.7 Up till
now, the most synthetic methodologies of oxazole derivatives are
with other organometallic reagents.10 However, the reports for the
metal-free catalyzed approach to oxazoles are less known.5g,11
Recently, we reported an efficient in situ trapping of unstable
a-ketoaldehyde intermediates strategy to construct diverse com-
pounds (Scheme 1),5p,5q,11e,12 which all these methods share the
same thematic concept but were quite different from each other in
reactions, substrates and/or mechanistic implications. This strategy
provides a new way for direct synthesis of pharmacologically
interesting heterocycles from simple substrates. As a continuation
of our work, we herein report a metal-free and peroxide-free
I2-promoted direct self-sequence synthesis of 2,5-disubstituted
* Corresponding authors. Tel./fax: þ86 027 6786 7773; e-mail addresses: nfshe@
Scheme 1. In situ trapping of unstable a-ketoaldehyde intermediates strategy to
construct diverse compounds.
mail.ccnu.edu.cn (N.-F. She), chwuax@mail.ccnu.edu.cn (A.-X. Wu).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.10.072

Q.-H. Gao et al. / Tetrahedron 69 (2013) 22e28
23
oxazoles via dual sp3 CeH functionalization from easily available
methyl ketones and benzylamines (Scheme 2).
Table 2
Reaction scope of methyl ketonesa
Entry
1 (R1)
3
Yieldsb (%)
Scheme 2. I2-promoted direct synthesis of 2,5-disubstituted oxazole via dual sp3 CeH
functionalization.
1
2
3
4
5
6
7
8
1a (C6H5)
1b (4-MeOC6H4)
1c (4-EtOC6H4)
1d (3-MeOC6H4)
1e (2,4-OMe2C6H3)
1f (3,4-OCH2OC6H3)
1g (3,4-OCH2CH2OC6H3)
1h (4-NO2C6H4)
1i (4-PhC6H4)
3aa
3ba
3ca
3da
3ea
3fa
3ga
3ha
3ia
3ja
3ka
3la
3ma
3na
3oa
3pa
3qa
83
87
80
85
82
85
91
78
79
80
82
84
72
76
74
94
0
2. Results and discussion
We initiated the present study with acetophenone (1a) and
benzylamine (2a) as model substrates under conditions similar to
those previously reported.11b,13 It was found that the reaction led to
the desired product 2,5-diphenyloxazole (3aa) with a yield of 12%
(Table 1, entry 1). To our surprise, the reaction could perform in
moderate yield in the absence of TBHP (Table 1, entry 2). Much to our
satisfaction, by increasing the CuO and I2 loading to 1.5 equiv and
2.0 equiv, respectively, 3aa was obtained in 70% yield (Table 1, entry
5). Then other bases employed under this condition, but none of
them gave better results (Table 1, entries 6e9). It was also noted that
the yield increased to 83% when the reaction was at 100 ꢀC in the
absence of base (Table 1, entry 12). Without iodine, no product was
observed (Table 1, entry 13), which suggested that iodine played an
important role in this reaction. Finally, the dosage of 2a was in-
vestigated, where it was found that the addition of excess benzyl-
amine (1.5 equiv) gave 3aa in the highest yield (Table 1, entry 12).
9
10
11
12
13
14
15
16
17
1j (4-HOC6H4)
1k (2-Naphthyl)
1l (1-Naphthyl)
1m (2-Benzofuryl)
1n (2-Furyl)
1o (2-Thienyl)
1p (4-Morpholinyl C6H4)
1q ((E)-C6H5eCH]CH)
a
Reaction conditions: 1 (1.0 mmol), 2a (1.5 mmol), and I2 (2.0 mmol) in DMSO
(3 mL) at 100 ꢀC for 3e5 h.
b
Isolated yields.
obtained in 80% yield. Whereas, 2-naphthyl methyl ketone and
1-naphthyl methyl ketone also gave their corresponding products
3ka and 3la in 82% and 84% yields, respectively. Furthermore,
heteroaryl ketones, including benzofuryl, furanyl, thienyl, and
morpholinyl were also discovered to be adept in efficiently fur-
nishing the desired products in moderate to excellent yields
(72e94%; 3mae3pa). The structure of the product was further
confirmed by an X-ray crystallographic study of 3ba (Fig. 1).14
However, the use of unsaturated methyl ketones was shown to be
unsuccessful (3qa).
Table 1
Optimization of the reaction conditionsa
Entry
I2 (equiv)
Base (equiv)
Oxidant
TBHP
Temp (ꢀC)
Yield (%)b
1
2
3
4
5
6
7
8
1.0
1.0
1.0
1.5
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
CuO (1.0)
CuO (1.0)
CuO (1.5)
CuO (1.5)
CuO (1.5)
K2CO3 (1.5)
DBU (1.5)
DABCO (1.5)
Et3N (1.5)
90
90
90
90
90
90
90
90
90
90
80
100
100
100
100
12
65
67
67
70
38
30
18
15
78
74
83
0
9
10
11
12
13
14c
15d
2.0
2.0
45
69
Fig. 1. X-ray crystal structure of compound 3ba.
a
Reaction conditions: 1a (1.0 mmol), 2a (1.5 mmol) in 3 mL DMSO.
Isolated yields.
Reaction conditions: 1a (1.0 mmol), 2a (1.0 mmol) in 3 mL DMSO.
Reaction conditions: 1a (1.0 mmol), 2a (2.0 mmol) in 3 mL DMSO.
Subsequently, different benzylamine derivatives were
investigated as summarized in Table 3. The electronic nature of the
substrates was shown to strongly influence dual sp3 CeH func-
tionalization. Electron-deficient substituents were found to
increase the product yields. On the other hand, the steric effects of
substituents also had a slightly adverse influence on the reaction.
