Chemoselective intramolecular wittig reactions for the synthesis of oxazoles and benzofurans

Article abstract of DOI:10.1021/jo502232q

A chemoselective approach was developed for the synthesis of highly functionalized oxazoles and benzofurans using an intramolecular Wittig reaction as the key step. By choosing proper trapping reagent or method of addition of reagents, chemoselectivity ca

Full text of DOI:10.1021/jo502232q

Article
pubs.acs.org/joc
Chemoselective Intramolecular Wittig Reactions for the Synthesis of
Oxazoles and Benzofurans
Yu-Shiou Fan,† Utpal Das,† Ming-Yu Hsiao, Meng-Hsien Liu, and Wenwei Lin*
Department of Chemistry, National Taiwan Normal University, Taipei 11677, Taiwan, R.O.C.
S
* Supporting Information
ABSTRACT: A chemoselective approach was developed for the synthesis of highly functionalized oxazoles and benzofurans
using an intramolecular Wittig reaction as the key step. By choosing proper trapping reagent or method of addition of reagents,
chemoselectivity can be controlled toward either oxazole or benzofuran derivatives.
obtained by treating 1a (1.2 equiv) and 2a (1 equiv) in the
presence of Bu3P (1.1 equiv) and Et3N (1.3 equiv) in anhydrous
dichloromethane at room temperature (entry 1, Table 1, see
Supporting Information (SI) for details).12 However, formation
of benzofuran 4a (8%) was also noticed. During this study it was
observed that by alteration of reaction condition, benzofuran 4
was the major product instead of oxazole 3 (condition B; Table
2). It is also revealed that proper choice of the trapping reagent
(acyl chloride or anhydride) can alter the course of the reaction
toward chemoselective formation of oxazole (condition A; entry
15, Table 1 and see Scheme 4) or benzofuran (condition C; entry
16, Table 1 and Table 3).
Under the optimal condition, various Michael acceptors (1a−
c) and acyl chlorides (2a−g) were examined for the generality of
the methodology (entries 1−14; Table 1). Michael acceptors 1b
and 1c were also employed successfully with 2a in our optimized
condition to provide the oxazole products 3b (68%) and 3c
(59%) along with minor benzofuran products (entries 2 and 3).
Next we have tested various acyl chlorides (2b−g) with 1a and 1c
(entries 4−14). In most of the cases, chemoselective formation of
oxazoles was observed in preference to benzofurans. However,
when 1a was treated with acyl chlorides 2d−f, rearranged oxazole
products 3f′−h′ (28−34%) were obtained as the major products
along with normal oxazoles 3f−h (21−23%) and benzofurans
4f−h (1−14%; entries 6−8). Eventually, we observed that
trifluoroacetic anhydride (TFAA, 2h) was very reactive toward
Michael acceptor 1a, and the reaction proceeded very efficiently
to furnish the product 3o with complete chemoselectivity in just
30 min with 77% yield (entry 15). Although the reaction
presented in Table 1 showed inclination toward chemoselective
formation of oxazole (or isomeric oxazole), we found a complete
reversal of chemoselectivity by using pivaloyl chloride (2i) as the
INTRODUCTION
■
Oxazole units can be found in a large number of natural products
and bioactive molecules.1,2 As a result, a lot of attention has been
paid to the synthesis of highly functionalized oxazoles, and
several efficient methods are known. One of the methods
available for the synthesis of this five-membered heteroaromatic
ring is direct oxidation of oxazolines.3 Alternative routes to
oxazole synthesis rely on the transition metal- or organocatalyst-
mediated4 cyclization of acyclic precursors, functionalization of
oxazoles,5 and others.6
Recently, we have demonstrated an efficient and metal-free
method for the synthesis of trisubstituted oxazoles via intra-
molecular Wittig reactions starting from acyl imines.7 Although
significant progress has been done, the rich chemistry of fully
substituted oxazole compounds (as a pharmacologically
important moiety1,2) are of huge interest in diversity-oriented
synthesis.8 Employing this strategy, a library of functionalized
oxazoles were prepared in a one-pot operation.7 This reaction
mode aroused our interest to explore a chemoselective
intramolecular Wittig reaction9 for the synthesis of oxazoles 3
starting from Michael acceptors 1, Bu3P and acyl chlorides 2
(Scheme 1). Chemoselective reactions are highly desirable as an
atom- and step-economic process.10 Inspired by our previous
report on chemoselective synthesis of benzofurans starting from
1′ (Scheme 1),9f we became curious in using analogous
compounds 1 as the electrophilic components to investigate
the reaction outcome. It is worth mentioning that benzofuran
constitutes an important class of privileged structural unit and
can be found in many natural products.11
RESULTS AND DISCUSSION
■
Initially, we employed Michael acceptor 1a and benzoyl chloride
(2a) as the model reaction partners in the presence of phosphine
and base. Chemoselective formation of oxazole 3a (56%) was
observed as the major product in just 1.5 h. The best result was
Received: September 29, 2014
© XXXX American Chemical Society
A
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Scheme 1. Chemoselective Intramolecular Wittig Reaction of 1 or 1′
a
Table 1. Synthesis of Oxazole and Benzofuran Derivatives via Intramolecular Wittig Reaction
b
entry
R1
Br
1
R2 (2)
Ph, 2a
t (h)
product 3/3′/4
yield (%)
1
1a
1b
1c
1a
1a
1a
1a
1a
1c
1c
1c
1c
1c
1c
1a
1a
1.5
1.0
0.5
1.0
1.0
1.0
1.0
2.0
1.0
1.0
1.0
1.0
1.0
2.0
0.5
0.5
3a/4a13
3b/4b
56/8
68/14
59/7
45
2
Cl
Ph, 2a
3
OMe
Br
Ph, 2a
3c/4c
4
4-NO2C6H4, 2b
4-BrC6H4, 2c
4-OMeC6H4, 2d
2-furyl, 2e
3d
5
Br
3e13/4e
3f/3f′13/4f
3g13/3g′13/4g13
3h13/3h′13/4h
3i
43/1
23/28/14
21/31/3
21/34/1
59
6
Br
7
Br
8
Br
2-thienyl, 2f
4-NO2C6H4, 2b
4-BrC6H4, 2c
4-OMeC6H4, 2d
2-furyl, 2e
9
OMe
OMe
OMe
OMe
OMe
OMe
Br
10
11
12
13
14
3j
65
3k/4k
46/22
57/4
60/5
49/6
77
3l13/3l′
3m13/4m
3n/4n
2-thienyl, 2f
2-BrC6H4, 2g
TFAA, 2h
c
15
d
3o13
4o13
16
Br
t-Bu, 2i
77
a
Compound 1 (1.2 equiv) was treated with 2 (0.3 mmol) in the presence of Bu3P (1.1 equiv) and Et3N (1.1 equiv) in anhydrous CH2Cl2 (1.5 mL)
b
c
at rt under inert atmosphere. Isolated yields. Compound 1a (0.3 mmol) was treated with Ph3P (1.1 equiv) and TFAA (1.1 equiv) followed by Et3N
(1.3 equiv) in toluene at rt under inert atmosphere. In 0.6 mL of anhydrous CH2Cl2.
d
trapping reagent. Thus, treatment of 1a with 2i at room
temperature led to benzofuran product (4o) with complete
chemoselectivity within 30 min in 77% yield (entry 16). These
results suggest that chemoselective formation of phosphorus
ylides is possible, which would be a useful route for the synthesis
of either oxazoles or benzofurans. The key ylide intermediates
(5−7) that furnished intramolecular Wittig reaction leading to
products 3, 3′ and 4 are shown in Table 1.
We were also pleased to find that the chemoselective outcome
of this transformation is dependent on how the reagents are
added. For example, when 1a was treated with Bu3P in
dichloromethane for 30 min followed by addition of 2a and
B
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Table 2. Chemoselective Formation of Benzofuran (4) via
Intramolecular Wittig Reaction
Scheme 2. Controlled Experiments to Identify the
Intermediates 8
a
b
entry
R1
1
R2 (2)
Ph, 2a
t (h) product 3/4 yield (%)
1
2
3
4
5
Br
Cl
Br
Br
Br
1a
1c
1a
1a
1a
1.5
1.5
1.5
1.5
1.5
4a
49
Ph, 2a
3b/4b
4e
4/60
57
4-BrC6H4, 2c
4-OMeC6H4, 2d
2-furyl, 2e
4f
57
4g
57
a
1 (1.2 equiv) was treated with Bu3P (1.1 equiv) in anhydrous CH2Cl2
(1.5 mL) for 0.5 h followed by addition of 2 (0.3 mmol) and Et3N (1.1
b
equiv) under inert atmosphere (Condition B). Isolated yields.
Table 3. Chemoselective Synthesis of Benzofuran (4o−s)
a
Starting from N-Acyl Imines
from N-acyl imines are further demonstrated by in-corporating
various Michael acceptors containing aromatic or aliphatic
substituents (entry 15 in Table 1 and Scheme 4). Thus, upon
treatment of compound 1 was treated with Ph3P, trifluoroacetic
anhydride, and Et3N in toluene at room temperature, function-
alized oxazoles 3o−y were obtained in very good yields within 1
h.
The substrate scope for chemoselective synthesis of
benzofuran derivatives (4) using pivaloyl chloride (2i) via
intramolecular Wittig reaction starting from N-acyl imines (1)
was further exemplified in Table 3. Under the optimized reaction
condition (for optimization data, see SI),12 various Michael
acceptors (1a−e) containing an electron-donating or electron-
withdrawing group were employed along with 2i for the synthesis
of benzofuran products (4o−s). As presented in Table 3,
corresponding products were obtained in good yields (entries 1−
6). A high degree of chemoselectivity was observed in all the
cases; however, formation of rearranged benzofuran product as
minor isomer (4s′) was also detected (entry 6). Remarkably, in
case of using 2-thienyl substituted Michael acceptor 1f,
rearranged benzofuran 4t′ was the only product (entry 7).
Furthermore, condition B was also found to proceed with
chemoselective formation of benzofuran (4o; entry 8).
The synthetic utility of the present protocol is further
illustrated by converting some selected products into potentially
useful new compounds. For example, benzamide-substituted
benzofuran (such as 8a), which was obtained by treating 1a with
Bu3P (Scheme 2, eq 1), was prepared by treatment of 4 in the
presence of HCl solution in dioxane. Compounds 8a−c was
obtained in quantitative yield and was further converted to the
corresponding N-protected derivatives 10a−d. For the protec-
tion of an amide group, relatively few methods are available14 but
in the present case, the products were obtained in good chemical
yields (Scheme 5; eq 1). Again benzoate-protected oxazoles (3a,
3o−q) were successfully deprotected by treatment with sodium
methoxide in THF/MeOH solvent mixture. The corresponding
oxazoles bearing the phenol moiety (11a−d) were obtained in
high chemical yields (76−90%). These oxazoles (11a−d) were
then converted to the corresponding phenoxy ether-substituted
oxazoles (12a−c) after treatment with benzyne generated from
o-(trimethylsilyl)phenyl triflate (Scheme 5; eq 2).15
b
entry
R1
Br
Ar
1
t (h) product 4/4′ yield (%)
1
2
3
4
6
7
Ph
Ph
Ph
1a
1b
1c
1d
1e
1f
0.5
0.5
2.0
0.5
0.5
1.0
1.5
4o
77
Cl
4p12
4q
69
OMe
H
79
4-BrC6H4
4-BrC6H4
2-thienyl
Ph
4r
93
OMe
Br
4s12/4s′12
4t′12
4o/8a
67/10
73
c
8
Br
1a
40/3
a
Reactions were performed with 2i (0.3 mmol), 1 (1.2 equiv), Bu3P
(1.1 equiv) and Et3N (1.1 equiv) in anhydrous CH2Cl2 (0.6 mL)
under inert atmosphere (Condition C). Isolated yields. Condition B.
b
c
Et3N, exclusive formation of benzofuran 4a (49%) was observed
(entry 1, Table 2). As shown in Table 2, this protocol was also
applicable to Michael acceptor 1c (entry 2) and acyl chlorides
2c−e (entries 3−5) and chemoselective formation of benzofuran
products 4 was obtained in good yields (57−60%) within 1.5 h.
To understand the actual nature of the intermediate species 8,
some controlled experiments were performed (Scheme 2).
When the compound 1a was treated with Bu3P in dichloro-
methane at room temperature, 8a was obtained in 27% yield after
1 h (eq 1). The compound 4a (68%) was obtained after
treatment of 8a with 2a in the presence of catalytic amount of
Bu3P (10 mol %), but no conversion of 8a was observed without
the activation of Bu3P (eq 2−3). This result indicates that Bu3P
activates 2a, which performs N-acylation of 8a leading to the
formation of 4a (eq 4).
On the basis of the results obtained from Scheme 2, formation
of the compound 4 can be explained by the mechanism as
presented in Scheme 3. We believe that the zwitterionic species
9a (which is generated from Michael addition of Bu3P to 1a)
provided the ylide 9a′ when the reaction was stirred for long time
via proton exchange, which was followed by an intramolecular
Wittig reaction to furnish the compound 8a.
The synthetic utility of chemoselective synthesis of function-
alized oxazoles containing a trifluoromethyl substituent starting
C
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Scheme 3. Plausible Reaction Mechanism for the Intermediate 8a
a b
,
Scheme 4. Chemoselective Synthesis of Trifluoromethyl-Substituted Oxazoles 3o−y from N-Acyl Imines 1
a
b
Reactions were performed with 1 (0.3 mmol) in anhydrous toluene (1.5 mL) under inert atmosphere (Condition A). Isolated yields.
Scheme 5. Transformation of the Products
On the basis of the experimental results (Tables 1−3 and
Schemes 2−4), a plausible reaction mechanism is presented in
Scheme 6 to explain the formation of products 3 (3′) and 4 (4′).
The reaction initiates via nucleophilic addition of Bu3P to 1
giving rise to the corresponding zwitterionic species 9.
Chemoselective O-acylation of 9 by acyl chloride leads to the
formation of 13. The ylide 5, which is generated via
deprotonation of 13 with Et3N, undergoes an intramolecular
Wittig reaction to furnish oxazole 3 (path a). Formation of
benzofuran 4 can be explained by path b which starts via N-
acylation of zwitterionic species 9 to give 18, deprotonated 18 of
by Et3N, and then intramolecular Wittig reaction of ylide 7.
D
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Scheme 6. Proposed Mechanism for Synthesis of 3, 3′ and 4
Intramolecular acyl group (R3CO) transfer from 9 provides
species 14, which furnished 15 after O-acylation by acyl chloride
2. The second R3CO group (15) transferring and then
deprotonation of 16 with Et3N gives the ylide 6, which performs
intramolecular Wittig reaction to afford oxazole 3′ (path c).
Again intramolecular acyl group (R2CO) transfer from species
14 (path d) generates species 19, which was then N-acylated with
pivaloyl chloride (2i). Deprotonation by Et3N and intra-
molecular Wittig reaction (of 21) provides benzofuran 4′
EXPERIMENTAL SECTION
■
Aldehyde precursors, α-amido sulfone precursors and N-acyl imines 1
were prepared according to the reported literature.16 All the reactions
were carried out in anhydrous solvent under a nitrogen atmosphere in
dried glassware. The starting materials purchased from commercial
sources were used without further purification. Chemical shifts are
reported in δ ppm referenced to an internal TMS standard for 1H NMR
and chloroform-d (δ 77.0 ppm) for 13C NMR. The X-ray diffraction
measurements were carried out at 298 K on a CCD area detector system
equipped with a graphite monochromator and a Mo Kα fine-focus
sealed tube (k = 0.71073 Å). High resolution mass spectra (HRMS)
were recorded using MALDI (TOF analyzer), ESI (TOF analyzer), fast
atom bombardment (FAB+) (Magnetic Sector Analyzer), and EI
(Magnetic Sector Analyzer). Analytical thin layer chromatography
(TLC) was performed using precoated silica gel plate (0.2 mm
thickness). Compounds were purified by flash-chromatography
Typical Procedure for the Preparation of Oxazoles 3,
Oxazoles 3′ and Benzofurans 4 (Table 1). A flame-dried and
nitrogen-flushed 10 mL Schlenk tube, equipped with a magnetic stirring
bar and a septum, was charged with a solution of 1 (1.2 equiv) in
anhydrous dichloromethane (1.5 mL). To this stirred reaction mixture,
Bu3P (82 μL, 1.1 equiv), acyl chloride 2 (0.3 mmol) and Et3N (46 μL,
1.1 equiv) were added in sequence. The reaction mixture was further
stirred for the indicated time at room temperature and was monitored by
1H NMR data analysis. The solvent was removed by evaporation in
SUMMARY AND CONCLUSIONS
■
In summary, we have presented a general method for the
synthesis of highly functionalized oxazoles and benzofurans. The
reaction conditions are very mild with a broad substrate scope. By
choosing proper reaction condition, the course of the reaction
can be altered for chemoselective formation of either oxazole or
benzofuran. We have also proposed a mechanism to explain the
product formation. In general, intramolecular Wittig reaction of
the presumable phosphorus ylide is the key step. We have also
demonstrated some useful synthetic utility of the products.
Further synthetic application of this concept for the preparation
of useful heterocycles and studies for the detailed mechanism is
underway in our laboratory.
vacuo. Purification by flash chromatography furnished the desired
adducts 3, 3′ and 4.
4-Bromo-2-(2,5-diphenyloxazol-4-yl)phenyl benzoate (3a). White
solid (83.2 mg, 56% yield): Rf 0.26 (ethyl acetate/hexanes 1/20); mp
E
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125.9−126.7 °C; 1H NMR (400 MHz, CDCl3, 25 °C) δ/ppm 8.01 (dd,
2H, J = 7.6 Hz, 2.1 Hz), 7.91 (d, 1H, J = 2.5 Hz), 7.64 (d, 2H, J = 7.8 Hz),
7.57 (dd, 1H, J = 8.7 Hz, 2.5 Hz), 7.51−7.48 (m, 2H), 7.45−7.38 (m,
4H), 7.29−7.27 (m, 3H), 7.25−7.19 (m, 3H); 13C NMR (100 MHz,
CDCl3, 25 °C) δ/ppm 164.1, 160.2, 147.5, 147.1, 133.9, 133.2, 132.4,
131.0, 130.4, 129.9, 128.7, 128.6, 128.5, 128.2, 128.0, 127.9, 126.9, 126.3,
°C) δ/ppm 8.11 (d, 2H, J = 8.9 Hz), 8.06 (dd, 2H, J = 7.8 Hz, 1.7 Hz),
7.91 (d, 1H, J = 2.4 Hz), 7.67−7.61 (m, 5H), 7.51−7.43 (m, 4H), 7.30
(d, 1H, J = 8.7 Hz), 7.25 (t, 2H, J = 8.0 Hz); 13C NMR (100 MHz,
CDCl3, 25 °C) δ/ppm 163.9, 161.6, 147.5, 147.2, 144.9, 134.4, 134.1,
133.9, 133.6, 133.3, 131.2, 129.8, 128.8, 128.5, 128.2, 127.1, 126.7, 126.4,
126.2, 125.2, 123.9, 119.4; IR (KBr) ν
̃
(cm−1) 3063 (w), 1748 (s), 1600
125.9, 125.0, 119.1; IR (KBr) ν
̃
(cm−1) 3084 (w), 1686 (s), 1458 (m),
(m), 1550 (w), 1517 (s), 1340 (s), 1199 (s), 702 (s); MS (70 eV, EI) m/
z (%) 542 [M+2]+ (28), 540 [M]+ (33), 150 (5), 105 (100), 77 (34);
HRMS (ESI) for C28H18BrN2O5, [M + H]+ (541.0399), found
541.0396.
1377 (m), 1259 (s), 698 (s); MS (70 eV, EI) m/z (%) 497 [M+2]+ (13),
495 [M]+ (17), 180 (2), 152 (6), 105 (100), 77 (80); HRMS (ESI) for
C28H19BrNO3, [M + H]+ (496.0548), found 496.0543.