For example, the reaction proceeded efficiently when para
substituted benzylamines were employed (Table 3, entry 1, 10);
however, meta substituents were found to have a negative effect on
the transformation (Table 3, entry 4, 11). It is also worth noting that
halo-substituted benzylamine were well tolerated (Table 3, entries
1, 2, 4, 5, 14, 15). Several heteroaryl amines were subsequently used
in this system, affording the corresponding oxazoles in good yields
(Table 3, entries 6, 7, 8). However, the desired product was not
detected with n-BuNH2 as the substrate (Table 3, entry 9).
b
c
d
With the optimal reaction conditions in hand, the scope of ox-
idative cyclization for the synthesis of oxazole derivatives was ex-
plored using a series of aryl methyl ketones and benzylamine as the
substrates. As illustrated in Table 2, Aryl methyl ketones with both
electron-rich (4-OMe, 4-OEt, 3-OMe, 2,4-OMe2, 3,4-OCH2O, 3,4-
OCH2CH2O) and electron-deficient (4-NO2, 4-Ph) methyl ketones
participated in this reaction smoothly to afford the expected oxa-
zoles in moderate to excellent yields (78e91%; 3aae3ia). Generally,
an electron-donating substituent on the aromatic ring was seen to
cause a considerable increase in the yield. Unprotected phenol
moiety was tolerated under the reaction conditions, and 3ja was

24
Q.-H. Gao et al. / Tetrahedron 69 (2013) 22e28
Table 3
Reaction scope of methyl ketones and benzylamine derivativesa
Entry
1 (R1)
2 (R2)
3
Yieldsb (%)
1
2
3
4
5
6
7
8
1a (C6H5)
2b (4-ClC6H4)
2c (4-FC6H4)
2d (4-CF3C6H4)
2e (3-ClC6H4)
2f (2,4-Cl2C6H3)
2g (2-Furyl)
2n (4-Pyridyl)
2i (3-Pyridyl)
2j (CH3CH2CH2)
2k (4-MeOC6H4)
2l (3-MeOC6H4)
2m (4-MeC6H4)
2n (3-NO2C6H4)
2o (2-ClC6H4)
2b (4-ClC6H4)
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
3aj
3bk
3bl
3bm
3bn
3bo
3rb
78
76
78
72
88
78
87
76
0
70
66
75
72
80
75
9
10
11
12
13
14
15
1b (4-MeOC6H4)
1r (4-BrC6H4)
a
Reaction conditions: 1 (1.0 mmol), 2a (1.5 mmol), and I2 (2.0 mmol) in DMSO
(3 mL) at 100 ꢀC for 3e5 h.
b
Isolated yields.
Encouraged by the established scope of this reaction, we turned
our attention to the 4,40-diacetylbiphenyl, 1,3-diacetylbenzene, and
1,3-phenylenedimethanamine. It was satisfying to find that 4,40-
diacetylbiphenyl and 1,3-phenylenedimethanamine smoothly
afforded the corresponding products. Unfortunately, 1,3-
diacetylbenzene could transformed into the desired products in
very low yield, even with longer time (Scheme 3).
Scheme 4. The controlled experiment to prove the mechanism.
phenylglyoxal aldehyde group (1bb) and the hemiacetal group
(1bc), respectively (Fig. 2). With the consumption of 1b, the in-
termediate 1bb and 1bc appeared and the concentration sub-
sequently increased over time. Through comparison with an
authentic sample, the signal at 4.05 ppm was assigned to the
eCH2e group of benzylamine (2a). In addition, the signals at
3.84 ppm and 3.82 ppm were assigned to the eOCH3 group of
phenylglyoxal (1bb) or hydrated hemiacetal (1bc) and the eOCH3
group of 2,5-diphenyloxazole (3ba). With the consumption of 2a,
Scheme 3. Further scope of methyl ketones and benzylamine derivatives.
To gain some insights into the mechanism of the reaction, a series
of control experiments were carried out. Acetophenone (1a) was
converted into a-iodo acetophenone (1aa) in 96% yield using the I2/
CuO system (Scheme 4 (1)).15 When acetophenone 1a was heated
with I2 in DMSO at 100 ꢀC in the absence of benzylamine (2a), the
substrate was transformed into phenylglyoxal (1ab) or hydrated
hemiacetal (1ac) in quantitative conversion (Scheme 4 (2)). Sub-
sequently, 1aa and 1ac were subjected to the standard reaction
conditions and 3aa was obtained in 84% and 95% yields, respectively
(Scheme 4 (3, 4, 5)). This result clearly confirmed phenacyl iodine
1aa and phenylglyoxal 1ab were the key intermediates for this
transformation. However, when 1ac was tested in the absence of I2,
3aa was not observed (Scheme 4 (6, 7)). This results indicated that
iodine played an important role in the condensation/cyclization
process.
To further investigate the reaction process, we monitored the
reaction of 1b (0.1 mmol), 2a (0.12 mmol) with I2 (0.2 mmol) in
DMSO-d6 by 1H NMR spectroscopy. Through comparison with the
previous report,5p the signal at 4.53 ppm was assigned to the
Fig. 2. The reaction process of 1b (0.1 mmol) with I2 (0.2 mmol) was monitored by 1
NMR (600 MHz, DMSO-d6, 298ꢁ0.5 K) over time.
H
eCH2e group of
a-iodo aryl methyl ketone 1ba at 5e15 min. In
addition, the signals at 9.54 ppm and 5.64 ppm were assigned to the

Q.-H. Gao et al. / Tetrahedron 69 (2013) 22e28
25
1bb, and 1bc, the product 3ba appeared, and the concentration was
3. Conclusion
seen to increase over time (Fig. 3). These results disclosed that
phenacyl iodine (1ba) and phenylglyoxal (1bb) were important
intermediates in the whole transformation.
In conclusion, we have developed an I2-promoted domino oxi-
dative cyclization process to construct oxazole derivatives from
easily available methyl ketones and benzylic amines. It is notable
that this metal-free and peroxide-free transformation involves dual
functionalization of two types of C(sp3)eH bonds (sp3
a-CeH of
carbonyl and sp3
a-CeH of nitrogen atom). Applications of I2-pro-
moted sp3 CeH functionalization for the construction of other
heterocycles are currently being investigated in our laboratory.
4. Experimental
4.1. General
All substrates and reagents were commercially available and
used without further purification. TLC analysis was performed
using pre-coated glass plates. Column chromatography was per-
formed using silica gel (200e300 mesh). IR spectra were recorded
on a PerkineElmer PE-983 infrared spectrometer as KBr pellets
with absorption in cmꢂ1
DMSO on 400/600 MHz NMR spectrometers and resonances (
.
1H spectra were recorded in CDCl3 or
) are
d
given in parts per million relative to tetramethylsilane. Data are
reported as follows: chemical shift, multiplicity (s¼singlet,
d¼doublet, t¼triplet, m¼multiplet), coupling constants (Hertz) and
integration. 13C spectra were recorded in CDCl3 or DMSO on
Fig. 3. The reaction process of 1b (0.1 mmol) with I2 (0.2 mmol) was monitored by 1
H
NMR for 25 min, then 2a (0.12 mmol) was added. This process was monitored by 1H
NMR (600 MHz, DMSO-d6, 298ꢁ0.5 K) over time.
100 MHz NMR spectrometers and resonances (d) are given in ppm.
HRMS were obtained on a Bruker 7-T FT-ICR MS equipped with
APCI. MS was carried out on a Finnigan Trace MS spectrometer (EI,
70 eV). The X-ray crystal structure determination of 3ba was
obtained on a Bruker SMART APEX CCD system. Melting points
were determined using XT-4 apparatus and not corrected.
On the basis of the results described above and previous
reports,11a,11b,13 a plausible mechanism for I2-promoted dual sp3
CeH functionalization was proposed using acetophenone (1a) and
benzylamine (2a) as an example (Scheme 5). Initially, the substrate
1a was converted into the intermediate a-iodo acetophenone (1aa)
in the presence of I2. Subsequently, oxidation of intermediate 1aa
by DMSO could take place to yield intermediate phenylglyoxal
(1ab). Then, benzylamine (2a) reacted with the aldehyde group of
phenylglyoxal (1ab) to afford A or its enolizational isomer B, which
underwent an intramolecular cyclization via an oxygen atom
attacking to double bonds and providing the intermediate C. Con-
sequently, intermediate C converted into intermediate D un-
derwent deprotonation and it further furnished the desired
product 3aa in the presence of the excess or regenerated iodide.5p,16
In the process, byproduct HI could be oxidized by DMSO to re-
generate at least 0.5 equiv of iodine.17
4.2. General procedure for synthesis of 3 (3aa as an example)
A mixture of acetophenone 1a (120 mg, 1.0 mmol), benzylamine
2a (160.7 mg, 1.5 mmol), and iodine (507.6 mg, 2.0 mmol) in DMSO
(3 mL) was stirred at 100 ꢀC for 5 h. After disappearance of the
reactant (monitored by TLC), and added 50 mL water to the mix-
ture, then extracted with EtOAc three times (3ꢃ50 mL). The extract
was washed with 10% Na2S2O3 solution (w/w), dried over anhy-
drous Na2SO4 and evaporation. The residue was purified by column
chromatography on silica gel (petroleum ether/EtOAc¼100:1) to
yield the desired product 3aa as a white solid (183.4 mg, 83% yield).
4.3. Characterization data
4.3.1. 2,5-Diphenyloxazole (3aa).11b Yield 83%; white solid; mp
65e68 ꢀC; IR (KBr): 3061, 1652, 1585, 1542, 1482, 1282, 1131, 1065,
1024, 949, 906, 824, 763, 704, 479 cmꢂ1; 1H NMR (400 MHz, CDCl3):
d
(ppm)8.10(d, J¼7.6Hz, 2H), 7.71 (d, J¼7.6Hz, 2H), 7.48e7.37(m, 6H),
7.33 (t, J¼7.4 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d (ppm) 161.1, 151.2,
130.3, 128.9, 128.8, 128.4, 128.0, 127.4, 126.2, 124.1, 123.4; HRMS
(APCI): m/z [MþH]þ calcd for C15H12NO: 222.0913; found: 222.0914.
4.3.2. 5-(4-Methoxyphenyl)-2-phenyloxazole (3ba).11b Yield 87%;
light yellow solid; mp 73e76 ꢀC; IR (KBr): 3057, 2969, 2840, 1656,
1607, 1498, 1252, 1173, 1021, 949, 825, 689, 613, 522 cmꢂ1; 1H NMR
(400 MHz, CDCl3):
2H), 7.55e7.38 (m, 3H), 7.31 (s, 1H), 6.96 (d, J¼8.4 Hz, 2H), 3.84 (s,
3H); 13C NMR (100 MHz, CDCl3)
(ppm) 160.5, 159.8, 151.3, 130.1,
d
(ppm) 8.09 (d, J¼7.2 Hz, 2H), 7.64 (d, J¼8.4 Hz,
d
128.7, 127.5, 126.1, 125.7, 121.9, 120.8, 114.4, 55.3; HRMS (APCI): m/z
[MþH]þ calcd for C16H14NO2: 252.1019; found: 252.1021.
4.3.3. 5-(4-Ethoxyphenyl)-2-phenyloxazole (3ca). Yield 80%; white
solid; mp 89e92 ꢀC; IR (KBr): 3104, 2973, 1612, 1568, 1542, 1500,
Scheme 5. The plausible mechanism of the present reaction.

26
Q.-H. Gao et al. / Tetrahedron 69 (2013) 22e28
1389, 1289, 1248, 1174, 1111, 1044, 919, 823, 689, 523 cmꢂ1; 1H NMR
(400 MHz, CDCl3):
1443, 1274, 1171, 1133, 948, 842, 805, 707, 618, 524 cmꢂ1
;
1H NMR
d
(ppm) 8.09 (d, J¼7.6 Hz, 2H), 7.63 (d, J¼7.6 Hz,
(400 MHz, DMSO-d6): (ppm) 9.86 (s,1H), 8.05 (br s, 2H), 7.77e7.62
d
2H), 7.51e7.39 (m, 3H), 7.31 (s, 1H), 6.95 (d, J¼8.0 Hz, 2H), 4.05 (q,
(m, 2H), 7.58 (s, 1H), 7.56e7.42 (m, 3H), 6.99 (d, J¼7.2 Hz, 1H), 6.89
J¼7.2 Hz, 2H), 1.43 (t, J¼7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3)
(d, J¼6.4 Hz, 1H); 13C NMR (100 MHz, DMSO-d6)
d (ppm) 158.0,
d
(ppm) 160.4, 159.1, 151.3, 130.0, 128.7, 127.5, 126.1, 125.7, 121.8,
157.1, 151.3, 149.7, 134.4, 130.2, 129.1, 127.0, 125.8, 121.8, 120.6, 118.6,
115.9; HRMS (APCI): m/z [MþH]þ calcd for C15H12NO2: 238.0863;
found: 238.0865.