N-Benzoyl-N-(5-bromo-2-phenylbenzofuran-3-yl)benzamide
(4a). White solid (11.9 mg, 8% yield; in Table 1, entry 1) (72.8 mg, 49%
yield; in Table 2, entry 1): Rf 0.17 (ethyl acetate/hexanes 1/20); mp
203.9−205.0 °C; 1H NMR (400 MHz, CDCl3, 25 °C) δ/ppm 7.60 (d,
3H, J = 3.2 Hz), 7.58 (d, 2H, J = 3.2 Hz), 7.55−7.53 (m, 2H), 7.46−7.42
(m, 3H), 7.40−7.36 (m, 4H), 7.28 (t, 5H, J = 7.8 Hz); 13C NMR (100
MHz, CDCl3, 25 °C) δ/ppm 172.6, 153.0, 152.0, 133.8, 132.6, 129.9,
128.9, 128.5, 128.43, 128.41, 127.9, 126.9, 120.9, 117.0, 116.8, 113.5; IR
4-Bromo-2-(5-(4-bromophenyl)-2-phenyloxazol-4-yl)phenyl ben-
zoate (3e). White solid (73.9 mg, 43% yield): Rf 0.24 (dichloro-
1
methane/hexanes 1/3); mp 164.6−164.7 °C; H NMR (400 MHz,
CDCl3, 25 °C) δ/ppm 8.03−8.01 (m, 2H), 7.92 (d, 1H, J = 2.4 Hz), 7.67
(d, 2H, J = 8.0 Hz), 7.61 (dd, 1H, J = 8.7 Hz, 2.5 Hz), 7.50−7.47 (m,
1H), 7.44−7.39 (m, 5H), 7.33−7.21 (m, 3H), 7.27−7.23 (m, 2H); 13C
NMR (100 MHz, CDCl3, 25 °C) δ/ppm 164.1, 160.6, 147.4, 146.2,
133.9, 133.4, 132.7, 131.8, 131.6, 130.6, 130.0, 128.7, 128.6, 128.2, 127.6,
(KBr) ν
̃
(cm−1) 3084 (w), 2924 (w), 1699 (s), 1600 (w), 1455 (m),
127.4, 127.2, 126.8, 126.4, 125.1, 122.8, 119.3; IR (KBr) ν
̃
(cm−1) 3063
1257 (s), 697 (m); MS (70 eV, EI) m/z (%) 497 [M+2]+ (17), 495 [M]+
(17), 105 (100), 77 (83); HRMS (EI) for C28H18BrNO3, [M]+
(495.0470), found 495.0459.
(w), 1741 (s), 1613 (w), 1491 (m), 1258 (s), 1202 (s), 704 (s); MS (70
eV, EI) m/z (%) 575 [M+2]+ (89), 573 [M]+ (100), 105 (14), 77 (2);
HRMS (ESI) for C28H18Br2NO3, [M + H]+ (573.9653), found
573.9667.
4-Chloro-2-(2,5-diphenyloxazol-4-yl)phenyl benzoate (3b). White
solid (92.0 mg, 68% yield; in Table 1, entry 2) (5.4 mg, 4% yield; in
Table 2, entry 2): Rf 0.21 (ethyl acetate/hexanes 1/20); mp 131.8−
132.6 °C; 1H NMR (400 MHz, CDCl3, 25 °C) δ/ppm 8.03−8.01 (m,
2H), 7.76 (d, 1H, J = 2.6 Hz), 7.66 (dd, 2H, J = 8.3 Hz, 1.2 Hz), 7.53−
7.50 (m, 2H), 7.48−7.41 (m, 5H), 7.32−7.30 (m, 4H), 7.25 (t, 2H, J =
8.2 Hz); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 164.3, 160.3,
147.2, 147.0, 131.5, 131.2, 131.0, 130.4, 130.0, 129.5, 128.8, 128.72,
128.68, 128.6, 128.3, 128.1, 127.6, 127.0, 126.4, 126.0, 124.7; IR (KBr)
N-Benzoyl-4-bromo-N-(5-bromo-2-phenylbenzofuran-3-yl)-
benzamide (4e). White solid (1.9 mg, 1% yield; in Table 1, entry 5)
(98.0 mg, 57% yield; in Table 2, entry 3): Rf 0.29 (dichloromethane/
hexanes 1/3); mp 173.3−174.3 °C; 1H NMR (400 MHz, CDCl3, 25 °C)
δ/ppm 7.58 (d, 3H, J = 8.3 Hz), 7.54−7.51 (m, 2H), 7.47−7.36 (m,
10H), 7.29 (t, 2H, J = 7.8 Hz); 13C NMR (100 MHz, CDCl3, 25 °C) δ/
ppm 172.4, 171.7, 153.0, 151.9, 133.5, 132.8, 132.6, 131.8, 130.0, 129.9,
128.9, 128.53, 128.51, 128.50, 127.71, 127.66, 127.5, 126.9, 120.7, 117.1,
116.5, 113.6; IR (KBr) ν
̃
(cm−1) 3069 (w), 2924 (m), 1695 (s), 1589
(m), 1257 (s), 1131 (m), 693 (m); MS (70 eV, EI) m/z (%) 575 [M
+2]+ (43), 573 [M]+ (15), 183 (22), 105 (100), 77 (20); HRMS (EI) for
C28H17Br2NO3, [M]+ (572.9575), found 572.9570.
ν
̃
(cm−1) 3056 (s), 1738 (s), 1601 (m), 1476 (s), 1246 (s), 1052 (s), 698
(s); HRMS (MALDI) for C28H19ClNO3, [M + H]+ (452.1048), found
452.1055.
N-Benzoyl-N-(5-chloro-2-phenylbenzofuran-3-yl)benzamide (4b).
White solid (18.9 mg, 14% yield; in Table 1, entry 2) (81.2 mg, 60%
yield; in Table 2, entry 2): Rf 0.13 (ethyl acetate/hexanes 1/20); mp
195.8−196.3 °C; 1H NMR (400 MHz, CDCl3, 25 °C) δ/ppm 7.59 (dd,
4H, J = 8.4 Hz, 1.2 Hz), 7.56−7.53 (m, 2H), 7.46−7.37 (m, 7H), 7.30−
7.24 (m, 5H); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 172.5, 153.1,
151.5, 133.7, 132.6, 129.8, 129.5, 128.8, 128.5, 128.4, 127.9, 127.3, 126.8,
4-Bromo-2-(5-(4-methoxyphenyl)-2-phenyloxazol-4-yl)phenyl
benzoate (3f). White solid (36.2 mg, 23% yield): Rf 0.18 (ethyl acetate/
1
hexanes 1/20); mp 76.0 °C; H NMR (400 MHz, CDCl3, 25 °C) δ/
ppm 8.01−7.99 (m, 2H), 7.90 (d, 1H, J = 2.3 Hz), 7.71 (d, 2H, J = 8.1
Hz), 7.58 (dd, 1H, J = 8.7 Hz, 2.4 Hz), 7.47 (t, 1H, J = 7.5 Hz), 7.43−
7.41 (m, 5H), 7.29−7.24 (m, 3H), 6.82 (d, 2H, J = 8.8 Hz), 3.82 (s, 3H);
13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 164.2, 160.1, 159.8, 147.5,
147.4, 134.0, 133.3, 132.2, 130.3, 130.1, 129.8, 128.9, 128.7, 128.1, 127.6,
125.7, 117.8, 116.9, 113.1; IR (KBr) ν
̃
(cm−1) 3081 (w), 1694 (s), 1597
(w), 1456 (m), 1258 (s), 694 (m); HRMS (MALDI) for C28H19ClNO3,
127.1, 126.3, 125.0, 121.0, 119.1, 114.1, 55.3; IR (KBr) ν
̃
(cm−1) 3061
[M + H]+ (452.1048), found 452.1051.
(w), 2923 (w), 1742 (m), 1613 (m), 1511 (m), 1255 (s), 1203 (s), 704
(s); MS (70 eV, EI) m/z (%) 528 [M+2]+ (74), 526 [M]+ (100), 135
(5), 105 (17), 77 (3); HRMS (ESI) for C29H21BrNO4, [M + H]+
(526.0654), found 526.0645.
2-(2,5-Diphenyloxazol-4-yl)-4-methoxyphenyl benzoate (3c). Yel-
low solid (79.1 mg, 59% yield): Rf 0.31 (ethyl acetate/hexanes 1/6); mp
108.0−108.5 °C; H NMR (400 MHz, CDCl3, 25 °C) δ/ppm 8.03−
1
8.00 (m, 2H), 7.69 (dd, 2H, J = 8.4 Hz, 1.2 Hz), 7.56−7.54 (m, 2H),
7.45−7.39 (m, 4H), 7.32−7.21 (m, 7H), 7.02 (dd, 1H, J = 8.9 Hz, 3.0
Hz), 3.82 (s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 164.8,
160.0, 157.3, 146.7, 142.0, 133.0, 132.3, 130.3, 129.9, 129.2, 128.6,
128.51, 128.47, 128.4, 128.0, 127.1, 126.5, 126.3, 126.0, 124.2, 55.7; IR
4-Bromo-2-(2,5-diphenyloxazol-4-yl)phenyl 4-methoxybenzoate
(3f′). White solid (44.1 mg, 28% yield): Rf 0.10 (ethyl acetate/hexanes
1
1/20); mp 168.8−169.0 °C; H NMR (400 MHz, CDCl3, 25 °C) δ/
ppm 8.05−8.03 (m, 2H), 7.90 (d, 1H, J = 2.4 Hz), 7.60−7.57 (m, 3H),
7.52−7.50 (m, 2H), 7.44−7.43 (m, 3H), 7.33−7.31 (m, 3H), 7.24 (d,
1H, J = 8.2 Hz), 6.71 (d, 2H, J = 8.8 Hz), 3.79 (s, 3H); 13C NMR (100
MHz, CDCl3, 25 °C) δ/ppm 163.8, 163.7, 160.3, 147.7, 147.2, 133.9,
132.5, 132.2, 131.1, 130.5, 128.7, 128.6, 128.3, 127.9, 127.0, 126.4, 126.0,
(KBr) ν
̃
(cm−1) 3069 (w), 2924 (m), 1726 (s), 1581 (m), 1490 (s), 1261
(s), 1192 (s), 701 (s), 690 (s); MS (70 eV, EI) m/z (%) 447 [M]+ (51),
342 (7), 314 (3), 168 (5), 139 (3), 105 (100), 77 (48); HRMS (EI) for
C29H21NO4, [M]+ (447.1471), found 447.1476.
125.1, 121.1, 119.0, 113.4, 55.4; IR (KBr) ν
̃
(cm−1) 3069 (w), 1733 (s),
N-Benzoyl-N-(5-methoxy-2-phenylbenzofuran-3-yl)benzamide
(4c). White solid (9.4 mg, 7% yield): Rf 0.28 (ethyl acetate/hexanes 1/
6); mp 132.9−133.4 °C; 1H NMR (400 MHz, CDCl3, 25 °C) δ/ppm
7.62 (dd, 4H, J = 8.3 Hz, 1.0 Hz), 7.57−7.55 (m, 2H), 7.44−7.36 (m,
6H), 7.26 (t, 4H, J = 7.8 Hz), 6.94−6.90 (m, 2H), 3.82 (s, 3H); 13C
NMR (100 MHz, CDCl3, 25 °C) δ/ppm 172.7, 156.7, 152.3, 148.1,
134.0, 132.4, 129.4, 128.8, 128.5, 128.3, 126.6, 117.5, 113.7, 112.6, 100.9,
1604 (s), 1512 (m), 1257 (s), 1166 (s), 693 (m); MS (70 eV, EI) m/z
(%) 527 [M+2]+ (6), 525 [M]+ (6), 135 (100), 105 (12), 77 (8); HRMS
(EI) for C29H20BrNO4, [M]+ (525.0576), found 525.0574.
N-Benzoyl-N-(5-bromo-2-phenylbenzofuran-3-yl)-4-methoxy-
benzamide (4f). White solid (22.1 mg, 14% yield; in Table 2, entry 6)
(89.8 mg, 57% yield; in Table 2, entry 4): Rf 0.08 (ethyl acetate/hexanes
1
56.0; IR (KBr) ν
̃
(cm−1) 3008 (w), 2931 (m), 1707 (s), 1688 (s), 1600
(m), 1482 (m), 1257 (s), 1131 (s), 846 (m), 693 (s); MS (70 eV, EI) m/
z (%) 447 [M]+ (13), 105 (100), 77 (33); HRMS (EI) for C29H21NO4,
[M]+ (447.1471), found 447.1467.
4-Bromo-2-(5-(4-nitrophenyl)-2-phenyloxazol-4-yl)phenyl ben-
zoate (3d). Yellow solid (72.9 mg, 45% yield): Rf 0.28 (ethyl acetate/
hexanes 1/20); mp 139.5−140.3 °C; 1H NMR (400 MHz, CDCl3, 25
1/20); mp 135.0−135.3 °C; H NMR (400 MHz, CDCl3, 25 °C) δ/
ppm 7.61−7.56 (m, 7H), 7.42 (td, 2H, J = 8.7 Hz, 1.9 Hz), 7.39−7.35
(m, 4H), 7.27 (t, 2H, J = 7.7 Hz), 6.76 (d, 2H, J = 8.8 Hz), 3.78 (s, 3H);
13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 172.7, 171.8, 163.3, 152.8,
151.9, 134.1, 132.4, 131.1, 129.8, 128.8, 128.5, 128.4, 128.3, 128.1, 128.0,
126.9, 125.8, 120.9, 117.1, 116.9, 113.8, 113.5, 55.4; IR (KBr) ν
̃
(cm−1)
1692 (s), 1603 (s), 1512 (m), 1319 (m); MS (70 eV, EI) m/z (%) 527
F
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The Journal of Organic Chemistry
Article
1
[M+2]+ (29), 525 [M]+ (28), 135 (100), 105 (13), 77 (4); HRMS
(MALDI) for C29H20BrNO4Na, [M + Na]+ (548.0468), found
548.0469.
acetate/hexanes 1/20); mp 168.8−170.0 °C; H NMR (400 MHz,
CDCl3, 25 °C) δ/ppm 7.71−7.66 (m, 4H), 7.59 (d, 1H, J = 1.8 Hz), 7.54
(dd, 1H, J = 3.9 Hz, 1.2 Hz), 7.50−7.44 (m, 3H), 7.42−7.39 (m, 4H),
7.35 (t, 2H, J = 7.8 Hz), 6.94 (dd, 1H, J = 8.9 Hz, 4.9 Hz); 13C NMR
(100 MHz, CDCl3, 25 °C) δ/ppm 172.5, 165.2, 153.1, 151.9, 136.2,
134.1, 133.8, 132.6, 130.0, 128.9, 128.53, 128.49, 128.45, 127.9, 127.6,
4-Bromo-2-(5-(furan-2-yl)-2-phenyloxazol-4-yl)phenyl benzoate
(3g). Brown solid (30.6 mg, 21% yield): Rf 0.29 (ethyl acetate/hexanes
1
1/20); mp 121.3−122.5 °C; H NMR (400 MHz, CDCl3, 25 °C) δ/
126.8, 121.0, 117.1, 116.5, 113.5; IR (KBr) ν
̃
(cm−1) 3084 (w), 1684 (s),
ppm 7.94−7.92 (m, 3H), 7.89 (d, 2H, J = 7.9 Hz), 7.59 (dd, 1H, J = 8.6
Hz, 2.4 Hz), 7.50 (t, 1H, J = 7.4 Hz), 7.43−7.29 (m, 7H), 6.60 (d, 1H, J =
3.3 Hz), 6.42 (dd, 1H, J = 3.3 Hz, 1.8 Hz); 13C NMR (100 MHz, CDCl3,
25 °C) δ/ppm 164.5, 160.1, 147.7, 143.3, 143.2, 139.7, 133.8, 133.4,
132.4, 131.1, 130.6, 130.1, 129.1, 128.6, 128.2, 126.8, 126.7, 126.4, 124.9,
1600 (w), 1455 (w), 1253 (s), 697 (w); MS (70 eV, EI) m/z (%) 503 [M
+2]+ (44), 501 [M]+ (53), 284 (8), 224 (27), 135 (53), 105 (100), 77
(34); HRMS (ESI) for C26H16BrNO3SNa, [M + Na]+ (523.9932),
found 523.9941.
118.8, 111.6, 109.3; IR (KBr) ν
̃
(cm−1) 3137 (w), 1730 (s), 1628 (m),
4-Methoxy-2-(5-(4-nitrophenyl)-2-phenyloxazol-4-yl)phenyl ben-
zoate (3i). Yellow solid (87.1 mg, 59% yield): Rf 0.25 (ethyl acetate/
hexanes 1/6); mp 158.8−159.2 °C; 1H NMR (400 MHz, CDCl3, 25 °C)
δ/ppm 8.13 (d, 2H, J = 8.9 Hz), 8.08−8.05 (m, 2H), 7.70 (dd, 2H, J =
8.2 Hz, 1.4 Hz), 7.67 (d, 2H, J = 9.0 Hz), 7.48−7.43 (m, 4H), 7.32 (d,
1H, J = 9.0 Hz), 7.25 (dd, 3H, J = 11.6 Hz, 4.2 Hz), 7.09 (dd, 1H, J = 8.9
Hz, 3.1 Hz), 3.87 (s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm
164.7, 161.4, 157.6, 147.0, 144.6, 142.0, 135.8, 134.4, 133.3, 131.0, 129.8,
129.0, 128.8, 128.2, 126.7, 126.6, 126.2, 125.8, 124.5, 123.9, 116.2, 115.7,
1507 (w), 1260 (s), 1205 (s), 708 (s); MS (70 eV, EI) m/z (%) 488 [M
+2]+ (88), 486 [M]+ (100), 353 (5), 105 (8), 77 (2); HRMS (ESI) for
C26H17BrNO4, [M + H]+ (486.0341), found 486.0337.
4-Bromo-2-(2,5-diphenyloxazol-4-yl)phenyl furan-2-carboxylate
(3g′). Yellow solid (45.1 mg, 31% yield): Rf 0.12 (ethyl acetate/hexanes
1
1/20); mp 175.4−176.7 °C; H NMR (400 MHz, CDCl3, 25 °C) δ/
ppm 8.07−8.04 (m, 2H), 7.91 (d, 1H, J = 2.4 Hz), 7.59 (dd, 1H, J = 8.7
Hz, 2.4 Hz), 7.53−7.50 (m, 2H), 7.46−7.44 (m, 4H), 7.35−7.30 (m,
3H), 7.26 (d, 1H, J = 8.7 Hz), 6.68 (d, 1H, J = 3.5 Hz), 6.35 (dd, 1H, J =
3.5 Hz, 1.7 Hz); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 160.3,
155.8, 147.3, 147.0, 146.7, 143.3, 134.0, 132.5, 130.9, 130.5, 128.8, 128.7,
128.6, 128.3, 127.8, 126.9, 126.4, 126.0, 124.9, 119.4, 119.3, 111.8; IR
55.8; IR (KBr) ν
̃
(cm−1) 3061 (w), 2931 (w), 1730 (s), 1600 (s), 1512
(s), 1341 (s), 1200 (s), 701 (s); MS (70 eV, EI) m/z (%) 492 [M]+ (21),
105 (100), 77 (61); HRMS (EI) for C29H20N2O6, [M]+ (492.1321),
found 492.1316.
(KBr) ν
̃
(cm−1) 3069 (w), 1749 (s), 1604 (w), 1550 (m), 1467 (m),
2-(5-(4-Bromophenyl)-2-phenyloxazol-4-yl)-4-methoxyphenyl
benzoate (3j). Yellow solid (102.4 mg, 65% yield): Rf 0.29 (ethyl
acetate/hexanes 1/6); mp 168.9−169.3 °C; 1H NMR (400 MHz,
CDCl3, 25 °C) δ/ppm 8.02 (dd, 2H, J = 7.6 Hz, 4.0 Hz), 7.70 (dd, 2H, J
= 8.4 Hz, 1.2 Hz), 7.46 (t, 1H, J = 7.4 Hz), 7.41−7.36 (m, 7H), 7.29−
7.24 (m, 4H), 7.03 (dd, 1H, J = 8.9 Hz, 3.1 Hz), 3.83 (s, 3H); 13C NMR
(100 MHz, CDCl3, 25 °C) δ/ppm 164.8, 160.3, 157.5, 145.8, 141.9,
133.2, 132.8, 131.7, 130.6, 129.9, 129.1, 128.7, 128.1, 127.5, 127.4, 126.8,
1288 (m), 1200 (s), 1070 (s), 701 (m); MS (70 eV, EI) m/z (%) 487 [M
+2]+ (25), 485 [M]+ (25), 105 (38), 95 (100), 77 (9); HRMS (EI) for
C26H16BrNO4, [M]+ (485.0263), found 485.0263.