120.6, 114.8, 63.5, 14.7; HRMS (APCI): m/z [MþH]þ calcd for
C17H16NO2: 266.1176; found: 266.1178.
4.3.4. 5-(3-Methoxyphenyl)-2-phenyloxazole (3da).11b Yield 85%;
light yellow solid; mp 90e92 ꢀC; IR (KBr): 3095, 2952, 2830, 1598,
1538,1484,1343,1293,1231,1044, 966, 837, 707, 685 cmꢂ1; 1H NMR
4.3.11. 5-(Naphthalen-2-yl)-2-phenyloxazole (3ka).11b Yield 82%;
light yellow solid; mp 93e96 ꢀC; IR (KBr): 3091, 2926, 1728, 1480,
1130, 970, 857, 817, 743, 685 cmꢂ1 1H NMR (400 MHz, CDCl3):
;
(400 MHz, CDCl3):
7.36e7.27 (m, 2H), 7.23 (s, 1H), 6.90e6.81 (m, 1H), 3.86 (s, 3H); 13C
NMR (100 MHz, CDCl3) (ppm) 161.1,159.9,151.0,130.3,130.0,129.1,
d
(ppm) 8.10e8.09 (m, 2H), 7.51e7.38 (m, 4H),
d
(ppm) 8.18e8.12 (m, 3H), 7.90e7.84 (m, 2H), 7.82 (d, J¼8.0 Hz, 1H),
7.76e7.73 (m, 1H), 7.54e7.44 (m, 6H); 13C NMR (100 MHz, CDCl3)
(ppm) 161.3, 151.3, 133.3, 133.0, 130.3, 128.8, 128.7, 128.2, 127.8,
d
d
128.8, 127.3, 126.2, 123.7, 116.7, 113.9, 109.7, 55.3; HRMS (APCI): m/z
[MþH]þ calcd for C16H14NO2: 252.1019; found: 252.1021.
127.4, 126.8, 126.5, 126.3, 125.2, 123.9, 122.9, 122.0; HRMS (APCI):
m/z [MþH]þ calcd for C19H14NO: 272.1070; found: 272.1072.
4.3.5. 5-(2,4-Dimethoxyphenyl)-2-phenyloxazole (3ea). Yield 82%;
white solid; mp 131e134 ꢀC; IR (KBr): 3063, 2942, 2835, 1677, 1609,
4.3.12. 5-(Naphthalen-1-yl)-2-phenyloxazole (3la).11b Yield 84%;
light yellow solid; mp 110e114 ꢀC; IR (KBr): 3052, 1554, 1481, 1444,
1393, 1152, 1116, 1066, 1025, 990, 920, 838, 793, 767, 683 cmꢂ1; 1H
1499, 1465, 1268, 1209, 1125, 1025, 811, 686 cmꢂ1 1H NMR
;
(400 MHz, CDCl3):
1H), 7.52 (s, 1H), 7.50e7.36 (m, 3H), 6.61 (d, J¼8.4 Hz, 1H), 6.55 (s,
1H), 3.95 (s, 3H), 3.86 (s, 3H); 13C NMR (100 MHz, CDCl3)
(ppm)
d
(ppm) 8.11 (d, J¼7.2 Hz, 2H), 7.80 (d, J¼8.4 Hz,
NMR (400 MHz, CDCl3):
J¼7.6 Hz, 2H), 7.88 (t, J¼8.0 Hz, 2H), 7.80 (d, J¼7.2 Hz, 1H), 7.59e7.43
(m, 7H); 13C NMR (100 MHz, CDCl3)
(ppm) 161.4, 150.5, 133.8,
d
(ppm) 8.35 (d, J¼8.0 Hz, 1H), 8.15 (d,
d
d
165.1, 160.7, 157.0, 147.9, 129.9, 128.7, 127.7, 126.7, 126.1, 125.6, 110.6,
105.0, 98.6, 55.6, 55.5; HRMS (APCI): m/z [MþH]þ calcd for
C17H16NO3: 282.1125; found: 282.1126.
130.4, 130.0, 129.5, 128.8, 128.7, 127.4, 127.1, 126.7, 126.3, 126.3,
126.2, 125.2 (ꢃ2), 124.8; HRMS (APCI): m/z [MþH]þ calcd for
C19H14NO: 272.1070; found: 272.1072.
4.3.6. 5-(Benzo[d][1,3]dioxol-5-yl)-2-phenyloxazole
(3fa).18 Yield
4.3.13. 5-(Benzofuran-2-yl)-2-phenyloxazole (3ma).11b Yield 72%;
White solid; mp 140e143 ꢀC; IR (KBr): 3063, 2924, 1545, 1445, 1254,
85%; light yellow solid; mp 133e136 ꢀC; IR (KBr): 3063, 2916, 1602,
1547, 1493, 1328, 1240, 1104, 1036, 963, 927, 871, 808, 705 cmꢂ1; 1H
1161, 1128, 1062, 879, 838, 789, 745, 703 cmꢂ1; H NMR (400 MHz,
1
NMR (600 MHz, CDCl3):
d
(ppm) 8.08 (d, J¼7.8 Hz, 2H), 7.50e7.42
CDCl3):
7.54e7.45 (m, 4H), 7.33 (t, J¼7.6Hz,1H),7.29e7.22(m,1H),7.05(s,1H);
13C NMR (100 MHz, CDCl3)
(ppm) 161.7, 154.8, 145.2, 143.4, 130.7,
d
(ppm) 8.15e8.08 (m, 2H), 7.61 (d, J¼7.6 Hz,1H), 7.57 (s, 1H),
(m, 3H), 7.32 (s, 1H), 7.24 (d, J¼7.8 Hz, 1H), 7.17 (s, 1H), 6.88 (d,
J¼7.8 Hz,1H), 6.01 (s, 2H); 13C NMR (100 MHz, CDCl3)
d
(ppm) 160.6,
d
151.1, 148.2, 147.9, 130.2, 128.8, 127.4, 126.1, 122.2, 122.1, 118.3, 108.8,
104.8, 101.4; HRMS (APCI): m/z [MþH]þ calcd for C16H12NO3:
266.0812; found: 266.0814.
128.9, 128.3, 126.9, 126.5, 125.6, 125.1, 123.4, 121.2, 111.2, 103.2; HRMS
(APCI): m/z [MþH]þ calcd for C17H12NO2: 262.0863; found: 262.0865.