N-Benzoyl-N-(5-bromo-2-phenylbenzofuran-3-yl)furan-2-carbox-
amide (4g). Brown solid (4.4 mg, 3% yield; in Table 1, entry 7) (82.9
mg, 57% yield; in Table 2, entry 5): Rf 0.07 (ethyl acetate/hexanes 1/
20); mp 176.3−176.8 °C; 1H NMR (400 MHz, CDCl3, 25 °C) δ/ppm
7.70−7.67 (m, 2H), 7.58 (d, 1H, J = 1.8 Hz), 7.51 (dd, 2H, J = 7.3 Hz, 1.0
Hz), 7.44−7.36 (m, 7H), 7.23 (td, 2H, J = 7.8 Hz, 1.1 Hz), 7.16 (d, 1H, J
= 3.6 Hz), 6.45 (dd, 1H, J = 3.6 Hz, 1.6 Hz); 13C NMR (100 MHz,
CDCl3, 25 °C) δ/ppm 171.8, 161.3, 152.9, 151.9, 147.0, 146.4, 133.8,
132.5, 129.9, 128.8, 128.4, 128.30, 128.26, 127.9, 126.7, 121.0, 119.7,
126.5, 126.0, 124.3, 122.6, 115.8, 115.5, 55.8; IR (KBr) ν
̃
(cm−1) 3015
(m), 2931 (m), 1737 (s), 1604 (s), 1482 (s), 1261 (s), 1192 (s), 712 (s),
690 (s); MS (70 eV, EI) m/z (%) 527 [M+2]+ (31), 525 [M]+ (31), 420
(4), 139 (6), 105 (100), 77 (70); HRMS (EI) for C29H20BrNO4, [M]+
(525.0576), found 525.0574.
116.9, 115.9, 113.4, 112.5; IR (KBr) ν
̃
(cm−1) 3113 (w), 1681 (s), 1593
(m), 1468 (m), 1262 (s), 694 (m); MS (70 eV, EI) m/z (%) 487 [M
+2]+ (22), 485 [M]+ (29), 105 (100), 77 (15); HRMS (ESI) for
C26H16BrNO4Na, [M + Na]+ (508.0160), found 508.0164.
4-Methoxy-2-(5-(4-methoxyphenyl)-2-phenyloxazol-4-yl)phenyl
benzoate (3k). White solid (65.8 mg, 46% yield): Rf 0.15 (ethyl acetate/
hexanes 1/10); mp 155.7−156.4 °C; 1H NMR (400 MHz, CDCl3, 25
°C) δ/ppm 8.01−7.99 (m, 2H), 7.75 (dd, 2H, J = 7.2 Hz, 1.1 Hz), 7.48−
7.45 (m, 3H), 7.40−7.38 (m, 3H), 7.28−7.24 (m, 4H), 7.00 (dd, 1H, J =
8.9 Hz, 3.1 Hz), 6.82 (d, 2H, J = 8.8 Hz), 3.82 (s, 3H), 3.80 (s, 3H); 13C
NMR (100 MHz, CDCl3, 25 °C) δ/ppm 164.9, 159.9, 159.5, 157.3,
146.9, 142.1, 133.0, 131.0, 130.1, 130.0, 129.4, 128.6, 128.0, 127.6, 127.2,
126.6, 126.2, 124.2, 121.2, 115.5, 115.4, 114.0, 55.7, 55.3; IR (KBr)
4-Bromo-2-(2-phenyl-5-(thiophen-2-yl)oxazol-4-yl)phenyl ben-
zoate (3h). White solid (31.6 mg, 21% yield): Rf 0.23 (ethyl acetate/
hexanes 1/20); mp 140.2−141.0 °C; 1H NMR (400 MHz, CDCl3, 25
°C) δ/ppm 7.97−7.95 (m, 2H), 7.90 (d, 1H, J = 2.4 Hz), 7.83 (dd, 2H, J
= 8.2 Hz, 1.3 Hz), 7.62 (dd, 1H, J = 8.8 Hz, 2.5 Hz), 7.49 (tt, 1H, J = 7.4
Hz, 1.1 Hz), 7.43−7.38 (m, 3H), 7.33−7.29 (m, 4H), 7.23 (dd, 1H, J =
3.8 Hz, 1.1 Hz), 7.04 (dd, 1H, J = 8.8 Hz, 5.0 Hz); 13C NMR (100 MHz,
CDCl3, 25 °C) δ/ppm 164.4, 159.9, 147.8, 143.2, 133.9, 133.4, 132.8,
130.6, 130.1, 129.5, 129.0, 128.8, 128.7, 128.3, 127.7, 127.2, 126.7, 126.5,
ν
̃
(cm−1) 3061 (w), 2939 (m), 2840 (m), 1737 (s), 1604 (s), 1486 (s),
1253 (s), 1029 (s), 693 (s); MS (70 eV, EI) m/z (%) 477 [M]+ (14), 372
(4), 226 (1), 198 (1), 135 (3), 105 (100), 77 (14); HRMS (EI) for
C30H23NO5, [M]+ (477.1576), found 477.1585.
126.4, 126.0, 125.1, 119.1; IR (KBr) ν
̃
(cm−1) 3069 (w), 1737 (s), 1604
N-Benzoyl-4-methoxy-N-(5-methoxy-2-phenylbenzofuran-3-yl)-
benzamide (4k). White solid (31.5 mg, 22% yield): Rf 0.10 (ethyl
acetate/hexanes 1/10); mp 73.1−73.9 °C; 1H NMR (400 MHz, CDCl3,
25 °C) δ/ppm 7.64−7.58 (m, 6H), 7.42−7.36 (m, 5H), 7.27 (t, 2H, J =
7.8 Hz), 6.93 (dd, 1H, J = 8.9 Hz, 2.5 Hz), 6.89 (d, 1H, J = 2.5 Hz), 6.75
(d, 2H, J = 8.8 Hz), 3.82 (s, 3H), 3.78 (s, 3H); 13C NMR (100 MHz,
CDCl3, 25 °C) δ/ppm 172.9, 172.1, 163.2, 156.7, 152.1, 148.2, 134.3,
132.3, 131.1, 129.3, 128.7, 128.6, 128.4, 128.3, 126.8, 126.6, 126.0, 117.8,
(w), 1478 (m), 1257 (s), 1200 (s), 1059 (m), 705 (s); MS (70 eV, EI)
m/z (%) 503 [M+2]+ (50), 501 [M]+ (50), 158 (11), 105 (100), 77
(81); HRMS (EI) for C26H16BrNO3S, [M]+ (501.0034), found
501.0030.
4-Bromo-2-(2,5-diphenyloxazol-4-yl)phenyl thiophene-2-carbox-
ylate (3h′). White solid (51.1 mg, 34% yield): Rf 0.18 (ethyl acetate/
hexanes 1/20); mp 164.6−165.2 °C; 1H NMR (400 MHz, CDCl3, 25
°C) δ/ppm 8.04 (dd, 2H, J = 9.7 Hz, 6.1 Hz), 7.89 (d, 1H, J = 2.4 Hz),
7.59 (dd, 1H, J = 8.7 Hz, 2.5 Hz), 7.53−7.50 (m, 2H), 7.47 (dd, 1H, J =
4.9 Hz, 1.2 Hz), 7.45−7.43 (m, 3H), 7.41 (dd, 1H, J = 3.5 Hz, 1.1 Hz),
7.33−7.27 (m, 4H), 6.94 (dd, 1H, J = 8.7 Hz, 4.9 Hz); 13C NMR (100
MHz, CDCl3, 25 °C) δ/ppm 160.3, 159.6, 147.3, 147.2, 134.6, 133.9,
133.5, 132.5, 132.2, 131.0, 130.5, 128.8, 128.7, 128.6, 128.2, 127.9, 127.5,
113.7, 112.5, 100.9, 56.0, 55.4; IR (KBr) ν
̃
(cm−1) 3061 (w), 2931 (w),
1691 (s), 1604 (m), 1482 (m), 1250 (s), 1170 (m), 697 (m); MS (70
eV, EI) m/z (%) 477 [M]+ (37), 343 (10), 135 (100), 105 (40), 77 (17);
HRMS (MALDI) for C30H24NO5, [M + H]+ (478.1654), found
478.1667.
2-(5-(Furan-2-yl)-2-phenyloxazol-4-yl)-4-methoxyphenyl ben-
zoate (3l). Brown solid (74.7 mg, 57% yield): Rf 0.29 (ethyl acetate/
hexanes 1/20); mp 130.6 °C; 1H NMR (400 MHz, CDCl3, 25 °C) δ/
ppm 7.92 (td, 4H, J = 7.6 Hz, 1.3 Hz), 7.48 (t, 1H, J = 7.5 Hz), 7.41−7.30
(m, 8H), 7.02 (dd, 1H, J = 8.9 Hz, 3.1 Hz), 6.60 (d, 1H, J = 3.1 Hz), 6.42
(dd, 1H, J = 3.4 Hz, 1.8 Hz), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3,
25 °C) δ/ppm 165.1, 159.8, 157.0, 143.5, 143.0, 142.2, 139.3, 133.1,
127.0, 126.4, 125.9, 125.0, 119.3; IR (KBr) ν
̃
(cm−1) 3061 (w), 1730 (s),
1604 (w), 1478 (m), 1200 (s), 701 (m); MS (70 eV, EI) m/z (%) 503
[M+2]+ (42), 501 [M]+ (42), 111 (100), 77 (27); HRMS (EI) for
C26H16BrNO3S, [M]+ (501.0034), found 501.0037.
N-Benzoyl-N-(5-bromo-2-phenylbenzofuran-3-yl)thiophene-2-
carboxamide (4h). White solid (1.5 mg, 1% yield): Rf 0.10 (ethyl
G
dx.doi.org/10.1021/jo502232q | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
132.4, 130.4, 130.0, 129.5, 128.6, 128.1, 126.8, 126.4, 125.3, 124.0, 115.5,
20); mp 104.5−105.0 °C; 1H NMR (400 MHz, CDCl3, 25 °C) δ/ppm
8.10 (dd, 2H, J = 8.5 Hz, 1.3 Hz), 7.89 (dd, 2H, J = 8.8 Hz, 1.3 Hz), 7.75
(d, 1H, J = 2.4 Hz), 7.65 (dd, 1H, J = 8.7 Hz, 2.4 Hz), 7.56 (t, 1H, J = 7.4
Hz), 7.47 (t, 1H, J = 7.4 Hz), 7.43−7.36 (m, 4H), 7.28 (d, 1H, J = 8.7
Hz); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 164.5, 162.2, 148.0,
137.3 (quart, J = 2.1 Hz), 135.3 (quart, J = 42.7 Hz), 133.80, 133.76,
133.7, 131.7, 130.3, 128.8, 128.5, 127.0, 125.5, 125.1, 124.7, 119.2
115.4, 111.5, 109.2, 55.7; IR (KBr) ν
̃
(cm−1) 3145 (w), 1730 (s), 1601
(m), 1500 (m), 1262 (s), 1194 (s); MS (70 eV, EI) m/z (%) 437 [M]+
(30), 332 (12), 105 (100), 77 (36); HRMS (EI) for C27H19NO5, [M]+
(437.1263), found 437.1258.
2-(2,5-Diphenyloxazol-4-yl)-4-methoxyphenyl furan-2-carboxy-
late (3l′). White solid (5.2 mg, 4% yield): Rf 0.12 (ethyl acetate/
hexanes 1/20); mp 176.0−176.3 °C; 1H NMR (400 MHz, CDCl3, 25
°C) δ/ppm 8.06 (dd, 2H, J = 6.4 Hz, 2.8 Hz), 7.56 (dd, 2H, J = 7.9 Hz,
1.8 Hz), 7.46−7.43 (m, 4H), 7.35−7.24 (m, 5H), 7.01 (dd, 1H, J = 8.9
Hz, 3.0 Hz), 6.70 (d, 1H, J = 3.4 Hz), 6.35 (dd, 1H, J = 3.5 Hz, 1.7 Hz),
3.83 (s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 160.1, 157.5,
156.6, 146.9, 146.7, 143.8, 141.2, 130.5, 128.7, 128.6, 128.50, 128.46,
126.5, 126.1, 124.2, 118.8, 115.8, 115.5, 111.7, 55.8; MS (70 eV, EI) m/z
(%) 437 [M]+ (100), 358 (8), 342 (17), 314 (7), 237 (11), 168 (8), 150
(37), 121 (5), 105 (50), 95 (44), 77 (13); HRMS (MALDI) for
C27H20NO5, [M + H]+ (438.1336), found 438.1336.
(quart, J = 268.4 Hz), 118.9; IR (KBr) ν
̃
(cm−1) 3053 (w), 1737 (s),
1608 (m), 1486 (m), 1417 (s), 1368 (s), 1124 (s), 697 (s); MS (70 eV,
EI) m/z (%) 489 [M+2]+ (24), 487 [M]+ (29), 105 (100), 77 (13);
HRMS (FAB) for C23H14BrF3NO3, [M + H]+ (488.0109), found
488.0102.
N-(5-Bromo-2-phenylbenzofuran-3-yl)-N-pivaloylbenzamide
(4o). White solid (109.7 mg, 77% yield; in Table 1, entry 16) (109.7 mg,
77% yield; in Table 3, entry 1) (57.0 mg, 40% yield; in Table 3, entry 8):
1
Rf 0.38 (ethyl acetate/hexanes 1/20); mp 149.5−150.7 °C; H NMR
(400 MHz, CDCl3, 25 °C) δ/ppm 7.61−7.58 (m, 2H), 7.55 (d, 1H, J =
1.8 Hz), 7.43−7.40 (m, 4H), 7.35−7.32 (m, 4H), 7.17 (t, 2H, J = 7.8
Hz), 1.39 (s, 9H); 13C NMR (125 MHz, CDCl3, 25 °C) δ/ppm 185.9,
173.0, 153.3, 151.8, 133.9, 132.2, 129.9, 128.8, 128.5, 128.2, 128.1, 128.0,
4-Methoxy-2-(2-phenyl-5-(thiophen-2-yl)oxazol-4-yl)phenyl ben-
zoate (3m). Yellow solid (81.6 mg, 60% yield): Rf 0.31 (ethyl acetate/
hexanes 1/20); mp 107.2−108.4 °C; 1H NMR (400 MHz, CDCl3, 25
°C) δ/ppm 7.97−7.94 (m, 2H), 7.86 (d, 2H, J = 7.4 Hz), 7.46 (t, 1H, J =
7.4 Hz), 7.40−7.36 (m, 3H), 7.32−7.24 (m, 6H), 7.05−7.00 (m, 2H),
3.83 (s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 165.0, 159.6,
157.2, 142.8, 142.2, 133.1, 131.8, 130.3, 130.0, 129.7, 129.4, 128.6, 128.1,
127.6, 126.8, 126.3, 126.1, 125.7, 125.6, 124.2, 115.8, 115.4, 55.7; IR
127.9, 126.9, 120.8, 116.9, 116.5, 113.5, 43.5, 28.7; IR (KBr) ν
̃
(cm−1)
3061 (w), 2961 (m), 1678 (s), 1600 (m), 1508 (w), 1451 (m), 1258 (s),
698 (s); MS (70 eV, EI) m/z (%) 477 [M+2]+ (72), 476 [M]+ (72), 393
(76), 105 (100), 77 (20), 57 (21); HRMS (ESI) for C26H23BrNO3, [M
+ H]+ (476.0861), found 476.0862.
(KBr) ν
̃
(cm−1) 3065 (m), 2944 (m), 1738 (s), 1581 (m), 1492 (s), 1246
Typical Procedure for the Preparation of Benzofurans 4
(Table 2). A flame-dried and nitrogen-flushed 10 mL Schlenk tube,
equipped with a magnetic stirring bar and a septum, was charged with a
solution of 1 (0.3 mmol) in anhydrous dichloromethane (1.5 mL). To
this reaction mixture, Bu3P (82 μL, 1.1 equiv) was added and stirred for
30 min. Acyl chloride 2 (0.3 mmol) and Et3N (46 μL, 1.1 equiv) were
added in sequence, and the resulting reaction mixture was further stirred
for 1 h at room temperature (monitored by 1H NMR data analysis). The
solvent was removed by evaporation in vacuo. Purification by flash
chromatography furnished the desired adduct 4.
Typical Procedure for the Preparation of Benzofuran 8a
Using PBu3 (Scheme 2). A flame-dried and nitrogen-flushed 10 mL
Schlenk tube, equipped with a magnetic stirring bar and a septum, was
charged with a solution of 1a (0.2 mmol) in anhydrous dichloromethane
(1.0 mL). To this stirred reaction mixture, Bu3P (55 μL, 1.1 equiv) was
added for 20 h at 40 °C. At this point, the solvent was removed under
reduced pressure and to the resulting white solid. This resulted in a
suspension that was filtered and washed with hexanes (3 × 10 mL) and
dichloromethane (3 × 5 mL). The benzofuran product 8a was dried in
vacuo and used without further purification.
Typical Procedure for the Preparation of Benzofuran 4a
(Scheme 2). A flame-dried and nitrogen-flushed 10 mL Schlenk tube,
equipped with a magnetic stirring bar and a septum, was charged with a
solution of 8a (0.1 mmol) in anhydrous dichloromethane (0.2 mL). To
this stirred reaction mixture, Bu3P (2.5 μL, 0.1 equiv), benzoyl chloride
2a (13 μL, 1.1 equiv) and Et3N (15 μL, 1.1 equiv) were added in
sequence. The reaction mixture was further stirred for 1 h at room
temperature and was monitored by 1H NMR data analysis. The solvent
was removed by evaporation in vacuo. Purification by flash
chromatography furnished the desired adduct 4a.
(s); MS (70 eV, EI) m/z (%) 453 [M]+ (41), 348 (8), 111 (18), 105
(100), 77 (48); HRMS (EI) for C27H19NO4S, [M]+ (453.1035), found
453.1026.
N-Benzoyl-N-(5-methoxy-2-phenylbenzofuran-3-yl)thiophene-2-
carboxamide (4m). Yellow solid (6.8 mg, 5% yield): Rf 0.13 (ethyl
1
acetate/hexanes 1/20); mp 168.7−169.1 °C; H NMR (400 MHz,
CDCl3, 25 °C) δ/ppm 7.71 (td, 4H, J = 7.9 Hz, 1.6 Hz), 7.56 (dd, 1H, J =
3.9 Hz, 1.3 Hz), 7.47−7.45 (m, 2H), 7.43−7.32 (m, 6H), 6.95−6.89 (m,
3H), 3.80 (s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 172.7,
165.4, 156.8, 152.4, 148.1, 136.4, 134.4, 134.0, 133.6, 132.4, 129.5, 128.8,
128.51, 128.48, 128.45, 127.5, 127.2, 126.5, 117.2, 114.1, 112.6, 100.7,
56.0; IR (KBr) ν
̃
(cm−1) 3061 (w), 2924 (s), 1691 (s), 1600 (m), 1482
(s), 1246 (s), 1109 (m), 693 (m); MS (70 eV, EI) m/z (%) 453 [M]+
(42), 167 (9), 149 (17), 111 (42), 105 (100), 77 (17); HRMS (MALDI)
for C27H20NO4S, [M + H]+ (454.1113), found 454.1123.
2-(5-(2-Bromophenyl)-2-phenyloxazol-4-yl)-4-methoxyphenyl
benzoate (3n). Colorless oil (77.2 mg, 49% yield): Rf 0.36 (ethyl
1
acetate/hexanes 1/6); H NMR (400 MHz, CDCl3, 25 °C) δ/ppm
7.94−7.89 (m, 4H), 7.56−7.52 (m, 2H), 7.41−7.32 (m, 6H), 7.24−7.15
(m, 3H), 7.07 (d, 1H, J = 3.0 Hz), 6.94 (dd, 1H, J = 8.9 Hz, 3.1 Hz), 3.73
(s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 165.2, 160.7,
157.1, 145.6, 141.9, 134.9, 133.6, 133.1, 131.8, 130.5, 130.3, 130.2, 130.1,
129.5, 128.6, 128.1, 127.4, 127.1, 126.4, 125.7, 124.1, 123.1, 115.3, 114.8,
55.5; MS (70 eV, EI) m/z (%) 527 [M+2]+ (46), 525 [M]+ (54), 341
(17), 298 (13), 185 (5), 139 (9), 125 (19), 105 (100), 77 (6); HRMS
(MALDI) for C29H21BrNO4, [M + H]+ (526.0648), found 526.0637.
N-Benzoyl-2-bromo-N-(5-methoxy-2-phenylbenzofuran-3-yl)-
benzamide (4n). White solid (9.5 mg, 6% yield): Rf 0.31 (ethyl acetate/
hexanes 1/6); mp 162.8−163.1 °C; 1H NMR (400 MHz, CDCl3, 25 °C)
δ/ppm 7.60 (dd, 1H, J = 7.7 Hz, 1.6 Hz), 7.57 (dd, 1H, J = 8.0 Hz, 0.9
Hz), 7.50−7.47 (m, 2H), 7.42−7.36 (m, 5H), 7.31 (dd, 1H, J = 7.8 Hz,
1.8 Hz), 7.26 (dt, 3H, J = 8.8 Hz, 1.6 Hz), 7.22 (d, 1H, J = 2.5 Hz), 7.05
(t, 2H, J = 7.9 Hz), 6.96 (dd, 1H, J = 8.9 Hz, 2.6 Hz), 3.90 (s, 3H); 13C
NMR (100 MHz, CDCl3, 25 °C) δ/ppm 171.2, 170.2, 156.6, 152.1,
148.2, 137.7, 133.2, 133.1, 132.2, 131.4, 129.6, 129.4, 128.8, 128.5, 128.4,
127.7, 127.6, 126.7, 126.4, 118.7, 117.0, 114.2, 112.6, 102.0, 56.0; IR
Typical Procedure for the Preparation of Trifluoromethyl-
Substituted Oxazoles (3o−y) (Scheme 4). A flame-dried and
nitrogen-flushed 10 mL Schlenk tube, equipped with a magnetic stirring
bar and a septum, was charged with a solution of 1 (0.3 mmol) and PPh3
(87.4 mg, 1.1 equiv) in anhydrous toluene (1.5 mL). To this stirred
reaction mixture, TFAA 2h (46 μL, 1.1 equiv) and Et3N (54 μL, 1.3
equiv) were added in sequence. The reaction mixture was further stirred
1
(KBr) ν
̃
(cm−1) 3048 (w), 2919 (m), 1694 (s), 1597 (w), 1480 (m),
for the indicated time at room temperature (monitored by H NMR
1266 (s), 1250 (s), 690 (m); MS (70 eV, EI) m/z (%) 527 [M+2]+ (30),
525 [M]+ (30), 421 (10), 342 (12), 238 (14), 183 (98), 149 (10), 105
(100), 77 (8); HRMS (EI) for C29H20BrNO4, [M]+ (525.0576), found
525.0574.
data analysis). The solvent was removed by evaporation in vacuo.
Purification by flash chromatography furnished the desired adduct 3.
4-Chloro-2-(2-phenyl-5-(trifluoromethyl)oxazol-4-yl)phenyl ben-
zoate (3p). White solid (113.0 mg, 85% yield): Rf 0.48 (ethyl acetate/
hexanes 1/10); mp 76.1−77.3 °C; 1H NMR (400 MHz, CDCl3, 25 °C)
δ/ppm 8.10 (dd, 2H, J = 8.5 Hz, 1.3 Hz), 7.88 (dd, 2H, J = 8.6 Hz, 1.4
Hz), 7.60 (d, 1H, J = 2.4 Hz), 7.55 (t, 1H, J = 7.5 Hz), 7.50 (dd, 1H, J =
4-Bromo-2-(2-phenyl-5-(trifluoromethyl)oxazol-4-yl)phenyl ben-
zoate (3o). White solid (112.5 mg, 77% yield; in Table 1, entry 15)
(112.5 mg, 77% yield; in Scheme 4): Rf 0.25 (ethyl acetate/hexanes 1/
H
dx.doi.org/10.1021/jo502232q | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
8.8 Hz, 2.6 Hz), 7.48−7.35 (m, 5H), 7.33 (d, 1H, J = 8.7 Hz); 13C NMR
(100 MHz, CDCl3, 25 °C) δ/ppm 164.6, 162.2, 147.5, 137.5 (quart, J =
2.1 Hz), 135.2 (quart, J = 42.7 Hz), 133.6, 131.7, 131.4, 130.8, 130.3,
128.9, 128.8, 128.5, 127.0, 125.5, 124.8, 124.3, 119.2 (quart, J = 268.4
113.6, 55.7, 55.4; IR (KBr) ν
̃
(cm−1) 3008 (w), 2927 (m), 1734 (s), 1601
(s), 1512 (s), 1375 (s); MS (70 eV, EI) m/z (%) 469 [M]+ (32), 135
(100), 77 (2); HRMS (MALDI) for C25H19F3NO5, [M + H]+
(470.1215), found 470.1226.
Hz); IR (KBr) ν
̃
(cm−1) 3061 (m), 1741 (s), 1600 (m), 1558 (m), 1421
4-Chloro-2-(2-phenyl-5-(trifluoromethyl)oxazol-4-yl)phenyl 4-
bromobenzoate (3v). White solid (85.4 mg, 82% yield): Rf 0.51
(ethyl acetate/hexanes 1/20); mp 161.5−161.8 °C; H NMR (400
(s), 1124 (s), 693 (s); MS (70 eV, EI) m/z (%) 445 [M+2]+ (15), 443
[M]+ (45), 338 (11), 243 (17), 213 (12), 110 (87), 105 (99), 77 (100);
HRMS (EI) for C23H13ClF3NO3, [M]+ (443.0536), found 443.0544.
2-(2-Phenyl-5-(trifluoromethyl)oxazol-4-yl)phenyl 4-bromoben-
zoate (3q). White solid (121.3 mg, 83% yield): Rf 0.25 (ethyl acetate/
hexanes 1/20); mp 105.4−105.7 °C; 1H NMR (400 MHz, CDCl3, 25
°C) δ/ppm 7.97 (d, 2H, J = 8.5 Hz), 7.83 (d, 2H, J = 7.3 Hz), 7.60 (d,
1H, J = 7.5 Hz), 7.52−7.50 (m, 3H), 7.42 (t, 1H, J = 7.3 Hz), 7.38−7.33
(m, 4H); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 164.1, 161.8,
148.7, 138.7 (quart, J = 2.1 Hz), 134.8 (quart, J = 42.5 Hz), 131.7,
131.63, 131.55, 131.0 (quart, J = 1.4 Hz), 130.9, 128.7, 128.6, 128.2,
126.8, 126.1, 125.5, 123.3, 122.4, 119.3 (quart, J = 268.3 Hz); IR (KBr)
1
MHz, CDCl3, 25 °C) δ/ppm 7.95 (d, 2H, J = 8.5 Hz), 7.88 (dd, 2H, J =
8.6 Hz, 1.4 Hz), 7.60 (d, 1H, J = 2.5 Hz), 7.56 (d, 2H, J = 8.6 Hz), 7.52−
7.48 (m, 2H), 7.41 (t, 2H, J = 7.7 Hz), 7.32 (d, 1H, J = 8.8 Hz); 13C
NMR (100 MHz, CDCl3, 25 °C) δ/ppm 164.0, 162.2, 147.2, 137.3
(quart, J = 2.2 Hz), 135.2 (quart, J = 42.8 Hz), 131.9, 131.7, 131.6, 130.9,
129.0, 128.9, 127.8, 127.0, 125.4, 124.7, 124.1, 119.1 (quart, J = 268.4
Hz); IR (KBr) ν
̃
(cm−1) 3065 (w), 1738 (s), 1589 (m), 1484 (m), 1419
(m), 1367 (m), 1125 (s), 835 (m), 714 (m); MS (70 eV, EI) m/z (%)
523 [M+2]+ (36), 521 [M]+ (28), 310 (5), 241 (10), 186 (8), 185 (100),
157 (19), 105 (5); HRMS (MALDI) for C23H12BrClF3NO3Na, [M +
Na]+ (543.9539), found 543.9552.
ν
̃
(cm−1) 3069 (w), 1741 (s), 1589 (m), 1486 (m), 1387 (s), 1261 (s),
1070 (s), 709 (m); MS (70 eV, EI) m/z (%) 489 [M+2]+ (13), 487 [M]+
(13), 207 (31), 183 (100), 157 (48), 105 (37), 77 (24); HRMS (EI) for
C23H13BrF3NO3, [M]+ (487.0031), found 487.0035.
4-Methoxy-2-(2-phenyl-5-(trifluoromethyl)oxazol-4-yl)phenyl 4-
bromobenzoate (3w). Yellow solid (122.5 mg, 79% yield): Rf 0.13
(ethyl acetate/hexanes 1/25); mp 102.0−102.9 °C; H NMR (400
1
MHz, CDCl3, 25 °C) δ/ppm 7.96 (d, 2H, J = 8.5 Hz), 7.86 (dd, 2H, J =
8.5 Hz, 1.2 Hz), 7.54 (d, 2H, J = 8.6 Hz), 7.47 (t, 1H, J = 7.3 Hz), 7.39 (t,
2H, J = 7.8 Hz), 7.27 (d, 1H, J = 8.9 Hz), 7.12 (d, 1H, J = 2.9 Hz), 7.07
(dd, 1H, J = 8.9 Hz, 3.0 Hz), 3.86 (s, 3H); 13C NMR (100 MHz, CDCl3,
25 °C) δ/ppm 164.6, 161.9, 157.2, 142.1, 138.6 (quart, J = 2.2 Hz),
134.9 (quart, J = 42.6 Hz), 131.8, 131.70, 131.68, 128.8, 128.6, 128.4,
126.9, 125.6, 124.2, 123.1, 119.3 (quart, J = 268.3 Hz), 116.5, 115.7
4-Methoxy-2-(2-phenyl-5-(trifluoromethyl)oxazol-4-yl)phenyl
benzoate (3r). White solid (105.4 mg, 80% yield): Rf 0.15 (ethyl
acetate/hexanes 1/20); mp 93.8−94.7 °C; 1H NMR (400 MHz, CDCl3,
25 °C) δ/ppm 8.12 (dd, 2H, J = 8.0 Hz, 1.4 Hz), 7.86 (dd, 2H, J = 8.7 Hz,
1.4 Hz), 7.52 (t, 1H, J = 7.4 Hz), 7.45−7.33 (m, 5H), 7.28 (d, 1H, J = 8.9
Hz), 7.12 (d, 1H, J = 3.0 Hz), 7.06 (dd, 1H, J = 8.9 Hz, 3.0 Hz), 3.84 (s,
3H); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 165.2, 161.9, 157.1,
142.4, 138.7 (quart, J = 2.3 Hz), 134.9 (quart, J = 42.5 Hz), 133.3, 131.5,
130.2, 129.5, 128.7, 128.3, 126.9, 125.7, 124.2, 123.2, 119.4 (quart, J =
(quart, J = 1.3 Hz), 55.7; IR (KBr) ν
̃
(cm−1) 3073 (w), 2927 (w), 1742
(s), 1605 (m), 1492 (s), 1198 (s), 685 (m); MS (70 eV, EI) m/z (%)
519 [M+2]+ (35), 517 [M]+ (35), 334 (6), 306 (7), 183 (100), 157 (35),
105 (23), 76 (14); HRMS (ESI) for C24H16BrF3NO4, [M + H]+
(518.0215), found 518.0220.
268.2 Hz), 116.4, 115.7, 55.7; IR (KBr) ν
̃
(cm−1) 3069 (w), 1749 (s),
1608 (m), 1497 (m), 1379 (s), 1200 (s), 701 (m); MS (70 eV, EI) m/z
(%) 439 [M]+ (17), 105 (99), 77 (100); HRMS (EI) for C24H16F3NO4,
[M]+ (439.1031), found 439.1030.
4-Bromo-2-(2-phenyl-5-(trifluoromethyl)oxazol-4-yl)phenyl thio-
phene-2-carboxylate (3x). Yellow solid (110.9 mg, 75% yield): Rf 0.35
2-(2-Phenyl-5-(trifluoromethyl)oxazol-4-yl)phenyl 4-chloroben-
zoate (3s). White solid (91.7 mg, 69% yield): Rf 0.26 (ethyl acetate/
hexanes 1/20); mp 91.0−92.0 °C; 1H NMR (400 MHz, CDCl3, 25 °C)
δ/ppm 8.06 (d, 2H, J = 8.6 Hz), 7.85 (dd, 2H, J = 8.7 Hz, 1.4 Hz), 7.61
(d, 1H, J = 7.6 Hz), 7.54 (td, 1H, J = 7.8 Hz, 1.7 Hz), 7.46 (t, 1H, J = 7.4
Hz), 7.40−7.36 (m, 6H); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm
164.0, 161.9, 148.7, 140.0, 138.7 (quart, J = 2.2 Hz), 134.9 (quart, J =
42.5 Hz), 131.63, 131.60, 131.1 (quart, J = 1.2 Hz), 131.0. 128.8, 127.8,
126.9, 126.1, 125.6, 123.4, 122.5, 119.3 (quart, J = 268.1 Hz); IR (KBr)
1
(ethyl acetate/hexanes 1/10); mp 108.2−109.8 °C; H NMR (400
MHz, CDCl3, 25 °C) δ/ppm 7.92−7.88 (m, 3H), 7.73 (d, 1H, J = 2.4
Hz), 7.63 (dd, 1H, J = 8.5 Hz, 2.4 Hz), 7.56 (dd, 1H, J = 4.9 Hz, 1.0 Hz),
7.46 (t, 1H, J = 7.3 Hz), 7.39 (t, 2H, J = 7.8 Hz), 7.28 (d, 1H, J = 8.7 Hz),
7.07 (dd, 1H, J = 8.7 Hz, 4.9 Hz); 13C NMR (100 MHz, CDCl3, 25 °C)
δ/ppm 162.2, 159.8, 147.6, 137.2 (quart, J = 2.2 Hz), 135.2 (quart, J =
42.6 Hz), 135.0, 133.9, 133.73, 133.66, 132.1, 131.7, 128.8, 127.9, 127.0,
125.5, 125.0, 124.6, 119.1 (quart, J = 268.4 Hz), 119.0; IR (KBr)
ν
̃
(cm−1) 3065 (w), 1746 (s), 1593 (m), 1484 (m), 1387 (s), 1165 (s),
ν
̃
(cm−1) 3089 (w), 1730 (s), 1609 (s), 1556 (s), 1415 (s), 1367 (s), 710
746 (m); MS (70 eV, EI) m/z (%) 445 [M+2]+ (15), 443 [M]+ (48),
304 (11), 256 (7), 207 (18), 183 (12), 152 (7), 139 (100), 111 (11);
HRMS (MADLI) for C23H14ClF3NO3, [M + H]+ (444.0609), found
444.0604.
(s); HRMS (MALDI) for C21H11BrF3NO3SNa, [M + Na]+ (515.9493),
found 515.9504.
4-Bromo-2-(2-phenyl-5-(trifluoromethyl)oxazol-4-yl)phenyl cy-
clohexanecarboxylate (3y). Colorless oil (130.2 mg, 88% yield): Rf
0.39 (ethyl acetate/hexanes 1/20); 1H NMR (400 MHz, CDCl3, 25 °C)
δ/ppm 8.11 (dd, 2H, J = 8.4 Hz, 1.6 Hz), 7.66 (d, 1H, J = 2.3 Hz), 7.59
(dd, 1H, J = 8.8 Hz, 2.5 Hz), 7.57−7.48 (m, 3H), 7.11 (d, 1H, J = 8.7
Hz), 2.44 (tt, 1H, J = 11.1 Hz, 3.6 Hz), 1.90−1.87 (m, 2H), 1.70−1.65
(m, 2H), 1.60−1.56 (m, 1H), 1.43 (qd, 2H, J = 11.4 Hz, 3.1 Hz), 1.28−
1.10 (m, 3H); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 173.5, 162.2,
148.0, 137.3 (quart, J = 1.9 Hz), 135.4 (quart, J = 42.7 Hz), 133.7, 131.9,
129.0, 127.1, 125.6, 124.8, 124.6, 119.1 (quart, J = 268.3 Hz), 118.5;
HRMS (ESI) for C23H19BrF3NO3Na, [M + Na]+ (516.0393), found
516.0378.
Typical Procedure for the Preparation of Benzofurans (4o−t′)
(Table 3). A flame-dried and nitrogen-flushed 10 mL Schlenk tube,
equipped with a magnetic stirring bar and a septum, was charged with a
solution of 1 (1.2 equiv) in anhydrous dichloromethane (0.6 mL). To
this stirred reaction mixture, Bu3P (82 μL, 1.1 equiv), pivaloyl chloride
2i (37 μL, 0.3 mmol) and Et3N (46 μL, 1.1 equiv) were added in
sequence. The reaction mixture was further stirred for the indicated time
at room temperature and was monitored by 1H NMR data analysis. The
solvent was removed by evaporation in vacuo. Purification by flash
chromatography furnished the desired adduct 4.
2-(2-Phenyl-5-(trifluoromethyl)oxazol-4-yl)phenyl 4-methoxy-
benzoate (3t). Yellow oil (77.7 mg, 59% yield): Rf 0.12 (ethyl
1
acetate/hexanes 1/20); H NMR (400 MHz, CDCl3, 25 °C) δ/ppm
8.07 (d, 2H, J = 8.8 Hz), 7.90 (dd, 2H, J = 8.7 Hz, 1.4 Hz), 7.60 (d, 1H, J
= 7.6 Hz), 7.54 (td, 1H, J = 7.9 Hz, 1.6 Hz), 7.46 (t, 1H, J = 7.5 Hz),
7.40−7.35 (m, 4H), 6.88 (d, 2H, J = 8.9 Hz), 3.82 (s, 3H); 13C NMR
(100 MHz, CDCl3, 25 °C) δ/ppm 164.5, 163.8, 161.9, 149.1, 138.8
(quart, J = 2.2 Hz), 134.9 (quart, J = 42.5 Hz), 132.4, 131.5, 131.0, 130.9,
128.7, 127.0, 125.8, 123.5, 122.7, 121.7, 119.4 (quart, J = 268.2 Hz),
113.7, 55.4; MS (70 eV, EI) m/z (%) 439 [M]+ (12), 135 (100), 107
(17), 77 (23); HRMS (EI) for C24H16F3NO4, [M]+ (439.1031), found
439.1024.
4-Methoxy-2-(2-phenyl-5-(trifluoromethyl)oxazol-4-yl)phenyl 4-
methoxybenzoate (3u). White solid (81.6 mg, 58% yield): Rf 0.38
(ethyl acetate/hexanes 1/4); mp 106.1−106.3 °C; 1H NMR (400 MHz,
CDCl3, 25 °C) δ/ppm 8.06 (d, 2H, J = 8.8 Hz), 7.91 (dd, 2H, J = 8.6 Hz,
1.4 Hz), 7.47 (t, 1H, J = 7.4 Hz), 7.39 (t, 2H, J = 7.8 Hz), 7.27 (d, 1H, J =
8.9 Hz), 7.11 (d, 1H, J = 3.0 Hz), 7.06 (dd, 1H, J = 8.9 Hz, 3.1 Hz), 6.88
(d, 2H, J = 9.0 Hz), 3.86 (s, 3H), 3.82 (s, 3H); 13C NMR (100 MHz,
CDCl3, 25 °C) δ/ppm 164.9, 163.7, 161.9, 157.0, 142.5, 138.7 (quart, J =
2.3 Hz), 134.9 (quart, J = 42.5 Hz), 132.3, 131.5, 128.7, 127.0, 125.8,
124.3, 123.3, 121.7, 119.3 (quart, J = 268.2 Hz), 116.5, 115.58, 115.57,
N-(5-Chloro-2-phenylbenzofuran-3-yl)-N-pivaloylbenzamide
(4p). White solid (89.2 mg, 69% yield): Rf 0.3 (ethyl acetate/hexanes 1/
I
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The Journal of Organic Chemistry
Article
20); mp 148.5−149.0 °C; 1H NMR (400 MHz, CDCl3, 25 °C) δ/ppm
7.61−7.58 (m, 2H), 7.43−7.40 (m, 4H), 7.37−7.33 (m, 4H), 7.28 (dd,
1H, J = 8.8 Hz, 2.1 Hz), 7.17 (t, 2H, J = 7.8 Hz), 1.40 (s, 9H); 13C NMR
(100 MHz, CDCl3, 25 °C) δ/ppm 185.9, 173.0, 153.5, 151.4, 134.0,
132.2, 129.9, 129.5, 128.8, 128.1, 128.0, 127.9, 126.9, 125.5, 117.7, 116.7,
N-(5-Bromo-2-phenylbenzofuran-3-yl)benzamide (8a). White
solid (39.1 mg, 3% yield): mp 256.4−257.0 °C; H NMR (400 MHz,
1
DMSO-d6, 25 °C) δ/ppm 10.44 (s, 1H), 8.01 (d, 2H, J = 7.4 Hz), 7.91
(d, 2H, J = 7.6 Hz), 7.68−7.64 (m, 3H), 7.59 (t, 2H, J = 7.6 Hz), 7.55−
7.51 (m, 3H), 7.44 (t, 1H, J = 7.3 Hz); 13C NMR (100 MHz, DMSO-d6,
25 °C) δ/ppm 166.6, 151.6, 149.6, 134.0, 132.5, 129.8, 129.7, 129.5,
129.4, 129.1, 128.4, 128.2, 126.3, 123.0, 115.9, 115.4, 114.0; IR (KBr)
113.0, 43.5, 28.7; IR (KBr) ν
̃
(cm−1) 2960 (m), 1681 (s), 1597 (w), 1440
(m), 1262 (s), 1133 (s), 685 (m); MS (70 eV, EI) m/z (%) 433 [M+2]+
(24), 431 [M]+ (47), 349 (5), 347 (14), 105 (100), 77 (36), 57 (37);
HRMS (EI) for C26H22ClNO3, [M]+ (431.1288), found 431.1291.