4.3.14. 5-(Furan-2-yl)-2-phenyloxazole (3na).11b Yield 76%; White
solid; mp 71e74 ꢀC; IR (KBr): 3318, 2962, 1639, 1547, 1482, 1449,
4.3.7. 5-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-2-phenyloxazole
(3ga). Yield 91%; white solid; mp 127e130 ꢀC; IR (KBr): 3042, 2932,
1589, 868, 1500, 1316, 1278, 1119, 1060, 891, 858, 799, 701 cmꢂ1; 1H
1261, 1159, 1005, 882, 801, 744, 682 cmꢂ1 1H NMR (400 MHz,
;
CDCl3):
d (ppm) 8.13e8.04 (m, 2H), 7.53e7.43 (m, 4H), 7.35 (s, 1H),
NMR (400 MHz, CDCl3):
d
(ppm)8.11e8.03(m, 2H), 7.52e7.39 (m, 3H),
6.70 (d, J¼3.2 Hz, 1H), 6.54e6.50 (m, 1H); 13C NMR (100 MHz,
7.30 (s, 1H), 7.25e7.16 (m, 2H), 6.92 (d, J¼8.4 Hz, 1H), 4.29 (s, 4H); 13C
CDCl3) d (ppm) 160.6, 143.6(4), 143.5(9), 142.8, 130.4, 128.7, 127.0,
NMR (100 MHz, CDCl3)
d
(ppm) 160.6, 151.0, 143.9, 143.8, 130.1, 128.7,
126.3, 123.3, 111.5, 107.2; HRMS (APCI): m/z [MþH]þ calcd for
127.4,126.1,122.3,121.6,117.8,117.7,113.2, 64.4, 64.3;HRMS(APCI): m/
C13H10NO2: 212.0707; found: 212.0706.
z [MþH]þ calcd for C17H14NO3: 280.0968; found: 280.0970.
4.3.15. 2-Phenyl-5-(thiophen-2-yl)oxazole (3oa). Yield 74%; light
green solid; mp 71e74 ꢀC; IR (KBr): 3098, 1583, 1475, 1443, 1256,
4.3.8. 5-(4-Nitrophenyl)-2-phenyloxazole (3ha). Yield 78%; yellow
solid; mp 190e193 ꢀC; IR (KBr): 3074, 1602, 1517, 1479, 1447, 1336,
1127, 1019, 908, 814, 686 cmꢂ1; 1H NMR (400 MHz, CDCl3):
d (ppm)
1142, 1108, 950, 848, 712 cmꢂ1; 1H NMR (400 MHz, CDCl3):
d
(ppm)
8.32(d, J¼8.8 Hz, 2H), 8.13 (br s, 2H), 7.87 (d, J¼8.4 Hz, 2H), 7.65 (s,1H),
7.52 (br s, 3H); 13C NMR (100 MHz, CDCl3)
(ppm) 162.7, 149.1, 147.0,
8.10e8.02 (m, 2H), 7.51e7.40 (m, 3H), 7.37e7.35 (m, 1H), 7.33 (d,
J¼4.8 Hz, 1H), 7.30 (s, 1H), 7.10e7.04 (m, 1H); 13C NMR (100 MHz,
d
CDCl3) d (ppm) 160.6, 146.7, 130.3, 129.8, 128.8, 127.8, 127.1, 126.2,
133.6, 131.1, 128.9, 126.9, 126.7, 126.6, 124.5, 124.4; HRMS (APCI): m/z
[MþH]þ calcd for C15H11N2O3: 267.0764; found: 267.0766.
125.6, 124.2, 123.1; HRMS (APCI): m/z [MþH]þ calcd for C13H10NOS:
228.0478; found: 228.0479.
4.3.9. 5-([1,10-Biphenyl]-4-yl)-2-phenyloxazole (3ia). Yield 79%;
light yellow solid; mp 140e143 ꢀC; IR (KBr): 3060, 2924, 1671, 1541,
4.3.16. 4-(4-(2-Phenyloxazol-5-yl)phenyl)morpholine (3pa). Yield
94%; light yellow solid; mp 179e182 ꢀC; IR (KBr): 3122, 2962, 2852,
1612, 1546, 1505, 1447, 1382, 1350, 1268, 1240, 1122, 1068, 928, 817,
1478, 1134, 1060, 949, 835, 764, 688 cmꢂ1 1H NMR (400 MHz,
;
CDCl3):
d
(ppm) 8.14 (d, J¼6.4 Hz, 2H), 7.80 (d, J¼8.4 Hz, 2H), 7.69 (d,
778, 705, 659, 529 cmꢂ1; 1H NMR (400 MHz, CDCl3):
d (ppm) 8.09 (d,
J¼8.0 Hz, 2H), 7.64 (d, J¼7.2 Hz, 2H), 7.55e7.43 (m, 6H), 7.38 (d,
J¼7.6 Hz, 2H), 7.62 (d, J¼7.6 Hz, 2H), 7.50e7.39 (m, 3H), 7.30 (s, 1H),
J¼7.2 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d (ppm) 161.1, 151.0, 141.1,
6.95 (d, J¼8.0 Hz, 2H), 3.87 (t, J¼4.6 Hz, 4H), 3.21 (t, J¼4.6 Hz, 4H); 13C
140.2, 130.3, 128.8(2), 128.7(7), 127.6, 127.5, 127.3, 126.9, 126.8,
126.2, 124.5, 123.5; HRMS (APCI): m/z [MþH]þ calcd for C21H16NO:
298.1226; found: 298.1228.
NMR (100 MHz, CDCl3) d (ppm) 160.3,151.4,151.1,130.9,130.0,128.7,
127.6,126.0,125.3,121.6,115.3, 66.7, 48.6; HRMS (APCI): m/z [MþH]þ
calcd for C19H19N2O2: 307.1441; found: 307.1443.