N-(5-Methoxy-2-phenylbenzofuran-3-yl)-N-pivaloylbenzamide
(4q). White solid (101.2 mg, 79% yield): Rf 0.55 (ethyl acetate/hexanes
ν
̃
(cm−1) 3252 (s), 3023 (m), 2954 (m), 1688 (m), 1650 (s), 1528 (s),
1444 (s), 1208 (m), 804 (m), 709 (s), 690 (s); MS (70 eV, EI) m/z (%)
393 [M+2]+ (57), 391 [M]+ (83), 288 (7), 208 (3), 207 (11), 179 (18),
152 (11), 105 (100), 77 (80); HRMS (EI) for C21H14BrNO2, [M]+
(391.0208), found 391.0202.
1
1/20); mp 135.0−135.9 °C; H NMR (400 MHz, CDCl3, 25 °C) δ/
Typical Procedure for the Preparation of Benzamide 8
(Scheme 5). A flame-dried and nitrogen-flushed 10 mL Schlenk tube,
equipped with a magnetic stirring bar and a septum, was charged with a
solution of 4 (0.1 mmol) in HCl/1,4-dioxane (0.5 mL). The reaction
mixture was stirred for indicated time at room temperature. The solvent
was removed by evaporation in vacuo to afford 8.
ppm 7.59 (dd, 2H, J = 8.1 Hz, 1.5 Hz), 7.42−7.30 (m, 7H), 7.14 (t, 2H, J
= 7.6 Hz), 6.92−6.88 (m, 2H), 3.84 (s, 3H), 1.41 (s, 9H); 13C NMR
(100 MHz, CDCl3, 25 °C) δ/ppm 186.1, 173.1, 156.7, 152.8, 148.0,
134.1, 132.0, 129.4, 128.7, 128.5, 128.0, 127.9, 127.1, 126.6, 117.3, 113.6,
112.5, 100.8, 55.9, 43.5, 28.7; IR (KBr) ν
̃
(cm−1) 3053 (w), 2962 (s),
2924 (s), 1707 (s), 1680 (s), 1604 (m), 1482 (s), 1288 (s), 693 (s); MS
(70 eV, EI) m/z (%) 427 [M]+ (27), 343 (47), 238 (18), 105 (100), 77
(47), 57 (96); HRMS (EI) for C27H25NO4, [M]+ (427.1784), found
427.1782.
N-(5-Bromo-2-phenylbenzofuran-3-yl)benzamide (8a). Reaction
condition, 5 h; white solid (39.1 mg, quantitative yield): mp 256.4−
257.0 °C; 1H NMR (400 MHz, DMSO-d6, 25 °C) δ/ppm 10.44 (s, 1H),
8.01 (d, 2H, J = 7.4 Hz), 7.91 (d, 2H, J = 7.6 Hz), 7.68−7.64 (m, 3H),
7.59 (t, 2H, J = 7.6 Hz), 7.55−7.51 (m, 3H), 7.44 (t, 1H, J = 7.3 Hz); 13C
NMR (100 MHz, DMSO-d6, 25 °C) δ/ppm 166.6, 151.6, 149.6, 134.0,
132.5, 129.8, 129.7, 129.5, 129.4, 129.1, 128.4, 128.2, 126.3, 123.0, 115.9,
N-(2-(4-Bromophenyl)benzofuran-3-yl)-N-pivaloylbenzamide
(4r). Yellow solid (132.5 mg, 93% yield): Rf 0.33 (ethyl acetate/hexanes
1
1/20); mp 148.8−150.3 °C; H NMR (400 MHz, CDCl3, 25 °C) δ/
ppm 7.60 (dd, 2H, J = 8.2 Hz, 1.6 Hz), 7.50−7.38 (m, 5H), 7.34−7.31
(m, 2H), 7.26 (d, 2H, J = 8.5 Hz), 7.14 (d, 2H, J = 8.4 Hz), 1.41 (s, 9H);
13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 186.0, 172.1, 153.1, 152.2,
133.0, 131.3, 129.6, 129.4, 128.8, 128.3, 126.8, 126.7, 126.3, 125.4, 123.9,
115.4, 114.0; IR (KBr) ν
̃
(cm−1) 3252 (s), 3023 (m), 2954 (m), 1688
(m), 1650 (s), 1528 (s), 1444 (s), 1208 (m), 804 (m), 709 (s), 690 (s);
MS (70 eV, EI) m/z (%) 393 [M+2]+ (57), 391 [M]+ (83), 288 (7), 208
(3), 207 (11), 179 (18), 152 (11), 105 (100), 77 (80); HRMS (EI) for
C21H14BrNO2, [M]+ (391.0208), found 391.0202.
117.9, 117.0, 112.1, 43.5, 28.7; IR (KBr) ν
̃
(cm−1) 3061 (w), 2962 (w),
1695 (s), 1589 (m), 1478 (m), 1257 (s), 750 (s); MS (70 eV, EI) m/z
(%) 477 [M+2]+ (52), 475 [M]+ (53), 393 (18), 298 (20), 262 (3), 240
(47), 185 (21), 105 (100), 77 (15), 57 (61); HRMS (EI) for
C26H22BrNO3, [M]+ (475.0783), found 475.0782.
N-(5-Chloro-2-phenylbenzofuran-3-yl)benzamide (8b). Reaction
condition, 5 h; white solid (34.7 mg, quantitative yield): mp 239.2−
239.9 °C; 1H NMR (400 MHz, DMSO-d6, 25 °C) δ/ppm 10.46 (s, 1H),
8.10 (d, 2H, J = 7.2 Hz), 7.92 (d, 2H, J = 7.3 Hz), 7.71 (d, 1H, J = 8.8
Hz), 7.66 (t, 1H, J = 8.8 Hz), 7.60 (t, 2H, J = 7.7 Hz), 7.55−7.51 (m,
3H), 7.45 (d, 1H, J = 7.3 Hz), 7.41 (dd, 2H, J = 8.6 Hz, 2.0 Hz); 13C
NMR (100 MHz, DMSO-d6, 25 °C) δ/ppm 166.6, 151.3, 149.8, 134.0,
132.5, 129.7, 129.5, 129.4, 129.3, 129.1, 128.4, 128.1, 126.3, 125.5, 120.0,
N-(2-(4-Bromophenyl)-5-methoxybenzofuran-3-yl)-N-pivaloyl-
benzamide (4s). White solid (101.5 mg, 67% yield): Rf 0.33 (ethyl
1
acetate/hexanes 1/20); mp 129.4−130.5 °C; H NMR (400 MHz,
CDCl3, 25 °C) δ/ppm 7.55 (d, 2H, J = 8.6 Hz), 7.46 (d, 2H, J = 8.6 Hz),
7.38−7.34 (m, 4H), 7.18 (t, 2H, J = 7.6 Hz), 6.94 (dd, 1H, J = 8.9 Hz, 2.5
Hz), 6.88 (d, 1H, J = 2.4 Hz), 3.87 (s, 3H), 1.41 (s, 9H); 13C NMR (100
MHz, CDCl3, 25 °C) δ/ppm 186.1, 173.0, 156.8, 151.8, 148.1, 133.9,
132.2, 132.0, 128.2, 128.02, 127.96, 127.5, 127.0, 123.7, 117.7, 114.0,
115.6, 113.6; IR (KBr) ν
̃
(cm−1) 3069 (w), 2969 (m), 1707 (s), 1695 (s),
1272 (s), 1112 (m), 693 (m); MS (70 eV, EI) m/z (%) 349 [M+2]+
(33), 347 [M]+ (88), 242 (15), 207 (24), 179 (24), 151 (17), 105 (100),
77 (73); HRMS (EI) for C21H14ClNO2, [M]+ (347.0713), found
347.0714.
112.6, 100.8, 55.9, 43.5, 28.7; IR (KBr) ν
̃
(cm−1) 3056 (w), 2960 (m),
1690 (s), 1613 (m), 1480 (s), 1278 (s), 694 (m); MS (70 eV, EI) m/z
(%) 507 [M+2]+ (28), 505 [M]+ (28), 423 (10), 237 (5), 183 (3), 105
(100), 77 (25), 57 (60); HRMS (ESI) for C27H24BrNO4Na, [M + Na]+
(528.0786), found 528.0788.
N-(2-(4-Bromophenyl)-5-methoxybenzofuran-3-yl)benzamide
(8c). Reaction condition, 3 h; white solid (42.1 mg, quantitative yield):
1
mp 259.5−260.0 °C; H NMR (400 MHz, DMSO-d6, 25 °C) δ/ppm
10.56 (s, 1H), 8.09 (d, 2H, J = 7.3 Hz), 7.80 (d, 1H, J = 8.6 Hz), 7.70 (d,
2H, J = 8.6 Hz), 7.65 (t, 1H, J = 7.2 Hz), 7.58 (t, 3H, J = 8.2 Hz), 7.00−
6.96 (m, 2H), 3.78 (s, 3H); 13C NMR (100 MHz, DMSO-d6, 25 °C) δ/
ppm 166.4, 156.3, 148.0, 147.8, 134.1, 132.5, 132.4, 129.2, 129.1, 128.4,
4-Bromo-N-(5-methoxy-2-phenylbenzofuran-3-yl)-N-pivaloyl-
benzamide (4s′). White solid (15.2 mg, 10% yield): Rf 0.38 (ethyl
1
acetate/hexanes 1/20); mp 125.4−126.6 °C; H NMR (400 MHz,
CDCl3, 25 °C) δ/ppm 7.58 (dd, 2H, J = 7.9 Hz, 1.4 Hz), 7.43−7.36 (m,
4H), 7.28 (d, 2H, J = 8.5 Hz), 7.17 (d, 2H, J = 8.5 Hz), 6.94 (dd, 1H, J =
8.9 Hz, 2.5 Hz), 6.85 (d, 1H, J = 2.5 Hz), 3.86 (s, 3H), 1.41 (s, 9H); 13C
NMR (100 MHz, CDCl3, 25 °C) δ/ppm 186.1, 172.1, 156.7, 152.9,
148.1, 133.0, 131.3, 129.5, 129.4, 128.8, 128.4, 126.9, 126.8, 126.6, 117.0,
128.3, 127.9, 122.4, 116.7, 114.8, 112.6, 102.6, 56.2; IR (KBr) ν
̃
(cm−1)
3234 (s), 3032 (w), 2815 (w), 1645 (s), 1613 (m), 1528 (s), 1476 (s),
1218 (s), 827 (m), 690 (m); MS (70 eV, EI) m/z (%) 422 [M+2]+ (95),
421 [M]+ (100), 318 (5), 237 (25), 219 (6), 194 (21), 139 (6), 105
(99), 77 (20); HRMS (MALDI) for C22H17BrNO3, [M + H]+
(422.0386), found 422.0384.
113.6, 112.7, 100.7, 55.9, 43.5, 28.7; IR (KBr) ν
̃
(cm−1) 3065 (w), 2919
(m), 1710 (s), 1673 (s), 1585 (m), 1480 (s), 1254 (s), 698 (m); MS (70
eV, EI) m/z (%) 507 [M+2]+ (27), 505 [M]+ (23), 423 (33), 238 (22),
185 (60), 155 (9), 105 (13), 57 (100); HRMS (ESI) for
C27H24BrNO4Na, [M + Na]+ (528.0786), found 528.0788.
Typical Procedure for the Preparation of Benzamide 10
(Scheme 5). A solution of benzamide 8 (0.2 mmol) in anhydrous THF
(1.5 mL) was treated with NaH (1.54 equiv) at 0 °C, and the resulting
mixture was stirred at room temperature. To this mixture was added
iodomethane (1.54 equiv) for 10a and 10b; allyl bromide (3.08 equiv)
for 10c; and 4-nitrobenzoyl chloride 2b (1.54 equiv) for 10d at room
temperature. The resulting mixture was stirred at room temperature for
indicated time, and quenched with water. The product was extracted
into ethyl acetate. The organic layer was washed with water and brine,
dried (MgSO4), filtered, and concentrated.
N-(5-Bromo-2-phenylbenzofuran-3-yl)-N-pivaloylthiophene-2-
carboxamide (4t′). Yellow solid (105.3 mg, 73% yield): Rf 0.4 (ethyl
1
acetate/hexanes 1/10); mp 120.8−121.5 °C; H NMR (400 MHz,
CDCl3, 25 °C) δ/ppm 7.77 (dd, 2H, J = 8.2 Hz, 1.8 Hz), 7.54 (d, 1H, J =
1.7 Hz), 7.49−7.40 (m, 7H), 6.89 (dd, 1H, J = 8.8 Hz, 4.8 Hz), 1.38 (s,
9H); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 186.1, 165.7, 153.1,
151.8, 136.2, 133.5, 133.2, 130.0, 129.1, 128.9, 128.3, 127.9, 127.5, 126.8,
N-(5-Bromo-2-phenylbenzofuran-3-yl)-N-methylbenzamide
(10a). Reaction condition, 2 h; white solid (58.3 mg, 72% yield): Rf 0.39
(ethyl acetate/hexanes 1/5); mp 156.6−157.4 °C; 1H NMR (400 MHz,
CDCl3, 25 °C) δ/ppm 7.65 (d, 1H, J = 1.3 Hz), 7.64 (d, 2H, J = 1.8 Hz),
121.1, 117.0, 116.5, 113.4, 43.7, 28.6; IR (KBr) ν
̃
(cm−1) 3105 (w), 2960
(m), 1681 (s), 1516 (m), 1258 (s), 1129 (s), 726 (s); HRMS (EI) for
C24H20BrNO3S, [M]+ (481.0347), found 481.0352.
J
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The Journal of Organic Chemistry
Article
7.44 (t, 2H, J = 7.6 Hz), 7.41−7.38 (m, 2H), 7.29 (d, 1H, J = 8.7 Hz),
7.13−7.09 (m, 3H), 6.96 (t, 2H, J = 7.7 Hz), 3.52 (s, 3H); 13C NMR
(100 MHz, CDCl3, 25 °C) δ/ppm 171.7, 151.4, 150.3, 135.0, 130.0,
129.5, 129.0, 128.4, 128.3, 128.2, 127.5, 126.9, 125.7, 121.2, 120.9, 116.7,
4-Bromo-2-(2-phenyl-5-(trifluoromethyl)oxazol-4-yl)phenol
(11b). Reaction condition, 16 h; white solid (30.0 mg, 78% yield): Rf
0.18 (dichloromethane/hexanes 1/6); mp 124.1−124.4 °C; H NMR
1
(400 MHz, CDCl3, 25 °C) δ/ppm 10.36 (s, 1H), 8.09 (d, 2H, J = 7.0
Hz), 7.65 (d, 1H, J = 2.1 Hz), 7.62−7.52 (m, 3H), 7.42 (dd, 1H, J = 8.8
Hz, 2.4 Hz), 6.94 (d, 1H, J = 8.8 Hz); 13C NMR (100 MHz, CDCl3, 25
°C) δ/ppm 161.1, 155.8, 139.2 (quart, J = 2.7 Hz), 134.5, 133.6 (quart, J
= 43.6 Hz), 132.6, 130.8 (quart, J = 4.3 Hz), 129.3, 127.3, 124.6, 119.9,
113.2, 36.0; IR (KBr) ν
̃
(cm−1) 3056 (m), 2927 (m), 1641 (s), 1492 (m),
1351 (s), 690 (s); MS (70 eV, EI) m/z (%) 407 [M+2]+ (33), 405 [M]+
(25), 300 (15), 252 (5), 239 (14), 220 (37), 192 (30), 163 (17), 139 (8),
118 (19), 105 (100), 77 (53); HRMS (MADLI) for C22H17BrNO2, [M
+ H]+ (406.0437), found 406.0424.
119.4 (quart, J = 268.4 Hz), 114.1, 111.7; IR (KBr) ν
̃
(cm−1) 3069 (m),
3015 (m), 1600 (m), 1558 (m), 1421 (m), 1131 (s), 712 (m); MS (70
eV, EI) m/z (%) 385 [M+2]+ (45), 383 [M]+ (62), 365 (7), 288 (23),
211 (10), 185 (14), 105 (100), 76 (53); HRMS (EI) for
C16H9BrF3NO2, [M]+ (382.9769), found 382.9762.
N-(5-Chloro-2-phenylbenzofuran-3-yl)-N-methylbenzamide
(10b). Reaction condition, 2 h; white solid (52.7 mg, 73% yield): Rf 0.43
(ethyl acetate/hexanes 1/5); mp 138.5−139.1 °C; 1H NMR (400 MHz,
CDCl3, 25 °C) δ/ppm 7.65 (dd, 2H, J = 7.0 Hz, 1.4 Hz), 7.79−7.38 (m,
4H), 7.34 (d, 1H, J = 8.8 Hz), 7.25 (dd, 1H, J = 8.7 Hz, 2.0 Hz), 7.13−
7.09 (m, 3H), 6.96 (t, 2H, J = 7.3 Hz), 3.51 (s, 3H); 13C NMR (100
MHz, CDCl3, 25 °C) δ/ppm 171.7, 151.0, 150.5, 135.0, 130.0, 129.5,
129.3, 129.0, 128.3, 127.8, 127.5, 126.9, 125.6, 125.5, 121.4, 117.9, 112.8,
4-Chloro-2-(2-phenyl-5-(trifluoromethyl)oxazol-4-yl)phenol
(11c). Reaction condition, 24 h; white solid (30.5 mg, 90% yield): Rf
0.45 (ethyl acetate/hexanes 1/10); mp 119.9−120.1 °C; 1H NMR (400
MHz, CDCl3, 25 °C) δ/ppm 10.34 (s, 1H), 8.09 (d, 2H, J = 7.5 Hz),
7.61−7.51 (m, 4H), 7.28 (dd, 1H, J = 8.8 Hz, 2.1 Hz), 6.99 (d, 1H, J = 8.8
Hz); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 161.0, 155.3, 139.3
(quart, J = 2.8 Hz), 133.6 (quart, J = 43.6 Hz), 132.6, 131.6, 129.2, 127.8
(quart, J = 4.2 Hz), 127.2, 124.7, 124.5, 119.44, 119.40 (quart, J = 268.4
36.0; IR (KBr) ν
̃
(cm−1) 3056 (w), 2919 (w), 1641 (s), 1492 (m), 1351
(s), 1254 (m), 1069 (m), 690 (s); MS (70 eV, EI) m/z (%) 363 [M+2]+
(17), 361 [M]+ (55), 256 (22), 221 (44), 165 (14), 118 (28), 105 (100),
77 (23); HRMS (MALDI) for C22H17ClNO2, [M + H]+ (362.0948),
found 362.0958.
Hz), 113.5; IR (KBr) ν
̃
(cm−1) 3084 (m), 3023 (m), 1600 (m), 1474 (s),
1417 (s), 1131 (s), 712 (s); MS (70 eV, EI) m/z (%) 341 [M+2]+ (27),
339 [M]+ (100), 319 (11), 242 (34), 241 (20), 169 (5), 167 (14), 111
(20), 105 (64), 75 (15); HRMS (EI) for C16H9ClF3NO2, [M]+
(339.0274), found 339.0277.
N-Allyl-N-(5-bromo-2-phenylbenzofuran-3-yl)benzamide (10c).
Reaction condition, 5 h; white solid (66.4 mg, 77% yield): Rf 0.5
(ethyl acetate/hexanes 1/5); mp 141.8−142.4 °C; 1H NMR (400 MHz,
CDCl3, 25 °C) δ/ppm 7.73 (d, 2H, J = 7.2 Hz), 7.60 (d, 1H, J = 1.9 Hz),
7.46−7.35 (m, 4H), 7.27 (d, 1H, J = 8.7 Hz), 7.17 (d, 2H, J = 7.5 Hz),
7.11 (t, 1H, J = 7.4 Hz), 6.96 (t, 2H, J = 7.7 Hz), 6.10 (ddt, 1H, J = 16.8
Hz, 10.0 Hz, 6.8 Hz), 5.22−5.15 (m, 2H), 4.84 (dd, 1H, J = 14.2 Hz, 6.3
Hz), 4.25 (dd, 1H, J = 14.2 Hz, 7.2 Hz); 13C NMR (100 MHz, CDCl3,
25 °C) δ/ppm 171.1, 151.4, 150.6, 135.2, 132.3, 130.1, 129.5, 129.1,
128.9, 128.4, 128.1, 127.5, 127.0, 125.8, 121.6, 120.0, 119.8, 116.6, 113.1,
2-(2-Phenyl-5-(trifluoromethyl)oxazol-4-yl)phenol (11d). Reaction
condition, 6 h; white solid (23.2 mg, 76% yield): Rf 0.49 (ethyl acetate/
hexanes 1/10); mp 127.2−128.5 °C; 1H NMR (400 MHz, CDCl3, 25
°C) δ/ppm 10.34 (s, 1H), 8.11 (dd, 2H, J = 6.8 Hz, 1.5 Hz), 7.60−7.52
(m, 4H), 7.35 (td, 1H, J = 8.5 Hz, 1.4 Hz), 7.06 (dd, 1H, J = 8.3 Hz, 0.6
Hz), 6.96 (td, 1H, J = 8.1 Hz, 0.8 Hz); 13C NMR (100 MHz, CDCl3, 25
°C) δ/ppm 160.8, 156.7, 140.6 (quart, J = 2.6 Hz), 133.2 (quart, J = 43.4
Hz), 132.4, 131.8, 129.2, 128.5 (quart, J = 3.8 Hz), 127.3, 124.9, 119.9,
119.7 (quart, J = 268.1 Hz), 118.0, 112.4; MS (70 eV, EI) m/z (%) 305
[M]+ (36), 208 (10), 202 (34), 200 (100), 182 (35), 152 (42), 119 (5),
103 (36), 77 (5); HRMS (EI) for C16H10F3NO2, [M]+ (305.0664),
found 305.0668.
51.8; IR (KBr) ν
̃
(cm−1) 3056 (m), 2927 (m), 1653 (s), 1492 (m), 1254
(s), 1117 (s), 690 (s); HRMS (EI) for C24H18BrNO2, [M]+ (431.0521),
found 431.0510.
N-Benzoyl-N-(5-bromo-2-phenylbenzofuran-3-yl)-4-nitrobenza-
mide (10d). Reaction condition, 1 h; yellow solid (62.6 mg, 58% yield):
1
Rf 0.28 (ethyl acetate/hexanes 1/10); mp 197.6−198.3 °C; H NMR
(400 MHz, CDCl3, 25 °C) δ/ppm 8.13 (d, 2H, J = 8.7 Hz), 7.69 (d, 2H, J
= 8.8 Hz), 7.57 (dd, 3H, J = 10.2 Hz, 1.9 Hz), 7.51−7.46 (m, 4H), 7.43−
7.38 (m, 4H), 7.30 (t, 2H, J = 7.8 Hz); 13C NMR (100 MHz, CDCl3, 25
°C) δ/ppm 172.1, 170.7, 153.2, 151.9, 149.6, 139.5, 133.2, 132.9, 130.2,
129.1, 129.0, 128.8, 128.6, 128.5, 127.5, 127.3, 126.8, 123.6, 120.6, 117.3,
Typical Procedure for the Preparation of Trisubstituted
Oxazoles 12a−c from Aryne (Scheme 5). A flame-dried and
nitrogen-flushed 10 mL Schlenk tube, equipped with a magnetic stirring
bar and a septum, was charged with a solution of oxazoles 11 (0.1 mmol)
and CsF (45.6 mg, 3.0 equiv) in anhydrous MeCN (1.0 mL). To this
stirred reaction mixture, 2-(trimethylsilyl)phenyl trifluoromethanesul-
fonate (30 μL, 1.2 equiv) was added slowly at 60 °C. The reaction
mixture was further stirred for indicated time at 60 °C (monitored by 1H
NMR data analysis). Thereafter the resulting mixture was extracted with
ethyl acetate followed by washing with sat. NaHCO3(aq). The organic
layer was dried over anhydrous MgSO4 and the solvent was removed by
evaporation in vacuo. Purification by flash chromatography furnished
the desired adduct 12.
116.0, 113.8; IR (KBr) ν
̃
(cm−1) 3089 (w), 1685 (s), 1601 (m), 1528 (s),
1347 (s), 1238 (s), 1081 (m), 685 (m); HRMS (EI) for C28H17BrN2O5,
[M]+ (540.0321), found 540.0322.
Typical Procedure for the Preparation of Oxazoles 11
(Scheme 5). A flame-dried and nitrogen-flushed 10 mL Schlenk tube,
equipped with a magnetic stirring bar and a septum, was charged with a
solution of 3 (0.1 mmol) in THF (0.15 mL) and methanol (0.15 mL).
To this stirred reaction mixture, sodium methoxide (10.8 mg, 2.0 equiv)
was added. The reaction mixture was further stirred for indicated time at
room temperature. Thereafter the resulting mixture was extracted with
CH2Cl2 followed by washing with 1 N HCl(aq). The organic layer was
dried over anhydrous MgSO4 and then the solvent was removed by
evaporation in vacuo. Purification by flash chromatography furnished
the desired adduct 11.
4-(5-Bromo-2-phenoxyphenyl)-2,5-diphenyloxazole (12a). Reac-
tion condition, 17 h; white solid (29.0 mg, 62% yield): Rf 0.44 (ethyl
1
acetate/hexanes 1/20); mp 140.1−141.2 °C; H NMR (400 MHz,
CDCl3, 25 °C) δ/ppm 8.13−8.10 (m, 2H), 7.89 (d, 1H, J = 2.6 Hz), 7.57
(dd, 2H, J = 8.3 Hz, 1.5 Hz), 7.49−7.44 (m, 4H), 7.41−7.34 (m, 3H),
7.16 (t, 2H, J = 8.0 Hz), 6.97 (t, 1H, J = 7.3 Hz), 6.81 (d, 1H, J = 8.8 Hz),
6.63 (dd, 1H, J = 8.7 Hz, 0.9 Hz); 13C NMR (100 MHz, CDCl3, 25 °C)
δ/ppm 160.1, 156.0, 153.9, 147.6, 134.4, 132.7, 131.2, 130.5, 129.5,
128.9, 128.8, 128.5, 128.4, 127.2, 126.5, 126.2, 125.9, 123.5, 120.0, 118.7,
115.9; MS (70 eV, EI) m/z (%) 469 [M+2]+ (21), 467 [M]+ (21), 364
(7), 283 (11), 255 (17), 226 (11), 180 (69), 152 (39), 126 (13), 105
(100), 77 (55); HRMS (EI) for C27H18BrNO2, [M]+ (467.0521), found
467.0529.
4-Bromo-2-(2,5-diphenyloxazol-4-yl)phenol (11a). Reaction con-
dition, 26 h; white solid (31.7 mg, 81% yield): Rf 0.64 (ethyl acetate/
hexanes 1/10); mp 147.7−148.3 °C; 1H NMR (400 MHz, CDCl3, 25
°C) δ/ppm 10.66 (s, 1H), 8.08 (dd, 2H, J = 9.7 Hz, 3.7 Hz), 7.72 (dd,
2H, J = 7.9 Hz, 1.5 Hz), 7.60 (d, 1H, J = 2.4 Hz), 7.52−7.46 (m, 6H),
7.29 (dd, 1H, J = 8.8 Hz, 2.4 Hz), 6.92 (d, 1H, J = 8.7 Hz); 13C NMR
(100 MHz, CDCl3, 25 °C) δ/ppm 159.5, 155.2, 146.2, 132.8, 132.7,
131.2, 129.8, 129.1, 128.99, 128.97, 128.2, 127.7, 126.6, 125.9, 119.6,
4-(5-Bromo-2-phenoxyphenyl)-2-phenyl-5-(trifluoromethyl)-
oxazole (12b). Reaction condition, 1 h; colorless oil (40.4 mg, 88%
yield): Rf 0.38 (dichloromethane/hexanes 1/3.5); 1H NMR (400 MHz,
CDCl3, 25 °C) δ/ppm 8.10 (dd, 2H, J = 7.8 Hz, 1.6 Hz), 7.78 (d, 1H, J =
2.6 Hz), 7.53−7.43 (m, 4H), 7.32 (t, 2H, J = 8.0 Hz), 7.11 (t, 1H, J = 7.4
Hz), 6.99 (dd, 2H, J = 8.7 Hz, 1.0 Hz), 6.78 (d, 1H, J = 8.8 Hz); 13C
117.2, 111.0; IR (KBr) ν
̃
(cm−1) 3718 (w), 3056 (m), 1605 (w), 1556
(m), 1472 (s), 1282 (s), 1238 (s), 681 (s); MS (70 eV, EI) m/z (%) 393
[M+2]+ (39), 391 [M]+ (31), 288 (24), 259 (6), 207 (5), 181 (5), 152
(15), 126 (3), 105 (100), 77 (57); HRMS (EI) for C21H14BrNO2, [M]+
(391.0208), found 391.0200.
K
dx.doi.org/10.1021/jo502232q | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
NMR (100 MHz, CDCl3, 25 °C) δ/ppm 162.2, 155.7, 154.4, 136.7
(quart, J = 2.2 Hz), 135.8 (quart, J = 42.6 Hz), 133.83, 133.75, 131.7,
129.9, 128.9, 127.1, 125.9, 124.2, 122.9, 119.5, 119.3 (quart, J = 268.0
Hz), 119.0, 115.2; MS (70 eV, EI) m/z (%) 461 [M+2]+ (93), 459 [M]+
(100), 369 (4), 366 (11), 327 (9), 279 (10), 249 (15), 190 (8), 180 (32),
152 (28), 105 (89), 77 (63); HRMS (EI) for C22H13BrF3NO2, [M]+
(459.0082), found 459.0090.
MS (70 eV, EI) m/z (%) 409 [M+2]+ (17), 407 [M]+ (17), 304 (5), 224
(7), 185 (41), 183 (53), 157 (26), 155 (28), 121 (2), 105 (100), 77
(59); HRMS (EI) for C21H14BrNO3, [M]+ (407.0157), found 407.0157.
(E)-2-((Benzoylimino)methyl)-4-methoxyphenyl 4-bromoben-
zoate (1e). Reaction condition, 1 h; white solid (297.2 mg, 68%
yield): 1H NMR (400 MHz, CDCl3, 25 °C) δ/ppm 8.84 (s, 1H), 8.06−
8.03 (m, 4H), 7.71 (d, 1H, J = 2.8 Hz), 7.64 (d, 2H, J = 8.5 Hz), 7.57 (tt,
1H, J = 7.4 Hz, 1.1 Hz), 7.43 (t, 2H, J = 7.6 Hz), 7.25 (d, 1H, J = 7.8 Hz),
7.20−7.17 (m, 1H), 3.92 (s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C)
δ/ppm 180.8, 164.6, 159.1, 157.7, 145.7, 133.6, 132.9, 132.1, 131.8,
130.1, 129.3, 128.5, 127.7, 127.4, 124.3, 121.1, 112.3, 55.9; MS (70 eV,
EI) m/z (%) 439 [M+2]+ (13), 437 [M]+ (13), 336 (9), 334 (12), 256
(12), 185 (20), 183 (20), 105 (100), 84 (2); HRMS (EI) for
C22H16BrNO4, [M]+ (437.0263), found 437.0254.
(E)-2-((Benzoylimino)methyl)-4-bromophenyl thiophene-2-car-
boxylate (1f). Reaction condition, 1 h; white solid (251.9 mg, 61%
yield): 1H NMR (400 MHz, CDCl3, 25 °C) δ/ppm 8.90 (s, 1H), 8.39 (s,
1H), 8.08 (d, 2H, J = 7.7 Hz), 7.99 (d, 1H, J = 3.2 Hz), 7.73 (d, 1H, J =
8.6 Hz), 7.69 (d, 1H, J = 4.8 Hz), 7.59 (t, 1H, J = 7.4 Hz), 7.46 (t, 2H, J =
7.5 Hz), 7.27 (d, 1H, J = 8.5 Hz), 7.18 (t, 1H, J = 4.3 Hz); 13C NMR (100
MHz, CDCl3, 25 °C) δ/ppm 180.5, 159.8, 158.1, 150.6, 136.8, 135.6,
134.6, 133.8, 132.8, 131.7, 131.3, 130.2, 128.6, 128.3, 125.1, 119.9;
HRMS (MALDI) for C19H12BrNO3SNa, [M + Na]+ (435.9619), found
435.9593.
(E)-2-((Benzoylimino)methyl)phenyl 4-chlorobenzoate (1g). Re-
action condition, 1 h; white solid (192.4 mg, 53% yield): 1H NMR (400
MHz, CDCl3, 25 °C) δ/ppm 8.90 (s, 1H), 8.22 (d, 1H, J = 6.9 Hz), 8.13
(d, 2H, J = 8.5 Hz), 8.04 (d, 2H, J = 7.5 Hz), 7.65 (t, 1H, J = 7.8 Hz), 7.54
(t, 1H, J = 7.4 Hz), 7.47−7.44 (m, 3H), 7.43−7.39 (m, 2H), 7.32 (d, 1H,
J = 8.1 Hz); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 180.8, 164.1,
159.5, 151.7, 140.6, 134.2, 133.6, 132.9, 131.7, 130.1, 129.1, 128.4, 127.1,
126.8, 126.6, 123.4; MS (70 eV, EI) m/z (%) 365 [M+2]+ (8), 363 [M]+
(14), 224 (5), 139 (100), 105 (54), 77 (25); HRMS (EI) for
C21H14ClNO3, [M]+ (363.0662), found 363.0671.
(E)-2-((Benzoylimino)methyl)phenyl 4-methoxybenzoate (1h).
Reaction condition, 40 min; white solid (4.5 mg, 60% yield): 1H
NMR (400 MHz, CDCl3, 25 °C) δ/ppm 8.94 (s, 1H), 8.25 (dd, 1H, J =
7.8 Hz, 1.4 Hz), 8.15 (d, 2H, J = 8.9 Hz), 8.07 (d, 2H, J = 7.6 Hz), 7.63
(td, 1H, J = 7.9 Hz, 1.6 Hz), 7.55 (td, 1H, J = 7.4 Hz, 1.4 Hz), 7.42 (td,
3H, J = 7.7 Hz, 1.6 Hz), 7.32 (d, 1H, J = 8.2 Hz), 6.96 (d, 2H, J = 8.9 Hz),
3.86 (s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 180.9, 164.5,
164.2, 159.5, 152.3, 134.1, 133.5, 133.0, 132.5, 130.1, 129.4, 128.4, 127.0,
126.3, 123.5, 120.8, 114.0, 55.5; MS (70 eV, EI) m/z (%) 360 [M]+ (27),
238 (13), 208 (27), 135 (100), 105 (7), 77 (5); HRMS (EI) for
C22H17NO4, [M]+ (359.1158), found 359.1158.
(E)-2-((Benzoylimino)methyl)-4-methoxyphenyl 4-methoxyben-
zoate (1i). Reaction condition, 40 min; white solid (245.1 mg, 63%
yield): 1H NMR (400 MHz, CDCl3, 25 °C) δ/ppm 8.87 (s, 1H), 8.14
(d, 2H, J = 8.8 Hz), 8.07 (d, 2H, J = 7.3 Hz), 7.74 (d, 1H, J = 2.9 Hz),
7.57 (t, 1H, J = 7.4 Hz), 7.44 (t, 2H, J = 7.8 Hz), 7.26−7.17 (m, 2H), 6.96
(d, 2H, J = 8.8 Hz), 3.91 (s, 3H), 3.88 (s, 3H); 13C NMR (100 MHz,
CDCl3, 25 °C) δ/ppm 181.0, 164.9, 164.2, 159.1, 157.5, 146.3, 133.5,
133.0, 132.5, 130.1, 128.5, 127.5, 124.5, 121.3, 120.9, 114.0, 111.5, 55.9,
55.5; MS (70 eV, EI) m/z (%) 389 [M]+ (34), 332 (1), 268 (2), 256 (7),
185 (5), 149 (2), 135 (100), 77 (7); HRMS (ESI) for C23H20NO5, [M +
H]+ (390.1341), found 390.1342.
(E)-2-((Benzoylimino)methyl)-4-chlorophenyl 4-bromobenzoate
(1j). Reaction condition, 12 min; white solid (48.5 mg, 22% yield): 1H
NMR (400 MHz, CDCl3, 25 °C) δ/ppm 8.84 (s, 1H), 8.24 (d, 1H, J =
2.6 Hz), 8.05 (t, 4H, J = 6.8 Hz), 7.65 (d, 2H, J = 8.5 Hz), 7.62−7.57 (m,
2H), 7.45 (t, 2H, J = 7.6 Hz), 7.29 (d, 1H, J = 8.7 Hz); 13C NMR (100
MHz, CDCl3, 25 °C) δ/ppm 180.5, 164.0, 158.2, 150.3, 134.0, 133.8,
132.7, 132.5, 132.3, 131.8, 130.2, 129.7, 129.1, 128.6, 128.2, 127.2,
124.9; MS (70 eV, EI) m/z (%) 443 [M+2]+ (36), 441 [M]+ (37), 191
(6), 185 (95), 183 (100), 157 (21), 155 (26), 105 (79), 77 (18); HRMS
(MALDI) for C21H14BrClNO3, [M + H]+ (441.9846), found 441.9858.
(E)-2-((Benzoylimino)methyl)-4-bromophenyl cyclohexanecar-
boxylate (1k). Reaction condition, 1 h; white solid (227.2 mg, 55%
yield): 1H NMR (400 MHz, CDCl3, 25 °C) δ/ppm 8.81 (s, 1H), 8.35
(d, 1H, J = 2.2 Hz), 8.13 (d, 2H, J = 7.6 Hz), 7.67 (dd, 1H, J = 8.9 Hz, 2.3
4-(5-Chloro-2-phenoxyphenyl)-2-phenyl-5-(trifluoromethyl)-
oxazole (12c). Reaction condition, 1 h; colorless oil (32.8 mg, 79%
1
yield): Rf 0.33 (ethyl acetate/hexanes 1/20); H NMR (400 MHz,
CDCl3, 25 °C) δ/ppm 8.10 (dd, 2H, J = 7.6 Hz, 1.2 Hz), 7.64 (d, 1H, J =
2.5 Hz), 7.54−7.47 (m, 3H), 7.34−7.30 (m, 3H), 7.11 (t, 1H, J = 7.5
Hz), 7.0 (d, 2H, J = 8.4 Hz), 6.85 (d, 1H, J = 8.9 Hz); 13C NMR (100
MHz, CDCl3, 25 °C) δ/ppm 162.2, 155.9, 153.8, 136.9 (quart, J = 2.3
Hz), 135.8 (quart, J = 42.6 Hz), 131.7, 131.0, 130.8, 129.9, 129.0, 128.1,
127.1, 125.9, 124.1, 122.5, 119.37, 119.36 (quart, J = 268.0 Hz), 118.8;
MS (70 eV, EI) m/z (%) 417 [M+2]+ (5), 415 [M]+ (14), 249 (4), 4 (6),
180 (5), 152 (16), 105 (100), 84 (40), 77 (30); HRMS (EI) for
C22H13ClF3NO2, [M]+ (415.0587), found 415.0580.