4.3.10. 4-(2-Phenyloxazol-5-yl)phenol (3ja).11b Yield 80%; yellow
solid; mp 197e202 ꢀC; IR (KBr): 3124, 1666, 1609, 1541, 1504, 1479,
4.3.17. 2-(4-Chlorophenyl)-5-phenyloxazole (3ab).11b Yield 78%;
light yellow solid; mp 117e120 ꢀC; IR (KBr): 3064, 2926, 1728, 1601,

Q.-H. Gao et al. / Tetrahedron 69 (2013) 22e28
27
1476, 1399, 1276, 1129, 1086, 947, 826, 760, 729, 687 cmꢂ1; 1H NMR
(t, J¼4.0 Hz, 2H), 7.47e7.30 (m, 5H); 13C NMR (100 MHz, CDCl3)
(400 MHz, CDCl3):
d
(ppm) 8.02 (d, J¼8.4 Hz, 2H), 7.69 (d, J¼7.6 Hz,
d (ppm) 158.6, 151.9, 150.8, 147.4, 133.2, 129.0, 128.9, 128.7, 127.4,
2H), 7.46e7.37 (m, 5H), 7.34 (t, J¼7.2 Hz, 1H); 13C NMR (100 MHz,
124.3, 124.2, 123.5; HRMS (APCI): m/z [MþH]þ calcd for C14H11N2O:
CDCl3)
d
(ppm) 160.1, 151.4, 136.3, 129.1, 128.9, 128.5, 127.7, 127.5,
223.0866; found: 223.0864.
125.8, 124.2, 123.5; HRMS (APCI): m/z [MþH]þ calcd for
C15H11ClNO: 256.0524; found: 256.0526.
4.3.25. 2,5-Bis(4-methoxyphenyl)oxazole (3bk). Yield 70%; light
yellow solid; mp 123e126 ꢀC; IR (KBr): 3010, 2929, 1611, 1302, 1251,
1171, 1055, 1021, 948, 832, 737, 701, 632 cmꢂ1; 1H NMR (400 MHz,
4.3.18. 2-(4-Fluorophenyl)-5-phenyloxazole (3ac).11b Yield 76%;
light yellow solid; mp 78e81 ꢀC; IR (KBr): 3052, 2924, 1652, 1604,
CDCl3):
d
(ppm) 8.02 (d, J¼8.0 Hz, 2H), 7.63 (d, J¼8.0 Hz, 2H), 7.28 (s,
1491, 1410, 1225, 1129, 1092, 949, 905, 837, 758, 731, 686 cmꢂ1
;
1H
1H) 6.97 (t, J¼8.4 Hz, 4H), 3.87 (s, 3H), 3.85 (s, 3H); 13C NMR
NMR (400 MHz, CDCl3):
d
(ppm) 8.12e8.04 (m, 2H), 7.69 (d, J¼7.6 Hz,
(100 MHz, CDCl3) d (ppm) 161.2, 160.6, 159.6, 150.7, 127.8, 125.6,
2H), 7.49e7.37 (m, 3H), 7.33 (t, J¼7.2 Hz,1H), 7.16 (t, J¼8.6 Hz, 2H); 13C
121.7, 121.0, 120.4, 114.3, 114.2, 55.5, 55.4; HRMS (APCI): m/z
NMR (100 MHz, CDCl3)
d (ppm) 165.2, 162.7, 151.3, 128.9, 128.4(3),
[MþH]þ calcd for C17H16NO3: 282.1125; found: 282.1127.
128.3(5), 128.3, 127.8, 124.1, 123.8, 123.3, 116.1, 115.8; HRMS (APCI):
m/z [MþH]þ calcd for C15H11FNO: 240.0819; found: 240.0821.
4.3.26. 2-(3-Methoxyphenyl)-5-(4-methoxyphenyl)oxazole
(3bl). Yield 66%; yellow solid; mp 73e76 ꢀC; IR (KBr): 3018, 2961,
1602, 1541, 1500, 1457, 1322, 1297, 1250, 1177, 1024, 826, 727, 682,
4.3.19. 5-Phenyl-2-(4-(trifluoromethyl)phenyl)oxazole
Yield 78%; light yellow solid; mp 108e112 ꢀC; IR (KBr): 3082, 2925,
1549, 1483, 1413, 1329, 1126, 948, 845, 760, 687 cmꢂ1 1H NMR
(3ad).11b
612 cmꢂ1; 1H NMR (400 MHz, CDCl3):
d
(ppm) 7.67 (d, J¼7.6 Hz,1H),
;
7.62 (d, J¼8.8 Hz, 3H), 7.36 (t, J¼7.8 Hz, 1H), 7.30 (s, 1H), 7.06e6.91
(400 MHz, CDCl3):
d
(ppm) 8.20 (d, J¼8.0 Hz, 2H), 7.80e7.70 (m,
(m, 3H), 3.87 (s, 3H), 3.82 (s, 3H); 13C NMR (100 MHz, CDCl3)
4H), 7.46 (t, J¼7.4 Hz, 3H), 7.37 (t, J¼7.4 Hz, 1H); 13C NMR (100 MHz,
d (ppm) 160.3, 159.8, 151.3, 129.7, 128.7, 125.8, 125.7, 121.8, 120.7,
CDCl3)
d
(ppm) 159.6, 152.1, 131.6, 130.5, 129.0, 128.8, 127.6, 126.4,
118.5, 116.5, 114.3, 110.7, 55.4, 55.3; HRMS (APCI): m/z [MþH]þ calcd
125.8(3), 125.8(0), 124.3, 123.8, 123.7; HRMS (APCI): m/z [MþH]þ
for C17H16NO3: 282.1125; found: 282.1122.
calcd for C16H11F3NO: 290.0787; found: 290.0789.
4.3.27. 5-(4-Methoxyphenyl)-2-(p-tolyl)oxazole (3bm). Yield 75%;
light green solid; mp 115e120 ꢀC; IR (KBr): 3123, 2925, 1656, 1611,
1584, 1499, 1293, 1254, 1175, 1110, 1056, 1025, 949, 827, 727, 630,
4.3.20. 2-(3-Chlorophenyl)-5-phenyloxazole (3ae).11b Yield 72%;
white solid; mp 100e103 ꢀC; IR (KBr): 3060, 1578, 1538, 1459, 1302,
1130, 1075, 950, 884, 822, 792, 761, 720, 681 cmꢂ1
;
1H NMR
498 cmꢂ1; 1H NMR (400 MHz, CDCl3):
d
(ppm) 7.98 (d, J¼8.0 Hz, 2H),
7.65 (d, J¼8.4 Hz, 2H), 7.36e7.27 (m, 3H), 6.97 (d, J¼8.4 Hz, 2H), 3.86(s,
3H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3)
(ppm) 160.7, 159.7,
(400 MHz, CDCl3):
d (ppm) 8.07 (s, 1H), 8.01e7.95 (m, 1H), 7.70 (d,
J¼7.2 Hz, 2H), 7.49e7.39 (m, 5H), 7.34 (t, J¼7.0 Hz, 1H); 13C NMR
d
(100 MHz, CDCl3)
d
(ppm) 159.7, 151.7, 134.9, 130.2, 130.1, 129.0,
150.9, 140.3, 129.4, 126.1, 125.6, 124.8, 121.7, 120.9, 114.3, 55.3, 21.5;
HRMS (APCI): m/z [MþH]þ calcd for C17H16NO2: 266.1176; found:
266.1178.