Typical Procedure for the Preparation of Imines 1. To a 50 mL
round-bottom flask equipped with a magnetic stirring bar was added
Cs2CO3 (1.6 g, 5.0 equiv) and Na2SO4 (717.4 mg, 5.0 equiv). The solids
were flame-dried under a high vacuum and allowed to cool. To the solids
were added CH2Cl2 (20 mL). The resulting slurry was vigorously stirred
under N2 and the requisite α-amido sulfone (1 mmol) was added in one
portion. After stirring room temperature for 1 h, hexanes (∼20 mL) was
added and the mixture was filtered through Celite. The Celite was rinsed
with hexanes (2 × 20 mL) and the resulting filtrate was concentrated
under reduced pressure. This resulted in a concentrated material that
was filtered and washed with hexanes (2 × 20 mL). The imine 1 was
dried in vacuo and used without further purification.
(E)-2-((Benzoylimino)methyl)-4-bromophenyl benzoate (1a). Re-
action condition, 1 h; white solid (219.8 mg, 54% yield): 1H NMR (400
MHz, CDCl3, 25 °C) δ/ppm 8.88 (s, 1H), 8.41 (d, 1H, J = 2.5 Hz), 8.19
(d, 2H, J = 7.5 Hz), 8.07 (d, 2H, J = 7.5 Hz), 7.75 (dd, 1H, J = 8.7 Hz, 2.5
Hz), 7.66 (t, 1H, J = 7.5 Hz), 7.58 (t, 1H, J = 7.5 Hz), 7.51 (t, 2H, J = 7.7
Hz), 7.45 (t, 2H, J = 7.7 Hz), 7.24 (s, 1H); 13C NMR (125 MHz, CDCl3,
25 °C) δ/ppm 180.6, 164.6, 158.1, 151.1, 136.9, 134.3, 133.8, 132.7,
131.8, 130.4, 130.2, 128.8, 128.6, 128.5, 128.3, 125.2, 119.8; MS (70 eV,
EI) m/z (%) 409 [M+2]+ (17), 407 [M]+ (8), 306 (20), 304 (33), 288
(5), 208 (8), 105 (100), 77 (95); HRMS (FAB) for C21H15BrNO3, [M +
H]+ (408.0235), found 408.0239.
(E)-2-((Benzoylimino)methyl)-4-chlorophenyl benzoate (1b). Re-
action condition, 1 h; white solid (167.0 mg, 46% yield): 1H NMR (400
MHz, CDCl3, 25 °C) δ/ppm 8.88 (s, 1H), 8.25 (d, 1H, J = 1.9 Hz), 8.18
(d, 2H, J = 7.6 Hz), 8.07 (d, 2H, J = 7.6 Hz), 7.65 (t, 1H, J = 7.4 Hz),
7.61−7.56 (m, 2H), 7.51 (t, 2H, J = 7.6 Hz), 7.44 (t, 2H, J = 7.5 Hz), 7.30
(d, 1H, J = 8.7 Hz); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 180.6,
164.6, 158.2, 150.6, 134.3, 133.9, 133.8, 132.7, 132.3, 130.4, 130.2, 128.8,
128.7, 128.5, 128.3, 128.2, 124.9; MS (70 eV, EI) m/z (%) 365 [M+2]+
(8), 363 [M]+ (28), 127 (1), 121 (14), 105 (100), 77 (42); HRMS (EI)
for C21H14ClNO3, [M]+ (363.0662), found 363.0662.
(E)-2-((Benzoylimino)methyl)-4-methoxyphenyl benzoate (1c).
1
Reaction condition, 1 h; white solid (251.4 mg, 70% yield): H NMR
(400 MHz, CDCl3, 25 °C) δ/ppm 8.88 (s, 1H), 8.19 (d, 2H, J = 7.5 Hz),
8.06 (d, 2H, J = 7.5 Hz), 7.73 (d, 1H, J = 2.0 Hz), 7.62 (t, 1H, J = 7.2 Hz),
7.55(t, 1H, J = 7.3 Hz), 7.50 (t, 2H, J = 7.5 Hz), 7.43 (t, 2H, J = 7.5 Hz),
7.25−7.17 (m, 2H), 3.90 (s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C)
δ/ppm 180.9, 165.2, 159.1, 157.6, 146.0, 134.0, 133.5, 133.0, 130.3,
130.1, 128.7, 128.4, 127.4, 124.4, 121.2, 111.8, 55.8; MS (70 eV, EI) m/z
(%) 359 [M]+ (31), 256 (60), 238 (7), 181 (1), 151 (19), 121(73), 105
(100), 77 (64), 51 (70); HRMS (EI) for C22H17NO4, [M]+ (359.1158),
found 359.1152.
(E)-2-((Benzoylimino)methyl)phenyl 4-bromobenzoate (1d). Re-
action condition, 1 h; white solid (305.3 mg, 75% yield): 1H NMR (400
MHz, CDCl3, 25 °C) δ/ppm 8.90 (s, 1H), 8.22 (dd, 1H, J = 7.8 Hz, 1.2
Hz), 8.06−8.03 (m, 4H), 7.67−7.62 (m, 3H), 7.55 (t, 1H, J = 7.4 Hz),
7.46−7.39 (m, 3H), 7.32 (d, 1H, J = 8.2 Hz); 13C NMR (100 MHz,
CDCl3, 25 °C) δ/ppm 180.7, 164.2, 159.5, 151.7, 134.2, 133.5, 133.0,
132.1, 131.8, 130.12, 130.09, 129.3, 128.4, 127.7, 126.9, 126.6, 123.4;
L
dx.doi.org/10.1021/jo502232q | J. Org. Chem. XXXX, XXX, XXX−XXX

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Hz), 7.61 (t, 1H, J = 7.4 Hz), 7.49 (t, 2H, J = 7.6 Hz), 7.08 (d, 1H, J = 8.6
Hz), 2.61 (tt, 1H, J = 11.2 Hz, 3.4 Hz), 2.06−2.04 (m, 2H), 1.82−1.78
(m, 2H), 1.69−1.66 (m, 1H), 1.58 (qd, 2H, J = 11.5 Hz, 2.7 Hz), 1.38−
1.23 (m, 3H); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 180.5, 173.7,
158.1, 151.2, 136.7, 133.8, 132.8, 131.3, 130.2, 128.6, 128.3, 125.0, 119.5,
43.1, 28.8, 25.5, 25.2; HRMS (ESI) for C21H21BrNO3, [M + H]+
(414.0699), found 414.0692.
Typical Procedure for the Preparation of α-Amido Sulfone
Precursors.16 To a flame-dried and nitrogen-flushed 500 mL flask
equipped with a magnetic stirring bar was added benzamide (917.7 mg,
1.5 equiv), p-toluene sulfinic acid sodium salt monohydrate (1.4 g, 1.5
equiv), anhydrous MeCN (100 mL), and aldehyde precursors (5.0
mmol), sequentially. The resulting slurry was then cooled to 0 °C (ice
bath), and TMSCl (1.3 mL, 2.0 equiv) was added over 15 min. The
reaction was allowed to warm to room temperature and stir for indicated
time. At this point, the solvent was removed under reduced pressure and
to the resulting white solid was added Et2O (∼25 mL). This resulted in a
suspension that was filtered and washed with Et2O (2 × 25 mL). The
crude α-amido sulfone was dried in vacuo and used without further
purification.
(d, 1H, J = 10.3 Hz), 8.03 (d, 2H, J = 8.4 Hz), 7.92 (d, 2H, J = 8.4 Hz),
7.78 (d, 1H, J = 2.6 Hz), 7.70 (d, 2H, J = 7.5 Hz), 7.55 (t, 3H, J = 7.8 Hz),
7.45 (t, 2H, J = 7.5 Hz), 7.34 (dd, 3H, J = 10.3 Hz, 2.7 Hz), 7.11 (dd, 1H,
J = 8.9 Hz, 2.7 Hz), 6.88 (d, 1H, J = 10.2 Hz), 3.82 (s, 3H), 2.33 (s, 3H);
13C NMR (100 MHz, DMSO-d6, 25 °C) δ/ppm 167.2, 163.6, 157.5,
145.5, 142.5, 134.3, 133.4, 132.7, 132.3, 132.0, 130.2, 129.1, 128.8, 128.6,
128.5, 128.3, 124.5, 124.1, 116.5, 115.9, 66.8, 56.4, 21.5; IR (KBr)
ν
̃
(cm−1) 3389 (m), 3084 (m), 2962 (m), 1745 (s), 1688 (s), 1592 (s),
1501 (s), 1326 (s), 1257 (s), 1139 (s), 712 (m); HRMS (ESI) for
C29H24BrNO6SNa, [M + Na]+ (616.0405), found 616.0399.
2-(Benzamido(tosyl)methyl)-4-bromophenyl thiophene-2-car-
boxylate (23f). Reaction condition, 120 h; white solid (1.1 g, 79%
yield): mp 196.2−197.0 °C; 1H NMR (400 MHz, DMSO-d6, 25 °C) δ/
ppm 9.83 (d, 1H, J = 10.3 Hz), 8.44 (d, 1H, J = 2.2 Hz), 8.20 (d, 1H, J =
4.2 Hz), 8.04 (d, 1H, J = 2.8 Hz), 7.75 (dd, 1H, J = 8.7 Hz, 2.4 Hz), 7.70
(d, 2H, J = 7.4 Hz), 7.56 (d, 3H, J = 8.2 Hz), 7.48−7.43 (m, 3H), 7.40 (t,
1H, J = 4.4 Hz), 7.32 (d, 2H, J = 8.1 Hz), 6.99 (d, 1H, J = 10.3 Hz), 2.32
(s, 3H); 13C NMR (100 MHz, DMSO-d6, 25 °C) δ/ppm 167.3, 159.1,
148.2, 145.9, 136.5, 136.0, 134.0, 133.9, 133.6, 133.2, 132.6, 131.7, 130.4,
129.5, 129.2, 128.8, 128.4, 126.0, 125.7, 119.1, 66.2, 21.7; IR (KBr)
ν
̃
(cm−1) 3363 (w), 3105 (w), 2952 (w), 1742 (s), 1685 (s), 1593 (w),
2-(Benzamido(tosyl)methyl)-4-bromophenyl benzoate (23a). Re-
action condition, 24 h; white solid (2.4 g, 85% yield): mp 161.0−162.0
°C; 1H NMR (400 MHz, CDCl3, 25 °C) δ/ppm 8.25 (d, 2H, J = 7.6 Hz),
7.82 (s, 1H), 7.73−7.57 (m, 9H), 7.49 (t, 1H, J = 7.2 Hz), 7.36 (t, 2H, J =
7.5 Hz), 7.30 (t, 1H, J = 8.7 Hz), 7.13 (d, 2H, J = 7.8 Hz), 6.90 (d, 1H, J =
10.3 Hz), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm
166.3, 163.4, 148.5, 145.6, 134.1, 133.6, 133.4, 132.52, 132.45, 132.4,
130.3, 129.8, 129.0, 128.9, 128.8, 128.6, 127.2, 125.1, 125.0, 119.1, 67.3,
1512 (m), 1214 (s), 702 (m); HRMS (MALDI) for C26H20BrNO5S2Na,
[M + Na]+ (591.9864), found 591.9877.
2-(Benzamido(tosyl)methyl)phenyl 4-chlorobenzoate (23g). Re-
action condition, 72 h; white solid (1.3 g, 98% yield): mp 174.7−175.2
°C; 1H NMR (400 MHz, DMSO-d6, 25 °C) δ/ppm 9.84 (d, 1H, J = 10.3
Hz), 8.20 (dd, 1H, J = 7.6 Hz, 0.9 Hz), 8.12 (d, 2H, J = 8.5 Hz), 7.79 (d,
2H, J = 8.5 Hz), 7.68 (d, 2H, J = 7.3 Hz), 7.56−7.52 (m, 4H), 7.46−7.40
(m, 4H), 7.32 (d, 2H, J = 8.1 Hz), 6.93 (d, 1H, J = 10.3 Hz), 2.32 (s, 3H);
13C NMR (100 MHz, DMSO-d6, 25 °C) δ/ppm 167.4, 163.3, 149.3,
145.7, 139.9, 134.3, 133.4, 132.6, 132.1, 131.3, 131.2, 130.4, 130.0, 129.2,
21.6; IR (KBr) ν
̃
(cm−1) 3374 (m), 3061 (m), 2962 (m), 1749 (s), 1680
(s), 1592 (m), 1509 (s), 1322 (s), 1219 (s), 701 (s); HRMS (FAB) for
C28H23BrNO5S, [M + H]+ (564.0480), found 564.0480.
128.8, 128.4, 128.1, 126.9, 123.8, 123.5, 66.6, 21.7; IR (KBr) ν
̃
(cm−1)
3379 (m), 3040 (w), 2960 (w), 1754 (s), 1673 (s), 1593 (m), 1516 (s),
1488 (s), 1315 (s), 1218 (s), 1060 (s), 714 (m); HRMS (ESI) for
C28H22ClNO5SNa, [M + Na]+ (542.0805), found 542.0802.
2-(Benzamido(tosyl)methyl)-4-chlorophenyl benzoate (23b). Re-
action condition, 48 h; white solid (2.0 g, 77% yield): mp 173.1−173.6
°C; 1H NMR (400 MHz, CDCl3, 25 °C) δ/ppm 8.25 (d, 2H, J = 7.6 Hz),
7.73−7.65 (m, 4H), 7.60−7.55 (m, 5H), 7.49 (t, 1H, J = 7.4 Hz), 7.44
(dd, 1H, J = 8.8 Hz, 2.2 Hz), 7.38−7.35 (m, 3H), 7.14 (d, 2H, J = 8.0
Hz), 6.90 (d, 1H, J = 10.3 Hz), 2.36 (s, 3H); 13C NMR (100 MHz,
CDCl3, 25 °C) δ/ppm 166.2, 163.5, 147.9, 145.6, 134.1, 133.4, 132.5,
132.4, 131.6, 130.7, 130.3, 129.9, 129.5, 129.0, 128.88, 128.86, 128.7,
2-(Benzamido(tosyl)methyl)phenyl 4-methoxybenzoate (23h).
Reaction condition, 48 h; white solid (2.3 g, 89% yield): mp 156.6−
157.0 °C; 1H NMR (400 MHz, CDCl3, 25 °C) δ/ppm 8.21 (d, 2H, J =
8.8 Hz), 7.64−7.62 (m, 3H), 7.59 (d, 2H, J = 8.1 Hz), 7.51−7.46 (m,
3H), 7.40−7.35 (m, 3H), 7.31 (t, 1H, J = 7.4 Hz), 7.16 (d, 2H, J = 8.0
Hz), 7.04 (d, 2H, J = 8.8 Hz), 6.88 (d, 1H, J = 10.4 Hz), 3.94 (s, 1H),
2.36 (s, 1H); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 166.3, 164.2,
163.4, 149.5, 145.3, 133.7, 132.8, 132.4, 132.1, 130.6, 129.9, 129.7, 129.0,
128.6, 127.1, 125.9, 123.4, 122.8, 121.3, 114.1, 68.0, 55.6, 21.6; IR (KBr)
127.2, 124.7, 124.6, 67.4, 21.7; IR (KBr) ν
̃
(cm−1) 3382 (m), 3069 (w),
2969 (w), 1749 (s), 1684 (s), 1596 (s), 1486 (s), 1326 (s), 1227 (s),
1139 (s), 705 (s); HRMS (ESI) for C28H22ClNO5SNa, [M + Na]+
(542.0805), found 542.0812.
2-(Benzamido(tosyl)methyl)-4-methoxyphenyl benzoate (23c).
Reaction condition, 48 h; white solid (1.9 g, 74% yield): mp 174.5−
175.2 °C; 1H NMR (400 MHz, CDCl3, 25 °C) δ/ppm 8.25 (d, 2H, J =
7.6 Hz), 7.70 (t, 1H, J = 7.3 Hz), 7.63 (d, 2H, J = 7.6 Hz), 7.59−7.55 (m,
5H), 7.47 (t, 1H, J = 7.2 Hz), 7.36−7.30 (m, 3H), 7.17 (s, 1H), 7.13 (d,
2H, J = 7.8 Hz), 7.00 (dd, 1H, J = 8.8 Hz, 2.0 Hz), 6.85 (d, 1H, J = 10.4
Hz), 3.76 (s, 3H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C) δ/
ppm 166.2, 164.2, 157.2, 145.3, 142.9, 133.8, 133.7, 132.9, 132.2, 130.2,
129.7, 129.3, 129.1, 128.8, 128.6, 127.2, 124.3, 123.6, 116.1, 114.8, 68.2,
ν
̃
(cm−1) 3382 (m), 3046 (w), 2977 (w), 1752 (s), 1676 (s), 1608 (s),
1512 (s), 1257 (s), 1219 (s), 1170 (s), 709 (m), 568 (s); HRMS (ESI)
for C29H25NO6SNa, [M + Na]+ (538.1300), found 538.1297.
2-(Benzamido(tosyl)methyl)-4-methoxyphenyl 4-methoxyben-
zoate (23i). Reaction condition, 48 h; white solid (1.2 g, 90% yield):
mp 164.6−165.3 °C; 1H NMR (400 MHz, CDCl3, 25 °C) δ/ppm 8.20
(d, 2H, J = 8.8 Hz), 7.62 (t, 4H, J = 9.6 Hz), 7.55 (d, 1H, J = 10.3 Hz),
7.47 (t, 1H, J = 7.4 Hz), 7.34 (t, 2H, J = 7.8 Hz), 7.29 (d, 1H, J = 9.0 Hz),
7.17−7.13 (m, 3H), 7.03 (d, 2H, J = 8.9 Hz), 6.99 (dd, 1H, J = 9.0 Hz, 3.0
Hz), 6.84 (d, 1H, J = 10.4 Hz), 3.93 (s, 3H), 3.77 (s, 3H), 2.36 (s, 3H);
13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 166.3, 164.1, 163.9, 157.1,
55.7, 21.6; IR (KBr) ν
̃
(cm−1) 3069 (s), 1749 (m), 1680 (m), 1592 (m),
1505 (m), 1333 (m), 1059 (m); HRMS (ESI) for C29H25NO6SNa, [M +
Na]+ (538.1300), found 538.1288.
2-(Benzamido(tosyl)methyl)phenyl 4-bromobenzoate (23d). Re-
action condition, 24 h; white solid (4.4 g, 79% yield): mp 167.8−168.4
°C; 1H NMR (400 MHz, CDCl3, 25 °C) δ/ppm 8.11 (d, 2H, J = 8.5 Hz),
7.75 (d, 1H, J = 7.8 Hz), 7.71 (d, 2H, J = 8.4 Hz), 7.63 (d, 3H, J = 7.2
Hz), 7.56 (d, 2H, J = 8.2 Hz), 7.48 (quart, 2H, J = 7.1 Hz), 7.49−7.29
(m, 4H), 7.14 (d, 2H, J = 8.1 Hz), 6.91 (d, 1H, J = 10.4 Hz), 2.36 (s, 3H);
13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 166.3, 163.1, 149.2, 145.4,
133.6, 132.7, 132.24, 132.18, 131.7, 130.7, 129.8, 129.2, 129.0, 128.6,
145.3, 143.1, 133.9, 132.9, 132.4, 132.2, 129.7, 129.1, 128.6, 127.2, 124.4,
123.6, 121.5, 116.1, 114.8, 114.1, 68.3, 55.8, 55.6, 21.6; IR (KBr)
ν
̃
(cm−1) 3387 (m), 3065 (w), 2968 (w), 1742 (s), 1681 (s), 1605 (s),
1512 (s), 1258 (s), 1165 (s); HRMS (MALDI) for C30H27NO7SNa, [M
+ Na]+ (568.1406), found 568.1421.
2-(Benzamido(tosyl)methyl)-4-chlorophenyl 4-bromobenzoate
(23j). Reaction condition, 36 h; white solid (2.5 g, 85% yield): mp
183.3−184.0 °C; 1H NMR (400 MHz, CDCl3, 25 °C) δ/ppm 8.10 (d,
2H, J = 8.5 Hz), 7.72 (d, 2H, J = 8.5 Hz), 7.67−7.63 (m, 3H), 7.58 (d,
2H, J = 8.2 Hz), 7.53 (t, 1H, J = 7.2 Hz), 7.46 (dd, 1H, J = 8.7 Hz, 2.4
Hz), 7.42−7.34 (m, 4H), 7.18 (d, 2H, J = 8.1 Hz), 6.82 (d, 1H, J = 10.4
Hz), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 166.1,
163.0, 147.8, 145.8, 133.4, 132.6, 132.5, 132.3, 131.9, 131.7, 130.8, 129.9,
129.5, 129.0, 128.8, 127.8, 127.1, 124.8, 124.6, 67.1, 21.7; IR (KBr)
128.1, 127.1, 126.3, 123.2, 122.9, 67.5, 21.6; IR (KBr) ν
̃
(cm−1) 3397
(m), 3061 (w), 1749 (s), 1684 (s), 1589 (s), 1520 (s), 1486 (s), 1257
(s), 1219 (s), 1074 (s), 579 (s); HRMS (ESI) for C28H22BrNO5SNa, [M
+ Na]+ (586.0300), found 586.0298.
2-(Benzamido(tosyl)methyl)-4-methoxyphenyl 4-bromobenzoate
(23e). Reaction condition, 24 h; white solid (2.8 g, 95% yield): mp
174.8−175.4 °C; 1H NMR (400 MHz, DMSO-d6, 25 °C) δ/ppm 9.84
ν
̃
(cm−1) 3403 (w), 3056 (m), 2960 (m), 1746 (s), 1685 (s), 1585 (s),
M
dx.doi.org/10.1021/jo502232q | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1516 (s), 1484 (s), 1222 (s), 1073 (s), 710 (s), 577 (s); HRMS (ESI) for
C28H21BrClNO5SNa, [M + Na]+ (619.9910), found 619.9913.
= 8.6 Hz), 7.68 (d, 2H, J = 8.5 Hz), 7.41 (dd, 1H, J = 2.0 Hz, 1.2 Hz),
7.22−7.21 (m, 2H), 3.88 (s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C)
δ/ppm 188.0, 164.7, 157.8, 145.8, 132.1, 131.7, 129.3, 128.6, 127.6,
2-(Benzamido(tosyl)methyl)-4-bromophenyl cyclohexanecarbox-
ylate (23k). Reaction condition, 144 h; white solid (839.4 mg, 59%
yield): mp 142.0−142.7 °C; 1H NMR (400 MHz, DMSO-d6, 25 °C) δ/
ppm 9.75 (d, 1H, J = 10.3 Hz), 8.36 (d, 1H, J = 2.4 Hz), 7.70−7.65 (m,
5H), 7.55 (t, 1H, J = 7.4 Hz), 7.46 (t, 2H, J = 7.8 Hz), 7.40 (d, 2H, J = 8.2
Hz), 7.19 (d, 1H, J = 8.7 Hz), 6.78 (d, 1H, J = 10.2 Hz), 2.61 (tt, 1H, J =
11.1 Hz, 3.6 Hz), 2.35 (s, 3H), 2.06−1.99 (m, 2H), 1.79−1.75 (m, 1H),
1.67−1.62 (m, 1H), 1.52 (qd, 2H, J = 12.1 Hz, 3.2 Hz), 1.38−1.35 (m,
2H), 1.29−1.22 (m, 1H); 13C NMR (100 MHz, DMSO-d6, 25 °C) δ/
ppm 173.5, 167.6, 149.0, 146.2, 134.2, 134.1, 133.9, 133.5, 132.9, 130.7,
129.6, 129.1, 128.6, 126.2, 125.9, 119.0, 66.4, 29.2, 29.1, 26.1, 25.53,
124.5, 122.2, 112.6, 55.9; IR (KBr) ν
̃
(cm−1) 3092 (w), 2969 (m), 2870
(m), 1726 (s), 1691 (s), 1589 (s), 1493 (s), 1265 (s), 1070 (s), 750 (s);
MS (70 eV, EI) m/z (%) 336 [M+2]+ (14), 334 [M]+ (14), 185 (97),
183 (100), 155 (26), 108 (8), 95 (16), 76 (30); HRMS (EI) for
C15H11BrO4, [M]+ (333.9841), found 333.9846.
4-Bromo-2-formylphenyl thiophene-2-carboxylate (22f). Reaction
condition, 1.5 h; white solid (1.5 g, 97% yield): mp 100.1−100.5 °C; 1H
NMR (400 MHz, CDCl3, 25 °C) δ/ppm 10.17 (s, 1H), 8.03 (d, 1H, J =
2.5 Hz), 8.02 (dd, 1H, J = 3.7 Hz, 1.1 Hz), 7.76−7.72 (m, 2H), 7.26 (d,
1H, J = 8.7 Hz), 7.21 (dd, 1H, J = 4.8 Hz, 3.9 Hz); 13C NMR (100 MHz,
CDCl3, 25 °C) δ/ppm 186.7, 159.7, 150.8, 137.9, 135.5, 134.6, 132.2,
25.47, 21.9; IR (KBr) ν
̃
(cm−1) 3206 (s), 3061 (s), 2931 (s), 2863 (s),
1752 (s), 1653 (s), 1615 (s), 1528 (s), 1330 (s), 1147 (s), 1109 (s), 697
(s); HRMS (ESI) for C28H28BrNO5SNa, [M + Na]+ (592.0764), found
592.0767.
Typical Procedure for the Preparation of Aldehyde Pre-
cursors.9f A dry and nitrogen-flushed 50 mL Schlenk flask, equipped
with a magnetic stirring bar and a septum, was charged with a solution of
salicylaldehyde (10.0 mmol) in dry THF (20 mL). Acyl chloride 2 (1.05
equiv) and NEt3 (1.5 mL, 1.1 equiv) was added, and the reaction mixture
was stirred for indicated time at room temperature. Thereafter the
resulting mixture was extracted with CH2Cl2 followed by washed with
sat. NaHCO3(aq). The organic layer was dried over anhydrous MgSO4
and then evaporated to afford aldehyde precursors.
131.1, 129.4, 128.3, 125.2, 119.8; IR (KBr) ν
̃
(cm−1) 3097 (m), 2871
(m), 1742 (s), 1685 (s), 1589 (m), 1468 (s), 1250 (s), 1048 (s), 718 (s);
HRMS (MALDI) for C12H7BrO3SNa, [M + Na]+ (332.9197), found
332.9213.
2-Formylphenyl 4-chlorobenzoate (22g). Reaction condition, 1 h;
white solid (2.5 g, 96% yield): mp 99.1−99.6 °C; 1H NMR (400 MHz,
CDCl3, 25 °C) δ/ppm 10.16 (s, 1H), 8.16 (d, 2H, J = 8.6 Hz), 7.94 (dd,
1H, J = 7.7 Hz, 1.7 Hz), 7.68 (td, 1H, J = 7.9 Hz, 1.7 Hz), 7.51 (d, 2H, J =
8.6 Hz), 7.44 (t, 1H, J = 7.5 Hz), 7.31 (dd, 1H, J = 8.3 Hz, 0.6 Hz); 13C
NMR (100 MHz, CDCl3, 25 °C) δ/ppm 188.3, 164.1, 151.7, 140.6,
135.3, 131.7, 130.9, 129.1, 128.2, 127.2, 126.6, 123.5; IR (KBr) ν
̃
(cm−1)
2839 (m), 2750 (m), 1738 (s), 1694 (s), 1601 (s), 1480 (s), 1395 (s),
1292 (s), 746 (s); MS (70 eV, EI) m/z (%) 262 [M+2]+ (8), 260 [M]+
(24), 141 (34), 139 (100), 113 (6), 111 (17); HRMS (MALDI) for
C14H9ClO3Na, [M + Na]+ (283.0132), found 283.0132.
4-Bromo-2-formylphenyl benzoate (22a). Reaction condition, 30
min; white solid (3 g, 99% yield): mp 117.0−118.0 °C; 1H NMR (400
MHz, CDCl3, 25 °C) δ/ppm 10.16 (s, 1H), 8.22 (dd, 2H, J = 7.2 Hz, 1.2
Hz), 8.07 (d, 1H, J = 2.4 Hz), 7.79 (dd, 1H, J = 8.6 Hz, 2.5 Hz), 7.70 (t,
1H, J = 7.4 Hz), 7.55 (t, 2H, J = 7.7 Hz), 7.25 (d, 2H, J = 8.9 Hz); 13C
NMR (100 MHz, CDCl3, 25 °C) δ/ppm 186.8, 164.5, 151.3, 137.9,
134.2, 132.4, 130.3, 130.1, 129.5, 128.8, 128.4, 128.2, 125.3, 119.8; MS
(70 eV, EI) m/z (%) 306 [M+2]+ (30), 304 [M]+ (28), 105 (100), 77
(58); HRMS (EI) for C14H9BrO3, [M]+ (303.9735), found 303.9739.
4-Chloro-2-formylphenyl benzoate (22b). Reaction condition, 1 h;
2-Formylphenyl 4-methoxybenzoate (22h). Reaction condition, 1
1
h; white solid (2.5 g, 99% yield): mp 81.3−81.8 °C; H NMR (400
MHz, CDCl3, 25 °C) δ/ppm 10.23 (s, 1H), 8.18 (d, 2H, J = 9.0 Hz),
7.95 (dd, 1H, J = 7.7 Hz, 1.6 Hz), 7.67 (td, 1H, J = 7.9 Hz, 1.6 Hz), 7.41
(t, 1H, J = 7.5 Hz), 7.32 (d, 1H, J = 8.1 Hz), 7.01 (d, 2H, J = 8.9 Hz), 3.91
(s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 188.4, 164.6,
164.3, 152.6, 135.3, 132.5, 129.8, 128.4, 126.3, 123.6, 120.8, 114.0, 55.5;
1
IR (KBr) ν
̃
(cm−1) 3069 (w), 2847 (m), 1726 (s), 1695 (s), 1604 (s),
white solid (2.5 g, 97% yield): mp 108.7−109.4 °C; H NMR (400
1509 (s), 1272 (s); MS (70 eV, EI) m/z (%) 256 [M]+ (17), 135 (100),
121 (4), 107 (8), 92 (12), 77 (13); HRMS (EI) for C15H12O4, [M]+
(256.0736), found 256.0732.
MHz, CDCl3, 25 °C) δ/ppm 10.16 (s, 1H), 8.20 (dd, 2H, J = 7.3 Hz, 1.3
Hz), 7.89 (d, 1H, J = 2.6 Hz), 7.67 (t, 1H, J = 7.6 Hz), 7.61 (dd, 1H, J =
8.6 Hz, 2.8 Hz), 7.53 (t, 2H, J = 7.7 Hz), 7.29 (d, 1H, J = 8.7 Hz); 13C
NMR (100 MHz, CDCl3, 25 °C) δ/ppm 186.8, 164.6, 150.7, 135.0,
2-Formyl-4-methoxyphenyl 4-methoxybenzoate (22i). Reaction
condition, 1 h; yellow solid (2.8 g, 99% yield): mp 113.5−114.2 °C; 1H
NMR (400 MHz, CDCl3, 25 °C) δ/ppm 10.18 (s, 1H), 8.17 (d, 2H, J =
8.8 Hz), 7.41 (d, 1H, J = 2.5 Hz), 7.21−7.20 (m, 2H), 7.00 (d, 2H, J = 8.9
Hz), 3.90 (s, 3H), 3.86 (s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C) δ/
ppm 188.1, 165.0, 164.2, 157.5, 146.7, 132.4, 128.7, 124.6, 122.4, 120.8,
134.2, 132.3, 130.3, 129.3, 129.2, 128.8, 128.2, 125.0; IR (KBr) ν
̃
(cm−1)
3092 (w), 2893 (w), 1745 (s), 1688 (s), 1592 (m), 1265 (s), 697 (s);
MS (70 eV, EI) m/z (%) 262 [M+2]+ (6), 260 [M]+ (15), 181 (11), 157
(9), 155 (32), 139 (13), 127 (43), 105 (100), 97 (4), 75 (77), 63 (97);
HRMS (EI) for C14H9ClO3, [M]+ (260.0240), found 260.0237.
2-Formyl-4-methoxyphenyl benzoate (22c). Reaction condition, 1
114.0, 111.4, 55.8, 55.5; IR (KBr) ν
̃
(cm−1) 3073 (w), 2968 (m), 2879
1
h; white solid (2.5 g, 99% yield): mp 75.7−76.7 °C; H NMR (400
(m), 1726 (s), 1694 (s), 1601 (s), 1492 (s); MS (70 eV, EI) m/z (%)
286 [M]+ (27), 185 (3), 152 (2), 135 (100), 107 (5), 86 (8), 57 (2);
HRMS (EI) for C16H14O5, [M]+ (286.0841), found 286.0847.
MHz, CDCl3, 25 °C) δ/ppm 10.19 (s, 1H), 8.23 (dd, 2H, J = 8.4 Hz, 1.4
Hz), 7.67 (tt, 1H, J = 7.5 Hz, 1.3 Hz), 7.54 (tt, 2H, J = 7.8 Hz, 1.3 Hz),
7.42 (d, 1H, J = 2.5 Hz), 7.26−7.20 (m, 2H), 3.88 (s, 3H); 13C NMR
(100 MHz, CDCl3, 25 °C) δ/ppm 188.0, 165.3, 157.7, 146.4, 134.0,
4-Chloro-2-formylphenyl 4-bromobenzoate (22j). Reaction con-
dition, 1 h; white solid (3.3 g, 99% yield): mp 153.7−154.1 °C; 1H NMR
(400 MHz, CDCl3, 25 °C) δ/ppm 10.11 (s, 1H), 8.07 (d, 2H, J = 8.5
Hz), 7.90 (d, 1H, J = 2.6 Hz), 7.69 (d, 2H, J = 8.6 Hz), 7.64 (dd, 1H, J =
8.7 Hz, 2.7 Hz), 7.29 (d, 1H, J = 8.7 Hz); 13C NMR (100 MHz, CDCl3,
25 °C) δ/ppm 186.9, 164.1, 150.3, 135.1, 132.6, 132.3, 131.8, 130.1,
130.3, 128.8, 124.6, 122.4, 111.9, 55.9; IR (KBr) ν
̃
(cm−1) 3000 (w),
2954 (w), 1730 (s), 1695 (s), 1600 (m), 1497 (s), 1269 (s), 693 (s); MS
(70 eV, EI) m/z (%) 256 [M]+ (17), 151 (8), 123 (3), 105 (100), 77
(77), 51 (26); HRMS (EI) for C15H12O4, [M]+ (256.0736), found
256.0730.
129.7, 129.2, 127.3, 125.0; IR (KBr) ν
̃
(cm−1) 3089 (w), 2871 (w), 1734
2-Formylphenyl 4-bromobenzoate (22d). Reaction condition, 30
min; white solid (3.0 g, 99% yield): mp 98.6−99.1 °C; 1H NMR (400
MHz, CDCl3, 25 °C) δ/ppm 10.16 (s, 1H), 8.08 (d, 2H, J = 8.5 Hz),
7.93 (dd, 1H, J = 7.7 Hz, 1.5 Hz), 7.70−7.66 (m, 3H), 7.44 (t, 1H, J = 7.5
Hz), 7.31 (d, 1H, J = 8.2 Hz); 13C NMR (100 MHz, CDCl3, 25 °C) δ/
ppm 188.4, 164.2, 151.7, 135.3, 132.1, 131.7, 130.9, 129.3, 128.2, 127.7,
(s), 1690 (s), 1585 (s), 1391 (s), 746 (s), 625 (m); MS (70 eV, EI) m/z
(%) 340 [M+2]+ (17), 338 [M]+ (16), 185 (100), 183 (98), 155 (18), 99
(2), 75 (8); HRMS (EI) for C14H8BrClO3, [M]+ (337.9345), found
337.9338.
4-Bromo-2-formylphenyl cyclohexanecarboxylate (22k). Reaction
condition, 50 min; white solid (1.5 g, 97% yield): mp 62.8−63.3 °C; 1H
NMR (400 MHz, CDCl3, 25 °C) δ/ppm 10.06 (s, 1H), 7.99 (d, 1H, J =
2.5 Hz), 7.71 (dd, 1H, J = 8.8 Hz, 2.4 Hz), 7.07 (d, 1H, J = 8.6 Hz), 2.66
(tt, 1H, J = 11.3 Hz, 3.6 Hz), 2.13−2.09 (m, 2H), 1.87−1.81 (m, 2H),
1.73−1.69 (m, 1H), 1.61 (qd, 2H, J = 12.0 Hz, 3.2 Hz), 1.43−1.24 (m,
3H); 13C NMR (100 MHz, CDCl3, 25 °C) δ/ppm 186.9, 173.8, 151.2,
137.8, 132.5, 129.4, 125.3, 119.5, 43.1, 28.8, 25.6, 25.2; IR (KBr)
126.6, 123.5; IR (KBr) ν
̃
(cm−1) 2840 (m), 1733 (m), 1684 (s), 1265 (s),
1067 (m), 758 (s); MS (70 eV, EI) m/z (%) 306 [M+2]+ (20), 304 [M]+
(20), 202 (58), 185 (100), 155 (52), 121 (38), 104 (8), 76 (39); HRMS
(EI) for C14H9BrO3, [M]+ (303.9735), found 303.9729.
2-Formyl-4-methoxyphenyl 4-bromobenzoate (22e). Reaction
condition, 1 h; white solid (3.3 g, 99% yield): mp 123.3−123.7 °C;
1H NMR (400 MHz, CDCl3, 25 °C) δ/ppm 10.13 (s, 1H), 8.07 (d, 2H, J
ν
̃
(cm−1) 3076 (m), 2924 (s), 2855 (s), 1756 (s), 1695 (s), 1592 (m),
N
dx.doi.org/10.1021/jo502232q | J. Org. Chem. XXXX, XXX, XXX−XXX

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Article
1470 (m), 1116 (s), 613 (w); HRMS (ESI) for C14H15BrO3Na, [M +
Na]+ (333.0097), found 333.0096.
Fan, J.; Wang, Z. Org. Lett. 2010, 12, 2338−2341. (e) Haas, D.; Mosrin,
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ASSOCIATED CONTENT
■
S
* Supporting Information
(c) Merkul, E.; Muller, T. J. J. Chem. Commun. 2006, 4817−4819.
̈
1H NMR and 13C NMR spectra. X-ray crystallographic data (CIF
files) have been deposited (CCDC 940039, 997351, 997355−
997356, 997359−997369, and 997377). This material is available
free of charge via the Internet at http://pubs.acs.org.
(d) Hashmi, A. S. K.; Schuster, A. M.; Gaillard, S.; Cavallo, L.; Poater, A.;
Nolan, S. P. Organometallics 2011, 30, 6328−6337. (e) Kison, C.; Opatz,
T. Chem.Eur. J. 2009, 15, 843−845. (f) Shi, B.; Blake, A. J.; Lewis, W.;
Campbell, I. B.; Judkins, B. D.; Moody, C. J. J. Org. Chem. 2010, 75,
152−161. (g) Jiang, H.; Huang, H.; Cao, H.; Qi, C. Org. Lett. 2010, 12,
́
AUTHOR INFORMATION
5561−5563. (h) Cano, I.; Alvarez, E.; Nicasio, M. C.; Per
́
ez, P. J. J. Am.
■
Chem. Soc. 2011, 133, 191−193. (i) He, W.; Li, C.; Zhang, L. J. Am.
Chem. Soc. 2011, 133, 8482−8485. (j) Davies, P. W.; Cremonesi, A.;
Dumitrescu, L. Angew. Chem., Int. Ed. 2011, 50, 8931−8935. (k) Xu, Z.;
Zhang, C.; Jiao, N. Angew. Chem., Int. Ed. 2012, 51, 11367−11370.
(l) Xue, W.-J.; Li, Q.; Zhu, Y.-P.; Wang, J.-G.; Wu, A.-X. Chem. Commun.
2012, 48, 3485−3487. (m) via aza-Wittig reaction, see: Takeuchi, H.;
Yanagida, S.-i.; Ozaki, T.; Hagiwara, S.; Eguchi, S. J. Org. Chem. 1989, 54,
431−434.
Corresponding Author
*E-mail: wenweilin@ntnu.edu.tw.
Author Contributions
†Y.-S. Fan and U. Das contributed equally.
Notes
The authors declare no competing financial interest.
(7) Tsai, Y.-L.; Fan, Y.-S.; Lee, C.-J.; Huang, C.-H.; Das, U.; Lin, W.
Chem. Commun. 2013, 49, 10266−10268.
ACKNOWLEDGMENTS
■
The authors thank the MOST of the R.O.C. (NSC 101-2113-M-
003-001-MY3) for financial support.
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997362 (3g′), 997365 (3h), 997369 (3h′), 997364 (4g), 997366 (3l),
997368 (3m), 997355 (3o), 997351 (4o), 997356 (4p), 997360 (4s),
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