128.9, 128.6, 127.7, 126.2, 124.3, 124.2, 123.5; HRMS (APCI): m/z
[MþH]þ calcd for C15H11ClNO: 256.0524; found: 256.0526.
4.3.21. 2-(2,4-Dichlorophenyl)-5-phenyloxazole (3af). Yield 88%;
white solid; mp 111e115 ꢀC; IR (KBr): 3070, 2927, 1729, 1554, 1481,
4.3.28. 5-(4-Methoxyphenyl)-2-(3-nitrophenyl)oxazole (3bn). Yield
72%; yellow solid; mp 155e158 ꢀC; IR (KBr): 3102, 2925, 1611, 1521,
1450,1387,1260,1132, 1101, 1031, 953, 869, 829, 757, 731, 685 cmꢂ1
;
1351, 1296,1256, 1179, 1104,1021, 900, 819, 740, 706, 614, 513 cmꢂ1
;
1H NMR (400 MHz, CDCl3):
J¼7.6 Hz, 2H), 7.53 (s, 1H), 7.50 (s, 1H), 7.44 (t, J¼7.6 Hz, 2H),
7.38e7.31 (m, 2H); 13C NMR (100 MHz, CDCl3)
(ppm) 158.1, 151.9,
d
(ppm) 8.04 (d, J¼8.4 Hz, 1H), 7.71 (d,
1H NMR (400 MHz, CDCl3):
d
(ppm) 8.88 (s, 1H), 8.40 (d, J¼7.6 Hz,
1H), 8.28 (d, J¼8.0 Hz,1H), 7.66 (t, J¼8.0 Hz, 3H), 7.37 (s,1H), 6.99 (d,
d
J¼8.4 Hz, 2H), 3.87 (s, 3H); 13C NMR (100 MHz, CDCl3)
d (ppm)
136.3, 132.9, 131.3, 131.1, 128.9, 128.7, 127.5, 127.3, 124.6, 124.3,
123.2; HRMS (APCI): m/z [MþH]þ calcd for C15H10Cl2NO: 290.0134;
found: 290.0137.
160.2, 158.1, 152.4, 131.6, 130.7, 129.9, 129.1, 126.0, 124.3, 122.3,
120.8, 120.1, 114.5, 55.4; HRMS (APCI): m/z [MþH]þ calcd for
C16H13N2O4: 297.0870; found: 297.0872.
4.3.22. 2-(Furan-2-yl)-5-phenyloxazole (3ag).11a Yield 78%; white
solid; mp 67e70 ꢀC; IR (KBr): 3137, 3058, 2924, 1625, 1516, 1449,
4.3.29. 2-(2-Chlorophenyl)-5-(4-methoxyphenyl)oxazole
(3bo).
Yield 80%; light yellow solid; mp 98e102 ꢀC; IR (KBr): 3121, 3048,
2926, 1690, 1613, 1573, 1498, 1453, 1345, 1291, 1252, 1176, 1028, 954,
836, 810, 764, 730, 650, 610, 525 cmꢂ1; 1H NMR (400 MHz, CDCl3):
1260, 1167, 1132, 1007, 936, 883, 830, 759, 717, 683 cmꢂ1 1H NMR
;
(400 MHz, CDCl3):
J¼7.6 Hz, 3H), 7.31 (t, J¼7.4 Hz, 1H), 7.06 (d, J¼3.2 Hz, 1H), 6.56e6.51
(m, 1H); 13C NMR (100 MHz, CDCl3)
(ppm) 153.8, 150.7, 144.3,
d
(ppm) 7.67 (d, J¼7.2 Hz, 2H), 7.56 (s,1H), 7.40 (t,
d
(ppm) 8.12e8.03 (m,1H), 7.64 (d, J¼8.8 Hz, 2H), 7.53e7.45 (m,1H),
d
7.38 (s,1H), 7.36e7.31 (m, 2H), 6.94 (d, J¼8.4 Hz, 2H), 3.81 (s, 3H); 13C
142.8, 128.8, 128.4, 127.5, 124.0, 123.1, 111.8, 111.3; HRMS (APCI): m/z
NMR (100 MHz, CDCl3) d (ppm) 159.8,158.2,151.6,132.0,131.2,130.6,
[MþH]þ calcd for C13H10NO2: 212.0706; found: 212.0708.
130.5, 126.7, 126.1, 125.8, 121.6, 120.5, 114.3, 55.2; HRMS (APCI): m/z
[MþH]þ calcd for C16H13ClNO2: 286.0629; found: 286.0631.
4.3.23. 5-Phenyl-2-(pyridin-4-yl)oxazole (3ah). Yield 87%; white
solid; mp 98e102 ꢀC; IR (KBr): 3373, 3102, 3050, 1606, 1533, 1480,
4.3.30. 5-(4-Bromophenyl)-2-(4-chlorophenyl)oxazole (3rb). Yield
75%; yellow solid; mp 145e149 ꢀC; IR (KBr): 3083, 1602, 1476, 1404,
1414, 1214, 1134, 996, 954, 870, 831, 758, 706, 683 cmꢂ1 1H NMR
;
(400 MHz, CDCl3):
2H), 7.5 (d, J¼7.6 Hz, 2H), 7.50 (s, 1H), 7.49e7.42 (m, 2H), 7.41e7.34
(m, 1H); 13C NMR (100 MHz, CDCl3)
(ppm) 158.6, 152.5, 150.4,
d
(ppm) 8.75 (d, J¼4.8 Hz, 2H), 7.93 (d, J¼5.2 Hz,
1133, 1096, 1008, 948, 826, 733, 495 cmꢂ1 1H NMR (400 MHz,
;
CDCl3):
d
(ppm) 8.00 (d, J¼6.4 Hz, 2H), 7.55 (s, 4H), 7.43 (d, J¼7.6 Hz,
d
3H); 13C NMR (100 MHz, CDCl3)
d
(ppm) 160.4, 150.4, 136.8, 136.6,
134.1,129.0(2),128.9(7),127.2, 124.4,123.9, 119.7; HRMS (APCI): m/z
132.1, 129.1, 127.5, 126.6, 125.6, 124.0, 122.4; HRMS (APCI): m/z
[MþH]þ calcd for C15H10BrClNO: 333.9629; found: 333.9631.
[MþH]þ calcd for C14H11N2O: 223.087; found: 223.0864.
4.3.24. 5-Phenyl-2-(pyridin-3-yl)oxazole (3ai).11a Yield 76%; white
solid; mp 85e87 ꢀC; IR (KBr): 3052, 1567, 1480, 1404, 1185, 1112,
4.3.31. 4,40-Bis(2-phenyloxazol-5-yl)-1,10-biphenyl (3sa). Yield 43%;
yellow solid; mp 167e171 ꢀC; IR (KBr): 3039, 2925, 2854, 1728,
1672, 1604, 1538, 1472, 1263, 1134, 1060, 950, 821, 710, 686,
1057, 1021, 948, 814, 763, 687 cmꢂ1 1H NMR (400 MHz, CDCl3):
;
d
(ppm) 9.33 (s, 1H), 8.70e8.66 (m, 1H), 8.33 (d, J¼8.0 Hz, 1H), 7.71
487 cmꢂ1
;
1H NMR (400 MHz, CDCl3):
d
(ppm) 8.14 (d, J¼7.6 Hz,

28
Q.-H. Gao et al. / Tetrahedron 69 (2013) 22e28
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Heterocyclic Compounds Oxazoles: Synthesis, Reactions, and Spectroscopy, Parts A
& B; Wiley: New Jersey, 2004; Vol. 60.
4H), 7.81 (d, J¼8.4 Hz, 4H), 7.72 (d, J¼8.0 Hz, 4H), 7.50 (d, J¼7.2 Hz,
8H); 13C NMR (100 MHz, CDCl3)
(ppm) 161.3, 151.0, 140.1, 130.9,
130.4, 128.9, 127.4, 126.3, 124.7, 123.8, 109.9; HRMS (APCI): m/z
[MþH]þ calcd for C30H21N2O2: 441.1598; found: 441.1595.
d
4.3.32. 1,3-Bis(5-phenyloxazol-2-yl)benzene (3ap). Yield 38%; white
solid; mp 176e179 ꢀC; IR (KBr): 3108, 3063, 1586, 1537, 1478, 1425,
1309, 1134, 1059, 1025, 939, 908, 824, 761, 709, 683, 492 cmꢂ1 1H
;
NMR (400 MHz, CDCl3):
d
(ppm) 8.82 (s, 1H), 8.21 (d, J¼7.2 Hz, 2H),
7.77 (d, J¼6.8 Hz, 4H), 7.62 (t, J¼7.6 Hz, 1H), 7.47 (t, J¼8.4 Hz, 6H),
7.37 (t, J¼6.6 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d (ppm) 160.4,
151.7, 129.4, 129.0, 128.6, 128.2, 127.9, 127.8, 124.4, 123.8, 123.6;
HRMS (APCI): m/z [MþH]þ calcd for C24H17N2O2: 365.1285; found:
365.1288.
Acknowledgements
7. Cheung, C. W.; Buchwald, S. L. J. Org. Chem. 2012, 77, 7526e7537 and references
cited therein.
8. (a) Yeh, V. Tetrahedron 2004, 60, 11995e12042; (b) Young, G. L.; Smith, S. A.;
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We thank the National Natural Science Foundation of China
(Grant 20902035, 21032001 and 21272085). We also thank Dr.
Xianggao Meng for his help with X-ray diffraction analysis and Dr.
Chuanqi Zhou, Hebei University, for analytical support.
Supplementary data
The general experimental methods and the 1H NMR titration
experiments of 3ba with HI. The reaction process of 1b (0.1 mmol),
2a (0.12 mmol) with I2 (0.2 mmol) was monitored by 1H NMR
(600 MHz, DMSO-d6, 298ꢁ0.5 K) and X-ray crystal structures of
compound 3ba are available in Supplementary data. Supplemen-
tary data related to this article can be found at http://dx.doi.org/
10.1016/j.tet.2012.10.072.
10. (a) Flegeau, E. F.; Popkin, M. E.; Greaney, M. F. Org. Lett. 2008, 10, 2717e2720; (b)
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References and notes
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3. (a) Dick, A. R.; Sanford, M. S. Tetrahedron 2006, 62, 2439e2463; (b) Godula, K.;
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14. Crystal structure data for compound 3ba: CCDC 899913, C32H24N2O5, chemical
ꢀ
ꢀ
formula weight: 516.53, Monoclinic space group C2/c, a¼26.784 A, b¼5.318 A,
3
ꢀ
ꢀ
ꢀ
c¼19.416 A;
a
¼90ꢀ,
b
¼101.14ꢀ,
g
¼90 , V¼2713.4 A , T¼298(2) K, Z¼4, DC¼1.
264 Mg/m3,
m
¼0.086 mm-1
¼0.71073 A, F(000) 1080, crystal size 0.20ꢃ0.10ꢃ
,
l
ꢀ
0.10 mm3, 2380 independent reflections [R(int)¼0.0518], reflections collected
7521, refinement method: full-matrix least-squares on F2: goodness-of-fit on F2
1.205, final R indices [I>2 (I)], R1¼0.1086, wR2¼0.2536, largest diff. peak and
s
ꢀꢂ3
hole 0.344 and ꢂ0.212 e A
.
15. Yin, G. D.; Gao, M.; She, N. F.; Hu, S. L.; Wu, A. X.; Pan, Y. J. Synthesis 2007, 20,
3113e3116.
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F.; Wu, A. X. Org. Lett. 2010, 12, 4026e4029.
18. Sengupta, S.; Mondal, S. Tetrahedron Lett. 1999, 40, 8685e8688.